The need for critical and intersectional approaches to equity efforts in postgraduate medical education: A critical narrative review.

BACKGROUND: Racialised trainees in Canada and the USA continue to disproportionately experience discrimination and harassment in learning environments despite equity, diversity, and inclusion (EDI) reform efforts. Using critical approaches to understand what problems have been conceptualised and operationalised as EDI issues within postgraduate medical education (PGME) is important to inform ongoing learning environment reform in resident training. METHODS: We conducted a critical narrative review of EDI literature from 2009-2022 using critical race theory (CRT) and the concept of intersectionality to analyse how issues of discrimination in PGME have been studied. Our search yielded 2244 articles that were narrowed down to 349 articles for relevance to Canadian and American PGME contexts. We attended to reflexivity and our positionality in analysing the database and identifying themes related to EDI reform. RESULTS: Interest convergence was noted in how EDI reform was rationalised primarily by increased productivity. Problems of learner representation, gender inequities and curricular problems were conceptualised as EDI issues. The role that racism played in EDI-related problems was largely invisible, as were explicit conceptualisations of race and gender as social constructs. Overall, there was a lack of critical or intersectional approaches in the literature reviewed. Misalignment was noted where studies would frame a problem through a critical lens, but then study the problem without attention to power. DISCUSSION: Interest convergence and epistemic injustice can account for the absence of critical approaches due to the alignment of existing EDI work with institutional interests and priorities. Interest convergence conceptually limits existing EDI reform efforts in PGME. CRT and intersectionality connect racialised learner experiences to systemic phenomena like racism and other forms of discrimination to challenge dominant assumptions. Because they attend to power, critical approaches are key to understanding why inequities have persisted to advance equity in learning environments for racialised and intersectionally marginalised learners.

COVID-19 vaccine acceptance among pregnant women and the reasons for hesitancy: A multi-centre cross-sectional survey.

BACKGROUND: On 9 June 2021, the Australian Technical Advisory Group on Immunisation and Royal Australian and New Zealand College of Obstetricians and Gynaecologists recommended that pregnant women receive Comirnaty (Pfizer) messenger RNA vaccine at any stage of pregnancy. AIM: This multi-centre study aimed to assess vaccine acceptance, reasons for hesitancy and determine if differences exist between health districts, to inform future policy strategies for COVID-19 vaccination in pregnancy. MATERIALS AND METHODS: An online survey (developed based on the World Health Organization Behavioural and Social Drivers survey and modified for the pregnant population) was administered to a sample population of pregnant women attending antenatal clinics at two metropolitan hospitals (Westmead and Royal North Shore Hospital (RNSH)) in New South Wales between 15 September 2021 and 22 October 2021. RESULTS: There were 287 pregnant women surveyed (Westmead 198 (69%), RNSH 66 (23%), no site 23 (8%)). There was a significantly lower Socio-Economic Indexes for Areas score (5.66 vs 9.45, P = 0.001), fewer women born in Australia (37% vs 53%, P = 0.02) and higher number of children (0.77 vs 0.41, P = 0.01) among Westmead respondents. There was lower vaccination uptake (68% vs 86%, P = 0.01) and willingness to receive vaccine (68% vs 88% P = 0.01) at Westmead compared to RNSH. There was an increased proportion of respondents who were concerned that the vaccine could cause harm to the unborn baby at Westmead (38% vs 11%, P = 0.01). CONCLUSIONS: Along with healthcare provider recommendation for vaccination in pregnancy, materials should be targeted to specific safety concerns of pregnant women.

Why clinicians overtest: development of a thematic framework.

BACKGROUND: Medical tests provide important information to guide clinical management. Overtesting, however, may cause harm to patients and the healthcare system, including through misdiagnosis, false positives, false negatives and overdiagnosis. Clinicians are ultimately responsible for test requests, and are therefore ideally positioned to prevent overtesting and its unintended consequences. Through this narrative literature review and workshop discussion with experts at the Preventing Overdiagnosis Conference (Sydney, 2019), we aimed to identify and establish a thematic framework of factors that influence clinicians to request non-recommended and unnecessary tests. METHODS: Articles exploring factors affecting clinician test ordering behaviour were identified through a systematic search of MedLine in April 2019, forward and backward citation searches and content experts. Two authors screened abstract titles and abstracts, and two authors screened full text for inclusion. Identified factors were categorised into a preliminary framework which was subsequently presented at the PODC for iterative development. RESULTS: The MedLine search yielded 542 articles; 55 were included. Another 10 articles identified by forward-backward citation and content experts were included, resulting in 65 articles in total. Following small group discussion with workshop participants, a revised thematic framework of factors was developed: "Intrapersonal" - fear of malpractice and litigation; clinician knowledge and understanding; intolerance of uncertainty and risk aversion; cognitive biases and experiences; sense of medical obligation "Interpersonal" - pressure from patients and doctor-patient relationship; pressure from colleagues and medical culture; "Environment/context" - guidelines, protocols and policies; financial incentives and ownership of tests; time constraints, physical vulnerabilities and language barriers; availability and ease of access to tests; pre-emptive testing to facilitate subsequent care; contemporary medical practice and new technology CONCLUSION: This thematic framework may raise awareness of overtesting and prompt clinicians to change their test request behaviour. The development of a scale to assess clinician knowledge, attitudes and practices is planned to allow evaluation of clinician-targeted interventions to reduce overtesting.

Evidence to justify retention of transvaginal mesh: comparison between laparoscopic sacral colpopexy and transvaginal Elevate™ mesh.

INTRODUCTION AND HYPOTHESIS: To determine if laparoscopic sacral colpopexy (LSC) offers better apical support with a lower exposure rate than transvaginal mesh surgery with Elevate™. METHODS: This was a retrospective cohort study comparing patients with apical prolapse (POP-Q point C ≥ -1) who underwent Elevate™ mesh repair (n = 146) with patients who underwent laparoscopic sacral colpopexy (n = 267). RESULTS: The sacral colpopexy group had a mean age of 59 years and a BMI of 25.7. Patients in the Elevate™ group were older, with a mean age of 63 and a BMI of 26.3. Most of the patients of both groups presented with pelvic organ prolapse stage III (LSC 73.8% and Elevate™ 87.0%) and their mean POP-Q point C were not significantly different (LSC 1.4 vs Elevate™ 1.2 cm). Operative time was longer in the LSC group (113 vs 91 min, p < 0.001), but estimated blood loss was lower (75 cm3 vs 137 cm3, p < 0.001). No difference in mesh exposure rate could be found between the two groups at one year (Elevate™ 0.7% vs LSC 2.6%, OR 0.26, 95% CI 0.03 to 2.10, p = 0.21). One-year objective cure rate, defined as no descent beyond the hymen, was 97.0% in the LSC group and 96.6% in the Elevate™ group (p = .81). The overall recurrence (objective, subjective recurrence or reoperation) was also not different between the groups (LSC 4.5% vs Elevate 4.8%, p = 0.89). CONCLUSION: Transvaginal Elevate™ mesh delivers comparable apical support with a low exposure rate similar to that of laparoscopic sacral colpopexy.

Brachialis periosteal avulsion injury: case report with magnetic resonance imaging findings.

Brachialis periosteal avulsion injury is an uncommon injury occurring in young children. The injury may be misinterpreted or overlooked because of misleading or subtle radiological findings. A case of 7-year-old child with post-traumatic elbow pain and subtle findings on elbow radiography is presented. The injury was initially misinterpreted as an avulsion fracture of the medial epicondyle. Following radiological review, a diagnosis of brachialis periosteal avulsion injury was made. The radiographic and magnetic resonance imaging (MRI) findings of this injury are presented to stress the value of comparing the radiographic findings with previous imaging and to increase awareness of this uncommon injury.

Association of multiple sclerosis with stroke: A comprehensive review.

Background: Multiple sclerosis (MS) is a chronic immune-mediated disorder characterized by the degradation of the myelin sheath in the central nervous system. Research indicates that individuals with MS exhibit a higher susceptibility to stroke compared to the general population. This association is rooted in shared underlying mechanisms, specifically involving neuroinflammatory processes. Methodology: We performed an extensive search on PubMed, MEDLINE, Embase, Scopus, and Google Scholar using specific terms. The search terms included variations of "multiple sclerosis," "stroke," "cerebrovascular disease," "vascular risk factors," "disease-modifying therapies," and "neuroinflammation." The search was limited to articles published from January 1, 2000, up to 31 May, 2023. Results and Discussion: Stroke, a global health burden characterized by significant mortality and adult disability, underscores the critical importance of understanding the link between MS and stroke. Despite a growing body of research establishing an elevated risk of stroke in MS patients, notable information gaps persist. Limited prospective multicenter studies on stroke incidence in MS patients contribute to an incomplete understanding of the precise relationship between these two conditions. Conclusion: In conclusion, this review underscores the critical need for a thorough understanding of the complex relationship between MS and stroke. The identified risk factors and the influence of MS DMTs on stroke risk necessitate further investigation to inform evidence-based preventive and therapeutic strategies. Bridging the existing information gaps through prospective multicenter studies is imperative for a comprehensive understanding of this association. The development of targeted diagnostic and therapeutic approaches for acute stroke risk in MS patients is paramount to mitigate the impact of these debilitating conditions. Ultimately, this review serves as a foundation for future efforts to enhance preventative measures and therapeutic interventions, thereby improving the overall quality of life for individuals with MS susceptible to strokes.

The effects of the interplay between vitamins, antibiotics, and gut microbiota on the pathogenesis and progression of dementia: A systematic review and meta-analysis.

Background: Given that there is already evidence of a neural network that connects the brain and gut and that the gut microbiota actively modulates gut health, it is crucial to know which foods, supplements, and medications to use or avoid when treating any disease that causes dementia or cognitive impairment. Previous research has examined the relationships between vitamins, antibiotics, and gut microbiota and the correlations between these factors and dementia. The question arises of how these three factors interact together and if evidence suggests one element is more important than the others in the pathogenesis and development of dementia. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) standards were followed when conducting this review. The papers' publication dates varied from (2012-2022). Cochrane/EMBASE, PEDro, and PubMed/Medline databases were searched. The precise terms "gut microbiota," vitamins," antibiotics," and "dementia" were included in the search method, along with the conjunctions "OR" and "AND." Results: Gut dysbiosis has a significant impact on cognition, brain function, and the development and progression of dementia. The two most popular probiotics used in studies linked to cognition benefits were Lactobacillus and Bifidobacterium. Numerous scales were used to evaluate cognition, but the mini-mental state examination was the most popular, and the most prevalent impairment was Alzheimer's disease. The supplements with the most significant impact on gut microbiota were vitamin B-12 and folic acid. Conclusion: This systematic review concluded that vitamins, gut microbiota and antibiotics have a close association with the development of dementia. More research is required to establish causality and elucidate the underlying mechanisms because there is still little evidence connecting the interactions of vitamins, medications, and microbiota with dementia. The complexity of interactions between genetics, lifestyle factors, and comorbidities, as well as the heterogeneity of dementia, may make it more challenging to interpret the findings.

Neurological, cardiac, musculoskeletal, and renal manifestations of scleroderma along with insights into its genetics, pathophysiology, diagnostic, and therapeutic updates.

Background: Scleroderma, also referred to as systemic sclerosis, is a multifaceted autoimmune condition characterized by abnormal fibrosis and impaired vascular function. Pathologically, it encompasses the persistent presence of inflammation, abnormal collagen buildup, and restructuring of blood vessels in various organs, resulting in a wide range of clinical symptoms. This review incorporates the most recent scientific literature on scleroderma, with a particular emphasis on its pathophysiology, clinical manifestations, diagnostic approaches, and treatment options. Methodology: A comprehensive investigation was carried out on numerous databases, such as PubMed, MEDLINE, Scopus, Web of Science, and Google Scholar, to collect pertinent studies covering diverse facets of scleroderma research. Results: Scleroderma presents with a range of systemic manifestations, such as interstitial lung disease, gastrointestinal dysmotility, Raynaud's phenomenon, pulmonary arterial hypertension, renal complications, neurological symptoms, and cardiac abnormalities. Serological markers, such as antinuclear antibodies, anti-centromere antibodies, and anti-topoisomerase antibodies, are important for classifying diseases and predicting their outcomes. Discussion: The precise identification of scleroderma is crucial for promptly and correctly implementing effective treatment plans. Treatment approaches aim to improve symptoms, reduce complications, and slow down the progression of the disease. An integrated approach that combines pharmacological agents, including immunosuppressants, endothelin receptor antagonists, and prostanoids, with nonpharmacological interventions such as physical and occupational therapy is essential for maximizing patient care. Conclusion: Through the clarification of existing gaps in knowledge and identification of emerging trends, our goal is to improve the accuracy of diagnosis, enhance the effectiveness of therapeutic interventions, and ultimately enhance the overall quality of life for individuals suffering from scleroderma. Ongoing cooperation and creative research are necessary to advance the field and achieve improved patient outcomes and new therapeutic discoveries.

Newer modalities in the management of Alzheimer's dementia along with the role of aducanumab and lecanemab in the treatment of its refractory cases.

Alzheimer's disease (AD) is a common neurological condition characterized by a gradual and progressive decline in memory, language, emotion, and cognition. It mainly affects elderly people. Due to the effects of AD, pharmaceutical medications and anticholinesterases have been vigorously promoted and approved by the FDA as a form of AD therapy. However, it was progressively found that these drugs did not address the underlying causes of AD pathogenesis; rather, they focused on the symptoms in order to enhance patients' cognitive outcomes. Consequently, a hunt for superior disease-modifying options is launched. Designing new therapeutic agents requires a thorough understanding of the neuroprotective processes and varied functions carried out by certain genes, and antibodies. In this comprehensive review article, we give an overview of the history of Alzheimer's disease, the significance of the blood-brain barrier in determining the scope of treatment options, as well as the advantages and disadvantages of the current therapeutic treatment options for stem cell therapy, immunotherapy, regenerative therapy, and improved Alzheimer's disease care and diagnosis. We have also included a discussion on the potential role of aducanumab and Lecanemab as a cutting-edge therapy in refractory Alzheimer's disease patients. Lecanemab has been recently approved by the FDA for the treatment of Alzheimer's disease.

Chronic mild stress paradigm as a rat model of depression: facts, artifacts, and future perspectives.

RATIONALE: The chronic mild stress (CMS) paradigm was first described almost 40 years ago and has become a widely used model in the search for antidepressant drugs for major depression disorder (MDD). It has resulted in the publication of almost 1700 studies in rats alone. Under the original CMS procedure, the expression of an anhedonic response, a key symptom of depression, was seen as an essential feature of both the model and a depressive state. The prolonged exposure of rodents to unpredictable/uncontrollable mild stressors leads to a reduction in the intake of palatable liquids, behavioral despair, locomotor inhibition, anxiety-like changes, and vegetative (somatic) abnormalities. Many of the CMS studies do not report these patterns of behaviors, and they often fail to include consistent molecular, neuroanatomical, and physiological phenotypes of CMS-exposed animals. OBJECTIVES: To critically review the CMS studies in rats so that conceptual and methodological flaws can be avoided in future studies. RESULTS: Analysis of the literature supports the validity of the CMS model and its impact on the field. However, further improvements could be achieved by (i) the stratification of animals into 'resilient' and 'susceptible' cohorts within the CMS animals, (ii) the use of more refined protocols in the sucrose test to mitigate physiological and physical artifacts, and (iii) the systematic evaluation of the non-specific effects of CMS and implementation of appropriate adjustments within the behavioral tests. CONCLUSIONS: We propose methodological revisions and the use of more advanced behavioral tests to refine the rat CMS paradigm, which offers a valuable tool for developing new antidepressant medications.

Neonatal heart rate variability: a contemporary scoping review of analysis methods and clinical applications.

BACKGROUND: Neonatal heart rate variability (HRV) is widely used as a research tool. However, HRV calculation methods are highly variable making it difficult for comparisons between studies. OBJECTIVES: To describe the different types of investigations where neonatal HRV was used, study characteristics, and types of analyses performed. ELIGIBILITY CRITERIA: Human neonates ≤1 month of corrected age. SOURCES OF EVIDENCE: A protocol and search strategy of the literature was developed in collaboration with the McGill University Health Center's librarians and articles were obtained from searches in the Biosis, Cochrane, Embase, Medline and Web of Science databases published between 1 January 2000 and 1 July 2020. CHARTING METHODS: A single reviewer screened for eligibility and data were extracted from the included articles. Information collected included the study characteristics and population, type of HRV analysis used (time domain, frequency domain, non-linear, heart rate characteristics (HRC) parameters) and clinical applications (physiological and pathological conditions, responses to various stimuli and outcome prediction). RESULTS: Of the 286 articles included, 171 (60%) were small single centre studies (sample size <50) performed on term infants (n=136). There were 138 different types of investigations reported: physiological investigations (n=162), responses to various stimuli (n=136), pathological conditions (n=109) and outcome predictor (n=30). Frequency domain analyses were used in 210 articles (73%), followed by time domain (n=139), non-linear methods (n=74) or HRC analyses (n=25). Additionally, over 60 different measures of HRV were reported; in the frequency domain analyses alone there were 29 different ranges used for the low frequency band and 46 for the high frequency band. CONCLUSIONS: Neonatal HRV has been used in diverse types of investigations with significant lack of consistency in analysis methods applied. Specific guidelines for HRV analyses in neonates are needed to allow for comparisons between studies.

NEI-01-Induced Arginine Deprivation Has Potent Activity Against Acute Myeloid Leukemia Cells Both In Vitro and In Vivo.

Recent studies have revealed that targeting amino acid metabolic enzymes is a promising strategy in cancer therapy. Acute myeloid leukemia (AML) downregulates the expression of argininosuccinate synthase (ASS1), a recognized rate-limiting enzyme for arginine synthesis, and yet displays a critical dependence on extracellular arginine for survival and proliferation. This dependence on extracellular arginine, also known as arginine auxotrophy, suggests that arginine deprivation would be a treatment strategy for AML. NEI-01, a novel arginine-depleting enzyme, is capable of binding to serum albumin to extend its circulating half-life, leading to a potent anticancer activity. Here we reported the preclinical activity of NEI-01 in arginine auxotrophic AMLs. NEI-01 efficiently depleted arginine both in vitro and in vivo NEI-01-induced arginine deprivation was cytotoxic to arginine auxotrophic AML cells through induction of cell-cycle arrest and apoptosis. Furthermore, the potent anti-leukemia activities of NEI-01 were observed in three different types of mouse models including human cell line-derived xenograft, mouse cell line-derived homografts in syngeneic mice and patient-derived xenograft. This preclinical data provide strong evidence to support the potential use of NEI-01 as a therapeutic approach in AML treatment.

Exploring the Socialization Experiences of Medical Students From Social Science and Humanities Backgrounds.

PURPOSE: To explore the structural, cultural, and interpersonal issues that may contribute to the inadvertent marginalization of medical students with social science and humanities (SSH) backgrounds. METHOD: Using the hidden curriculum as an analytic construct, the lead author interviewed 14 medical students with SSH backgrounds at the University of Toronto Faculty of Medicine from February to October 2015. The authors analyzed the interview transcripts for common themes around positive and negative cultural, structural, and interpersonal dimensions of the socialization process. RESULTS: Participants reported barriers to applying to medical school: needing to complete prerequisite courses and to do well on an exam geared toward those with a strong science background (the Medical College Admission Test) and lacking an application cohort. Some participants felt they were not ideal candidates for medical school. Participants appreciated how their SSH backgrounds and associated skill sets shaped both their perspectives on patient care and their developing professional identities. However, they perceived that others largely deemed their previous training as irrelevant, and they felt marginalized in medical school by peers, instructors, and the curriculum. These experiences led both to self-censorship, which enabled them to seem to conform to normative behaviors, and to the pursuit of reaffirming elective experiences. CONCLUSIONS: The existing hidden curriculum inadvertently marginalizes SSH medical students; their experiences likely reflect the socialization experiences of other students from underrepresented backgrounds. Curricular and institutional reforms are imperative to shift the hidden curriculum toward one of epistemological inclusion that better supports students from nontraditional backgrounds.

Humanism, the Hidden Curriculum, and Educational Reform: A Scoping Review and Thematic Analysis.

BACKGROUND: Medical educators have used the hidden curriculum concept for over three decades to make visible the effects of tacit learning, including how culture, structures, and institutions influence professional identity formation. In response to calls to see more humanistic-oriented training in medicine, the authors examined how the hidden curriculum construct has been applied in the English language medical education literature with a particular (and centering) look at its use within literature pertaining to humanism. They also explored the ends to which the hidden curriculum construct has been used in educational reform efforts (at the individual, organizational, and/or systems levels) related to nurturing and/or increasing humanism in health care. METHOD: The authors conducted a scoping review and thematic analysis that draws from the tradition of critical discourse analysis. They identified 1,887 texts in the literature search, of which 200 met inclusion criteria. RESULTS: The analysis documents a strong preoccupation with negative effects of the hidden curriculum, particularly the moral erosion of physicians and the perceived undermining of humanistic values in health care. A conflation between professionalism and humanism was noted. Proposals for reform largely target medical students and medical school faculty, with very little consideration for how organizations, institutions, and sociopolitical relations more broadly contribute to problematic behaviors. CONCLUSIONS: The authors argue that there is a need to transcend conceptualizations of the hidden curriculum as antithetical to humanism and offer suggestions for future research that explores the necessity and value of humanism and the hidden curriculum in medical education and training.

Synthesis of an in vivo MRI-detectable apoptosis probe.

Cellular apoptosis is a prominent feature of many diseases, and this programmed cell death typically occurs before clinical manifestations of disease are evident. A means to detect apoptosis in its earliest, reversible stages would afford a pre-clinical 'window' during which preventive or therapeutic measures could be taken to protect the heart from permanent damage. We present herein a simple and robust method to conjugate human Annexin V (ANX), which avidly binds to cells in the earliest, reversible stages of apoptosis, to superparamagnetic iron oxide (SPIO) nanoparticles, which serve as an MRI-detectable contrast agent. The conjugation method begins with an oxidation of the SPIO nanoparticles, which oxidizes carboxyl groups on the polysaccharide shell of SPIO. Purified ANX protein is then added in the setting of a sodium borate solution to facilitate covalent interaction of ANX with SPIO in a reducing buffer. A final reduction step with sodium borohydride is performed to complete the reduction, and then the reaction is quenched. Unconjugated ANX is removed from the mix by microcentrifuge filtration. The size and purity of the ANX-SPIO product is verified by dynamic light scattering (DLS). This method does not require addition to, or modification of, the polysaccharide SPIO shell, as opposed to cross-linked iron oxide particle conjugation methods or biotin-labeled nanoparticles. As a result, this method represents a simple, robust approach that may be extended to conjugation of other proteins of interest.