A Rational Approach to JAK2 Mutation Testing in Patients with Elevated Hemoglobin: Results from the JAK2 Prediction Cohort (JAKPOT) Study.

BACKGROUND: Erythrocytosis, most often measured as an increase in hemoglobin and/or hematocrit, is a common reason for referral to internal medicine and hematology clinics and a rational approach is required to effectively identify patients with polycythemia vera while avoiding over-investigation. AIM: We aimed to develop and validate a simple rule to predict JAK2 mutation positivity based on complete blood count parameters to aid in the diagnostic approach to patients referred for elevated hemoglobin. SETTING: Internal medicine and hematology clinics at an academic tertiary referral center. PARTICIPANTS: The JAK2 Prediction Cohort (JAKPOT), a large retrospective cohort (n = 901) of patients evaluated by internal medicine and hematology specialists for elevated hemoglobin. DESIGN: JAK2 mutation analysis was performed in all patients and clinical and laboratory variables were collected. Patients were randomly divided into derivation and validation cohorts. A prediction rule was developed using data from the derivation cohort and tested in the validation cohort. KEY RESULTS: The JAKPOT prediction rule included three variables: (i) red blood cell count >6.45×1012/L, (ii) platelets >350×109/L, and (iii) neutrophils >6.2×109/L; absence of all criteria was effective at ruling out JAK2-positivity with sensitivities 94.7% and 100%, and negative predictive values of 98.8% and 100% in the derivation and validation cohorts, respectively, with an overall low false negative rate of 0.4%. The rule was validated for three different methods of JAK2 testing. Applying this rule to our entire cohort would have resulted in over 50% fewer tests. CONCLUSION: In patients with elevated hemoglobin, the use of a simple prediction rule helps to accurately identify patients with a low likelihood of having a JAK2 mutation, potentially limiting costly over-investigation in this common referral population.

Technical Difficulties: Teaching Critical Philosophical Orientations toward Technology.

Issue: Technological innovation is accelerating, creating less time to reflect on the impact new technologies will have on the medical profession. Modern technologies are becoming increasingly embedded in routine medical practice with far-reaching impacts on the patient-physician relationship and the very essence of the health professions. These impacts are often difficult to predict and can create unintended consequences for medical education. This article is driven by a main question: How do we prepare trainees to critically assess technologies that we cannot foresee and effectively use technology to support equitable and compassionate care? Evidence: We translate insights from the philosophy of technology into a proposal for integrating critical technical consciousness in medical curricula. We identify three areas required to develop critical consciousness with regard to emerging technologies. The first area is technical literacy, which involves not just knowing how to use technology, but also understanding its limitations and appropriate contexts for use. The second area is the ability to assess the social impact of technology. This practice requires understanding that while technification creates new possibilities it can also have adverse, unintended consequences. The third area is critical reflection on the relationship between 'the human' and 'the technical' as it relates to the values of the medical profession and professional identity formation. Human and technology are two sides of the same coin; therefore, thinking critically about technology also forces us to think about what we consider 'the human side of medicine'. Implications: Critical technical consciousness can be fostered through an educational program underpinned by the recognition that, although technological innovation can create new possibilities for healing, technology is never neutral. Rather, it is imperative to emphasize that technology is interwoven with the social fabric that is essential to healing. Like medication, technology can be both potion and poison.

Thirty years of teaching evidence-based medicine: have we been getting it all wrong?

Evidence based medicine (EBM) has been synonymous to delivery of quality care for almost thirty years. Since the movement's inception, the assumption has been that decisions based on high quality evidence would translate to better care for patients. Despite EBM's many attractive features and the substantive attention it has received in the contemporary clinical and medical education literature, how it is defined and operationalized as a component of training is often unclear and problematic. How to practice EBM is not well articulated in the literature; therefore, it becomes difficult to teach and equally challenging to assess. In this paper, we put forward a call for deeper consideration of how EBM is taught, and for clarification on how it is defined and operationalized in medical education. In preparing this paper, we considered questions such as what it means to practice EBM, the role that medical education plays in helping realize EBM, how the teaching of EBM can change to reflect recent developments in clinical practice and education, and whether transformations in the practice of medicine necessitate a change in how we teach EBM. We end with four avenues that may be pursued to advance the teaching of EBM in medical education: (1) consensus on what we mean by EBM; (2) clear articulation of EBM-associated competencies; (3) empirically and theoretically supported means of promoting EBM competencies; (4) ways to assess both skill acquisition and use of EBM. We discuss implications for educators of EBM.

The Impact of Artificial Intelligence on Health Equity in Oncology: Scoping Review.

BACKGROUND: The field of oncology is at the forefront of advances in artificial intelligence (AI) in health care, providing an opportunity to examine the early integration of these technologies in clinical research and patient care. Hope that AI will revolutionize health care delivery and improve clinical outcomes has been accompanied by concerns about the impact of these technologies on health equity. OBJECTIVE: We aimed to conduct a scoping review of the literature to address the question, "What are the current and potential impacts of AI technologies on health equity in oncology?" METHODS: Following PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines for scoping reviews, we systematically searched MEDLINE and Embase electronic databases from January 2000 to August 2021 for records engaging with key concepts of AI, health equity, and oncology. We included all English-language articles that engaged with the 3 key concepts. Articles were analyzed qualitatively for themes pertaining to the influence of AI on health equity in oncology. RESULTS: Of the 14,011 records, 133 (0.95%) identified from our review were included. We identified 3 general themes in the literature: the use of AI to reduce health care disparities (58/133, 43.6%), concerns surrounding AI technologies and bias (16/133, 12.1%), and the use of AI to examine biological and social determinants of health (55/133, 41.4%). A total of 3% (4/133) of articles focused on many of these themes. CONCLUSIONS: Our scoping review revealed 3 main themes on the impact of AI on health equity in oncology, which relate to AI's ability to help address health disparities, its potential to mitigate or exacerbate bias, and its capability to help elucidate determinants of health. Gaps in the literature included a lack of discussion of ethical challenges with the application of AI technologies in low- and middle-income countries, lack of discussion of problems of bias in AI algorithms, and a lack of justification for the use of AI technologies over traditional statistical methods to address specific research questions in oncology. Our review highlights a need to address these gaps to ensure a more equitable integration of AI in cancer research and clinical practice. The limitations of our study include its exploratory nature, its focus on oncology as opposed to all health care sectors, and its analysis of solely English-language articles.

Genomic data in prognostic models-what is lost in translation? The case of deletion 17p and mutant TP53 in chronic lymphocytic leukaemia.

Genomic technologies are revolutionizing the practice of haematology-oncology, leading to improved disease detection, more accurate prognostication and targeted treatment decisions. These advances, however, have also introduced new clinical challenges, which include problems of prognostic underdetermination and its attendant risks of over- and undertreatment. Genomic data is generated from different technologies, from cytogenetics to next-generation sequencing, which are often interpreted interchangeably and in a binary fashion-as the presence or absence of a given chromosomal deletion or mutation-an oversimplification which may lead to mistaken prognosis. We discuss the clinical use of one such prognostic marker, represented by sequence and copy number alterations in TP53, located on chromosome 17p. Mutations in TP53 are strongly linked to poor prognosis in a variety of haematological malignancies, including chronic lymphocytic leukaemia (CLL). We review studies in CLL which utilize the 17p deletion or TP53 mutations for prognostic stratification with specific focus on the technologies used for detection, the thresholds established for clinical significance, and the clinical contexts in which these alterations are identified. The case of CLL illustrates issues arising from simplistic, binary interpretation of genetic testing and highlights the need to apply a critical lens when incorporating genomics into prognostic models.

From hermeneutics to heteroglossia: 'The Patient's View' revisited.

This article explores conceptual and methodological challenges surrounding the recovery of patients' voices in the history of medicine. We examine the debate that followed Roy Porter's seminal article, 'The Patient's View: Doing Medical History from Below' (1985). Porter argued that patients should be given a central role in medical history, aiming to restore to patients a voice and agency that is often lost in 'physician-centered' historical narratives. His work carried significant influence but also sparked an ongoing debate about the possibility of conducting 'patient-centered' history of medicine. The growth of the medical humanities has afforded renewed attention to patient narratives, supporting the need to recognise patients' voices in contemporary healthcare and medical education. However, several barriers complicate and problematise the expansion of a patient-centred epistemology across historical periods. Postmodern critics have expressed scepticism that 'the patient's view' can be recovered from history, with some claiming that 'the patient' is a construct of the 'medical gaze' whose subjectivity cannot be reconstituted outside of sociohistorical discourses of knowledge and power. Psychiatry in the mid-20th century presents a particular challenge for patient-centred history. We discuss the influence of postmodern theorists, especially Michel Foucault, whose work is seen as undermining the possibility of a patient-centred epistemology. We argue against Foucault's erasure of the patient, and instead explore alternate constructivist epistemologies, focusing on the hermeneutics of Hans-Georg Gadamer and dialogism of Mikhail Bakhtin, to help address historiographical challenges in recovering 'the patient's view'. To illustrate the value of Gadamerian and Bakhtinian approaches, we apply them to a case study from the Verdun Protestant Hospital (Québec, Canada) from 1941 to 1956, which sheds light on the introduction of the first antipsychotic, chlorpromazine, into clinical practice. We highlight how Gadamer's hermeneutics and Bakhtin's dialogism together offer insights into patient perspectives during this liminal period in the history of psychiatry.

Crusted scabies in a renal transplant recipient treated with daily ivermectin: A case report and literature review.

Crusted scabies is a rare disease variant associated with T-cell dysregulation. Transplant patients are at risk of developing crusted scabies as a consequence of their immunosuppressive regimens. We report a case of crusted scabies presenting with recurrent septicemia in a 65-year-old renal transplant recipient, treated with daily ivermectin for 7 days after initial failure of weekly ivermectin dosing. A literature review of crusted scabies in transplant recipients consisting of 19 cases reports was summarized. Pruritus was common, and initial misdiagnosis was frequent. Most were treated with topical therapy, with one-third receiving ivermectin. Three of seven cases presenting with a concomitant infection died. Crusted scabies is commonly misdiagnosed in transplant recipients owing to its rarity, varied appearance, and different skin distributions. It should be considered in the differential diagnosis of transplant recipients presenting with rash and pruritus, given its association with secondary infection and subsequent mortality.

Three visions of doctoring: a Gadamerian dialogue.

Medicine in the twenty-first century faces an 'identity crisis,' as it grapples with the emergence of various 'ways of knowing,' from evidence-based and translational medicine, to narrative-based and personalized medicine. While each of these approaches has uniquely contributed to the advancement of patient care, this pluralism is not without tension. Evidence-based medicine is not necessary individualized; personalized medicine may be individualized but is not necessarily person-centered. As novel technologies and big data continue to proliferate today, the focus of medical practice is shifting away from the dialogic encounter between doctor and patient, threatening the loss of humanism that many view as integral to medicine's identity. As medical trainees, we struggle to synthesize medicine's diverse and evolving 'ways of knowing' and to create a vision of doctoring that integrates new forms of medical knowledge into the provision of person-centered care. In search of answers, we turned to twentieth-century philosopher Hans-Georg Gadamer, whose unique outlook on "health" and "healing," we believe, offers a way forward in navigating medicine's 'messy pluralism.' Drawing inspiration from Gadamer's emphasis on dialogue and 'practical wisdom' (phronesis), we initiated a dialogue with the dean of our medical school to address the question of how medical trainees and practicing clinicians alike can work to create a more harmonious pluralism in medicine today. We propose that implementing a pluralistic approach ultimately entails 'bridging' the current divide between scientific theory and the practical art of healing, and involves an iterative and dialogic process of asking questions and seeking answers.

Three Problems with Big Data and Artificial Intelligence in Medicine.

The rise of big data and artificial intelligence (AI) in health care has engendered considerable excitement, claiming to improve approaches to diagnosis, prognosis, and treatment. Amidst the enthusiasm, the philosophical assumptions that underlie the big data and AI movement in medicine are rarely examined. This essay outlines three philosophical challenges faced by this movement: (1) the epistemological-ontological problem arising from the theory-ladenness of big data and measurement; (2) the epistemological-logical problem resulting from the inherent limitations of algorithms and attendant issues of reliability and interpretability; and (3) the phenomenological problem concerning the irreducibility of human experience to quantitative data. These philosophical issues demonstrate several important challenges for these technologies that must be considered prior to their integration into clinical care. Our article aims to initiate a critical dialogue on the impact of big data and AI in health care in order to allow for more robust evaluation of these technologies and to aid in the development of approaches to clinical care that better serve clinicians and their patients.

Emerging Trends in Clinical Research: With Implications for Population Health and Health Policy.

Policy Points: Significant advances in clinical medicine that have broader societal relevance may be less accessible to population health researchers and policymakers because of increased specialization within fields. We describe important recent clinical advances and discuss their broader societal impact. These advances include more expansive strategies for disease prevention, the rise of precision medicine, applications of human microbiome research, and new and highly successful treatments for hepatitis C infection. These recent developments in clinical research raise important issues surrounding health care costs and equitable resource allocation that necessitate an ongoing dialogue among the fields of clinical medicine, population health, and health policy. CONTEXT: Developments in clinical medicine have important implications for population health, and there is a need for interdisciplinary engagement among clinical medicine, the social sciences, and public health research. The aim of this article is to help bridge the divide between these fields by exploring major recent advances in clinical medicine that have important implications for population health. METHODS: We reviewed the most cited articles published from 2010 to 2015 in 5 high-impact clinical journals and selected 5 randomized controlled trials and 2 related clinical practice guidelines that are broadly relevant to population health and policy. FINDINGS: We discuss the following themes: (1) expanding indications for drug therapy and the inherent medicalization of the population as highlighted by studies and clinical guidelines supporting lower blood pressure targets or widespread statin use; (2) the tension in nutritional research between quantifying the impact of isolated nutrients and studying specific foods and dietary patterns, for example, the role of the Mediterranean diet in the primary prevention of cardiovascular disease; (3) the issue of high medication costs and the challenge of providing equitable access raised by the development of new and effective treatments for hepatitis C infection; (4) emerging clinical applications of research on the human microbiome as illustrated by fecal transplant to treat Clostridium difficile infections; and (5) the promise and limitations of precision medicine as demonstrated by the rise of novel targeted therapies in oncology. CONCLUSIONS: These developments in clinical science hold promise for improving individual and population health and raise important questions about resource allocation, the role of prevention, and health disparities.

Blood donation and testosterone replacement therapy.

BACKGROUND: Polycythemia is the most common adverse effect of testosterone replacement therapy (TRT) and may predispose patients to adverse vascular events. Current Canadian guidelines recommend regular laboratory monitoring and discontinuing TRT or reducing the dose if the hematocrit exceeds 54% (hemoglobin ≥180 g/L). This threshold has been interpreted by some physicians and patients to indicate the need for phlebotomy or blood donation while on TRT. STUDY DESIGN AND METHODS: We reviewed all male blood donors in Southwestern Ontario at Canadian Blood Services from December 2013 to March 2016 who self-identified or were found on donor screening to be on TRT. Hemoglobin concentration was measured at the time of donation or clinic visit and with each subsequent appointment in repeat donors. RESULTS: We identified 39 patients on TRT who presented for blood donation over a 2-year period. The mean hemoglobin level at all clinic visits was 173 g/L (range, 134-205 g/L; n = 108). Hemoglobin concentrations of 180 g/L or more (calculated hematocrit, ≥54%) were measured at 25% of appointments. Of the 27 repeat donors, 12 (44%) had persistently elevated hemoglobin levels (≥180 g/L) at subsequent donations. CONCLUSION: Hemoglobin concentrations were elevated in donors on TRT, and significant numbers had hemoglobin levels above those recommended by current guidelines. These data also suggest that repeat blood donation was insufficient to maintain a hematocrit below 54%. Our findings raise concerns about the persistent risk of vascular events in these donors, particularly when coupled with the misperception by patients and health care providers that donation has reduced or eliminated the risks of TRT-induced polycythemia.

I and Thou: learning the 'human' side of medicine.

This essay is a reflection on the doctor-patient relationship from the perspective of two medical students, which draws on the ideas of 20th-century philosopher Martin Buber. Although Buber never wrote about medicine directly, his 'philosophy of dialogue' raises fundamental questions about how human beings relate to one another, and can thus offer valuable insights into the nature of the clinical encounter. We argue that Buber's basic word pairs, 'I-You' and 'I-It', provide a useful heuristic for understanding different modes of caring for patients, which we illustrate using examples of illness narratives from two literary works: Tolstoy's Ivan Ilych and Margaret Edson's Wit Our essay demonstrates how the humanities in general and philosophy in particular can inform a more humanistic practice for healthcare trainees and practicing clinicians alike.

Blood Transfusion and the Body in Early Modern France.

This article examines medical discourse surrounding the first animal-to-human blood transfusion performed in 1667 by the French physician Jean-Baptiste Denis. During this period, new physiologies interacted with Galenic medicine in various social milieus that shaped discourse over the body. Although the practice of transfusion was based in contemporary theories of circulation, the therapeutic rationale for transfusion largely appealed to Galenic humouralism. This case reveals how social and intellectual contexts engendered an eclectic corporality, which integrated contemporary natural philosophy within a framework of medical Galenism. Medical discourse from this episode suggests a pluralistic conception of the body--a body that was broadly humoural but included accretions from new physiologies.

Hasty generalizations and generics in medical research: A systematic review.

It is unknown to what extent medical researchers generalize study findings beyond their samples when their sample size, sample diversity, or knowledge of conditions that support external validity do not warrant it. It is also unknown to what extent medical researchers describe their results with precise quantifications or unquantified generalizations, i.e., generics, that can obscure variations between individuals. We therefore systematically reviewed all prospective studies (n = 533) published in the top four highest ranking medical journals, Lancet, New England Journal of Medicine (NEJM), Journal of the American Medical Association (JAMA), and the British Medical Journal (BMJ), from January 2022 to May 2023. We additionally reviewed all NEJM Journal Watch clinical research summaries (n = 143) published during the same time. Of all research articles reporting prospective studies, 52.5% included generalizations beyond specific national study populations, with the numbers of articles with generics varying significantly between journals (JAMA = 12%; Lancet = 77%) (p < 0.001, V = 0.48). There was no evidence that articles containing broader generalizations or generics were correlated with larger or more nationally diverse samples. Moreover, only 10.2% of articles with generalizations beyond specific national populations reported external validity strengthening factors that could potentially support such extrapolations. There was no evidence that original research articles and NEJM Journal Watch summaries intended for practitioners differed in their use of broad generalizations, including generics. Finally, from the journal with the highest citation impact, articles containing broader conclusions were correlated with more citations. Since there was no evidence that studies with generalizations beyond specific national study populations or with generics were associated with larger, more nationally diverse samples, or with reports of population similarity that may permit extensions of conclusions, our findings suggest that the generalizations in many articles were insufficiently supported. Caution against overly broad generalizations in medical research is warranted.

Merkel cell carcinoma mimicking acute leukemia.

Bone marrow aspirate showed diffuse infiltration by a population of monomorphic cells with scant cytoplasm, markedly increased nuclear-to-cytoplasmic ratio, and numerous indistinct nucleoli. Bone marrow biopsy confirmed extensive marrow infiltration by a malignant neoplasm with strong and diffuse expression of synaptophysin by immunohistochemistry, consistent with metastases from Merkel Cell carcinoma.