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  • Quality Assurance of Undergraduate Medical Education in Israel by Continuous Monitoring and Prioritization of the Accreditation Standards

    External accreditation reviews of undergraduate medical curricula play an important role in their quality assurance. However, these reviews occur only at 4–10-year intervals and are not optimal for the immediate identification of problems related to teaching. Therefore, the Standards of Medical Education in Israel require medical schools to engage in continuous, ongoing monitoring of their teaching programs for compliance with accreditation standards. In this paper, we propose the following: (1) this monitoring be assigned to independent medical education units (MEUs), rather than to an infrastructure of the dean’s office, and such MEUs to be part of the school governance and draw their authority from university institu¬tions; and (2) the differences in the importance of the accreditation standards be addressed by discerning between the “most important” standards that have been shown to improve student well-being and/or patient health outcomes; “important” standards associated with student learning and/or performance; “possibly important” standards with face validity or conflicting evidence for validity; and “least important” standards that may lead to undesirable consequences. According to this proposal, MEUs will evolve into entities dedicated to ongoing monitoring of the education program for compliance with accreditation standards, with an authority to implement interventions. Hopefully, this will provide MEUs and faculty with the common purpose of meeting accreditation requirements, and an agreed-upon prioritization of accreditation standards will improve their communication and recommendations to faculty.
  • Biomarkers in External Apical Root Resorption: An Evidence-based Scoping Review in Biofluids

    Background: External apical root resorption (EARR), an unwanted sequela of orthodontic treatment, is difficult to diagnose radiographically. Hence, the current scoping review was planned to generate critical evidence related to biomarkers in oral fluids, i.e. gingival crevicular fluid (GCF), saliva, and blood, of patients showing root resorption, compared to no-resorption or physiologic resorption. Methods: A literature search was conducted in major databases along with a manual search of relevant articles in the library, and further search from references of the related articles in March 2021. The initial search was subjected to strict inclusion and exclusion criteria according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Results: Following PRISMA guidelines, 20 studies were included in the final review. The studies included human clinical trials and cross-sectional and prospective studies with/without control groups with no date/ language restriction. Various biomarkers identified in EARR included dentinal proteins, enzymes, cytokines, and salivary proteins. Severe resorption had higher dentin sialoprotein (DSP) and resorption protein concentrations as well as lower granulocyte-macrophage colony-stimulating factor (GM-CSF) as compared with mild resorption. Increased DSP and dentin phosphophoryn (DPP) expression was found in physiologic resorption. Compared to controls, resorbed teeth showed a higher receptor activator of nuclear factor kappa B ligand/ osteoprotegerin (RANKL/OPG) ratio. In contrast, levels of anti-resorptive mediators (IL-1RA, IL-4) was significantly decreased. Differences in force levels (150 g and 100 g) showed no difference in resorption, but a significant rise in biomarkers (aspartate transaminase [AST] and alkaline phosphatase [ALP]) for 150 g force. Moderate to severe resorption in young patients showed a rise in specific salivary proteins, requiring further validation. Limitations of the studies were heterogeneity in study design, biomarker collection, sample selection, and confounding inflammatory conditions. Conclusions: Various biomarkers in biofluids indicate active resorption, while resorption severity was associated with DSP and GM-CSF in GCF, and a few salivary proteins. However, a robust study design in the future is mandated.
  • Remembering Dr Mark/Meir Dvorjetski: Physician, Survivor, Teacher, Historian, and Pioneer of Shoah Medicine Research

    Meir Dvorjetski was a Holocaust survivor, teacher, and historian. He is best remembered for his descriptions of the medicine practiced by the Nazis during World War II, as well as the diseases, disorders, syndromes, and deaths resulting from such practice—particularly, though not solely, on the Jewish race. Dvorjetski’s contributions to Holocaust research at Bar-Ilan University in Israel, his underground partisan work, his contributions to society, and his testimony at the Eichmann trial have all been well documented. However, his earlier years—including his survival of the Holocaust, and his less-known medical achievements and contributions to historical records regarding the Holocaust—have not been covered as thoroughly. These latter items are the focus of this paper, with a closing commentary on the relevance of his work for the 21st century.
  • Navigating the Complexity of Alternating Hemiplegia in Childhood: A Comprehensive Review

    Alternating hemiplegia of childhood (AHC) is a complex neurodevelopmental disorder characterized by paroxysmal and transient events of unilateral or bilateral paresis, usually occurring before 18 months of age. Mutations in the ATP1A3 gene, mainly p.Asp801Asn, p.Glu815Lys, and p.Gly947Arg at the protein level, are found in around 80% of the individuals with AHC. Interestingly, these mutations reflect the degree of severity of the neurological symptoms (p.Glu815Lys > p.Asp801Asn > p.Gly947Arg). Some channels involved in this disorder are N-type voltage-gated calcium channels, ATP-sensitive potassium channels, and the sodium/calcium exchanger. In this context, the management of AHC should be divided into the treatment of attacks, prophylactic treatment, and management of comorbidities commonly found in this group of individuals, including epilepsy, attention-deficit/hyperactivity disorder, aggressive behavior, cognitive impairment, movement disorders, and migraine. The importance of an integrated approach with a multidisciplinary team, such as neuropsychologists and dietitians, is worth mentioning, as well as the follow-up with a neurologist. In the present study, we propose new diagnostic criteria for AHC, dividing it into clinical, laboratory, supporting, and atypical features. Also, we review the location of the mutations in the ATP1A3 protein of individuals with AHC, rapid-onset dystonia-parkinsonism (RDP) variants, and early infantile epileptic encephalopathy (variants with hemiplegic attack). We also include a section about the animal models for ATP1A3 disorders.
  • Technological Developments and Strategic Management for Overcoming the COVID-19 Challenge within the Hospital Setting in Israel

    The coronavirus disease 2019 (COVID-19) pandemic has remarkably challenged health care organizations and societies. A key strategy for confronting the disease implications on individuals and communities was based on harnessing multidisciplinary efforts to develop technologies for mitigating the disease spread and its deleterious clinical implications. One of the main challenging characteristics of COVID-19 is the provision of medical care to patients with a highly infective disease mandating the use of isolation measures. Such care is complicated by the need for complex critical care, dynamic treatment guidelines, and a vague knowledge regarding the disease’s pathophysiology. A second key component of this challenge was the over¬whelming surge in patient burden and the relative lack of trained staff and medical equipment which required rapid re-organization of large systems and augmenting health care efficiencies to unprecedented levels. In contrast to the risk management strategies employed to mitigate other serious threats and the billions of dollars that are invested in reducing these risks annually by governments around the world, no such preparation has been shown to be of effect during the current COVID-19 pandemic. Unmet needs were identified within the newly opened COVID-19 departments together with the urgent need for reliable information for effective decision-making at the state level. This review article describes the early research and development response in Israel under the scope of in-hospital patient care, such as non-contact sensing of patients’ vital signs, and how it could potentially be weaved into a practical big picture at the hospital or national level using a strategic management system. At this stage, some of the described technologies are still in developmental or clinical evidence generation phases with respect to COVID-19 settings. While waiting for future publications describing the results of the ongoing evidence generation efforts, one should be aware of this trend as these emerging tools have the potential to further benefit patients as well as caregivers and health care systems beyond the scope of the current pandemic as well as confronting future surges in the number of cases.
  • Israeli Position Paper: Triage Decisions for Severely Ill Patients During the COVID-19 Pandemic. Joint Commission of the Israel National Bioethics Council, the Ethics Bureau of the Israel Medical Association and Representatives from the Israeli Ministry of Health

    Objectives: This document provides an English translation of the Israeli Joint Commission’s national guidelines for triaging severely ill patients during the coronavirus disease 2019 (COVID-19) pandemic. Methods: Four subcommittees of medical, legal, ethical-social, and religious experts developed the general principles and practical medical criteria for triaging scarce life-saving resources. Results: The guidelines provide an overview of general principles as well as pragmatic medical criteria and a practical triage protocol to be followed should the healthcare system be overwhelmed due to COVID-19. Issues covered include triggers for activating the guidelines, guiding ethical, legal, and religious principles, equity in access, fair distribution, transparency, consistency, palliation, medical policy prioritization, problem-solving mechanisms, and public trust. Conclusions: The Israeli consensus document and pragmatic medical triage protocol offer a societal and medical roadmap for allocating scarce resources during the COVID-19 pandemic or other disasters.
  • Hydroxychloroquine and Coronavirus Disease 2019: A Systematic Review of a Scientific Failure

    Introduction: Hydroxychloroquine (HCQ) emerged early in the course of the coronavirus disease 2019 (COVID-19) pandemic as a possible drug with potential therapeutic and prophylactic benefits. It was quickly adopted in China, Europe, and the USA. We systematically reviewed the existing clinical evidence of HCQ use for the prevention and treatment of COVID-19. Methods: We screened for clinical studies describing HCQ administration to treat or prevent COVID-19 in PubMed. We included randomized controlled trials (RCTs), non-randomized comparative cohorts, and case series studies that had all undergone peer review. Results: A total of 623 studies were screened; 17 studies evaluating HCQ treatment were included. A total of 13 were observational studies, and 4 were RCTs. In terms of effect on mortality rates, observational studies provided conflicting results. As a whole, RCTs, including one large British RCT that has not yet been published, showed no significant effect of HCQ on mortality rates, clinical cure, and virologic response. The use of HCQ as a post-exposure prophylactic agent was found to be ineffective in one RCT. Conclusion: There is no evidence supporting HCQ for prophylaxis or treatment of COVID-19. Many observational trials were methodologically flawed. Scientific efforts have been disappointingly fragmented, and well-conducted trials have only recently been completed, more than 7 months and 600,000 deaths into the pandemic.
  • Post-Mortem Pedagogy: A Brief History of the Practice of Anatomical Dissection

    Anatomical dissection is almost ubiquitous in modern medical education, masking a complex history of its practice. Dissection with the express purpose of understanding human anatomy began more than two millennia ago with Herophilus, but was soon after disavowed in the third century BCE. Historical evidence suggests that this position was based on common beliefs that the body must remain whole after death in order to access the afterlife. Anatomical dissection did not resume for almost 1500 years, and in the interim anatomical knowledge was dominated by (often flawed) reports generated through the comparative dissection of animals. When a growing recognition of the utility of anatomical knowledge in clinical medicine ushered human dissection back into vogue, it recommenced in a limited setting almost exclusively allowing for dissection of the bodies of convicted criminals. Ultimately, the ethical problems that this fostered, as well as the increasing demand from medical education for greater volumes of human dissection, shaped new considerations of the body after death. Presently, body bequeathal programs are a popular way in which individuals offer their bodies to medical education after death, suggesting that the once widespread views of dissection as punishment have largely dissipated.
  • Alternating and Concurrent True Hyperkalemia and Pseudohyperkalemia in Adult Sickle Cell Disease

    Sickle cell disease (SCD) predisposes the patient to recurrent episodes of acute painful hemolytic crisis. Sickle cell nephropathy (SCN) is not uncommon in adult patients, and renal manifestations of SCN include renal ischemia, microinfarcts, renal papillary necrosis, and renal tubular abnormalities with variable clinical presentations. Intravascular hemolysis and reduced glomerular filtration rate with renal tubular dysfunction predispose to true hyperkalemia. Hemolytic crisis can be complicated by sepsis, leading to significant degrees of thrombocytosis, and thrombocytosis is a well-defined cause of pseudohyperkalemia. We describe a 40-year-old African American male patient with sickle cell anemia who exhibited alternating episodes of true hyperkalemia and pseudohyperkalemia, during consecutive hospital admissions. Clearly, true hyperkalemia is a potentially lethal condition. At the same time, the institution of inappropriate and intensive treatment of pseudohyperkalemia leading to severe hypokalemia is also potentially lethal. The need for this caution is most imperative with the recent introduction of the safer and more potent potassium binders, patiromer and sodium zirconium cyclosilicate.
  • Circulating Proprotein Convertase Subtilisin/Kexin Type 9 Levels Predict Future Cardiovascular Event Risks in Hemodialyzed Black African Patients

    Context and Objective: Cardiovascular diseases are the leading cause of mortality in patients. In this context, proprotein convertase subtilisin/kexin type 9 (PCSK9) appears to be the new biomarker identified as interfering in lipid homeostasis. This study aimed to investigate the association between PCSK9, dyslipidemia, and future risk of cardiovascular events in a population of black Africans. Methods: A cross-sectional study was conducted between August 2016 and July 2020 in six hemodialysis centers in the city of Kinshasa, Democratic Republic of the Congo. Serum PCSK9 was measured by ELISA; lipid levels of 251 chronic kidney disease grade 5 (CKD G5) hemodialysis patients and the Framingham predictive instrument were used for predicting cardiac events. Results: Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and triglycerides (TG) were significantly increased in the tertile with the highest PCSK9. By contrast, high-density lipoprotein cholesterol (HDL-c) was significantly decreased in the same tertile. A strong positive and significant correlation was found between PCSK9 and TC, TG, and LDL-c. Negative and significant correlation was observed between PCSK9 and HDL-c. The levels of PCSK9, smoking, overweight, and atherogenic dyslipidemia were associated with future risks for cardiovascular events in univariate analysis. After adjustment, all these variables persisted as independent determinants of future risk for cardiovascular events. The probability of having a cardiovascular event in this population was independently associated with PCSK9 levels. Compared to the patients having lowest PCSK9 tertile, patients with PCSK9 levels in the middle (aOR 5.9, 95% CI 2.06-17.3, P<0.001) and highest tertiles (aOR 8.9, 95% CI 3.02-25.08, P<0.001) presented a greater risk of cardiac event. Conclusion: Increased PCSK9 serum levels are associated with higher levels of TC, LDL-c, and TG and lower levels of HDL-c in black African hemodialysis patients. Serum PCSK9 levels in these patients predict increased risk of cardiovascular events, independent of traditional potential confounders.