COVID-19 critical care triage across Canada: a narrative synthesis and ethical analysis of early provincial triage protocols.

PURPOSE: The COVID-19 pandemic created conditions of scarcity that led many provinces within Canada to develop triage protocols for critical care resources. In this study, we sought to undertake a narrative synthesis and ethical analysis of early provincial pandemic triage protocols. METHODS: We collected provincial triage protocols through personal correspondence with academic and political stakeholders between June and August 2020. Protocol data were extracted independently by two researchers and compared for accuracy and agreement. We separated data into three categories for comparative content analysis: protocol development, ethical framework, and protocol content. Our ethical analysis was informed by a procedural justice framework. RESULTS: We obtained a total of eight provincial triage protocols. Protocols were similar in content, although age, physiologic scores, and functional status were variably incorporated. Most protocols were developed through a multidisciplinary, expert-driven, consensus process, and many were informed by influenza pandemic guidelines previously developed in Ontario. All protocols employed tiered morality-focused exclusion criteria to determine scarce resource allocation at the level of regional health care systems. None included a public engagement phase, although targeted consultation with public advocacy groups and relevant stakeholders was undertaken in select provinces. Most protocols were not publicly available in 2020. CONCLUSIONS: Early provincial COVID-19 triage protocols were developed by dedicated expert committees under challenging circumstances. Nonetheless, few were publicly available, and public consultation was limited. No protocols were ever implemented, including during periods of extreme critical care surge. A national approach to pandemic triage that incorporates additional aspects of procedural justice should be considered in preparation for future pandemics.

RéSUMé: OBJECTIF: La pandémie de COVID-19 a créé des conditions de pénurie qui ont amené de nombreuses provinces canadiennes à élaborer des protocoles de triage pour l'allocation des ressources en soins intensifs. Dans le cadre de cette étude, nous avons cherché à réaliser une synthèse narrative et une analyse éthique des premiers protocoles provinciaux de triage lors de la pandémie. MéTHODE: Nous avons recueilli les protocoles de triage provinciaux en correspondant de façon personnelle avec des intervenant·es universitaires et politiques entre juin et août 2020. Les données des protocoles ont été extraites indépendamment par deux personnes de l'équipe de recherche et comparées pour en vérifier l'exactitude et la concordance. Nous avons séparé les données en trois catégories pour l'analyse comparative du contenu : l'élaboration d'un protocole, le cadre éthique et le contenu du protocole. Notre analyse éthique s'est appuyée sur un cadre de justice procédurale. RéSULTATS: Nous avons obtenu un total de huit protocoles de triage provinciaux. Les protocoles étaient similaires dans leur contenu, bien que l'âge, les scores physiologiques et l'état fonctionnel aient été incorporés de manière variable. La plupart des protocoles ont été élaborés dans le cadre d'un processus consensuel multidisciplinaire dirigé par des expert·es, et bon nombre d'entre eux ont été élaborés en fonction des lignes directrices sur la pandémie de grippe élaborées antérieurement en Ontario. Tous les protocoles utilisaient des critères d'exclusion à plusieurs niveaux axés sur la moralité pour déterminer l'affectation de ressources limitées au niveau des systèmes de soins de santé régionaux. Aucun ne comportait de phase de mobilisation du public, bien que des consultations ciblées aient été menées auprès des groupes de défense des droits du public et des instances concernées dans certaines provinces. La plupart des protocoles n'étaient pas accessibles au public en 2020. CONCLUSION: Les premiers protocoles provinciaux de triage pour la COVID-19 ont été élaborés par des comités spécialisés d'expert·es dans des circonstances difficiles. Néanmoins, peu d'entre eux étaient accessibles au public et la consultation publique était limitée. Aucun protocole n'a été mis en œuvre, même pendant les périodes de pointe extrême en soins intensifs. Une approche nationale du triage en cas de pandémie qui intègre d'autres aspects de justice procédurale devrait être envisagée en prévision de futures pandémies.

Vibrio cholerae biofilms use modular adhesins with glycan-targeting and nonspecific surface binding domains for colonization.

Bacterial biofilms are formed on environmental surfaces and host tissues, and facilitate host colonization and antibiotic resistance by human pathogens. Bacteria often express multiple adhesive proteins (adhesins), but it is often unclear whether adhesins have specialized or redundant roles. Here, we show how the model biofilm-forming organism Vibrio cholerae uses two adhesins with overlapping but distinct functions to achieve robust adhesion to diverse surfaces. Both biofilm-specific adhesins Bap1 and RbmC function as a "double-sided tape": they share a ß-propeller domain that binds to the biofilm matrix exopolysaccharide, but have distinct environment-facing domains. Bap1 adheres to lipids and abiotic surfaces, while RbmC mainly mediates binding to host surfaces. Furthermore, both adhesins contribute to adhesion in an enteroid monolayer colonization model. We expect that similar modular domains may be utilized by other pathogens, and this line of research can potentially lead to new biofilm-removal strategies and biofilm-inspired adhesives.

'Swear by Thy Gracious Self': North American Medical Oath-Taking in 2014/2015.

Over the past century, six studies - the most recent data from 2000 - and one review have comprehensively examined the content of medical oaths and oath-taking practices, all focusing on North America, providing an insight into the ethical beliefs of each era. Our study sought to establish a new point of reference. In 2014/2015, oaths from 150 of all 153 US and Canadian medical schools were collected and analyzed. All but one school administered medical oaths and most schools administered more than one. Since 2000, student-written oaths became more popular, and new themes, such as self-care and professionalism, were identified in the oaths for the first time. However, as was identified in 2000, the oaths' contents are disparate and even conflicting at times, raising questions as to whether medicine is being taught or practiced with a coherent ethical worldview.

Regulation of the interactions between human eIF5 and eIF1A by the CK2 kinase.

Translation initiation in eukaryotes relies on a complex network of interactions that are continuously reorganized throughout the process. As more information becomes available about the structure of the ribosomal preinitiation complex (PIC) at various points in translation initiation, new questions arise about which interactions occur when, their roles, and regulation. The eukaryotic translation factor (eIF) 5 is the GTPase-activating protein (GAP) for the GTPase eIF2, which brings the initiator Met-tRNAi to the PIC. eIF5 also plays a central role in PIC assembly and remodeling through interactions with other proteins, including eIFs 1, 1A, and 3c. Phosphorylation by casein kinase 2 (CK2) significantly increases the eIF5 affinity for eIF2. The interaction between eIF5 and eIF1A was reported to be mediated by the eIF5 C-terminal domain (CTD) and the eIF1A N-terminal tail. Here, we report a new contact interface, between eIF5-CTD and the oligonucleotide/oligosaccharide-binding fold (OB) domain of eIF1A, which contributes to the overall affinity between the two proteins. We also show that the interaction is modulated by dynamic intramolecular interactions within both eIF5 and eIF1A. CK2 phosphorylation of eIF5 increases its affinity for eIF1A, offering new insights into the mechanisms by which CK2 stimulates protein synthesis and cell proliferation.

Tuberculosis Aortitis and Mycotic Pseudo-aneurysm of the Infra-renal Aorta after Intravesicular BCG Therapy.

We report a patient who presented with a rapidly expanding symptomatic tuberculous aortitis and mycotic pseudo-aneurysm of the infra-renal aorta, after intra-vesical BCG chemotherapy for bladder cancer, treated by required emergency open aneurysm repair. His case highlights this rare complication of intravesical BCG treatment, haematological seeding causing tuberculous aortitis and mycotic pseudo-aneurysm formation of the infra-renal aorta. It also illustrates successful treatment with emergency open surgery, local debridement of mycotic pseudoaneurysm, in-situ surgical reconstruction using a custom bovine-wrap interposition graft to create a neo-aorta and multi-agent anti-tuberculous chemotherapy.

Access-to-Care and Conscience: Conflicting or Coherent?

"Intervention" is not synonymous with "care." For an intervention to constitute care-which patients should have a right to access-it must be technically feasible and licit. Now these criteria do not prove sufficient; numerous archaic interventions remain feasible and legally permissible, yet are now bywords for spurious care. Therefore, we propound another necessary condition for an intervention to become care: the physician must rationally judge the intervention to be conducive to the patient's good. Consequently, the right of access-to-care relies on physicians being free to practice medicine in accord with their consciences, conscience being the rational faculty with which they judge the reasonableness of even mundane medical decisions. Since physicians operate as part of a community, it is further necessary to consider when central bodies may reasonably compel physicians to engage in interventions that the physician believes are not consistent with the patient's good and/or are not congruent with the purposes of medicine.

Dynamic interaction network involving the conserved intrinsically disordered regions in human eIF5.

Translation initiation in eukaryotes requires multiple eukaryotic translation initiation factors (eIFs) and involves continuous remodeling of the ribosomal preinitiation complex (PIC). The GTPase eIF2 brings the initiator Met-tRNAi to the PIC. Upon start codon selection and GTP hydrolysis, promoted by eIF5, eIF2-GDP is released in complex with eIF5. Here, we report that two intrinsically disordered regions (IDRs) in eIF5, the DWEAR motif and the C-terminal tail (CTT) dynamically contact the folded C-terminal domain (CTD) and compete with each other. The eIF5-CTD•CTT interaction favors eIF2ß binding to eIF5-CTD, whereas the eIF5-CTD•DWEAR interaction favors eIF1A binding, which suggests how intramolecular contact rearrangement could play a role in PIC remodeling. We show that eIF5 phosphorylation by CK2, which is known to stimulate translation and cell proliferation, significantly increases the eIF5 affinity for eIF2. Our results also indicate that the eIF2ß subunit has at least two, and likely three eIF5-binding sites.

The rule of right vs might: a reply to Wischik's 'Nazis, teleology, and the freedom of conscience'.

Wischik presents an extensive reply to our paper on conscientious objection, which explores the implications of distinguishing 'medical acts' from 'socioclinical acts'. He provides an extensive legal analysis of the issues surrounding conscientious objection, drawing on the concepts of professional practice and consequentialism. Invoking some of these concepts, we respond and demonstrate that Wischik does not seriously engage with our argument. Instead, he merely proffers his preference for legal positivism, which - when viewed as the fount of justice (as Wischik seems to hold) instead of a tool in its service - necessarily bases rightness on might rather than truth. We also argue that in several important areas, Wischik is factually mistaken.

Should parents be asked to consent for life-saving paediatric interventions?

Informed consent, when given by proxy, has limitations: chiefly, it must be made in the interest of the patient. Here we critique the standard approach to parental consent, as present in Canada and the UK. Parents are often asked for consent, but are not given the authority to refuse medically beneficial treatment in many situations. This prompts the question of whether it is possible for someone to consent if they cannot refuse. We present two alternative and philosophically more consistent frameworks for paediatric proxy consent. The first allows meaningful consent (parents may say 'yes' or 'no' to treatment), provided that parents are medically informed/competent and intend the health and well-being of their child. In the second solution, medical practitioners or the state consent for treatment, with parents only being consulted to help give insight to the child's circumstances. While we contend that either of these two options is superior to the insincerity of the present paradigm, we suggest that the first solution is preferable.

Medical Acts and Conscientious Objection: What Can a Physician be Compelled to Do?

A key question has been underexplored in the literature on conscientious objection: if a physician is required to perform 'medical activities,' what is a medical activity? This paper explores the question by employing a teleological evaluation of medicine and examining the analogy of military conscripts, commonly cited in the conscientious objection debate. It argues that physicians (and other healthcare professionals) can only be expected to perform and support medical acts - acts directed towards their patients' health. That is, physicians cannot be forced to provide or support services that are not medical in nature, even if such activities support other socially desirable pursuits. This does not necessarily mean that medical professionals cannot or should not provide non-medical services, but only that they are under no obligation to provide them.

To die, to sleep, perchance to dream? A response to DeMichelis, Shaul and Rapoport.

In developing their policy on paediatric medical assistance in dying (MAID), DeMichelis, Shaul and Rapoport decide to treat euthanasia and physician-assisted suicide as ethically and practically equivalent to other end-of-life interventions, particularly palliative sedation and withdrawal of care (WOC). We highlight several flaws in the authors' reasoning. Their argument depends on too cursory a dismissal of intention, which remains fundamental to medical ethics and law. Furthermore, they have not fairly presented the ethical analyses justifying other end-of-life decisions, analyses and decisions that were generally accepted long before MAID was legal or considered ethical. Forgetting or misunderstanding the analyses would naturally lead one to think MAID and other end-of-life decisions are morally equivalent. Yet as we recall these well-developed analyses, it becomes clear that approving of some forms of sedation and WOC does not commit one to MAID. Paediatric patients and their families can rationally and coherently reject MAID while choosing palliative care and WOC. Finally, the authors do not substantiate their claim that MAID is like palliative care in that it alleviates suffering. It is thus unreasonable to use this supposition as a warrant for their proposed policy.

Is the Writing on the Wall for Current Medical Oaths? A Brief Historical Review of Oath Taking at Medical Schools.

Oaths recited in medical schools provide valuable insight into the medical profession's evolving core of ethical commitments. This study presents a brief overview of medical oaths, and how they came to attain their current prominence. The authors examine medical oaths used in twentieth-century North America (the USA and Canada) through a critical review of six studies on oath administration and content that were undertaken between 1928 and 2004. While oath-taking became almost universally prevalent in twentieth-century North American medical schools, the ethical content of oaths grew increasingly heterogeneous. The findings challenge assumptions about the content of medical oaths. They also create dynamic markers for gauging the variability in the current ethical milieus of medical education, providing a basis for evaluating future direction.

Reasonable Parental and Medical Obligations in Pediatric Extraordinary Therapy.

The English cases of Charlie Gard and Alfie Evans involved a conflict between the desires of their parents to preserve their children's lives and judgments of their medical teams in pursuit of clinically appropriate therapy. The treatment the children required was clearly extraordinary, including a wide array of advanced life-sustaining technological support. The cases exemplify a clash of worldviews rooted in different philosophies of life and medical care. The article highlights the differing perspectives on parental authority in medical care in England, Canada, and the United States. Furthermore, it proposes a solution that accommodates for both reasonable parental desires and professional medical opinion. This is achieved by looking at concepts of extraordinary therapy, best interest, reasonable parenthood and medical objections. Summary: In cases where a child's treatment involves extraordinary therapy, there is often a conflict of opinion between the medical team and the parents with regard to the best course of action. The assumption should be that responsible, caring parents make reasonable and acceptable decisions for the good of their children. Rather than focusing on making a hypothetical best interest judgment, courts should in the first instance side with the parents. Only when parents act unreasonably or malevolently should their wishes be overridden. This should not affect the medics' right to conscientiously object towards carrying out procedures that they deem to be medically unnecessary or harmful.

Teleology and Defining Sex.

Disorders of sexual differentiation lead to what is often referred to as an intersex state. This state has medical, as well as some legal, recognition. Nevertheless, the question remains whether intersex persons occupy a state in between maleness and femaleness or whether they are truly men or women. To answer this question, another important conundrum needs to be first solved: what defines sex? The answer seems rather simple to most people, yet when morphology does not coincide with haplotypes, and genetics might not correlate with physiology the issue becomes more complex. This paper tackles both issues by establishing where the essence of sex is located and by superimposing that framework onto the issue of the intersex. This is achieved through giving due consideration to the biology of sexual development, as well as through the use of a teleological framework of the meaning of sex. Using a range of examples, the paper establishes that sex cannot be pinpointed to one biological variable but is rather determined by how the totality of one's biology is oriented towards biological reproduction. A brief consideration is also given to the way this situation could be comprehended from a Christian understanding of sex and suffering.