The COVID-19 pandemic and organ donation and transplantation: ethical issues.

BACKGROUND: The COVID-19 pandemic has had a significant impact on the health system worldwide. The organ and tissue donation and transplantation (OTDT) system is no exception and has had to face ethical challenges related to the pandemic, such as risks of infection and resource allocation. In this setting, many Canadian transplant programs halted their activities during the first wave of the pandemic. METHOD: To inform future ethical guidelines related to the COVID-19 pandemic or other public health emergencies of international concern, we conducted a literature review to summarize the ethical issues. RESULTS: This literature review identified three categories of ethical challenges. The first one describes the general ethical issues and challenges reported by OTDT organizations and transplantation programs, such as risks of COVID-19 transmission and infection to transplant recipients and healthcare professionals during the transplant process, risk of patient waitlist mortality or further resource strain where transplant procedures have been delayed or halted, and resource allocation. The second category describes ethical challenges related to informed consent in the context of uncertainty and virtual consent. Finally, the third category describes ethical issues related to organ allocation, such as social considerations in selecting transplant candidates. CONCLUSION: This literature review highlights the salient ethical issues related to OTDT during the current COVID-19 pandemic. As medical and scientific knowledge about COVID-19 increases, the uncertainties related to this disease will decrease and the associated ethical issues will continue to evolve.

Worldwide management of donors after neurological death: a systematic review and narrative synthesis of guidelines.

OBJECTIVE: The objectives of this study were to systematically identify and describe guidelines for the care of neurologically deceased donors and to evaluate their methodological quality, with the aim of informing and supporting the new Canadian guidelines for the management of organ donors. METHODOLOGY: Following a systematic search, we included any document endorsed by an organ donation organization, a professional society, or a government, that aims to direct the medical management of adult, neurologically deceased, multi-organ donors. We extracted recommendations pertaining to six domains: the autonomic storm, hemodynamic instability, hormone supplementation, ventilation, blood product transfusions, and general intensive care unit (ICU) care. Methodological quality of the guidelines was assessed by the validated AGREE-II tool. MAIN FINDINGS: This review includes 27 clinical practice guidelines representing 26 countries published between 1993 and 2019. Using the AGREE-II validated tool for the evaluation of guidelines' quality, documents generally scored well on their scope and clarity of presentation. Nevertheless, quality was limited in terms of the scientific rigor of guideline development. Recommendations varied substantially across the domains of managing the autonomic storm, subsequent management of hemodynamic instability, hormone therapy, mechanical ventilation, blood product transfusion, and general ICU care. We found consistent recommendations for low tidal volume ventilation subsequent to the publication of a landmark clinical trial. CONCLUSION: Highly inconsistent recommendations for deceased donor care summarized in this review likely reflect the relatively slow emergence of high-quality clinical research in this field, as well as a late uptake of recent validated guideline methodology. Even in this context of few randomized-controlled trials, our group supported the need for new Canadian guidelines for the management of organ donors that follow rigorous recognized methodology and grading of the evidence. TRIAL REGISTRATION: PROSPERO (CRD42018084012); registered 25 February 2016.

RéSUMé: OBJECTIF: Les objectifs de cette étude étaient d'identifier et de décrire de façon systématique les lignes directrices concernant les soins à prodiguer aux donneurs suivant un décès neurologique et d'évaluer leur qualité méthodologique, avec pour but d'informer et d'appuyer les nouvelles lignes directrices canadiennes de prise en charge des donneurs d'organes. MéTHODOLOGIE: À la suite d'une recherche systématique, nous avons inclus tout document endossé par un organisme de dons d'organes, une société professionnelle ou un gouvernement et ayant pour but d'orienter la prise en charge médicale des donneurs adultes d'organes multiples à la suite d'un décès neurologique. Nous avons extrait les recommandations touchant six domaines : la tempête catécholaminergique, l'instabilité hémodynamique, la supplémentation hormonale, la ventilation, les transfusions de produits sanguins et les soins généraux à l'unité de soins intensifs (USI). La qualité méthodologique des lignes directrices a été évaluée avec l'outil validé AGREE-II. CONSTATIONS PRINCIPALES: Cette revue porte sur 27 guides d'exercice cliniques représentant 26 pays et publiés entre 1993 et 2019. En se fondant sur l'outil validé AGREE-II pour l'évaluation de la qualité des lignes directrices, les documents ont en règle générale obtenu un bon score en ce qui touchait à leurs objectifs et à la clarté de leur présentation. Toutefois, la qualité était limitée en matière de rigueur scientifique employée pour la mise au point des lignes directrices. Les recommandations variaient considérablement concernant les questions pertinentes à la prise en charge de la tempête catécholaminergique, à la prise en charge subséquente de l'instabilité hémodynamique, à l'hormonothérapie, à la ventilation mécanique, à la transfusion de produits sanguins, et aux soins généraux à l'USI. À la suite de la publication d'une étude clinique importante, les recommandations concernant la ventilation à volume courant bas étaient constantes. CONCLUSION: Le manque de cohérence des lignes directrices touchant les soins aux donneurs décédés résumées dans cette revue est probablement le reflet de l'émergence relativement lente de recherches cliniques de qualité élevée dans ce domaine, ainsi que de l'adoption tardive des méthodologies récentes et validées pour l'élaboration de lignes directrices. Même dans le contexte actuel de rareté d'études randomisées contrôlées, notre groupe appuie la nécessité de nouvelles lignes directrices canadiennes concernant la prise en charge des donneurs d'organes qui respectent une méthodologie reconnue et rigoureuse ainsi qu'une classification des données probantes. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42018084012); enregistrée le 25 février 2016.

Higher Tumor Burden Neutralizes Negative Margin Status in Hepatectomy for Colorectal Cancer Liver Metastasis.

OBJECTIVE: The aim of this study was to examine if the prognostic significance of margin status in hepatectomy for colorectal cancer liver metastasis (CRLM) varies for different levels of tumor burden because hepatectomy indications for CRLM have been recently expanded to include patients with a higher tumor burden in whom achieving an R0 resection is difficult. METHODS: Clinicopathological variables in an exploration cohort of 290 patients receiving hepatectomy in Japan for CRLM were investigated. R0 resection was defined as a margin width > 0 mm. Tumor burden was assessed using the recently introduced Tumor Burden Score (TBS), which was calculated as TBS2 = (maximum tumor diameter in cm)2 + (number of lesions)2. The principal findings were validated using a cohort from the United States. RESULTS: R1 resection rates significantly increased as TBS increased: 4/86 (4.7%) in patients with TBS < 3, 29/171 (17.0%) in patients with TBS ≥ 3 and < 9, and 9/33 (27.3%) in patients with TBS ≥ 9 (p < 0.001). R0 resection was significantly superior to R1 resection in patients with TBS ≥ 5; however, this was not the case for TBS ≥ 6, as confirmed by both univariate and multivariate analyses. Furthermore, prehepatectomy chemotherapy was associated with significantly improved survival for patients with TBS ≥ 8. Analysis of the validation cohort yielded similar results. CONCLUSIONS: R0 resection appeared to have a positive impact on prognosis among patients with low tumor burden; however, this was not the case for patients with high tumor burden. As such, systemic treatment, in addition to surgery, may be central to achieving satisfactory outcomes in the latter patient population.

Development of the Nova Scotia Potential Donor Audit (PDA) Tool and 2020 Historic Performance Database: Lessons Learned From the First 1000 Medical Record Reviews.

Background: Legislation and accountability frameworks are key components of high-performing deceased-donation systems. In 2021, Nova Scotia (NS), Canada, became the first jurisdiction in North America to enact deemed consent legislation and concurrently implemented mandatory referral legislation similar to that found in other Canadian provinces. Frontline financial resources were provided by the government to support the development of program infrastructure, including implementation of means to evaluate system performance. Methods: The Organ Donation Program (ODP), in collaboration with other stakeholders, developed a Potential Donor Audit (PDA) tool and database for referral intake and manual performance audits. Medical record reviews of deaths in the year before legislative change were conducted to pilot and revise the PDA and evaluate missed donation opportunities. Results: The NS PDA was piloted on 1028 patient deaths. Of 518 patients (50.4%) who met clinical triggers for referral to the ODP, 72 (13.9%) were referred (86.1% missed referral rate). One hundred sixty-three patients met the NS definition of a potential donor; 53 (32.5%) were referred (110 missed potential donors). Referral consent rates reached 71.7% (n = 38 of 53 approaches). The actualized donation rate reported by Canadian Blood Services was 29.9 donors per million population (n = 34 donors). Discussion: We documented high rates of missed referrals and missed potential donors before the enactment of mandatory referral and deemed consent legislation. Conclusions: The ODP has intentionally broadened clinical criteria for referral to shift the responsibility of identifying medically suitable potential donors from bedside clinicians to organ donation specialists. Lessons learned from our experience developing a PDA include the importance of early involvement of multiple stakeholders and ongoing modification of fields and workflow based on data availability and utility for clinical, educational, research, and reporting purposes.

Self-perceived role and knowledge of community pharmacists in organ donation.

BACKGROUND: Although a majority of North Americans is in favor of organ donation, registration remains challenging. Community pharmacists are highly accessible frontline health care professionals that could contribute to a new common registration donation consent system. AIM: The objective of the study was to assess self-perceived professional role and organ donation knowledge of community pharmacists in Quebec. METHOD: We designed a telephone interview survey using a three round modified Delphi process. Following questionnaires testing, we randomly sampled 329 community pharmacists in Quebec. Following administration, we validated the questionnaire by conducting an exploratory factorial analysis using principal component followed by a varimax rotation and rearranging domains and items accordingly. RESULTS: A total of 443 pharmacists were contacted, 329 provided answers to the self-perception role and 216 of them completed the knowledge questionnaire. Overall, community pharmacists of Quebec had a positive view on organ donation and demonstrated interest in acquiring knowledge. Respondents have identified lack of time and high pharmacy attendance as non-limiting barriers to implementing the intervention. The average score on the knowledge questionnaire was 61.2%. CONCLUSION: With the implementation of an appropriate education program to address this knowledge gap, we believe that community pharmacists could be key players in registered organ donation consent.

Pediatric vs Adult or Mixed Trauma Centers in Children Admitted to Hospitals Following Trauma: A Systematic Review and Meta-Analysis.

Importance: Adult trauma centers (ATCs) have been shown to decrease injury mortality and morbidity in major trauma, but a synthesis of evidence for pediatric trauma centers (PTCs) is lacking. Objective: To assess the effectiveness of PTCs compared with ATCs, combined trauma centers (CTCs), or nondesignated hospitals in reducing mortality and morbidity among children admitted to hospitals following trauma. Data Sources: MEDLINE, Embase, and Web of Science through March 2023. Study Selection: Studies comparing PTCs with ATCs, CTCs, or nondesignated hospitals for pediatric trauma populations (aged ≤19 years). Data Extraction and Synthesis: This systematic review and meta-analysis was performed following the Preferred Reporting Items for Systematic Review and Meta-analysis and Meta-analysis of Observational Studies in Epidemiology guidelines. Pairs of reviewers independently extracted data and evaluated risk of bias using the Risk of Bias in Nonrandomized Studies of Interventions tool. A meta-analysis was conducted if more than 2 studies evaluated the same intervention-comparator-outcome and controlled minimally for age and injury severity. Subgroup analyses were planned for age, injury type and severity, trauma center designation level and verification body, country, and year of conduct. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to assess certainty of evidence. Main Outcome(s) and Measure(s): Primary outcomes were mortality, complications, functional status, discharge destination, and quality of life. Secondary outcomes were resource use and processes of care, including computed tomography (CT) and operative management of blunt solid organ injury (SOI). Results: A total of 56 studies with 286 051 participants were included overall, and 34 were included in the meta-analysis. When compared with ATCs, PTCs were associated with a 41% lower risk of mortality (OR, 0.59; 95% CI, 0.46-0.76), a 52% lower risk of CT use (OR, 0.48; 95% CI, 0.26-0.89) and a 64% lower risk of operative management for blunt SOI (OR, 0.36; 95% CI, 0.23-0.57). The OR for complications was 0.80 (95% CI, 0.41-1.56). There was no association for mortality for older children (OR, 0.71; 95% CI, 0.47-1.06), and the association was closer to the null when PTCs were compared with CTCs (OR, 0.73; 95% CI, 0.53-0.99). Results remained similar for other subgroup analyses. GRADE certainty of evidence was very low for all outcomes. Conclusions and Relevance: In this systematic review and meta-analysis, results suggested that PTCs were associated with lower odds of mortality, CT use, and operative management for SOI than ATCs for children admitted to hospitals following trauma, but certainty of evidence was very low. Future studies should strive to address selection and confounding biases.