Variability in deceased donor care in Canada: a report of the Canada-DONATE cohort study.

PURPOSE: Canadian donor management practices have not been reported. Our aim was to inform clinicians and other stakeholders about the range of current practices. METHODS: This prospective observational cohort study enrolled consecutive, newly consented organ donors from August 1 2015 to July 31 2018 at 27 academic and five community adult intensive care units in British Columbia, Alberta, Ontario, and Quebec. Research staff prospectively recorded donor management data. Provincial organ donation organizations verified the organs donated. We formally compared practices across provinces. RESULTS: Over a median collection period of eight months, 622 potential donors were classified at baseline as having neurologic determination of death (NDD donors; n = 403) or circulatory death (DCD donors; n = 219). Among NDD donors, 85.6% underwent apnea testing (rarely with carbon dioxide insufflation), 33.2% underwent ancillary testing, and subsequent therapeutic hypothermia (34-35°C) was rare. Neurologic determination of death donors were more hemodynamically unstable with most having received vasopressin and norepinephrine infusions, with a large majority having received high-dose corticosteroids and intravenous thyroxine. Among DCD donors, 61.6% received corticosteroids, and 8.9% received thyroxine. Most donors did not receive lung-protective ventilation strategies. Invasive procedures after donation consent included bronchoscopy (71.7%), cardiac catheterization (NDD donors only; 21.3%), and blood transfusions (19.3%). Physicians ordered intravenous antemortem heparin for 94.8% of DCD donors. The cohort donated 1,629 organs resulting in 1,532 transplants. Case selection, death determinations, and hormone, nutrition and heparin practices all varied across provinces. CONCLUSION: These study findings highlight areas for knowledge translation and further clinical research. Interprovincial discrepancies will likely pose unique challenges to national randomized trials. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT03114436); registered 10 April, 2017.

RéSUMé: OBJECTIF: Les pratiques canadiennes de prise en charge des donneurs n'ont pas été rapportées. Notre objectif était d'informer les cliniciens et autres parties intéressées quant à l'éventail des pratiques actuelles. MéTHODE: Cette étude de cohorte observationnelle et prospective a recruté des donneurs d'organes consécutifs ayant récemment consenti au don entre le 1er août 2015 et le 31 juillet 2018 dans 27 unités de soins intensifs universitaires et cinq unités de soins intensifs pour adultes en milieu communautaire en Colombie-Britannique, en Alberta, en Ontario et au Québec. Le personnel de recherche a enregistré de manière prospective les données de prise en charge des donneurs. Les organismes de dons d'organes provinciaux ont vérifié les organes donnés. Nous avons formellement comparé les pratiques d'une province à l'autre. RéSULTATS: Sur une période médiane de collecte de huit mois, 622 donneurs potentiels ont été catégorisés au départ comme ayant un diagnostic de décès neurologique (donneurs DDN; n = 403) ou un décès cardiocirculatoire (donneurs DDC; n = 219). Parmi les donneurs DDN, 85,6 % ont subi un test d'apnée (rarement avec insufflation de dioxyde de carbone), 33,2 % ont subi des tests complémentaires, et une hypothermie thérapeutique subséquente (34-35°C) était rare. Les donneurs par diagnostic de décès neurologique étaient plus instables hémodynamiquement, la plupart ayant reçu des perfusions de vasopressine et de norépinéphrine, et une vaste majorité de ces donneurs ont reçu des corticostéroïdes à forte dose ainsi que de la thyroxine intraveineuse. Parmi les donneurs par DDC, 61,6 % avaient reçu des corticostéroïdes, et 8,9 % de la thyroxine. La plupart des donneurs n'avaient pas bénéficié de stratégies de ventilation protectrice des poumons. Les interventions invasives réalisées après le consentement au don comprenaient la bronchoscopie (71,7 %), le cathétérisme cardiaque (donneurs DDN seulement; 21,3 %) et les transfusions sanguines (19,3 %). Les médecins ont prescrit de l'héparine intraveineuse ante mortem chez 94,8 % des donneurs DDC. La cohorte a donné 1629 organes, résultant en 1532 greffes. La sélection de cas, la détermination de décès et les pratiques hormonales, nutritionnelles et hépariniques variaient toutes d'une province à l'autre. CONCLUSION: Ces résultats soulignent des domaines propices à la transmission de connaissances et aux recherches cliniques plus poussées. Les différences interprovinciales poseront probablement des défis uniques pour les études randomisées nationales. Enregistrement de l'étude : www.clinicaltrials.gov (NCT03114436); enregistrée le 10 avril 2017.

The impact of bariatric surgery on insulin-treated type 2 diabetes patients.

INTRODUCTION: Bariatric surgery has been shown to lead to significant improvement in glucose homeostasis, resulting in greater rates of type 2 diabetes mellitus (T2DM) remission. While there is substantial evidence of the benefits of bariatric/metabolic surgery in obese diabetic patients on oral therapy (O-T2D), more evidence is necessary in the case of insulin-treated type 2 diabetes (I-T2D) patients and the selection of surgical procedure. METHODS: Analysis of the Ontario Bariatric Registry data was performed, comparing outcomes of Roux-en-Y-gastric bypass (RYGB) and sleeve gastrectomy (SG) on insulin-treated versus non-insulin-treated T2DM patients. We compared weight loss, medication use and remission rates during a 3-year follow up. RESULTS: A total of 3668 diabetic Bariatric Registry patients underwent surgery from Jan 2010 to Feb 2017, across 7 Bariatric Centers of Excellence in Ontario. Of these 2872 were O-T2D and 1187 were I-T2D. Weight loss was similar between the two groups at 3 years; with mean %WL of 30.1% for the insulin group vs. 28.3% non-insulin (p = 0.0673). At 3 years, 11.3% of the non-insulin and 59.6% of the insulin-dependent group were using anti-diabetic medication (p < 0.0001). Among insulin-dependent patients, RYGB showed greater reduction in insulin use with 26.5 and 40% compared to SG at 3 years. O-T2D patients experienced more complete diabetes remission, with 66.5 vs. 18.5% (p < 0.0001) at 3 years. Complete remission for I-T2D patients was higher in the RYGB group than SG (p < 0.0001) at years 1 and 2 (8.5 vs. 5.4% and 24.4 vs. 21.1%). The same trend was found regardless of insulin use; complete remission higher for RYGB at 1 and 2 years [50.7 vs. 39.8% (p < 0.0001), and 54.6 vs. 49.1% (p < 0.0001)]. CONCLUSION: While both RYGB and SG procedures provide effective treatment for I-T2D patients in terms of weight loss and diabetes, incidence of complete remission for insulin-dependent patients is higher with RYGB in earlier years.

The effect of an online referral system on referrals to bariatric surgery.

BACKGROUND: The Ontario Bariatric Network implemented an online referral system to completely replace a fax-based system in 2015. Strategies such as electronic information transfer have been suggested to improve the bariatric referral process but few studies exist demonstrating their efficacy. Therefore, the purpose of this study was to determine the impact on referral rates to bariatric surgery after converting to an online referral system from a fax-based system. METHODS: All referrals from 2011 to 2015 were included in the study. The main outcomes included the total number of referrals and whether a practitioner increased referrals after the implementation of the online referral system. A hierarchical logistic regression model was used for the final analysis. Predictors of interest included physician and neighbourhood level factors RESULTS: Referrals more than doubled overall and increased significantly across all health regions. Compared to practitioners in their first five years, all other experience groups were approximately 50% less likely to increase referrals. Compared to those within 50 km of a bariatric facility, practitioners 50-99 km (OR 0.76 95% CI 0.58-0.98 p = 0.04) and 100-199 km (OR 0.73 95% CI 0.55-0.96 p = 0.03) away were both significantly less likely to increase referrals. CONCLUSION: This study found that referrals increased significantly after implementing an online referral system. Furthermore, physicians in their first five years of practice as well as those practicing closer to bariatric centers were more likely to increase referrals. Our findings demonstrate that an online referral system may aid in increasing referrals to bariatric surgery.

The impact of a standardized program on short and long-term outcomes in bariatric surgery.

The purpose of this study was to determine whether there has been an improvement in short- and long-term clinical outcomes since 2010, when the Ontario Bariatric Network led a province-wide initiative to establish a standardized system of care for bariatric patients. The system includes nine bariatric centers, a centralized referral system, and a research registry. Standardization of procedures has progressed yearly, including guidelines for preoperative assessment and perioperative care. METHODS AND PROCEDURES: Analysis of the OBN registry data was performed by fiscal year between April 2010 and March 2015. Three-month overall postoperative complication rates and 30 day postoperative mortality were calculated. The mean percentage of weight loss at 1, 2, and 3 years postoperative, and regression of obesity-related diseases were calculated. The analysis of continuous and nominal data was performed using ANOVA, Chi-square, and McNemar's testing. A multiple logistic regression analysis was performed for factors affecting postoperative complication rate. RESULTS: Eight thousand and forty-three patients were included in the bariatric registry between April 2010 and March 2015. Thirty-day mortality was rare (<0.075 %) and showed no significant difference between years. Three-month overall postoperative complication rates significantly decreased with standardization (p < 0.001), as did intra-operative complication rates (p < -0.001). Regression analysis demonstrated increasing standardization to be a predictor of 3 month complication rate OR of 0.59 (95 %CI 0.41-0.85, p = 0.00385). The mean percentage of weight loss at 1, 2, and 3 years postoperative showed stability at 33.2 % (9.0 SD), 34.1 % (10.1 SD), and 32.7 % (10.1 SD), respectively. Sustained regression in obesity-related comorbidities was demonstrated at 1, 2, and 3 years postoperative. CONCLUSION: Evidence indicates the implementation of a standardized system of bariatric care has contributed to improvements in complication rates and supported prolonged weight loss and regression of obesity-related diseases in patients undergoing bariatric surgery in Ontario.

Calcineurin Inhibitor in NEuRoloGically deceased donors to decrease kidney delayed graft function study: study protocol of the CINERGY Pilot randomised controlled trial.

INTRODUCTION: Most solid organ transplants originate from donors meeting criteria for death by neurological criteria (DNC). Within the organ donor, physiological responses to brain death increase the risk of ischaemia reperfusion injury and delayed graft function. Donor preconditioning with calcineurin inhibition may reduce this risk. METHODS AND ANALYSIS: We designed a multicentre placebo-controlled pilot randomised trial involving nine organ donation hospitals and all 28 transplant programmes in the Canadian provinces of Ontario and Québec. We planned to enrol 90 DNC donors and their approximately 324 organ recipients, totalling 414 participants. Donors receive an intravenous infusion of either tacrolimus 0.02 mg/kg over 4 hours prior to organ retrieval, or a matching placebo, while monitored in an intensive care unit for any haemodynamic changes during the infusion. Among all study organ recipients, we record measures of graft function for the first 7 days in hospital and we will record graft survival after 1 year. We examine the feasibility of this trial with respect to the proportion of all eligible donors enrolled and the proportion of all eligible transplant recipients consenting to receive a CINERGY organ transplant and to allow the use of their health data for study purposes. We will report these feasibility outcomes as proportions with 95% CIs. We also record any barriers encountered in the launch and in the implementation of this trial with detailed source documentation. ETHICS AND DISSEMINATION: We will disseminate trial results through publications and presentations at participating sites and conferences. This study has been approved by Health Canada (HC6-24-c241083) and by the Research Ethics Boards of all participating sites and in Québec (MP-31-2020-3348) and Clinical Trials Ontario (Project #3309). TRIAL REGISTRATION NUMBER: NCT05148715.

Calcineurin Inhibition in Deceased Organ Donors: A Systematic Review and Meta-analysis of Preclinical Studies.

Background: Preconditioning deceased organ donors with calcineurin inhibitors (CNIs) may reduce ischemia-reperfusion injury to improve transplant outcomes. Methods: We searched MEDLINE, EMBASE, Cochrane Library, and conference proceedings for animal models of organ donation and transplantation, comparing donor treatment with CNIs with either placebo or no intervention, and evaluating outcomes for organ transplantation. Reviewers independently screened and selected studies, abstracted data, and assessed the risk of bias and clinical relevance of included studies. Where possible, we pooled results using meta-analysis; otherwise, we summarized findings descriptively. Results: Eighteen studies used various animals and a range of CNI agents and doses and evaluated their effects on a variety of transplant outcomes. The risk of bias and clinical applicability were poorly reported. Pooled analyses suggested benefit of CNI treatment on early graft function in renal transplants (3 studies; serum creatinine: ratio of means [RoM] 0.54; 95% confidence interval [CI], 0.34-0.86) but not for liver transplants (2 studies; serum alanine transaminase: RoM 0.61; 95% CI, 0.30-1.26; and serum aspartate aminotransferase: RoM 0.58; 95% CI, 0.26-1.31). We found no reduction in graft loss at 7 d (2 studies; risk ratio 0.54; 95% CI, 0.08-3.42). CNI treatment was associated with reduced transplant recipient levels of interleukin-6 (4 studies; RoM 0.36; 95% CI, 0.19-0.70), tumor necrosis factor-alpha (5 studies; RoM 0.36; 95% CI, 0.12-1.03), and cellular apoptosis (4 studies; RoM 0.30; 95% CI, 0.19-0.47). Conclusions: Although this compendium of animal experiments suggests that donor preconditioning with CNIs may improve early kidney graft function, the limited ability to reproduce a true clinical environment in animal experiments and to assess for risk of bias in these experiments is a serious weakness that precludes current clinical application.

A Landscape of Bariatric Surgery in Canada: For the Treatment of Obesity, Type 2 Diabetes and Other Comorbidities in Adults.

Obesity has escalated worldwide and in Canada. Many chronic conditions, including type 2 diabetes, are directly correlated with obesity, and although the benefits and effectiveness of bariatric surgery have been proven in terms of sustained weight loss and improving comorbidities, the procedure is underaccessed and underutilized in Canada. We explored the complex landscape of bariatric surgery in Canada, reviewing the current state and focusing on the volume of procedures nationwide and at the provincial level, the type of surgical procedures performed, their outcomes and their associated complications. Barriers and challenges curbing access to bariatric surgery are also explored. Approximately 8,583 publicly funded bariatric surgeries were performed in 9 of 10 provinces in 2015/2016; Roux-en-Y gastric bypass, sleeve gastrectomy, adjustable gastric banding and biliopancreatic diversion with or without duodenal switch are the most common procedures performed, and coverage varies among provinces and territories. Dedicated bariatric programs have been created and, in some instances, provincial networks have also emerged. Weight loss, resolution of comorbidities and rates of complications in Canada are similar to those found in the literature. The increase in the number of bariatric procedures performed over time has still not met the current demand. The rise in obesity rates, the speed and regional variations in the development and standardization of processes, adequate patient selection, funding and prioritization and gaps in knowledge and attitudes about the merits of bariatric surgery of patients, health providers and policy makers create considerable waiting times and are some of the barriers to better access to bariatric surgery.

Bariatric Surgery in the Elderly Is Associated with Similar Surgical Risks and Significant Long-Term Health Benefits.

PURPOSE: Older age (> 60) has been considered a relative contraindication for bariatric surgery due to increased complication risk. This study examined the risks and benefits of bariatric surgery for patients older than 60 years in Canadian population. METHODS: This was a retrospective cohort study of the Ontario Bariatric Registry: a database recording peri-operative and post-operative outcomes of publicly funded bariatric surgeries across the province. Patients who completed 1 year follow-up, who underwent laparoscopic gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) between January 2010 and May 2013, were divided into older (> 60) and younger (> 60) cohorts, and outcomes were compared. RESULTS: Between January 2010 and May 2013, 3166 registry patients underwent LRYGB or LSG and completed 1-year follow-up. Of these, 204 (6.5%) were older than 60 years, with 175 (85.8%) undergoing LRYGB and 29 (14.2%) LSG. Demographics were similar, except for a higher number of males in the older group (59 (28.9%) versus 452 (15.3%) (p < 0.001)). No significant difference in complication rate was noted (15% for younger cohort versus 13.8% (p = 0.889)). The average percentage of excess weight loss was significantly higher in the younger population (60.72% versus 56.25% (p < 0.05)) overall, however not significantly in the LSG group. Reduction in medication use post-surgery for management of co-morbidities was significantly higher in the older patients (- 0.91 versus - 2.03 (p < 0.001)). CONCLUSION: The older cohort who underwent LRYGB or LSG was at no greater risk for intra-operative and post-operative complications and showed greater reduction in medication use post-surgery when compared to the younger cohort.

The Effect of Bariatric Surgery on Mobility, Health-Related Quality of Life, Healthcare Resource Utilization, and Employment Status.

BACKGROUND: A sub-study of the Ontario Bariatric Registry was conducted to evaluate the impact of bariatric surgery on mobility, health-related quality of life (HRQoL), healthcare resource utilization (HRU), and employment status. METHODS: The 1-year change in mobility following bariatric surgery was evaluated using the mobility domain of the EuroQOL-5D-5L (EQ-5D-5L), which was self-administered at baseline and 1 year after bariatric surgery along with questions on HRU. Another questionnaire was used to document employment status at time of surgery and 1 year later. RESULTS: The population included 304 individuals (mean age = 46 years; 85 % female). At baseline, 68 % of participants had some problems in walking compared to 14 % at 1 year following surgery (p < 0.001). The EQ-5D-5L health utility score increased from 0.73 to 0.90 (p < 0.001). The number of hospitalizations increased significantly before and after surgery (p = 0.021). Of the 304 study participants, 138 completed the questionnaire and responses indicated that more individuals reported a change in their employment status within 1 year following surgery (26 %) compared to 1 year prior to the surgery (9 %) (p < 0.001). CONCLUSIONS: Within the limitations of this study, there is a suggestion that bariatric surgery has a major impact on mobility and HRQoL. More research is warranted to understand the benefits, costs, and cost-effectiveness of bariatric surgery in Canada.