Liberal or Restrictive Transfusion Strategy in Patients with Traumatic Brain Injury.

BACKGROUND: The effect of a liberal transfusion strategy as compared with a restrictive strategy on outcomes in critically ill patients with traumatic brain injury is unclear. METHODS: We randomly assigned adults with moderate or severe traumatic brain injury and anemia to receive transfusion of red cells according to a liberal strategy (transfusions initiated at a hemoglobin level of ≤10 g per deciliter) or a restrictive strategy (transfusions initiated at ≤7 g per deciliter). The primary outcome was an unfavorable outcome as assessed by the score on the Glasgow Outcome Scale-Extended at 6 months, which we categorized with the use of a sliding dichotomy that was based on the prognosis of each patient at baseline. Secondary outcomes included mortality, functional independence, quality of life, and depression at 6 months. RESULTS: A total of 742 patients underwent randomization, with 371 assigned to each group. The analysis of the primary outcome included 722 patients. The median hemoglobin level in the intensive care unit was 10.8 g per deciliter in the group assigned to the liberal strategy and 8.8 g per deciliter in the group assigned to the restrictive strategy. An unfavorable outcome occurred in 249 of 364 patients (68.4%) in the liberal-strategy group and in 263 of 358 (73.5%) in the restrictive-strategy group (adjusted absolute difference, restrictive strategy vs. liberal strategy, 5.4 percentage points; 95% confidence interval, -2.9 to 13.7). Among survivors, a liberal strategy was associated with higher scores on some but not all the scales assessing functional independence and quality of life. No association was observed between the transfusion strategy and mortality or depression. Venous thromboembolic events occurred in 8.4% of the patients in each group, and acute respiratory distress syndrome occurred in 3.3% and 0.8% of patients in the liberal-strategy and restrictive-strategy groups, respectively. CONCLUSIONS: In critically ill patients with traumatic brain injury and anemia, a liberal transfusion strategy did not reduce the risk of an unfavorable neurologic outcome at 6 months. (Funded by the Canadian Institutes of Health Research and others; HEMOTION ClinicalTrials.gov number, NCT03260478.).

Venous congestion in septic shock quantified with point-of-care ultrasound: a pilot prospective multicentre cohort study.

PURPOSE: Venous congestion is a pathophysiologic state that can result in organ dysfunction, particularly acute kidney injury (AKI). We sought to evaluate the feasibility of performing a definitive observational study to determine the impact of venous congestion quantified using point-of-care ultrasound (POCUS) in patients with septic shock. METHODS: We conducted a prospective observational feasibility study at two intensive care units (ICUs). We recruited adult patients with septic shock within 12 hr of ICU admission. Using the validated Venous Excess Ultrasound Score (VEXUS), we quantified venous congestion on day 1 and day 3 of ICU admission. The primary feasibility outcome was successful completion rate of the two VEXUS scores. We performed a survival analysis to quantify the hazard of renal replacement therapy (RRT). RESULTS: We enrolled 75 patients from January 2022 to January 2023. The success rate of completion for VEXUS scans was 94.5% (95% confidence interval [CI], 89.5 to 97.6). Severe venous congestion was present in 19% (14/75) of patients on ICU admission day 1 and in 16% (10/61) of patients on day 3. Venous congestion on ICU admission may be associated with a higher risk of requiring RRT (unadjusted hazard ratio, 3.35; 95% CI, 0.94 to 11.88; P = 0.06). CONCLUSIONS: It is feasible to conduct a definitive observational study exploring the association between venous congestion quantified with POCUS and clinical outcomes in patients with septic shock. We hypothesize that venous congestion may be associated with an increased hazard of receiving RRT.

RéSUMé: OBJECTIF: La congestion veineuse est un état physiopathologique qui peut entraîner un dysfonctionnement des organes, en particulier une insuffisance rénale aiguë (IRA). Nous avons cherché à évaluer la faisabilité de la réalisation d'une étude observationnelle définitive pour déterminer l'impact de la congestion veineuse quantifiée à l'aide de l'échographie ciblée (POCUS) chez des patient·es en choc septique. MéTHODE: Nous avons réalisé une étude de faisabilité observationnelle prospective dans deux unités de soins intensifs (USI). Nous avons recruté des patient·es adultes souffrant d'un choc septique dans les 12 heures suivant leur admission aux soins intensifs. À l'aide du score VEXUS (score d'échographie de l'excès veineux) validé, nous avons quantifié la congestion veineuse au jour 1 et au jour 3 de leur admission aux soins intensifs. Le principal critère de faisabilité était le taux de réussite des deux scores VEXUS. Nous avons réalisé une analyse de survie pour quantifier le risque de thérapie de substitution rénale (TSR). RéSULTATS: Nous avons recruté 75 patient·es de janvier 2022 à janvier 2023. Le taux de réussite des scores VEXUS était de 94,5 % (intervalle de confiance [IC] à 95 %, 89,5 à 97,6). Une congestion veineuse sévère était présente chez 19 % (14/75) des patient·es au jour 1 d'admission aux soins intensifs et chez 16 % (10/61) des patient·es au jour 3. La congestion veineuse lors de l'admission aux soins intensifs peut être associée à un risque plus élevé de nécessiter une TSR (rapport de risque non ajusté, 3,35; IC 95 %, 0,94 à 11,88; P = 0,06). CONCLUSION: Il est possible de mener une étude observationnelle définitive explorant l'association entre la congestion veineuse quantifiée par POCUS et les devenirs cliniques chez les patient·es en choc septique. Nous émettons l'hypothèse que la congestion veineuse peut être associée à un risque accru de recevoir une thérapie de substitution rénale.

Safety Outcomes of Direct Discharge Home From ICUs: An Updated Systematic Review and Meta-Analysis (Direct From ICU Sent Home Study).

OBJECTIVE: To evaluate the impact of direct discharge home (DDH) from ICUs compared with ward transfer on safety outcomes of readmissions, emergency department (ED) visits, and mortality. DATA SOURCES: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing and Allied Health Literature from inception until March 28, 2022. STUDY SELECTION: Randomized and nonrandomized studies of DDH patients compared with ward transfer were eligible. DATA EXTRACTION: We screened and extracted studies independently and in duplicate. We assessed risk of bias using the Newcastle-Ottawa Scale for observational studies. A random-effects meta-analysis model and heterogeneity assessment was performed using pooled data (inverse variance) for propensity-matched and unadjusted cohorts. We assessed the overall certainty of evidence for each outcome using the Grading Recommendations Assessment, Development and Evaluation approach. DATA SYNTHESIS: Of 10,228 citations identified, we included six studies. Of these, three high-quality studies, which enrolled 49,376 patients in propensity-matched cohorts, could be pooled using meta-analysis. For DDH from ICU, compared with ward transfers, there was no difference in the risk of ED visits at 30-day (22.4% vs 22.7%; relative risk [RR], 0.99; 95% CI, 0.95-1.02; p = 0.39; low certainty); hospital readmissions at 30-day (9.8% vs 9.6%; RR, 1.02; 95% CI, 0.91-1.15; p = 0.71; very low-to-low certainty); or 90-day mortality (2.8% vs 2.6%; RR, 1.06; 95% CI, 0.95-1.18; p = 0.29; very low-to-low certainty). There were no important differences in the unmatched cohorts or across subgroup analyses. CONCLUSIONS: Very low-to-low certainty evidence from observational studies suggests that DDH from ICU may have no difference in safety outcomes compared with ward transfer of selected ICU patients. In the future, this research question could be further examined by randomized control trials to provide higher certainty data.

Small-Volume Blood Collection Tubes to Reduce Transfusions in Intensive Care: The STRATUS Randomized Clinical Trial.

Importance: Blood collection for laboratory testing in intensive care unit (ICU) patients is a modifiable contributor to anemia and red blood cell (RBC) transfusion. Most blood withdrawn is not required for analysis and is discarded. Objective: To determine whether transitioning from standard-volume to small-volume vacuum tubes for blood collection in ICUs reduces RBC transfusion without compromising laboratory testing procedures. Design, Setting, and Participants: Stepped-wedge cluster randomized trial in 25 adult medical-surgical ICUs in Canada (February 5, 2019 to January 21, 2021). Interventions: ICUs were randomized to transition from standard-volume (n = 10 940) to small-volume tubes (n = 10 261) for laboratory testing. Main Outcomes and Measures: The primary outcome was RBC transfusion (units per patient per ICU stay). Secondary outcomes were patients receiving at least 1 RBC transfusion, hemoglobin decrease during ICU stay (adjusted for RBC transfusion), specimens with insufficient volume for testing, length of stay in the ICU and hospital, and mortality in the ICU and hospital. The primary analysis included patients admitted for 48 hours or more, excluding those admitted during a 5.5-month COVID-19-related trial hiatus. Results: In the primary analysis of 21 201 patients (mean age, 63.5 years; 39.9% female), which excluded 6210 patients admitted during the early COVID-19 pandemic, there was no significant difference in RBC units per patient per ICU stay (relative risk [RR], 0.91 [95% CI, 0.79 to 1.05]; P = .19; absolute reduction of 7.24 RBC units/100 patients per ICU stay [95% CI, -3.28 to 19.44]). In a prespecified secondary analysis (n = 27 411 patients), RBC units per patient per ICU stay decreased after transition from standard-volume to small-volume tubes (RR, 0.88 [95% CI, 0.77 to 1.00]; P = .04; absolute reduction of 9.84 RBC units/100 patients per ICU stay [95% CI, 0.24 to 20.76]). Median decrease in transfusion-adjusted hemoglobin was not statistically different in the primary population (mean difference, 0.10 g/dL [95% CI, -0.04 to 0.23]) and lower in the secondary population (mean difference, 0.17 g/dL [95% CI, 0.05 to 0.29]). Specimens with insufficient quantity for analysis were rare (≤0.03%) before and after transition. Conclusions and Relevance: Use of small-volume blood collection tubes in the ICU may decrease RBC transfusions without affecting laboratory analysis. Trial Registration: ClinicalTrials.gov Identifier: NCT03578419.

Outcomes After Direct Discharge Home From Critical Care Units: A Population-Based Cohort Analysis.

OBJECTIVES: To compare health service use and clinical outcomes for patients with and without direct discharge to home (DDH) from ICUs in Ontario. DESIGN: Population-based, observational, cohort study using propensity scoring to match patients who were DDH to those not DDH and a preference-based instrumental variable (IV) analysis using ICU-level DDH rate as the IV. SETTING: ICUs in Ontario. PATIENTS: Patients discharged home from a hospitalization either directly or within 48 hours of care in an ICU between April 1, 2015, and March 31, 2017. INTERVENTION: DDH from ICU. MEASUREMENTS AND MAIN RESULTS: Among 76,737 patients in our cohort, 46,859 (61%) were DDH from the ICU. In the propensity matched cohort, the odds for our primary outcome of hospital readmission or emergency department (ED) visit within 30 days were not significantly different for patients DDH (odds ratio [OR], 1.00; 95% CI, 0.96-1.04), and there was no difference in mortality at 90 days for patients DDH (OR, 1.08; 95% CI, 0.97-1.21). The effect on hospital readmission or ED visits was similar in the subgroup of patients discharged from level 2 (OR, 0.98; 95% CI, 0.92-1.04) and level 3 ICUs (OR, 1.02; 95% CI, 0.96-1.09) and in the subgroups with cardiac conditions (OR, 1.03; 95% CI, 0.96-1.12) and noncardiac conditions (OR, 0.98; 95% CI, 0.94-1.03). Similar results were obtained in the IV analysis (coefficient for hospital readmission or ED visit within 30 d = -0.03 ± 0.03 ( se ); p = 0.3). CONCLUSIONS: There was no difference in outcomes for patients DDH compared with ward transfer prior to discharge when two approaches were used to minimize confounding within a large health systemwide observational cohort. We did not evaluate how patients are selected for DDH. Our results suggest that with careful patient selection, this practice might be feasible for routine implementation to ensure efficient and safe use of limited healthcare resources.

Airway injury from the presence of endotracheal tubes and the association with subglottic secretion drainage: a prospective observational study.

PURPOSE: Laryngeal and tracheal injuries are known complications of endotracheal intubation. Endotracheal tubes (ETTs) with subglottic suction devices (SSDs) are commonly used in the critical care setting. There is concern that herniation of tissue into the suction port of these devices may lead to tracheal injury resulting in serious clinical consequences such as tracheal stenosis. We aimed to describe the type and location of tracheal injuries seen in intubated critically ill patients and assess injuries at the suction port as well as in-hospital complications associated with those injuries. METHODS: We conducted a prospective observational study of 57 critically ill patients admitted to a level 3 intensive care unit who were endotracheally intubated and underwent percutaneous tracheostomy. Investigators performed bronchoscopy and photographic evaluation of the airway during the percutaneous tracheostomy procedure to evaluate tracheal and laryngeal injury. RESULTS: Forty-one (72%) patients intubated with ETT with SSD and sixteen (28%) patients with standard ETT were included in the study. Forty-seven (83%) patients had a documented airway injury ranging from hyperemia to deep ulceration of the mucosa. A common tracheal injury was at the site of the tracheal cuff. Injury at the site of the subglottic suction device was seen in 5/41 (12%) patients. There were no in-hospital complications. CONCLUSIONS: Airway injury was common in critically ill patients following endotracheal intubation, and tracheal injury commonly occurred at the site of the endotracheal cuff. Injury occurred at the site of the subglottic suction port in some patients although the clinical consequences of these injuries remain unclear.

RéSUMé: OBJECTIF: Les lésions laryngées et trachéales sont des complications connues de l'intubation endotrachéale. Les sondes endotrachéales (SET) avec dispositifs d'aspiration sous-glottiques (DASG) sont couramment utilisées aux soins intensifs. On craint qu'une hernie tissulaire dans l'orifice d'aspiration de ces dispositifs n'entraîne des lésions trachéales, résultant en de graves conséquences cliniques telles qu'une sténose trachéale. Nous avons cherché à décrire le type et l'emplacement des lésions trachéales observées chez les patients gravement malades intubés et à évaluer les lésions au port d'aspiration ainsi que les complications hospitalières associées à ces lésions. MéTHODE: Nous avons mené une étude observationnelle prospective auprès de 57 patients gravement malades admis dans une unité de soins intensifs de niveau 3 qui ont été intubés par voie endotrachéale et ont subi une trachéostomie percutanée. Les chercheurs ont réalisé une bronchoscopie et une évaluation photographique des voies aériennes au cours de la trachéostomie percutanée afin d'évaluer les lésions trachéales et laryngées. RéSULTATS: Quarante et un (72 %) intubés par SET avec DASG et seize (28 %) patients avec SET standard ont été inclus dans l'étude. Quarante-sept (83 %) patients ont présenté une lésion documentée des voies aériennes allant de l'hyperémie à l'ulcération profonde de la muqueuse. Une lésion trachéale commune était localisée sur le site du ballonnet trachéal. Une lésion au site du dispositif d'aspiration sous-glottique a été observée chez 5/41 (12 %) patients. Il n'y a pas eu de complications à l'hôpital. CONCLUSION: Les lésions des voies aériennes étaient fréquentes chez les patients gravement malades après une intubation endotrachéale, et les lésions trachéales se produisaient généralement au site du ballonnet endotrachéal. Des lésions se sont produites au site de l'orifice d'aspiration sous-glottique chez certains patients, bien que les conséquences cliniques de ces lésions restent incertaines.

Incidence of Intra-Abdominal Hypertension and Abdominal Compartment Syndrome: A Systematic Review.

OBJECTIVE: To determine the contemporary prevalence of intra-abdominal hypertension (IAH) and abdominal compartment syndrome in critically ill patients. DATA SOURCES: Medline, Embase, and Central databases. STUDY SELECTION: Studies reporting on the prevalence of IAH in consecutively admitted critically ill patients using the World Society of Abdominal Compartment Syndrome (WSACS) consensus guidelines for intra-abdominal pressure (IAP) measurement. DATA EXTRACTION: Duplicate independent review and data abstraction. DATA SYNTHESIS: The search identified 2428 titles with 6 eligible studies (n = 1965). Reported prevalence ranged from 30% to 49%. Despite abiding by the WSACS guidelines for IAP measurement, studies varied in their definition of IAH, frequency and duration of IAP measurement, and reporting of outcomes. Three of 6 studies reported that IAH, especially at higher grades, was an independent predictor of mortality. CONCLUSIONS: Intra-abdominal hypertension is a common finding in critically ill patients and may be associated with increased mortality, especially at higher grades. Further prospective research is required to examine the effect of screening and treatment of IAH on patient outcomes.

Effect of Probiotics on Incident Ventilator-Associated Pneumonia in Critically Ill Patients: A Randomized Clinical Trial.

Importance: Growing interest in microbial dysbiosis during critical illness has raised questions about the therapeutic potential of microbiome modification with probiotics. Prior randomized trials in this population suggest that probiotics reduce infection, particularly ventilator-associated pneumonia (VAP), although probiotic-associated infections have also been reported. Objective: To evaluate the effect of Lactobacillus rhamnosus GG on preventing VAP, additional infections, and other clinically important outcomes in the intensive care unit (ICU). Design, Setting, and Participants: Randomized placebo-controlled trial in 44 ICUs in Canada, the United States, and Saudi Arabia enrolling adults predicted to require mechanical ventilation for at least 72 hours. A total of 2653 patients were enrolled from October 2013 to March 2019 (final follow-up, October 2020). Interventions: Enteral L rhamnosus GG (1 × 1010 colony-forming units) (n = 1321) or placebo (n = 1332) twice daily in the ICU. Main Outcomes and Measures: The primary outcome was VAP determined by duplicate blinded central adjudication. Secondary outcomes were other ICU-acquired infections including Clostridioides difficile infection, diarrhea, antimicrobial use, ICU and hospital length of stay, and mortality. Results: Among 2653 randomized patients (mean age, 59.8 years [SD], 16.5 years), 2650 (99.9%) completed the trial (mean age, 59.8 years [SD], 16.5 years; 1063 women [40.1%.] with a mean Acute Physiology and Chronic Health Evaluation II score of 22.0 (SD, 7.8) and received the study product for a median of 9 days (IQR, 5-15 days). VAP developed among 289 of 1318 patients (21.9%) receiving probiotics vs 284 of 1332 controls (21.3%; hazard ratio [HR], 1.03 (95% CI, 0.87-1.22; P = .73, absolute difference, 0.6%, 95% CI, -2.5% to 3.7%). None of the 20 prespecified secondary outcomes, including other ICU-acquired infections, diarrhea, antimicrobial use, mortality, or length of stay showed a significant difference. Fifteen patients (1.1%) receiving probiotics vs 1 (0.1%) in the control group experienced the adverse event of L rhamnosus in a sterile site or the sole or predominant organism in a nonsterile site (odds ratio, 14.02; 95% CI, 1.79-109.58; P < .001). Conclusions and Relevance: Among critically ill patients requiring mechanical ventilation, administration of the probiotic L rhamnosus GG compared with placebo, resulted in no significant difference in the development of ventilator-associated pneumonia. These findings do not support the use of L rhamnosus GG in critically ill patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02462590.

Drug use in Canadian patients with trauma after cannabis legalization.

Background: The federal Cannabis Act came into force on Oct. 17, 2018, in Canada, making Canada only the second country in the world to legalize the cultivation, acquisition, possession and consumption of cannabis and its by-products. This provided a unique opportunity to evaluate the impact of this legislation on drug-related trauma. Methods: We performed a prospective observational study on the use of cannabis and other illicit drugs in the trauma population at a lead Canadian trauma centre in London, Ontario, in the 3 months before (July 1 to Sept. 30, 2018) and 3 months after (Nov. 1, 2018, to Jan. 31, 2019) the legalization of cannabis in Canada. We defined cannabis use as a positive cannabinoid screen result at the time of assessment by the trauma team. We also screened for opioids, amphetamines and cocaine. Results: A total of 210 patients were assessed by our trauma service between July 1 and Sept. 30, 2018, and 141 patients were assessed between Nov. 1, 2018, and Jan. 31, 2019. Motor vehicle collisions were the most common cause of trauma both before (101 [48.1%]) and after (67 [47.5%]) legalization. The mean Injury Severity Score was 17.6 (standard deviation [SD] 13.0) and 19.7 (SD 14.8), respectively. Drug screens were done in 88 patients (41.9%) assessed before legalization and 99 patients (70.2%) assessed after legalization. There was no difference in the rate of positive cannabinoid screen results before and after legalization (22 [25%] v. 22 [22%]). There was a trend toward higher rates of positive cannabinoid screen results (2/10 [20%] v. 5/8 [62%]) and positive toxicology screen results (5/10 [50%] v. 6/8 [75%]) after legalization among patients with penetrating trauma, but our sample was too small to achieve statistical significance. Conclusion: We found no difference in the rates of positive cannabinoid screen results among patients assessed at our trauma centre in the 3 months before and the 3 months after legalization of cannabis; however, there was a trend toward an increase in the rates of positive results of toxicology screens and cannabinoid screens among those with penetrating trauma. These preliminary single-centre data showing no increased rates of cannabis use in patients with trauma after legalization are reassuring.

Contexte: La Loi fédérale sur le cannabis est entrée en vigueur ici le 17 octobre 2018, faisant du Canada le second pays à légaliser la culture, l'acquisition, la possession et la consommation du cannabis et de ses produits dérivés. Cette situation fournit une occasion unique d'évaluer l'impact de cette loi sur les traumatismes liés aux drogues. Méthodes: Nous avons procédé à une étude d'observation prospective sur la consommation du cannabis et d'autres drogues illicites chez une population de victimes de traumatismes dans un grand centre canadien de traumatologie de London, en Ontario, au cours des 3 mois précédant (1er juillet au 30 septembre 2018) et des 3 mois suivant (1er novembre 2018 au 31 janvier 2019) la légalisation du cannabis au Canada. La consommation de cannabis était confirmée par l'obtention de résultats positifs aux tests de dépistage des cannabinoïdes demandés par l'équipe de traumatologie. Nous avons aussi effectué un dépistage des opioïdes, des amphétamines et de la cocaïne. Résultats: En tout, notre service de traumatologie a vu 210 patients entre le 1er juillet et le 30 septembre 2018, et 141 entre le 1er novembre 2018 et le 31 janvier 2019. Les accidents de la route ont été la plus fréquente cause de traumatisme avant (101 [48,1 %]) et après (67 [47,5 %]) la légalisation. L'indice moyen de gravité des blessures a été de 17,6 (écart-type [É.-T.] 13,0) et 19,7 (É.-T. 14,8), respectivement. Un dépistage de drogues a été effectué chez 88 patients (41,9 %) vus avant la légalisation et chez 99 patients (70,2 %) vus après la légalisation. On n'a observé aucune différence quant aux taux de résultats positifs aux tests de dépistage des cannabinoïdes enregistrés avant et après la légalisation (22 [25 %] c. 22 [22 %]). Les taux de résultats positifs aux tests de dépistage des cannabinoïdes (2/10 [20 %] c. 5/8 [62 %]) et aux tests toxicologiques (5/10 [50 %] c. 6/8 [75 %]) ont eu tendance à être plus élevés après la légalisation chez les patients victimes de traumatismes pénétrants, mais notre échantillon était trop petit pour atteindre une portée statistique. Conclusion: Nous n'avons observé aucune différence quant aux taux de résultats positifs au dépistage des cannabinoïdes au cours des 3 mois précédant et suivant la légalisation du cannabis; par contre, les taux de résultats positifs aux tests de dépistage des drogues et du cannabis ont eu tendance à être plus élevés chez les victimes de traumatismes pénétrants. Ces données préliminaires provenant d'un seul centre qui ne montrent pas d'augmentation des taux de consommation de cannabis chez les polytraumatisés sont rassurantes.

Determinants of Direct Discharge Home From Critical Care Units: A Population-Based Cohort Analysis.

OBJECTIVE: To describe trends and patient and system factors associated with direct discharge from critical care to home in a large health system. DESIGN: Population-based cohort study of direct discharge to home rates annually over 10 years. We used a multivariable, multilevel random-effects regression model to analyze current factors associated with direct discharge home in a subcohort from the most recent 2 years. SETTING: One hundred seventy-four ICUs in 101 hospitals in Ontario. PATIENTS: All patients discharged from an ICU between April 1, 2007, and March 31, 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Overall, 237,200 patients (21.1%) were discharged directly home from an ICU. The rate of direct discharge to home increased from 18.6% in 2007 to 23.1% in 2017 (annual increase of 1.02; 95% CI, 1.02-1.03). There were marked variations in rates of direct discharge to home across all critical care units. For medical and surgical units, the median odds ratio was 1.76 (95% CI, 1.59-1.92). In these units, direct discharge to home was associated with younger age (odds ratio, 0.36; 95% CI, 0.34-0.39 for age 80-105 vs age 18-39), fewer comorbidities (odds ratio, 1.74; 95% CI, 1.63-1.85 for Charlson comorbidity index of 0 vs 2), diagnoses of overdose/poisoning (odds ratio, 1.35; 95% CI, 1.23-1.47) and diabetic complications (odds ratio, 1.35; 95% CI, 1.2-1.51), and admission after a same-day procedure (odds ratio, 2.82; 95% CI, 2.46-3.23 compared with emergency department). ICU occupancy was inversely associated with direct discharge to home with an odds ratio of 0.88 (95% CI, 0.87-0.88) for each 10% increase. CONCLUSIONS: High rates of direct discharge to home with evidence of significant practice variation combined with identifiable patient characteristics suggest that further evaluation of this increasingly common transition in care is warranted.

Impact of Critical Care Transesophageal Echocardiography in Medical-Surgical ICU Patients: Characteristics and Results From 274 Consecutive Examinations.

OBJECTIVE: Critical care echocardiography has become an integral tool in the assessment and management of critically ill patients. Critical care transesophageal echocardiography (TEE) offers diagnostic reliability, superior image quality, and an expanded diagnostic scope to transthoracic echocardiography. Despite its favorable attributes, TEE use in North American intensive care units (ICUs) remains relatively undescribed. In this article, we seek to characterize the feasibility, indications, and clinical impact of a critical care TEE program. DESIGN: Retrospective, observational study. SETTING: Tertiary care, academic critical care program consisting of 2 hospitals in Ontario, Canada. PARTICIPANTS: Consecutive critical care TEE examinations on ICU patients performed between December 2012 and December 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Consecutive critical care TEE studies on ICU patients from December 1, 2012, to December 31, 2016, were reviewed. The TEEs performed on cardiac surgery patients and those without reports were excluded. Examination details, including indications, complications, examination complexity (number of views, Doppler techniques), and clinical recommendations were aggregated and analyzed. Two hundred seventy-four TEE studies were performed by 38 operators. Common indications for TEE studies were hemodynamic instability (45.2%), assessment for infective endocarditis (22.2%), and cardiac arrest (20.1%). A change in patient management was proposed following 79.5% of TEE studies. Thirty-eight percent of TEE studies were performed during evening hours or on weekends. There were no mechanical complications. CONCLUSIONS: Our observational data support intensivist-performed TEE as being safe and therapeutically influential across a broad range of indications. Our program's demonstrated feasibility and impact may act as a model for TEE adoption in other North American ICUs.

Anesthesiologist and Emergency Medicine Physician Attitudes and Knowledge Regarding Etomidate for Intubation.

PURPOSE: The use of etomidate as an induction agent for critically ill patients is controversial. While its favorable hemodynamic profile is enviable, etomidate has been shown to cause transient adrenal suppression. The clinical consequences of transient adrenal suppression are poorly understood. Anecdotally, some clinicians advocate strongly for etomidate, while others feel it can cause significant harm. To better understand the current clinical environment with respect to single-dose etomidate use in critically ill patients, Canadian anesthesiologists and Canadian emergency medicine (EM) physicians were questioned regarding their opinions, knowledge, and preferences about etomidate use as an induction agent. METHODS: Invitations to participate with the electronic survey were sent to 100 Canadian EM physicians and 260 Canadian anesthesiologists. The survey had 4 general parts: demographics, familiarity with the current literature, choice of induction agent given various clinical scenarios, and opinions on the controversy. The Pearson γ2 test was used to detect whether significant differences exist between physician groups. RESULTS: Ninety three anesthesiologists and 42 EM physicians responded for response rates of 36% and 42%. There were no self-reported differences in knowledge about etomidate properties between EM physicians and anesthesiologists. There were significant differences in etomidate use between EM physicians and anesthesiologists in general rapid sequence intubation, noncritically ill patients, and those with undifferentiated hypotension. Both EM physicians and anesthesiologists describe the current etomidate controversy as significant and not adequately resolved. CONCLUSION: There is no significant difference in self-reported etomidate knowledge between anesthesiologists and EM physicians; however, significant practice pattern differences exist with EM physicians using etomidate more often. Broad agreement supports future research to investigate etomidate's impact in critically ill patients.

Clinical Predictors for Unsafe Direct Discharge Home Patients From Intensive Care Units.

PURPOSE: To describe factors (demographics and clinical characteristics) that predict patients who are at an increased risk of adverse events or unplanned return visits to a health-care facility following discharge direct to home (DDH) from intensive care units (ICUs). METHODS: Prospective cohort study of all adult patients who survived their stay in our medical-surgical-trauma ICU between February 2016 and 2017 and were discharged directly home. Patients were followed for 8 weeks postdischarge. Univariable and multivariable logistic regression analyses were performed to identify factors associated with adverse events or unplanned return visits to a health-care facility following DDH from ICU. RESULTS: A total of 129 DDH patients were enrolled and completed the 8-week follow-up. We identified 39 unplanned return visits (URVs). There was 0% mortality at 8 weeks postdischarge. Eight potential predictors of hospital URVs (P < .2) were identified in the univariable analysis: prior substance abuse (odds ratio [OR] of URV of 2.50 [95% confidence interval: 1.08-5.80], hepatitis (OR: 6.92 [1.68-28.48]), sepsis (OR: 11.03 [1.19-102.29]), admission nine equivalents of nursing manpower score (NEMS) <24 (OR: 2.28 [1.03-5.04], no fixed address (OR: 22.9 [1.2-437.3]), ICU length of stay (LOS) <2 days (OR: 2.95 [1.28-6.78]), home discharge within London, Ontario (OR: 2.44 [1.00-5.92]), and left against medical advice (AMA; OR: 6.06 [2.04-17.98]). CONCLUSIONS: Our study identified 8 covariates that were potential predictors of URV: prior substance abuse, hepatitis, sepsis, admission NEMS <24, no fixed address, ICU LOS <2 days, home discharge within London, Ontario, and left AMA. The practice of direct discharges home from the ICU would benefit from adequately powered multicenter study in order to construct a clinical prediction model (that would require further testing and validation).

Patient, Family, and Physician Satisfaction With Planning for Direct Discharge to Home From Intensive Care Units: Direct From ICU Sent Home Study.

BACKGROUND: In the new era of decreasing hospital bed availability, there is an increasing rate of direct discharge to home (DDH) from intensive care units (ICUs), despite sparse literature informing this practice. OBJECTIVES: To evaluate patient, family, and ICU attending physician satisfaction with planning for DDH from the ICU and intensivists' current DDH practices and perceptions. METHODS: Prospective cohort study, using convenience sampling, of adult patients undergoing DDH from an ICU between February 2016 and February 2017 using a modified FS-ICU 24 satisfaction survey completed by patients, family members, and attending physicians at the time of patient discharge to home from the ICU. RESULTS: Seventy-two percent of patients, 37% of family members, and 100% of ICU physicians recruited completed the survey. A majority of patients (89%) and families (78%) were satisfied or very satisfied with DDH. Only 6% of patients and 8% of families were dissatisfied to very dissatisfied with DDH. Conversely, ICU physician satisfaction varied, with only 5% being very comfortable with DDH and the majority (50%) only somewhat comfortable. Twenty percent of staff consultants were uncomfortable to very uncomfortable with the practice of DDH. Thirty-one percent of staff physician respondents felt that patient and family discomfort would be barriers to DDH. Compared to physicians and other allied health professionals, nurses were identified as the most helpful members of the health-care team in preparation for DDH by 98% of patients and 92% of family members. The DDH rates have increased for the past 12 years in our ICUs but declined during the study period (February 2016 to February 2017). CONCLUSIONS: Patients and family members are satisfied with the practice of DDH from ICU, although ICU physician satisfaction is more variable. Physician comfort may be improved by data informing which patients may be safely DDH from the ICU.

Outcomes and Costs of Patients Admitted to the Intensive Care Unit Due to Accidental or Intentional Poisoning.

INTRODUCTION: Acute poisoning represents a major cause of morbidity and mortality, and many of these patients are admitted to the intensive care unit (ICU). However, little is known regarding ICU costs of acute poisoning. METHODS: This was a retrospective matched database analysis of patients admitted to the ICU with acute poisoning from 2011 to 2014. It was performed in 2 ICUs within a single tertiary care hospital system. All patient information, outcomes, and costs were stored in the hospital data warehouse. Control patients were defined as randomly selected age-, sex-, severity index-, and comorbidity index-matched nonpoisoned ICU patients (1:4 matching ratio). RESULTS: A total of 8452 critically ill patients were admitted during the study period, of whom 277 had a diagnosis of acute poisoning. The mean age was 44.5 years, and the most common xenobiotics implicated were sedative hypnotics (20.2%), antidepressants (15.2%), and opioids (10.5%). Of these, 73.6% of poisonings were deemed intentional. In-hospital mortality of poisoned patients was 5.1%, compared to 11.1% for control patients (P < .01). The median ICU length of stay (LOS) for poisoned patients was 3.0 days, compared with 4.0 days for control patients (P < .01). The mean total cost for poisoned patients was CAD$18 958. Control patients had a significantly higher mean total cost of CAD$60 628 (P < .01). The xenobiotics associated with the highest costs were acetaminophen (CAD$18 585), toxic alcohols (CAD$16 771), and opioids (CAD$12 967). CONCLUSIONS: In our cohort, we confirmed the long-held belief that patients admitted to the ICU with a primary diagnosis of poisoning have a lower mortality rate, ICU LOS, and overall cost per ICU admission than nonpoisoned patients. However, poisoned patients still accrue significant daily costs, with the highest costs attributed to xenobiotics with known antidotes, such as acetaminophen, toxic alcohols, and opioids.

The impact of neurologically deceased donors' blood pressures on clinical outcomes in transplant recipients: a systematic review.

PURPOSE: We performed a systematic review of the literature to identify the ideal blood pressure (BP) target in neurologically deceased organ donors to optimize outcomes of recipient organ function and survival, and organs transplanted per donor. SOURCE: We searched MEDLINE and EMBASE from inception to December 2018 for studies that evaluated BP targets in neurologically deceased organ donors. A two-step review process with three independent reviewers was employed. We assessed the risk of bias and applied Grading of Recommendations Assessment, Development, and Evaluation methodology to evaluate the certainty of the evidence by outcome. PRINCIPAL FINDINGS: Twelve cohort studies were included in our final analysis. Seven studies showed that hypotension was associated with worse post-transplant graft function or survival, while three studies found no association between hypotension and post-transplant graft function or survival. Two other studies showed no association between hypotension and organs transplanted per donor. Overall, six of the identified studies had serious risk of bias. CONCLUSION: A systolic BP less 90 mmHg may be associated with graft dysfunction in kidney recipients, but this is based on very low certainty in evidence. Although an ideal and universal BP target in neurologically deceased organ donors is not clearly identifiable in the literature, this could reflect the complexity of donor hemodynamics and the need for individualized targets for different organs. Further prospective research is required to address these questions.

RéSUMé: OBJECTIF: Nous avons réalisé une revue systématique de la littérature afin d'identifier la tension artérielle (TA) idéale chez les donneurs d'organes après un décès neurologique en vue d'optimiser les devenirs en matière de fonctionnement d'organes et de survie, ainsi que le nombre d'organes transplantés par donneur. SOURCE: Nous avons effectué des recherches dans les bases de données MEDLINE et EMBASE de leur création jusqu'en décembre 2018 afin d'en extraire les études évaluant les cibles de TA chez les donneurs d'organes après un décès neurologique. Nous avons utilisé un processus de révision en deux étapes comprenant trois réviseurs indépendants. Nous avons évalué le risque de biais et appliqué la méthodologie GRADE (Grading of Recommendations Assessment, Development and Evaluation) afin d'évaluer la certitude des données probantes par résultat. CONSTATATIONS PRINCIPALES: Douze études de cohorte ont été incluses dans notre analyse finale. Sept études ont révélé que l'hypotension était associée à un fonctionnement moins bon ou une survie moins bonne du greffon après la greffe, alors que trois études n'ont trouvé aucune association entre l'hypotension et le fonctionnement ou la survie du greffon post-transplantation. Deux autres études n'ont montré aucune association entre l'hypotension et le nombre d'organes transplantés par donneur. Dans l'ensemble, six des études identifiées comportaient un important risque de biais. CONCLUSION: Une TA systolique de moins de 90 mmHg pourrait être associée à un dysfonctionnement du greffon chez les récipiendaires de reins, mais ce risque se fonde sur une certitude très faible des données probantes. Bien qu'une cible de TA idéale et universelle chez les donneurs d'organes après un décès neurologique ne soit pas clairement identifiée dans la littérature, cela pourrait refléter la complexité de l'hémodynamie des donneurs et le besoin de cibles individualisées selon les différents organes. Des recherches prospectives supplémentaires sont nécessaires pour explorer ces questions.

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.

Acceptability of cardiac donation after circulatory determination of death: a survey of the Canadian public.

PURPOSE: Cardiac transplantation is a definitive therapy for end-stage heart failure, but demand exceeds supply. Cardiac donation after circulatory determination of death (cardiac DCDD) can be performed using direct procurement and perfusion (DPP), where cardiac activity is restored after heart recovery, or (NRP), where brain blood supply is surgically interrupted, circulation to the thoraco-abdominal organs is restored within the donor's body, followed by heart recovery. While cardiac DCDD would increase the number of heart donors, uptake of programs has been slowed in part because of ethical concerns within the medical community. These debates have been largely devoid of discussion regarding public perceptions. We conducted a national survey of public perceptions regarding cardiac DCDD. METHODS: We surveyed 1,001 Canadians about their attitudes towards cardiac DCDD using a rigorously designed and pre-tested survey. RESULTS: We found that 843 of 1,001 respondents (84.2%; 95% confidence interval [CI], 81.8 to 86.3) accepted the DPP approach, 642 (64.1%; 95% CI, 61.1 to 67.0) would agree to donate their heart using DPP, and 696 (69.5%; 95% CI, 66.6 to 72.3) would consent to the same for a family member. We found that 779 respondents of 1,001 respondents (77.8%; 95% CI, 75.1 to 80.3) accepted the NRP approach, 587 (58.6%; 95% CI, 55.5 to 61.6) would agree to donate their heart using NRP, and 636 (63.5%; 95% CI, 60.5 to 66.4) would consent to the same for a family member. Most respondents supported the implementation of DPP (738 respondents or 73.7%; 95% CI, 70.9 to 76.3) and NRP (655 respondents or 65.4%; 95% CI, 62.4 to 68.3) in Canada. CONCLUSION: The results of this national survey of public attitudes towards cardiac DCDD will inform the implementation of cardiac DCDD programs in a manner that is consistent with public values.

Attitudes of healthcare providers towards cardiac donation after circulatory determination of death: a Canadian nation-wide survey.

PURPOSE: The number of patients on cardiac transplant waitlists exceeds the number of available donor organs. Cardiac donation is currently limited to those declared dead by neurologic criteria in all but three countries. Cardiac donation after circulatory determination of death (cardiac DCDD) can be conducted using direct procurement and perfusion (DPP) or normothermic regional perfusion (NRP). Implementation of cardiac DCDD in many countries has been slowed by ethical debates within the donation and transplantation community. We conducted a national survey to determine the perceptions of healthcare providers regarding cardiac DCDD. METHODS: We conducted an electronic survey of 398 healthcare providers who are involved in the management of heart donors and/or heart transplant recipients in Canada (226 nurses, 82 critical care physicians, 31 donation specialists, and 59 transplant specialists). Our primary outcomes were their attitudes towards and concerns regarding cardiac DCDD protocols and their implementation in Canada. We distributed the survey electronically through several Canadian donation and transplantation organizations. RESULTS: We identified that 361 of 391 respondents (92.3%; 95% confidence interval [CI], 89.6 to 95.1) believed that DPP is acceptable, and 329 of 377 respondents (87.3%; 95% CI, 83.9 to 90.7) supported its implementation in Canada. We found that 301 of 384 respondents (78.4%; 95% CI, 74.2 to 82.6) believed that NRP is acceptable and 266 of 377 respondents (70.6%; 95% CI, 66.0 to 75.2) supported its implementation in Canada. CONCLUSION: This is the first survey describing the attitudes of healthcare providers towards cardiac DCDD. We identified widespread support for cardiac DCDD and its implementation in Canada among Canadian healthcare providers within the organ donation and transplantation community in Canada.

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.