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Background:The response of Canada’s research community to the COVID-19 pandemic provides a unique opportunity to examine the country’s clinical health research ecosystem. We sought to describe patterns of enrolment across Canadian Institutes of Health Research (CIHR)–funded studies on COVID-19.Methods:We identified COVID-19 studies funded by the CIHR and that enrolled participants from Canadian acute care hospitals between January 2020 and April 2023. We collected information on study-and site-level variables from study leads, site investigators, and public domain sources. We described and evaluated factors associated with cumulative enrolment.Results:We obtained information for 23 out of 26 (88%) eligible CIHR-funded studies (16 randomized controlled trials [RCTs] and 7 cohort studies). The 23 studies were managed by 12 Canadian and 3 international coordinating centres. Of 419 Canadian hospitals, 97 (23%) enrolled a total of 28 973 participants — 3876 in RCTs across 78 hospitals (median cumulative enrolment per hospital 30, interquartile range [IQR] 10–61), and 25 097 in cohort studies across 62 hospitals (median cumulative enrolment per hospital 158, IQR 6–348). Of 78 hospitals recruiting participants in RCTs, 13 (17%) enrolled 50% of all RCT participants, whereas 6 of 62 hospitals (9.7%) recruited 54% of participants in cohort studies.Interpretation:A minority of Canadian hospitals enrolled the majority of participants in CIHR-funded studies on COVID-19. This analysis sheds light on the Canadian health research ecosystem and provides information for multiple key partners to consider ways to realize the full research potential of Canada’s health systems.

IMPORTANCE: Reducing low-value care has the potential to improve patient experiences and outcomes and free up health care resources. Sixteen quality indicators were recently developed targeting reductions in low-value trauma care based on a synthesis of the best available evidence, expert consensus, and patient preferences. OBJECTIVE: To assess the validity of quality indicators on low-value trauma care using trauma registry data. DESIGN, SETTING, AND PARTICIPANTS: Data from an inclusive Canadian provincial trauma system were used in this analysis. Included were all admissions for injury to any of the 57 provincial adult trauma centers between April 1, 2013, and March 31, 2020. Metrics for quality indicators were developed iteratively with clinical experts. MAIN OUTCOMES AND MEASURES: Validity was assessed using a priori criteria based on 5 parameters: frequency (incidence and case volume), discrimination (interhospital variation), construct validity (correlation with quality indicators on high-value care), predictive validity (correlation with quality indicators on risk-adjusted outcomes), and forecasting (correlation over time). RESULTS: The study sample included 136 783 patient admissions (mean [SD] age, 63 [22] years; 68 428 men [50%]). Metrics were developed for 12 of the 16 quality indicators. Six quality indicators showed moderate or high validity on all measurable parameters: initial head, cervical spine, or whole-body computed tomography for low-risk patients; posttransfer repeated computed tomography; neurosurgical consultation for mild complicated traumatic brain injury; and spine service consultation for isolated thoracolumbar process fractures. Red blood cell transfusion in low-risk patients had low frequency but had moderate or high validity on all other parameters. Five quality indicators had low validity on at least 2 parameters: repeated head CT and intensive care unit admission for mild complicated traumatic brain injury, hospital admission for minor blunt abdominal trauma, orthosis for thoracolumbar burst fractures, and surgical exploration in penetrating neck injury without hard signs. CONCLUSIONS AND RELEVANCE: This cohort study shows the feasibility of assessing low-value trauma care using routinely collected data. It provided data on quality indicators properties that can be used to decide which quality indicators are most appropriate in a given system. Results suggest that 6 quality indicators have moderate to high validity. Their implementation now needs to be tested.

IMPORTANCE: The use of quality indicators has been shown to improve injury care processes and outcomes. However, trauma quality indicators proposed to date exclusively target the underuse of recommended practices. Initiatives such as Choosing Wisely publish lists of practices to be questioned, but few apply to trauma care, and most have not successfully been translated to quality indicators. OBJECTIVE: To develop a set of evidence and patient-informed, consensus-based quality indicators targeting reductions in low-value clinical practices in acute, in-hospital trauma care. DESIGN, SETTING, AND PARTICIPANTS: This 2-round Research and Development/University of California at Los Angeles (RAND/UCLA) consensus study, conducted from April 20 to June 9, 2021, comprised an online questionnaire and a virtual workshop led by 2 independent moderators. Two panels of international experts from Canada, Australia, the US, and the UK, and local stakeholders from Québec, Canada, represented key clinical expertise involved in trauma care and included 3 patient partners. MAIN OUTCOMES AND MEASURES: Panelists were asked to rate 50 practices on a 7-point Likert scale according to 4 quality indicator criteria: importance, supporting evidence, actionability, and measurability. RESULTS: Of 49 eligible experts approached, 46 (94%; 18 experts [39%] aged ≥50 years; 37 men [80%]) completed at least 1 round and 36 (73%) completed both rounds. Eleven quality indicators were selected overall, 2 more were selected by the international panel and a further 3 by the local stakeholder panel. Selected indicators targeted low-value clinical practices in the following aspects of trauma care: (1) initial diagnostic imaging (head, cervical spine, ankle, and pelvis), (2) repeated diagnostic imaging (posttransfer computed tomography [CT] and repeated head CT), (3) consultation (neurosurgical and spine), (4) surgery (penetrating neck injury), (5) blood product administration, (6) medication (antibiotic prophylaxis and late seizure prophylaxis), (7) trauma service admission (blunt abdominal trauma), (8) intensive care unit admission (mild complicated traumatic brain injury), and (9) routine blood work (minor orthopedic surgery). CONCLUSIONS AND RELEVANCE: In this consensus study, a set of consensus-based quality indicators were developed that were informed by the best available evidence and patient priorities, targeting low-value trauma care. Selected indicators represented a trauma-specific list of practices, the use of which should be questioned. Trauma quality programs in high-income countries may use these study results as a basis to select context-specific quality indicators to measure and reduce low-value care.

We evaluated characteristics associated with neuromuscular blockade (NMB) use, center-level variation, and whether NMB mediated excess mortality among patients assigned to high-frequency oscillatory ventilation (HFOV) in the OSCILLATE trial.

Purpose: Hemodynamic management of adults with distributive shock often includes the use of catecholamine-based vasoconstricting medications. It is unclear whether adding vasopressin or vasopressin analogues to catecholamine therapy is beneficial in the management of patients with distributive shock. The purpose of this guideline was to develop an evidence-based recommendation regarding the addition of vasopressin to catecholamine vasopressors in the management of adults with distributive shock. Methods: We summarized the evidence informing this recommendation by updating a recently published meta-analysis. Then, a multidisciplinary panel from the Canadian Critical Care Society developed the recommendation using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Results: The updated systematic review identified 25 randomized controlled trials including a total of 3,737 patients with distributive shock. Compared with catecholamine therapy alone, the addition of vasopressin or its analogues was associated with a reduced risk of mortality (relative risk [RR], 0.91; 95% confidence interval [CI], 0.85 to 0.99; low certainty), reduced risk of atrial fibrillation (RR, 0.77; 95% CI, 0.67 to 0.88; high certainty), and increased risk of digital ischemia (RR, 2.56; 95% CI, 1.24 to 5.25; moderate certainty). Conclusions: After considering certainty in the evidence, values and preferences, cost, and other factors, the expert guideline panel suggests using vasopressin or vasopressin analogues in addition to catecholamines over catecholamine vasopressors alone for the management of distributive shock (conditional recommendation, low certainty evidence).

Vasodilatory shock is common in critically ill patients and vasopressors are a mainstay of therapy. A meta-analysis suggested that use of a higher, as opposed to a lower, mean arterial pressure target to guide titration of vasopressor therapy, could be associated with a higher risk of death in older critically ill patients. The 65 trial is a pragmatic, multi-centre, parallel-group, open-label, randomised clinical trial of permissive hypotension (a mean arterial pressure target of 60–65 mmHg during vasopressor therapy) versus usual care in critically ill patients aged 65 years or over with vasodilatory hypotension. The trial is conducted in 2600 patients from 65 United Kingdom adult, general critical care units. The primary outcome is all-cause mortality at 90 days. An economic evaluation is embedded. The 65 trial received favourable ethical opinion from the South Central – Oxford C Research Ethics Committee and approval from the Health Research Authority. The results will be presented at national and international conferences and published in peer-reviewed medical journals.Trial registration: ISRCTN10580502

Purpose: Elevated cardiac troponin concentrations in people with critical illness are associated with an increased risk of death. We aimed to assess the feasibility of a larger study to ascertain the utility of cardiac troponin as a prognostic tool for mortality in critically ill patients. Methods: Patients admitted to participating intensive care units during the one-month enrolment period were eligible. We excluded cardiac surgical patients and patients who were admitted and either died or were discharged within 12 hr. In enrolled patients, we measured high-sensitivity cardiac troponin I (hs-cTnI) and obtained electrocardiograms to ascertain the incidence of myocardial infarction (MI) and isolated troponin elevation. Our feasibility objectives were to measure recruitment rate, the proportion of patients who consented under a deferred consent model, and time required for data collection and study procedures. Results: Over a four-week enrolment period, 280 patients were enrolled using a deferred consent model. We obtained subsequent consent from 81% of patients. Study procedures and data collection required 1.7 hr per participant. Overall, 86 (38%) suffered a MI, 23 (10%) had an isolated hs-cTnI elevation, and 117 (52%) had no hs-cTnI elevation. The crude hospital mortality rate was 10% without an hs-cTnI elevation, 29% with an isolated hs-cTnl elevation (relative risk [RR]) 2.2; 95% confidence interval [CI], 1.0 to 6.0) and 29% with an MI (RR, 2.6; 95% CI, 1.4 to 5.1). Conclusion: Myocardial injury with elevated hs-cTnI concentrations and MIs occur frequently during critical illness. This pilot study has established the feasibility of conducting a large-scale investigation addressing this issue.

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BACKGROUND:Most deaths in critically ill patients with severe traumatic brain injury are associated with a decision to withdraw life-sustaining treatments. We aimed to identify the behavioural determinants that influence recommendations by critical care physicians to consider the withdrawal of life-sustaining treatments in this population.METHODS:We conducted a descriptive qualitative study based on the Theoretical Domains Framework of critical care physicians caring for patients with severe traumatic brain injury across Canada. We stratified critical care physicians by regions and used a purposive sampling strategy. We conducted semistructured phone interviews using a piloted and pretested interview guide. We transcribed the interviews verbatim and verified the content for accuracy. We performed the analysis using a 3-step approach: coding, generation of specific beliefs and generation of specific themes.RESULTS:We recruited 20 critical care physicians across 4 geographic regions. After reaching saturation, we identified 7 core themes across 4 Theoretical Domains Framework domains for factors relevant to the decision to withdraw life-sustaining treatments. Four factors (i.e., clinical triggers, social triggers, interaction with families and intentions with medical decisions) were identified before the decision is made and 3 were identified during the decision-making process (i.e., considerations, priorities and knowledge needs). We identified multiple themes reflecting internal (n= 18, 8 Theoretical Domains Framework domains) and external (n= 15, 6 Theoretical Domains Framework domains) influences on the decision to withdraw life-sustaining treatments.INTERPRETATION:We identified several core themes and domains considered by critical care physicians in Canada in the decision to withdraw life-sustaining treatments in critically ill patients with severe traumatic brain injury. Future research should aim at identifying the factors influencing surrogate decision-makers in the decision to withdraw life-sustaining treatments in these patients.

BACKGROUND:Perioperative corticosteroid use may reduce acute kidney injury. We sought to test whether methylprednisolone reduces the risk of acute kidney injury after cardiac surgery.METHODS:We conducted a prespecified substudy of a randomized controlled trial involving patients undergoing cardiac surgery with cardiopulmonary bypass (2007–2014); patients were recruited from 79 centres in 18 countries. Eligibility criteria included a moderate-to-high risk of perioperative death based on a preoperative score of 6 or greater on the European System for Cardiac Operative Risk Evaluation I. Patients (n= 7286) were randomly assigned (1:1) to receive intravenous methylprednisolone (250 mg at anesthetic induction and 250 mg at initiation of cardiopulmonary bypass) or placebo. Patients, caregivers, data collectors and outcome adjudicators were unaware of the assigned intervention. The primary outcome was postoperative acute kidney injury, defined as an increase in the serum creatinine concentration (from the preoperative value) of 0.3 mg/dL or greater (≥ 26.5 μmol/L) or 50% or greater in the 14-day period after surgery, or use of dialysis within 30 days after surgery.RESULTS:Acute kidney injury occurred in 1479/3647 patients (40.6%) in the methylprednisolone group and in 1426/3639 patients (39.2%) in the placebo group (adjusted relative risk 1.04, 95% confidence interval 0.96 to 1.11). Results were consistent across several definitions of acute kidney injury and in patients with preoperative chronic kidney disease.INTERPRETATION:Intraoperative corticosteroid use did not reduce the risk of acute kidney injury in patients with a moderate-to-high risk of perioperative death who had cardiac surgery with cardiopulmonary bypass. Our results do not support the prophylactic use of steroids during cardiopulmonary bypass surgery. Trial registration:ClinicalTrials.gov, no. NCT00427388

Individuals vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), when infected, can still develop disease that requires hospitalization. It remains unclear whether these patients differ from hospitalized unvaccinated patients with regard to presentation, coexisting comorbidities, and outcomes.

Improving the medical care of deceased organ donors to increase transplant rates and improve allograft function requires an understanding of the current epidemiology and clinical practices of deceased donation within intensive care units (ICUs). Herein, we report the results of our investigation into the feasibility of a multicentre prospective cohort study addressing the afformentioned issues. We conducted a 12-month prospective observational cohort study in six ICUs and one coronary care unit in Hamilton, Canada. We included consecutive children and adults following consent for deceased organ donation (including neurologic determination of death [NDD] or donation after circulatory death [DCD]). Intensive care unit research staff recorded donor management data from hospital records, extending from one day prior to the consent for organ donation up to the time of organ retrieval. The provincial Organ Donation Organization (ODO) supplemented these data and, additionally, provided data on corresponding organ recipients. We identified, evaluated, and measured three potential obstacles to the feasibility of a national cohort study: obtaining authorization to implement the study with a waiver of research consent, accessibility of transplant recipient data, and the time required to complete very detailed case report forms (CRFs), with valuable lessons learned for implementation in future projects. The local Research Ethics Board and the ODO Privacy Office both authorized the recording of donor and recipient study data with a waiver of research consent. Sixty-seven consecutive consented donors were included (31 NDD and 36 DCD donors); 50 of them provided 144 organs for transplantation to 141 recipients. We identified the age and sex of the recipients as well as the location and date of transplant for all organ recipients in Ontario; however, we obtained no recipient data for six organs transported outside of Ontario. Intensive care unit research staff estimated that future CRF completion will require five to seven hours per patient. The Hamilton-DONATE pilot study supports the feasibility of a larger cohort study to describe the epidemiology and clinical practices related to deceased donor care in Canada. wwwclinicaltrials.gov (NCT02902783). Registered 16 September 2016. L’amélioration des soins de donneurs d’organes décédés pour augmenter les taux de transplantation et améliorer la fonction des allogreffes nécessite de comprendre l’épidémiologie et les pratiques cliniques actuelles du don d’organe de donneur décédé dans les unités de soins intensifs (USI). Nous présentons ici les résultats de notre enquête sur la faisabilité d’une étude de cohorte prospective multicentrique visant à répondre à ces questions. Nous avons mené une étude de cohorte observationnelle prospective de 12 mois dans six USI et une unité de soins coronariens à Hamilton (Canada). Nous avons inclus les enfants et adultes consécutifs après consentement du don d’organe d’un donneur décédé (incluant la détermination neurologique du décès [DND] ou don après décès cardiocirculatoire [DDC]). Le personnel de recherche des unités de soins intensifs a consigné les données de la gestion médicale des donneurs à partir des dossiers hospitaliers, commençant une journée avant le consentement au don d’organe jusqu’au moment du prélèvement. L’organisme provincial responsable des dons d’organes (ODO) a complété ces données ainsi que celles des receveurs d’organes correspondants. Nous avons identifié, évalué et mesuré trois obstacles potentiels à la faisabilité d’une étude de cohorte nationale : l’obtention de l’autorisation de mise en place d’une étude avec dérogation de consentement à la recherche, l’accessibilité des données concernant les receveurs de greffes et le temps nécessaire pour remplir des cahiers d’observation très détaillés; nous en avons tiré des points importants pour la mise en œuvre de futurs projets. Le Comité local d’éthique de la recherche et le bureau de la protection de la vie privée de l’ODO ont tous deux autorisé l’enregistrement des données d’étude du donneur et du receveur avec une dérogation du consentement à la recherche. Soixante-sept donneurs consentants consécutifs (31 donneurs DND et 36 donneurs DDC) ont été inclus; parmi eux, 50 donneurs ont fourni 144 organes qui ont été greffés chez 141 receveurs. Nous avons identifié l’âge et le sexe des receveurs, ainsi que l’emplacement et la date de la transplantation pour tous les receveurs d’organes en Ontario; toutefois, nous n’avons pas obtenu de données pour six organes transportés hors de la province. Le personnel de recherche des unités de soins intensifs a estimé que le remplissage des cahiers d’observation futurs prendrait de 5 à 7 heures par patient. L’étude pilote Hamilton-DONATE confirme la faisabilité d’une grande étude de cohorte visant à décrire l’épidémiologie et les pratiques cliniques pour les soins aux donneurs décédés au Canada. wwwclinicaltrials.gov (NCT02902783). Enregistré le 16 septembre 2016.

The 2013–16 Ebola virus disease outbreak in west Africa was associated with unprecedented challenges in the provision of care to patients with Ebola virus disease, including absence of pre-existing isolation and treatment facilities, patients' reluctance to present for medical care, and limitations in the provision of supportive medical care. Case fatality rates in west Africa were initially greater than 70%, but decreased with improvements in supportive care. To inform optimal care in a future outbreak of Ebola virus disease, we employed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to develop evidence-based guidelines for the delivery of supportive care to patients admitted to Ebola treatment units. Key recommendations include administration of oral and, as necessary, intravenous hydration; systematic monitoring of vital signs and volume status; availability of key biochemical testing; adequate staffing ratios; and availability of analgesics, including opioids, for pain relief.

Clinicians must balance the risks from hypotension with the potential adverse effects of vasopressors. Experts have recommended a mean arterial pressure (MAP) target of at least 65 mmHg, and higher in older patients and in patients with chronic hypertension or atherosclerosis. We conducted a systematic review of randomized-controlled trials comparing higher vslower blood pressure targets for vasopressor therapy administered to hypotensive critically ill patients. We searched MEDLINE®, EMBASE™, and the Cochrane Central Register of Controlled Trials for studies of higher vslower blood pressure targets for vasopressor therapy in critically ill hypotensive adult patients. Two reviewers independently assessed trial eligibility based on titles and abstracts, and they then selected full-text reports. Outcomes, subgroups, and analyses were prespecified. We used GRADE (Grading of Recommendations Assessment, Development and Evaluation) to rate the overall confidence in the estimates of intervention effects. Of 8001 citations, we retrieved 57 full-text articles and ultimately included two randomized-controlled trials (894 patients). Higher blood pressure targets were not associated with lower mortality (relative risk [RR], 1.05; 95% confidence interval [CI], 0.90 to 1.23; P= 0.54), and neither age (P= 0.17) nor chronic hypertension (P= 0.32) modified the overall effect. Nevertheless, higher blood pressure targets were associated with a greater risk of new-onset supraventricular cardiac arrhythmia (RR, 2.08; 95% CI, 1.28 to 3.38; P< 0.01). Current evidence does not support a MAP target > 70 mmHg in hypotensive critically ill adult patients requiring vasopressor therapy. Les cliniciens doivent équilibrer les risques liés à l’hypotension aux complications potentielles des vasopresseurs. Des experts ont recommandé de cibler une tension artérielle moyenne (TAM) d’au moins 65 mmHg, et une TAM plus élevée chez les patients atteints d’hypertension chronique, d’athérosclérose ou plus âgés. Nous avons réalisé une revue systématique des études randomisées contrôlées comparant des cibles de tension artérielle plus élevées à plus basses chez des patients hypotendus en état critique recevant un traitement vasopresseur. Nous avons fait des recherches dans les bases de données Medline, EMBASE et dans le registre central des études contrôlées Cochrane afin d’en extraire les études comparant des cibles de tension artérielle plus élevées ou plus basses chez des patients adultes hypotendus et en état critique recevant un traitement vasopresseur. Deux examinateurs ont évalué de façon indépendante l’éligibilité des études selon leur titre et leur résumé, puis sélectionné les articles intégraux. Les critères d’évaluation, sous-groupes et analyses étaient spécifiés au préalable. Nous avons utilisé le système GRADE (Grading of Recommendations Assessment, Development and Evaluation) afin d’évaluer la confiance globale dans les estimations des effets de l’intervention. Parmi les 8001 citations, nous avons extrait 57 articles intégraux et finalement inclus deux études randomisées contrôlées (894 patients). Les cibles de tension artérielle plus élevées n’étaient pas associées à une mortalité plus basse (risque relatif [RR] 1,05; intervalle de confiance [IC] 95 %, 0,90 à 1,23; P= 0,54), et ni l’âge (P= 0,17) ni l’hypertension chronique (P= 0,32) n’ont modifié l’effet global. Cependant, les cibles de tension artérielle plus élevées étaient associées à un risque plus élevé de nouvelle apparition d’une arythmie cardiaque supraventriculaire (RR, 2,08; IC 95 %, 1,28 à 3,38; P< 0,01). Les données probantes actuelles n’appuient pas une cible de TAM supérieure à 70 mmHg chez les patients adultes hypotendus et gravement malades nécessitant un traitement vasopresseur.

The recent large outbreak of Ebola virus disease (EVD) in Western Africa resulted in greatly increased accumulation of human genotypic, phenotypic and clinical data, and improved our understanding of the spectrum of clinical manifestations. As a result, the WHO disease classification of EVD underwent major revision.

Physicians often prescribe vasopressors to correct pathological vasodilation and improve tissue perfusion in patients with septic shock, but the evidence to inform practice on vasopressor dosing is weak. We undertook a systematic review of clinical studies evaluating different blood pressure targets for the dosing of vasopressors in septic shock. We searched MEDLINE, EMBASE, CENTRAL (to November 2013), reference lists from included articles, and trial registries for randomized controlled trials (RCTs) and observational and crossover intervention studies comparing different blood pressure targets for vasopressor therapy in septic shock. Two reviewers independently selected eligible studies and extracted data on standardized forms. We identified 2 RCTs and 10 crossover trials but no observational studies meeting our criteria. Only one RCT measured clinical outcomes after comparing mean arterial pressure targets of 80 to 85 mmHg versus 65 to 70 mmHg. There was no effect on 28-day mortality, but confidence intervals were wide (hazard ratio, 95 confidence interval 95 CI 0.84 – 1.38). In contrast, this intervention was associated with a greater risk of atrial fibrillation (relative risk, 2.36; 95 CI, 1.18 – 4.72) and a lower risk of renal replacement therapy in hypertensive patients (relative risk, 0.75; 95 CI, 0.57 – 1.0). Crossover trials suggest that achieving higher blood pressure targets by increasing vasopressor doses increases heart rate and cardiac index with no effect on serum lactate. Our findings underscore the paucity of clinical evidence to guide the administration of vasopressors in critically ill patients with septic shock. Further rigorous research is needed to establish an evidence base for vasopressor administration in this population.

IMPORTANCE: Seriously ill hospitalized patients have identified communication and decision making about goals of care as high priorities for quality improvement in end-of-life care. Interventions to improve care are more likely to succeed if tailored to existing barriers. OBJECTIVE: To determine, from the perspective of hospital-based clinicians, (1) barriers impeding communication and decision making about goals of care with seriously ill hospitalized patients and their families and (2) their own willingness and the acceptability for other clinicians to engage in this process. DESIGN, SETTING, AND PARTICIPANTS: Multicenter survey of medical teaching units of nurses, internal medicine residents, and staff physicians from participating units at 13 university-based hospitals from 5 Canadian provinces. MAIN OUTCOMES AND MEASURES: Importance of 21 barriers to goals of care discussions rated on a 7-point scale (1 = extremely unimportant; 7 = extremely important). RESULTS: Between September 2012 and March 2013, questionnaires were returned by 1256 of 1617 eligible clinicians, for an overall response rate of 77.7% (512 of 646 nurses [79.3%], 484 of 634 residents [76.3%], 260 of 337 staff physicians [77.2%]). The following family member–related and patient-related factors were consistently identified by all 3 clinician groups as the most important barriers to goals of care discussions: family members’ or patients’ difficulty accepting a poor prognosis (mean [SD] score, 5.8 [1.2] and 5.6 [1.3], respectively), family members’ or patients’ difficulty understanding the limitations and complications of life-sustaining treatments (5.8 [1.2] for both groups), disagreement among family members about goals of care (5.8 [1.2]), and patients’ incapacity to make goals of care decisions (5.6 [1.2]). Clinicians perceived their own skills and system factors as less important barriers. Participants viewed it as acceptable for all clinician groups to engage in goals of care discussions—including a role for advance practice nurses, nurses, and social workers to initiate goals of care discussions and be a decision coach. CONCLUSIONS AND RELEVANCE: Hospital-based clinicians perceive family member–related and patient-related factors as the most important barriers to goals of care discussions. All health care professionals were viewed as playing important roles in addressing goals of care. These findings can inform the design of future interventions to improve communication and decision making about goals of care.

The efficacy of systemic corticosteroids in many critical illnesses remains uncertain. Our primary objective was to survey intensivists in North America about their perceived use of corticosteroids in clinical practice. Self-administered paper survey. Intensivists in academic hospitals with clinical trial expertise in critical illness. We generated questionnaire items in focus groups and refined them after assessments of clinical sensibility and test-retest reliability and pilot testing. We administered the survey to experienced intensivists practicing in selected North American centres actively enrolling patients in the multicentre Oscillation for ARDS Treated Early (OSCILLATE) Trial (ISRCTN87124254). Respondents used a four-point scale to grade how frequently they would administer corticosteroids in 14 clinical settings. They also reported their opinions on 16 potential near-absolute indications or contraindications for the use of corticosteroids. Our response rate was 82% (103/125). Respondents were general internists (50%), respirologists (22%), anesthesiologists (21%), and surgeons (7%) who practiced in mixed medical-surgical units. A majority of respondents reported almost always prescribing corticosteroids in the setting of significant bronchospasm in a mechanically ventilated patient (94%), recent corticosteroid use and low blood pressure (93%), and vasopressor-refractory septic shock (52%). Although more than half of respondents stated they would almost never prescribe corticosteroids in severe community-acquired pneumonia (81%), acute lung injury (ALI, 76%), acute respiratory distress syndrome (ARDS, 65%), and severe ARDS (51%), variability increased with severity of acute lung injury. Near-absolute indications selected by most respondents included known adrenal insufficiency (99%) and suspicion of cryptogenic organizing pneumonia (89%), connective tissue disease (85%), or other potentially corticosteroid-responsive illnesses (85%). Respondents reported rarely prescribing corticosteroids for ALI, but accepted them for bronchospasm, suspected adrenal insufficiency due to previous corticosteroid use, and vasopressor-refractory septic shock. These competing indications will complicate the design and interpretation of any future large-scale trial of corticosteroids in critical illness. L’efficacité des corticostéroïdes systémiques demeure incertaine pour plusieurs maladies graves. Notre objectif primaire était d’obtenir l’opinion des intensivistes en Amérique du Nord concernant leur perception de l’utilisation des corticostéroïdes dans la pratique clinique. Sondage auto-administré sur papier. Intensivistes dans des hôpitaux universitaires ayant une expertise en matière d’études cliniques sur les maladies graves. Les éléments du questionnaire ont été créés dans des groupes de discussion; nous les avons ensuite peaufinés après avoir évalué leur sensibilité clinique et leur fiabilité de répétition et après des essais pilotes. Nous avons fait parvenir le sondage à des intensivistes d’expérience pratiquant dans certains centres nord-américains sélectionnés recrutant des patients pour l’étude multicentrique OSCILLATE (Oscillation for ARDS Treated Early) (ISRCTN87124254). Les répondants ont utilisé une échelle en quatre points pour noter la fréquence à laquelle ils administreraient des corticostéroïdes dans 14 contextes cliniques. On leur a également demandé de donner leur opinion concernant 16 indications ou contre-indications potentielles quasi absolues pour l’utilisation de corticostéroïdes. Notre taux de réponse était de 82 % (103/125). Les répondants comprenaient des internistes généraux (50 %), des pneumologues (22 %), des anesthésiologistes (21 %) et des chirurgiens (7 %) pratiquant dans des unités médico-chirurgicales mixtes. La majorité des répondants a rapporté prescrire, dans la plupart des cas, des corticostéroïdes lors de bronchospasme significatif chez un patient sous ventilation mécanique (94%), en présence d’hypotension artérielle peu après un traitement aux corticostéroïdes (93 %), et pour un choc septique réfractaire aux vasopresseurs (52 %). Bien que plus de la moitié des répondants ait déclaré qu’elle ne prescrirait presque jamais de corticostéroïdes pour traiter une pneumonie d’origine communautaire (81%), une lésion pulmonaire aiguë (LPA, 76 %), un syndrome de détresse respiratoire aiguë (SDRA, 65 %), et un SDRA grave (51 %), la variabilité augmentait en fonction de l’acuité de la lésion pulmonaire. Les indications quasi absolues retenues par la plupart des répondants étaient une insuffisance surrénale connue (99 %) et la suspicion d’une pneumonie organisée cryptogénique (89 %), une maladie des tissus conjonctifs (85 %), ou d’autres maladies réagissant potentiellement aux corticostéroïdes (85 %). Les répondants ont rapporté qu’ils prescrivaient rarement des corticostéroïdes pour traiter une LPA, mais qu’ils les jugeaient acceptables pour soigner les bronchospasmes, les insuffisances surrénales soupçonnées en raison d’utilisation précédente de corticostéroïdes, et les chocs septiques réfractaires aux vasopresseurs. Ces indications vont compliquer la conception et l’interprétation de toute étude future à grande échelle portant sur les corticostéroïdes utilisés pour le traitement des maladies graves.

To categorize, quantify and interpret findings documented in feedback letters of monitoring or auditing visits for an investigator-initiated, peer-review funded multicenter randomized trial testing probiotics for critically ill patients.

Vasodilatory shock is common in critically ill patients and vasopressors are a mainstay of therapy. A meta-analysis suggested that use of a higher, as opposed to a lower, mean arterial pressure target to guide titration of vasopressor therapy, could be associated with a higher risk of death in older critically ill patients. The 65 trial is a pragmatic, multi-centre, parallel-group, open-label, randomised clinical trial of permissive hypotension (a mean arterial pressure target of 60 -65 mmHg during vasopressor therapy) versus usual care in critically ill patients aged 65 years or over with vasodilatory hypotension. The trial is conducted in 2600 patients from 65 United Kingdom adult, general critical care units. The primary outcome is all-cause mortality at 90 days. An economic evaluation is embedded. The 65 trial received favourable ethical opinion from the South Central - Oxford C Research Ethics Committee and approval from the Health Research Authority. The results will be presented at national and international conferences and published in peer-reviewed medical journals. Trial registration: ISRCTN10580502

BACKGROUND: Survey data suggest that Canadian intensivists administer corticosteroids to critically ill patients primarily in response to airway obstruction, perceived risk for adrenal insufficiency and hemodynamic instability.OBJECTIVE: To describe variables independently associated with systemic corticosteroid therapy during an influenza outbreak.METHODS: The present analysis was retrospective cohort study involving critically ill patients with influenza in two Canadian cities. Hospital records were reviewed for critically ill patients treated in the intensive care units (ICUs) of eight hospitals in Canada during the 2008 to 2009 and 2009 to 2010 influenza outbreaks. Abstracted data included demographic information, symptoms at disease onset, chronic comorbidities and baseline illness severity scores. Corticosteroid use data were extracted for every ICU day and expressed as hydrocortisone dose equivalent in mg. Multivariable regression models were constructed to identify variables independently associated with corticosteroid therapy in the ICU.RESULTS: The study cohort included 90 patients with a mean (± SD) age of 55.0±17.3 years and Acute Physiology and Chronic Health Evaluation II score of 19.8±8.3. Patients in 2009 to 2010 were younger with more severe lung injury but similar exposure to corticosteroids. Overall, 54% of patients received corticosteroids at a mean daily dose of 343±330 mg of hydrocortisone for 8.5±4.8 days. Variables independently associated with corticosteroid therapy in the ICU were history of airway obstruction (OR 4.8 [95% CI 1.6 to 14.9]) and hemodynamic instability (OR 4.6 [95% CI 1.2 to 17.8]).CONCLUSION: Observational data revealed that hemodynamic instability and airway obstruction were associated with corticosteroid therapy in the critical care setting, similar to a recent survey of stated practice. Efforts to determine the effects of corticosteroids in the ICU for these specific clinical situations are warranted.

ObjectivesTo determine the ability and accuracy of the S-100β protein in predicting prognosis after a moderate or severe traumatic brain injury.DesignSystematic review and meta-analysis of randomised controlled trials and observational studies.Data sourcesMedline, Embase, Cochrane Central Register of Controlled Trials, BIOSIS (from their inception to April 2012), conference abstracts, bibliographies of eligible articles, and relevant narrative reviews.Study selectionTwo reviewers independently reviewed citations and selected eligible studies, defined as cohort studies or randomised control trials including patients with moderate or severe traumatic brain injury and evaluating the prognostic value of S-100β protein. Outcomes evaluated were mortality, score on the Glasgow outcome scale, or brain death.Data extractionTwo independent reviewers extracted data using a standardised form and evaluated the methodological quality of included studies. Pooled results were presented with geometric means ratios and analysed with random effect models. Prespecified sensitivity analyses were performed to explain heterogeneity.ResultsThe search strategy yielded 9228 citations. Two randomised controlled trials and 39 cohort studies were considered eligible (1862 patients). Most studies (n=23) considered Glasgow outcome score ≤3 as an unfavourable outcome. All studies reported at least one measurement of S-100β within 24 hours after traumatic brain injury. There was a significant positive association between S-100β protein concentrations and mortality (12 studies: geometric mean ratio 2.55, 95% confidence interval 2.02 to 3.21, I2=56%) and score ≤3 (18 studies: 2.62, 2.01 to 3.42, I2=79%). Sensitivity analysis based on sampling time, sampling type, blinding of outcome assessors, and timing of outcome assessment yielded similar results. Thresholds for serum S-100β protein values with 100% specificity ranged from 1.38 to 10.50 µg/L for mortality (six studies) and from 2.16 to 14.00 µg/L for unfavourable neurological prognosis as defined by the Glasgow outcome score.ConclusionsAfter moderate or severe traumatic brain injury, serum S-100β protein concentrations are significantly associated with unfavourable prognosis in the short, mid, or long term. Optimal thresholds for discrimination remain unclear. Measuring the S-100β protein could be useful in evaluating the severity of traumatic brain injury and in the determination of long term prognosis in patients with moderate and severe injury.