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Background Treatment for coronavirus disease 2019 (COVID-19) evolved between pandemic waves. Our objective was to compare treatments, acute care utilization, and outcomes of COVID-19 patients presenting to emergency departments (ED) across pandemic waves. Methods This observational study enrolled consecutive eligible COVID-19 patients presenting to 46 EDs participating in the Canadian COVID-19 ED Rapid Response Network (CCEDRRN) between March 1 and December 31, 2020. We collected data by retrospective chart review. Our primary outcome was in-hospital mortality. Secondary outcomes included treatments, hospital and ICU admissions, ED revisits and readmissions. Logistic regression modeling assessed the impact of pandemic wave on outcomes. Results We enrolled 9,967 patients in 8 provinces, 3,336 from the first and 6,631 from the second wave. Patients in the second wave were younger, fewer met criteria for severe COVID-19, and more were discharged from the ED. Adjusted for patient characteristics and disease severity, steroid use increased (odds ratio [OR] 7.4; 95% confidence interval [CI] 6.2–8.9), and invasive mechanical ventilation decreased (OR 0.5; 95% CI 0.4–0.7) in the second wave compared to the first. After adjusting for differences in patient characteristics and disease severity, the odds of hospitalization (OR 0.7; 95% CI 0.6–0.8) and critical care admission (OR 0.7; 95% CI 0.6–0.9) decreased, while mortality remained unchanged (OR 0.7; 95% CI 0.5–1.1). Interpretation In patients presenting to cute care facilities, we observed rapid uptake of evidence-based therapies and less use of experimental therapies in the second wave. We observed increased rates of ED discharges and lower hospital and critical care resource use over time. Substantial reductions in mechanical ventilation were not associated with increasing mortality. Advances in treatment strategies created health system efficiencies without compromising patient outcomes. Trial registration Clinicaltrials.gov, NCT04702945.

Background Cooling thermal burns with running water is a recommended first aid intervention. However, guidance on the ideal duration of cooling remains controversial and inconsistent across organisations. Aim To perform a systematic review of the evidence for the question; Among adults and children with thermal burn, does active cooling using running water as an immediate first aid intervention for 20 minutes or more, compared with active cooling using running water for any other duration, change the outcomes of burn size, burn depth, pain, adverse outcome (hypothermia) or complications? Method We searched Medline, Embase, Cochrane Database of Systematic Reviews and used ROBINS-I to assess for risk of bias. We used Grading of Recommendations, Assessment, Development and Evaluation methodology for determining the certainty of evidence. We included all studies that compared the selected outcomes of the duration of cooling of thermal burns with water in all patient ages. (PROSPERO registration number: CRD42021180665). From 560 screened references, we included four observational studies. In these studies, 48% of burns were cooled for 20 minutes or more. We found no benefit for a duration of 20 minutes or more of cooling when compared with less than 20 minutes of cooling for the outcomes of size and depth of burn, re-epithelialization, or the need for skin grafting. The evidence is of very low certainty owing to limitations in study design, risk of bias and indirectness. Conclusion The optimal duration of cooling for thermal burns remains unknown and future prospective research is required to better define this treatment recommendation.

Predicting mortality from COVID-19 using information available when patients present to the emergency department can inform goals-of-care decisions and assist with ethical allocation of critical care resources. The study objective was to develop and validate a clinical score to predict emergency department and in-hospital mortality among consecutive nonpalliative patients with COVID-19; in this study, we define palliative patients as those who do not want resuscitative measures, such as intubation, intensive care unit care or cardiopulmonary resuscitation.This derivation and validation study used observational cohort data recruited from 46 hospitals in 8 Canadian provinces participating in the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN). We included adult (age ≥ 18 yr) nonpalliative patients with confirmed COVID-19 who presented to the emergency department of a participating site between Mar. 1, 2020, and Jan. 31, 2021. We randomly assigned hospitals to derivation or validation, and prespecified clinical variables as candidate predictors. We used logistic regression to develop the score in a derivation cohort and examined its performance in predicting emergency department and in-hospital mortality in a validation cohort.Of 8761 eligible patients, 618 (7.0%) died. The CCEDRRN COVID-19 Mortality Score included age, sex, type of residence, arrival mode, chest pain, severe liver disease, respiratory rate and level of respiratory support. The area under the curve was 0.92 (95% confidence interval [CI] 0.90-0.93) in derivation and 0.92 (95% CI 0.90-0.93) in validation. The score had excellent calibration. These results suggest that scores of 6 or less would categorize patients as being at low risk for in-hospital death, with a negative predictive value of 99.9%. Patients in the low-risk group had an in-hospital mortality rate of 0.1%. Patients with a score of 15 or higher had an observed mortality rate of 81.0%.The CCEDRRN COVID-19 Mortality Score is a simple score that can be used for level-of-care discussions with patients and in situations of critical care resource constraints to accurately predict death using variables available on emergency department arrival. The score was derived and validated mostly in unvaccinated patients, and before variants of concern were circulating widely and newer treatment regimens implemented in Canada.ClinicalTrials.gov, no. NCT04702945.

Background Although several Utstein variables are known to independently improve survival, how they moderate the effect of emergency medical service (EMS) response times on survival is unknown. Objectives To quantify how public location, witnessed status, bystander CPR, and bystander AED shock individually and jointly moderate the effect of EMS response time delays on OHCA survival. Methods This retrospective cohort study was a secondary analysis of the Resuscitation Outcomes Consortium Epistry-Cardiac Arrest database (December 2005 to June 2015). We included all adult, non-traumatic, non-EMS witnessed, and EMS-treated OHCAs from eleven sites across the US and Canada. We trained a logistic regression model with standard Utstein control variables and interaction terms between EMS response time and the four aforementioned OHCA characteristics. Results 102,216 patients were included. Three of the four characteristics – witnessed OHCAs (OR = 0.962), bystander CPR (OR = 0.968) and public location (OR = 0.980) – increased the negative effect of a one-minute delay on the odds of survival. In contrast, a bystander AED shock decreased the negative effect of a one-minute response time delay on the odds of survival (OR = 1.064). The magnitude of the effect of a one-minute delay in EMS response time on the odds of survival ranged from 1.3% to 9.8% (average: 5.3%), depending on the underlying OHCA characteristics. Conclusions Delays in EMS response time had the largest reduction in survival odds for OHCAs that did not receive a bystander AED shock but were witnessed, occurred in public, and/or received bystander CPR. A bystander AED shock appears to be protective against a delay in EMS response time.

his is the sixth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. This summary addresses the most recently published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. Topics covered by systematic reviews include cardiopulmonary resuscitation during transport; approach to resuscitation after drowning; passive ventilation; minimizing pauses during cardiopulmonary resuscitation; temperature management after cardiac arrest; use of diagnostic point-of-care ultrasound during cardiac arrest; use of vasopressin and corticosteroids during cardiac arrest; coronary angiography after cardiac arrest; public-access defibrillation devices for children; pediatric early warning systems; maintaining normal temperature immediately after birth; suctioning of amniotic fluid at birth; tactile stimulation for resuscitation immediately after birth; use of continuous positive airway pressure for respiratory distress at term birth; respiratory and heart rate monitoring in the delivery room; supraglottic airway use in neonates; prearrest prediction of in-hospital cardiac arrest mortality; basic life support training for likely rescuers of high-risk populations; effect of resuscitation team training; blended learning for life support training; training and recertification for resuscitation instructors; and recovery position for maintenance of breathing and prevention of cardiac arrest. Members from 6 task forces have assessed, discussed, and debated the quality of the evidence using Grading of Recommendations Assessment, Development, and Evaluation criteria and generated consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections, and priority knowledge gaps for future research are listed. This is the sixth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. This summary addresses the most recently published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. Topics covered by systematic reviews include cardiopulmonary resuscitation during transport; approach to resuscitation after drowning; passive ventilation; minimizing pauses during cardiopulmonary resuscitation; temperature management after cardiac arrest; use of diagnostic point-of-care ultrasound during cardiac arrest; use of vasopressin and corticosteroids during cardiac arrest; coronary angiography after cardiac arrest; public-access defibrillation devices for children; pediatric early warning systems; maintaining normal temperature immediately after birth; suctioning of amniotic fluid at birth; tactile stimulation for resuscitation immediately after birth; use of continuous positive airway pressure for respiratory distress at term birth; respiratory and heart rate monitoring in the delivery room; supraglottic airway use in neonates; prearrest prediction of in-hospital cardiac arrest mortality; basic life support training for likely rescuers of high-risk populations; effect of resuscitation team training; blended learning for life support training; training and recertification for resuscitation instructors; and recovery position for maintenance of breathing and prevention of cardiac arrest. Members from 6 task forces have assessed, discussed, and debated the quality of the evidence using Grading of Recommendations Assessment, Development, and Evaluation criteria and generated consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections, and priority knowledge gaps for future research are listed.

Importance Emergency research is challenging to do well as it involves time sensitive interventions in unstable patients. There is limited time to obtain informed consent from the patient or their legally authorized representative (LAR). Such research is permitted under exception from informed consent (EFIC) if specific criteria are met, including notification after enrollment. Some question whether the risks of EFIC outweighs its benefits. To date, there is limited empiric information about time to notification (TTN) and rates of withdrawal in such trials. Objective To describe variation in TTN and rates of withdrawal among that patients enrolled in EFIC trials over a twelve-year period. Design We performed post hoc descriptive analyses of data from five trials conducted under EFIC. Setting Emergency medical services and receiving hospitals participating in the Resuscitation Outcomes Consortium in the United States and Canada. Participants Patients with out-of-hospital cardiac arrest or life-threatening traumatic injury. Exposures Notification strategies were specified at each site before initiation of enrollment by a local institutional review board. We monitored TTN within each site centrally throughout each study’s enrollment period. Outcomes TTN was defined as time from randomization to first-reported notification of patient or LAR of enrollment. Withdrawal was defined as patient or LAR opt out of ongoing participation at the time of notification. Results Of 35,442 patients enrolled in five trials, 33,805 had cardiac arrest; and 1636 had traumatic injury. TTN varied overall and by patient outcome. Among those with cardiac arrest, TTN ranged from median (5%ile, 95%ile) of 6 (1,27) days to 28 (2, 53) days across sites. 0.3% of notified patients with cardiac arrest withdrew. Among those with traumatic injury, TTN ranged from 0 (0, 5) days to 36 (5, 68) days across sites. 7.7% of notified patients with traumatic injury withdrew. Conclusions and Relevance There is large variation in TTN in trials conducted under EFIC for emergency research. This may be due to several factors. It may or may not be modifiable. Overall rates of withdrawal are low, which suggests current practices related to EFIC are acceptable to those who have participated in emergency research.

Background Analyses of data recorded by monitor-defibrillators that measure CPR depth with different methods show significant relationships between the process and outcome of CPR. Our objective was to evaluate whether chest compression depth was significantly associated with outcome based on accelerometer-recordings obtained with monitor-defibrillators from a single manufacturer, and to assess whether an accelerometer-based analysis corroborated evidence-based practice guidelines on performance of CPR. Methods and results We included 5434 adult patients treated from seven US and Canadian cities between January 2007 and May 2015. These had mean (SD) age of 64.2 (17.2) years, mean compression depth of 45.9 (12.7) mm, ROSC sustained to ED arrival of 26%, and survival to hospital discharge of 8%. For survival to discharge, the adjusted odds ratios were 1.15 (95% CI, 0.86, 1.55) for cases within 2005 depth range (38–51 mm), and 1.17 (95% CI, 0.91, 1.50) for cases within 2010 depth range (>50 mm) compared to those with an average depth of Conclusions This analysis of patients with OHCA demonstrated that increased chest compression depth measured by accelerometer is associated with better survival. It confirms that current evidence-based recommendations to compress within 50–60 mm are likely associated with greater survival than compressing to another depth.

ImportanceEarly and accurate diagnostic testing for SARS-CoV-2 is essential to initiate appropriate treatment and infection control and prevention measures among patients presenting to the hospital.ObjectiveTo evaluate the diagnostic sensitivity of the SARS-CoV-2 nucleic acid amplification test (NAAT) performed within 24 hours of arrival to the emergency department among a nationally representative sample of patients.Design, Setting, and ParticipantsThis diagnostic study was conducted at 47 hospitals across 7 provinces in Canada participating in the Canadian COVID-19 Rapid Response Emergency Department Network among consecutive eligible patients presenting to a participating emergency department who were tested for SARS-CoV-2 from March 1, 2020, to December 31, 2021. Patients not tested within 24 hours of arrival and those presenting with a positive result from a test performed in the community were excluded.Main Outcomes and MeasuresThe primary outcome was a positive result from the SARS-CoV-2 NAAT. Outcome measures were the diagnostic sensitivity and yield of the SARS-CoV-2 NAAT.ResultsOf 132 760 eligible patients (66 433 women [50.0%]; median age, 57 years [IQR, 37-74 years]), 17 174 (12.9%) tested positive for SARS-CoV-2 within 14 days of their first NAAT. The diagnostic sensitivity of the SARS-CoV-2 NAAT was 96.2% (17 070 of 17 740 [95% CI, 95.9%-96.4%]) among all of the tests performed. Estimates ranged from a high of 97.7% (1710 of 1751 [95% CI, 96.8%-98.3%]) on day 2 of symptoms to a low of 90.4% (170 of 188 [95% CI, 85.3%-94.2%]) on day 11 of symptoms among patients presenting with COVID-19 symptoms. Among patients reporting COVID-19 symptoms, the sensitivity of the SARS-CoV-2 NAAT was 97.1% (11 870 of 12 225 [95% CI, 96.7%-97.3%]) compared with 87.6% (812 of 927 [95% CI, 85.2%-89.6%]) among patients without COVID-19 symptoms. The diagnostic yield of the SARS-CoV-2 NAAT was 12.0% (18 985 of 158 004 [95% CI, 11.8%-12.2%]) and varied from a high of 20.0% (445 of 2229 [95% CI, 18.3%-21.6%]) among patients tested on day 10 after symptom onset to a low of 8.1% (1686 of 20 719 [95% CI, 7.7%-8.5%]) among patients presenting within the first 24 hours of symptom onset.Conclusions and RelevanceThis study suggests that the diagnostic sensitivity was high for the first SARS-CoV-2 NAAT performed in the hospital and did not vary significantly by symptom duration. Repeated testing of patients with negative test results should be avoided unless their pretest probability of disease is high.

Aim To evaluate the optimal timing and doses of epinephrine for Infants and children suffering in-hospital or out-of-hospital cardiac arrest. Methods We searched Medline, EMBASE, and Cochrane Controlled Register of Trials (CENTRAL) for human randomized clinical trials and observational studies including comparative cohorts. Two investigators reviewed relevance of studies, extracted the data, conducted meta-analyses and assessed the risk of bias using the GRADE and CLARITY frameworks. Authors of the eligible studies were contacted to obtain additional data. Critically important outcomes included return of spontaneous circulation, survival to hospital discharge and survival with good neurological outcome. Results We identified 7 observational studies suitable for meta-analysis and no randomized clinical trials. The overall certainty of evidence was very low. For the critically important outcomes, the earlier administration of epinephrine was favorable for both in-hospital and out-of-hospital cardiac arrest. Because of a limited number of eligible studies and the presence of severe confounding factors, we could not determine the optimal interval of epinephrine administration. Conclusions Earlier administration of the first epinephrine dose could be more favorable in non-shockable pediatric cardiac arrest. The optimal interval for epinephrine administration remains unclear.

Background: Studies examining gender-based differences in outcomes of patients experiencing out-of-hospital cardiac arrest have demonstrated that, despite a higher likelihood of return of spontaneous circulation, women do not have higher survival. Methods: Patients successfully resuscitated from out-of-hospital cardiac arrest enrolled in the CCC trial (Trial of Continuous or Interrupted Chest Compressions during CPR) were included. Hierarchical multivariable logistic regression models were constructed to evaluate the association between gender and survival after adjustment for age, gender, cardiac arrest rhythm, witnessed status, bystander cardiopulmonary resuscitation, episode location, epinephrine dose, emergency medical services response time, and duration of resuscitation. Do not resuscitate (DNR) and withdrawal of life-sustaining therapy (WLST) order status were used to assess whether differences in postresuscitation outcomes were modified by baseline prognosis. The analysis was replicated among ALPS trial (Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest) participants. Results: Among 4875 successfully resuscitated patients, 1825 (37.4%) were women and 3050 (62.6%) were men. Women were older (67.5 versus 65.3 years), received less bystander cardiopulmonary resuscitation (49.1% versus 54.9%), and had a lower proportion of cardiac arrests that were witnessed (55.1% versus 64.5%) or had shockable rhythm (24.3% versus 44.6%, P P =0.009) and had WLST (32.8% versus 29.8%, P =0.03). Discharge survival was significantly lower in women (22.5% versus 36.3%, P P =0.005). The association between gender and survival to discharge was modified by DNR and WLST order status such that women had significantly reduced survival to discharge among patients who were not designated DNR (31.3% versus 49.9%, P =0.005; adjusted odds ratio, 0.74 [95% CI, 0.60–0.91]) or did not have WLST (32.3% versus 50.7%, P =0.002; adjusted odds ratio, 0.73 [95% CI, 0.60–0.89]). In contrast, no gender difference in survival was noted among patients receiving a DNR order (6.7% versus 7.4%, P =0.90) or had WLST (2.8% versus 2.4%, P =0.93). Consistent patterns of association between gender and postresuscitation outcomes were observed in the secondary cohort. Conclusions: Among patients resuscitated after experiencing out-of-hospital cardiac arrest, discharge survival was significantly lower in women than in men, especially among patients considered to have a favorable prognosis.

Background: Substantial variation in survival following out-of-hospital cardiac arrest (OHCA) is described both internationally and nationally. The Utstein factors account for half of the variation, but the remaining is not fully understood. Local regulations or guidelines concerning the withholding and termination of resuscitation may influence the reporting of cardiac arrests when comparing outcomes between different Emergency Medical Service systems. Method: We have developed an online cross-sectional mixed-methods explanatory design survey aimed at describing the international and national variations in the initiation, the termination of resuscitation, and the refraining from resuscitation of adult patients (>18 years of age) suffering from non-traumatic OHCA. The respondents will be national experts and the questionnaire will be distributed among members of European Prehospital Research Alliance, the International Liaison Committee of Resuscitation, the European Resuscitation Council, and the Resuscitation Academy. Each invited country will have to identify at least two national experts with special expertise in prehospital resuscitation practices. We exclude countries with less than two respondents. Results: The survey will provide both quantitative and qualitative data. Quantitative data will be presented as frequencies and proportions. Qualitative data will be analyzed using content analysis. Conclusion: This survey could be of importance in understanding the multiple factors leading to the substantial variation in survival found following OHCA. Furthermore, the interpretation of future studies on OHCA from different settings may be improved to further increase survival following OHCA.

Background Despite high-quality cardiopulmonary resuscitation (CPR), early defibrillation, and antiarrhythmic medications, some patients remain in refractory ventricular fibrillation (VF) during out-of-hospital cardiac arrest. These patients have worse outcomes compared to patients who respond to initial treatment. Double sequential external defibrillation (DSED) and vector change (VC) defibrillation have been proposed as viable options for patients in refractory VF. However, the evidence supporting the use of novel defibrillation strategies is inconclusive. The objective of this study is to compare two novel therapeutic defibrillation strategies (DSED and VC) against standard defibrillation for patients with treatment refractory VF or pulseless ventricular tachycardia (pVT) during out-of-hospital cardiac arrest. Research question Among adult (≥ 18 years) patients presenting in refractory VF or pulseless ventricular tachycardia (pVT) during out-of-hospital cardiac arrest, does DSED or VC defibrillation result in greater rates of survival to hospital discharge compared to standard defibrillation? Methods This will be a three-arm, cluster randomized trial with repeated crossover conducted in six regions of Ontario, Canada (Peel, Halton, Toronto, Simcoe, London, and Ottawa), over 3 years. All adult (≥ 18 years) patients presenting in refractory VF (defined as patients presenting in VF/pVT and remaining in VF/pVT after three consecutive standard defibrillation attempts during out-of-hospital cardiac arrest of presumed cardiac etiology will be treated by one of three strategies: (1) continued resuscitation using standard defibrillation, (2) resuscitation involving DSED, or (3) resuscitation involving VC (change of defibrillation pads from anterior-lateral to anterior-posterior pad position) defibrillation. The primary outcome will be survival to hospital discharge. Secondary outcomes will include return of spontaneous circulation (ROSC), VF termination after the first interventional shock, VF termination inclusive of all interventional shocks, and number of defibrillation attempts to obtain ROSC. We will also perform an a priori subgroup analysis comparing rates of survival for those who receive “early DSED,” or first DSED shock is shock 4–6, to those who receive “late DSED,” or first DSED shock is shock 7 or later. Discussion A well-designed randomized controlled trial employing a standardized approach to alternative defibrillation strategies early in the treatment of refractory VF is urgently required to determine if the treatments of DSED or VC defibrillation impact clinical outcomes. Trial registration ClinicalTrials.gov NCT04080986. Registered on 6 September 2019.

This 2020 International Consensus on Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care Science With Treatment Recommendations on basic life support summarizes evidence evaluations performed for 20 topics that were prioritized by the Basic Life Support Task Force of the International Liaison Committee on Resuscitation. The evidence reviews include 16 systematic reviews, 3 scoping reviews, and 1 evidence update. Per agreement within the International Liaison Committee on Resuscitation, new or revised treatment recommendations were only made after a systematic review. Systematic reviews were performed for the following topics: dispatch diagnosis of cardiac arrest, use of a firm surface for CPR, sequence for starting CPR (compressions-airway-breaths versus airway-breaths-compressions), CPR before calling for help, duration of CPR cycles, hand position during compressions, rhythm check timing, feedback for CPR quality, alternative techniques, public access automated external defibrillator programs, analysis of rhythm during chest compressions, CPR before defibrillation, removal of foreign-body airway obstruction, resuscitation care for suspected opioid-associated emergencies, drowning, and harm from CPR to victims not in cardiac arrest. The topics that resulted in the most extensive task force discussions included CPR during transport, CPR before calling for help, resuscitation care for suspected opioid-associated emergencies, feedback for CPR quality, and analysis of rhythm during chest compressions. After discussion of the scoping reviews and the evidence update, the task force prioritized several topics for new systematic reviews.

This2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendationsfor advanced life support includes updates on multiple advanced life support topics addressed with 3 different types of reviews. Topics were prioritized on the basis of both recent interest within the resuscitation community and the amount of new evidence available since any previous review. Systematic reviews addressed higher-priority topics, and included double-sequential defibrillation, intravenous versus intraosseous route for drug administration during cardiac arrest, point-of-care echocardiography for intra-arrest prognostication, cardiac arrest caused by pulmonary embolism, postresuscitation oxygenation and ventilation, prophylactic antibiotics after resuscitation, postresuscitation seizure prophylaxis and treatment, and neuroprognostication. New or updated treatment recommendations on these topics are presented. Scoping reviews were conducted for anticipatory charging and monitoring of physiological parameters during cardiopulmonary resuscitation. Topics for which systematic reviews and new Consensuses on Science With Treatment Recommendations were completed since 2015 are also summarized here. All remaining topics reviewed were addressed with evidence updates to identify any new evidence and to help determine which topics should be the highest priority for systematic reviews in the next 1 to 2 years.

BACKGROUND No Food and Drug Administration-approved medication improves outcomes following traumatic brain injury (TBI). A forthcoming clinical trial that evaluated the effects of two prehospital tranexamic acid (TXA) dosing strategies compared with placebo demonstrated no differences in thromboelastography (TEG) values. We proposed to explore the impact of TXA on markers of coagulation and fibrinolysis in patients with moderate to severe TBI. METHODS Data were extracted from a placebo-controlled clinical trial in which patients 15 years or older with TBI (Glasgow Coma Scale, 3-12) and systolic blood pressure of ≥90 mm Hg were randomized prehospital to receive placebo bolus/placebo infusion (placebo), 1 g of TXA bolus/1 g of TXA infusion (bolus maintenance), or 2 g of TXA bolus/placebo infusion (bolus only). Thromboelastography was performed, and coagulation measures including prothrombin time, activated partial thromboplastin time, international ratio, fibrinogen, D-dimer, plasmin-antiplasmin (PAP), thrombin antithrombin, tissue plasminogen activator, and plasminogen activator inhibitor 1 were quantified at admission and 6 hours later. RESULTS Of 966 patients receiving study drug, 700 had laboratory tests drawn at admission and 6 hours later. There were no statistically significant differences in TEG values, including LY30, between groups (p > 0.05). No differences between prothrombin time, activated partial thromboplastin time, international ratio, fibrinogen, thrombin antithrombin, tissue plasminogen activator, and plasminogen activator inhibitor 1 were demonstrated across treatment groups. Concentrations of D-dimer in TXA treatment groups were less than placebo at 6 hours (p < 0.001). Concentrations of PAP in TXA treatment groups were less than placebo on admission (p < 0.001) and 6 hours (p = 0.02). No differences in D-dimer and PAP were observed between bolus maintenance and bolus only. CONCLUSION While D-dimer and PAP levels reflect a lower degree of fibrinolysis following prehospital administration of TXA when compared with placebo in a large prehospital trial of patients with TBI, TEG obtained on admission and 6 hours later did not demonstrate any differences in fibrinolysis between the two TXA dosing regimens and placebo. LEVEL OF EVIDENCE Diagnostic test, level III.

Background Remote ischemic conditioning (RIC) is a noninvasive therapeutic strategy that uses brief cycles of blood pressure cuff inflation and deflation to protect the myocardium against ischemia-reperfusion injury. We sought to compare major adverse cardiovascular events (MACE) for patients who received RIC before PCI for ST-segment–elevation myocardial infarction (STEMI) compared with standard care. Methods We conducted a pre- and postimplementation study. In the preimplementation phase, STEMI patients were taken directly to the PCI lab. After implementation, STEMI patients received 4 cycles of RIC by paramedics or emergency department staff before PCI. The primary outcome was MACE at 90 days. Secondary outcomes included MACE at 30, 60, and 180 days. Inverse probability of treatment weighting using propensity scores estimated causal effects independent from baseline covariables. Results A total of 1667 (866 preimplementation, 801 postimplementation) patients were included. In the preimplementation phase, 13.4% had MACE at 90 days compared with 11.8% in the postimplementation phase (odds ratio [OR] 0.86, 95% CI 0.62-1.21). There were no significant differences in MACE at 30, 60, and 180 days. Patients presenting with cardiogenic shock or cardiac arrest before PCI were less likely to have MACE at 90 days (42.7% pre vs 27.8% post) if they received RIC before PCI (OR 0.52, 95% CI 0.27-0.98). Conclusions A strategy of RIC before PCI for STEMI did not reduce 90-day MACE. Future research should explore the impact of RIC before PCI for longer-term clinical outcomes and for patients presenting with cardiogenic shock or cardiac arrest.

ObjectiveOur study objective was to describe the Canadian emergency medicine (EM) research community landscape prior to the initiation of a nationwide network.MethodsA two-phase electronic survey was sent to 17 Canadian medical schools. ThePhase 1 Environmental Scanwas administered to department chairs/hospital EM chiefs, to identify EM physicians conducting clinical or educational research. ThePhase 2 Surveywas sent to the identified EM researchers to assess four themes: 1) geographic distribution, 2) training/career satisfaction, 3) time/financial compensation, and 4) research facilitators/barriers. Descriptive analyses were conducted, and results were stratified by Canadian regions.ResultsA total of 92 EM researchers were identified inPhase 1; 67 (73%) responded to thePhase 2 Survey. Of those, 42 (63%) reported being clinical researchers, and 19 (45%) had a graduate degree. Three provinces encompassed most of the researchers (n = 35). Of the respondents, 61% had a research degree, 66% felt adequately trained for their research career, 73% had financial support, 83% had access to office spaces, 52% had no mentor during their first years of their career, 69% felt satisfied with their research career, and 82% suggested that they will still be conducting research in 5 years.ConclusionEM researchers reported being adequately trained, even though only a little over half had a graduate degree. Only two-thirds had financial support, and mentorship was lacking in one-third of the participants. Not all respondents had a form of infrastructure, but most felt optimistic about their careers. The Canadian EM research environment could be improved to ensure better research capacity.

Objectives The primary objective was to determine the feasibility and safety of a cluster randomized controlled trial (RCT) with crossover comparing vector change defibrillation (VC) or double sequential external defibrillation (DSED) to standard defibrillation for patients experiencing refractory ventricular fibrillation (VF). Secondary objectives were to assess the rates of VF termination (VFT) and return of spontaneous circulation (ROSC). Methods We conducted a pilot cluster RCT with crossover in four Canadian paramedic services including all treated adult OHCA patients who presented in VF and received a minimum of three successive defibrillation attempts. Each EMS service was randomly assigned to provide standard defibrillation, VC or DSED. Agencies crossed over to an alternate defibrillation strategy after six months. Results 152 patients were enrolled. With respect to feasibility, 89.5% of cases received the defibrillation strategy they were randomly allocated to, and 93.1% of cases received a VC or DSED shock prior to the sixth defibrillation attempt. There were no safety concerns reported. In the standard group, 66.6% of cases resulted in VFT, compared to 82.0% in VC and 76.3% in the DSED group. ROSC was achieved in 25.0%, 39.3% and 40.0% of standard, VC and DSED groups, respectively. Conclusions Our findings suggest the DOSE-VF protocol is feasible and safe. Rates of VFT and ROSC were higher in the VC and DSED than standard defibrillation. The results of this pilot trial will allow us to inform a multicenter cluster RCT with crossover to determine if alternate defibrillation strategies for refractory VF may impact clinical outcomes.

Background: Antiarrhythmic drugs have not proven to significantly improve overall survival after out-of-hospital cardiac arrest from shock-refractory ventricular fibrillation/pulseless ventricular tachycardia. How this might be influenced by the route of drug administration is not known. Methods: In this prespecified analysis of a randomized, placebo-controlled clinical trial, we compared the differences in survival to hospital discharge in adults with shock-refractory ventricular fibrillation/pulseless ventricular tachycardia out-of-hospital cardiac arrest who were randomly assigned by emergency medical services personnel to an antiarrhythmic drug versus placebo in the ALPS trial (Resuscitation Outcomes Consortium Amiodarone, Lidocaine or Placebo Study), when stratified by the intravenous versus intraosseous route of administration. Results: Of 3019 randomly assigned patients with a known vascular access site, 2358 received ALPS drugs intravenously and 661 patients by the intraosseous route. Intraosseous and intravenous groups differed in sex, time-to-emergency medical services arrival, and some cardiopulmonary resuscitation characteristics, but were similar in others, including time-to-intravenous/intrasosseous drug receipt. Overall hospital discharge survival was 23%. In comparison with placebo, discharge survival was significantly higher in recipients of intravenous amiodarone (adjusted risk ratio, 1.26 [95% CI, 1.06–1.50]; adjusted absolute survival difference, 5.5% [95% CI, 1.5–9.5]) and intravenous lidocaine (adjusted risk ratio, 1.21 [95% CI, 1.02–1.45]; adjusted absolute survival difference, 4.7% [95% CI, 0.7–8.8]); but not in recipients of intraosseous amiodarone (adjusted risk ratio, 0.94 [95% CI, 0.66–1.32]) or intraosseous lidocaine (adjusted risk ratio, 1.03 [95% CI, 0.74–1.44]). Survival to hospital admission also increased significantly when drugs were given intravenously but not intraosseously, and favored improved neurological outcome at discharge. There were no outcome differences between intravenous and intraosseous placebo, indicating that the access route itself did not demarcate patients with poor prognosis. The study was underpowered to assess intravenous/intraosseous drug interactions, which were not statistically significant. Conclusions: We found no significant effect modification by drug administration route for amiodarone or lidocaine in comparison with placebo during out-of-hospital cardiac arrest. However, point estimates for the effects of both drugs in comparison with placebo were significantly greater for the intravenous than for the intraosseous route across virtually all outcomes and beneficial only for the intravenous route. Given that the study was underpowered to statistically assess interactions, these findings signal the potential importance of the drug administration route during resuscitation that merits further investigation.

Large animal studies are an important step in the translation pathway, but single laboratory experiments do not replicate the variability in patient populations. Our objective was to demonstrate the feasibility of performing a multicenter, preclinical, randomized, double-blinded, placebo-controlled cardiac arrest trial. We evaluated the effect of epinephrine on coronary perfusion pressure (CPP) as previous single laboratory studies have reported mixed results.Forty-five swine from 5 different laboratories (Ann Arbor, MI; Baltimore, MD; Los Angeles, CA; Pittsburgh, PA; Toronto, ON) using a standard treatment protocol. Ventricular fibrillation was induced and left untreated for 6 min before starting continuous cardiopulmonary resuscitation (CPR). After 2 min of CPR, 9 animals from each lab were randomized to 1 of 3 interventions given over 12 minutes: (1) Continuous IV epinephrine infusion (0.00375 mg/kg/min) with placebo IV normal saline (NS) boluses every 4 min, (2) Continuous placebo IV NS infusion with IV epinephrine boluses (0.015 mg/kg) every 4 min or (3) Placebo IV NS for both infusion and boluses. The primary outcome was mean CPP during the 12 mins of drug therapy.There were no significant differences in mean CPP between the three groups: 14.4 ± 6.8 mmHg (epinephrine Infusion), 16.9 ± 5.9 mmHg (epinephrine bolus), and 14.4 ± 5.5 mmHg (placebo) (p = NS). Sensitivity analysis demonstrated inter-laboratory variability in the magnitude of the treatment effect (p = 0.004).This study demonstrated the feasibility of performing a multicenter, preclinical, randomized, double-blinded cardiac arrest trials. Standard dose epinephrine by bolus or continuous infusion did not increase coronary perfusion pressure during CPR when compared to placebo.

Background The coronavirus disease 2019 (COVID-19) pandemic has significantly influenced epidemiology, yet its impact on out-of-hospital cardiac arrest (OHCA) remains unclear. We aimed to evaluate the impact of the pandemic on the incidence and case fatality rate (CFR) of OHCA. We also evaluated the impact on intermediate outcomes and clinical characteristics. Methods PubMed, EMBASE, Web of Science, Scopus, and Cochrane Library databases were searched from inception to May 3, 2021. Studies were included if they compared OHCA processes and outcomes between the pandemic and historical control time periods. Meta-analyses were performed for primary outcomes [annual incidence, mortality, and case fatality rate (CFR)], secondary outcomes [field termination of resuscitation (TOR), return of spontaneous circulation (ROSC), survival to hospital admission, and survival to hospital discharge], and clinical characteristics (shockable rhythm and etiologies). This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42021253879). Results The COVID-19 pandemic was associated with a 39.5% increase in pooled annual OHCA incidence (p p Conclusion Compared to the pre-pandemic period, the COVID-19 pandemic period was significantly associated with increased OHCA incidence and worse outcomes.

Background Opioid overdose epidemic is a public health crisis that is impacting communities around the world. Overdose education and naloxone distribution programs equip and train lay people to respond in the event of an overdose. We aimed to design an open-access naloxone kit and ultra-brief education session for use in point-of-care settings. Methods We hosted a multi-stakeholder co-design workshop to elicit suggestions for the kit and education session. We recruited people with lived experience of opioid overdose, community representatives, and other stakeholders from family practice, emergency medicine, addictions medicine, and public health to participate in a one-day facilitated co-design discussion wherein large and small group discussions were audio-recorded, transcribed and analysed using thematic approaches. Results A total of twenty four participants participated in the multi-stakeholder workshop from five stakeholder groups including geographic and setting diversity. Collaborative dialogue and shared storytelling which revealed seven design considerations: recognizing overdose, how much naloxone, impact of stigma, legal risk of responding, position as conventional first aid, friends and family as responders, support to call 911. Conclusion To create an open access kit and ultra-brief education session for distribution in emergency departments, family practice and substance use treatment services, stigma is a central design consideration. Design choices that reference the iconography, type, and form of materials associated with first aid have the potential to satisfy the need to de-stigmatize overdose response.

Treatment for coronavirus disease 2019 (COVID-19) evolved between pandemic waves. Our objective was to compare treatments, acute care utilization, and outcomes of COVID-19 patients presenting to emergency departments (ED) across pandemic waves.This observational study enrolled consecutive eligible COVID-19 patients presenting to 46 EDs participating in the Canadian COVID-19 ED Rapid Response Network (CCEDRRN) between March 1 and December 31, 2020. We collected data by retrospective chart review. Our primary outcome was in-hospital mortality. Secondary outcomes included treatments, hospital and ICU admissions, ED revisits and readmissions. Logistic regression modeling assessed the impact of pandemic wave on outcomes.We enrolled 9,967 patients in 8 provinces, 3,336 from the first and 6,631 from the second wave. Patients in the second wave were younger, fewer met criteria for severe COVID-19, and more were discharged from the ED. Adjusted for patient characteristics and disease severity, steroid use increased (odds ratio [OR] 7.4; 95% confidence interval [CI] 6.2-8.9), and invasive mechanical ventilation decreased (OR 0.5; 95% CI 0.4-0.7) in the second wave compared to the first. After adjusting for differences in patient characteristics and disease severity, the odds of hospitalization (OR 0.7; 95% CI 0.6-0.8) and critical care admission (OR 0.7; 95% CI 0.6-0.9) decreased, while mortality remained unchanged (OR 0.7; 95% CI 0.5-1.1).In patients presenting to cute care facilities, we observed rapid uptake of evidence-based therapies and less use of experimental therapies in the second wave. We observed increased rates of ED discharges and lower hospital and critical care resource use over time. Substantial reductions in mechanical ventilation were not associated with increasing mortality. Advances in treatment strategies created health system efficiencies without compromising patient outcomes.Clinicaltrials.gov, NCT04702945.RéSUMé: CONTEXTE: Le traitement de la maladie à coronavirus 2019 (COVID-19) a évolué entre les vagues pandémiques. Notre objectif était de comparer les traitements, l'utilisation des soins aigus et les résultats des patients atteints de la maladie COVID-19 se présentant aux urgences à travers les vagues de pandémie. MéTHODES: Cette étude observationnelle a recruté des patients COVID-19 éligibles consécutifs se présentant à 46 services d'urgence participant au Réseau canadien de réponse rapide aux services d'urgence COVID-19 (CCEDRRN) entre le 1er mars et le 31 décembre 2020. Nous avons recueilli des données au moyen d’un examen rétrospectif des dossiers. Notre principal résultat a été la mortalité à l’hôpital. Les résultats secondaires incluaient les traitements, les admissions à l'hôpital et aux soins intensifs, les revisites aux urgences et les réadmissions. La modélisation par régression logistique a évalué l'impact de la vague de pandémie sur les résultats. RéSULTATS: Nous avons recruté 9 967 patients dans 8 provinces, 3 336 de la première vague et 6 631 de la deuxième vague. Les patients de la deuxième vague étaient plus jeunes, moins nombreux à répondre aux critères de gravité de la COVID-19 et plus nombreux à quitter les urgences. Après ajustement en fonction des caractéristiques des patients et de la gravité de la maladie, le recours aux stéroïdes a augmenté (rapport de cotes [RC] 7.4 ; intervalle de confiance à 95 % [IC] 6.2–8.9) et la ventilation mécanique invasive a diminué (RC 0.5 ; IC à 95 % 0.4–0.7) lors de la deuxième vague par rapport à la première. Après ajustement pour tenir compte des différences dans les caractéristiques des patients et la gravité de la maladie, les probabilités d'hospitalisation (RC 0.7 ; IC à 95 % 0.6–0.8) et d'admission en soins intensifs (RC 0.7 ; IC à 95 % 0.6–0.9) ont diminué, tandis que la mortalité est restée inchangée (RC 0.7 ; IC à 95 % 0.5–1.1). INTERPRéTATION: Chez les patients se présentant dans les établissements de soins de santé, nous avons observé une adoption rapide des thérapies fondées sur des données probantes et un moindre recours aux thérapies expérimentales lors de la deuxième vague. Nous avons observé une augmentation des taux de sortie des services d'urgence et une diminution de l'utilisation des ressources hospitalières et des soins intensifs au fil du temps. Les réductions substantielles de la ventilation mécanique n'étaient pas associées à une augmentation de la mortalité. Les progrès réalisés dans les stratégies de traitement ont permis d'améliorer l'efficacité des systèmes de santé sans compromettre les résultats pour les patients.

Aim Quantifying the ratio describing the difference between “true route” and “straight-line” distances from out-of-hospital cardiac arrests (OHCAs) to the closest accessible automated external defibrillator (AED) can help correct likely overestimations in AED coverage. Furthermore, we aimed to examine to what extent the closest AED based on true route distance differed from the closest AED using “straight-line”. Methods OHCAs (1994–2016) and AEDs (2016) in Copenhagen, Denmark and in Toronto, Canada (2007–2015 and 2015, respectively) were identified. Three distances were calculated between OHCA and target AED: 1) the straight-line distance (“straight-line”) to the closest AED, 2) the corresponding true route distance to the same AED (“true route”), and 3) the closest AED based only on true route distance (“shortest true route”). The ratio between “true route” and “straight-line” distance was calculated and differences in AED coverage (an OHCA ≤ 100 m of an accessible AED) were examined. Results The “straight-line” AED coverage of 100 m was 24.2% (n = 2008/8295) in Copenhagen and 6.9% (n = 964/13916) in Toronto. The corresponding “true route” distance reduced coverage to 9.5% (n = 786) and 3.8% (n = 529), respectively. The median ratio between “true route” and “straight-line” distance was 1.6 in Copenhagen and 1.4 in Toronto. In 26.1% (n = 2167) and 22.9% (n = 3181) of all Copenhagen and Toronto OHCAs respectively, the closest AED in “shortest true route” was different than the closest AED initially found by “straight-line”. Conclusions Straight-line distance is not an accurate measure of distance and overestimates the actual AED coverage compared to a more realistic true route distance by a factor 1.4–1.6.

The opioid crisis is a growing public health emergency and increasing resources are being directed towards overdose education. Simulation has emerged as a novel strategy for training overdose response, yet little is known about training non-clinicians in bystander resuscitation. Understanding the perspectives of individuals who are likely to experience or witness opioid overdose is critical to ensure that emergency response is effective. The Surviving Opioid Overdose with Naloxone Education and Resuscitation (SOONER) study evaluates the effectiveness of a novel naloxone education and distribution tool among people who are non-clinicians and likely to witness opioid overdose. Participants’ resuscitation skills are evaluated using a realistic overdose simulation as the primary outcome of the trial. The purpose of our study is to describe the experience of participants with the simulation process in the SOONER study. We employed a semi-structured debriefing interview and a follow up qualitative interview to understand the experience of participants with simulation. A qualitative content analysis was performed using data from 21 participants who participated in the SOONER study. Our qualitative analysis identified 5 themes and 17 subthemes which described the experience of participants within the simulation process. These themes included realism, valuing practical experience, improving self-efficacy, gaining new perspective and bidirectional learning. Our analysis found that simulation was a positive and empowering experience for participants in the SOONER trial, most of whom are marginalized in society. Our study supports the notion that expanding simulation-based education to non-clinicians may offer an acceptable and effective way of supplementing current opioid overdose education strategies. Increasing the accessibility of simulation-based education may represent a paradigm shift whereby simulation is transformed from a primarily academic practice into a patient-based community resource.

We plan to conduct a randomised clinical trial among people likely to witness opioid overdose to compare the educational effectiveness of point-of-care naloxone distribution with best-available care, by observing participants' resuscitation skills in a simulated overdose. This mixed methods feasibility study aims to assess the effectiveness of recruitment and retention strategies and acceptability of study procedures.We implemented candidate-driven recruitment strategies with verbal consent and destigmatizing study materials in a family practice, emergency department, and addictions service. People ≥16 years of age who are likely to witness overdose were randomized to point-of-care naloxone distribution or referral to an existing program. We evaluated participant skills as a responder to a simulated overdose 3-14 days post-recruitment. Retention strategies included flexible scheduling, reminders, cash compensation and refreshments. The primary outcome was recruitment and retention feasibility, defined as the ability to recruit 28 eligible participants in 28 days, with50% attrition at the outcome simulation. Acceptability of study procedures and motivations for participation were assessed in a semi-structured interview.We enrolled 30 participants over 24 days, and retained 21 participants (70%, 95%CI 56.7-100). The most common motivation for participation was a desire to serve the community or loved ones in distress. Participants reported that study procedures were acceptable and that the outcome simulation provided a supportive and affirming environment.The planned trial is ready for implementation. Recruitment and retention is feasible and study processes are acceptable for people who are likely to witness overdose. (Registration: NCT03821649).

BackgroundTreatment strategies for coronavirus disease 2019 (COVID-19) evolved between pandemic waves. Our objective was to compare treatments, acute care resource utilization, and outcomes of COVID-19 patients presenting to Emergency Departments across two pandemic waves.MethodsThis observational study enrolled consecutive eligible COVID-19 patients presenting to 46 Emergency Departments participating in the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN) between March 1 and December 31, 2020. We collected data by retrospective chart review. Our primary outcome was in-hospital mortality. We used logistic regression modeling to assess the impact of pandemic wave on outcomes.ResultsWe enrolled 9,967 patients in 8 provinces, 3,336 from the first and 6,631 from the second wave. Patients in the second wave were younger, fewer met criteria for severe COVID-19, and more were discharged from the Emergency Department. Adjusted for patient characteristics and disease severity, steroid use increased (odds ratio [OR] 8.0; 95% confidence interval [CI] 6.4 – 10.0), while the use of invasive mechanical ventilation decreased (OR 0.5; 95%CI 0.4 – 0.6) in the second wave. After adjusting for differences in patient characteristics and disease severity, the odds of hospitalization (OR 0.7; 95%CI 0.6 – 0.8) and critical care admission (OR 0.6; 95%CI 0.4 – 0.7) decreased, while mortality remained unchanged (OR 1.0; 95%CI 0.7-1.4).InterpretationIn patients presenting to Canadian acute care facilities, rapid uptake of steroid therapy was evident. Mortality was stable despite lower critical care utilization in the second wave.Trial RegistrationClinicaltrials.gov, NCT04702945

BackgroundPredicting mortality from coronavirus disease 2019 (COVID-19) using information available when patients present to the Emergency Department (ED) can inform goals-of-care decisions and assist with ethical allocation of critical care resources.MethodsWe conducted an observational study to develop and validate a clinical score to predict ED and in-hospital mortality among consecutive non-palliative COVID-19 patients. We recruited from 44 hospitals participating in the Canadian COVID-19 ED Rapid Response Network (CCEDRRN) between March 1, 2020 and January 31, 2021. We randomly assigned hospitals to derivation or validation, and pre-specified clinical variables as candidate predictors. We used logistic regression to develop the score in a derivation cohort, and examined its performance in predicting ED and in-hospital mortality in a validation cohort.ResultsOf 8,761 eligible patients, 618 (7·01%) died. The score included age, sex, type of residence, arrival mode, chest pain, severe liver disease, respiratory rate, and level of respiratory support. The area under the curve was 0·92 (95% confidence intervals [CI] 0·91–0·93) in derivation and 0·92 (95%CI 0·89–0·93) in validation. The score had excellent calibration. Above a score of 15, the observed mortality was 81·0% (81/100) with a specificity of 98·8% (95%CI 99·5–99·9%).InterpretationThe CCEDRRN COVID Mortality Score is a simple score that accurately predicts mortality with variables that are available on patient arrival without the need for diagnostic tests.Trial registrationClinicaltrials.gov, NCT04702945

ObjectivesTo develop and validate a clinical risk score that can accurately quantify an emergency department patient’s probability of SARS-CoV-2 infection without the need for laboratory testingDesignCohort study of participants in the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN) registry. Regression models were fitted to predict a positive SARS-CoV-2 test result using clinical and demographic predictors, as well as an indicator of local SARS-CoV-2 incidence.Setting32 emergency departments in eight Canadian provincesParticipants27,665 consecutively-enrolled patients who were tested for SARS-CoV-2 in participating emergency departments between March 1-October 30,2020Main outcome measuresPositive SARS-CoV-2 nucleic acid test result within 14 days of an index emergency department encounter for suspected COVID-19 diseaseResultsWe derived a 10-item CCEDRRN COVID-19 Infection Score using data from 21,743 patients. This score included variables from history and physical examination, and an indicator of local disease incidence. The score had a c-statistic of 0.838 with excellent calibration. We externally validated the rule in 5,295 patients. The score maintained excellent discrimination and calibration, and had superior performance compared to another previously published risk score. Score cutoffs were identified that can rule-in or rule-out SARS-CoV-2 infection without the need for nucleic acid testing with 97.4 % sensitivity (95% CI 96.4–98..3) and 95.9% specificity (95% CI 95.5-96.0).ConclusionsThe CCEDRRN COVID-19 Infection Score uses clinical characteristics and publicly available indicators of disease incidence to quantify a patient’s probability of SARS-CoV-2 infection. The score can identify patients at sufficiently high risk of SARS-CoV-2 infection to warrant isolation and empiric therapy prior to test confirmation, while also identifying patients at sufficiently low risk of infection that they may not need testing.Trial registrationCCEDRRN is registered at clinicaltrials.gov (NCT04702945).FundingThe network is funded by the Canadian Institutes of Health Research (447679), BC Academic Health Science Network Society, BioTalent Canada, Genome BC (COV024; VAC007), Ontario Ministry of Colleges and Universities (C-655-2129), the Saskatchewan Health Research Foundation (5357) and the Fondation CHU de Québec (Octroi #4007). These organizations are not-for-profit, and had no role in study conduct, analysis, or manuscript preparation.

Scientific evidence is often poorly implemented or misinterpreted when it is incorporated into clinical practice.1 Trends in clinical care after publication of the first TTM (Target Temperature Man...

Aim: We plan to conduct a randomised clinical trial among people likely to witness opioid overdose to compare the educational effectiveness of point-of-care naloxone distribution with best-available care, by observing participants’ resuscitation skills in a simulated overdose. This mixed methods feasibility study aims to assess the effectiveness of recruitment and retention strategies and acceptability of study procedures. Methods: We implemented candidate-driven recruitment strategies with verbal consent and destigmatizing study materials in a family practice, emergency department, and addictions service. People ≥16 years of age who are likely to witness overdose were randomized to point-of-care naloxone distribution or referral to an existing program. We evaluated participant skills as a responder to a simulated overdose 3–14 days post-recruitment. Retention strategies included flexible scheduling, reminders, cash compensation and refreshments. The primary outcome was recruitment and retention feasibility, defined as the ability to recruit 28 eligible participants in 28 days, with