Considerations for the design of overdose education and naloxone distribution interventions: results of a multi-stakeholder workshop.

INTRODUCTION: 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 understand factors to consider for the design of naloxone distribution programs in point-of-care settings from the point of view of community stakeholders. METHODS: We hosted a multi-stakeholder co-design workshop to elicit suggestions for a naloxone distribution program. 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 full-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 revealed seven considerations for the design of naloxone distribution programs specific to training needs and the provision of naloxone, these are: 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 naloxone distribution program in emergency departments, family practice and substance use treatment services, stigma is a central design consideration for training and naloxone kits. 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.

The burden of incidental SARS-CoV-2 infections in hospitalized patients across pandemic waves in Canada.

Many health authorities differentiate hospitalizations in patients infected with SARS-CoV-2 as being "for COVID-19" (due to direct manifestations of SARS-CoV-2 infection) versus being an "incidental" finding in someone admitted for an unrelated condition. We conducted a retrospective cohort study of all SARS-CoV-2 infected patients hospitalized via 47 Canadian emergency departments, March 2020-July 2022 to determine whether hospitalizations with "incidental" SARS-CoV-2 infection are less of a burden to patients and the healthcare system. Using a priori standardized definitions applied to hospital discharge diagnoses in 14,290 patients, we characterized COVID-19 as (i) the "Direct" cause for the hospitalization (70%), (ii) a potential "Contributing" factor for the hospitalization (4%), or (iii) an "Incidental" finding that did not influence the need for admission (26%). The proportion of incidental SARS-CoV-2 infections rose from 10% in Wave 1 to 41% during the Omicron wave. Patients with COVID-19 as the direct cause of hospitalization exhibited significantly longer LOS (mean 13.8 versus 12.1 days), were more likely to require critical care (22% versus 11%), receive COVID-19-specific therapies (55% versus 19%), and die (17% versus 9%) compared to patients with Incidental SARS-CoV-2 infections. However, patients hospitalized with incidental SARS-CoV-2 infection still exhibited substantial morbidity/mortality and hospital resource use.

Defibrillation Strategies for Refractory Ventricular Fibrillation.

BACKGROUND: Despite advances in defibrillation technology, shock-refractory ventricular fibrillation remains common during out-of-hospital cardiac arrest. Double sequential external defibrillation (DSED; rapid sequential shocks from two defibrillators) and vector-change (VC) defibrillation (switching defibrillation pads to an anterior-posterior position) have been proposed as defibrillation strategies to improve outcomes in patients with refractory ventricular fibrillation. METHODS: We conducted a cluster-randomized trial with crossover among six Canadian paramedic services to evaluate DSED and VC defibrillation as compared with standard defibrillation in adult patients with refractory ventricular fibrillation during out-of-hospital cardiac arrest. Patients were treated with one of these three techniques according to the strategy that was randomly assigned to the paramedic service. The primary outcome was survival to hospital discharge. Secondary outcomes included termination of ventricular fibrillation, return of spontaneous circulation, and a good neurologic outcome, defined as a modified Rankin scale score of 2 or lower (indicating no symptoms to slight disability) at hospital discharge. RESULTS: A total of 405 patients were enrolled before the data and safety monitoring board stopped the trial because of the coronavirus disease 2019 pandemic. A total of 136 patients (33.6%) were assigned to receive standard defibrillation, 144 (35.6%) to receive VC defibrillation, and 125 (30.9%) to receive DSED. Survival to hospital discharge was more common in the DSED group than in the standard group (30.4% vs. 13.3%; relative risk, 2.21; 95% confidence interval [CI], 1.33 to 3.67) and more common in the VC group than in the standard group (21.7% vs. 13.3%; relative risk, 1.71; 95% CI, 1.01 to 2.88). DSED but not VC defibrillation was associated with a higher percentage of patients having a good neurologic outcome than standard defibrillation (relative risk, 2.21 [95% CI, 1.26 to 3.88] and 1.48 [95% CI, 0.81 to 2.71], respectively). CONCLUSIONS: Among patients with refractory ventricular fibrillation, survival to hospital discharge occurred more frequently among those who received DSED or VC defibrillation than among those who received standard defibrillation. (Funded by the Heart and Stroke Foundation of Canada; DOSE VF ClinicalTrials.gov number, NCT04080986.).

Derivation and validation of a clinical decision rule to risk-stratify COVID-19 patients discharged from the emergency department: The CCEDRRN COVID discharge score.

Objective: To risk-stratify COVID-19 patients being considered for discharge from the emergency department (ED). Methods: We conducted an observational study to derive and validate a clinical decision rule to identify COVID-19 patients at risk for hospital admission or death within 72 hours of ED discharge. We used data from 49 sites in the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN) between March 1, 2020, and September 8, 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 short-term adverse outcomes in a validation cohort. Results: Of 15,305 eligible patient visits, 535 (3.6%) experienced the outcome. The score included age, sex, pregnancy status, temperature, arrival mode, respiratory rate, and respiratory distress. The area under the curve was 0.70 (95% confidence interval [CI] 0.68-0.73) in derivation and 0.71 (95% CI 0.68-0.73) in combined derivation and validation cohorts. Among those with a score of 3 or less, the risk for the primary outcome was 1.9% or less, and the sensitivity of using 3 as a rule-out score was 89.3% (95% CI 82.7-94.0). Among those with a score of ≥9, the risk for the primary outcome was as high as 12.2% and the specificity of using 9 as a rule-in score was 95.6% (95% CI 94.9-96.2). Conclusion: The CCEDRRN COVID discharge score can identify patients at risk of short-term adverse outcomes after ED discharge with variables that are readily available on patient arrival.

Sensitivity and Diagnostic Yield of the First SARS-CoV-2 Nucleic Acid Amplification Test Performed for Patients Presenting to the Hospital.

Importance: Early 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. Objective: To 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 Participants: This 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 Measures: The 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. Results: Of 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 Relevance: This 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.

Treatments, resource utilization, and outcomes of COVID-19 patients presenting to emergency departments across pandemic waves: an observational study by the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN).

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.

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] 6.2­8.9) et la ventilation mécanique invasive a diminué (RC 0.5 ; IC à 95 % 0.4­0.7) 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 % 0.6­0.8) et d'admission en soins intensifs (RC 0.7 ; IC à 95 % 0.6­0.9) ont diminué, tandis que la mortalité est restée inchangée (RC 0.7 ; IC à 95 % 0.5­1.1). 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.

The CCEDRRN COVID-19 Mortality Score to predict death among nonpalliative patients with COVID-19 presenting to emergency departments: a derivation and validation study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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%. INTERPRETATION: 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. STUDY REGISTRATION: ClinicalTrials.gov, no. NCT04702945.

Impact of the COVID-19 pandemic on the epidemiology of out-of-hospital cardiac arrest: a systematic review and meta-analysis.

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 < 0.001). Pooled CFR was increased by 2.65% (p < 0.001), with a pooled odds ratio (OR) of 1.95 for mortality [95% confidence interval (95%CI) 1.51-2.51]. There was increased field TOR (OR = 2.46, 95%CI 1.62-3.74). There were decreased ROSC (OR = 0.65, 95%CI 0.55-0.77), survival to hospital admission (OR = 0.65, 95%CI 0.48-0.89), and survival to discharge (OR = 0.52, 95%CI 0.40-0.69). There was decreased shockable rhythm (OR = 0.73, 95%CI 0.60-0.88) and increased asphyxial etiology of OHCA (OR = 1.17, 95%CI 1.02-1.33). CONCLUSION: Compared to the pre-pandemic period, the COVID-19 pandemic period was significantly associated with increased OHCA incidence and worse outcomes.

CCEDRRN COVID-19 Infection Score (CCIS): development and validation in a Canadian cohort of a clinical risk score to predict SARS-CoV-2 infection in patients presenting to the emergency department with suspected COVID-19.

OBJECTIVES: To develop and validate a clinical risk score that can accurately quantify the probability of SARS-CoV-2 infection in patients presenting to an emergency department without the need for laboratory testing. DESIGN: Cohort 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. SETTING: 32 emergency departments in eight Canadian provinces. PARTICIPANTS: 27 665 consecutively enrolled patients who were tested for SARS-CoV-2 in participating emergency departments between 1 March and 30 October 2020. MAIN OUTCOME MEASURES: Positive SARS-CoV-2 nucleic acid test result within 14 days of an index emergency department encounter for suspected COVID-19 disease. RESULTS: We 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 5295 patients. The score maintained excellent discrimination and calibration and had superior performance compared with another previously published risk score. Score cut-offs 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 to 98.3) and 95.9% specificity (95% CI 95.5 to 96.0). CONCLUSIONS: The 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 empirical therapy prior to test confirmation while also identifying patients at sufficiently low risk of infection that they may not need testing. TRIAL REGISTRATION NUMBER: NCT04702945.

Development of the Canadian COVID-19 Emergency Department Rapid Response Network population-based registry: a methodology study.

BACKGROUND: Emergency physicians lack high-quality evidence for many diagnostic and treatment decisions made for patients with suspected or confirmed coronavirus disease 2019 (COVID-19). Our objective is to describe the methods used to collect and ensure the data quality of a multicentre registry of patients presenting to the emergency department with suspected or confirmed COVID-19. METHODS: This methodology study describes a population-based registry that has been enrolling consecutive patients presenting to the emergency department with suspected or confirmed COVID-19 since Mar. 1, 2020. Most data are collected from retrospective chart review. Phone follow-up with patients at 30 days captures the World Health Organization clinical improvement scale and contextual, social and cultural variables. Phone follow-up also captures patient-reported quality of life using the Veterans Rand 12-Item Health Survey at 30 days, 60 days, 6 months and 12 months. Fifty participating emergency departments from 8 provinces in Canada currently enrol patients into the registry. INTERPRETATION: Data from the registry of the Canadian COVID-19 Emergency Department Rapid Response Network will be used to derive and validate clinical decision rules to inform clinical decision-making, describe the natural history of the disease, evaluate COVID-19 diagnostic tests and establish the real-world effectiveness of treatments and vaccines, including in populations that are excluded or underrepresented in clinical trials. This registry has the potential to generate scientific evidence to inform our pandemic response, and to serve as a model for the rapid implementation of population-based data collection protocols for future public health emergencies. TRIAL REGISTRATION: Clinicaltrials.gov, no. NCT04702945.