CEPP: Canadian Extracorporeal Life Support (ECLS) Protocol Project

Background: Extracorporeal life support (ECLS) is associated with high morbidity and mortality. Complications and mortality are higher at lower-volume centres. Most Canadian ECLS institutions are low-volume centres. Protocols offer one way to share best practices among institutions to improve outcomes. Whether Canadian centres have ECLS protocols, and whether these protocols are comprehensive and homogenous across centres, is unknown. Methods: Purposeful sampling with mixed methods was used. A Delphi panel defined key elements relevant to the ECLS process. Documentation used in the delivery of ECLS services was requested from programs. Institutional protocols were assessed using deductive coding to determine the presence of key elements. Results: A total of 37 key elements spanning 5 domains (referral, initiation, maintenance, termination, and administration) were identified. Documentation from 13 institutions across 10 provinces was obtained. Institutions with heart or lung transplantation programs had more-complete documentation than did non-transplantation programs. Only 5 key elements were present in at least 50% of protocols (anticoagulation strategy, ventilation strategy, defined referral process, selection criteria, weaning process), and variation was seen in how institutions approached each of these elements. Conclusions: The completeness of ECLS protocols varies across Canada. Programs describe variable approaches to key elements. This variability might represent a lack of evidence or consensus in these areas and creates the opportunity for collaboration among institutions to share protocols and best practice. The key-element framework provides a common language that programs can use to develop ECLS programs, initiate quality-improvement projects, and identify research agendas

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

One‐year survival after out‐of‐ hospital cardiac arrest: Sex‐based survival analysis in a Canadian population

Abstract Objective We investigated sex differences in 1‐year survival in a cohort of patients who survived out‐of‐hospital cardiac arrest (OHCA) to hospital discharge. We hypothesized that female sex is associated with higher 1‐year posthospital discharge survival. Methods A retrospective analysis of linked data (2011–2017) from clinical databases in British Columbia (BC) was conducted. We used Kaplan–Meier curves, stratified by sex, to display survival up to 1‐year, and the log‐rank test to test for significant sex differences. This was followed by multivariable Cox proportional hazards analysis to investigate the association between sex and 1‐year mortality. The multivariable analysis adjusted for variables known to be associated with survival, including variables related to OHCA characteristics, comorbidities, medical diagnoses, and in‐hospital interventions. Results We included 1278 hospital‐discharge survivors; 284 (22.2%) were female. Females had a lower proportion of OHCA occurring in public locations (25.7% vs. 44.0%, P < 0.001), a lower proportion with a shockable rhythm (57.7% vs. 77.4%, P < 0.001), and fewer hospital‐based acute coronary diagnoses and interventions. One‐year survival for females and males was 90.5% and 92.4%, respectively (log‐rank P = 0.31). Unadjusted (hazard ratio [HR] males vs. females 0.80, 95% confidence interval [CI] 0.51–1.24, P = 0.31) and adjusted (HR males vs. females 1.14, 95% CI 0.72–1.81, P = 0.57) models did not detect differences in 1‐year survival by sex. Conclusion Females have relatively unfavorable prehospital characteristics in OHCA and fewer hospital‐based acute coronary diagnoses and interventions. However, among survivors to hospital discharge, we found no significant difference between males and females in 1‐year survival, even after adjustment

Rapid agitation control with ketamine in the emergency department (RACKED): a randomized controlled trial protocol

Background: The rapid control of patients presenting to the emergency department (ED) with psychomotor agitation and violent behavior is paramount for the safety of patients and ED staff. The use of intramuscular (IM) ketamine in the pre-hospital and ED settings has demonstrated promising preliminary results to provide rapid and safe behavioral control. A prospective, randomized controlled trial is required to measure the potential superiority of IM ketamine compared to current standard care (IM benzodiazepines plus antipsychotics). Methods: This will be a parallel, prospective, randomized, controlled trial of 5 mg/kg IM ketamine compared to a combination of 5 mg IM midazolam and 5 mg IM haloperidol. The study will enroll approximately 184 patients, randomized equally to two study arms. There will be one study visit during which study medication will be administered and assessments will be completed. A follow-up safety visit will occur on day 3. The primary objective of this study is to compare IM ketamine to a combination of IM midazolam and haloperidol with regards to the time required for adequate behavioral control, in minutes, in patients presenting to the ED with psychomotor agitation and violent behavior, as measured by the Richmond Agitation-Sedation Scale (RASS). Discussion: We present a novel study to determine whether ketamine is a rapid and safe option, compared to a combination of midazolam and haloperidol for the sedation of patients presenting to the ED with psychomotor agitation and violent behavior. To our knowledge, this study is the first randomized controlled trial to compare ketamine to current standard care for this indication. We have attempted to address numerous logistical issues with the design of this study including a waiver of consent, ensuring adequate blinding of outcome assessors, patient enrolment, and data monitoring. Trial registration: Clinicaltrials.gov, NCT03375671 . Registered on 18 December 2017.Medicine, Faculty ofOther UBCEmergency Medicine, Department ofOccupational Science and Occupational Therapy, Department ofPopulation and Public Health (SPPH), School ofPsychiatry, Department ofReviewedFacult

BrainNetCNN: Convolutional neural networks for brain networks; towards predicting neurodevelopment

We propose BrainNetCNN, a convolutional neural network (CNN) framework to predict clinical neurodevelopmental outcomes from brain networks. In contrast to the spatially local convolutions done in traditional image-based CNNs, our BrainNetCNN is composed of novel edge-to-edge, edge-to-node and node-to-graph convolutional filters that leverage the topological locality of structural brain networks. We apply the BrainNetCNN framework to predict cognitive and motor developmental outcome scores from structural brain networks of infants born preterm. Diffusion tensor images (DTI) of preterm infants, acquired between 27 and 46 weeks gestational age, were used to construct a dataset of structural brain connectivity networks. We first demonstrate the predictive capabilities of BrainNetCNN on synthetic phantom networks with simulated injury patterns and added noise. BrainNetCNN outperforms a fully connected neural-network with the same number of model parameters on both phantoms with focal and diffuse injury patterns. We then apply our method to the task of joint prediction of Bayley-III cognitive and motor scores, assessed at 18 months of age, adjusted for prematurity. We show that our BrainNetCNN framework outperforms a variety of other methods on the same data. Furthermore, BrainNetCNN is able to identify an infant's postmenstrual age to within about 2 weeks. Finally, we explore the high-level features learned by BrainNetCNN by visualizing the importance of each connection in the brain with respect to predicting the outcome scores. These findings are then discussed in the context of the anatomy and function of the developing preterm infant brain.The authors thank the families for their participation, as well as Anne Synnes for her assistance with gathering and interpreting the infant data and also the staff in the Neonatal Follow-Up Program of BC Children's & Women's Hospitals for their valuable contribution in assessing these children. This work is supported by Canadian Institutes for Health Research (CIHR) operating grants MOP-79262 (S.P.M.) and MOP-86489 (R.E.G.). S.P.M. is currently the Bloorview Children's Hospital Chair in Pediatric Neuroscience. R.E.G. is supported by a Senior Scientist Award from the Child & Family Research Institute. J.G.Z. is supported by a Michael Smith Foundation for Health Research Scholar Award and a Canadian Child Health Clinician Scientist Program Career Enhancement Award. We also thank the Natural Sciences and Engineering Research Council of Canada (NSERC) for partial funding. Finally, we thank the reviewers for their valuable feedback that resulted in a much improved paper

The association of extreme environmental heat with incidence and outcomes of out-of-hospital cardiac arrest in British Columbia: A time series analysis

Background: The impact of extreme heat on out-of-hospital cardiac arrest (OHCA) incidence and outcomes is under-studied. We investigated OHCA incidence and outcomes over increasing temperatures. Methods: We included non-traumatic EMS (Emergency Medical Services)-assessed OHCAs in British Columbia during the warm seasons of 2020–2021. We fit a time-series quasi-Poisson generalized linear model to estimate the association between temperature and incidence of both EMS-assessed, EMS-treated, and EMS-untreated OHCAs. Second, we employed a logistic regression model to estimate the association between “heatwave” periods (defined as a daily mean temperature > 99th percentile for ≥ 2 consecutive days, plus 3 lag days) with survival and favourable neurological outcomes (cerebral performance category ≤ 2) at hospital discharge. Results: Of 5478 EMS-assessed OHCAs, 2833 were EMS-treated. OHCA incidence increased with increasing temperatures, especially exceeding a daily mean temperature of 25 °C Compared to the median daily mean temperature (16.9 °C), the risk of EMS-assessed (relative risk [RR] 3.7; 95%CI 3.0–4.6), EMS-treated (RR 2.9; 95%CI 2.2–3.9), and EMS-untreated (RR 4.3; 95%CI 3.2–5.7) OHCA incidence were higher during days with a temperature over the 99th percentile. Of EMS-treated OHCAs, during the heatwave (n = 179) and non-heatwave (n = 2654) periods, 4 (2.2%) and 270 (10%) survived and 4 (2.2%) and 241 (9.2%) had favourable neurological outcomes, respectively. Heatwave period OHCAs had decreased odds of survival (adjusted OR 0.28; 95%CI 0.10–0.79) and favourable neurological outcome (adjusted OR 0.31; 95%CI 0.11–0.89) at hospital discharge, compared to other periods. Conclusion: Extreme heat was associated with a higher incidence of OHCA, and lower odds of survival and favourable neurological status at hospital discharge

Intraarrest transport, extracorporeal cardiopulmonary resuscitation, and early invasive management in refractory out-of-hospital cardiac arrest: an individual patient data pooled analysis of two randomised trials

Background: Refractory out-of-hospital cardiac arrest (OHCA) treated with standard advanced cardiac life support (ACLS) has poor outcomes. Transport to hospital followed by in-hospital extracorporeal cardiopulmonary resuscitation (ECPR) initiation may improve outcomes. We performed a pooled individual patient data analysis of two randomised controlled trials evaluating ECPR based approach in OHCA. Methods: The individual patient data from two published randomised controlled trials (RCTs) were pooled: ARREST (enrolled Aug 2019–June 2020; NCT03880565) and PRAGUE-OHCA (enrolled March 1, 2013–Oct 25, 2020; NCT01511666). Both trials enrolled patients with refractory OHCA and compared: intra-arrest transport with in-hospital ECPR initiation (invasive approach) versus continued standard ACLS. The primary outcome was 180-day survival with favourable neurological outcome (defined as Cerebral Performance Category 1–2). Secondary outcomes included: cumulative survival at 180 days, 30-day favourable neurological survival, and 30-day cardiac recovery. Risk of bias in each trial was assessed by two independent reviewers using the Cochrane risk-of-bias tool. Heterogeneity was assessed via Forest plots. Findings: The two RCTs included 286 patients. Of those randomised to the invasive (n = 147) and standard (n = 139) groups, respectively: the median age was 57 (IQR 47–65) and 58 years (IQR 48–66), and the median duration of resuscitation was 58 (IQR 43–69) and 49 (IQR 33–71) minutes (p = 0.17). In a modified intention to treat analysis, 45 (32.4%) in the invasive and 29 (19.7%) patients in the standard arm survived to 180 days with a favourable neurological outcome [absolute difference (AD), 95% CI: 12.7%, 2.6–22.7%, p = 0.015]. Forty-seven (33.8%) and 33 (22.4%) patients survived to 180 days [HR 0.59 (0.43–0.81); log rank test p = 0.0009]. At 30 days, 44 (31.7%) and 24 (16.3%) patients had favourable neurological outcome (AD 15.4%, 5.6–25.1%, p = 0.003), 60 (43.2%), and 46 (31.3%) patients had cardiac recovery (AD: 11.9%, 0.7–23%, p = 0.05), in the invasive and standard arms, respectively. The effect was larger in patients presenting with shockable rhythms (AD 18.8%, 7.6–29.4; p = 0.01; HR 2.26 [1.23–4.15]; p = 0.009) and prolonged CPR (>45 min; HR 3.99 (1.54–10.35); p = 0.005). Interpretation: In patients with refractory OHCA, the invasive approach significantly improved 30- and 180-day neurologically favourable survival. Funding: None.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Intraarrest transport, extracorporeal cardiopulmonary resuscitation, and early invasive management in refractory out-of-hospital cardiac arrest: an individual patient data pooled analysis of two randomised trialsResearch in context

Summary: Background: Refractory out-of-hospital cardiac arrest (OHCA) treated with standard advanced cardiac life support (ACLS) has poor outcomes. Transport to hospital followed by in-hospital extracorporeal cardiopulmonary resuscitation (ECPR) initiation may improve outcomes. We performed a pooled individual patient data analysis of two randomised controlled trials evaluating ECPR based approach in OHCA. Methods: The individual patient data from two published randomised controlled trials (RCTs) were pooled: ARREST (enrolled Aug 2019–June 2020; NCT03880565) and PRAGUE-OHCA (enrolled March 1, 2013–Oct 25, 2020; NCT01511666). Both trials enrolled patients with refractory OHCA and compared: intra-arrest transport with in-hospital ECPR initiation (invasive approach) versus continued standard ACLS. The primary outcome was 180-day survival with favourable neurological outcome (defined as Cerebral Performance Category 1–2). Secondary outcomes included: cumulative survival at 180 days, 30-day favourable neurological survival, and 30-day cardiac recovery. Risk of bias in each trial was assessed by two independent reviewers using the Cochrane risk-of-bias tool. Heterogeneity was assessed via Forest plots. Findings: The two RCTs included 286 patients. Of those randomised to the invasive (n = 147) and standard (n = 139) groups, respectively: the median age was 57 (IQR 47–65) and 58 years (IQR 48–66), and the median duration of resuscitation was 58 (IQR 43–69) and 49 (IQR 33–71) minutes (p = 0.17). In a modified intention to treat analysis, 45 (32.4%) in the invasive and 29 (19.7%) patients in the standard arm survived to 180 days with a favourable neurological outcome [absolute difference (AD), 95% CI: 12.7%, 2.6–22.7%, p = 0.015]. Forty-seven (33.8%) and 33 (22.4%) patients survived to 180 days [HR 0.59 (0.43–0.81); log rank test p = 0.0009]. At 30 days, 44 (31.7%) and 24 (16.3%) patients had favourable neurological outcome (AD 15.4%, 5.6–25.1%, p = 0.003), 60 (43.2%), and 46 (31.3%) patients had cardiac recovery (AD: 11.9%, 0.7–23%, p = 0.05), in the invasive and standard arms, respectively. The effect was larger in patients presenting with shockable rhythms (AD 18.8%, 7.6–29.4; p = 0.01; HR 2.26 [1.23–4.15]; p = 0.009) and prolonged CPR (>45 min; HR 3.99 (1.54–10.35); p = 0.005). Interpretation: In patients with refractory OHCA, the invasive approach significantly improved 30- and 180-day neurologically favourable survival. Funding: None