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In a trial involving patients with refractory ventricular fibrillation, double sequential external defibrillation or vector-change defibrillation improved survival as compared with standard defibrillation.

AbstractObjectiveTo compare the effects of treatments for coronavirus disease 2019 (covid-19).DesignLiving systematic review and network meta-analysis.Data sourcesWHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, up to 3 December 2021 and six additional Chinese databases up to 20 February 2021. Studies identified as of 1 December 2021 were included in the analysis.Study selectionRandomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles.MethodsAfter duplicate data abstraction, a bayesian network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development, and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance.Results463 trials enrolling 166 581 patients were included; 267 (57.7%) trials and 89 814 (53.9%) patients are new from the previous iteration; 265 (57.2%) trials evaluating treatments with at least 100 patients or 20 events met the threshold for inclusion in the analyses. Compared with standard care, three drugs reduced mortality in patients with mostly severe disease with at least moderate certainty: systemic corticosteroids (risk difference 23 fewer per 1000 patients, 95% credible interval 40 fewer to 7 fewer, moderate certainty), interleukin-6 receptor antagonists when given with corticosteroids (23 fewer per 1000, 36 fewer to 7 fewer, moderate certainty), and Janus kinase inhibitors (44 fewer per 1000, 64 fewer to 20 fewer, high certainty). Compared with standard care, two drugs probably reduce hospital admission in patients with non-severe disease: nirmatrelvir/ritonavir (36 fewer per 1000, 41 fewer to 26 fewer, moderate certainty) and molnupiravir (19 fewer per 1000, 29 fewer to 5 fewer, moderate certainty). Remdesivir may reduce hospital admission (29 fewer per 1000, 40 fewer to 6 fewer, low certainty). Only molnupiravir had at least moderate quality evidence of a reduction in time to symptom resolution (3.3 days fewer, 4.8 fewer to 1.6 fewer, moderate certainty); several others showed a possible benefit. Several drugs may increase the risk of adverse effects leading to drug discontinuation; hydroxychloroquine probably increases the risk of mechanical ventilation (moderate certainty).ConclusionCorticosteroids, interleukin-6 receptor antagonists, and Janus kinase inhibitors probably reduce mortality and confer other important benefits in patients with severe covid-19. Molnupiravir and nirmatrelvir/ritonavir probably reduce admission to hospital in patients with non-severe covid-19.Systematic review registrationThis review was not registered. The protocol is publicly available in the supplementary material.Readers’ noteThis article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This is the fifth version of the original article published on 30 July 2020 (BMJ 2020;370:m2980), and previous versions can be found as data supplements. When citing this paper please consider adding the version number and date of access for clarity.

In response to the COVID-19 pandemic, the Ontario Ministry of Health introduced a pilot program of 14 virtual urgent care (VUC) initiatives across the province to encourage physical distancing and provision of care by telephone and video-enabled visits. The implementation of the VUC pilot is currently being evaluated by an external academic team. The objective of this study was to understand patient experiences with VUC to determine barriers and facilitators to optimal virtual care as it rapidly expands during the current pandemic and beyond. The qualitative component of the evaluation used one-on-one telephone interviews with patients, families, providers, and program administrators as the main method of data collection. Patient and family participants were invited to participate by the triage nurse after their VUC visit. Data analysis, using thematic analysis, occurred in conjunction with data collection to monitor emerging themes and areas for further exploration. Between April and October 2021, we completed 14 patient and/or family interviews from a representative cross-section of 6 pilot sites. Participants had a range of presenting complaints including infection, injury, medication side effects, and abdominal pain. The vast majority of participants were female (90%), and 70% were VUC patients themselves. Our analysis identified three key themes in the data which characterise patient and family member experience with VUC: a) emphasis on access to the ED; b) efficiency and quality of care; c) obtaining reassurance and next steps. Virtual care options are valued by patients and families; however, the nature of care needed by those accessing VUC and who can best provide that care needs to be evaluated to position it for sustainability. Understanding how virtual care performs from both a provider and patient perspective during the current crisis has implications for designing alternative care options beyond the COVID-19 pandemic.

Purpose Targeted temperature management (TTM) may improve survival and functional outcome in comatose survivors of out-of-hospital cardiac arrest (OHCA), though the optimal target temperature remains unknown. We conducted a systematic review and network meta-analysis to investigate the efficacy and safety of deep hypothermia (31–32 °C), moderate hypothermia (33–34 °C), mild hypothermia (35–36 °C), and normothermia (37–37.8 °C) during TTM. Methods We searched six databases from inception to June 2021 for randomized controlled trials (RCTs) evaluating TTM in comatose OHCA survivors. Two reviewers performed screening, full text review, and extraction independently. The primary outcome of interest was survival with good functional outcome. We used GRADE to rate our certainty in estimates. Results We included 10 RCTs (4218 patients). Compared with normothermia, deep hypothermia (odds ratio [OR] 1.30, 95% confidence interval [CI] 0.73–2.30), moderate hypothermia (OR 1.34, 95% CI 0.92–1.94) and mild hypothermia (OR 1.44, 95% CI 0.74–2.80) may have no effect on survival with good functional outcome (all low certainty). Deep hypothermia may not improve survival with good functional outcome, as compared to moderate hypothermia (OR 0.97, 95% CI 0.61–1.54, low certainty). Moderate hypothermia (OR 1.23, 95% CI 0.86–1.77) and deep hypothermia (OR 1.27, 95% CI 0.70–2.32) may have no effect on survival, as compared to normothermia. Finally, incidence of arrhythmia was higher with moderate hypothermia (OR 1.45, 95% CI 1.08–1.94) and deep hypothermia (OR 3.58, 95% CI 1.77–7.26), compared to normothermia (both high certainty). Conclusions Mild, moderate, or deep hypothermia may not improve survival or functional outcome after OHCA, as compared to normothermia. Moderate and deep hypothermia were associated with higher incidence of arrhythmia. Routine use of moderate or deep hypothermia in comatose survivors of OHCA may potentially be associated with more harm than benefit.

AbstractUpdatesThis is the second version (first update) of the living systematic review, replacing the previous version (available as a data supplement). When citing this paper please consider adding the version number and date of access for clarity.ObjectiveTo determine and compare the effects of drug prophylaxis on severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (covid-19).DesignLiving systematic review and network meta-analysis (NMA).Data sourcesWHO covid-19 database, a comprehensive multilingual source of global covid-19 literature to 4 March 2022.Study selectionRandomised trials in which people at risk of covid-19 were allocated to prophylaxis or no prophylaxis (standard care or placebo). Pairs of reviewers independently screened potentially eligible articles.MethodsAfter duplicate data abstraction, we conducted random-effects bayesian network meta-analysis. We assessed risk of bias of the included studies using a modification of the Cochrane risk of bias 2.0 tool and assessed the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach.ResultsThe second iteration of this living NMA includes 32 randomised trials which enrolled 25 147 participants and addressed 21 different prophylactic drugs; adding 21 trials (66%), 18 162 participants (75%) and 16 (76%) prophylactic drugs. Of the 16 prophylactic drugs analysed, none provided convincing evidence of a reduction in the risk of laboratory confirmed SARS-CoV-2 infection. For admission to hospital and mortality outcomes, no prophylactic drug proved different than standard care or placebo. Hydroxychloroquine and vitamin C combined with zinc probably increase the risk of adverse effects leading to drug discontinuation—risk difference for hydroxychloroquine (RD) 6 more per 1000 (95% credible interval (CrI) 2 more to 10 more); for vitamin C combined with zinc, RD 69 more per 1000 (47 more to 90 more), moderate certainty evidence.ConclusionMuch of the evidence remains very low certainty and we therefore anticipate future studies evaluating drugs for prophylaxis may change the results for SARS-CoV-2 infection, admission to hospital and mortality outcomes. Both hydroxychloroquine and vitamin C combined with zinc probably increase adverse effects.Systematic review registrationThis review was not registered. The protocol established a priori is included as a supplement.FundingThis study was supported by the Canadian Institutes of Health Research (grant CIHR-IRSC:0579001321).

When direct and indirect estimates of treatment effects are coherent, network meta-analysis (NMA) estimates should have increased precision (narrower confidence or credible intervals compared with relying on direct estimates alone), a benefit of NMA. We have, however, observed cases of sparse networks in which combining direct and indirect estimates results in marked widening of the confidence intervals. In many cases, the assumption of common between-study heterogeneity across the network seems to be responsible for this counterintuitive result. Although the assumption of common between-study heterogeneity across paired comparisons may, in many cases, not be appropriate, it is required to ensure the feasibility of estimating NMA treatment effects. This is especially the case in sparse networks, in which data are insufficient to reliably estimate different variances across the network. The result, however, may be spuriously wide confidence intervals for some of the comparisons in the network (and, in the Grading of Recommendations Assessment, Development, and Evaluation approach, inappropriately low ratings of the certainty of the evidence through rating down for serious imprecision). Systematic reviewers should be aware of the problem and plan sensitivity analyses that produce intuitively sensible confidence intervals. These sensitivity analyses may include using informative priors for the between-study heterogeneity parameter in the Bayesian framework and the use of fixed effects models.

Intracranial hemorrhage (ICH) after head injury is a concern among older adult patients on anticoagulation. We evaluated the risk of ICH after an emergency department visit for head injury among patients 65 years and older taking warfarin or a direct oral anticoagulant (DOAC) compared with patients not taking anticoagulants. We also evaluated risk of 30-day mortality and neurosurgical intervention among patients with ICH. In this retrospective cohort study, we used population-based data of patients 65 years and older seen in an Ontario emergency department with a head injury. We matched patients on the propensity score to create 3 pairwise-matched cohorts based on anticoagulation status (warfarin v. DOAC, warfarin v. no anticoagulant, DOAC v. no anticoagulant). For each cohort, we calculated the relative risk of ICH at the index emergency department visit and 30-day mortality. We also calculated the hazard of neurosurgical intervention among patients with ICH. We identified 77 834 patients with head injury, including 64 917 (83.4%) who were not on anticoagulation, 9214 (11.8%) who were on DOACs and 3703 (4.8%) who were on warfarin. Of these, 5.9% of patients had ICH at the index emergency department visit. Patients on warfarin had an increased risk of ICH compared with matched patients on DOACs (relative risk [RR] 1.43, 95% confidence interval [CI] 1.20–1.69) and patients not on anticoagulation (RR 1.36, 95% CI 1.15–1.61). We did not observe a difference in ICH between patients on DOACs compared with matched patients not on anticoagulation. In patients with ICH, 30-day mortality did not differ by anticoagulation status or type. Patients on warfarin had an increased hazard of neurosurgery compared with patients not on anticoagulation. Patients on warfarin seen in the emergency department with a head injury had higher relative risks of ICH than matched patients on a DOAC and patients not on anticoagulation, respectively. The risk of ICH for patients on a DOAC was not significantly different compared with no anticoagulation. Further research should confirm that older adults using warfarin are the only group at higher risk of ICH after head injury.

Virtual urgent care (VUC) is intended to support diversion of patients with low-acuity complaints and reduce the need for in-person emergency department visits. We aimed to describe subsequent health care utilization and outcomes of patients who used VUC compared with similar patients who had an in-person emergency department visit. We used patient-level encounter data that were prospectively collected for patients using VUC services provided by 14 pilot programs in Ontario, Canada. We linked the data to provincial administrative databases to identify subsequent 30-day health care utilization and outcomes. We defined 2 subgroups of VUC users; those with a documented prompt referral to an emergency department by a VUC provider, and those without. We matched patients in each cohort to an equal number of patients presenting to an emergency department in person, based on encounter date, medical concern and the logit of a propensity score. For the subgroup of patients not promptly referred to an emergency department, we matched patients to those who were seen in an emergency department and then discharged home. Of the 19 595 patient VUC visits linked to administrative data, we matched 2129 patients promptly referred to the emergency department by a VUC provider to patients presenting to the emergency department in person. Index visit hospital admissions (9.4% v. 8.7%), 30-day emergency department visits (17.0% v. 17.5%), and hospital admissions (12.9% v. 11.0%) were similar between the groups. We matched 14 179 patients who were seen by a VUC provider with no documented referral to the emergency department. Patients seen by VUC were more likely to have a subsequent in-person emergency department visit within 72 hours (13.7% v. 7.0%), 7 days (16.5% v. 10.3%) and 30 days (21.9% v. 17.9%), but hospital admissions were similar within 72 hours (1.1% v. 1.3%), and higher within 30 days for patients who were discharged home from the emergency department (2.6% v. 3.4%). The impact of the provincial VUC pilot program on subsequent health care utilization was limited. There is a need to better understand the inherent limitations of virtual care and ensure future virtual providers have timely access to in-person outpatient resources, to prevent subsequent emergency department visits.

ABSTRACTBackgroundAlthough suspicions of cancer may be raised in patients who visit the emergency department, little is known about emergency department use before a cancer diagnosis. We sought to describe emergency department use among patients in Ontario within the 90 days before confirmed cancer diagnosis and to evaluate factors associated with this emergency department use. MethodsWe conducted a retrospective, population-based study of patients aged 18 years or older who had a confirmed cancer diagnosis in Ontario from 2014 to 2021 using linked administrative databases. The primary outcome was any emergency department visit within 90 days before the cancer diagnosis date. We used multivariable logistic regression to evaluate factors associated with emergency department use, such as demographics (e.g., age, sex, rurality, Ontario Health region, indicators of marginalization), comorbidities, previous emergency department visits and hospital admissions, continuity of primary care, type of cancer, and year of cancer diagnosis. ResultsWe included 651 071 patients with cancer. Of these, 229 683 (35.3%) had an emergency department visit within 90 days before diagnosis, 51.4% of whom were admitted to hospital from the emergency department. Factors associated with increased odds of emergency department use before cancer diagnosis included rurality (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.13–1.17), residence in northern Ontario (North East region OR 1.14, 95% CI 1.10–1.17 and North West region OR 1.27, 95% CI 1.21–1.32, v. Toronto region), and living in the most marginalized areas (material resources OR 1.37, 95% CI 1.35–1.40 and housing OR 1.09, 95% CI 1.06–1.11, v. least marginalized quintile). We observed significant variation in emergency department use by cancer type, with high odds of emergency department use among patients with intracranial, pancreatic, liver or gallbladder, or thoracic cancer. InterpretationEmergency department use is common before cancer diagnosis, with about one-third of patients with cancer in Ontario using the emergency department before diagnosis. Understanding why patients visit the emergency department before cancer diagnosis is important, particularly for patients who live in rural or marginalized areas, or those who have specific cancer types.

Direct oral anticoagulants (DOACs) are increasingly being used over low molecular weight heparin (LMWH) and vitamin K antagonists for the treatment of venous thromboembolism (VTE). The objective of this study was to examine predictors of anticoagulant type (DOAC vs. LMWH) prescribed at discharge from the emergency department (ED) among patients diagnosed with VTE in the ED. We conducted a retrospective chart review of adult (>17 years) patients discharged from an Ontario, Canada ED in a tertiary care centre with an ED diagnosis of deep vein thrombosis or pulmonary embolism from January 2019 to December 2021. A multivariable logistic regression model was used to examine the predictors of the anticoagulant (DOAC vs. LMWH) prescribed at discharge. Covariables included: age, sex, history of major bleeding, history of cancer, and previous anticoagulation. VTE was confirmed in 390 ED visits by 365 unique patients. Among unique patients, 239 (65.5 %) patients were discharged from the ED and included in analysis. Of the 239 patients included, 12.1 % of patients were over the age of 80, 46.4 % were female and 29.7 % had a history of cancer. The majority of patients discharged from the ED were prescribed DOACs (70.7 %,169/239). Cancer history was associated with anticoagulation with LMWH (vs. DOAC) on discharge (adjusted odds ratio [aOR] =12.81, 95 % CI: 6.60–25.90). While most patients diagnosed with VTE in the ED setting were discharged with DOACs, most cancer patients included in our study were treated with LMWH over DOACs, despite increasing evidence around the efficacy and safety of DOACs in most cancer patients. Further research is needed to understand longitudinal trends in anticoagulation.