Ryan Zarychanski's research while affiliated with University of Manitoba and other places
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Publications (311)
Importance:
Randomized clinical trials (RCTs) of therapeutic-dose heparin in patients hospitalized with COVID-19 produced conflicting results, possibly due to heterogeneity of treatment effect (HTE) across individuals. Better understanding of HTE could facilitate individualized clinical decision-making.
Objective:
To evaluate HTE of therapeutic-...
Introduction:
We aimed to analyze intensive care unit (ICU)-acquired pneumonia according to 7 definitions, estimating associated hospital mortality.
Methods:
This cohort study was nested within an international randomized trial, evaluating the effect of probiotics on ICU-acquired pneumonia in 2650 mechanically ventilated adults. Each clinically...
Background
Considering the alterations in gait patterns and increase in metabolic demands during walking on an inclined surface, inclined treadmill training (ITT) may be an alternative treatment to non-inclined treadmill training (NITT) for improving gait and balance among people with chronic stroke.
Design
We searched eight electronic databases (...
Importance:
The longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown.
Objective:
To determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes.
Design, setting, and participants:
Prespecified secondary analysis of an ongoing adaptive platform...
Objective:
The optimal timing of tracheostomy in nonneurologically injured mechanically ventilated critically ill adult patients is uncertain. We conducted a systematic review of randomized controlled trials to evaluate the effect of early versus late tracheostomy or prolonged intubation in this population.
Data sources:
We searched MEDLINE, Emb...
Abstract
Purpose
We sought to compare the cost-effectiveness of probiotics and usual care with usual care without probiotics in mechanically ventilated, intensive care unit patients alongside the Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial (PROSPECT).
Methods
We conducted a health economic evaluation alongside the PR...
Introduction:
Traumatic brain injury (TBI) is the leading cause of mortality and long-term disability in young adults. Despite the high prevalence of anaemia and red blood cell transfusion in patients with TBI, the optimal haemoglobin (Hb) transfusion threshold is unknown. We undertook a randomised trial to evaluate whether a liberal transfusion s...
Background: The role of remdesivir in the treatment of hospitalized patients with COVID-19 remains ill-defined. We conducted a
cost-effectiveness analysis alongside the Canadian Treatments for COVID-19 (CATCO) open-label, randomized clinical trial evaluating remdesivir.
Methods: Patients with COVID-19 in Canadian hospitals from Aug. 14, 2020, to Ap...
Background
Perampanel a third-generation antiseizure medication, belongs to a new promising class of drugs called AMPA receptor antagonists, approved to treat focal-onset seizures with or without focal to bilateral tonic clonic seizures and primary generalized tonic-clonic seizures.
Methods
This review included RCTs on patients with epilepsy expos...
Importance:
Platform trial design allows the introduction of new interventions after the trial is initiated and offers efficiencies to clinical research. However, limited guidance exists on the economic resources required to establish and maintain platform trials.
Objective:
To compare cost (US dollars) and time requirements of conducting a plat...
Purpose:
Septic shock is associated with a mortality of 20-40%. The white blood cell count (WBC) at hospital admission correlates with prognosis in septic shock. Here, we explore whether the trajectory of WBC after admission provides further information about outcomes. We aimed to identify groups of patients with different WBC trajectories and the...
Antithrombotic agents reduce risk of thromboembolism in severely ill patients. Patients with coronavirus disease 2019 (COVID‐19) may realize additional benefits from heparins. Optimal dosing and timing of these treatments and benefits of other antithrombotic agents remain unclear. In October 2021, ISTH assembled an international panel of content ex...
Objectives:
To identify, critically appraise and summarise evidence on the impact of employing primary healthcare professionals (PHCPs: family physicians/general practitioners (GPs), nurse practitioners (NP) and nurses with increased authority) in the emergency department (ED) triage, on patient flow outcomes.
Methods:
We searched Medline (Ovid)...
Importance:
The efficacy of antiplatelet therapy in critically ill patients with COVID-19 is uncertain.
Objective:
To determine whether antiplatelet therapy improves outcomes for critically ill adults with COVID-19.
Design, setting, and participants:
In an ongoing adaptive platform trial (REMAP-CAP) testing multiple interventions within multip...
Background:
The role of remdesivir in the treatment of patients in hospital with COVID-19 remains ill defined in a global context. The World Health Organization Solidarity randomized controlled trial (RCT) evaluated remdesivir in patients across many countries, with Canada enrolling patients using an expanded data collection format in the Canadian...
Importance
Platelets represent a potential therapeutic target for improved clinical outcomes in patients with COVID-19.
Objective
To evaluate the benefits and risks of adding a P2Y12 inhibitor to anticoagulant therapy among non–critically ill patients hospitalized for COVID-19.
Design, Setting, and Participants
An open-label, bayesian, adaptive r...
Despite decades of preclinical research, no experimentally derived therapies for sepsis have been successfully adopted into routine clinical practice. Factors that contribute to this crisis of translation include poor representation by preclinical models of the complex human condition of sepsis, bias in preclinical studies, as well as limitations o...
Background
Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause morta...
The efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear. Although most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content could influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with...
Objective:
To identify prognostic factors for the development of venous thromboembolism in the ICU.
Data sources:
We searched MEDLINE, EMBASE, and Cochrane CENTRAL from inception to March 1, 2021.
Study selection:
We included English-language studies describing prognostic factors associated with the development of venous thromboembolism among...
Importance:
The evidence for benefit of convalescent plasma for critically ill patients with COVID-19 is inconclusive.
Objective:
To determine whether convalescent plasma would improve outcomes for critically ill adults with COVID-19.
Design, setting, and participants:
The ongoing Randomized, Embedded, Multifactorial, Adaptive Platform Trial f...
Aims:
Orthopaedic surgeries are complex, frequently performed procedures associated with significant haemorrhage and perioperative blood transfusion. Given refinements in surgical techniques and changes to transfusion practices, we aim to describe contemporary transfusion practices in orthopaedic surgery in order to inform perioperative planning a...
Importance
Growing interest in microbial dysbiosis during critical illness has raised questions about the therapeutic potential of microbiome modification with probiotics. Prior randomized trials in this population suggest that probiotics reduce infection, particularly ventilator-associated pneumonia (VAP), although probiotic-associated infections...
Background:
Thrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19.
Methods:
In an open-label, adaptive, multiplatform, randomized clinical trial, critically...
Purpose:
Intravenous immune globulin (IVIG) may improve survival in people with septic shock. Current utilization patterns of IVIG are unknown. We sought to characterize adult patients with septic shock requiring vasopressors who received IVIG, describes IVIG regimens, and evaluate determinants of IVIG use in patients with septic shock.
Methods:...
PurposeTo study the efficacy of lopinavir-ritonavir and hydroxychloroquine in critically ill patients with coronavirus disease 2019 (COVID-19).Methods
Critically ill adults with COVID-19 were randomized to receive lopinavir-ritonavir, hydroxychloroquine, combination therapy of lopinavir-ritonavir and hydroxychloroquine or no antiviral therapy (cont...
The efficacy of convalescent plasma for COVID-19 is unclear. While most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content may influence patient outcomes.
We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen withi...
Background
Anemia is common in neurocritically ill patients. Considering the limited clinical evidence in this population, preclinical data may provide some understanding of the potential impact of anemia and of red blood cell transfusion in these patients. We aim to estimate the association between different transfusion strategies and neurobehavio...
Background
Thrombo-inflammation may contribute to morbidity and mortality in Covid-19. We hypothesized that therapeutic-dose anticoagulation may improve outcomes in non-critically ill patients hospitalized for Covid-19.
Methods
In an open-label adaptive multiplatform randomized controlled trial, non-critically ill patients hospitalized for Covid-19...
Background
Convalescent plasma has been used for numerous viral diseases including influenza, severe acute respiratory syndrome, Middle East respiratory syndrome and Ebola virus; however, evidence to support its use is weak. SARS-CoV-2 is a novel coronavirus responsible for the 2019 global pandemic of COVID-19 community acquired pneumonia. We have...
Background:
Tranexamic acid (TXA) reduces transfusion in a wide range of surgical populations, although its real-world use in non-cardiac surgeries has not been well described. The objective of this study was to describe prophylactic TXA use in non-cardiac surgeries at high risk for transfusion.
Methods:
This is a retrospective cohort study of a...
Objectives
To conduct a scoping review to identify and summarise the existing literature on interventions involving primary healthcare professionals to manage emergency department (ED) overcrowding.
Design
A scoping review.
Data sources
A comprehensive database search of Medline (Ovid), EMBASE (Ovid), Cochrane Library (Wiley) and CINAHL (EBSCO) d...
Background
Thrombosis may contribute to morbidity and mortality in Covid-19. We hypothesized that therapeutic anticoagulation would improve outcomes in critically ill patients with Covid-19.
Methods
We conducted an open-label, adaptive, multiplatform, randomized, clinical trial. Patients with severe Covid-19, defined as the requirement for organ su...
This article was updated to correct Alexis F. Turgeon’s name and affiliations.
Background
The efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear.
Methods
We evaluated tocilizumab and sarilumab in an ongoing international, multifactorial, adaptive platform trial. Adult patients with Covid-19, within 24 hours after starting organ support in the intensiv...
Background: Convalescent plasma has been used for numerous viral diseases including influenza, severe acute respiratory syndrome, Middle East respiratory syndrome and Ebola virus; however, evidence to support its use is weak. SARS-CoV-2 is a novel coronavirus responsible for the 2019 global pandemic of COVID-19 community acquired pneumonia. We have...
PurposeThis national survey evaluated the perceived efficacy and safety of intravenous immune globulin (IVIG) in septic shock, self-reported utilization patterns, barriers to use, the population of interest for further trials and willingness to participate in future research of IVIG in septic shock.Methods
We conducted a cross-sectional survey of c...
Purpose:
Tranexamic acid (TXA) reduces red blood cell transfusion in various orthopedic surgeries, yet the degree of practice variation in its use among anesthesiologists and surgeons has not been described. To target future knowledge transfer and implementation strategies, and to better understand determinants of variability in prophylactic TXA u...
Background:
The coronavirus disease 2019 pandemic continues to affect millions worldwide. Given the rapidly growing evidence base, we implemented a living guideline model to provide guidance on the management of patients with severe or critical coronavirus disease 2019 in the ICU.
Methods:
The Surviving Sepsis Campaign Coronavirus Disease 2019 p...
Background: Topical microbicide gels are a potential method to reduce sexually transmitted human immunodeficiency virus (HIV) infection, especially in women. Several randomized controlled trials (RCTs) of topical microbicides to prevent HIV transmission have yielded promising results, however trial results have been inconsistent. The objective of t...
The response to the COVID-19 epidemic is generating severe shortages of personal protective equipment around the world. In particular, the supply of N95 respirator masks has become severely depleted, with supplies having to be rationed and health care workers having to use masks for prolonged periods in many countries. We sought to test the ability...
Background: Multiple myeloma is a heterogenous plasma cell cancer characterized by expression of a monoclonal protein (M-protein) or free light chains (FLC). Although survival has improved over the past 15 years, outcomes are variable and not fully predicted by conventional prognostic markers. Survival is associated with depth and duration of respo...
Background: Red blood cell (RBC) transfusions are often used to treat patients with iron deficiency who present to the emergency department (ED) with symptomatic anemia. Intravenous (IV) iron is the preferred treatment in this setting, as it has been shown to increase hemoglobin concentration rapidly and durably. We aim to determine the incidence o...
Background: In Canada, septic shock accounts for approximately 30,000 hospitalizations annually and is associated with a mortality rate of 30%. Thrombocytopenia in septic shock is associated with a poor prognosis including increased length of stay, longer duration of organ support, increased major bleeding events and mortality. The trajectory of th...
Background
Use of hydroxychloroquine in hospitalized patients with coronavirus disease 2019 (COVID-19), especially in combination with azithromycin, has raised safety concerns. Here, we report safety data from 3 outpatient randomized clinical trials.
Methods
We conducted 3 randomized, double-blind, placebo-controlled trials investigating hydroxych...
Background: Anemia is common in neurocritically ill patients. Considering the limited clinical evidence in this population, preclinical data may provide some understanding of the potential impact of anemia and of red blood cell transfusion in these patients. We aim to estimate the association between different transfusion strategies and neurobehavi...
Introduction:
Coronavirus disease (COVID-19) is associated with a high incidence of thrombosis and mortality despite standard anticoagulant thromboprophylaxis. There is equipoise regarding the optimal dose of anticoagulant intervention in hospitalized patients with COVID-19 and consequently, immediate answers from high-quality randomized trials ar...
Background
Colonoscopies are effective means of detecting and removing precancerous adenomatous polyps. The adenoma detection rate (ADR) is a marker of colonoscopy quality and an independent predictor of colorectal cancer incidence. Focused training interventions may improve an endoscopist’s ADR, but the supporting research is limited. This systema...
Background
Mortality from COVID-19 is high among hospitalized patients and effective therapeutics are lacking. Hypercoagulability, thrombosis and hyperinflammation occur in COVID-19 and may contribute to severe complications. Therapeutic anticoagulation may improve clinical outcomes through anti-thrombotic, anti-inflammatory and anti-viral mechanis...
Importance
Mindfulness-based interventions (MBIs), grounded in mindfulness, focus on purposely paying attention to experiences occurring at the present moment without judgment. MBIs are increasingly used by patients with cancer for the reduction of anxiety, but it remains unclear if MBIs reduce anxiety in patients with cancer.
Objective
To evaluat...
Introduction:
Checkpoint inhibitor drugs including ipilimumab have been reported to induce intestinal injury.
Objective:
We aimed to evaluate the risk of chronic (> 6 weeks) enterocolitis following ipilimumab administration, and the likelihood that an enteritis vs colitis or enterocolitis is seen.
Patients and methods:
We searched MEDLINE, EMB...
Perioperative bleeding is a major indication for red blood cell (RBC) transfusion, yet transfusion data in many major non-cardiac surgeries is lacking and does not reflect recent blood conservation efforts. We aim to describe transfusion practices in non-cardiac surgeries at high risk for RBC transfusion.
We completed a retrospective cohort study t...
Background:
No effective oral therapy exists for early coronavirus disease 2019 (COVID-19).
Objective:
To investigate whether hydroxychloroquine could reduce COVID-19 severity in adult outpatients.
Design:
Randomized, double-blind, placebo-controlled trial conducted from 22 March through 20 May 2020. (ClinicalTrials.gov: NCT04308668).
Setting...
Importance
The appropriate approach for weight loss among children and adolescents with overweight and obesity remains unclear.
Objective
To evaluate the difference in the treatment outcomes associated with behavioral weight loss interventions led by laypersons and professionals in comparison with unsupervised control arms among children and adole...
Objective
To externally validate 3 pSAH identification models.
Study Design and Setting
We evaluated 3 models that identify pSAH using recursive partitioning (A), logistic regression (B), and a prevalence adjusted logistic regression(C), respectively. Blinded chart review and/or linkage to existing registries determined pSAH status. We included al...
Background
Widely used for acute pain management, the clinical benefit from perioperative use of gabapentinoids is uncertain. The aim of this systematic review was to assess the analgesic effect and adverse events with the perioperative use of gabapentinoids in adult patients.
Methods
Randomized controlled trials studying the use of gabapentinoids...
Background
Coronavirus disease 2019 (Covid-19) occurs after exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For persons who are exposed, the standard of care is observation and quarantine. Whether hydroxychloroquine can prevent symptomatic infection after SARS-CoV-2 exposure is unknown.
Methods
We conducted a randomized,...
