Nicole Zytaruk

• McMaster University

Background Understanding site-related factors that influence enrolment within multicenter randomized controlled trials (RCT) may help reduce trial delays and cost over-runs and prevent early trial discontinuation. In this analysis of PROSPECT (Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial), we describe patient enrol...

Importance The COVID-19 pandemic created unprecedented challenges for clinical trials worldwide, threatening premature closure and trial integrity. Every phase of research operations was affected, often requiring modifications to protocol design and implementation. Objectives To identify the barriers, solutions, and opportunities associated with c...

Background: Whether proton-pump inhibitors are beneficial or harmful for stress ulcer prophylaxis in critically ill patients undergoing invasive ventilation is unclear. Methods: In this international, randomized trial, we assigned critically ill adults who were undergoing invasive ventilation to receive intravenous pantoprazole (at a dose of 40...

Background During the COVID-19 pandemic, many intensive care units (ICUs) halted research to focus on COVID-19-specific studies. Objective To describe the conduct of an international randomized trial of stress ulcer prophylaxis (Re-Evaluating the Inhibition of Stress Erosions in the ICU [REVISE]) during the pandemic, addressing enrolment patterns,...

Background Ascertainment of the severity of the primary outcome of upper gastrointestinal (GI) bleeding is integral to stress ulcer prophylaxis trials. This protocol outlines the adjudication process for GI bleeding events in an international trial comparing pantoprazole to placebo in critically ill patients (REVISE: Re-Evaluating the Inhibition of...

Background The REVISE (Re-Evaluating the Inhibition of Stress Erosions in the ICU) trial will evaluate the impact of the proton pump inhibitor pantoprazole compared to placebo in invasively ventilated critically ill patients. Objective To outline the statistical analysis plan for the REVISE trial. Methods REVISE is a randomized clinical trial ong...

Introduction The R e- Ev aluating the I nhibition of S tress E rosions (REVISE) Trial aims to determine the impact of the proton pump inhibitor pantoprazole compared with placebo on clinically important upper gastrointestinal (GI) bleeding in the intensive care unit (ICU), 90-day mortality and other endpoints in critically ill adults. The objective...

Background: Critically ill patients commonly receive proton pump inhibitors (PPIs) to prevent gastrointestinal (GI) bleeding from stress-induced ulceration. Despite widespread use in the intensive care unit (ICU), observational data suggest that PPIs may be associated with adverse outcomes in patients with COVID-19 infection. This preplanned study...

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...

Introduction: Clostridioides difficile infection (CDI) is a serious complication of critical illness. The objective of the study was to determine its incidence, prevalence, timing, severity, predictors, and outcomes. Methods: We performed a prospective nested cohort study of CDI within a randomized trial comparing Lactobacillus rhamnosus GG to p...

Purpose Neurocritical care patients are at risk of stress-induced gastrointestinal ulceration. We performed a systematic review and meta-analysis of stress ulcer prophylaxis (SUP) in critically ill adults admitted with a primary neurologic injury. Materials and methods We included randomized controlled trials (RCTs) comparing SUP with histamine-2-...

Purpose To categorize, quantify and interpret findings documented in feedback letters of monitoring or auditing visits for an investigator-initiated, peer-review funded multicenter randomized trial testing probiotics for critically ill patients. Materials & methods In 37 Canadian centers, monitoring and auditing visits were performed by 3 trained...

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 Scaling-up and sustaining healthcare interventions can be challenging. Our objective was to describe how the 3 Wishes Project (3WP), a personalized end-of-life intervention, was scaled-up and sustained in an intensive care unit (ICU). Methods In a longitudinal mixed-methods study from January 12,013 - December 31, 2018, dying patients a...

Background: Scaling-up and sustaining healthcare interventions can be challenging. Our objective was to describe how the 3 Wishes Project (3WP), a personalized end-of-life intervention, was scaled-up and sustained in an intensive care unit (ICU). Methods: In a longitudinal mixed-methods study from January 1,2013 - December 31, 2018, dying patients...

Objectives: To describe the importance of critical care clinical research that is not pandemic-focused during pandemic times; outline principles to assist in the prioritization of nonpandemic research during pandemic times; and propose a guiding framework for decisions about whether, when and how to continue nonpandemic research while still honori...

Purpose Alterations in bowel habits are common during critical illness, and bowel protocols are gaining acceptance. Our objective was to characterize bowel protocols in a cross-sectional analysis of ICUs. Materials and methods We engaged 44 adult ICUs and performed content analysis of bowel protocols, addressing initiation criteria, medications in...

Background Critical care research coordinators implement study protocols in intensive care units, yet little is known about their experiences. Objective To identify the responsibilities, stressors, motivators, and job satisfaction of critical care research coordinators in Canada. Methods Responses to a self-administered survey were collected in o...

To determine if a set of time-varying biological indicators can be used to: 1) predict the sepsis mortality risk over time and 2) generate mortality risk profiles. Design: Prospective observational study. Setting: Nine Canadian ICUs. Subjects: Three-hundred fifty-six septic patients. Interventions: None. Measurements and main results: Cli...

Introduction Ventilator-associated pneumonia (VAP) is the most common healthcare-associated infection in critically ill patients. Prior studies suggest that probiotics may reduce VAP and other infections in critically ill patients; however, most previous randomised trials were small, single centre studies. The Probiotics: Prevention of Severe Pneum...

Background Host-associated microbial communities have important roles in tissue homeostasis and overall health. Severe perturbations can occur within these microbial communities during critical illness due to underlying diseases and clinical interventions, potentially influencing patient outcomes. We sought to profile the microbial composition of c...

Introduction: A decreased frequency of upper gastrointestinal bleeding and a possible association of proton pump inhibitor use with Clostridium difficile and ventilator-associated pneumonia have raised concerns recently. The Reevaluating the Inhibition of Stress Erosions Pilot Trial determined the feasibility of undertaking a larger trial investig...

Introduction Lumbar puncture is one of the oldest and most commonly performed procedures in medicine, used to diagnose and treat disease. Headache following lumbar puncture remains a frequent complication, causing significant patient discomfort and often requiring narcotic analgesia or invasive therapy. Needle tip design has been proposed to affect...

INTRODUCTION: Clinicians routinely administer stress ulcer prophylaxis to mechanically ventilated patients in the intensive care unit (ICU), most commonly prescribing proton pump inhibitors (PPIs). However, the incidence of gastrointestinal (GI) bleeding from stress ulceration is low and recent observational studies suggest these agents may increas...

Objective The Word Cloud is a frequent wish in the 3 Wishes Project developed to nurture peace and ease the grieving process for dying critically ill patients. The objective was to examine whether Word Clouds can act as a heuristic approach to encourage a narrative orientation to medicine. Narrative medicine is an approach which can strengthen rela...

Introduction: Clinicians routinely administer stress ulcer prophylaxis to mechanically ventilated patients in the intensive care unit (ICU), most commonly prescribing proton pump inhibitors (PPIs). However, the incidence of gastrointestinal (GI) bleeding from stress ulceration is low and recent observational studies suggest these agents may increa...

Objectives: Angiopoietins modulate endothelial permeability via endothelial cell junctions. Angiopoietin-2 blocks the angiopoietin-1/Tie-2 interaction that stabilizes these junctions, and elevated plasma angiopoietin-2 levels are associated with vascular leakage. We hypothesized that plasma angiopoietin-1 and angiopoietin-2 levels are associated w...

Dying in the complex, efficiency-driven environment of the intensive care unit can be dehumanizing for the patient and have profound, long-lasting consequences for all persons attendant to that death. To bring peace to the final days of a patient's life and to ease the grieving process. Mixed-methods study. 21-bed medical-surgical intensive care un...

Heparin is safe and prevents venous thromboembolism in critical illness. We aimed to determine the guideline concordance for thromboprophylaxis in critically ill patients and its predictors, and to analyze factors associated with the use of low molecular weight heparin (LMWH), as it may be associated with a lower risk of pulmonary embolism and hepa...

Importance: Critically ill patients are at risk of venous thrombosis, and therefore guidelines recommend daily thromboprophylaxis. Deep vein thrombosis (DVT) commonly occurs in the lower extremities but can occur in other sites including the head and neck, trunk, and upper extremities. The risk of nonleg deep venous thromboses (NLDVTs), predisposi...

Thrombocytopenia occurs in 20% to 45% of critically ill medical-surgical patients. The 4Ts heparin-induced thrombocytopenia (HIT) score (with 4 domains: Thrombocytopenia, Timing of thrombocytopenia, Thrombosis and oTher reason[s] for thrombocytopenia) might reliably identify patients at low risk for HIT. Interobserver agreement on 4Ts scoring is un...

Purpose: To analyze the frequency, rationale and determinants of attending physicians requesting that their eligible patients not be approached for participation in a thromboprophylaxis trial. Methods: Research personnel in 67 centers prospectively documented eligible non-randomized patients due to physicians declining to allow their patients to...

Background: Prediction scores for pretest probability of pulmonary embolism (PE) validated in outpatient settings are occasionally used in the intensive care unit (ICU). Objective: To evaluate the correlation of Geneva and Wells scores with adjudicated categories of PE in ICU patients. Methods: In a randomized trial of thromboprophylaxis, pati...

Bleeding frequently complicates critical illness and may have serious consequences. Our objectives are to describe the predictors of major bleeding and the association between bleeding and mortality in medical-surgical critically ill patients receiving heparin thromboprophylaxis. We prospectively studied patients from 67 intensive care units and si...

Critically ill patients lack capacity for decisions about research participation. Consent to enrol these patients in studies is typically obtained from substitute decision-makers. To present strategies that may optimise the process of obtaining informed consent from substitute decision-makers for participation of critically ill patients in trials....

Objective: To review the effect of alendronate on bone density and fractures in postmenopausal women. Data Source: We searched MEDLINE, EMBASE, Current Contents, and the Cochrane Controlled trials registry from 1980 to 1999, and we examined citations of relevant articles and proceedings of international meetings. Study Selection: We included 11 tri...

Background: In a recent multicenter randomized trial comparing unfractionated heparin (UFH) with low-molecular-weight heparin (dalteparin) for thromboprophylaxis in 3,746 critically ill patients, 17 patients (0.5%) developed heparin-induced thrombocytopenia (HIT) based on serotonin-release assay-positive (SRA+) status. A trend to a lower frequency...

Introduction: Measuring bleeding in critical care trials is challenging. We determined the reliability of adjudicated bleeding assessments in a large thromboprophylaxis trial in the intensive care unit (ICU). Materials and methods: PROphylaxis for ThromboEmbolism in Critical Care Trial (PROTECT) was an international randomized controlled trial t...

Introduction Research on co-enrollment practices and their impact are limited in the ICU setting. The objectives of this study were: 1) to describe patterns and predictors of co-enrollment of patients in a thromboprophylaxis trial, and 2) to examine the consequences of co-enrollment on clinical and trial outcomes. Methods In an observational analy...

Clinical suspicion of heparin-induced thrombocytopenia (HIT) may prompt changes in drug management and alert clinicians to an increased risk of thrombosis. However, thrombocytopenia in the ICU occurs in about 50% of patients, is multifactorial and is due to HIT in <1%. We aimed to describe the consequences of suspected HIT among medical-surgical cr...

Bleeding frequently complicates critical illness. Our objectives were to describe the incidence, locations and predictors of major bleeding in patients with low risk of bleeding receiving thromboprophylaxis.

Research ethics board (REB) review of scientific protocols is essential, ensuring participants' dignity, safety, and rights. The objectives of this study were to examine the time from submission to approval, to analyze predictors of approval time, and to describe the scope of conditions from REBs evaluating an international thromboprophylaxis trial...

4669 Background Thrombocytopenia occurs in 20–45% of critically-ill medical-surgical patients. The ‘4Ts’ HIT score (with 4 domains: Thrombocytopenia, Timing of thrombocytopenia, Thrombosis and oTher reason for thrombocytopenia) might reliably identify patients at low risk of HIT. Agreement on 4Ts scoring is uncertain in this setting. Objective To...

198FN2 Introduction Many critically ill patients are frequently suspected of having HIT because heparin exposure is nearly universal and up to 45% of medical-surgical ICU patients have a platelet count of less than 150 × 109. Methods Our objectives were: (1) To estimate the incidence of suspected and objectively confirmed HIT; and (2) To evaluate...

The effects of thromboprophylaxis with low-molecular-weight heparin, as compared with unfractionated heparin, on venous thromboembolism, bleeding, and other outcomes are uncertain in critically ill patients. In this multicenter trial, we tested the superiority of dalteparin over unfractionated heparin by randomly assigning 3764 patients to receive...

Background: This article reports the preparatory studies as well as the design, implementation, and a priori analysis plans of PROphylaxis for ThromboEmbolism in Critical Care Trial (PROTECT) before dissemination of results. PROphylaxis for ThromboEmbolism in Critical Care Trial (NCT00182143) is a randomized, stratified, concealed international tr...

Heparin-induced thrombocytopenia (HIT) is commonly considered but rarely confirmed in critically ill patients. The 4Ts score (Thrombocytopenia, Timing of thrombocytopenia, Thrombosis, and oTher reason) might identify individual patients at risk of having this disorder. The aim of the study was to evaluate the value of the 4Ts HIT score in compariso...

2471 Poster Board II-448 Background Adjudication in clinical trials can confirm or refute eligibility, describe cointerventions, judge appropriateness of care, or assess the severity of morbidity outcomes. Objective To refine the adjudication process, calibrate 4 adjudicators, and measure agreement on bleeding severity in an international trial o...

3995 Poster Board III-931 Heparin-induced thrombocytopenia (HIT) is commonly suspected, but rarely confirmed, in the critically ill. The lack of readily available rapid diagnostic tests makes the timely diagnosis of HIT challenging. As a result, when HIT is suspected, heparin is often stopped and an alternative anticoagulant is initiated until diag...

The objective of this report is to describe the roles, responsibilities and recommendations of a 3-member Event Adjudication Committee (EAC) and a 5-member data monitoring committee (DMC) for a prospective multicenter observational study of critically ill patients with renal insufficiency examining the bioaccumulation and bleeding risk associated w...

Use of low-molecular-weight heparins is avoided in patients with renal insufficiency because of concerns about an excessive anticoagulant effect and increased bleeding risk. To challenge this premise, we evaluated if deep vein thrombosis (DVT) prophylaxis with dalteparin sodium confers an excessive anticoagulant effect in critically ill patients wi...

As critical care practice increases in scope, size, and complexity, enrollment of critically ill patients into clinical studies is increasing. To understand the experiences, beliefs, and practices of the Canadian Critical Care Trials Group and Australian and New Zealand Intensive Care Society Clinical Trials Group regarding enrollment of critically...

Critically ill patients with renal insufficiency are predisposed to both deep vein thrombosis (DVT) and bleeding. The objective of the present study was to evaluate the prevalence, incidence and predictors of DVT and the incidence of bleeding in intensive care unit (ICU) patients with estimated creatinine clearance <30 ml/min. In a multicenter, ope...

To estimate the incidence, severity, duration and consequences of bleeding during critical illness, and to test the performance characteristics of a new bleeding assessment tool. Clinical bleeding assessments were performed prospectively on 100 consecutive patients admitted to a medical-surgical intensive care unit (ICU) using a novel bleeding meas...

Human parathyroid hormone (hPTH)(1-34) was approved in 2004 for the treatment of severe osteoporosis. Members of the Osteoporosis Canada clinical guidelines committee conducted a systematic review of randomized controlled trials (RCTs) to assess the efficacy and safety of hPTH for fracture prevention in postmenopausal women and men with osteoporosi...

To describe practice patterns in the management of osteoporosis after fragility fracture. Systematic review of articles in MEDLINE, EMBASE, Cochrane, and CINAHL databases (1996 to February 2005). Diagnostic outcomes included clinical osteoporosis diagnoses, laboratory tests, and bone density scans. Treatment outcomes included initiation of calcium,...