Deborah J. Cook

Bio: Deborah J. Cook is an academic researcher from McMaster University. The author has contributed to research in topics: Intensive care & Intensive care unit. The author has an hindex of 173, co-authored 907 publications receiving 148928 citations. Previous affiliations of Deborah J. Cook include McMaster University Medical Centre & Queen's University.

New strategies for clinical trials in patients with sepsis and septic shock.

Abstract: OBJECTIVE: The difficulty in identifying new treatment modalities that significantly reduce the mortality and morbidity rates associated with sepsis has highlighted the need to reevaluate the approach to clinical trial design. The United Kingdom Medical Research Council convened an International Working Party to address these issues. DATA SOURCES: The subject areas that were to be the focus of discussion were identified by the co-chairs, and group leaders were nominated. Preconference reading material was circulated to group members. STUDY SELECTION AND DATA EXTRACTION: Small-group discussion fed into an iterative process of feedback from plenary sessions, followed by the formulation of recommendations. Finally, each working group prepared a summary of its recommendations and these are reported herein. DATA SYNTHESIS: There were five key recommendations. First, investigators should no longer rely solely on the American College of Chest Physicians/Society of Critical Care Medicine definitions of sepsis or sepsis syndrome as the basis of trial entry. Entry criteria should be based on three principles: a) All patients should have infection; b) there should be evidence of a pathologic process that represents a biologically plausible target for the proposed intervention, for example, an abnormal circulating level of a biological marker pertinent to the study drug; and c) patients should fall into an appropriate category of severity (usually severe sepsis). Second, investigators should use a scoring system for organ dysfunctions that has been validated and that can be incorporated into all sepsis studies; agreement on the use of a single system would simplify comparisons between studies. Third, the primary outcome measure generally should be mortality rates, but under appropriate circumstances major morbidities could be considered as primary end points. Regardless of choice of the duration to primary end point, patients should be followed for > or =90 days. Fourth, sample size needs to be based on a realistic assessment of achievable effect size based on knowledge of the at-risk population. Fifth, subgroups should be few in number and should be defined a priori on the basis of variables present before randomization. CONCLUSIONS: Important changes in several aspects of trial design may improve the quality of clinical studies in sepsis and maximize the chance of identifying effective therapeutic agents.

REducing Deaths due to OXidative Stress (The REDOXS© Study): rationale and study design for a randomized trial of glutamine and antioxidant supplementation in critically-ill patients

Abstract: Critically-ill patients experience an extent of hyperinflammation, cellular immune dysfunction, oxidative stress and mitochondrial dysfunction. Supplementation with key nutrients, such as glutamine and antioxidants, is most likely to have a favourable effect on these physiological derangements, leading to an improvement in clinical outcomes. The results of two meta-analyses suggest that glutamine and antioxidants may be associated with improved survival. The purpose of the present paper is to report the background rationale and study protocol for the evaluation of the effect of high-dose glutamine and antioxidant supplementation on mortality in a large-scale randomized trial in 1200 mechanically-ventilated, critically-ill patients. Patients admitted to an intensive care unit (ICU) with clinical evidence of severe organ dysfunction will be randomized to one of four treatments in a 2 x 2 factorial design: (1) glutamine; (2) antioxidant therapy; (3) glutamine and antioxidant therapy; (4) placebo. The primary outcome for this study is 28 d mortality. The secondary outcomes are duration of stay in ICU, adjudicated diagnosis of infection, multiple organ dysfunction, duration of mechanical ventilation, length of stay in hospital and health-related quality of life at 3 and 6 months. A novel design feature is the combined use of parenteral and enteral study nutrients dissociated from the nutrition support. The therapeutic strategies tested in the randomized trial may lead to less morbidity and improved survival in critically-ill patients. The trial will be conducted in approximately twenty tertiary-care ICU in Canada and the first results are expected in 2009.

Users' Guides to the Medical Literature: VII. How to Use a Clinical Decision Analysis B. What Are the Results and Will They Help Me in Caring for My Patients?

Abstract: YOU RECALL from the first of our two articles concerning clinical decision analysis1that your patient is a middle-aged man with heart failure from an idiopathic dilated cardiomyopathy. You are trying to decide whether to recommend anticoagulation with warfarin to prevent systemic or pulmonary thromboembolism. Your literature search showed that no randomized clinical trials of warfarin for this use have been published. The search did discover a clinical decision analysis,2and in the first article, we showed you how to evaluate its validity. In this article, we will show you how to interpret the results and generalizability of a clinical decision analysis (Table). As shown in the Figure, decision trees are displayed graphically, oriented from left to right, with the decision to be analyzed on the left, the compared strategies in the center, and the clinical outcomes on the right. The square box, termed a "decision node," represents

Toward understanding evidence uptake: semirecumbency for pneumonia prevention.

Abstract: Objective: Randomized trials show that the semirecumbent position compared with the supine position is associated with less gastroesophageal aspiration and pneumonia in patients receiving mechanical ventilation. However, semirecumbency is inconsistently used in practice. The objective of this study was to understand the perspectives of intensive care unit clinicians regarding the determinants and consequences of semirecumbency. Design: Qualitative study using semistructured interviews and focus groups. Setting: Three university-affiliated intensive care units. Participants: A total of 93 intensive care unit clinicians, including bedside nurses, respiratory therapists, physiotherapists, nutritionists, residents, fellows, and intensivists. Methods: We elicited perceptions about benefits and harms of semirecumbency, factors promoting and deterring use, and health systems changes to encourage semirecumbency. Interview and focus group notes were analyzed inductively to identify emerging themes. Validation methods involved triangulation by multidisciplinary analysis of several data sources collected through multiple methods and member checking. Measurements and Main Results: Intensivists and nutritionists were familiar with semirecumbency as a potential pneumonia prevention strategy, whereas other clinicians were not. When made aware of the evidence, all participants endorsed semirecumbency. Nurses perceived that the main determinant of semirecumbency was physicians’ orders, whereas intensivists perceived that the main determinant was nursing preference. Participants identified barriers to semirecumbency related to useful alternative positions (e.g., lateral position), contraindications (e.g., hemodynamic instability), risk of harm (e.g., decubitus ulcers), safety (e.g., sliding out of the bed), and resources (e.g., insufficient beds facilitating semirecumbency). Education, guidelines, reminders, audit and feedback, charting, and quality improvement initiatives were advocated to promote semirecumbency. Conclusions: Under-utilization of semirecumbency for pneumonia prevention is influenced by insufficient awareness of its benefit, real and perceived deterrents, poor agreement about implementation responsibility, and lack of enabling and reinforcing strategies. Cognitive, behavioral, and administrative approaches to enhancing evidence uptake may be needed in the complex, dynamic intensive care unit setting. (Crit Care Med 2002; 30:1472‐1477)

Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement

Abstract: David Moher and colleagues introduce PRISMA, an update of the QUOROM guidelines for reporting systematic reviews and meta-analyses

Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement.

Abstract: Systematic reviews and meta-analyses have become increasingly important in health care. Clinicians read them to keep up to date with their field,1,2 and they are often used as a starting point for developing clinical practice guidelines. Granting agencies may require a systematic review to ensure there is justification for further research,3 and some health care journals are moving in this direction.4 As with all research, the value of a systematic review depends on what was done, what was found, and the clarity of reporting. As with other publications, the reporting quality of systematic reviews varies, limiting readers' ability to assess the strengths and weaknesses of those reviews. Several early studies evaluated the quality of review reports. In 1987, Mulrow examined 50 review articles published in 4 leading medical journals in 1985 and 1986 and found that none met all 8 explicit scientific criteria, such as a quality assessment of included studies.5 In 1987, Sacks and colleagues6 evaluated the adequacy of reporting of 83 meta-analyses on 23 characteristics in 6 domains. Reporting was generally poor; between 1 and 14 characteristics were adequately reported (mean = 7.7; standard deviation = 2.7). A 1996 update of this study found little improvement.7 In 1996, to address the suboptimal reporting of meta-analyses, an international group developed a guidance called the QUOROM Statement (QUality Of Reporting Of Meta-analyses), which focused on the reporting of meta-analyses of randomized controlled trials.8 In this article, we summarize a revision of these guidelines, renamed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses), which have been updated to address several conceptual and practical advances in the science of systematic reviews (Box 1). Box 1 Conceptual issues in the evolution from QUOROM to PRISMA

Measuring inconsistency in meta-analyses

Abstract: Cochrane Reviews have recently started including the quantity I 2 to help readers assess the consistency of the results of studies in meta-analyses. What does this new quantity mean, and why is assessment of heterogeneity so important to clinical practice? Systematic reviews and meta-analyses can provide convincing and reliable evidence relevant to many aspects of medicine and health care.1 Their value is especially clear when the results of the studies they include show clinically important effects of similar magnitude. However, the conclusions are less clear when the included studies have differing results. In an attempt to establish whether studies are consistent, reports of meta-analyses commonly present a statistical test of heterogeneity. The test seeks to determine whether there are genuine differences underlying the results of the studies (heterogeneity), or whether the variation in findings is compatible with chance alone (homogeneity). However, the test is susceptible to the number of trials included in the meta-analysis. We have developed a new quantity, I 2, which we believe gives a better measure of the consistency between trials in a meta-analysis. Assessment of the consistency of effects across studies is an essential part of meta-analysis. Unless we know how consistent the results of studies are, we cannot determine the generalisability of the findings of the meta-analysis. Indeed, several hierarchical systems for grading evidence state that the results of studies must be consistent or homogeneous to obtain the highest grading.2–4 Tests for heterogeneity are commonly used to decide on methods for combining studies and for concluding consistency or inconsistency of findings.5 6 But what does the test achieve in practice, and how should the resulting P values be interpreted? A test for heterogeneity examines the null hypothesis that all studies are evaluating the same effect. The usual test statistic …