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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.


Papers
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Journal ArticleDOI
TL;DR: An introduction to multiple testing issues in clinical trials is provided, and options for carrying out multiplicity adjustments in terms of trial design factors including Population, Intervention/Comparison, Outcome, Time frame and Analysis (PICOTA).
Abstract: In clinical trials it is not uncommon to face a multiple testing problem which can have an impact on both type I and type II error rates, leading to inappropriate interpretation of trial results. Multiplicity issues may need to be considered at the design, analysis and interpretation stages of a trial. The proportion of trial reports not adequately correcting for multiple testing remains substantial. The purpose of this article is to provide an introduction to multiple testing issues in clinical trials, and to reduce confusion around the need for multiplicity adjustments. We use a tutorial, question-and-answer approach to address the key issues of why, when and how to consider multiplicity adjustments in trials. We summarize the relevant circumstances under which multiplicity adjustments ought to be considered, as well as options for carrying out multiplicity adjustments in terms of trial design factors including Population, Intervention/Comparison, Outcome, Time frame and Analysis (PICOTA). Results are presented in an easy-to-use table and flow diagrams. Confusion about multiplicity issues can be reduced or avoided by considering the potential impact of multiplicity on type I and II errors and, if necessary pre-specifying statistical approaches to either avoid or adjust for multiplicity in the trial protocol or analysis plan.

210 citations

Journal ArticleDOI
TL;DR: This consensus statement provides 23 different recommendations concerning the management of patients with severe acute pancreatitis, which differ in several ways from previous recommendations because of the release of recent data concerning themanagement of these patients and alsoBecause of the focus on the critically ill patient.

209 citations

Journal ArticleDOI
TL;DR: Vasopressin may reduce progression to renal failure and mortality in patients at risk of kidney injury who have septic shock and the interaction of treatment group and RIFLE category was significant in predicting mortality.
Abstract: To compare the effects of vasopressin versus norepinephrine infusion on the outcome of kidney injury in septic shock Post-hoc analysis of the multi-center double-blind randomized controlled trial of vasopressin versus norepinephrine in adult patients who had septic shock (VASST) Seven hundred seventy-eight patients were randomized to receive a blinded infusion of either low-dose vasopressin (001–003 U/min) or norepinephrine infusion (5–15 μg/min) in addition to open-label vasopressors and were included in the outcome analysis All vasopressors were titrated and weaned to maintain a target blood pressure RIFLE criteria for acute kidney injury were used to compare the effects of vasopressin versus norepinephrine In view of multiple simultaneous comparisons, a p value of 001 was considered statistically significant Kidney injury was present in 464 patients (596%) at study entry In patients in the RIFLE “Risk” category (n = 106), vasopressin as compared with norepinephrine was associated with a trend to a lower rate of progression to renal “Failure” or “Loss” categories (208 vs 396%, respectively, p = 003), and a lower rate of use of renal replacement therapy (170 vs 377%, p = 002) Mortality rates in the “Risk” category patients treated with vasopressin compared to norepinephrine were 308 versus 547%, p = 001, but this did not reach significance in a multiple logistic regression analysis (OR = 033, 99% CI 010–109, p = 002) The interaction of treatment group and RIFLE category was significant in predicting mortality Vasopressin may reduce progression to renal failure and mortality in patients at risk of kidney injury who have septic shock

208 citations

Journal ArticleDOI
TL;DR: Evidence from experimental data in critically ill patients suggests that enteral nutrition may have a favourable impact on gastrointestinal immunological function and infectious morbidity.
Abstract: To examine the relationship between enteral nutrition (EN) and infection in the critically ill.Setting: Computerized search of published research and review of relevant reference lists.Study selection: 151 citations were reviewed and 39 articles met selection criteria. Primary studies were included if they evaluated EN in critically ill humans and its effect on infectious morbidity and mortality. Relevant data were abstracted on the timing and impact of EN on morbidity, the optimal route of administration, composition and pH of EN, and bacterial contamination of EN. The evidence from human studies that EN, particularly early EN, results in reduced septic morbidity as compared to parenteral nutrition is limited to small, unblinded studies with non-rigorous definitions of pneumonia. There is no evidence to support a preference of feeding into the stomach versus the small bowel. The addition of fish oil, arginine, glutamine and fiber to enteral feeds has a variable impact on survival in animal models; there are no trials in critically ill patients that demonstrate a reduction in infectious morbidity and mortality. Acidification of enteral nutrition results in decreased bacterial colonization of the stomach in critically ill patients. Bacterial contamination of enteral nutrition is an important source of infection. Evidence from experimental data in critically ill patients suggests that enteral nutrition may have a favourable impact on gastrointestinal immunological function and infectious morbidity.

207 citations

Journal ArticleDOI
TL;DR: Overt gastrointestinal bleeding in critically ill patients is reduced by prophylaxis with antacids or histamine-2-receptor antagonists and are more effective than no treatment at reducing the incidence of clinically important bleeding.

205 citations


Cited by
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Journal ArticleDOI
TL;DR: Moher et al. as mentioned in this paper introduce PRISMA, an update of the QUOROM guidelines for reporting systematic reviews and meta-analyses, which is used in this paper.
Abstract: David Moher and colleagues introduce PRISMA, an update of the QUOROM guidelines for reporting systematic reviews and meta-analyses

62,157 citations

Journal Article
TL;DR: The QUOROM Statement (QUality Of Reporting Of Meta-analyses) as mentioned in this paper was developed to address the suboptimal reporting of systematic reviews and meta-analysis of randomized controlled trials.
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

46,935 citations

Journal ArticleDOI
04 Sep 2003-BMJ
TL;DR: A new quantity is developed, I 2, which the authors believe gives a better measure of the consistency between trials in a meta-analysis, which is susceptible to the number of trials included in the meta- analysis.
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 …

45,105 citations

Journal ArticleDOI
TL;DR: A structured summary is provided including, as applicable, background, objectives, data sources, study eligibility criteria, participants, interventions, study appraisal and synthesis methods, results, limitations, conclusions and implications of key findings.

31,379 citations