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.

Effect of Probiotics on Incident Ventilator-Associated Pneumonia in Critically Ill Patients: A Randomized Clinical Trial.

Abstract: 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 have also been reported. Objective To evaluate the effect of Lactobacillus rhamnosus GG on preventing VAP, additional infections, and other clinically important outcomes in the intensive care unit (ICU). Design, setting, and participants Randomized placebo-controlled trial in 44 ICUs in Canada, the United States, and Saudi Arabia enrolling adults predicted to require mechanical ventilation for at least 72 hours. A total of 2653 patients were enrolled from October 2013 to March 2019 (final follow-up, October 2020). Interventions Enteral L rhamnosus GG (1 × 1010 colony-forming units) (n = 1321) or placebo (n = 1332) twice daily in the ICU. Main outcomes and measures The primary outcome was VAP determined by duplicate blinded central adjudication. Secondary outcomes were other ICU-acquired infections including Clostridioides difficile infection, diarrhea, antimicrobial use, ICU and hospital length of stay, and mortality. Results Among 2653 randomized patients (mean age, 59.8 years [SD], 16.5 years), 2650 (99.9%) completed the trial (mean age, 59.8 years [SD], 16.5 years; 1063 women [40.1%.] with a mean Acute Physiology and Chronic Health Evaluation II score of 22.0 (SD, 7.8) and received the study product for a median of 9 days (IQR, 5-15 days). VAP developed among 289 of 1318 patients (21.9%) receiving probiotics vs 284 of 1332 controls (21.3%; hazard ratio [HR], 1.03 (95% CI, 0.87-1.22; P = .73, absolute difference, 0.6%, 95% CI, -2.5% to 3.7%). None of the 20 prespecified secondary outcomes, including other ICU-acquired infections, diarrhea, antimicrobial use, mortality, or length of stay showed a significant difference. Fifteen patients (1.1%) receiving probiotics vs 1 (0.1%) in the control group experienced the adverse event of L rhamnosus in a sterile site or the sole or predominant organism in a nonsterile site (odds ratio, 14.02; 95% CI, 1.79-109.58; P Conclusions and relevance Among critically ill patients requiring mechanical ventilation, administration of the probiotic L rhamnosus GG compared with placebo, resulted in no significant difference in the development of ventilator-associated pneumonia. These findings do not support the use of L rhamnosus GG in critically ill patients. Trial registration ClinicalTrials.gov Identifier: NCT02462590.

Antibiotic management of suspected nosocomial ICU-acquired infection: does prolonged empiric therapy improve outcome?

Abstract: To characterize empiric antibiotic use in patients with suspected nosocomial ICU-acquired infections (NI), and determine the impact of prolonged therapy in the absence of infection. Multicenter prospective cohort, with eight medical-surgical ICUs in North America and Europe. 195 patients with suspected NI. The diagnosis of NI was adjudicated by a blinded Clinical Evaluation Committee using retrospective review of clinical, radiological, and culture data. Empiric antibiotics were prescribed for 143 of 195 (73.3%) patients with suspected NI; only 39 of 195 (20.0%) were adjudicated as being infected. Infection rates were similar in patients who did (26 of 143, 18.2%), or did not (13 of 52, 25.0%) receive empiric therapy ( p = 0.3). Empiric antibiotics were continued for more than 4 days in 56 of 95 (59.0%) patients without adjudicated NI. Factors associated with continued empiric therapy were increased age ( p = 0.02), ongoing SIRS ( p = 0.03), and hospital ( p = 0.004). Patients without NI who received empiric antibiotics for longer than 4 days had increased 28-day mortality (18 of 56, 32.1%), compared with those whose antibiotics were discontinued (3 of 39, 7.7%; OR = 5.7, 95% CI 1.5–20.9, p = 0.005). When the influence of age, admission diagnosis, vasopressor use, and multiple organ dysfunction was controlled by multivariable analysis, prolonged empiric therapy was not independently associated with mortality (OR = 3.8, 95% CI 0.9–15.5, p = 0.07). Empiric antibiotics were initiated four times more often than NI was confirmed, and frequently continued in the absence of infection. We found no evidence that prolonged use of empiric antibiotics improved outcome for ICU patients, but rather a suggestion that the practice may be harmful.

Risk factors and impact of major bleeding in critically ill patients receiving heparin thromboprophylaxis

Abstract: 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 six countries enrolled in a thromboprophylaxis trial (NCT00182143) comparing dalteparin with unfractionated heparin. Patients with trauma, orthopedic surgery or neurosurgery were excluded. Trained research coordinators used a validated tool to document bleeding, which underwent duplicate independent blinded adjudication. Major bleeding was defined as hypovolemic shock, bleeding into critical sites, requiring an invasive intervention or transfusion of at least two units of red blood cells, or associated with hypotension or tachycardia in the absence of other causes. Adjusted Cox proportional hazard regression analysis was used to identify major bleeding predictors and the association between bleeding and mortality. Among 3,746 patients, bleeding occurred in 208 [5.6 %, 95 % confidence interval (CI) 4.9–6.3 %]. Time-dependent predictors were prolonged activated partial thromboplastin time [hazard ratio (HR) 1.10, 1.05–1.14 per 10 s increase], lower platelet count (HR 1.16, 1.09–1.24 per 50 × 109/L decrease), therapeutic heparin (HR 3.26, 1.72–6.17), antiplatelet agents (HR 1.38, 1.02–1.88), renal replacement therapy (HR 1.75, 1.20–2.56), and recent surgery (HR 1.64, 1.01–2.65). Type of pharmacologic thromboprophylaxis was not associated with bleeding. Patients with bleeding had a higher risk of in-hospital death (HR 2.09, 1.69–2.57). As major bleeding has modifiable risk factors and is associated with in-hospital mortality, strategies to mitigate these factors should be evaluated in critically ill patients.

Gay and lesbian physicians in training: a qualitative study

Abstract: Background: Gay and lesbian physicians in training face considerable challenges as they become professionalized. Qualitative research is necessary to understand the social and cultural factors that influence their medical training. In this study we explored the significance of gay or lesbian identity on the experiences of medical training using naturalistic methods of inquiry. Methods: Semi-structured interviews, focus groups and an email listserv were used to explore professional and personal issues of importance to 29 gay and lesbian medical students and residents in 4 Canadian cities. Data, time, method and investigator triangulation were used to identify and corroborate emerging themes. The domains explored included career choice, “coming out,” becoming a doctor, the environment and career implications. Results: Gay or lesbian medical students and residents experienced significant challenges. For all participants, sexual orientation had an effect on their decisions to enter and remain in medicine. Once in training, the safety of a variety of learning environments was of paramount importance, and it affected subsequent decisions about identity disclosure, residency and career path. Respondents’ assessment of professional and personal risk was influenced by the presence of identifiable supports, curricula inclusive of gay and lesbian sexuality and health issues and effective policies censuring discrimination based on sexual orientation. The need for training programs to be proactive in acknowledging and supporting diversity was identified. Interpretation: Considerable energy and emotion are spent by gay and lesbian medical students and residents navigating training programs, which may be, at best, indifferent and, at worst, hostile.

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 …