Showing papers by "Deborah J. Cook published in 2018"

Efficacy and safety of stress ulcer prophylaxis in critically ill patients: a network meta-analysis of randomized trials

Abstract: Stress ulcer prophylaxis (SUP) is commonly prescribed in the intensive care unit. However, data from systematic reviews and conventional meta-analyses are limited by imprecision and restricted to direct comparisons. We conducted a network meta-analysis of randomized clinical trials (RCTs) to examine the safety and efficacy of drugs available for SUP in critically ill patients. We searched MEDLINE, EMBASE, and the Cochrane Library Central Register of Controlled Trials through April 2017 for randomized controlled trials that examined the efficacy and safety of proton pump inhibitors (PPIs), histamine-2 receptor antagonists (H2RAs), and sucralfate for SUP in critically ill patients. No date or language restrictions were applied. Data on study characteristics, methods, outcomes, and risk of bias were abstracted by two reviewers. Of 96 potentially eligible studies, we included 57 trials enrolling 7293 patients. The results showed that PPIs are probably more effective for preventing clinically important gastrointestinal bleeding (CIB) than H2RAs [odds ratio (OR) 0.38; 95% confidence interval (95% CI) 0.20, 0.73], sucralfate (OR 0.30; 95% CI 0.13, 0.69), and placebo (OR 0.24; 95% CI 0.10, 0.60) (all moderate quality evidence). There were no convincing differences among H2RA, sucralfate, and placebo. PPIs probably increase the risk of developing pneumonia compared with H2RAs (OR 1.27; 95% CI 0.96, 1.68), sucralfate (OR 1.65; 95% CI 1.20, 2.27), and placebo (OR 1.52; 95% CI 0.95, 2.42) (all moderate quality). Mortality is probably similar across interventions (moderate quality). Estimates of baseline risks of bleeding varied significantly across studies, and only one study reported on Clostridium difficile infection. Definitions of pneumonia varied considerably. Most studies on sucralfate predate pneumonia prevention strategies. Our results provide moderate quality evidence that PPIs are the most effective agents in preventing CIB, but they may increase the risk of pneumonia. The balance of benefits and harms leaves the routine use of SUP open to question.

The Speaker Gender Gap at Critical Care Conferences.

Abstract: OBJECTIVES To review women's participation as faculty at five critical care conferences over 7 years. DESIGN Retrospective analysis of five scientific programs to identify the proportion of females and each speaker's profession based on conference conveners, program documents, or internet research. SETTING Three international (European Society of Intensive Care Medicine, International Symposium on Intensive Care and Emergency Medicine, Society of Critical Care Medicine) and two national (Critical Care Canada Forum, U.K. Intensive Care Society State of the Art Meeting) annual critical care conferences held between 2010 and 2016. SUBJECTS Female faculty speakers. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Male speakers outnumbered female speakers at all five conferences, in all 7 years. Overall, women represented 5-31% of speakers, and female physicians represented 5-26% of speakers. Nursing and allied health professional faculty represented 0-25% of speakers; in general, more than 50% of allied health professionals were women. Over the 7 years, Society of Critical Care Medicine had the highest representation of female (27% overall) and nursing/allied health professional (16-25%) speakers; notably, male physicians substantially outnumbered female physicians in all years (62-70% vs 10-19%, respectively). Women's representation on conference program committees ranged from 0% to 40%, with Society of Critical Care Medicine having the highest representation of women (26-40%). The female proportions of speakers, physician speakers, and program committee members increased significantly over time at the Society of Critical Care Medicine and U.K. Intensive Care Society State of the Art Meeting conferences (p < 0.05), but there was no temporal change at the other three conferences. CONCLUSIONS There is a speaker gender gap at critical care conferences, with male faculty outnumbering female faculty. This gap is more marked among physician speakers than those speakers representing nursing and allied health professionals. Several organizational strategies can address this gender gap.

Prophylaxis against Upper Gastrointestinal Bleeding in Hospitalized Patients.

Abstract: Preventing Gastrointestinal Bleeding in the Hospital Acid suppression is widely used to lower the risk of gastrointestinal bleeding in critically ill patients, and the practice has spread to patien...

Aspirin in Patients With Previous Percutaneous Coronary Intervention Undergoing Noncardiac Surgery

Abstract: Uncertainty remains about the effects of aspirin in patients with prior percutaneous coronary intervention (PCI) having noncardiac surgery. This substudy from a large multicenter trial examines ben...

Pooled analysis of higher versus lower blood pressure targets for vasopressor therapy septic and vasodilatory shock

Abstract: Guidelines for shock recommend mean arterial pressure (MAP) targets for vasopressor therapy of at least 65 mmHg and, until recently, suggested that patients with underlying chronic hypertension and atherosclerosis may benefit from higher targets. We conducted an individual patient-data meta-analysis of recent trials to determine if patient variables modify the effect of different MAP targets. We searched the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials for randomized controlled trials of higher versus lower blood pressure targets for vasopressor therapy in adult patients in shock (until November 2017). After obtaining individual patient data from both eligible trials, we used a modified version of the Cochrane Collaboration’s instrument to assess the risk of bias of included trials. The primary outcome was 28-day mortality. Included trials enrolled 894 patients. Controlling for trial and site, the OR for 28-day mortality for the higher versus lower MAP targets was 1.15 (95% CI 0.87–1.52). Treatment effect varied by duration of vasopressors before randomization (interaction p = 0.017), but not by chronic hypertension, congestive heart failure or age. Risk of death increased in higher MAP groups among patients on vasopressors > 6 h before randomization (OR 3.00, 95% CI 1.33–6.74). Targeting higher blood pressure targets may increase mortality in patients who have been treated with vasopressors for more than 6 h. Lower blood pressure targets were not associated with patient-important adverse events in any subgroup, including chronically hypertensive patients.

Microbial dysbiosis and mortality during mechanical ventilation: a prospective observational study

Abstract: 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 critically ill mechanically ventilated patients, and to determine whether microbial diversity is associated with illness severity and mortality. We conducted a prospective, observational study of mechanically ventilated critically ill patients with a high incidence of pneumonia in 2 intensive care units (ICUs) in Hamilton, Canada, nested within a randomized trial for the prevention of healthcare-associated infections. The microbial profiles of specimens from 3 anatomical sites (respiratory, and upper and lower gastrointestinal tracts) were characterized using 16S ribosomal RNA gene sequencing. We collected 65 specimens from 34 ICU patients enrolled in the trial (29 endotracheal aspirates, 26 gastric aspirates and 10 stool specimens). Specimens were collected at a median time of 3 days (lower respiratory tract and gastric aspirates; interquartile range [IQR] 2–4) and 6 days (stool; IQR 4.25–6.75) following ICU admission. We observed a loss of biogeographical distinction between the lower respiratory tract and gastrointestinal tract microbiota during critical illness. Moreover, microbial diversity in the respiratory tract was inversely correlated with APACHE II score (r = − 0.46, p = 0.013) and was associated with hospital mortality (Median Shannon index: Discharged alive; 1.964 vs. Deceased; 1.348, p = 0.045). The composition of the host-associated microbial communities is severely perturbed during critical illness. Reduced microbial diversity reflects high illness severity and is associated with mortality. Microbial diversity may be a biomarker of prognostic value in mechanically ventilated patients. ClinicalTrials.gov ID NCT01782755 . Registered February 4 2013.

International Practice Variation in Weaning Critically Ill Adults from Invasive Mechanical Ventilation.

Abstract: Rationale: Randomized trials and meta-analyses have informed several aspects of weaning. Results are rarely replicated in practice, as evidence is applied in intensive care units that differ from t...

7 versus 14 days of antibiotic treatment for critically ill patients with bloodstream infection: a pilot randomized clinical trial.

Abstract: Shorter-duration antibiotic treatment is sufficient for a range of bacterial infections, but has not been adequately studied for bloodstream infections. Our systematic review, survey, and observational study indicated equipoise for a trial of 7 versus 14 days of antibiotic treatment for bloodstream infections; a pilot randomized clinical trial (RCT) was a necessary next step to assess feasibility of a larger trial. We conducted an open, pilot RCT of antibiotic treatment duration among critically ill patients with bloodstream infection across 11 intensive care units (ICUs). Antibiotic selection, dosing and route were at the discretion of the treating team; patients were randomized 1:1 to intervention arms consisting of two fixed durations of treatment – 7 versus 14 days. We recruited adults with a positive blood culture yielding pathogenic bacteria identified while in ICU. We excluded patients with severe immunosuppression, foci of infection with an established requirement for prolonged treatment, single cultures with potential contaminants, or cultures yielding Staphylococcus aureus or fungi. The primary feasibility outcomes were recruitment rate and adherence to treatment duration protocol. Secondary outcomes included 90-day, ICU and hospital mortality, relapse of bacteremia, lengths of stay, mechanical ventilation and vasopressor duration, antibiotic-free days, Clostridium difficile, antibiotic adverse events, and secondary infection with antimicrobial-resistant organisms. We successfully achieved our target sample size (n = 115) and average recruitment rate of 1 (interquartile range (IQR) 0.3–1.5) patient/ICU/month. Adherence to treatment duration was achieved in 89/115 (77%) patients. Adherence differed by underlying source of infection: 26/31 (84%) lung; 18/29 (62%) intra-abdominal; 20/26 (77%) urinary tract; 8/9 (89%) vascular-catheter; 4/4 (100%) skin/soft tissue; 2/4 (50%) other; and 11/12 (92%) unknown sources. Patients experienced a median (IQR) 14 (8–17) antibiotic-free days (of the 28 days after blood culture collection). Antimicrobial-related adverse events included hepatitis in 1 (1%) patient, Clostridium difficile infection in 4 (4%), and secondary infection with highly resistant microorganisms in 10 (9%). Ascertainment was complete for all study outcomes in ICU, in hospital and at 90 days. It is feasible to conduct a RCT to determine whether 7 versus 14 days of antibiotic treatment is associated with comparable 90-day survival. ClinicalTrials.gov , identifier: NCT02261506 . Registered on 26 September 2014.

Critical Care Nurses' Experiences With Spiritual Care: The SPIRIT Study.

Abstract: Background Little is known about the effect of chaplains on critical care nurses who are caring for critically ill patients and their families. Objective To understand nurses' experiences when they make a referral to the Spiritual Care Department for a patient or the family of a patient who is dying or deceased. Specific aims were to explore spiritual care's effect on nurses and how nurses understand the role of spiritual care in practice. Methods A qualitative descriptive study using in-person, semistructured interviews in a 21-bed medical-surgical intensive care unit in a teaching hospital. Purposeful sampling identified nurses who had at least 5 years of experience and had cared for at least 5 patients who died on their shift and at least 5 patients for whom they initiated a spiritual care referral. Interviews were digitally recorded and anonymized; conventional content analysis was used to analyze transcripts. Three investigators independently coded 5 transcripts and developed the preliminary coding list. As analysis proceeded, investigators organized codes into categories and themes. Results A total of 25 nurses were interviewed. The central theme that emerged was presence, described through 3 main categories: the value of having chaplains present in the intensive care unit and their role, nurses' experiences working with chaplains, and nurses' experiences providing spiritual care. Conclusion Nurses considered spiritual care essential to holistic care and valued the support chaplains provide to patients, families, and staff in today's spiritually diverse society.

The Deferred Consent Model in a Prospective Observational Study Evaluating Myocardial Injury in the Intensive Care Unit.

Abstract: Background:Informed consent is a hallmark of ethical clinical research. An inherent challenge in critical care research is obtaining consent when patients lack decision-making capacity. One solutio...

Low-molecular-weight heparin venous thromboprophylaxis in critically ill patients with renal dysfunction: A subgroup analysis of the PROTECT trial.

Abstract: Introduction There is concern about excessive bleeding when low-molecular-weight heparins (LMWHs) are used for venous thromboembolism (VTE) prophylaxis in renal dysfunction. Our objective was to evaluate whether LMWH VTE prophylaxis was safe and effective in critically ill patients with renal dysfunction by conducting a subgroup analysis of PROTECT, a randomized blinded trial.

Enhancing research publications and advancing scientific writing in health research collaborations: sharing lessons learnt from the trenches.

Abstract: Background Disseminating research protocols, processes, methods or findings via peer-reviewed publications has substantive merits and benefits to various stakeholders. Purpose In this article, we share strategies to enhance research publication contents (ie, what to write about) and to facilitate scientific writing (ie, how to write) in health research collaborations. Methods Empirical experience sharing. Results To enhance research publication contents, we encourage identifying appropriate opportunities for publications, publishing protocols ahead of results papers, seeking publications related to methodological issues, considering justified secondary analyses, and sharing academic process or experience. To advance writing, we suggest setting up scientific writing as a goal, seeking an appropriate mentorship, making full use of scientific meetings and presentations, taking some necessary formal training in areas such as effective communication and time and stress management, and embracing the iterative process of writing. Conclusion All the strategies we share are dependent upon each other; and they advocate gradual academic accomplishments through study and training in a "success-breeds-success" way. It is expected that the foregoing shared strategies in this paper, together with other previous guidance articles, can assist one with enhancing research publications, and eventually one's academic success in health research collaborations.

Chloride and Other Electrolyte Concentrations in Commonly Available 5% Albumin Products.

Abstract: Objective:Use of hyperchloremic IV fluids for resuscitation in sepsis may be associated with increased mortality and use of renal replacement therapy. After crystalloids, 5% human albumin represents the second most common resuscitation fluid in the ICU. Its chloride concentration is rarely considere

FLUID trial: a protocol for a hospital-wide open-label cluster crossover pragmatic comparative effectiveness randomised pilot trial.

Abstract: Introduction 0.9% saline and Ringer’s lactate are the two most common resuscitation crystalloid fluids. 0.9% saline may lead to hyperchloraemic metabolic acidosis and may be associated with impaired kidney function and death. Few large multicentre randomised trials have been conducted to evaluate the effect of these two fluids on clinically important outcomes. Methods FLUID is a pragmatic pilot cluster randomised crossover trial in which four hospitals will be randomised to normal saline or Ringer’s lactate for 14 weeks, then crossover to the alternative fluid for the subsequent 14 weeks after 1 to 3 week transition. With waiver of informed consent, all adult and paediatric patients admitted to participating sites will be included in the FLUID trial except for neonates. Primary feasibility outcome is study fluid protocol adherence (target:≥80%). Secondary feasibility outcomes include time to research ethics board (REB) approval and readiness to trial initiation (≤3 months from REB submission and approval). Primary (composite of death or re-admission to hospital in first 90 days of index hospitalisation) and secondary clinical outcomes for the future large FLUID trial will be described. Protocol adherence will be collected by site at specified time points. All clinical data will be obtained at patient level through provincial health administrative data held at the Institute for Clinical Evaluative Sciences (ICES). Event rates for the primary and secondary outcomes will be described using frequencies and proportions with 95% CIs. Intracluster and interperiod correlation coefficients will be calculated from population-level data available at ICES. Ethics and dissemination The study protocol has been approved by the Ottawa Health Science Research Ethics Board. The FLUID pilot will determine feasibility, and ICES data across all potential sites in Ontario will allow calculation of sample size parameter estimates to inform the design and implementation of the large trial. Trial registration number NCT02721485; Pre-results.

Advancing Randomized Controlled Trials in Pediatric Critical Care: The Perspectives of Trialists.

Abstract: Objectives Clinical research is a complex scientific and social enterprise. Our objective was to identify strategies that pediatric critical care trialists consider acceptable, feasible, and effective to improve the design and conduct randomized controlled trials in pediatric critical care. Design Qualitative descriptive study using semistructured individual interviews. Subjects We interviewed 26 pediatric critical care researchers from seven countries who have published a randomized controlled trial (2005-2015). We used purposive sampling to achieve diversity regarding researcher characteristics and randomized controlled trial characteristics. Interventions None. Measurements and main results Most participants (24 [92%]) were from high-income countries, eight (31%) had published more than one randomized controlled trial, 17 (65%) had published a multicenter randomized controlled trial, and eight (31%) had published a multinational randomized controlled trial. An important theme was "building communities"-groups of individuals with similar interests, shared experiences, and common values, bound by professional and personal relationships. Participants described a sense of community as a source of motivation and encouragement and as a means to larger, more rigorous trials, increasing researcher and clinician engagement and maintaining enthusiasm. Strategies to build communities stressed in-person interactions (both professional and social), capable leadership, and trust. Another important theme was "getting started." Participants highlighted the importance of formal research training and high-quality experiential learning through collaboration on other's projects, guided by effective mentorship. Also important was "working within the system"-ensuring academic credit for a range of contributions, not only for the principal investigator role. The longitudinal notion of "building on success" was also underscored as a cross-cutting theme. Conclusions Coordinated, deliberate actions to build community and ensure key training and practical experiences for new investigators may strengthen the research enterprise in pediatric critical care. These strategies, potentially in combination with other novel approaches, may vitalize clinical research in this field.

Hamilton-DONATE: a city-wide pilot observational study of the ICU management of deceased organ donors

Abstract: Improving the medical care of deceased organ donors to increase transplant rates and improve allograft function requires an understanding of the current epidemiology and clinical practices of deceased donation within intensive care units (ICUs). Herein, we report the results of our investigation into the feasibility of a multicentre prospective cohort study addressing the afformentioned issues. We conducted a 12-month prospective observational cohort study in six ICUs and one coronary care unit in Hamilton, Canada. We included consecutive children and adults following consent for deceased organ donation (including neurologic determination of death [NDD] or donation after circulatory death [DCD]). Intensive care unit research staff recorded donor management data from hospital records, extending from one day prior to the consent for organ donation up to the time of organ retrieval. The provincial Organ Donation Organization (ODO) supplemented these data and, additionally, provided data on corresponding organ recipients. We identified, evaluated, and measured three potential obstacles to the feasibility of a national cohort study: obtaining authorization to implement the study with a waiver of research consent, accessibility of transplant recipient data, and the time required to complete very detailed case report forms (CRFs), with valuable lessons learned for implementation in future projects. The local Research Ethics Board and the ODO Privacy Office both authorized the recording of donor and recipient study data with a waiver of research consent. Sixty-seven consecutive consented donors were included (31 NDD and 36 DCD donors); 50 of them provided 144 organs for transplantation to 141 recipients. We identified the age and sex of the recipients as well as the location and date of transplant for all organ recipients in Ontario; however, we obtained no recipient data for six organs transported outside of Ontario. Intensive care unit research staff estimated that future CRF completion will require five to seven hours per patient. The Hamilton-DONATE pilot study supports the feasibility of a larger cohort study to describe the epidemiology and clinical practices related to deceased donor care in Canada. wwwclinicaltrials.gov (NCT02902783). Registered 16 September 2016.

The Young Investigator Retreat of the Canadian Critical Care Trials Group: mentorship and self-discovery.

Abstract: The Canadian Critical Care Trials Group (CCCTG) was created in 1989 to improve the care of critically ill patients through investigator-initiated research and to provide a national forum for continuing education about research methods. In 2004, a group of clinical and basic scientists interested in the basic mechanisms of critical illness formed the Canadian Critical Care Translational Biology Group (CCCTBG). The two groups have grown from the original 25 participants in 1989 to over 300 researchers today. The CCCTG and CCCTBG meet together and currently support over 40 research programs with more than 100 peer-reviewed publications to their credit. The most important ingredients for this success are the collegiality and mentorship of these groups. A research mentor has many potential roles in developing the career of a young investigator, some of which include acting as advisor, advocate, coach, or supervisor, guiding the mentee with intent, commitment, and spirit. Given the need for sustainability and growth, the CCCTG and CCCTBG have an explicit mandate to mentor their junior and senior investigators and to foster their independent success. This mandate is addressed through several activities, including the ‘‘community mentoring’’ model of our thrice yearly meetings, explicit linkage between each young investigator who presents at these meetings and a CCCTG mentor, encouragement of junior members to participate in national committees, interdisciplinary young investigator grants, the Deborah J. Cook Mentorship Award to honour individuals who have made exceptional contributions in this domain, and the creation of the CCCTG Young Investigator Retreat. Dr. I. M. Ball, MD, MSc (&) Departments of Medicine, Epidemiology and Biostatistics, Western University, London, ON, Canada e-mail: Ian.Ball@lhsc.on.ca

Abstract P-334: RESEARCH COLLABORATION IN PEDIATRIC CRITICAL CARE A SOCIAL NETWORK ANALYSIS OF COAUTHORSHIP

Abstract: • Productivity: the total number of RCTs coauthored. • Impact: the total number of citations of all of the RCTs coauthored by each researcher. • Collaborators: the total number of researchers with whom a researcher has coauthored a publication. • Betweenness: the number of times each researcher connects pairs of researchers (directly and indirectly). • Closeness: the mean distance (the number of ties on the shortest path) from a researcher to all other researchers. • Eigenvector centrality: considers not only the number of connections to other researchers, but their importance.