scispace - formally typeset
Search or ask a question

Showing papers by "Deborah J. Cook published in 2015"


Journal ArticleDOI
TL;DR: Transfusion of fresh red cells, as compared with standard-issueRed cells, did not decrease the 90-day mortality among critically ill adults and there were no significant between-group differences in any of the secondary outcomes or in the subgroup analyses.
Abstract: BackgroundFresh red cells may improve outcomes in critically ill patients by enhancing oxygen delivery while minimizing the risks of toxic effects from cellular changes and the accumulation of bioactive materials in blood components during prolonged storage. MethodsIn this multicenter, randomized, blinded trial, we assigned critically ill adults to receive either red cells that had been stored for less than 8 days or standard-issue red cells (the oldest compatible units available in the blood bank). The primary outcome measure was 90-day mortality. ResultsBetween March 2009 and May 2014, at 64 centers in Canada and Europe, 1211 patients were assigned to receive fresh red cells (fresh-blood group) and 1219 patients were assigned to receive standard-issue red cells (standard-blood group). Red cells were stored a mean (±SD) of 6.1±4.9 days in the fresh-blood group as compared with 22.0±8.4 days in the standard-blood group (P<0.001). At 90 days, 448 patients (37.0%) in the fresh-blood group and 430 patients (...

501 citations


Journal ArticleDOI
TL;DR: In mechanically ventilated adults, Delirium was common and associated with longer duration of ventilation and hospitalization and physical restraint was most strongly associated with delirium.
Abstract: Objective:Delirium is common during critical illness and associated with adverse outcomes. We compared characteristics and outcomes of delirious and nondelirious patients enrolled in a multicenter trial comparing protocolized sedation with protocolized sedation plus daily sedation interruption.Desig

257 citations


Journal ArticleDOI
TL;DR: Clinically important GI bleeding was not associated with increased adjusted 90-day mortality, which largely can be explained by severity of comorbidity, other organ failures and age.
Abstract: To describe the prevalence of, risk factors for, and prognostic importance of gastrointestinal (GI) bleeding and use of acid suppressants in acutely ill adult intensive care patients. We included adults without GI bleeding who were acutely admitted to the intensive care unit (ICU) during a 7-day period. The primary outcome was clinically important GI bleeding in ICU, and the analyses included estimations of baseline risk factors and potential associations with 90-day mortality. A total of 1,034 patients in 97 ICUs in 11 countries were included. Clinically important GI bleeding occurred in 2.6 % (95 % confidence interval 1.6-3.6 %) of patients. The following variables at ICU admission were independently associated with clinically important GI bleeding: three or more co-existing diseases (odds ratio 8.9, 2.7-28.8), co-existing liver disease (7.6, 3.3-17.6), use of renal replacement therapy (6.9, 2.7-17.5), co-existing coagulopathy (5.2, 2.3-11.8), acute coagulopathy (4.2, 1.7-10.2), use of acid suppressants (3.6, 1.3-10.2) and higher organ failure score (1.4, 1.2-1.5). In ICU, 73 % (71-76 %) of patients received acid suppressants; most received proton pump inhibitors. In patients with clinically important GI bleeding, crude and adjusted odds for mortality were 3.7 (1.7-8.0) and 1.7 (0.7-4.3), respectively. In ICU patients clinically important GI bleeding is rare, and acid suppressants are frequently used. Co-existing diseases, liver failure, coagulopathy and organ failures are the main risk factors for GI bleeding. Clinically important GI bleeding was not associated with increased adjusted 90-day mortality, which largely can be explained by severity of comorbidity, other organ failures and age.

189 citations


Journal ArticleDOI
TL;DR: One-quarter of patients aged 80 years or older who are admitted to ICU survived and returned to baseline levels of physical function at 1 year and routine assessment of baseline physical function and frailty status could aid in prognostication and informed decision-making for very old critically ill patients.
Abstract: Increasingly, very old patients are admitted to Intensive Care Units (ICUs). The objective of this study was to describe 12-month outcomes of these patients and determine which characteristics are associated with a return to baseline physical function 1 year later. In this prospective cohort study in 22 Canadian hospitals, we recruited 610 patients aged 80 years or older who were admitted to ICU for at least 24 h. At baseline, we completed a comprehensive geriatric assessment and followed patients to determine 12-month survival and physical function. Our primary outcome was physical recovery from critical illness at 12 months, defined as being alive with Short Form-36 physical function score of at least 10 points, and not 10 or more points below baseline. We used regression analysis to examine factors associated with physical recovery. Patients were on average 84 years old (range 80–99). Mortality was 14 % in ICU, 26 % in hospital and 44 % at 12 months after admission. Of 505 patients evaluable at 12 months, 26 % achieved physical recovery. In the multivariable model, physical recovery was significantly associated with younger age, lower APACHE II score, lower Charlson comorbidity score, lower frailty index, lower baseline physical function score, and specific admission diagnoses. One-quarter of patients aged 80 years or older who are admitted to ICU survived and returned to baseline levels of physical function at 1 year. Routine assessment of baseline physical function and frailty status could aid in prognostication and informed decision-making for very old critically ill patients. (ClinicalTrials.gov number NCT01293708).

170 citations


Journal ArticleDOI
TL;DR: Heparin in patients with sepsis, septic shock, and disseminated intravascular coagulation associated with infection may be associated with decreased mortality; however, the overall impact remains uncertain.
Abstract: Objective:To evaluate the efficacy and safety of heparin in patients with sepsis, septic shock, or disseminated intravascular coagulation associated with infection.Design:Systematic review and metaanalysis.Data Sources:Randomized controlled trials from MEDLINE, EMBASE, CENTRAL, Global Health, Scopus

140 citations


Journal ArticleDOI
TL;DR: No significant differences were found in death or disability at 24 months, bronchopulmonary dysplasia, retinopathy of prematurity, neurodevelopmental outcomes, or hearing loss at24 months, and the quality of evidence for these outcomes was moderate to low.
Abstract: Importance The optimal oxygen saturation (SpO 2 ) target for extremely preterm infants is unknown. Objective To systematically review evidence evaluating the effect of restricted vs liberal oxygen exposure on morbidity and mortality in extremely preterm infants. Data Sources MEDLINE, PubMed, CENTRAL, and CINAHL databases from their inception to March 31, 2014, and abstracts submitted to Pediatric Academic Societies from 2000 to 2014. Study Selection All published randomized trials evaluating the effect of restricted (SpO 2 , 85%-89%) vs liberal (SpO 2 , 91%-95%) oxygen exposure in preterm infants ( Data Extraction and Synthesis All meta-analyses were performed using Review Manager 5.2. The Cochrane risk-of-bias tool was used to assess study quality. The summary of the findings and the level of confidence in the estimate of effect were assessed using GRADEpro. Treatment effect was analyzed using a random-effects model. Main Outcomes and Measures Death before hospital discharge, death or severe disability before 24 months, death before 24 months, neurodevelopmental outcomes, hearing loss, bronchopulmonary dysplasia, necrotizing enterocolitis, and severe retinopathy of prematurity. Results Five trials were included in the final synthesis. These studies had a similar design with a prespecified composite outcome of death/disability at 18 to 24 months corrected for prematurity; however, this outcome has not been reported for 2 of the 5 trials. There was no difference in the outcome of death/disability before 24 months (risk ratio [RR], 1.02 [95% CI, 0.92-1.14]). Mortality before 24 months was not different (RR, 1.13 [95% CI, 0.97-1.33]); however, a significant increase in mortality before hospital discharge was found in the restricted oxygen group (RR, 1.18 [95% CI, 1.03-1.36]). The rates of bronchopulmonary dysplasia, neurodevelopmental outcomes, hearing loss, and retinopathy of prematurity were similar between the 2 groups. Necrotizing enterocolitis occurred more frequently in infants on restricted oxygen (RR, 1.24 [95% CI, 1.05-1.47]). Using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) criteria, we found that the quality of evidence for these outcomes was moderate to low. Conclusions and Relevance Although infants cared for with a liberal oxygen target had significantly lower mortality before hospital discharge than infants cared for with a restricted oxygen target, the quality of evidence for this estimate of effect is low. Necrotizing enterocolitis occurred less frequently in the liberal oxygen group. We found no significant differences in death or disability at 24 months, bronchopulmonary dysplasia, retinopathy of prematurity, neurodevelopmental outcomes, or hearing loss at 24 months.

134 citations


Journal ArticleDOI
TL;DR: After adjustment for baseline covariates, early provision of high-dose glutamine administered separately from artificial nutrition was not beneficial and may be associated with increased mortality in critically ill patients with multiorgan failure.
Abstract: Background: The recent large randomized controlled trial of glutamine and antioxidant supplementation suggested that high-dose glutamine is associated with increased mortality in critically ill patients with multiorgan failure. The objectives of the present analyses were to reevaluate the effect of supplementation after controlling for baseline covariates and to identify potentially important subgroup effects. Materials and Methods: This study was a post hoc analysis of a prospective factorial 2 × 2 randomized trial conducted in 40 intensive care units in North America and Europe. In total, 1223 mechanically ventilated adult patients with multiorgan failure were randomized to receive glutamine, antioxidants, both glutamine and antioxidants, or placebo administered separate from artificial nutrition. We compared each of the 3 active treatment arms (glutamine alone, antioxidants alone, and glutamine + antioxidants) with placebo on 28-day mortality. Post hoc, treatment effects were examined within subgroups ...

116 citations


Journal ArticleDOI
TL;DR: Although patients with traumatic brain injury randomly assigned to intensive compared to conventional glucose control experienced moderate and severe hypoglycemia more frequently, it was found no significant difference in clinically important outcomes.
Abstract: Purpose: To compare the effect of intensive versus conventional blood glucose control in patients with traumatic brain injury. Methods: In a large international randomized trial patients were randomly assigned to a target blood glucose (BG) range of either 4.5–6.0 mmol/L (intensive control) or <10 mmol/L (conventional control). Patients with traumatic brain injury (TBI) were identified at randomization and data were collected to examine the extended Glasgow outcome score (includes mortality) at 24 months. Results: Of the 6104 randomized patients, 391 satisfied diagnostic criteria for TBI; 203 (51.9 %) were assigned to intensive and 188 (48.1 %) to conventional control; the primary outcome was available for 166 (81.8 %) and 149 (79.3 %) patients, respectively. The two groups had similar baseline characteristics. At 2 years 98 (58.7 %) patients in the intensive group and 79 (53.0 %) in the conventional group had a favorable neurological outcome (odds ratio [OR] 1.26, 95 % CI 0.81–1.97; P = 0.3); 35 patients (20.9 %) in the intensive group and 34 (22.8 %) in the conventional group had died (OR 0.90, 95 % CI 0.53–1.53; P = 0.7); moderate hypoglycemia (BG 2.3–3.9 mmol/L; 41–70 mg/dL) occurred in 160/202 (79.2 %) and 17/188 (9.0 %), respectively (OR 38.3, 95 % CI 21.0–70.1; P < 0.0001); severe hypoglycemia (BG ≤ 2.2 mmol/L; ≤40 mg/dL) in 10 (4.9 %) and 0 (0.0 %), respectively (OR 20.5 95 % CI 1.2–351.6, P = 0.003). Conclusion: Although patients with traumatic brain injury randomly assigned to intensive compared to conventional glucose control experienced moderate and severe hypoglycemia more frequently, we found no significant difference in clinically important outcomes.

114 citations


Journal ArticleDOI
TL;DR: Failure of standard thromboprophylaxis using low-molecular-weight heparin or unfractionated heparIn is more likely in ICU patients with elevated body mass index, those with a personal or family history of venous thromboembolism, and those receiving vasopressors.
Abstract: Objectives:To identify risk factors for failure of anticoagulant thromboprophylaxis in critically ill patients in the ICU.Design:Multivariable regression analysis of thrombosis predictors from a randomized thromboprophylaxis trial.Setting:Sixty-seven medical-surgical ICUs in six countries.Patients:T

100 citations


Journal ArticleDOI
TL;DR: The 3 Wishes Project was developed to try to bring peace to the final days of critically ill patients and to ease the grieving process, by eliciting and implementing a set of wishes identified by patients, families, clinicians, or the project team.
Abstract: Background 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. Objective To bring peace to the final days of a patient's life and to ease the grieving process. Design Mixed-methods study. Setting 21-bed medical-surgical intensive care unit. Participants Dying patients and their families and clinicians. Intervention To honor each patient, a set of wishes was generated by patients, family members, or clinicians. The wishes were implemented before or after death by patients, families, clinicians (6 of whom were project team members), or the project team. Measurements Quantitative data included demographic characteristics, processes of care, and scores on the Quality of End-of-Life Care-10 instrument. Semistructured interviews of family members and clinicians were transcribed verbatim, and qualitative description was used to analyze them. Results Participants included 40 decedents, at least 1 family member per patient, and 3 clinicians per patient. The 159 wishes were implemented and classified into 5 categories: humanizing the environment, tributes, family reconnections, observances, and "paying it forward." Scores on the Quality of End-of-Life Care-10 instrument were high. The central theme from 160 interviews of 170 persons was how the 3 Wishes Project personalized the dying process. For patients, eliciting and customizing the wishes honored them by celebrating their lives and dignifying their deaths. For families, it created positive memories and individualized end-of-life care for their loved ones. For clinicians, it promoted interprofessional care and humanism in practice. Limitation Impaired consciousness limited understanding of patients' viewpoints. Conclusion The 3 Wishes Project facilitated personalization of the dying process through explicit integration of palliative and spiritual care into critical care practice. Primary funding source Hamilton Academy of Health Science Research Organization, Canadian Intensive Care Foundation.

74 citations


Journal ArticleDOI
TL;DR: It is hypothesized that patient selection for SUP varies both within and between countries, but the risk of infection may be increased.
Abstract: Background: Stress ulcer prophylaxis (SUP) may decrease the incidence of gastrointestinal bleeding in patients in the intensive care unit (ICU), but the risk of infection may be increased. In this study, we aimed to describe SUP practices in adult ICUs. We hypothesised that patient selection for SUP varies both within and between countries. MethodsAdult ICUs were invited to participate in the survey. We registered country, type of hospital, type and size of ICU, preferred SUP agent, presence of local guideline, reported indications for SUP, criteria for discontinuing SUP, and concerns about adverse effects. Fisher's exact test was used to assess differences between groups. ResultsNinety-seven adult ICUs in 11 countries participated (eight European). All but one ICU used SUP, and 64% (62/97) reported having a guideline for the use of SUP. Proton pump inhibitors were the most common SUP agent, used in 66% of ICUs (64/97), and H2-receptor antagonists were used 31% (30/97) of the units. Twenty-three different indications for SUP were reported, the most frequent being mechanical ventilation. All patients were prescribed SUP in 26% (25/97) of the ICUs. Adequate enteral feeding was the most frequent reason for discontinuing SUP, but 19% (18/97) continued SUP upon ICU discharge. The majority expressed concern about nosocomial pneumonia and Clostridium difficile infection with the use of SUP. ConclusionsIn this international survey, most participating ICUs reported using SUP, primarily proton pump inhibitors, but many did not have a guideline; indications varied considerably and concern existed about infectious complications. (Less)

Journal ArticleDOI
TL;DR: Among the patients with sepsis, fluid resuscitation with crystalloids compared to starch resulted in reduced use of RRT; the same may be true for albumin versus starch.
Abstract: Fluid resuscitation, along with the early administration of antibiotics, is the cornerstone of treatment for patients with sepsis. However, whether differences in resuscitation fluids impact on the requirements for renal replacement therapy (RRT) remains unclear. To examine this issue, we performed a network meta-analysis (NMA), including direct and indirect comparisons, that addressed the effect of different resuscitation fluids on the use of RRT in patients with sepsis. The data sources MEDLINE, EMBASE, ACPJC, CINAHL and Cochrane Central Register were searched up to March 2014. Eligible studies included randomized trials reported in any language that enrolled adult patients with sepsis or septic shock and addressed the use of RRT associated with alternative resuscitation fluids. The risk of bias for individual studies and the overall certainty of the evidence were assessed. Ten studies (6664 patients) that included a total of nine direct comparisons were assessed. NMA at the four-node level showed that an increased risk of receiving RRT was associated with fluid resuscitation with starch versus crystalloid [odds ratio (OR) 1.39, 95% credibility interval (CrI) 1.17-1.66, high certainty]. The data suggested no difference between fluid resuscitation with albumin and crystalloid (OR 1.04, 95% CrI 0.78-1.38, moderate certainty) or starch (OR 0.74, 95% CrI 0.53-1.04, low certainty). NMA at the six-node level showed a decreased risk of receiving RRT with balanced crystalloid compared to heavy starch (OR 0.50, 95% CrI 0.34-0.74, moderate certainty) or light starch (OR 0.70, 95% CrI 0.49-0.99, high certainty). There was no significant difference between balanced crystalloid and saline (OR 0.85, 95% CrI 0.56-1.30, low certainty) or albumin (OR 0.82, 95% CrI 0.49-1.37, low certainty). Of note, these trials vary in terms of case mix, fluids evaluated, duration of fluid exposure and risk of bias. Imprecise estimates contributed to low confidence in most estimates of effect. Among the patients with sepsis, fluid resuscitation with crystalloids compared to starch resulted in reduced use of RRT; the same may be true for albumin versus starch.

Journal ArticleDOI
TL;DR: There is incongruity between family values and preferences for end-of-life care and actual care received for very elderly patients who are admitted to the intensive care unit, and defects in communication and decision-making may be associated with prolonged use of life-sustaining treatments in very elderly critically ill patients.
Abstract: Background:Little is known about the perspectives and experiences of family members of very elderly patients who are admitted to the intensive care unit.Aim:To describe family members’ perspectives about care provided to very elderly critically ill patients.Design:Multicenter, prospective, cohort study.Participants and setting:In total, 535 family members of patients aged 80 years or older admitted to 22 intensive care units for more than 24 h.Results:Family members reported that the “patient be comfortable and suffer as little as possible” was their most important value and “the belief that life should be preserved at all costs” was their least important value considered in making treatment decisions. Most family members (57.9%) preferred that life support be used for their family member, whereas 24.1% preferred comfort measures only, and 14.4% were unsure of their treatment preferences. Only 57.3% reported that a doctor had talked to them about treatment options for the patient. Overall, 29.7% of patien...

Journal ArticleDOI
TL;DR: The results highlight the need to evolve inter-jurisdictional resource sharing during periods of substantial increase in demand, and provide background data for the development of appropriate critical care capacity benchmarks.
Abstract: Introduction Intensive Care Units (ICUs) provide life-supporting treatment; however, resources are limited, so demand may exceed supply in the event of pandemics, environmental disasters, or in the context of an aging population. We hypothesized that comprehensive national data on ICU resources would permit a better understanding of regional differences in system capacity.

Journal ArticleDOI
TL;DR: The results showed that coagulation and platelet function are impaired by all 3 colloids, and the liberal use of colloids may be called into question because of the negative effects on coagulations and difficulties in reversing the effects.
Abstract: It is not uncommon for patients to have an expected death in an ICU. This review covers issues related to the end of life in the absence of discordance between the patient's family and caregivers.

Journal ArticleDOI
TL;DR: The perceptions of acute care practitioners in Canada were explored to determine whether they perceived nonbeneficial treatment to be a problem, to generate an acceptable definition of non Beneficial treatment, and to learn about their perceptions of the impact and causes of nonBeneficial treatment.
Abstract: Objective:Many healthcare workers are concerned about the provision of nonbeneficial treatment in the acute care setting. We sought to explore the perceptions of acute care practitioners to determine whether they perceived nonbeneficial treatment to be a problem, to generate an acceptable definition

Journal ArticleDOI
TL;DR: Lack of ICU recall and delusional memories were common after ICU discharge despite the use of sedation strategies that promoted wakefulness and types of memories reported were not influenced by the trial sedation strategy.
Abstract: Objectives:To 1) describe factual, emotional, and delusional memories of ICU stay for patients enrolled in the SLEAP (Daily sedation interruption in mechanically ventilated critically ill patients cared for with a sedation protocol) trial; 2) compare characteristics of patients with and without ICU

Journal ArticleDOI
TL;DR: It is found that there is no significant difference in rates of mucosal prolapse or defecation scores for LAARP compared to OPEN for children with RB/RP-ARMs, however, studies are small and of poor-moderate quality and results are heterogeneous.
Abstract: The laparoscopically-assisted anorectal pull-through (LAARP) for recto-bladderneck and recto-prostatic anorectal malformations (RB/RP-ARMs) is believed to improve patient outcomes. We performed a systematic review of the effect of LAARP on postoperative mucosal prolapse and defecation dysfunction. A comprehensive search of MEDLINE, EMBASE, CENTRAL, and grey literature was performed (2000–2014). Full-text screening, data abstraction and quality appraisal were conducted in duplicate. Included studies reported a primary diagnosis of RB/RP-ARM and compared LAARP versus open repair (OPEN). From 3681 retrieved articles, 7 studies enrolling 187 patients were analyzed. One was a randomized control trial, 6 were retrospective observational studies, and all were single-centre. The majority were of poor-moderate quality (MINORS scores: mean 16.42 (SD 2.225) out of 24). Mucosal prolapse was not significantly different after LAARP versus OPEN (p = 0.18). Defecation outcomes were inconsistently reported but were no different between LAARP and OPEN for either children >3 years old (p = 0.84), or all ages combined (p = 0.11). We found no significant difference in rates of mucosal prolapse or defecation scores for LAARP compared to OPEN for children with RB/RP-ARMs. However, studies are small and of poor-moderate quality and results are heterogeneous. Comprehensive, standardized, reliable reporting is necessary to guide practice and inform postoperative guidelines. 1c.


Journal ArticleDOI
23 Dec 2015-PLOS ONE
TL;DR: There is considerable variation in current rounding practices in Canadian medical/surgical ICUs and opportunities exist to improve ICU rounds including ensuring the engagement of essential participants, clearly defining participant roles, establishing a standardized approach to the rounding process, minimizing interruptions, modifying the role of teaching, and developing a metric for measuring rounding quality.
Abstract: Objective To describe rounding practices in Canadian adult Intensive Care Units (ICU) and identify opportunities for improvement. Design Mixed methods design. Cross sectional survey of Canadian Adult ICUs (n = 180) with purposefully sampled follow-up interviews (n = 7). Measurements and Main Results Medical directors representing 111 ICUs (62%) participated in the survey. Rounding practices varied across ICUs with the majority reporting the use of interprofessional rounds (81%) that employed an open (94%) and collaborative (86%) approach, occurred at the patient’s bedside (82%), and started at a standard time (79%) and standard location (56%). Most participants reported that patients (83%) and family members (67%) were welcome to attend rounds. Approximately half of ICUs (48%) used tools to facilitate rounds. Interruptions during rounds were reported to be common (i.e., ≥1 interruption for ≥50% of patients) in 46% of ICUs. Four themes were identified from qualitative analysis of participant responses to open-ended survey questions and interviews: multidisciplinarity, patient and family involvement, factors influencing productivity, and teaching and learning. Conclusions There is considerable variation in current rounding practices in Canadian medical/surgical ICUs. Opportunities exist to improve ICU rounds including ensuring the engagement of essential participants, clearly defining participant roles, establishing a standardized approach to the rounding process, minimizing interruptions, modifying the role of teaching, utilizing a structured rounding tool, and developing a metric for measuring rounding quality.

Journal ArticleDOI
18 Apr 2015-Trials
TL;DR: The BALANCE pilot trial will inform the design and execution of the subsequent BALANCE main trial, which will evaluate shorter versus longer duration treatment for bacteremia in critically ill patients, and thereby provide an evidence basis for treatment duration decisions for these infections.
Abstract: Bacteremia is a leading cause of mortality and morbidity in critically ill adults. No previous randomized controlled trials have directly compared shorter versus longer durations of antimicrobial treatment in these patients. This is a multicenter pilot randomized controlled trial in critically ill patients with bacteremia. Eligible patients will be adults with a positive blood culture with pathogenic bacteria identified while in the intensive care unit. Eligible, consented patients will be randomized to either 7 days or 14 days of adequate antimicrobial treatment for the causative pathogen(s) detected on blood cultures. The diversity of pathogens and treatment regimens precludes blinding of patient and clinicians, but allocation concealment will be extended to day 7 and outcome adjudicators will be blinded. The primary outcome for the main trial will be 90-day mortality. The primary outcome for the pilot trial is feasibility defined by (i) rate of recruitment exceeding 1 patient per site per month and (ii) adherence to treatment duration protocol ≥ 90%. Secondary outcomes include intensive care unit, hospital and 90-day mortality rates, relapse rates of bacteremia, antibiotic-related side effects and adverse events, rates of Clostridium difficile infection, rates of secondary infection or colonization with antimicrobial resistant organisms, ICU and hospital lengths of stay, mechanical ventilation and vasopressor duration in intensive care unit, and procalcitonin levels on the day of randomization, and day 7, 10 and 14 after the index blood culture. The BALANCE pilot trial will inform the design and execution of the subsequent BALANCE main trial, which will evaluate shorter versus longer duration treatment for bacteremia in critically ill patients, and thereby provide an evidence basis for treatment duration decisions for these infections. The Pilot Trial was registered on 26 September 2014. Trial registration number: NCT02261506 .

Journal ArticleDOI
22 Oct 2015-PLOS ONE
TL;DR: A community-based participatory research approach engaged a diverse group of stakeholders to identify 9 priorities for improving the quality and value of critical care and could serve as a model to prioritize areas for research quality improvement across other settings.
Abstract: Background Large amounts of scientific evidence are generated, but not implemented into patient care (the ‘knowledge-to-care’ gap). We identified and prioritized knowledge-to-care gaps in critical care as opportunities to improve the quality and value of healthcare. Methods We used a multi-method community-based participatory research approach to engage a Network of all adult (n = 14) and pediatric (n = 2) medical-surgical intensive care units (ICUs) in a fully integrated geographically defined healthcare system serving 4 million residents. Participants included Network oversight committee members (n = 38) and frontline providers (n = 1,790). Network committee members used a modified RAND/University of California Appropriateness Methodology, to serially propose, rate (validated 9 point scale) and revise potential knowledge-to-care gaps as priorities for improvement. The priorities were sent to frontline providers for evaluation. Results were relayed back to all frontline providers for feedback. Results Initially, 68 knowledge-to-care gaps were proposed, rated and revised by the committee (n = 32 participants) over 3 rounds of review and resulted in 13 proposed priorities for improvement. Then, 1,103 providers (62% response rate) evaluated the priorities, and rated 9 as ‘necessary’ (median score 7–9). Several factors were associated with rating priorities as necessary in multivariable logistic regression, related to the provider (experience, teaching status of ICU) and topic (strength of supporting evidence, potential to benefit the patient, potential to improve patient/family experience, potential to decrease costs). Conclusions A community-based participatory research approach engaged a diverse group of stakeholders to identify 9 priorities for improving the quality and value of critical care. The approach was time and cost efficient and could serve as a model to prioritize areas for research quality improvement across other settings.


Journal ArticleDOI
TL;DR: This study suggests that enrollment in trials of mechanical ventilation may be associated with improved outcomes compared with standard care and highlights the need for prospective tracking and transparent reporting of ENE patients as part of trial management.
Abstract: Rationale: Patients eligible for randomized controlled trials may not be enrolled for various reasons. Nonenrollment may affect study generalizability and lengthen the time required for trial completion.Objectives: To describe characteristics and outcomes of eligible nonenrolled (ENE) patients in a multicenter trial of mechanical ventilation strategies.Methods: Within the OSCILLATE trial of high-frequency oscillation (HFO) versus conventional ventilation (CV) in adults with adult respiratory distress syndrome, and with approval from research ethics boards, we collected a minimal dataset on patients who satisfied eligibility criteria but were not enrolled. We categorized ENE patients as ENE-HFO and ENE-CV based on receipt of HFO at any time. We used multivariable logistic regression to assess the association between ENE status and mortality.Measurements and Main Results: A total of 548 patients were randomized, and 546 were ENE. The most common reasons for ENE were no consent (42%), physician refusal (24%)...

Journal ArticleDOI
TL;DR: The PROSPECT Pilot Trial is the initial step toward rigorously evaluating whether probiotics decrease nosocomial infections, have no effect, or actually cause infections in critically ill patients.
Abstract: Probiotics are defined as live microorganisms that may confer health benefits when ingested. Meta-analysis of probiotic trials suggests a 25 % lower ventilator-associated pneumonia (VAP) and 18 % lower infection rates overall when administered to patients in the intensive care unit (ICU). However, prior trials are small, largely single center, and at high risk of bias. Before a large rigorous trial is launched, testing whether probiotics confer benefit, harm, or have no impact, a pilot trial is needed. The aim of the PROSPECT Pilot Trial is to determine the feasibility of performing a larger trial in mechanically ventilated critically ill patients investigating Lactobacillus rhamnosus GG. A priori, we determined that the feasibility of the larger trial would be based on timely recruitment, high protocol adherence, minimal contamination, and an acceptable VAP rate. Patients ≥18 years old in the ICU who are anticipated to receive mechanical ventilation for ≥72 hours will be included. Patients are excluded if they are at increased risk of probiotic-associated infection, have strict enteral medication contraindications, are pregnant, previously enrolled in a related trial, or are receiving palliative care. Following informed consent, patients are randomized in variable unspecified block sizes in a fixed 1:1 ratio, stratified by ICU, and medical, surgical, or trauma admitting diagnosis. Patients receive 1 × 1010 colony forming units of L. rhamnosus GG (Culturelle, Locin Industries Ltd) or an identical placebo suspended in tap water administered twice daily via nasogastric tube in the ICU. Clinical and research staff, patients, and families are blinded. The primary outcomes for this pilot trial are the following: (1) recruitment success, (2) ≥90 % protocol adherence, (3) ≤5 % contamination, and (4) ~10 % VAP rate. Additional clinical outcomes are VAP, other infections, diarrhea (total, antibiotic associated, and Clostridium difficile), ICU and hospital length of stay, and mortality. The morbidity, mortality, and cost of VAP underscore the need for cost-effective prophylactic interventions. The PROSPECT Pilot Trial is the initial step toward rigorously evaluating whether probiotics decrease nosocomial infections, have no effect, or actually cause infections in critically ill patients. ClinicalTrials.gov. NCT01782755

Journal ArticleDOI
TL;DR: Clinical research related to the effect of clonidine on sedation, signs and symptoms of withdrawal, and other adverse events among mechanically ventilated children is summarized to support current widespread use.
Abstract: Objective. To summarize clinical research related to the effect of clonidine on sedation, signs and symptoms of withdrawal, and other adverse events among mechanically ventilated children. Data Sources. We searched MEDLINE, EMBASE, CINAHL, LILACS and the Cochrane Central Register of Controlled Trials, trial registries and conference proceedings. Study Selection. We included all observational and experimental studies that reported the transdermal, intravenous or enteral administration of clonidine to mechanically ventilated, critically ill pediatric patients. Data Extraction. We extracted data on the effect of clonidine on sedation, withdrawal, duration of ventilation and adverse effects and did not attempt to quantitatively combine the results due to the heterogeneous study design and patient populations. Data Synthesis. This review includes 4 case reports, two retrospective cohort studies (total of 58 children), two prospective uncontrolled studies (total of 55 children) and one randomized controlled trial (69 children). In general, efforts to minimize known sources of bias were modest and all studies used non-validated tools for measuring withdrawal. Small observational studies suggest an improvement in withdrawal symptoms and adequacy of sedation with clonidine therapy; however, the small randomized trial found no effect on these or on the duration of ventilation. Results of these small studies have limited generalizability and provide imprecise estimates of treatment effects. Conclusions. Clonidine has been used as a sedative and analgesic agent to prevent and treat withdrawal in critically ill intubated children. Current clinical studies are inadequate to assess its benefits and harms, and do not support current widespread use.

Journal ArticleDOI
TL;DR: Coenrollment occurred in 23% of patients, commonly in younger patients, in smaller centers with more research infrastructure, and in Canada, and the effect of coenrollment on safety and the trial outcome did not influence patient safety or trial results.
Abstract: Objective: Enrollment of individual patients into more than one study has been poorly evaluated. The objective of this study was to describe the characteristics of patients, researchers and centers involved in coenrollment, studies precluding coenrollment, and the prevalence, patterns, predictors, and outcomes of coenrollment in a randomized clinical trial. Design, Setting, Methods: We conducted an observational study nested within the OSCILLation for Acute Respiratory Distress Syndrome Treated Early Trial, which compared high-frequency oscillatory ventilation to conventional ventilation. We collected patient, center, and study data on coenrollment in randomized patients. Multilevel regression examined factors independently associated with coenrollment, considering clustering within centers. We examined the effect of coenrollment on safety and the trial outcome. Interventions None. Measurements and Main Results: Overall, 127 of 548 randomized patients (23.2%) were coenrolled in 25 unique studies. Coenrollment was reported in 17 of 39 centers (43.6%). Patients were most commonly coenrolled in one additional randomized clinical trial (76; 59.8%). Coenrollment was less likely in older patients (odds ratio, 0.87; 95% CI, 0.76–0.997), and in ICUs with greater than 26 beds (odds ratio, 0.56; 95% CI, 0.34–0.94), and more likely by investigators with more than 11 years of experience (odds ratio, 1.73; 95% CI, 1.06–2.82), by research coordinators with more than 8 years of experience (odds ratio, 1.87; 95% CI, 1.11–3.18) and in Canada (odds ratio, 4.66; 95% CI, 1.43–15.15). Serious adverse events were similar between coenrolled high-frequency oscillatory ventilation and control patients. Coenrollment did not modify the treatment effect of high-frequency oscillatory ventilation on hospital mortality. Conclusions: Coenrollment occurred in 23% of patients, commonly in younger patients, in smaller centers with more research infrastructure, and in Canada. Coenrollment did not influence patient safety or trial results.

Journal ArticleDOI
TL;DR: The relative importance of many factors that clinicians consider when making decisions about medications varies by demographics, and depends on the clinical problem.
Abstract: OBJECTIVE Changing clinician practice in pediatric critical care is often difficult. Tailored knowledge translation interventions may be more effective than other types of interventions. To inform the design of tailored interventions, the primary objective of this survey was to describe the importance of specific factors that influence physicians and pharmacists when they make decisions about medications in critically ill children. DESIGN In this postal survey, respondents used 7-point scales to rate the importance of specific factors that influence their decisions in the following scenarios: corticosteroids for shock, intensive insulin therapy, stress ulcer prophylaxis, surfactant for acute respiratory distress syndrome, and sedation interruption. We used generalized estimating equations to examine the association between the importance of specific factors influencing decision making and the scenario and respondents' practice, views, and demographics. SETTING Canadian PICUs. PARTICIPANTS One hundred and seventeen physicians and pharmacists practicing in 18 PICUs. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS The response rate was 61%. The three factors reported to most strongly influence clinician decision making overall were: severity of illness (mean [SD] 5.8 [1.8]), physiologic rationale (5.2 [1.3]), and adverse effects (5.1 [1.9]). Factors least likely to influence decision making were drug costs (2.0 [1.5]), unit policies (2.9 [1.9]), and non-critical care randomized controlled trials (3.1 [1.9]). The relative importance of 8 of the 10 factors varied significantly among the five scenarios: only randomized controlled trials in critically ill children and other clinical research did not vary. Clinician characteristics associated with the greatest difference in importance ratings were: frequent use of the intervention in that scenario (seven factors), profession (five factors), and respondents' assessment of the quality of evidence (five factors). CONCLUSIONS The relative importance of many factors that clinicians consider when making decisions about medications varies by demographics, and depends on the clinical problem. This variability should be considered in quality improvement and knowledge translation interventions in this setting.

Journal ArticleDOI
TL;DR: The objectives of this study were to evaluate the efficacy and safety of heparin in patients with sepsis, septic shock or disseminated intravascular coagulation (DIC) associated with infection.
Abstract: Septic shock is characterized by systemic inflammation coupled with upregulation of coagulation. Heparin is an inexpensive and widely available anticoagulant with anti-inflammatory properties. The objectives our study were to evaluate the efficacy and safety of heparin in patients with sepsis, septic shock or disseminated intravascular coagulation (DIC) associated with infection.

Journal ArticleDOI
TL;DR: This systematic review of pilot trials in pediatric critical care described their conclusions about the clinical implications of the results, and the need for future research and to determine the frequency of large follow-up trials.
Abstract: Objectives Pilot trials are smaller randomized controlled trials conducted to inform the design and assess the feasibility of a large-scale trials. The objectives of this systematic review were to describe pilot trials in pediatric critical care, their conclusions about the clinical implications of the results, and the need for future research and to determine the frequency of large follow-up trials. Data sources The Evidence in Pediatric Intensive Care database (http://epicc.mcmaster.ca), a comprehensive repository of published pediatric critical care randomized controlled trials and the World Health Organization's Clinical Trials Registry Platform. Study selection Randomized controlled trials described in the publication as "pilot," "feasibility," "proof-of-concept," "exploratory," "phase 2," "vanguard," or "preliminary." Data extraction Pairs of reviewers screened studies for eligibility and abstracted data independently. Data synthesis We found 32 pilot trials (12.2% of all pediatric critical care randomized controlled trials) published before July 2014, varying in size from 6 to 165 children. Pilot trials were significantly smaller than those not described as pilots, but other key characteristics were not significantly different. The authors of 16 publications (48.4%) included explicit and specific conclusions about the design or feasibility of larger trials based on the results of the pilot trial. In 20 publications (64.5%), the authors made conclusions about clinical efficacy based on results of the pilot trial. Four of the 32 pilot trials (12.9%) led to larger trials, two of which have been published. Conclusions Published pilot trials in pediatric critical care often focus on clinical outcomes. They uncommonly report explicit feasibility outcomes, criteria for success, or rationale for the pilot sample size. These pilot trials infrequently lead to larger trials. Understanding and addressing the reasons for this are key to the success of pediatric critical care research.