Karen E A Burns

Publications (37)248.02 Total impact

• Article: Corticosteroid use in the intensive care unit: a survey of intensivists.

  François Lamontagne, Hector Quiroz Martinez, Neill K J Adhikari, Deborah J Cook, Karen K Y Koo, François Lauzier, Alexis F Turgeon, Michelle E Kho, Karen E A Burns, Clarence Chant, Rob Fowler, Ivor Douglas, Yannick Poulin, Karen Choong, Niall D Ferguson, Maureen O Meade
  [show abstract] [hide abstract]
  ABSTRACT: OBJECTIVE: The efficacy of systemic corticosteroids in many critical illnesses remains uncertain. Our primary objective was to survey intensivists in North America about their perceived use of corticosteroids in clinical practice. DESIGN: Self-administered paper survey. POPULATION: Intensivists in academic hospitals with clinical trial expertise in critical illness. MEASUREMENTS: We generated questionnaire items in focus groups and refined them after assessments of clinical sensibility and test-retest reliability and pilot testing. We administered the survey to experienced intensivists practicing in selected North American centres actively enrolling patients in the multicentre Oscillation for ARDS Treated Early (OSCILLATE) Trial (ISRCTN87124254). Respondents used a four-point scale to grade how frequently they would administer corticosteroids in 14 clinical settings. They also reported their opinions on 16 potential near-absolute indications or contraindications for the use of corticosteroids. MAIN RESULTS: Our response rate was 82% (103/125). Respondents were general internists (50%), respirologists (22%), anesthesiologists (21%), and surgeons (7%) who practiced in mixed medical-surgical units. A majority of respondents reported almost always prescribing corticosteroids in the setting of significant bronchospasm in a mechanically ventilated patient (94%), recent corticosteroid use and low blood pressure (93%), and vasopressor-refractory septic shock (52%). Although more than half of respondents stated they would almost never prescribe corticosteroids in severe community-acquired pneumonia (81%), acute lung injury (ALI, 76%), acute respiratory distress syndrome (ARDS, 65%), and severe ARDS (51%), variability increased with severity of acute lung injury. Near-absolute indications selected by most respondents included known adrenal insufficiency (99%) and suspicion of cryptogenic organizing pneumonia (89%), connective tissue disease (85%), or other potentially corticosteroid-responsive illnesses (85%). CONCLUSIONS: Respondents reported rarely prescribing corticosteroids for ALI, but accepted them for bronchospasm, suspected adrenal insufficiency due to previous corticosteroid use, and vasopressor-refractory septic shock. These competing indications will complicate the design and interpretation of any future large-scale trial of corticosteroids in critical illness.
  Canadian Anaesthetists? Society Journal 04/2013; · 2.31 Impact Factor
• Article: Research Recruitment Practices of Critically Ill Patients: A Multicenter, Cross-Sectional Study (The Consent Study).

  Karen E A Burns, Celia Zubrinich, Wylie Tan, Stavroula Raptis, Wei Xiong, Orla Smith, Ellen McDonald, John C Marshall, Raphael Saginur, Ron Heslegrave, Gordon Rubenfeld, Deborah J Cook
  [show abstract] [hide abstract]
  ABSTRACT: RATIONALE: Limited cross-sectional data exist to characterize the challenges of enrolling critically ill patients into research studies. OBJECTIVES: We aimed to describe recruitment practices, document factors that impact recruitment, and identify factors that may enhance future research feasibility. METHODS: We conducted a prospective, observational study of all critically ill adults eligible to participate in research studies at 23 Canadian intensive care units (ICUs). We characterized eligibility events into one of five consent outcomes, identified reasons why opportunities to recruit were missed or infeasible, and documented decision-maker's rationale for providing or declining consent. MEASUREMENTS AND MAIN RESULTS: Only 8.9% of eligible patients made decisions for themselves. In 453 eligibility events, consent was not required in 14 (3.1%), missed in 131 (28.9%), infeasible due to operational reasons in 129 (28.5%), obtained in 140 (30.9%) and declined in 39 (8.6%). Over half (57%) of all opportunities to recruit patients were missed or infeasible largely due to research team workload, limited availability, narrow time windows for inclusion, difficulties in contacting families, non-existent substitute decision makers (SDMs), physician refusals and protocols prohibiting co-enrollment. The rationale for providing consent differed between patients and SDMs. Greater research coordinator experience and site research volume were significant predictors of fewer declined consents. CONCLUSIONS: A large gap exists between eligibility and the frequency with which consent encounters occur in ICU research. Recruitment is susceptible to personnel availability, given the need to interact with SDMs, and to design and procedural inefficiencies that hinder recruitment. Current enrolment practices under-represent study populations.
  American Journal of Respiratory and Critical Care Medicine 03/2013; · 11.08 Impact Factor
• Source

  Available from: Karen Choong

  Article: Early Mobilization in Critically Ill Children: A Survey of Canadian Practice.

  Karen Choong, Karen K Y Koo, Heather Clark, Rong Chu, Lehana Thabane, Karen E A Burns, Deborah J Cook, Margaret S Herridge, Maureen O Meade
  [show abstract] [hide abstract]
  ABSTRACT: OBJECTIVES:: While early mobilization is safe and enhances functional recovery in critically ill adults, rehabilitation practices in critically ill children are not well characterized. The objective of this study was to evaluate the knowledge, perceptions, and stated practices of early mobilization among physicians and physiotherapists practicing in Canadian pediatric critical care units. DESIGN AND MEASUREMENTS:: A self-administered survey was mailed to 102 physicians and 35 physiotherapists. Survey domains included barriers to early mobilization, the timing, nature and thresholds for rehabilitation, and staffing workload. We assessed for associations using chi-square tests. MAIN RESULTS:: The overall response rate was 64.2% (88 of 137), representing 59.8% (61 of 102) physicians and 77.1% (27 of 35) physiotherapists, respectively. Key institutional barriers to early mobilization included a lack of practice guidelines (75.4% physician, 48.1% physiotherapist respondents; p = 0.01) and the need for physician orders prior to initiating physiotherapy (26.2% physician vs. 55.6% physiotherapist, p = 0.008). Only 3.4% of respondents reported having local guidelines for early mobilization. Conflicting perceptions regarding the clinical thresholds for early mobilization and the safety of early mobilization were the most commonly reported patient-level barriers. Increasing illness severity was associated with decreased clinician comfort with early mobilization. Respiratory physiotherapy and passive range of motion were the most frequently applied rehabilitation interventions (77.8%), while pregait physiotherapy and ambulation were only sometimes or infrequently (70.4%) used. The type and extent of physiotherapy varied depending on the time of day and week. CONCLUSIONS:: There are numerous perceived institutional, patient- and provider-level barriers to early mobilization in Canadian pediatric critical care units, and diverse opinions on the appropriateness of early mobilization. Limited awareness of existing literature and the lack of practice guidelines on early mobilization are not surprising in light of the paucity of pediatric-specific evidence. These results strongly support the need for further research, evaluating the feasibility, safety, and efficacy of early mobilization in critically ill children.
  Critical care medicine 03/2013; · 6.37 Impact Factor
• Article: Participation of ICUs in Critical Care Pandemic Research: A Province Wide, Cross-Sectional Survey.

  Karen E A Burns, Leena Rizvi, Wylie Tan, John C Marshall, Karen Pope
  [show abstract] [hide abstract]
  ABSTRACT: OBJECTIVE:: Little information exists to identify barriers to participation in pandemic research involving critically ill patients. We sought to characterize clinical research activity during the recent influenza A pandemic and to understand the experiences, beliefs, and practices of key stakeholders involved in pandemic research implementation. DESIGN:: Cross-sectional, provincial postal questionnaire. SETTING:: Level III ICUs. PARTICIPANTS:: ICU administrators and research coordinators. MEASUREMENTS:: We used rigorous survey methodology to identify potential respondents and to develop, test, and administer two-related questionnaires. MAIN RESULTS:: We analyzed responses from 39 research coordinators and 139 administrators (response rates: 70.9% and 73.2%, respectively). Compared with non-influenza A studies, influenza A studies were less likely to be randomized trials and most often investigator-initiated and peer-review funded. Whereas both respondent groups felt that pandemic research would be helpful in providing care during future pandemics, research coordinators placed significantly greater importance on their ICU's participation in pandemic research. Both respondent groups expressed a need for rapid approval processes, designated funding for research personnel, adequate funding for start-up and patient screening, preapproved template protocols and consent forms, and clearer guidance regarding co-enrollment. Research coordinators acknowledged a need for alternative consent models to increase their capacity to participate in future pandemic research. More administrators expressed willingness to participate in the next pandemic if the required research resources were made available to them. CONCLUSIONS:: Whereas research personnel and administrators support participation in pandemic ICU research, several modifiable barriers to participation exist. Pandemic research preparedness planning with regulatory bodies and dedicated funding to support research infrastructure, especially in community settings, are required to optimize future pandemic research participation.
  Critical care medicine 02/2013; · 6.37 Impact Factor
• Article: Determination of Neurological Prognosis and Clinical Decision Making in Adult Patients With Severe Traumatic Brain Injury: A Survey of Canadian Intensivists, Neurosurgeons, and Neurologists.

  Alexis F Turgeon, François Lauzier, Karen E A Burns, Maureen O Meade, Damon C Scales, Ryan Zarychanski, Lynne Moore, David A Zygun, Lauralyn A McIntyre, Salmaan Kanji, Paul C Hébert, Valérie Murat, Giuseppe Pagliarello, Dean A Fergusson
  [show abstract] [hide abstract]
  ABSTRACT: OBJECTIVES:: Accurate prognostic information in patients with severe traumatic brain injury remains limited, but mortality following the withdrawal of life-sustaining therapies is high and variable across centers. We designed a survey to understand attitudes of physicians caring for patients with severe traumatic brain injury toward the determination of prognosis and clinical decision making on the level of care. DESIGN, SETTING, AND PARTICIPANTS:: We conducted a cross-sectional study of intensivists, neurosurgeons, and neurologists that participate in the care of patients with severe traumatic brain injury at all Canadian level 1 and level 2 trauma centers. INTERVENTION:: None. MEASUREMENTS:: The main outcome measure was physicians' perceptions of prognosis and recommendations on the level of care. MAIN RESULTS:: Our response rate was 64% (455/712). Most respondents (65%) reported that an accurate prediction of prognosis would be most helpful during the first seven days. Most respondents (>80%) identified bedside monitoring, clinical exam, and imaging to be useful for evaluating prognosis, whereas fewer considered electrophysiology tests (<60%) and biomarkers (<15%). In a case-based scenario, approximately one third of respondents agreed, one third were neutral, and one third disagreed that the patient prognosis would be unfavorable at one year. About 10% were comfortable recommending withdrawal of life-sustaining therapies. CONCLUSIONS:: A significant variation in perceptions of neurological prognosis and in clinical decision making on the level of care was found among Canadian intensivists, neurosurgeons, and neurologists. Improved understanding of the factors that can accurately predict prognosis for patients with traumatic brain injury is urgently needed.
  Critical care medicine 02/2013; · 6.37 Impact Factor
• Article: Factors Associated with the Withdrawal of Life-Sustaining Therapies in Patients with Severe Traumatic Brain Injury: A Multicenter Cohort Study.

  Nicolas Côte, Alexis F Turgeon, François Lauzier, Lynne Moore, Damon C Scales, Francis Bernard, Ryan Zarychanski, Karen E A Burns, Maureen O Meade, David Zygun, Jean-François Simard, Amélie Boutin, Jacques G Brochu, Dean A Fergusson
  [show abstract] [hide abstract]
  ABSTRACT: PURPOSE: To identify factors associated with decisions to withdraw life-sustaining therapies in patients with severe traumatic brain injury (TBI). MATERIALS AND METHODS: We conducted a 2-year multicenter retrospective cohort study (2005-2006) in mechanically ventilated patients aged 16 years and older admitted to the intensive care units (ICUs) of six Canadian level I trauma centers following severe TBI. One hundred and twenty charts were randomly selected at each center (n = 720). Data on ICU management strategies, patients' clinical condition, surgical procedures, diagnostic imaging, and decision to withdraw life-sustaining therapies were collected. The association of factors pertaining to the injury, interventions, and management strategies with decisions to withdraw life-sustaining therapies was evaluated among non-survivors. RESULTS: Among the 228 non-survivors, 160 died following withdrawal of life-sustaining therapies. Patients were predominantly male (69.7 %) with a mean age of 50.7 (±21.7) years old. Brain herniation was more often reported in patients who died following decisions to withdraw life-sustaining therapies (odds ratio [OR] 2.91, 95 % confidence interval [CI] 1.16-7.30, p = 0.02) compared to those who died due to other causes (e.g., cardiac arrest, shock, etc.). Epidural hematomas (OR 0.18, 95 % CI 0.06-0.56, p < 0.01), craniotomies (OR 0.12, 95 % CI 0.02-0.68, p = 0.02), and other non-neurosurgical procedures (OR 0.08, 95 % CI 0.02-0.43, p < 0.01) were less often associated with death following withdrawal of life-sustaining therapies than death from other causes. CONCLUSIONS: Death following decisions to withdraw life-sustaining therapies is associated with specific patient and clinical factors, and the intensity of care.
  Neurocritical Care 10/2012; · 2.47 Impact Factor
• Article: Epidemiology of acute kidney injury in Canadian critical care units: a prospective cohort study.

  Ayodele Odutayo, Neill K J Adhikari, James Barton, Karen E A Burns, Jan O Friedrich, David Klein, Stephen Lapinsky, Sasha Litwin, Aleksander Meret, Rahim Moineddin, Bonnie Richardson, Robert Richardson, Alina Zaltzman, Michelle Hladunewich, Ron Wald
  [show abstract] [hide abstract]
  ABSTRACT: PURPOSE: We undertook this study to characterize the epidemiology of acute kidney injury (AKI) in Canadian critical care units. We aimed to identify predictors of mortality for patients diagnosed with AKI. METHODS: We conducted a prospective cohort study of consecutive patients admitted to critical care units at five Canadian hospitals over a 30-day period. Each patient was followed until hospital discharge or for a maximum of 30 days. The serum creatinine criteria for the Acute Kidney Injury Network (AKIN-SCr) system were used to identify, classify, and characterize patients who developed AKI. We used multivariable logistic regression to predict 30-day mortality among patients with AKI. RESULTS: We identified 603 patients, 161 (26.7%) of whom developed AKI. Compared to patients without AKI, those with AKI were more likely to die (29.2% vs 8.6%, P < 0.001). The risk of death increased with increasing AKIN-SCr stage (P < 0.001). In all, 19 patients (11.8% of those with AKI) commenced dialysis a median of one day (interquartile range, one to two days) after AKI diagnosis. At AKI diagnosis, the blood urea nitrogen (BUN) level (adjusted odds ratio [OR] 1.68, 95% confidence interval [CI] 1.01 to 2.79/10 mmol·L(-1)) and serum bicarbonate (adjusted OR 0.88, 95% CI 0.81 to 0.95/1 mmol·L(-1)) were associated with 30-day mortality and predicted death with an area under the receiver-operating characteristic curve of 0.79 (95% CI 0.71 to 0.86). CONCLUSIONS: Acute kidney injury is a common complication of critical illness in Canada. The development of even the mildest stage of AKI is associated with a substantially higher risk of death. At AKI diagnosis, routine clinical data may be helpful for predicting adverse outcomes.
  Canadian Anaesthetists? Society Journal 07/2012; 59(10):934-942. · 2.31 Impact Factor
• Article: Timing the initiation of renal replacement therapy for acute kidney injury in Canadian intensive care units: a multicentre observational study.

  Edward Clark, Ron Wald, Adeera Levin, Josée Bouchard, Neill K J Adhikari, Michelle Hladunewich, Robert M A Richardson, Matthew T James, Michael W Walsh, Andrew A House, Louise Moist, Daniel E Stollery, Karen E A Burns, Jan O Friedrich, James Barton, Jean-Philippe Lafrance, Neesh Pannu, Sean M Bagshaw
  [show abstract] [hide abstract]
  ABSTRACT: The optimal timing for starting renal replacement therapy (RRT) in patients with acute kidney injury (AKI) is unknown. Defining current practice is necessary to design interventional trials. We describe the current Canadian practice regarding the timing of RRT initiation for AKI. An observational study of patients undergoing RRT for AKI was undertaken at 11 intensive care units (ICUs) across Canada. Data were captured on demographics, clinical and laboratory findings, indications for RRT, and timing of RRT initiation. Among 119 consecutive patients, the most common ICU admission diagnosis was sepsis/septic shock, occurring in 54%. At the time of RRT initiation, the median and interquartile range (IQR) serum creatinine level was 322 (221-432) μmol·L(-1). The mean (SD) values for other parameters were as follows: Sequential Organ Failure Assessment (SOFA) score 13.4 (4.1), pH 7.25 (0.15), potassium 4.6 (1.0) mmol·L(-1). Also, 64% fulfilled the serum creatinine-based criterion for Acute Kidney Injury Network (AKIN) stage 3. Severity of illness, measured using Acute Physiology and Chronic Health Evaluation (APACHE II) and SOFA scores, did not correlate with AKI severity as defined by the serum creatinine-based AKIN criteria. Median (IQR) time from hospital and ICU admission to the start of RRT was 2.0 (1.0-7.0) days and 1.0 (0-2.0) day, respectively. Patients admitted to an ICU who were started on RRT generally had advanced AKI, high-grade illness severity, and multiorgan dysfunction. Also, they were started on RRT shortly after hospital presentation. We describe the current state of practice in Canada regarding the initiation of RRT for AKI in critically ill patients, which can inform the designs of future interventional trials.
  Canadian Anaesthetists? Society Journal 06/2012; 59(9):861-70. · 2.31 Impact Factor
• Article: ACP Journal Club. IV salbutamol increased mortality in patients with the acute respiratory distress syndrome.

  Clarence Chant, Karen E A Burns
  Annals of internal medicine 05/2012; 156(10):JC5-6. · 16.73 Impact Factor
• Article: The authors respond.

  Alexis F Turgeon, Francois Lauzier, Damon C Scales, Karen E A Burns, Lynne Moore, David Zygun, Francis Bernard, Maureen O Meade, Dean A Fergusson
  Canadian Medical Association Journal 02/2012; 184(3):326. · 8.22 Impact Factor
• Article: Mortality associated with withdrawal of life-sustaining therapy for patients with severe traumatic brain injury: a Canadian multicentre cohort study.

  Alexis F Turgeon, François Lauzier, Jean-François Simard, Damon C Scales, Karen E A Burns, Lynne Moore, David A Zygun, Francis Bernard, Maureen O Meade, Tran Cong Dung, Mohana Ratnapalan, Stephanie Todd, John Harlock, Dean A Fergusson
  [show abstract] [hide abstract]
  ABSTRACT: Severe traumatic brain injury often leads to death from withdrawal of life-sustaining therapy, although prognosis is difficult to determine. To evaluate variation in mortality following the withdrawal of life-sustaining therapy and hospital mortality in patients with critical illness and severe traumatic brain injury, we conducted a two-year multicentre retrospective cohort study in six Canadian level-one trauma centres. The effect of centre on hospital mortality and withdrawal of life-sustaining therapy was evaluated using multivariable logistic regression adjusted for baseline patient-level covariates (sex, age, pupillary reactivity and score on the Glasgow coma scale). We randomly selected 720 patients with traumatic brain injury for our study. The overall hospital mortality among these patients was 228/720 (31.7%, 95% confidence interval [CI] 28.4%-35.2%) and ranged from 10.8% to 44.2% across centres (χ(2) test for overall difference, p < 0.001). Most deaths (70.2% [160/228], 95% CI 63.9%-75.7%) were associated with withdrawal of life-sustaining therapy, ranging from 45.0% (18/40) to 86.8% (46/53) (χ(2) test for overall difference, p < 0.001) across centres. Adjusted odd ratios (ORs) for the effect of centre on hospital mortality ranged from 0.61 to 1.55 (p < 0.001). The incidence of withdrawal of life-sustaining therapy varied by centre, with ORs ranging from 0.42 to 2.40 (p = 0.001). About one half of deaths that occurred following the withdrawal of life-sustaining therapies happened within the first three days of care. We observed significant variation in mortality across centres. This may be explained in part by regional variations in physician, family or community approaches to the withdrawal of life-sustaining therapy. Considering the high proportion of early deaths associated with the withdrawal of life-sustaining therapy and the limited accuracy of current prognostic indicators, caution should be used regarding early withdrawal of life-sustaining therapy following severe traumatic brain injury.
  Canadian Medical Association Journal 09/2011; 183(14):1581-8. · 8.22 Impact Factor
• Article: Clinical factors associated with initiation of renal replacement therapy in critically ill patients with acute kidney injury-a prospective multicenter observational study.

  Sean M Bagshaw, Ron Wald, Jim Barton, Karen E A Burns, Jan O Friedrich, Andrew A House, Matthew T James, Adeera Levin, Louise Moist, Neesh Pannu, Daniel E Stollery, Michael W Walsh
  [show abstract] [hide abstract]
  ABSTRACT: Our objective was to describe the current practice for initiation of RRT in this population. There is uncertainty regarding the optimal time to initiate renal replacement therapy (RRT) in critically ill patients with acute kidney injury (AKI). Prospective study of patients receiving RRT in 6 intensive care units (ICUs) at 3 hospitals from July 2007 to August 2008. We characterized factors associated with start of RRT and evaluated their relationship with mortality. We included 234 patients. RRT was initiated 1 day (0-4) after ICU admission (median [interquartile range]). Median creatinine was 331 μmol/L (225-446 μmol/L), urea 22.9 mmol/L (13.9-32.9 mmol/L), and RIFLE-Failure in 76.9%. Of traditional indications, Pao(2)/Fio(2) < 200 (54.5%) and oliguria (32.9%) were most common. ICU and hospital mortality were 45.3% and 51.9%, respectively. In adjusted analysis, mortality at RRT initiation was associated with creatinine <332 μmol/L (odds ratio [OR] 2.8; 95% confidence interval [CI] 1.5-5.4), change in urea from admission >8.9 mmol/L (OR 1.8; 95% CI, 1.0-3.4), urine output <82 mL/24 hours (OR 3.0; 95% CI, 1.4-6.5), fluid balance >3.0 L/24 hours (OR 2.3; 95% CI, 1.2-4.5), percentage of fluid overload >5% (OR 2.3; 95% CI, 1.2-4.7), 3 or more failing organs (OR 4.5; 95% CI, 1.2-4.2), Sequential Organ Failure Assessment score >14 (OR 2.3; 95% CI, 1.3-4.3), and start 4 days or more after admission (OR 4.3; 95% CI, 1.9-9.5). Mortality was higher as factors accumulated. In ICU patients requiring RRT, there was marked variation in factors that influence start of RRT. RRT initiation with fewer clinical triggers was associated with lower mortality. Timing of RRT may modify survival but requires appraisal in a randomized trial.
  Journal of critical care 07/2011; 27(3):268-75. · 2.13 Impact Factor
• Source

  Available from: Alexis F Turgeon

  Article: Vasopressor administration and sepsis: a survey of Canadian intensivists.

  Francois Lamontagne, Deborah J Cook, Neill K J Adhikari, Matthias Briel, Mark Duffett, Michelle E Kho, Karen E A Burns, Gordon Guyatt, Alexis F Turgeon, Qi Zhou, Maureen O Meade
  [show abstract] [hide abstract]
  ABSTRACT: Patients with septic shock often receive intravenous vasopressor infusions, with little evidence available to guide their titration. We surveyed Canadian intensivists to document self-reported vasopressor titration strategies for patients with septic shock. We identified Canadian intensivists caring for adult patients by merging membership lists of 3 Canadian critical care associations. We invited respondents to complete a scenario-based questionnaire to understand triggers for vasopressor use, target blood pressure values, and the influence of chronic comorbidities and acute illnesses on vasopressor prescription. Sixty-three percent of eligible intensivists completed our survey. Most respondents (82.6%) would frequently or always administer vasopressor therapy for isolated hypotension but not for other isolated signs of organ failure (such as elevated serum lactate or low urine output). Respondents defined low blood pressure using mean arterial pressure (83.7%) and aimed for higher values when resuscitating a patient with multiple organ failure. Chronic comorbidities and acute concurrent illnesses had variable effects on stated vasopressor prescription. Norepinephrine (94.8%) was the preferred first-line vasopressor. Self-reported vasopressor use for the treatment of septic shock is relatively uniform among Canadian intensivists; however, practice is variable in patients with chronic comorbidities or acute concurrent illnesses.
  Journal of critical care 03/2011; 26(5):532.e1-7. · 2.13 Impact Factor
• Source

  Available from: Jamal A Alhashemi

  Article: A Canadian Critical Care Trials Group project in collaboration with the international forum for acute care trialists - Collaborative H1N1 Adjuvant Treatment pilot trial (CHAT): study protocol and design of a randomized controlled trial.

  Karen E A Burns, Clarence Chant, Orla Smith, Brian Cuthbertson, Robert Fowler, Deborah J Cook, Peter Kruger, Steve Webb, Jamal Alhashemi, Guillermo Dominguez-Cherit, Carlos Zala, Gordon D Rubenfeld, John C Marshall
  [show abstract] [hide abstract]
  ABSTRACT: Swine origin influenza A/H1N1 infection (H1N1) emerged in early 2009 and rapidly spread to humans. For most infected individuals, symptoms were mild and self-limited; however, a small number developed a more severe clinical syndrome characterized by profound respiratory failure with hospital mortality ranging from 10 to 30%. While supportive care and neuraminidase inhibitors are the main treatment for influenza, data from observational and interventional studies suggest that the course of influenza can be favorably influenced by agents not classically considered as influenza treatments. Multiple observational studies have suggested that HMGCoA reductase inhibitors (statins) can exert a class effect in attenuating inflammation. The Collaborative H1N1 Adjuvant Treatment (CHAT) Pilot Trial sought to investigate the feasibility of conducting a trial during a global pandemic in critically ill patients with H1N1 with the goal of informing the design of a larger trial powered to determine impact of statins on important outcomes. A multi-national, pilot randomized controlled trial (RCT) of once daily enteral rosuvastatin versus matched placebo administered for 14 days for the treatment of critically ill patients with suspected, probable or confirmed H1N1 infection. We propose to randomize 80 critically ill adults with a moderate to high index of suspicion for H1N1 infection who require mechanical ventilation and have received antiviral therapy for ≤ 72 hours. Site investigators, research coordinators and clinical pharmacists will be blinded to treatment assignment. Only research pharmacy staff will be aware of treatment assignment. We propose several approaches to informed consent including a priori consent from the substitute decision maker (SDM), waived and deferred consent. The primary outcome of the CHAT trial is the proportion of eligible patients enrolled in the study. Secondary outcomes will evaluate adherence to medication administration regimens, the proportion of primary and secondary endpoints collected, the number of patients receiving open-label statins, consent withdrawals and the effect of approved consent models on recruitment rates. Several aspects of study design including the need to include central randomization, preserve allocation concealment, ensure study blinding compare to a matched placebo and the use novel consent models pose challenges to investigators conducting pandemic research. Moreover, study implementation requires that trial design be pragmatic and initiated in a short time period amidst uncertainty regarding the scope and duration of the pandemic. ISRCTN45190901.
  Trials 03/2011; 12:70. · 2.02 Impact Factor
• Article: Clinical practice guidelines for the use of noninvasive positive-pressure ventilation and noninvasive continuous positive airway pressure in the acute care setting.

  Sean P Keenan, Tasnim Sinuff, Karen E A Burns, John Muscedere, Jim Kutsogiannis, Sangeeta Mehta, Deborah J Cook, Najib Ayas, Neill K J Adhikari, Lori Hand, Damon C Scales, Rose Pagnotta, Lynda Lazosky, Graeme Rocker, Sandra Dial, Kevin Laupland, Kevin Sanders, Peter Dodek
  Canadian Medical Association Journal 02/2011; 183(3):E195-214. · 8.22 Impact Factor
• Source

  Available from: PubMed Central

  Article: Pressure and volume limited ventilation for the ventilatory management of patients with acute lung injury: a systematic review and meta-analysis.

  Karen E A Burns, Neill K J Adhikari, Arthur S Slutsky, Gordon H Guyatt, Jesus Villar, Haibo Zhang, Qi Zhou, Deborah J Cook, Thomas E Stewart, Maureen O Meade
  [show abstract] [hide abstract]
  ABSTRACT: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life threatening clinical conditions seen in critically ill patients with diverse underlying illnesses. Lung injury may be perpetuated by ventilation strategies that do not limit lung volumes and airway pressures. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing pressure and volume-limited (PVL) ventilation strategies with more traditional mechanical ventilation in adults with ALI and ARDS. We searched Medline, EMBASE, HEALTHSTAR and CENTRAL, related articles on PubMed™, conference proceedings and bibliographies of identified articles for randomized trials comparing PVL ventilation with traditional approaches to ventilation in critically ill adults with ALI and ARDS. Two reviewers independently selected trials, assessed trial quality, and abstracted data. We identified ten trials (n = 1,749) meeting study inclusion criteria. Tidal volumes achieved in control groups were at the lower end of the traditional range of 10-15 mL/kg. We found a clinically important but borderline statistically significant reduction in hospital mortality with PVL [relative risk (RR) 0.84; 95% CI 0.70, 1.00; p = 0.05]. This reduction in risk was attenuated (RR 0.90; 95% CI 0.74, 1.09, p = 0.27) in a sensitivity analysis which excluded 2 trials that combined PVL with open-lung strategies and stopped early for benefit. We found no effect of PVL on barotrauma; however, use of paralytic agents increased significantly with PVL (RR 1.37; 95% CI, 1.04, 1.82; p = 0.03). This systematic review suggests that PVL strategies for mechanical ventilation in ALI and ARDS reduce mortality and are associated with increased use of paralytic agents.
  PLoS ONE 01/2011; 6(1):e14623. · 4.09 Impact Factor
• Article: Attitudes and Views of the General Public Toward Research Participation.

  Karen E A Burns, Nora Magyarody, Depeng Jiang, Ron Wald
  [show abstract] [hide abstract]
  ABSTRACT: Background: While the challenges of recruitment into clinical trials are well described, little is known about the public's perceptions toward research. Aims: We sought to describe the attitudes, beliefs and knowledge of the public toward research and research participation, focusing on clinical trials; contrast these attributes among individuals with different relationships with the health care system and identify predictors of willingness to participate. Methods: We conducted a self-administered cross-sectional survey of patients and their significant others in 2 clinics and 2 intensive care unit waiting rooms and in 3 public venues. Results: We analyzed responses from 417 respondents (102 and 105 in dialysis and oncology clinics, and 106 in ICU waiting rooms, 104 in public locations). While most (68.3%) respondents favored the use of humans in clinical trials, 53% felt that trial participants always or almost always receive the best quality of care, only 30.4% had participated in clinical research. Approximately 70% felt that subjects are always advised of the risks and benefits of participation, and 30% expressed ambiguity regarding whether participants are informed of their involvement. Oncology and dialysis respondents were the most and least informed regarding research methods and ethics. The perceived risks and benefits associated with clinical circumstances influence research participation decisions and vary with health care experiences. We identified 6 predictors of willingness to participate. Conclusion: Attitudes of the public toward research participation are beleaguered by misconceptions. Stakeholders in clinical research must educate the general public regarding research methods and ethics.
  Internal Medicine Journal 01/2011; · 1.54 Impact Factor
• Article: Attitudes of the general public toward alternative consent models.

  Karen E A Burns, Nora M Magyarody, Mark Duffett, Rosane Nisenbaum, Deborah J Cook
  [show abstract] [hide abstract]
  ABSTRACT: To assess the general public's attitudes toward various consent models and data management strategies for critically ill adults eligible to participate in a low-risk randomized trial. A self-administered survey was conducted at public locations in Toronto to elucidate the general public's attitudes toward various consent models for participation in a low-risk randomized trial when a substitute decision maker was available, unavailable, or did not exist, as well as to assess attitudes toward strategies for data management in patients enrolled under a substitute decision maker's consent who later decline further participation. We surveyed 221 citizens. Most respondents (64%-74%) wanted to be considered for participation. When a substitute decision maker was available, similar proportions of respondents were comfortable with the substitute decision maker providing consent, deferred consent, and their substitute decision maker being asked if the respondent would "object to participating." If a substitute existed but was unavailable, most participants were comfortable with waived consent. If a substitute did not exist, respondents expressed comfort with 4 consent models: an attending physician model, a 2-physician model (1 involved in care), deferred consent, and waived consent. Compared with any physician, respondents preferred their attending physician to be involved in decisions about their research participation, especially in the absence of a substitute decision maker. Nearly three-fourths of respondents supported data management strategies that enabled use of their primary outcome; moreover, 58% believed that data collected before their decision to decline further participation should be included. Most respondents were interested in participating in a low-risk trial. Respondents endorsed a variety of approaches to obtaining consent in the presence or absence of substitute decision makers and many would be comfortable if their data were used despite a decision to decline further participation.
  American Journal of Critical Care 04/2010; 20(1):75-83. · 1.66 Impact Factor
• Article: Stopping randomized trials early for benefit and estimation of treatment effects: systematic review and meta-regression analysis.

  Dirk Bassler, Matthias Briel, Victor M Montori, Melanie Lane, Paul Glasziou, Qi Zhou, Diane Heels-Ansdell, Stephen D Walter, Gordon H Guyatt, David N Flynn, [......], Edward J Mills, Femida Gwadry-Sridhar, Haresh Kirpalani, Heloisa P Soares, Paul J Karanicolas, Karen E A Burns, Per Olav Vandvik, Fernando Coto-Yglesias, Pedro Paulo M Chrispim, Tim Ramsay
  [show abstract] [hide abstract]
  ABSTRACT: Theory and simulation suggest that randomized controlled trials (RCTs) stopped early for benefit (truncated RCTs) systematically overestimate treatment effects for the outcome that precipitated early stopping. To compare the treatment effect from truncated RCTs with that from meta-analyses of RCTs addressing the same question but not stopped early (nontruncated RCTs) and to explore factors associated with overestimates of effect. Search of MEDLINE, EMBASE, Current Contents, and full-text journal content databases to identify truncated RCTs up to January 2007; search of MEDLINE, Cochrane Database of Systematic Reviews, and Database of Abstracts of Reviews of Effects to identify systematic reviews from which individual RCTs were extracted up to January 2008. Selected studies were RCTs reported as having stopped early for benefit and matching nontruncated RCTs from systematic reviews. Independent reviewers with medical content expertise, working blinded to trial results, judged the eligibility of the nontruncated RCTs based on their similarity to the truncated RCTs. Reviewers with methodological expertise conducted data extraction independently. The analysis included 91 truncated RCTs asking 63 different questions and 424 matching nontruncated RCTs. The pooled ratio of relative risks in truncated RCTs vs matching nontruncated RCTs was 0.71 (95% confidence interval, 0.65-0.77). This difference was independent of the presence of a statistical stopping rule and the methodological quality of the studies as assessed by allocation concealment and blinding. Large differences in treatment effect size between truncated and nontruncated RCTs (ratio of relative risks <0.75) occurred with truncated RCTs having fewer than 500 events. In 39 of the 63 questions (62%), the pooled effects of the nontruncated RCTs failed to demonstrate significant benefit. Truncated RCTs were associated with greater effect sizes than RCTs not stopped early. This difference was independent of the presence of statistical stopping rules and was greatest in smaller studies.
  JAMA The Journal of the American Medical Association 03/2010; 303(12):1180-7. · 30.03 Impact Factor
• Source

  Available from: blood.ca

  Article: The design and interpretation of pilot trials in clinical research in critical care.

  Donald M Arnold, Karen E A Burns, Neill K J Adhikari, Michelle E Kho, Maureen O Meade, Deborah J Cook
  [show abstract] [hide abstract]
  ABSTRACT: Pilot trials are important to ensure that large randomized trials are rigorous, feasible, and economically justifiable. The objective of this review is to highlight the importance of randomized pilot trials and to describe key features of their design and interpretation using examples from critical care. We searched MEDLINE (1997-2007) and contacted experts to identify pilot randomized trials to exemplify and summarize their key methodologic features including objectives, sample size determination, outcomes, analysis, and reporting. Pilot trials can have distinct and broad objectives. Investigators can predefine explicit criteria for determining their success. Surrogate outcome analyses are common in pilot trials, yet are usually underpowered to detect meaningful differences in clinically important end points and thus, should be cautiously interpreted. Pilot trials can facilitate successful conduct of large clinical trials by informing study design and streamlining protocol implementation. We recommend that investigators define suitable objectives, determine sample size estimates, and select outcomes that will address their specific pilot trial objectives. Clinical effects documented in pilot trials should be reported with caution to avoid undue enthusiasm or pessimism about unstable estimates. Further methodologic work is required to identify optimal pilot trial design, indexing, and reporting.
  Critical care medicine 02/2009; 37(1 Suppl):S69-74. · 6.37 Impact Factor