Michèle Shemilt

Red Blood Cell Transfusion in Patients With Traumatic Brain Injury: A Systematic Review and Meta-Analysis

Our objectives were to evaluate the frequency of red blood cell (RBC) transfusion in patients with traumatic brain injury (TBI) as well as potential determinants and outcomes associated with RBC transfusion in this population. We conducted a systematic review of cohort studies and randomized trials of patients with TBI. We searched Medline, Embase, the Cochrane Library, and BIOSIS databases from their inception up to April 2015. We selected studies of adult patients with acute TBI reporting data on RBC transfusions. Cumulative incidences of transfusion were pooled using random-effect models with a DerSimonian approach. To evaluate the association between RBC transfusion and potential determinants or clinical outcomes, we pooled risk ratios or mean differences with random-effect models and the Mantel-Haenszel method. We identified 24 eligible studies (17414 patients). After pooling data from 23 studies (7524 patients), approximately 36% (95% confidence interval [CI], 28-44; I(2) = 98%) of patients received RBC transfusion at some point during their hospital stay. Hemoglobin thresholds for transfusion were rarely available (reported in 9 studies) and varied from 6 to 10 g/dL. Glasgow Coma Scale scores at admission were lower in patients who were transfused than those who were not (3 cohort studies; 1371 patients; mean difference of 1.38 points [95% CI, 0.86-1.89]; I(2) = 12%). Mortality was not significantly different among transfused and nontransfused patients in univariate and multivariate meta-analyses. Hospital length of stay was longer among patients receiving RBC transfusion compared to those who did not (3 studies; n = 455; mean difference, 9.58 days [95% CI, 3.94-15.22]; I(2) = 74%). Results should be considered cautiously due to the high heterogeneity and high risk of confounding from the observational nature of included studies. Red blood cell transfusion is frequent in patients with TBI, and transfusion practices varied widely between studies. Current published data highlight the lack of clinical evidence guiding transfusion strategies in TBI.

Clinical outcomes, predictors, and prevalence of anterior pituitary disorders following traumatic brain injury: a systematic review.

Objectives:To assess the clinical outcomes, predictors, and prevalence of anterior pituitary disorders following traumatic brain injury. Data Sources:We searched Medline, Embase, Cochrane Registry, BIOSIS, and Trip Database up to February 2012 and consulted bibliographies of narrative reviews and selected articles. Study Selection:We included cohort, case-control, cross-sectional studies and randomized trials enrolling at least five adults with blunt traumatic brain injury in whom at least one anterior pituitary axis was assessed. We excluded case series and studies in which other neurological conditions were indistinguishable from traumatic brain injury. Data Extraction:Two independent reviewers selected citations, extracted data, and assessed the risk of bias using a standardized form. Data Synthesis:We performed meta-analyses using random effect models and assessed heterogeneity using the I2 index. Results:We included 66 studies (5,386 patients) evaluating prevalence, 14 evaluating clinical outcomes, and 27 evaluating predictors. Thirty studies were at low risk of bias. Anterior pituitary disorders were associated with a trend toward increased ICU mortality (risk ratio, 1.79; 95% CI, 0.99–3.21; four studies) and no difference in Glasgow Outcome Scale score (mean difference, –0.45; 95% CI, –1.10 to 0.20; three studies). Age (mean difference, 3.19; 95% CI, 0.31–6.08; 19 studies), traumatic brain injury severity (risk ratio, 2.15; 95% CI, 1.20–3.86 for patients with severe vs nonsevere traumatic brain injury; seven studies), and skull fractures (risk ratio, 1.73; 95% CI, 1.03–2.91; six studies) predicted anterior pituitary disorders. Over the long term, 31.6% (95% CI, 23.6–40.1%; 27 studies) of patients had at least one anterior pituitary disorder. We observed significant heterogeneity that was not solely explained by the risk of bias or traumatic brain injury severity. Conclusions:Approximately one third of traumatic brain injury patients have persistent anterior pituitary disorder. Older age, traumatic brain injury severity, and skull fractures predict anterior pituitary disorders, which in turn may be associated with higher ICU mortality. Further high-quality studies are warranted to better define the burden of anterior pituitary disorders and to identify high-risk patients.

The prognostic value of magnetic resonance imaging in moderate and severe traumatic brain injury: a systematic review and meta-analysis protocol

BackgroundTraumatic brain injury (TBI) is a devastating condition with significant long-term mortality and morbidity. Despite current need for objective indicators to guide initial decision-making, few reliable acute phase prognostic factors have been identified. Early magnetic resonance imaging (MRI) has been investigated as a prognostic tool, but uncertainty remains in both its discriminative predictive value and which acute phase lesion patterns correlate with long-term outcome.MethodsWe will conduct a systematic review of observational cohort studies and randomized controlled trials of adult moderate or severe TBI patients who underwent MRI in the acute phase after trauma. A high sensitivity search strategy will be employed in MEDLINE, EMBASE, BIOSIS, and Cochrane CENTRAL to identify citations. Two reviewers will independently screen all identified references for eligibility and extract data into a standardized form. Data will be collected on study design, baseline demographics, trauma characteristics, magnetic resonance (MR) technical specifications, lesion patterns, and outcomes as related to acute MRI imaging. If meta-analysis is possible, quantitative data for each outcome will be pooled per type of lesion pattern using random effects models and expressed as Mantel-Haenszel relative risks in order to determine the prognostic value of lesions detected on acute MRI and their strength as discriminatory predictors of long-term outcome. Statistical heterogeneity will be evaluated with the I2 statistics, and risk of bias and reporting quality will be assessed with standardized scales. Subgroup analyses are planned as a function of TBI severity, MRI-timing post-TBI, MRI field strength, MRI sequence, timing of outcome assessment, and risk of bias.DiscussionWe expect significant clinical heterogeneity, as eligible studies will likely encompass different periods in evolving MRI technology in addition to significant variability of image sequence protocols and timing of acquisition between centers. Based on existing studies in TBI, we expect lesions detected in the brainstem to be of significant predictive value as MRI is particularly sensitive for imaging the brain’s posterior fossa. Our systematic review will allow clinicians to more accurately interpret MRI in the context of determining prognosis for moderate and severe TBI patients and inform researchers in this domain to improve the methodology of future studies.Systematic review registrationProspero CRD42015017074

Red blood cell transfusion in patients with traumatic brain injury: a systematic review protocol

BackgroundAnemia is a prevalent condition in critically ill patients and red blood cell transfusions are frequent. Although transfusions at low hemoglobin levels have been shown to be associated with equivalent or better outcomes than higher hemoglobin thresholds, clinical equipoise persists in patients with traumatic brain injury considering their susceptibility to secondary cerebral insults such as those from hypoxemia.MethodsOur objectives are to estimate the frequency of red blood cell transfusion in patients with traumatic brain injury and to evaluate transfusion thresholds, determinants and outcomes associated with transfusion strategies.We will conduct a systematic review of cohort studies and randomized controlled trials of patients with traumatic brain injury. We will search MEDLINE, Embase, BIOSIS and the Cochrane Library for eligible studies. Two independent reviewers will screen all identified references. Studies including adult patients with traumatic brain injury reporting data on red blood cell transfusions will be eligible. We will collect data on baseline demographics, trauma characteristics, hemoglobin thresholds, blood transfusions and clinical outcomes (mortality, length of stay, complications, and so on). Two independent reviewers will extract data using a standardized form. We will pool cumulative incidences using DerSimonian and Lair random-effect models after a Freeman-Tukey transformation to stabilize variances. We will pool risk ratios or mean differences with random-effect models and Mantel-Haenszel or inverse variance methods in order to evaluate the association between red blood cell transfusion and potential determinants or outcomes. Sensitivity and subgroup analysis according to timing of red blood cell transfusion, traumatic brain injury severity, year of conduction of the study, risk of bias, notably, are planned.DiscussionWe expect to observe high heterogeneity in the proportion of transfused patients across studies and that the global proportion will be similar to the frequency observed in the general medical critically ill population. Our systematic review will allow us to better describe and understand current transfusion practices in patients with traumatic brain injury, a clinical population in which liberal transfusions are still advocated in the absence of evidence-based data.Systematic review registrationPROSPERO: CRD42014007402.

Impact of trauma system structure on injury outcomes: a systematic review protocol.

BackgroundInjury represents one of the greatest public health challenges of our time with over 5 million deaths and 100 million people temporarily or permanently disabled every year worldwide. The effectiveness of trauma systems in decreasing injury mortality and morbidity has been well demonstrated. However, the organisation of trauma care varies significantly across trauma systems and we know little about which components of trauma systems contribute to their effectiveness. The objective of the study described in this protocol is to systematically review evidence of the impact of trauma system components on clinically significant outcomes including mortality, function and disability, quality of life, and resource utilization.MethodsWe will perform a systematic review of studies evaluating the association between at least one trauma system component (e.g. accreditation by a central agency, interfacility transfer agreements) and at least one injury outcome (e.g. mortality, disability, resource use). We will search MEDLINE, EMBASE, COCHRANE central, and BIOSIS/Web of Knowledge databases, thesis holdings, key injury organisation websites and conference proceedings for eligible studies. Pairs of independent reviewers will evaluate studies for eligibility and extract data from included articles. Methodological quality will be evaluated using elements of the ROBINS-I tool and the Cochrane risk of bias tool for non-randomized and randomized studies, respectively. Strength of evidence will be evaluated using the GRADE tool.DiscussionWe expect to advance knowledge on the components of trauma systems that contribute to their effectiveness. This may lead to recommendations on trauma system structure that will help policy-makers make informed decisions as to where resources should be focused. The review may also lead to specific recommendations for future research efforts.Systematic review registrationThis protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 28-06-2016. PROSPERO 2016:CRD42016041336 Available from http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42016041336.

Trauma center performance evaluation based on costs: a systematic review of cohort studies.

BACKGROUND In 2000, more than 50 million Americans were treated in hospitals following injury, with costs estimated at

The Prognostic Value of Mri in Moderate and Severe Traumatic Brain Injury: A Systematic Review and Meta-analysis

80 billion, yet no performance indicator based on costs has been developed and validated specifically for acute trauma care. This study aimed to describe how data on costs have been used to evaluate the performance of acute trauma care hospitals. METHODS A systematic review using MEDLINE, EMBASE, Web of Science, The Cochrane Library, CINAHL, TRIP, and ProQuest was performed in December 2012. Cohort studies evaluating hospital performance for the treatment of injury inpatients in terms of costs were considered eligible. Two authors conducted the screening and the data abstraction independently using a piloted electronic data abstraction form. Methodological quality was evaluated using seven criteria from the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement and the Downs and Black tool. RESULTS The search retrieved 6,635 studies, of which 10 were eligible for inclusion. Nine studies were conducted in the United States and one in Europe. Six studies used patient charges as a proxy for patient costs, of which four used cost-to-charge ratios. One study estimated costs using average unit costs, and three studies were based on the real costs obtained from a hospital accounting system. Average costs per patient in 2013 US dollar varied between 2,568 and 74,435. Four studies (40%) were considered to be of good methodological quality. CONCLUSION Studies evaluating the performance of trauma hospitals in terms of costs are rare. Most are based on charges rather than costs, and they have low methodological quality. Further research is needed to develop and validate a performance indicator based on inpatient costs that will enable us to monitor trauma centers in terms of resource use. LEVEL OF EVIDENCE Systematic review, evidence, level III.

Prognostication in critically ill patients with severe traumatic brain injury: the TBI-Prognosis multicentre feasibility study

Objectives: Traumatic brain injury is a major cause of death and disability, yet many predictors of outcome are not precise enough to guide initial clinical decision-making. Although increasingly used in the early phase following traumatic brain injury, the prognostic utility of MRI remains uncertain. We thus undertook a systematic review and meta-analysis of studies evaluating the predictive value of acute MRI lesion patterns for discriminating clinical outcome in traumatic brain injury. Data Sources: MEDLINE, EMBASE, BIOSIS, and CENTRAL from inception to November 2015. Study Selection: Studies of adults who had MRI in the acute phase following moderate or severe traumatic brain injury. Our primary outcomes were all-cause mortality and the Glasgow Outcome Scale. Data Extraction: Two authors independently performed study selection and data extraction. We calculated pooled effect estimates with a random effects model, evaluated the risk of bias using a modified version of Quality in Prognostic Studies and determined the strength of evidence with the Grading of Recommendations, Assessment, Development, and Evaluation. Data Synthesis: We included 58 eligible studies, of which 27 (n = 1,652) contributed data to meta-analysis. Brainstem lesions were associated with all-cause mortality (risk ratio, 1.78; 95% CI, 1.01–3.15; I2 = 43%) and unfavorable Glasgow Outcome Scale (risk ratio, 2.49; 95% CI, 1.72–3.58; I2 = 81%) at greater than or equal to 6 months. Diffuse axonal injury patterns were associated with an increased risk of unfavorable Glasgow Outcome Scale (risk ratio, 2.46; 95% CI, 1.06–5.69; I2 = 74%). MRI scores based on lesion depth demonstrated increasing risk of unfavorable neurologic outcome as more caudal structures were affected. Most studies were at high risk of methodological bias. Conclusions: MRI following traumatic brain injury yields important prognostic information, with several lesion patterns significantly associated with long-term survival and neurologic outcome. Given the high risk of bias in the current body of literature, large well-controlled studies are necessary to better quantify the prognostic role of early MRI in moderate and severe traumatic brain injury.

Incidence and impact of withdrawal of life-sustaining therapies in clinical trials of severe traumatic brain injury: A systematic review:

Objective Severe traumatic brain injury is a significant cause of morbidity and mortality in young adults. Assessing long-term neurological outcome after such injury is difficult and often characterised by uncertainty. The objective of this feasibility study was to establish the feasibility of conducting a large, multicentre prospective study to develop a prognostic model of long-term neurological outcome in critically ill patients with severe traumatic brain injury. Design A prospective cohort study. Setting 9 Canadian intensive care units enrolled patients suffering from acute severe traumatic brain injury. Clinical, biological, radiological and electrophysiological data were systematically collected during the first week in the intensive care unit. Mortality and functional outcome (Glasgow Outcome Scale extended) were assessed on hospital discharge, and then 3, 6 and 12 months following injury. Outcomes The compliance to protocolised test procedures was the primary outcome. Secondary outcomes were enrolment rate and compliance to follow-up. Results We successfully enrolled 50 patients over a 12-month period. Most patients were male (80%), with a median age of 45 years (IQR 29.0–60.0), a median Injury Severity Score of 38 (IQR 25–50) and a Glasgow Coma Scale of 6 (IQR 3–7). Mortality was 38% (19/50) and most deaths occurred following a decision to withdraw life-sustaining therapies (18/19). The main reasons for non-enrolment were the time window for inclusion being after regular working hours (35%, n=23) and oversight (24%, n=16). Compliance with protocolised test procedures ranged from 92% to 100% and enrolment rate was 43%. No patients were lost to follow-up at 6 months and 2 were at 12 months. Conclusions In this multicentre prospective feasibility study, we achieved feasibility objectives pertaining to compliance to test, enrolment and follow-up. We conclude that the TBI-Prognosis prospective multicentre study in severe traumatic brain injury patients in Canada is feasible.

Intermittent vs Continuous Androgen Deprivation Therapy for Prostate Cancer: A Systematic Review and Meta-analysis.

Background Most deaths following severe traumatic brain injury follow decisions to withdraw life-sustaining therapies. However, the incidence of the withdrawal of life-sustaining therapies and its potential impact on research data interpretation have been poorly characterized. The aim of this systematic review was to assess the reporting and the impact of withdrawal of life-sustaining therapies in randomized clinical trials of patients with severe traumatic brain injury. Methods We searched Medline, Embase, Cochrane Central, BIOSIS, and CINAHL databases and references of included trials. All randomized controlled trials published between January 2002 and August 2015 in the six highest impact journals in general medicine, critical care medicine, and neurocritical care (total of 18 journals) were considered for eligibility. Randomized controlled trials were included if they enrolled adult patients with severe traumatic brain injury (Glasgow Coma Scale ≤ 8) and reported data on mortality. Our primary objective was to assess the proportion of trials reporting the withdrawal of life-sustaining therapies in a publication. Our secondary objectives were to describe the overall mortality rate, the proportion of deaths following the withdrawal of life-sustaining therapies, and to assess the impact of the withdrawal of life-sustaining therapies on trial results. Results From 5987 citations retrieved, we included 41 randomized trials (n = 16,364, ranging from 11 to 10,008 patients). Overall mortality was 23% (range = 3%–57%). Withdrawal of life-sustaining therapies was reported in 20% of trials (8/41, 932 patients in trials) and the crude number of deaths due to the withdrawal of life-sustaining therapies was reported in 17% of trials (7/41, 884 patients in trials). In these trials, 63% of deaths were associated with the withdrawal of life-sustaining therapies (105/168). An analysis carried out by imputing a 4% differential rate in instances of withdrawal of life-sustaining therapies between study groups yielded different results and conclusions in one third of the trials. Conclusion Data on the withdrawal of life-sustaining therapies are incompletely reported in randomized controlled trials of patients with severe traumatic brain injury. Given the high proportion of deaths due to the withdrawal of life-sustaining therapies in severe traumatic brain injury patients, and the potential of this medical decision to influence the results of clinical trials, instances of withdrawal of life-sustaining therapies should be systematically reported in clinical trials in this group of patients.