The prospective, observational, multicenter, major trauma transfusion (PROMMTT) study: Comparative effectiveness of a time-varying treatment with competing risks
University of Texas Health Science Center at Houston1, University of California, San Francisco2, Oregon Health & Science University3, University of Pittsburgh4, Medical College of Wisconsin5, University of Washington6, University of Cincinnati7, University of Texas Health Science Center at San Antonio8, University of Texas Southwestern Medical Center9, San Antonio Military Medical Center10
TL;DR: Higher plasma and platelet ratios early in resuscitation were associated with decreased mortality in patients who received transfusions of at least 3 units of blood products during the first 24 hours after admission, and among survivors at 24 hours, the subsequent risk of death by day 30 was not associated with plasma or Platelet ratios.
Abstract: Objective To relate in-hospital mortality to early transfusion of plasma and/or platelets and to time-varying plasma:red blood cell (RBC) and platelet:RBC ratios. Design Prospective cohort study documenting the timing of transfusions during active resuscitation and patient outcomes. Data were analyzed using time-dependent proportional hazards models. Setting Ten US level I trauma centers. Patients Adult trauma patients surviving for 30 minutes after admission who received a transfusion of at least 1 unit of RBCs within 6 hours of admission (n = 1245, the original study group) and at least 3 total units (of RBCs, plasma, or platelets) within 24 hours (n = 905, the analysis group). Main Outcome Measure In-hospital mortality. Results Plasma:RBC and platelet:RBC ratios were not constant during the first 24 hours (P Conclusions Higher plasma and platelet ratios early in resuscitation were associated with decreased mortality in patients who received transfusions of at least 3 units of blood products during the first 24 hours after admission. Among survivors at 24 hours, the subsequent risk of death by day 30 was not associated with plasma or platelet ratios.
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University of Texas Health Science Center at Houston1, Medical College of Wisconsin2, Oregon Health & Science University3, University of Washington4, University of California, San Francisco5, University of Tennessee Health Science Center6, University of Southern California7, University of Alabama at Birmingham8, University of Cincinnati9, University of Arizona10, University of Toronto11, University of Maryland, Baltimore12, Sunnybrook Health Sciences Centre13, American College of Surgeons14, National Institutes of Health15
TL;DR: In this article, the effectiveness and safety of transfusing patients with severe trauma and major bleeding using plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1 :1:2 ratio was evaluated.
Abstract: Importance Severely injured patients experiencing hemorrhagic shock often require massive transfusion. Earlier transfusion with higher blood product ratios (plasma, platelets, and red blood cells), defined as damage control resuscitation, has been associated with improved outcomes; however, there have been no large multicenter clinical trials. Objective To determine the effectiveness and safety of transfusing patients with severe trauma and major bleeding using plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio. Design, Setting, and Participants Pragmatic, phase 3, multisite, randomized clinical trial of 680 severely injured patients who arrived at 1 of 12 level I trauma centers in North America directly from the scene and were predicted to require massive transfusion between August 2012 and December 2013. Interventions Blood product ratios of 1:1:1 (338 patients) vs 1:1:2 (342 patients) during active resuscitation in addition to all local standard-of-care interventions (uncontrolled). Main Outcomes and Measures Primary outcomes were 24-hour and 30-day all-cause mortality. Prespecified ancillary outcomes included time to hemostasis, blood product volumes transfused, complications, incidence of surgical procedures, and functional status. Results No significant differences were detected in mortality at 24 hours (12.7% in 1:1:1 group vs 17.0% in 1:1:2 group; difference, −4.2% [95% CI, −9.6% to 1.1%]; P = .12) or at 30 days (22.4% vs 26.1%, respectively; difference, −3.7% [95% CI, −10.2% to 2.7%]; P = .26). Exsanguination, which was the predominant cause of death within the first 24 hours, was significantly decreased in the 1:1:1 group (9.2% vs 14.6% in 1:1:2 group; difference, −5.4% [95% CI, −10.4% to −0.5%]; P = .03). More patients in the 1:1:1 group achieved hemostasis than in the 1:1:2 group (86% vs 78%, respectively; P = .006). Despite the 1:1:1 group receiving more plasma (median of 7 U vs 5 U, P P Conclusions and Relevance Among patients with severe trauma and major bleeding, early administration of plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio did not result in significant differences in mortality at 24 hours or at 30 days. However, more patients in the 1:1:1 group achieved hemostasis and fewer experienced death due to exsanguination by 24 hours. Even though there was an increased use of plasma and platelets transfused in the 1:1:1 group, no other safety differences were identified between the 2 groups. Trial Registration clinicaltrials.gov Identifier:NCT01545232
1,643 citations
TL;DR: The guideline now recommends that patients be transferred directly to an appropriate trauma treatment centre and encourages use of a restricted volume replacement strategy during initial resuscitation, and may also serve as a basis for local implementation.
Abstract: Severe trauma continues to represent a global public health issue and mortality and morbidity in trauma patients remains substantial. A number of initiatives have aimed to provide guidance on the management of trauma patients. This document focuses on the management of major bleeding and coagulopathy following trauma and encourages adaptation of the guiding principles to each local situation and implementation within each institution. The pan-European, multidisciplinary Task Force for Advanced Bleeding Care in Trauma was founded in 2004 and included representatives of six relevant European professional societies. The group used a structured, evidence-based consensus approach to address scientific queries that served as the basis for each recommendation and supporting rationale. Expert opinion and current clinical practice were also considered, particularly in areas in which randomised clinical trials have not or cannot be performed. Existing recommendations were reconsidered and revised based on new scientific evidence and observed shifts in clinical practice; new recommendations were formulated to reflect current clinical concerns and areas in which new research data have been generated. This guideline represents the fourth edition of a document first published in 2007 and updated in 2010 and 2013. The guideline now recommends that patients be transferred directly to an appropriate trauma treatment centre and encourages use of a restricted volume replacement strategy during initial resuscitation. Best-practice use of blood products during further resuscitation continues to evolve and should be guided by a goal-directed strategy. The identification and management of patients pre-treated with anticoagulant agents continues to pose a real challenge, despite accumulating experience and awareness. The present guideline should be viewed as an educational aid to improve and standardise the care of the bleeding trauma patients across Europe and beyond. This document may also serve as a basis for local implementation. Furthermore, local quality and safety management systems need to be established to specifically assess key measures of bleeding control and outcome. A multidisciplinary approach and adherence to evidence-based guidance are key to improving patient outcomes. The implementation of locally adapted treatment algorithms should strive to achieve measureable improvements in patient outcome.
1,247 citations
Cites background from "The prospective, observational, mul..."
...30 However, recent large prospective cohort studies showed that a high platelet:RBC ratio was 31 associated with survival benefit as early as 6 h after admission, suggesting that survivor bias 32 is unlikely [469, 471]....
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...between higher platelet ratios and mortality was concentrated during the first 6 h only, in 34 contrast to high plasma ratios which were protective throughout the first 24 h [471]....
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TL;DR: The ninth edition of the ATLS course continues to emphasize one safe way to care for the trauma patient during initial assessment; it is not meant to incorporate the most advanced, cutting edge information or technology.
Abstract: T Advanced Trauma Life Support (ATLS) course was introduced in 1978 and is currently taught in more than 60 countries. It continues to be a widely accepted standard for the initial care of the trauma patient. Begun as a consensus view of recognized experts on safe initial management of a trauma patient, it combines didactic information with procedural skills, culminating with management of simulated patients. Evidence of its effectiveness includes ascertainment and retention of both knowledge and skills as well as reduced morbidity and mortality after introduction of the ATLS program. The ATLS course undergoes revision approximately every 4 years, with early editions primarily revising old and incorporating new content. The eight edition, published in 2008, established a new process for incorporating change. All content changes in that edition and all subsequent editions required evidence rather than opinion for change. Suggestions for change are submitted directly to the ATLS revision Web site, with the opportunity to provide references and the level of evidence. The ninth edition continues to rely on evidence to support changes in ATLS content. However, the major changes in the ninth edition are format and delivery changes rather than content changes. The drivers for format changes come primarily from the increasing understanding of adult education along with the educational preferences of the next generations. In both content and format, two principles in addition to level of evidence continue to guide any changes to the ATLS course. The course continues to emphasize one safe way to care for the trauma patient during initial assessment; it is not meant to incorporate the most advanced, cutting edge information or technology. In addition, with the increasing penetrance of ATLS around the world, there is increasing variation in local resources and practice. The ATLS vision is to embrace those differences that do not affect the ultimate delivery of safe care and allow flexibility for course directors to choose safe options that reflect their local practice.
655 citations
TL;DR: In injured patients at risk for hemorrhagic shock, the prehospital administration of thawed plasma was safe and resulted in lower 30‐day mortality and a lower median prothrombin‐time ratio than standard‐care resuscitation.
Abstract: Background After a person has been injured, prehospital administration of plasma in addition to the initiation of standard resuscitation procedures in the prehospital environment may reduc
496 citations
TL;DR: Utilization of a goal-directed, TEG-guided MTP to resuscitate severely injured patients improves survival compared with an MTP guided by CCA and utilizes less plasma and platelet transfusions during the early phase of resuscitation.
Abstract: Background
Massive transfusion protocols (MTPs) have become standard of care in the management of bleeding injured patients, yet strategies to guide them vary widely. We conducted a pragmatic, randomized clinical trial (RCT) to test the hypothesis that an MTP goal directed by the viscoelastic assay thrombelastography (TEG) improves survival compared with an MTP guided by conventional coagulation assays (CCA).
479 citations
Cites background from "The prospective, observational, mul..."
...A proposed alternative to goal-directed guidance of MTPs has been ratio-based transfusion.39 When using such formulaic approach, it remains unclear at what point administration of higher plasma and platelet to RBC ratios is no longer beneficial40,41 and can lead to unnecessary use of blood products; particularly because the same ratio of blood products is given to every patient, at every time point in the MTP.39,42 Recent characterization of 2 distinct phenotypes of trauma-induced coagulopathy by principal component analyses of coagulation proteins and er Health, Inc....
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...A proposed alternative to goal-directed guidance of MTPs has been ratio-based transfusion.(39) When using such formulaic approach, it remains unclear at what point administration of higher plasma and platelet to RBC ratios is no longer beneficial(40,41) and can lead to unnecessary use of blood products; particularly because the same ratio of blood products is given to every patient, at every time point in the MTP....
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...When using such formulaic approach, it remains unclear at what point administration of higher plasma and platelet to RBC ratios is no longer beneficial(40,41) and can lead to unnecessary use of blood products; particularly because the same ratio of blood products is given to every patient, at every time point in the MTP.(39,42) Recent characterization of 2 distinct phenotypes of trauma-induced coagulopathy by principal component analyses of coagulation proteins and...
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...Rather, it was designed to represent how clinicians deliver care in 2 real-world clinical scenarios: a trauma center that only has CCA available to guide an MTP, and a trauma center that has TEG available to guide an MTP....
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...Using a traditional random-sequence system for each patient at the time of MTP activation could potentially delay care and lead to confusion because of the multidisciplinary personnel required to execute an MTP....
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References
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TL;DR: The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) initiative developed recommendations on what should be included in an accurate and complete report of an observational study, resulting in a checklist of 22 items (the STROBE statement) that relate to the title, abstract, introduction, methods, results, and discussion sections of articles.
Abstract: Much biomedical research is observational. The reporting of such research is often inadequate, which hampers the assessment of its strengths and weaknesses and of a study's generalisability. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Initiative developed recommendations on what should be included in an accurate and complete report of an observational study. We defined the scope of the recommendations to cover three main study designs: cohort, case-control, and cross-sectional studies. We convened a 2-day workshop in September 2004, with methodologists, researchers, and journal editors to draft a checklist of items. This list was subsequently revised during several meetings of the coordinating group and in e-mail discussions with the larger group of STROBE contributors, taking into account empirical evidence and methodological considerations. The workshop and the subsequent iterative process of consultation and revision resulted in a checklist of 22 items (the STROBE Statement) that relate to the title, abstract, introduction, methods, results, and discussion sections of articles. 18 items are common to all three study designs and four are specific for cohort, case-control, or cross-sectional studies. A detailed Explanation and Elaboration document is published separately and is freely available on the Web sites of PLoS Medicine, Annals of Internal Medicine, and Epidemiology. We hope that the STROBE Statement will contribute to improving the quality of reporting of observational studies.
15,454 citations
TL;DR: The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Initiative developed recommendations on what should be included in an accurate and complete report of an observational study, resulting in a checklist of 22 items that relate to the title, abstract, introduction, methods, results, and discussion sections of articles.
9,603 citations
TL;DR: The STROBE Statement is a checklist of items that should be addressed in articles reporting on the 3 main study designs of analytical epidemiology: cohort, casecontrol, and cross-sectional studies; these recommendations are not prescriptions for designing or conducting studies.
Abstract: Much biomedical research is observational. The reporting of such research is often inadequate, which hampers the assessment of its strengths and weaknesses and of a study's generalizability. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Initiative developed recommendations on what should be included in an accurate and complete report of an observational study. We defined the scope of the recommendations to cover 3 main study designs: cohort, case-control, and cross-sectional studies. We convened a 2-day workshop in September 2004, with methodologists, researchers, and journal editors, to draft a checklist of items. This list was subsequently revised during several meetings of the coordinating group and in e-mail discussions with the larger group of STROBE contributors, taking into account empirical evidence and methodological considerations. The workshop and the subsequent iterative process of consultation and revision resulted in a checklist of 22 items (the STROBE Statement) that relate to the title, abstract, introduction, methods, results, and discussion sections of articles. Eighteen items are common to all 3 study designs and 4 are specific for cohort, case-control, or cross-sectional studies. A detailed Explanation and Elaboration document is published separately and is freely available at http://www.annals.org and on the Web sites of PLoS Medicine and Epidemiology. We hope that the STROBE Statement will contribute to improving the quality of reporting of observational studies.
9,000 citations
Additional excerpts
...At admission Age, y 38 (24-54) 1244 37 (24-53) 904 Male, No....
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...6) 904 Time to first units transfused, min RBCs 30 (12-99) 1222 25 (11-77) 905 Plasma 69 (35-133) 815b 69 (35-130) 778b Platelets 123 (81-190) 357b 121 (80-187) 343b Total units At 6 h RBCs 4 (2-7) 1224 5 (3-9) 905 Plasma 2 (0-5) 1224 4 (2-7) 905 Platelets 0 (0-6) 1224 0 (0-6) 905 At 24 h RBCs 5 (2-9) 1244 6 (4-11) 905 Plasma 4 (0-8) 1245 5 (2-9) 905 Platelets 0 (0-6) 1245 0 (0-6) 905 Unadjusted in-hospital mortality, No....
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Book•
07 Mar 2008TL;DR: Applied Survival Analysis, Second Edition is an ideal book for graduate-level courses in biostatistics, statistics, and epidemiologic methods and serves as a valuable reference for practitioners and researchers in any health-related field or for professionals in insurance and government.
Abstract: THE MOST PRACTICAL, UP-TO-DATE GUIDE TO MODELLING AND ANALYZING TIME-TO-EVENT DATANOW IN A VALUABLE NEW EDITION Since publication of the first edition nearly a decade ago, analyses using time-to-event methods have increase considerably in all areas of scientific inquiry mainly as a result of model-building methods available in modern statistical software packages. However, there has been minimal coverage in the available literature to9 guide researchers, practitioners, and students who wish to apply these methods to health-related areas of study. Applied Survival Analysis, Second Edition provides a comprehensive and up-to-date introduction to regression modeling for time-to-event data in medical, epidemiological, biostatistical, and other health-related research. This book places a unique emphasis on the practical and contemporary applications of regression modeling rather than the mathematical theory. It offers a clear and accessible presentation of modern modeling techniques supplemented with real-world examples and case studies. Key topics covered include: variable selection, identification of the scale of continuous covariates, the role of interactions in the model, assessment of fit and model assumptions, regression diagnostics, recurrent event models, frailty models, additive models, competing risk models, and missing data. Features of the Second Edition include: Expanded coverage of interactions and the covariate-adjusted survival functions The use of the Worchester Heart Attack Study as the main modeling data set for illustrating discussed concepts and techniques New discussion of variable selection with multivariable fractional polynomials Further exploration of time-varying covariates, complex with examples Additional treatment of the exponential, Weibull, and log-logistic parametric regression models Increased emphasis on interpreting and using results as well as utilizing multiple imputation methods to analyze data with missing values New examples and exercises at the end of each chapter Analyses throughout the text are performed using Stata Version 9, and an accompanying FTP site contains the data sets used in the book. Applied Survival Analysis, Second Edition is an ideal book for graduate-level courses in biostatistics, statistics, and epidemiologic methods. It also serves as a valuable reference for practitioners and researchers in any health-related field or for professionals in insurance and government.
3,507 citations
TL;DR: An algorithm which automates the purposeful selection of covariates within which an analyst makes a variable selection decision at each step of the modeling process and has the capability of retaining important confounding variables, resulting potentially in a slightly richer model.
Abstract: Background
The main problem in many model-building situations is to choose from a large set of covariates those that should be included in the "best" model. A decision to keep a variable in the model might be based on the clinical or statistical significance. There are several variable selection algorithms in existence. Those methods are mechanical and as such carry some limitations. Hosmer and Lemeshow describe a purposeful selection of covariates within which an analyst makes a variable selection decision at each step of the modeling process.
2,577 citations
Additional excerpts
...At admission Age, y 38 (24-54) 1244 37 (24-53) 904 Male, No....
[...]
...6) 904 Time to first units transfused, min RBCs 30 (12-99) 1222 25 (11-77) 905 Plasma 69 (35-133) 815b 69 (35-130) 778b Platelets 123 (81-190) 357b 121 (80-187) 343b Total units At 6 h RBCs 4 (2-7) 1224 5 (3-9) 905 Plasma 2 (0-5) 1224 4 (2-7) 905 Platelets 0 (0-6) 1224 0 (0-6) 905 At 24 h RBCs 5 (2-9) 1244 6 (4-11) 905 Plasma 4 (0-8) 1245 5 (2-9) 905 Platelets 0 (0-6) 1245 0 (0-6) 905 Unadjusted in-hospital mortality, No....
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