2013
Perel, Pablo; Ker, Katharine; Uribe, Carlos Hernando Morales; Roberts, Ian
Tranexamic acid for reducing mortality in emergency and urgent surgery. Journal Article
In: The Cochrane database of systematic reviews, vol. 1, no. 1, pp. CD010245–, 2013.
@article{lshtm639014,
title = {Tranexamic acid for reducing mortality in emergency and urgent surgery.},
author = {Pablo Perel and Katharine Ker and Carlos Hernando Morales Uribe and Ian Roberts},
url = {http://researchonline.lshtm.ac.uk/id/eprint/639014/},
year = {2013},
date = {2013-01-01},
journal = {The Cochrane database of systematic reviews},
volume = {1},
number = {1},
pages = {CD010245--},
publisher = {Cochrane Collaboration},
abstract = {BACKGROUND: Emergency or urgent surgery, which can be defined as surgery which must be done promptly to save life, limb, or functional capacity, is associated with a high risk of bleeding and death. Antifibrinolytic agents, such as tranexamic acid, inhibit blood clot breakdown (fibrinolysis) and can reduce perioperative bleeding. Tranexamic acid has been shown to reduce the need for a blood transfusion in adult patients undergoing elective surgery but its effects in patients undergoing emergency or urgent surgery is unclear. OBJECTIVES: To assess the effects of tranexamic acid on mortality, blood transfusion and thromboembolic events in adults undergoing emergency or urgent surgery. SEARCH METHODS: We searched the following electronic databases: the Cochrane Injuries Group's Specialised Register (22 August 2012); Cochrane Central Register of Controlled Trials (2012, issue 8 of 12); MEDLINE (Ovid SP) 1950 to August Week 2, 2012; PubMed 1 June 2012 to 22 August 2012; EMBASE (Ovid SP) 1980 to 2012 Week 33; ISI Web of Science: Conference Proceedings Citation Index-Science (CPCI-S) 1990 to 22 August 2012; ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) 1970 to 22 August 2012. We also searched online trial registers on 22 August 2012 to identify unpublished studies. SELECTION CRITERIA: Randomised controlled trials comparing tranexamic acid with no tranexamic acid or placebo in adults undergoing emergency or urgent surgery. DATA COLLECTION AND ANALYSIS: Two authors examined titles, abstracts and keywords of citations from the electronic databases for eligibility and extracted data for analysis and risk of bias assessment. Outcome measures of interest were mortality, receipt of a blood transfusion, units of blood transfused, reoperation, seizures and thromboembolic events (myocardial infarction, stroke, deep vein thrombosis and pulmonary embolism). MAIN RESULTS: We identified five trials involving 372 people that met the inclusion criteria. Three trials (260 patients) contributed data to the analyses. The effect of tranexamic acid on mortality (RR 1.01; 95% CI 0.14 to 7.3) is uncertain. However, tranexamic acid reduces the probability of receiving a blood transfusion by 30% although the estimate is imprecise (RR 0.70; 95% CI 0.52 to 0.94). The effect on deep venous thrombosis (RR 2.29; 95% CI 0.68 to 7.66), and stroke (RR 2.79; 95% CI 0.12 to 67.10) is uncertain. There were no events of pulmonary embolism or myocardial infarction. None of the trials reported units of blood transfused, reoperation, or seizure outcomes. AUTHORS' CONCLUSIONS: There is evidence that tranexamic acid reduces blood transfusion in patients undergoing emergency or urgent surgery. There is a need for a large pragmatic clinical trial to assess the effects of routine use of tranexamic acid on mortality in a heterogeneous group of urgent and emergency surgical patients.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Emergency or urgent surgery, which can be defined as surgery which must be done promptly to save life, limb, or functional capacity, is associated with a high risk of bleeding and death. Antifibrinolytic agents, such as tranexamic acid, inhibit blood clot breakdown (fibrinolysis) and can reduce perioperative bleeding. Tranexamic acid has been shown to reduce the need for a blood transfusion in adult patients undergoing elective surgery but its effects in patients undergoing emergency or urgent surgery is unclear. OBJECTIVES: To assess the effects of tranexamic acid on mortality, blood transfusion and thromboembolic events in adults undergoing emergency or urgent surgery. SEARCH METHODS: We searched the following electronic databases: the Cochrane Injuries Group's Specialised Register (22 August 2012); Cochrane Central Register of Controlled Trials (2012, issue 8 of 12); MEDLINE (Ovid SP) 1950 to August Week 2, 2012; PubMed 1 June 2012 to 22 August 2012; EMBASE (Ovid SP) 1980 to 2012 Week 33; ISI Web of Science: Conference Proceedings Citation Index-Science (CPCI-S) 1990 to 22 August 2012; ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) 1970 to 22 August 2012. We also searched online trial registers on 22 August 2012 to identify unpublished studies. SELECTION CRITERIA: Randomised controlled trials comparing tranexamic acid with no tranexamic acid or placebo in adults undergoing emergency or urgent surgery. DATA COLLECTION AND ANALYSIS: Two authors examined titles, abstracts and keywords of citations from the electronic databases for eligibility and extracted data for analysis and risk of bias assessment. Outcome measures of interest were mortality, receipt of a blood transfusion, units of blood transfused, reoperation, seizures and thromboembolic events (myocardial infarction, stroke, deep vein thrombosis and pulmonary embolism). MAIN RESULTS: We identified five trials involving 372 people that met the inclusion criteria. Three trials (260 patients) contributed data to the analyses. The effect of tranexamic acid on mortality (RR 1.01; 95% CI 0.14 to 7.3) is uncertain. However, tranexamic acid reduces the probability of receiving a blood transfusion by 30% although the estimate is imprecise (RR 0.70; 95% CI 0.52 to 0.94). The effect on deep venous thrombosis (RR 2.29; 95% CI 0.68 to 7.66), and stroke (RR 2.79; 95% CI 0.12 to 67.10) is uncertain. There were no events of pulmonary embolism or myocardial infarction. None of the trials reported units of blood transfused, reoperation, or seizure outcomes. AUTHORS' CONCLUSIONS: There is evidence that tranexamic acid reduces blood transfusion in patients undergoing emergency or urgent surgery. There is a need for a large pragmatic clinical trial to assess the effects of routine use of tranexamic acid on mortality in a heterogeneous group of urgent and emergency surgical patients.
Caballero-Albarado, José; Dewan, Yashbir; Elsayed, Hesham Fathy; Gogichaishvili, Tamar; Gupta, Sanjay; Hunt, BJ; Iribhogbe, Pius; Izurieta, Mario; Khamis, Hussein; Komolafe, Edward O; Mejía-Mantilla, Jorge H; Miranda, Jaime; Morales-Uribe, Carlos H; Olaomi, Oluwole; Olldashi, Fatos; Perel, Pablo; Ramana, PV; Ravi, RR; Roberts, Ian; Shakur-Still, Haleema
Tranexamic acid in trauma: we need stronger global health policy. Journal Article
In: BMJ (Clinical research ed), vol. 347, no. jul23, pp. f4593–, 2013.
@article{lshtm1229307,
title = {Tranexamic acid in trauma: we need stronger global health policy.},
author = {José Caballero-Albarado and Yashbir Dewan and Hesham Fathy Elsayed and Tamar Gogichaishvili and Sanjay Gupta and BJ Hunt and Pius Iribhogbe and Mario Izurieta and Hussein Khamis and Edward O Komolafe and Jorge H Mejía-Mantilla and Jaime Miranda and Carlos H Morales-Uribe and Oluwole Olaomi and Fatos Olldashi and Pablo Perel and PV Ramana and RR Ravi and Ian Roberts and Haleema Shakur-Still},
url = {http://researchonline.lshtm.ac.uk/id/eprint/1229307/},
year = {2013},
date = {2013-01-01},
journal = {BMJ (Clinical research ed)},
volume = {347},
number = {jul23},
pages = {f4593--},
publisher = {BMJ Publishing Group},
abstract = {Tranexamic acid substantially reduces death in bleeding trauma patients. So why are the World Health Organization, the United Nations, the World Bank, and Unicef not ensuring global implementation, ask Ian Roberts and colleagues},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Tranexamic acid substantially reduces death in bleeding trauma patients. So why are the World Health Organization, the United Nations, the World Bank, and Unicef not ensuring global implementation, ask Ian Roberts and colleagues
Edwards, Phil; Shakur-Still, Haleema; Barnetson, Lin; Prieto, David; Evans, Stephen; Roberts, Ian
Central and statistical data monitoring in the Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage (CRASH-2) trial. Journal Article
In: Clinical trials (London, England), vol. 11, no. 3, pp. 336–343, 2013.
@article{lshtm1440263,
title = {Central and statistical data monitoring in the Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage (CRASH-2) trial.},
author = {Phil Edwards and Haleema Shakur-Still and Lin Barnetson and David Prieto and Stephen Evans and Ian Roberts},
url = {http://researchonline.lshtm.ac.uk/id/eprint/1440263/},
year = {2013},
date = {2013-01-01},
journal = {Clinical trials (London, England)},
volume = {11},
number = {3},
pages = {336--343},
publisher = {SAGE Publications},
abstract = {Background The purpose of monitoring in clinical trials is to ensure the rights, safety, and well-being of trial patients and the accuracy of the trial data. In the Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage (CRASH-2) trial, which recruited over 20,000 adult trauma patients worldwide, the nature and extent of monitoring was based on a risk assessment undertaken before recruitment started. Purpose We report the methods used for central and statistical monitoring in the CRASH-2 trial and explain how central monitoring was used to target on-site investigations. Methods To ensure that trial participants met the inclusion criteria, we monitored event rates for the primary (death) and secondary outcomes (blood transfusion given). We monitored four quantitative variables (systolic blood pressure (SBP), heart rate (HR), respiratory rate, and capillary refill time) as indicators of the severity of bleeding. We used the coefficient of variation (CV) to identify sites with too much or too little variability. To ensure the accuracy of the data on side effects, we monitored thromboembolic events at each site. Sites with higher or lower than expected event rates were identified for further evaluation. Results A total of 274 sites recruited patients: 145 sites recruited ?20; patients, and 52 sites recruited ?100 patients. Sites with low case fatality and low blood transfusion rates were found to be including patients with relatively mild haemorrhage. One site with a high rate of thromboembolic events was found to be using clinical judgement alone. Measurements of SBP and HR varied by about one-fifth of their average value, and capillary refill time measurements varied by around one-third of their average; between-site variation was lowest for blood pressure. Limitations A comparison of mean and median CV indicated that the distributions are slightly skewed to the right. Our simple approach to calculating 95% confidence intervals for the CV may be improved by using a logarithmic transformation of CV for each variable. Conclusions Central and statistical monitoring of data can be used to monitor clinical trials, particularly large, pragmatic, international trials where 100% on-site monitoring is neither necessary nor cost-effective. In the CRASH-2 trial, re-education about trial protocol and the development of guidance helped resolve the issues identified during monitoring.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background The purpose of monitoring in clinical trials is to ensure the rights, safety, and well-being of trial patients and the accuracy of the trial data. In the Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage (CRASH-2) trial, which recruited over 20,000 adult trauma patients worldwide, the nature and extent of monitoring was based on a risk assessment undertaken before recruitment started. Purpose We report the methods used for central and statistical monitoring in the CRASH-2 trial and explain how central monitoring was used to target on-site investigations. Methods To ensure that trial participants met the inclusion criteria, we monitored event rates for the primary (death) and secondary outcomes (blood transfusion given). We monitored four quantitative variables (systolic blood pressure (SBP), heart rate (HR), respiratory rate, and capillary refill time) as indicators of the severity of bleeding. We used the coefficient of variation (CV) to identify sites with too much or too little variability. To ensure the accuracy of the data on side effects, we monitored thromboembolic events at each site. Sites with higher or lower than expected event rates were identified for further evaluation. Results A total of 274 sites recruited patients: 145 sites recruited ?20; patients, and 52 sites recruited ?100 patients. Sites with low case fatality and low blood transfusion rates were found to be including patients with relatively mild haemorrhage. One site with a high rate of thromboembolic events was found to be using clinical judgement alone. Measurements of SBP and HR varied by about one-fifth of their average value, and capillary refill time measurements varied by around one-third of their average; between-site variation was lowest for blood pressure. Limitations A comparison of mean and median CV indicated that the distributions are slightly skewed to the right. Our simple approach to calculating 95% confidence intervals for the CV may be improved by using a logarithmic transformation of CV for each variable. Conclusions Central and statistical monitoring of data can be used to monitor clinical trials, particularly large, pragmatic, international trials where 100% on-site monitoring is neither necessary nor cost-effective. In the CRASH-2 trial, re-education about trial protocol and the development of guidance helped resolve the issues identified during monitoring.
Fine, Paul; Victora, Cesar G; Rothman, Kenneth J; Moore, Patrick S; Chang, Yuan; Curtis, Val; Heymann, David L; Slutkin, Gary; May, Robert M; Patel, Vikram; Roberts, Ian; Wortley, Richard; Torgerson, Carole; Deaton, Angus
John Snow's legacy: epidemiology without borders. Journal Article
In: Lancet, vol. 381, no. 9874, pp. 1302–1311, 2013.
@article{lshtm790328,
title = {John Snow's legacy: epidemiology without borders.},
author = {Paul Fine and Cesar G Victora and Kenneth J Rothman and Patrick S Moore and Yuan Chang and Val Curtis and David L Heymann and Gary Slutkin and Robert M May and Vikram Patel and Ian Roberts and Richard Wortley and Carole Torgerson and Angus Deaton},
url = {http://researchonline.lshtm.ac.uk/id/eprint/790328/},
year = {2013},
date = {2013-01-01},
journal = {Lancet},
volume = {381},
number = {9874},
pages = {1302--1311},
publisher = {Elsevier},
abstract = {This Review provides abstracts from a meeting held at the London School of Hygiene and Tropical Medicine, on April 11-12, 2013, to celebrate the legacy of John Snow. They describe conventional and unconventional applications of epidemiological methods to problems ranging from diarrhoeal disease, mental health, cancer, and accident care, to education, poverty, financial networks, crime, and violence. Common themes appear throughout, including recognition of the importance of Snow's example, the philosophical and practical implications of assessment of causality, and an emphasis on the evaluation of preventive, ameliorative, and curative interventions, in a wide variety of medical and societal examples. Almost all self-described epidemiologists nowadays work within the health arena, and this is the focus of most of the societies, journals, and courses that carry the name epidemiology. The range of applications evident in these contributions might encourage some of these institutions to consider broadening their remits. In so doing, they may contribute more directly to, and learn from, non-health-related areas that use the language and methods of epidemiology to address many important problems now facing the world.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
This Review provides abstracts from a meeting held at the London School of Hygiene and Tropical Medicine, on April 11-12, 2013, to celebrate the legacy of John Snow. They describe conventional and unconventional applications of epidemiological methods to problems ranging from diarrhoeal disease, mental health, cancer, and accident care, to education, poverty, financial networks, crime, and violence. Common themes appear throughout, including recognition of the importance of Snow's example, the philosophical and practical implications of assessment of causality, and an emphasis on the evaluation of preventive, ameliorative, and curative interventions, in a wide variety of medical and societal examples. Almost all self-described epidemiologists nowadays work within the health arena, and this is the focus of most of the societies, journals, and courses that carry the name epidemiology. The range of applications evident in these contributions might encourage some of these institutions to consider broadening their remits. In so doing, they may contribute more directly to, and learn from, non-health-related areas that use the language and methods of epidemiology to address many important problems now facing the world.
Guerriero, Carla; Cairns, John; Roberts, Ian; Rodgers, Anthony; Whittaker, Robyn; Free, Caroline
The cost-effectiveness of smoking cessation support delivered by mobile phone text messaging: Txt2stop. Journal Article
In: The European journal of health economics, vol. 14, no. 5, pp. 789–797, 2013.
@article{lshtm251242,
title = {The cost-effectiveness of smoking cessation support delivered by mobile phone text messaging: Txt2stop.},
author = {Carla Guerriero and John Cairns and Ian Roberts and Anthony Rodgers and Robyn Whittaker and Caroline Free},
url = {http://researchonline.lshtm.ac.uk/id/eprint/251242/},
year = {2013},
date = {2013-01-01},
journal = {The European journal of health economics},
volume = {14},
number = {5},
pages = {789--797},
publisher = {Springer Verlag},
abstract = {BACKGROUND: The txt2stop trial has shown that mobile-phone-based smoking cessation support doubles biochemically validated quitting at 6 months. This study examines the cost-effectiveness of smoking cessation support delivered by mobile phone text messaging. METHODS: The lifetime incremental costs and benefits of adding text-based support to current practice are estimated from a UK NHS perspective using a Markov model. The cost-effectiveness was measured in terms of cost per quitter, cost per life year gained and cost per QALY gained. As in previous studies, smokers are assumed to face a higher risk of experiencing the following five diseases: lung cancer, stroke, myocardial infarction, chronic obstructive pulmonary disease, and coronary heart disease (i.e. the main fatal or disabling, but by no means the only, adverse effects of prolonged smoking). The treatment costs and health state values associated with these diseases were identified from the literature. The analysis was based on the age and gender distribution observed in the txt2stop trial. Effectiveness and cost parameters were varied in deterministic sensitivity analyses, and a probabilistic sensitivity analysis was also performed. FINDINGS: The cost of text-based support per 1,000 enrolled smokers is pounds16,120, which, given an estimated 58 additional quitters at 6 months, equates to pounds278 per quitter. However, when the future NHS costs saved (as a result of reduced smoking) are included, text-based support would be cost saving. It is estimated that 18 LYs are gained per 1,000 smokers (0.3 LYs per quitter) receiving text-based support, and 29 QALYs are gained (0.5 QALYs per quitter). The deterministic sensitivity analysis indicated that changes in individual model parameters did not alter the conclusion that this is a cost-effective intervention. Similarly, the probabilistic sensitivity analysis indicated a ensuremath>90 % chance that the intervention will be cost saving. INTERPRETATION: This study shows that under a wide variety of conditions, personalised smoking cessation advice and support by mobile phone message is both beneficial for health and cost saving to a health system.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: The txt2stop trial has shown that mobile-phone-based smoking cessation support doubles biochemically validated quitting at 6 months. This study examines the cost-effectiveness of smoking cessation support delivered by mobile phone text messaging. METHODS: The lifetime incremental costs and benefits of adding text-based support to current practice are estimated from a UK NHS perspective using a Markov model. The cost-effectiveness was measured in terms of cost per quitter, cost per life year gained and cost per QALY gained. As in previous studies, smokers are assumed to face a higher risk of experiencing the following five diseases: lung cancer, stroke, myocardial infarction, chronic obstructive pulmonary disease, and coronary heart disease (i.e. the main fatal or disabling, but by no means the only, adverse effects of prolonged smoking). The treatment costs and health state values associated with these diseases were identified from the literature. The analysis was based on the age and gender distribution observed in the txt2stop trial. Effectiveness and cost parameters were varied in deterministic sensitivity analyses, and a probabilistic sensitivity analysis was also performed. FINDINGS: The cost of text-based support per 1,000 enrolled smokers is pounds16,120, which, given an estimated 58 additional quitters at 6 months, equates to pounds278 per quitter. However, when the future NHS costs saved (as a result of reduced smoking) are included, text-based support would be cost saving. It is estimated that 18 LYs are gained per 1,000 smokers (0.3 LYs per quitter) receiving text-based support, and 29 QALYs are gained (0.5 QALYs per quitter). The deterministic sensitivity analysis indicated that changes in individual model parameters did not alter the conclusion that this is a cost-effective intervention. Similarly, the probabilistic sensitivity analysis indicated a ensuremath>90 % chance that the intervention will be cost saving. INTERPRETATION: This study shows that under a wide variety of conditions, personalised smoking cessation advice and support by mobile phone message is both beneficial for health and cost saving to a health system.
Hemingway, Harry; Croft, Peter; Perel, Pablo; Hayden, Jill A; Abrams, Keith; Timmis, Adam; Briggs, Andrew; Udumyan, Ruzan; Moons, Karel GM; Steyerberg, Ewout W; Roberts, Ian; Schroter, Sara; Altman, Douglas G; Riley, Richard D; Group, PROGRESS
Prognosis research strategy (PROGRESS) 1: a framework for researching clinical outcomes. Journal Article
In: BMJ (Clinical research ed), vol. 346, no. feb05, pp. e5595–, 2013.
@article{lshtm705552,
title = {Prognosis research strategy (PROGRESS) 1: a framework for researching clinical outcomes.},
author = {Harry Hemingway and Peter Croft and Pablo Perel and Jill A Hayden and Keith Abrams and Adam Timmis and Andrew Briggs and Ruzan Udumyan and Karel GM Moons and Ewout W Steyerberg and Ian Roberts and Sara Schroter and Douglas G Altman and Richard D Riley and PROGRESS Group},
url = {http://researchonline.lshtm.ac.uk/id/eprint/705552/},
year = {2013},
date = {2013-01-01},
journal = {BMJ (Clinical research ed)},
volume = {346},
number = {feb05},
pages = {e5595--},
publisher = {BMJ Publishing Group},
abstract = {The PROGRESS series (www.progress-partnership.org) sets out a framework of four interlinked prognosis research themes and provides examples from several disease fields to show why evidence from prognosis research is crucial to inform all points in the translation of biomedical and health related research into better patient outcomes. Recommendations are made in each of the four papers to improve current research standards What is prognosis research? Prognosis research seeks to understand and improve future outcomes in people with a given disease or health condition. However, there is increasing evidence that prognosis research standards need to be improved Why is prognosis research important? More people now live with disease and conditions that impair health than at any other time in history; prognosis research provides crucial evidence for translating findings from the laboratory to humans, and from clinical research to clinical practice This first article introduces the framework of four interlinked prognosis research themes and then focuses on the first of the themes - fundamental prognosis research, studies that aim to describe and explain future outcomes in relation to current diagnostic and treatment practices, often in relation to quality of care Fundamental prognosis research provides evidence informing healthcare and public health policy, the design and interpretation of randomised trials, and the impact of diagnostic tests on future outcome. It can inform new definitions of disease, may identify unanticipated benefits or harms of interventions, and clarify where new interventions are required to improve prognosis.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The PROGRESS series (www.progress-partnership.org) sets out a framework of four interlinked prognosis research themes and provides examples from several disease fields to show why evidence from prognosis research is crucial to inform all points in the translation of biomedical and health related research into better patient outcomes. Recommendations are made in each of the four papers to improve current research standards What is prognosis research? Prognosis research seeks to understand and improve future outcomes in people with a given disease or health condition. However, there is increasing evidence that prognosis research standards need to be improved Why is prognosis research important? More people now live with disease and conditions that impair health than at any other time in history; prognosis research provides crucial evidence for translating findings from the laboratory to humans, and from clinical research to clinical practice This first article introduces the framework of four interlinked prognosis research themes and then focuses on the first of the themes - fundamental prognosis research, studies that aim to describe and explain future outcomes in relation to current diagnostic and treatment practices, often in relation to quality of care Fundamental prognosis research provides evidence informing healthcare and public health policy, the design and interpretation of randomised trials, and the impact of diagnostic tests on future outcome. It can inform new definitions of disease, may identify unanticipated benefits or harms of interventions, and clarify where new interventions are required to improve prognosis.
Ker, Katharine; Beecher, Deirdre; Roberts, Ian
Topical application of tranexamic acid for the reduction of bleeding. Journal Article
In: The Cochrane database of systematic reviews, vol. 7, no. 7, pp. CD010562–, 2013.
@article{lshtm1105220,
title = {Topical application of tranexamic acid for the reduction of bleeding.},
author = {Katharine Ker and Deirdre Beecher and Ian Roberts},
url = {http://researchonline.lshtm.ac.uk/id/eprint/1105220/},
year = {2013},
date = {2013-01-01},
journal = {The Cochrane database of systematic reviews},
volume = {7},
number = {7},
pages = {CD010562--},
publisher = {Cochrane Collaboration},
abstract = {BACKGROUND: Intravenous tranexamic acid reduces bleeding in surgery, however, its effect on the risk of thromboembolic events is uncertain and an increased risk remains a theoretical concern. Because there is less systemic absorption following topical administration, the direct application of tranexamic acid to the bleeding surface has the potential to reduce bleeding with minimal systemic effects. OBJECTIVES: To assess the effects of the topical administration of tranexamic acid in the control of bleeding. SEARCH METHODS: We searched the Cochrane Injuries Group Specialised Register; Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library; Ovid MEDLINE?, Ovid MEDLINE? In-Process & Other Non-Indexed Citations, Ovid MEDLINE? Daily and Ovid OLDMEDLINE?; Embase Classic + Embase (OvidSP); PubMed and ISI Web of Science (including Science Citation Index Expanded and Social Science Citation Index (SCI-EXPANDED & CPCI-S)). We also searched online trials registers to identify ongoing or unpublished trials. The search was run on the 31st May 2013. SELECTION CRITERIA: Randomised controlled trials comparing topical tranexamic acid with no topical tranexamic acid or placebo in bleeding patients. DATA COLLECTION AND ANALYSIS: Two authors examined the titles and abstracts of citations from the electronic databases for eligibility. Two authors extracted the data and assessed the risk of bias for each trial. Outcome measures of interest were blood loss, mortality, thromboembolic events (myocardial infarction, stroke, deep vein thrombosis and pulmonary embolism) and receipt of a blood transfusion. MAIN RESULTS: We included 29 trials involving 2612 participants. Twenty-eight trials involved patients undergoing surgery and one trial involved patients with epistaxis (nosebleed). Tranexamic acid (TXA) reduced blood loss by 29% (pooled ratio 0.71, 95% confidence interval (CI) 0.69 to 0.72; P ensuremath< 0.0001). There was uncertainty regarding the effect on death (risk ratio (RR) 0.28, 95% CI 0.06 to 1.34; P = 0.11), myocardial infarction (RR 0.33, 95% CI 0.04 to 3.08; P = 0.33), stroke (RR 0.33, 95% CI 0.01 to 7.96; P = 0.49), deep vein thrombosis (RR 0.69, 95% CI 0.31 to 1.57; P = 0.38) and pulmonary embolism (RR 0.52, 95% CI 0.09 to 3.15; P = 0.48). TXA reduced the risk of receiving a blood transfusion by a relative 45% (RR 0.55, 95% CI 0.55 to 0.46; P ensuremath< 0.0001). There was substantial statistical heterogeneity between trials for the blood loss and blood transfusion outcomes. AUTHORS' CONCLUSIONS: There is reliable evidence that topical application of tranexamic acid reduces bleeding and blood transfusion in surgical patients, however the effect on the risk of thromboembolic events is uncertain. The effects of topical tranexamic acid in patients with bleeding from non-surgical causes has yet to be reliably assessed. Further high-quality trials are warranted to resolve these uncertainties before topical tranexamic acid can be recommended for routine use.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Intravenous tranexamic acid reduces bleeding in surgery, however, its effect on the risk of thromboembolic events is uncertain and an increased risk remains a theoretical concern. Because there is less systemic absorption following topical administration, the direct application of tranexamic acid to the bleeding surface has the potential to reduce bleeding with minimal systemic effects. OBJECTIVES: To assess the effects of the topical administration of tranexamic acid in the control of bleeding. SEARCH METHODS: We searched the Cochrane Injuries Group Specialised Register; Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library; Ovid MEDLINE?, Ovid MEDLINE? In-Process & Other Non-Indexed Citations, Ovid MEDLINE? Daily and Ovid OLDMEDLINE?; Embase Classic + Embase (OvidSP); PubMed and ISI Web of Science (including Science Citation Index Expanded and Social Science Citation Index (SCI-EXPANDED & CPCI-S)). We also searched online trials registers to identify ongoing or unpublished trials. The search was run on the 31st May 2013. SELECTION CRITERIA: Randomised controlled trials comparing topical tranexamic acid with no topical tranexamic acid or placebo in bleeding patients. DATA COLLECTION AND ANALYSIS: Two authors examined the titles and abstracts of citations from the electronic databases for eligibility. Two authors extracted the data and assessed the risk of bias for each trial. Outcome measures of interest were blood loss, mortality, thromboembolic events (myocardial infarction, stroke, deep vein thrombosis and pulmonary embolism) and receipt of a blood transfusion. MAIN RESULTS: We included 29 trials involving 2612 participants. Twenty-eight trials involved patients undergoing surgery and one trial involved patients with epistaxis (nosebleed). Tranexamic acid (TXA) reduced blood loss by 29% (pooled ratio 0.71, 95% confidence interval (CI) 0.69 to 0.72; P ensuremath< 0.0001). There was uncertainty regarding the effect on death (risk ratio (RR) 0.28, 95% CI 0.06 to 1.34; P = 0.11), myocardial infarction (RR 0.33, 95% CI 0.04 to 3.08; P = 0.33), stroke (RR 0.33, 95% CI 0.01 to 7.96; P = 0.49), deep vein thrombosis (RR 0.69, 95% CI 0.31 to 1.57; P = 0.38) and pulmonary embolism (RR 0.52, 95% CI 0.09 to 3.15; P = 0.48). TXA reduced the risk of receiving a blood transfusion by a relative 45% (RR 0.55, 95% CI 0.55 to 0.46; P ensuremath< 0.0001). There was substantial statistical heterogeneity between trials for the blood loss and blood transfusion outcomes. AUTHORS' CONCLUSIONS: There is reliable evidence that topical application of tranexamic acid reduces bleeding and blood transfusion in surgical patients, however the effect on the risk of thromboembolic events is uncertain. The effects of topical tranexamic acid in patients with bleeding from non-surgical causes has yet to be reliably assessed. Further high-quality trials are warranted to resolve these uncertainties before topical tranexamic acid can be recommended for routine use.
Roberts, I; Shakur-Still, Haleema; Coats, T; Hunt, B; Balogun, E; Barnetson, L; Cook, L; Kawahara, T; Perel, P; Prieto-Merino, D; Ramos, M; Cairns, J; Guerriero, C
In: Health technology assessment (Winchester, England), vol. 17, no. 10, pp. 1–79, 2013.
@article{lshtm660643,
title = {The CRASH-2 trial: a randomised controlled trial and economic evaluation of the effects of tranexamic acid on death, vascular occlusive events and transfusion requirement in bleeding trauma patients.},
author = {I Roberts and Haleema Shakur-Still and T Coats and B Hunt and E Balogun and L Barnetson and L Cook and T Kawahara and P Perel and D Prieto-Merino and M Ramos and J Cairns and C Guerriero},
url = {http://researchonline.lshtm.ac.uk/id/eprint/660643/},
year = {2013},
date = {2013-01-01},
journal = {Health technology assessment (Winchester, England)},
volume = {17},
number = {10},
pages = {1--79},
publisher = {NIHR Journals Library},
abstract = {BACKGROUND Among trauma patients who survive to reach hospital, exsanguination is a common cause of death. A widely practicable treatment that reduces blood loss after trauma could prevent thousands of premature deaths each year. The CRASH-2 trial aimed to determine the effect of the early administration of tranexamic acid on death and transfusion requirement in bleeding trauma patients. In addition, the effort of tranexamic acid on the risk of vascular occlusive events was assessed.
OBJECTIVE Tranexamic acid (TXA) reduces bleeding in patients undergoing elective surgery. We assessed the effects and cost-effectiveness of the early administration of a short course of TXA on death, vascular occlusive events and the receipt of blood transfusion in trauma patients.
DESIGN Randomised placebo-controlled trial and economic evaluation. Randomisation was balanced by centre, with an allocation sequence based on a block size of eight, generated with a computer random number generator. Both participants and study staff (site investigators and trial co-ordinating centre staff) were masked to treatment allocation. All analyses were by intention to treat. A Markov model was used to assess cost-effectiveness. The health outcome was the number of life-years (LYs) gained. Cost data were obtained from hospitals, the World Health Organization database and UK reference costs. Cost-effectiveness was measured in international dollars ($) per LY. Deterministic and probabilistic sensitivity analyses were performed to test the robustness of the results to model assumptions.
SETTING Two hundred and seventy-four hospitals in 40 countries.
PARTICIPANTS Adult trauma patients (n = 20,211) with, or at risk of, significant bleeding who were within 8 hours of injury.
INTERVENTIONS Tranexamic acid (loading dose 1 g over 10 minutes then infusion of 1 g over 8 hours) or matching placebo.
MAIN OUTCOME MEASURES The primary outcome was death in hospital within 4 weeks of injury, and was described with the following categories: bleeding, vascular occlusion (myocardial infarction, stroke and pulmonary embolism), multiorgan failure, head injury and other.
RESULTS Patients were allocated to TXA (n = 10,096) and to placebo (n = 10,115), of whom 10,060 and 10,067 patients, respectively, were analysed. All-cause mortality at 28 days was significantly reduced by TXA [1463 patients (14.5%) in the TXA group vs 1613 patients (16.0%) in the placebo group; relative risk (RR) 0.91; 95% confidence interval (CI) 0.85 to 0.97; p = 0.0035]. The risk of death due to bleeding was significantly reduced [489 patients (4.9%) died in the TXA group vs 574 patients (5.7%) in the placebo group; RR 0.85; 95% CI 0.76 to 0.96; p = 0.0077]. We recorded strong evidence that the effect of TXA on death due to bleeding varied according to the time from injury to treatment (test for interaction p < 0.0001). Early treatment ($łeq$ 1 hour from injury) significantly reduced the risk of death due to bleeding [198 out of 3747 patients (5.3%) died in the TXA group vs 286 out of 3704 patients (7.7%) in the placebo group; RR 0.68; 95% CI 0.57 to 0.82; p < 0.0001]. Treatment given between 1 and 3 hours also reduced the risk of death due to bleeding [147 out of 3037 patients (4.8%) died in the TXA group vs 184 out of 2996 patients (6.1%) in the placebo group; RR 0.79; 95% CI 0.64 to 0.97; p = 0.03]. Treatment given after 3 hours seemed to increase the risk of death due to bleeding [144 out of 3272 patients (4.4%) died in the TXA group vs 103 out of 3362 patients (3.1%) in the placebo group; RR 1.44; 95% CI1.12 to 1.84; p = 0.004]. We recorded no evidence that the effect of TXA on death due to bleeding varied by systolic blood pressure, Glasgow Coma Scale score or type of injury. Administering TXA to bleeding trauma patients within 3 hours of injury saved an estimated 755 LYs per 1000 trauma patients in the UK. The cost of giving TXA to 1000 patients was estimated at $30,830. The incremental cost of giving TXA compared with not giving TXA was $48,002. The incremental cost per LY gained of administering TXA was $64.
CONCLUSIONS Early administration of TXA safely reduced the risk of death in bleeding trauma patients and is highly cost-effective. Treatment beyond 3 hours of injury is unlikely to be effective. Future work [the Clinical Randomisation of an Antifibrinolytic in Significant Head injury-3 (CRASH-3) trial] will evaluate the effectiveness and safety of TXA in the treatments of isolated traumatic brain injury (http://crash3.lshtm.ac.uk/).
TRIAL REGISTRATION Current Controlled Trials ISRCTN86750102, ClinicalTrials.gov NCT00375258 and South African Clinical Trial Register DOH-27-0607-1919.
FUNDING The project was funded by the Bupa Foundation, the J P Moulton Charitable Foundation and the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 10. See HTA programme website for further project information.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND Among trauma patients who survive to reach hospital, exsanguination is a common cause of death. A widely practicable treatment that reduces blood loss after trauma could prevent thousands of premature deaths each year. The CRASH-2 trial aimed to determine the effect of the early administration of tranexamic acid on death and transfusion requirement in bleeding trauma patients. In addition, the effort of tranexamic acid on the risk of vascular occlusive events was assessed.
OBJECTIVE Tranexamic acid (TXA) reduces bleeding in patients undergoing elective surgery. We assessed the effects and cost-effectiveness of the early administration of a short course of TXA on death, vascular occlusive events and the receipt of blood transfusion in trauma patients.
DESIGN Randomised placebo-controlled trial and economic evaluation. Randomisation was balanced by centre, with an allocation sequence based on a block size of eight, generated with a computer random number generator. Both participants and study staff (site investigators and trial co-ordinating centre staff) were masked to treatment allocation. All analyses were by intention to treat. A Markov model was used to assess cost-effectiveness. The health outcome was the number of life-years (LYs) gained. Cost data were obtained from hospitals, the World Health Organization database and UK reference costs. Cost-effectiveness was measured in international dollars ($) per LY. Deterministic and probabilistic sensitivity analyses were performed to test the robustness of the results to model assumptions.
SETTING Two hundred and seventy-four hospitals in 40 countries.
PARTICIPANTS Adult trauma patients (n = 20,211) with, or at risk of, significant bleeding who were within 8 hours of injury.
INTERVENTIONS Tranexamic acid (loading dose 1 g over 10 minutes then infusion of 1 g over 8 hours) or matching placebo.
MAIN OUTCOME MEASURES The primary outcome was death in hospital within 4 weeks of injury, and was described with the following categories: bleeding, vascular occlusion (myocardial infarction, stroke and pulmonary embolism), multiorgan failure, head injury and other.
RESULTS Patients were allocated to TXA (n = 10,096) and to placebo (n = 10,115), of whom 10,060 and 10,067 patients, respectively, were analysed. All-cause mortality at 28 days was significantly reduced by TXA [1463 patients (14.5%) in the TXA group vs 1613 patients (16.0%) in the placebo group; relative risk (RR) 0.91; 95% confidence interval (CI) 0.85 to 0.97; p = 0.0035]. The risk of death due to bleeding was significantly reduced [489 patients (4.9%) died in the TXA group vs 574 patients (5.7%) in the placebo group; RR 0.85; 95% CI 0.76 to 0.96; p = 0.0077]. We recorded strong evidence that the effect of TXA on death due to bleeding varied according to the time from injury to treatment (test for interaction p < 0.0001). Early treatment ($łeq$ 1 hour from injury) significantly reduced the risk of death due to bleeding [198 out of 3747 patients (5.3%) died in the TXA group vs 286 out of 3704 patients (7.7%) in the placebo group; RR 0.68; 95% CI 0.57 to 0.82; p < 0.0001]. Treatment given between 1 and 3 hours also reduced the risk of death due to bleeding [147 out of 3037 patients (4.8%) died in the TXA group vs 184 out of 2996 patients (6.1%) in the placebo group; RR 0.79; 95% CI 0.64 to 0.97; p = 0.03]. Treatment given after 3 hours seemed to increase the risk of death due to bleeding [144 out of 3272 patients (4.4%) died in the TXA group vs 103 out of 3362 patients (3.1%) in the placebo group; RR 1.44; 95% CI1.12 to 1.84; p = 0.004]. We recorded no evidence that the effect of TXA on death due to bleeding varied by systolic blood pressure, Glasgow Coma Scale score or type of injury. Administering TXA to bleeding trauma patients within 3 hours of injury saved an estimated 755 LYs per 1000 trauma patients in the UK. The cost of giving TXA to 1000 patients was estimated at $30,830. The incremental cost of giving TXA compared with not giving TXA was $48,002. The incremental cost per LY gained of administering TXA was $64.
CONCLUSIONS Early administration of TXA safely reduced the risk of death in bleeding trauma patients and is highly cost-effective. Treatment beyond 3 hours of injury is unlikely to be effective. Future work [the Clinical Randomisation of an Antifibrinolytic in Significant Head injury-3 (CRASH-3) trial] will evaluate the effectiveness and safety of TXA in the treatments of isolated traumatic brain injury (http://crash3.lshtm.ac.uk/).
TRIAL REGISTRATION Current Controlled Trials ISRCTN86750102, ClinicalTrials.gov NCT00375258 and South African Clinical Trial Register DOH-27-0607-1919.
FUNDING The project was funded by the Bupa Foundation, the J P Moulton Charitable Foundation and the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 10. See HTA programme website for further project information.
OBJECTIVE Tranexamic acid (TXA) reduces bleeding in patients undergoing elective surgery. We assessed the effects and cost-effectiveness of the early administration of a short course of TXA on death, vascular occlusive events and the receipt of blood transfusion in trauma patients.
DESIGN Randomised placebo-controlled trial and economic evaluation. Randomisation was balanced by centre, with an allocation sequence based on a block size of eight, generated with a computer random number generator. Both participants and study staff (site investigators and trial co-ordinating centre staff) were masked to treatment allocation. All analyses were by intention to treat. A Markov model was used to assess cost-effectiveness. The health outcome was the number of life-years (LYs) gained. Cost data were obtained from hospitals, the World Health Organization database and UK reference costs. Cost-effectiveness was measured in international dollars ($) per LY. Deterministic and probabilistic sensitivity analyses were performed to test the robustness of the results to model assumptions.
SETTING Two hundred and seventy-four hospitals in 40 countries.
PARTICIPANTS Adult trauma patients (n = 20,211) with, or at risk of, significant bleeding who were within 8 hours of injury.
INTERVENTIONS Tranexamic acid (loading dose 1 g over 10 minutes then infusion of 1 g over 8 hours) or matching placebo.
MAIN OUTCOME MEASURES The primary outcome was death in hospital within 4 weeks of injury, and was described with the following categories: bleeding, vascular occlusion (myocardial infarction, stroke and pulmonary embolism), multiorgan failure, head injury and other.
RESULTS Patients were allocated to TXA (n = 10,096) and to placebo (n = 10,115), of whom 10,060 and 10,067 patients, respectively, were analysed. All-cause mortality at 28 days was significantly reduced by TXA [1463 patients (14.5%) in the TXA group vs 1613 patients (16.0%) in the placebo group; relative risk (RR) 0.91; 95% confidence interval (CI) 0.85 to 0.97; p = 0.0035]. The risk of death due to bleeding was significantly reduced [489 patients (4.9%) died in the TXA group vs 574 patients (5.7%) in the placebo group; RR 0.85; 95% CI 0.76 to 0.96; p = 0.0077]. We recorded strong evidence that the effect of TXA on death due to bleeding varied according to the time from injury to treatment (test for interaction p < 0.0001). Early treatment ($łeq$ 1 hour from injury) significantly reduced the risk of death due to bleeding [198 out of 3747 patients (5.3%) died in the TXA group vs 286 out of 3704 patients (7.7%) in the placebo group; RR 0.68; 95% CI 0.57 to 0.82; p < 0.0001]. Treatment given between 1 and 3 hours also reduced the risk of death due to bleeding [147 out of 3037 patients (4.8%) died in the TXA group vs 184 out of 2996 patients (6.1%) in the placebo group; RR 0.79; 95% CI 0.64 to 0.97; p = 0.03]. Treatment given after 3 hours seemed to increase the risk of death due to bleeding [144 out of 3272 patients (4.4%) died in the TXA group vs 103 out of 3362 patients (3.1%) in the placebo group; RR 1.44; 95% CI1.12 to 1.84; p = 0.004]. We recorded no evidence that the effect of TXA on death due to bleeding varied by systolic blood pressure, Glasgow Coma Scale score or type of injury. Administering TXA to bleeding trauma patients within 3 hours of injury saved an estimated 755 LYs per 1000 trauma patients in the UK. The cost of giving TXA to 1000 patients was estimated at $30,830. The incremental cost of giving TXA compared with not giving TXA was $48,002. The incremental cost per LY gained of administering TXA was $64.
CONCLUSIONS Early administration of TXA safely reduced the risk of death in bleeding trauma patients and is highly cost-effective. Treatment beyond 3 hours of injury is unlikely to be effective. Future work [the Clinical Randomisation of an Antifibrinolytic in Significant Head injury-3 (CRASH-3) trial] will evaluate the effectiveness and safety of TXA in the treatments of isolated traumatic brain injury (http://crash3.lshtm.ac.uk/).
TRIAL REGISTRATION Current Controlled Trials ISRCTN86750102, ClinicalTrials.gov NCT00375258 and South African Clinical Trial Register DOH-27-0607-1919.
FUNDING The project was funded by the Bupa Foundation, the J P Moulton Charitable Foundation and the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 10. See HTA programme website for further project information.
Roberts, I; Shakur-Still, Haleema; Coats, T; Hunt, B; Balogun, E; Barnetson, L; Cook, L; Kawahara, T; Perel, P; Prieto-Merino, D; Ramos, M; Cairns, J; Guerriero, C
In: Health technology assessment (Winchester, England), vol. 17, no. 10, pp. 1–79, 2013.
@article{lshtm1012258,
title = {The CRASH-2 trial: a randomised controlled trial and economic evaluation of the effects of tranexamic acid on death, vascular occlusive events and transfusion requirement in bleeding trauma patients.},
author = {I Roberts and Haleema Shakur-Still and T Coats and B Hunt and E Balogun and L Barnetson and L Cook and T Kawahara and P Perel and D Prieto-Merino and M Ramos and J Cairns and C Guerriero},
url = {http://researchonline.lshtm.ac.uk/id/eprint/1012258/},
year = {2013},
date = {2013-01-01},
journal = {Health technology assessment (Winchester, England)},
volume = {17},
number = {10},
pages = {1--79},
publisher = {NIHR Journals Library},
abstract = {BACKGROUND: Among trauma patients who survive to reach hospital, exsanguination is a common cause of death. A widely practicable treatment that reduces blood loss after trauma could prevent thousands of premature deaths each year. The CRASH-2 trial aimed to determine the effect of the early administration of tranexamic acid on death and transfusion requirement in bleeding trauma patients. In addition, the effort of tranexamic acid on the risk of vascular occlusive events was assessed. OBJECTIVE: Tranexamic acid (TXA) reduces bleeding in patients undergoing elective surgery. We assessed the effects and cost-effectiveness of the early administration of a short course of TXA on death, vascular occlusive events and the receipt of blood transfusion in trauma patients. DESIGN: Randomised placebo-controlled trial and economic evaluation. Randomisation was balanced by centre, with an allocation sequence based on a block size of eight, generated with a computer random number generator. Both participants and study staff (site investigators and trial co-ordinating centre staff) were masked to treatment allocation. All analyses were by intention to treat. A Markov model was used to assess cost-effectiveness. The health outcome was the number of life-years (LYs) gained. Cost data were obtained from hospitals, the World Health Organization database and UK reference costs. Cost-effectiveness was measured in international dollars ($) per LY. Deterministic and probabilistic sensitivity analyses were performed to test the robustness of the results to model assumptions. SETTING: Two hundred and seventy-four hospitals in 40 countries. PARTICIPANTS: Adult trauma patients (n = 20,211) with, or at risk of, significant bleeding who were within 8 hours of injury. INTERVENTIONS: Tranexamic acid (loading dose 1 g over 10 minutes then infusion of 1 g over 8 hours) or matching placebo. MAIN OUTCOME MEASURES: The primary outcome was death in hospital within 4 weeks of injury, and was described with the following categories: bleeding, vascular occlusion (myocardial infarction, stroke and pulmonary embolism), multiorgan failure, head injury and other. RESULTS: Patients were allocated to TXA (n = 10,096) and to placebo (n = 10,115), of whom 10,060 and 10,067 patients, respectively, were analysed. All-cause mortality at 28 days was significantly reduced by TXA [1463 patients (14.5%) in the TXA group vs 1613 patients (16.0%) in the placebo group; relative risk (RR) 0.91; 95% confidence interval (CI) 0.85 to 0.97; p = 0.0035]. The risk of death due to bleeding was significantly reduced [489 patients (4.9%) died in the TXA group vs 574 patients (5.7%) in the placebo group; RR 0.85; 95% CI 0.76 to 0.96; p = 0.0077]. We recorded strong evidence that the effect of TXA on death due to bleeding varied according to the time from injury to treatment (test for interaction p ensuremath< 0.0001). Early treatment ($łeq$ 1 hour from injury) significantly reduced the risk of death due to bleeding [198 out of 3747 patients (5.3%) died in the TXA group vs 286 out of 3704 patients (7.7%) in the placebo group; RR 0.68; 95% CI 0.57 to 0.82; p ensuremath< 0.0001]. Treatment given between 1 and 3 hours also reduced the risk of death due to bleeding [147 out of 3037 patients (4.8%) died in the TXA group vs 184 out of 2996 patients (6.1%) in the placebo group; RR 0.79; 95% CI 0.64 to 0.97; p = 0.03]. Treatment given after 3 hours seemed to increase the risk of death due to bleeding [144 out of 3272 patients (4.4%) died in the TXA group vs 103 out of 3362 patients (3.1%) in the placebo group; RR 1.44; 95% CI1.12 to 1.84; p = 0.004]. We recorded no evidence that the effect of TXA on death due to bleeding varied by systolic blood pressure, Glasgow Coma Scale score or type of injury. Administering TXA to bleeding trauma patients within 3 hours of injury saved an estimated 755 LYs per 1000 trauma patients in the UK. The cost of giving TXA to 1000 patients was estimated at $30,830. The incremental cost of giving TXA compared with not giving TXA was $48,002. The incremental cost per LY gained of administering TXA was $64. CONCLUSIONS: Early administration of TXA safely reduced the risk of death in bleeding trauma patients and is highly cost-effective. Treatment beyond 3 hours of injury is unlikely to be effective. Future work [the Clinical Randomisation of an Antifibrinolytic in Significant Head injury-3 (CRASH-3) trial] will evaluate the effectiveness and safety of TXA in the treatments of isolated traumatic brain injury (http://crash3.lshtm.ac.uk/). TRIAL REGISTRATION: Current Controlled Trials ISRCTN86750102, ClinicalTrials.gov NCT00375258 and South African Clinical Trial Register DOH-27-0607-1919. FUNDING: The project was funded by the Bupa Foundation, the J P Moulton Charitable Foundation and the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 10. See HTA programme website for further project information.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Among trauma patients who survive to reach hospital, exsanguination is a common cause of death. A widely practicable treatment that reduces blood loss after trauma could prevent thousands of premature deaths each year. The CRASH-2 trial aimed to determine the effect of the early administration of tranexamic acid on death and transfusion requirement in bleeding trauma patients. In addition, the effort of tranexamic acid on the risk of vascular occlusive events was assessed. OBJECTIVE: Tranexamic acid (TXA) reduces bleeding in patients undergoing elective surgery. We assessed the effects and cost-effectiveness of the early administration of a short course of TXA on death, vascular occlusive events and the receipt of blood transfusion in trauma patients. DESIGN: Randomised placebo-controlled trial and economic evaluation. Randomisation was balanced by centre, with an allocation sequence based on a block size of eight, generated with a computer random number generator. Both participants and study staff (site investigators and trial co-ordinating centre staff) were masked to treatment allocation. All analyses were by intention to treat. A Markov model was used to assess cost-effectiveness. The health outcome was the number of life-years (LYs) gained. Cost data were obtained from hospitals, the World Health Organization database and UK reference costs. Cost-effectiveness was measured in international dollars ($) per LY. Deterministic and probabilistic sensitivity analyses were performed to test the robustness of the results to model assumptions. SETTING: Two hundred and seventy-four hospitals in 40 countries. PARTICIPANTS: Adult trauma patients (n = 20,211) with, or at risk of, significant bleeding who were within 8 hours of injury. INTERVENTIONS: Tranexamic acid (loading dose 1 g over 10 minutes then infusion of 1 g over 8 hours) or matching placebo. MAIN OUTCOME MEASURES: The primary outcome was death in hospital within 4 weeks of injury, and was described with the following categories: bleeding, vascular occlusion (myocardial infarction, stroke and pulmonary embolism), multiorgan failure, head injury and other. RESULTS: Patients were allocated to TXA (n = 10,096) and to placebo (n = 10,115), of whom 10,060 and 10,067 patients, respectively, were analysed. All-cause mortality at 28 days was significantly reduced by TXA [1463 patients (14.5%) in the TXA group vs 1613 patients (16.0%) in the placebo group; relative risk (RR) 0.91; 95% confidence interval (CI) 0.85 to 0.97; p = 0.0035]. The risk of death due to bleeding was significantly reduced [489 patients (4.9%) died in the TXA group vs 574 patients (5.7%) in the placebo group; RR 0.85; 95% CI 0.76 to 0.96; p = 0.0077]. We recorded strong evidence that the effect of TXA on death due to bleeding varied according to the time from injury to treatment (test for interaction p ensuremath< 0.0001). Early treatment ($łeq$ 1 hour from injury) significantly reduced the risk of death due to bleeding [198 out of 3747 patients (5.3%) died in the TXA group vs 286 out of 3704 patients (7.7%) in the placebo group; RR 0.68; 95% CI 0.57 to 0.82; p ensuremath< 0.0001]. Treatment given between 1 and 3 hours also reduced the risk of death due to bleeding [147 out of 3037 patients (4.8%) died in the TXA group vs 184 out of 2996 patients (6.1%) in the placebo group; RR 0.79; 95% CI 0.64 to 0.97; p = 0.03]. Treatment given after 3 hours seemed to increase the risk of death due to bleeding [144 out of 3272 patients (4.4%) died in the TXA group vs 103 out of 3362 patients (3.1%) in the placebo group; RR 1.44; 95% CI1.12 to 1.84; p = 0.004]. We recorded no evidence that the effect of TXA on death due to bleeding varied by systolic blood pressure, Glasgow Coma Scale score or type of injury. Administering TXA to bleeding trauma patients within 3 hours of injury saved an estimated 755 LYs per 1000 trauma patients in the UK. The cost of giving TXA to 1000 patients was estimated at $30,830. The incremental cost of giving TXA compared with not giving TXA was $48,002. The incremental cost per LY gained of administering TXA was $64. CONCLUSIONS: Early administration of TXA safely reduced the risk of death in bleeding trauma patients and is highly cost-effective. Treatment beyond 3 hours of injury is unlikely to be effective. Future work [the Clinical Randomisation of an Antifibrinolytic in Significant Head injury-3 (CRASH-3) trial] will evaluate the effectiveness and safety of TXA in the treatments of isolated traumatic brain injury (http://crash3.lshtm.ac.uk/). TRIAL REGISTRATION: Current Controlled Trials ISRCTN86750102, ClinicalTrials.gov NCT00375258 and South African Clinical Trial Register DOH-27-0607-1919. FUNDING: The project was funded by the Bupa Foundation, the J P Moulton Charitable Foundation and the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 10. See HTA programme website for further project information.
Roberts, Ian
The CRASH-2 trial was not about global scientific supremacy. Journal Article
In: Lancet, vol. 382, no. 9888, pp. 207–208, 2013.
@article{lshtm1229260,
title = {The CRASH-2 trial was not about global scientific supremacy.},
author = {Ian Roberts},
url = {http://researchonline.lshtm.ac.uk/id/eprint/1229260/},
year = {2013},
date = {2013-01-01},
journal = {Lancet},
volume = {382},
number = {9888},
pages = {207--208},
publisher = {Elsevier},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Roberts, Ian
Scientific letter: could tranexamic acid use in surgery reduce perioperative myocardial infarction? Journal Article
In: Heart (British Cardiac Society), vol. 99, no. 23, pp. 1785–, 2013.
@article{lshtm1462881,
title = {Scientific letter: could tranexamic acid use in surgery reduce perioperative myocardial infarction?},
author = {Ian Roberts},
url = {http://researchonline.lshtm.ac.uk/id/eprint/1462881/},
year = {2013},
date = {2013-01-01},
journal = {Heart (British Cardiac Society)},
volume = {99},
number = {23},
pages = {1785--},
publisher = {BMJ Publishing Group},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Roberts, Ian; Jackson, Rod
Beyond disease burden: towards solution-oriented population health. Journal Article
In: Lancet, vol. 381, no. 9884, pp. 2219–2221, 2013.
@article{lshtm682477,
title = {Beyond disease burden: towards solution-oriented population health.},
author = {Ian Roberts and Rod Jackson},
url = {http://researchonline.lshtm.ac.uk/id/eprint/682477/},
year = {2013},
date = {2013-01-01},
journal = {Lancet},
volume = {381},
number = {9884},
pages = {2219--2221},
publisher = {Elsevier},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Shakur-Still, Haleema; Roberts, Ian; Piot, Peter; Horton, Richard; Krug, Etienne; Mersch, Jeannot
A promise to save 100,000 trauma patients. Journal Article
In: Lancet, vol. 380, no. 9859, pp. 2062–2063, 2013.
@article{lshtm533927,
title = {A promise to save 100,000 trauma patients.},
author = {Haleema Shakur-Still and Ian Roberts and Peter Piot and Richard Horton and Etienne Krug and Jeannot Mersch},
url = {http://researchonline.lshtm.ac.uk/id/eprint/533927/},
year = {2013},
date = {2013-01-01},
journal = {Lancet},
volume = {380},
number = {9859},
pages = {2062--2063},
publisher = {Elsevier},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Smith, Anna Jo Bodurtha; Tennison, Imogen; Roberts, Ian; Cairns, John; Free, Caroline
The carbon footprint of behavioural support services for smoking cessation. Journal Article
In: Tobacco control, vol. 22, no. 5, pp. 302–307, 2013.
@article{lshtm1152776,
title = {The carbon footprint of behavioural support services for smoking cessation.},
author = {Anna Jo Bodurtha Smith and Imogen Tennison and Ian Roberts and John Cairns and Caroline Free},
url = {http://researchonline.lshtm.ac.uk/id/eprint/1152776/},
year = {2013},
date = {2013-01-01},
journal = {Tobacco control},
volume = {22},
number = {5},
pages = {302--307},
publisher = {BMJ Publishing Group},
abstract = {OBJECTIVE: To estimate the carbon footprint of behavioural support services for smoking cessation: text message support, telephone counselling, group counselling and individual counselling. DESIGN: Carbon footprint analysis. DATA SOURCE: Publicly available data on National Health Service Stop Smoking Services and per unit carbon emissions; published effectiveness data from the txt2stop trial and systematic reviews of smoking cessation services. MAIN OUTCOME MEASURES: Carbon dioxide equivalents (CO2e) per 1000 smokers, per lifetime quitter, and per quality-adjusted life year gained, and cost-effectiveness, including social cost of carbon, of smoking cessation services. RESULTS: Emissions per 1000 participants were 8143 kg CO2e for text message support, 8619 kg CO2e for telephone counselling, 16 114 kg CO2e for group counselling and 16 372 kg CO2e for individual counselling. Emissions per intervention lifetime quitter were 636 (95% CI 455 to 958) kg CO2e for text message support, 1051 (95% CI 560 to 2873) kg CO2e for telephone counselling, 1143 (95% CI 695 to 2270) kg CO2e for group counselling and 2823 (95% CI 1688 to 6549) kg CO2e for individual counselling. Text message, telephone and group counselling remained cost-effective when cost-effectiveness analysis was revised to include the environmental and economic cost of damage from carbon emissions. CONCLUSIONS: All smoking cessation services had low emissions compared to the health gains produced. Text message support had the lowest emissions of the services evaluated. Smoking cessation services have small carbon footprints and were cost-effective after accounting for the societal costs of greenhouse gas emissions.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE: To estimate the carbon footprint of behavioural support services for smoking cessation: text message support, telephone counselling, group counselling and individual counselling. DESIGN: Carbon footprint analysis. DATA SOURCE: Publicly available data on National Health Service Stop Smoking Services and per unit carbon emissions; published effectiveness data from the txt2stop trial and systematic reviews of smoking cessation services. MAIN OUTCOME MEASURES: Carbon dioxide equivalents (CO2e) per 1000 smokers, per lifetime quitter, and per quality-adjusted life year gained, and cost-effectiveness, including social cost of carbon, of smoking cessation services. RESULTS: Emissions per 1000 participants were 8143 kg CO2e for text message support, 8619 kg CO2e for telephone counselling, 16 114 kg CO2e for group counselling and 16 372 kg CO2e for individual counselling. Emissions per intervention lifetime quitter were 636 (95% CI 455 to 958) kg CO2e for text message support, 1051 (95% CI 560 to 2873) kg CO2e for telephone counselling, 1143 (95% CI 695 to 2270) kg CO2e for group counselling and 2823 (95% CI 1688 to 6549) kg CO2e for individual counselling. Text message, telephone and group counselling remained cost-effective when cost-effectiveness analysis was revised to include the environmental and economic cost of damage from carbon emissions. CONCLUSIONS: All smoking cessation services had low emissions compared to the health gains produced. Text message support had the lowest emissions of the services evaluated. Smoking cessation services have small carbon footprints and were cost-effective after accounting for the societal costs of greenhouse gas emissions.
Smith, RD; Keogh-Brown, MR; Jensen, HT; Chalabi, Z; Dangour, AD; Davies, M; Edwards, P; Garnett, T; Givoni, M; Griffiths, UK; Hamilton, I; Jarrett, J; Roberts, I; Wilkinson, P; Woodcock, J; Haines, A
The macro-economic effects of health co-benefits associated with climate change mitigation strategies Unpublished
2013.
@unpublished{lshtm1217046,
title = {The macro-economic effects of health co-benefits associated with climate change
mitigation strategies},
author = {RD Smith and MR Keogh-Brown and HT Jensen and Z Chalabi and AD Dangour and M Davies and P Edwards and T Garnett and M Givoni and UK Griffiths and I Hamilton and J Jarrett and I Roberts and P Wilkinson and J Woodcock and A Haines},
url = {http://researchonline.lshtm.ac.uk/id/eprint/1217046/},
year = {2013},
date = {2013-01-01},
abstract = {The UK government has specific targets for greenhouse gas (GHG) emission reduction to
lower the risk of dangerous climate change. Strategies to reduce GHG emissions are
sometimes perceived as expensive and difficult to implement but previous work has
demonstrated significant potential health co-benefits from ?Active Travel and low carbon
driving?, ?Housing Insulation/Ventilation?, and ?Healthy Diet? scenarios which may be
attractive to policymakers. Here a Computable General Equilibrium model is used to assess
the financial effects of such health co-benefits on the wider economy including changes in
labour force, social security payments and healthcare costs averted. Results suggest that for
all scenarios the financial impacts of the health co-benefits will be positive and increased
active travel in particular is likely to make a substantial contribution, largely due to health
care costs averted.
Strategies to reduce GHG emissions and improve health are likely to result in substantial and
increasing positive contributions to the economy which may offset some potential economic
costs and thereby be seen more favourably in times of economic austerity.},
keywords = {},
pubstate = {published},
tppubtype = {unpublished}
}
The UK government has specific targets for greenhouse gas (GHG) emission reduction to
lower the risk of dangerous climate change. Strategies to reduce GHG emissions are
sometimes perceived as expensive and difficult to implement but previous work has
demonstrated significant potential health co-benefits from ?Active Travel and low carbon
driving?, ?Housing Insulation/Ventilation?, and ?Healthy Diet? scenarios which may be
attractive to policymakers. Here a Computable General Equilibrium model is used to assess
the financial effects of such health co-benefits on the wider economy including changes in
labour force, social security payments and healthcare costs averted. Results suggest that for
all scenarios the financial impacts of the health co-benefits will be positive and increased
active travel in particular is likely to make a substantial contribution, largely due to health
care costs averted.
Strategies to reduce GHG emissions and improve health are likely to result in substantial and
increasing positive contributions to the economy which may offset some potential economic
costs and thereby be seen more favourably in times of economic austerity.
lower the risk of dangerous climate change. Strategies to reduce GHG emissions are
sometimes perceived as expensive and difficult to implement but previous work has
demonstrated significant potential health co-benefits from ?Active Travel and low carbon
driving?, ?Housing Insulation/Ventilation?, and ?Healthy Diet? scenarios which may be
attractive to policymakers. Here a Computable General Equilibrium model is used to assess
the financial effects of such health co-benefits on the wider economy including changes in
labour force, social security payments and healthcare costs averted. Results suggest that for
all scenarios the financial impacts of the health co-benefits will be positive and increased
active travel in particular is likely to make a substantial contribution, largely due to health
care costs averted.
Strategies to reduce GHG emissions and improve health are likely to result in substantial and
increasing positive contributions to the economy which may offset some potential economic
costs and thereby be seen more favourably in times of economic austerity.
2012
Roberts, Ian; Sydenham, Emma
Barbiturates for acute traumatic brain injury. Journal Article
In: The Cochrane database of systematic reviews, vol. 12, pp. CD000033–, 2012.
@article{lshtm512813,
title = {Barbiturates for acute traumatic brain injury.},
author = {Ian Roberts and Emma Sydenham},
url = {http://researchonline.lshtm.ac.uk/id/eprint/512813/},
year = {2012},
date = {2012-12-01},
journal = {The Cochrane database of systematic reviews},
volume = {12},
pages = {CD000033--},
publisher = {Cochrane Collaboration},
abstract = {BACKGROUND: Raised intracranial pressure (ICP) is an important complication of severe brain injury, and is associated with high mortality. Barbiturates are believed to reduce ICP by suppressing cerebral metabolism, thus reducing cerebral metabolic demands and cerebral blood volume. However, barbiturates also reduce blood pressure and may, therefore, adversely effect cerebral perfusion pressure. OBJECTIVES: To assess the effects of barbiturates in reducing mortality, disability and raised ICP in people with acute traumatic brain injury. To quantify any side effects resulting from the use of barbiturates. SEARCH METHODS: The following electronic databases were searched on 26 September 2012: CENTRAL (The Cochrane Library), MEDLINE (Ovid SP), PubMed, EMBASE (Ovid SP), PsycINFO (Ovid SP), PsycEXTRA (Ovid SP), ISI Web of Science: Science Citation Index and Conference Proceedings Citation Index-Science. Searching was not restricted by date, language or publication status. We also searched the reference lists of the included trials and review articles. We contacted researchers for information on ongoing studies. SELECTION CRITERIA: Randomised controlled trials of one or more of the barbiturate class of drugs, where study participants had clinically diagnosed acute traumatic brain injury of any severity. DATA COLLECTION AND ANALYSIS: Two review authors screened the search results, extracted data and assessed the risk of bias in the trials. MAIN RESULTS: Data from seven trials involving 341 people are included in this review.For barbiturates versus no barbiturate, the pooled risk ratio (RR) of death from three trials was 1.09 (95% confidence interval (CI) 0.81 to 1.47). Death or disability, measured using the Glasgow Outcome Scale was assessed in two trials, the RR with barbiturates was 1.15 (95% CI 0.81 to 1.64). Two trials examined the effect of barbiturate therapy on ICP. In one, a smaller proportion of patients in the barbiturate group had uncontrolled ICP (68% versus 83%); the RR for uncontrolled ICP was 0.81 (95% CI 0.62 to 1.06). In the other, mean ICP was also lower in the barbiturate group. Barbiturate therapy results in an increased occurrence of hypotension (RR 1.80; 95% CI 1.19 to 2.70). For every four patients treated, one developed clinically significant hypotension. Mean body temperature was significantly lower in the barbiturate group.In one study of pentobarbital versus mannitol there was no difference in death between the two study groups (RR 1.21; 95% CI 0.75 to 1.94). Pentobarbital was less effective than mannitol for control of raised ICP (RR 1.75; 95% CI 1.05 to 2.92).In one study the RR of death with pentobarbital versus thiopental was 1.78 (95% CI 1.03 to 3.08) in favour of thiopental. Fewer people had uncontrollable ICP with thiopental (RR 1.64; 95% CI 1.03 to 2.60). There was no significant difference in the effects of pentobarbital versus thiopental for death or disability, measured using the Glasgow Outcome Scale (RR 1.31; 95% CI 0.88 to 1.94), or hypotension (RR 0.95; 95% CI 0.81 to 1.12). AUTHORS' CONCLUSIONS: There is no evidence that barbiturate therapy in patients with acute severe head injury improves outcome. Barbiturate therapy results in a fall in blood pressure in one in four patients. This hypotensive effect will offset any ICP lowering effect on cerebral perfusion pressure.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Raised intracranial pressure (ICP) is an important complication of severe brain injury, and is associated with high mortality. Barbiturates are believed to reduce ICP by suppressing cerebral metabolism, thus reducing cerebral metabolic demands and cerebral blood volume. However, barbiturates also reduce blood pressure and may, therefore, adversely effect cerebral perfusion pressure. OBJECTIVES: To assess the effects of barbiturates in reducing mortality, disability and raised ICP in people with acute traumatic brain injury. To quantify any side effects resulting from the use of barbiturates. SEARCH METHODS: The following electronic databases were searched on 26 September 2012: CENTRAL (The Cochrane Library), MEDLINE (Ovid SP), PubMed, EMBASE (Ovid SP), PsycINFO (Ovid SP), PsycEXTRA (Ovid SP), ISI Web of Science: Science Citation Index and Conference Proceedings Citation Index-Science. Searching was not restricted by date, language or publication status. We also searched the reference lists of the included trials and review articles. We contacted researchers for information on ongoing studies. SELECTION CRITERIA: Randomised controlled trials of one or more of the barbiturate class of drugs, where study participants had clinically diagnosed acute traumatic brain injury of any severity. DATA COLLECTION AND ANALYSIS: Two review authors screened the search results, extracted data and assessed the risk of bias in the trials. MAIN RESULTS: Data from seven trials involving 341 people are included in this review.For barbiturates versus no barbiturate, the pooled risk ratio (RR) of death from three trials was 1.09 (95% confidence interval (CI) 0.81 to 1.47). Death or disability, measured using the Glasgow Outcome Scale was assessed in two trials, the RR with barbiturates was 1.15 (95% CI 0.81 to 1.64). Two trials examined the effect of barbiturate therapy on ICP. In one, a smaller proportion of patients in the barbiturate group had uncontrolled ICP (68% versus 83%); the RR for uncontrolled ICP was 0.81 (95% CI 0.62 to 1.06). In the other, mean ICP was also lower in the barbiturate group. Barbiturate therapy results in an increased occurrence of hypotension (RR 1.80; 95% CI 1.19 to 2.70). For every four patients treated, one developed clinically significant hypotension. Mean body temperature was significantly lower in the barbiturate group.In one study of pentobarbital versus mannitol there was no difference in death between the two study groups (RR 1.21; 95% CI 0.75 to 1.94). Pentobarbital was less effective than mannitol for control of raised ICP (RR 1.75; 95% CI 1.05 to 2.92).In one study the RR of death with pentobarbital versus thiopental was 1.78 (95% CI 1.03 to 3.08) in favour of thiopental. Fewer people had uncontrollable ICP with thiopental (RR 1.64; 95% CI 1.03 to 2.60). There was no significant difference in the effects of pentobarbital versus thiopental for death or disability, measured using the Glasgow Outcome Scale (RR 1.31; 95% CI 0.88 to 1.94), or hypotension (RR 0.95; 95% CI 0.81 to 1.12). AUTHORS' CONCLUSIONS: There is no evidence that barbiturate therapy in patients with acute severe head injury improves outcome. Barbiturate therapy results in a fall in blood pressure in one in four patients. This hypotensive effect will offset any ICP lowering effect on cerebral perfusion pressure.
Dewan, Yashbir; Komolafe, Edward O; Mejía-Mantilla, Jorge H; Perel, Pablo; Roberts, Ian; Shakur-Still, Haleema; Collaborators, CRASH-3
In: TRIALS, vol. 13, no. 1, pp. 87–, 2012.
@article{lshtm4654357,
title = {CRASH-3 - tranexamic acid for the treatment of significant traumatic brain injury: study protocol for an international randomized, double-blind, placebo-controlled trial.},
author = {Yashbir Dewan and Edward O Komolafe and Jorge H Mejía-Mantilla and Pablo Perel and Ian Roberts and Haleema Shakur-Still and CRASH-3 Collaborators},
url = {http://researchonline.lshtm.ac.uk/id/eprint/4654357/},
year = {2012},
date = {2012-06-01},
journal = {TRIALS},
volume = {13},
number = {1},
pages = {87--},
publisher = {BMC},
abstract = {BACKGROUND: Worldwide, over 10 million people are killed or hospitalized because of traumatic brain injury each year. About 90% of deaths occur in low- and middle-income countries. The condition mostly affects young adults, and many experience long lasting or permanent disability. The social and economic burden is considerable. Tranexamic acid (TXA) is commonly given to surgical patients to reduce bleeding and the need for blood transfusion. It has been shown to reduce the number of patients receiving a blood transfusion by about a third, reduces the volume of blood transfused by about one unit, and halves the need for further surgery to control bleeding in elective surgical patients. METHODS/DESIGN: The CRASH-3 trial is an international, multicenter, pragmatic, randomized, double-blind, placebo-controlled trial to quantify the effects of the early administration of TXA on death and disability in patients with traumatic brain injury. Ten thousand adult patients who fulfil the eligibility criteria will be randomized to receive TXA or placebo. Adults with traumatic brain injury, who are within 8 h of injury and have any intracranial bleeding on computerized tomography (CT scan) or Glasgow Coma Score (GCS) of 12 or less can be included if the responsible doctor is substantially uncertain as to whether or not to use TXA in this patient. Patients with significant extracranial bleeding will be excluded since there is evidence that TXA improves outcome in these patients. Treatment will entail a 1 g loading dose followed by a 1 g maintenance dose over 8 h.The main analyses will be on an íntention-to-treat' basis, irrespective of whether the allocated treatment was received. Results will be presented as appropriate effect estimates with a measure of precision (95% confidence intervals). Subgroup analyses for the primary outcome will be based on time from injury to randomization, the severity of the injury, location of the bleeding, and baseline risk. Interaction tests will be used to test whether the effect of treatment differs across these subgroups. A study with 10,000 patients will have approximately 90% power to detect a 15% relative reduction from 20% to 17% in all-cause mortality. TRIAL REGISTRATION: Current Controlled Trials ISRCTN15088122; Clinicaltrials.gov NCT01402882.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Worldwide, over 10 million people are killed or hospitalized because of traumatic brain injury each year. About 90% of deaths occur in low- and middle-income countries. The condition mostly affects young adults, and many experience long lasting or permanent disability. The social and economic burden is considerable. Tranexamic acid (TXA) is commonly given to surgical patients to reduce bleeding and the need for blood transfusion. It has been shown to reduce the number of patients receiving a blood transfusion by about a third, reduces the volume of blood transfused by about one unit, and halves the need for further surgery to control bleeding in elective surgical patients. METHODS/DESIGN: The CRASH-3 trial is an international, multicenter, pragmatic, randomized, double-blind, placebo-controlled trial to quantify the effects of the early administration of TXA on death and disability in patients with traumatic brain injury. Ten thousand adult patients who fulfil the eligibility criteria will be randomized to receive TXA or placebo. Adults with traumatic brain injury, who are within 8 h of injury and have any intracranial bleeding on computerized tomography (CT scan) or Glasgow Coma Score (GCS) of 12 or less can be included if the responsible doctor is substantially uncertain as to whether or not to use TXA in this patient. Patients with significant extracranial bleeding will be excluded since there is evidence that TXA improves outcome in these patients. Treatment will entail a 1 g loading dose followed by a 1 g maintenance dose over 8 h.The main analyses will be on an íntention-to-treat' basis, irrespective of whether the allocated treatment was received. Results will be presented as appropriate effect estimates with a measure of precision (95% confidence intervals). Subgroup analyses for the primary outcome will be based on time from injury to randomization, the severity of the injury, location of the bleeding, and baseline risk. Interaction tests will be used to test whether the effect of treatment differs across these subgroups. A study with 10,000 patients will have approximately 90% power to detect a 15% relative reduction from 20% to 17% in all-cause mortality. TRIAL REGISTRATION: Current Controlled Trials ISRCTN15088122; Clinicaltrials.gov NCT01402882.
Walpole, Sarah Catherine; Prieto-Merino, David; Edwards, Phil; Cleland, John; Stevens, Gretchen; Roberts, Ian
The weight of nations: an estimation of adult human biomass. Journal Article
In: BMC PUBLIC HEALTH, vol. 12, no. 1, pp. 439–, 2012.
@article{lshtm4654142,
title = {The weight of nations: an estimation of adult human biomass.},
author = {Sarah Catherine Walpole and David Prieto-Merino and Phil Edwards and John Cleland and Gretchen Stevens and Ian Roberts},
url = {http://researchonline.lshtm.ac.uk/id/eprint/4654142/},
year = {2012},
date = {2012-06-01},
journal = {BMC PUBLIC HEALTH},
volume = {12},
number = {1},
pages = {439--},
publisher = {BIOMED CENTRAL LTD},
abstract = {BACKGROUND: The energy requirement of species at each trophic level in an ecological pyramid is a function of the number of organisms and their average mass. Regarding human populations, although considerable attention is given to estimating the number of people, much less is given to estimating average mass, despite evidence that average body mass is increasing. We estimate global human biomass, its distribution by region and the proportion of biomass due to overweight and obesity. METHODS: For each country we used data on body mass index (BMI) and height distribution to estimate average adult body mass. We calculated total biomass as the product of population size and average body mass. We estimated the percentage of the population that is overweight (BMI ensuremath> 25) and obese (BMI ensuremath> 30) and the biomass due to overweight and obesity. RESULTS: In 2005, global adult human biomass was approximately 287 million tonnes, of which 15 million tonnes were due to overweight (BMI ensuremath> 25), a mass equivalent to that of 242 million people of average body mass (5% of global human biomass). Biomass due to obesity was 3.5 million tonnes, the mass equivalent of 56 million people of average body mass (1.2% of human biomass). North America has 6% of the world population but 34% of biomass due to obesity. Asia has 61% of the world population but 13% of biomass due to obesity. One tonne of human biomass corresponds to approximately 12 adults in North America and 17 adults in Asia. If all countries had the BMI distribution of the USA, the increase in human biomass of 58 million tonnes would be equivalent in mass to an extra 935 million people of average body mass, and have energy requirements equivalent to that of 473 million adults. CONCLUSIONS: Increasing population fatness could have the same implications for world food energy demands as an extra half a billion people living on the earth.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: The energy requirement of species at each trophic level in an ecological pyramid is a function of the number of organisms and their average mass. Regarding human populations, although considerable attention is given to estimating the number of people, much less is given to estimating average mass, despite evidence that average body mass is increasing. We estimate global human biomass, its distribution by region and the proportion of biomass due to overweight and obesity. METHODS: For each country we used data on body mass index (BMI) and height distribution to estimate average adult body mass. We calculated total biomass as the product of population size and average body mass. We estimated the percentage of the population that is overweight (BMI ensuremath> 25) and obese (BMI ensuremath> 30) and the biomass due to overweight and obesity. RESULTS: In 2005, global adult human biomass was approximately 287 million tonnes, of which 15 million tonnes were due to overweight (BMI ensuremath> 25), a mass equivalent to that of 242 million people of average body mass (5% of global human biomass). Biomass due to obesity was 3.5 million tonnes, the mass equivalent of 56 million people of average body mass (1.2% of human biomass). North America has 6% of the world population but 34% of biomass due to obesity. Asia has 61% of the world population but 13% of biomass due to obesity. One tonne of human biomass corresponds to approximately 12 adults in North America and 17 adults in Asia. If all countries had the BMI distribution of the USA, the increase in human biomass of 58 million tonnes would be equivalent in mass to an extra 935 million people of average body mass, and have energy requirements equivalent to that of 473 million adults. CONCLUSIONS: Increasing population fatness could have the same implications for world food energy demands as an extra half a billion people living on the earth.
Perel, Pablo; Roberts, Ian
Colloids versus crystalloids for fluid resuscitation in critically ill patients. Journal Article
In: The Cochrane database of systematic reviews, vol. 6, no. 6, pp. CD000567–, 2012.
@article{lshtm21092,
title = {Colloids versus crystalloids for fluid resuscitation in critically ill patients.},
author = {Pablo Perel and Ian Roberts},
url = {http://researchonline.lshtm.ac.uk/id/eprint/21092/},
year = {2012},
date = {2012-06-01},
journal = {The Cochrane database of systematic reviews},
volume = {6},
number = {6},
pages = {CD000567--},
publisher = {Cochrane Collaboration},
abstract = {BACKGROUND: Colloid solutions are widely used in fluid resuscitation of critically ill patients. There are several choices of colloid and there is ongoing debate about the relative effectiveness of colloids compared to crystalloid fluids. OBJECTIVES: To assess the effects of colloids compared to crystalloids for fluid resuscitation in critically ill patients. SEARCH METHODS: We searched the Cochrane Injuries Group Specialised Register (searched 16 March 2012), Cochrane Central Register of Controlled Trials 2011, issue 3 (The Cochrane Library), MEDLINE (Ovid) 1946 to March 2012, Embase (Ovid) 1980 to March 2012, ISI Web of Science: Science Citation Index Expanded (1970 to March 2012), ISI Web of Science: Conference Proceedings Citation Index-Science (1990 to March 2012), PubMed (searched 16 March 2012), www.clinical trials.gov and www.controlled-trials.com. We also searched the bibliographies of relevant studies and review articles. SELECTION CRITERIA: Randomised controlled trials (RCTs) of colloids compared to crystalloids, in patients requiring volume replacement. We excluded cross-over trials and trials in pregnant women and neonates. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and rated quality of allocation concealment. We analysed trials with a 'double-intervention', such as those comparing colloid in hypertonic crystalloid to isotonic crystalloid, separately. We stratified the analysis according to colloid type and quality of allocation concealment. MAIN RESULTS: We identified 74 eligible trials; 66 of these presented mortality data.Colloids compared to crystalloids Albumin or plasma protein fraction - 24 trials reported data on mortality, including a total of 9920 patients. The pooled relative risk (RR) from these trials was 1.01 (95% confidence interval (CI) 0.93 to 1.10). When we excluded the trial with poor quality allocation concealment, pooled RR was 1.00 (95% CI 0.92 to 1.09). Hydroxyethyl starch - 21 trials compared hydroxyethyl starch with crystalloids},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Colloid solutions are widely used in fluid resuscitation of critically ill patients. There are several choices of colloid and there is ongoing debate about the relative effectiveness of colloids compared to crystalloid fluids. OBJECTIVES: To assess the effects of colloids compared to crystalloids for fluid resuscitation in critically ill patients. SEARCH METHODS: We searched the Cochrane Injuries Group Specialised Register (searched 16 March 2012), Cochrane Central Register of Controlled Trials 2011, issue 3 (The Cochrane Library), MEDLINE (Ovid) 1946 to March 2012, Embase (Ovid) 1980 to March 2012, ISI Web of Science: Science Citation Index Expanded (1970 to March 2012), ISI Web of Science: Conference Proceedings Citation Index-Science (1990 to March 2012), PubMed (searched 16 March 2012), www.clinical trials.gov and www.controlled-trials.com. We also searched the bibliographies of relevant studies and review articles. SELECTION CRITERIA: Randomised controlled trials (RCTs) of colloids compared to crystalloids, in patients requiring volume replacement. We excluded cross-over trials and trials in pregnant women and neonates. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and rated quality of allocation concealment. We analysed trials with a 'double-intervention', such as those comparing colloid in hypertonic crystalloid to isotonic crystalloid, separately. We stratified the analysis according to colloid type and quality of allocation concealment. MAIN RESULTS: We identified 74 eligible trials; 66 of these presented mortality data.Colloids compared to crystalloids Albumin or plasma protein fraction - 24 trials reported data on mortality, including a total of 9920 patients. The pooled relative risk (RR) from these trials was 1.01 (95% confidence interval (CI) 0.93 to 1.10). When we excluded the trial with poor quality allocation concealment, pooled RR was 1.00 (95% CI 0.92 to 1.09). Hydroxyethyl starch - 21 trials compared hydroxyethyl starch with crystalloids
van Leeuwen, Nikki; Lingsma, Hester F; Perel, Pablo; Lecky, Fiona; Roozenbeek, Bob; Lu, Juan; Shakur-Still, Haleema; Weir, James; Steyerberg, Ewout W; Maas, Andrew IR; on Prognosis, International Mission; in, Clinical Trial Design; Trial, Corticosteroid Randomization After Significant Head Injury; Audit, Trauma; Network, Research
Prognostic value of major extracranial injury in traumatic brain injury: an individual patient data meta-analysis in 39,274 patients. Journal Article
In: Neurosurgery, vol. 70, no. 4, pp. 811–818, 2012.
@article{lshtm185,
title = {Prognostic value of major extracranial injury in traumatic brain injury: an individual patient data meta-analysis in 39,274 patients.},
author = {Nikki van Leeuwen and Hester F Lingsma and Pablo Perel and Fiona Lecky and Bob Roozenbeek and Juan Lu and Haleema Shakur-Still and James Weir and Ewout W Steyerberg and Andrew IR Maas and International Mission on Prognosis and Clinical Trial Design in and Corticosteroid Randomization After Significant Head Injury Trial and Trauma Audit and Research Network},
url = {http://researchonline.lshtm.ac.uk/id/eprint/185/},
year = {2012},
date = {2012-01-01},
journal = {Neurosurgery},
volume = {70},
number = {4},
pages = {811--818},
publisher = {Oxford University Press (OUP)},
abstract = {BACKGROUND: Major extracranial injury (MEI) is common in traumatic brain injury (TBI) patients, but the effect on outcome is controversial. OBJECTIVE: To assess the prognostic value of MEI on mortality after TBI in an individual patient data meta-analysis of 3 observational TBI studies (International Mission on Prognosis and Clinical Trial Design in TBI [IMPACT]), a randomized controlled trial (Corticosteroid Randomization After Significant Head Injury [CRASH]), and a trauma registry (Trauma Audit and Research Network [TARN]). METHODS: MEI (extracranial injury with an Abbreviated Injury Scale ≥ 3 or requiring hospital admission) was related to mortality with logistic regression analysis, adjusted for age, Glasgow Coma Scale motor score, and pupil reactivity and stratified by TBI severity. We pooled odds ratios (ORs) with random-effects meta-analysis. RESULTS: We included 39,274 patients. Mortality was 25%, and 32% had MEI. MEI was a strong predictor for mortality in TARN, with adjusted odds ratios of 2.81 (95% confidence interval [CI], 2.44-3.23) in mild, 2.18 (95% CI, 1.80-2.65) in moderate, and 2.14 (95% CI, 1.95-2.35) in severe TBI patients. The prognostic effect was smaller in IMPACT and CRASH, with pooled adjusted odds ratios of 2.14 (95% CI, 0.93-4.91) in mild, 1.46 (95% CI, 1.14-1.85) in moderate, and 1.18 (95% CI, 1.03-1.55) in severe TBI. When patients who died within 6 hours after injury were excluded from TARN, the effect of MEI was comparable with IMPACT and CRASH. CONCLUSION: MEI is an important prognostic factor for mortality in TBI patients. However, the effect varies by population, which explains the controversy in the literature. The strength of the effect is smaller in patients with more severe brain injury and depends on time of inclusion in a study.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Major extracranial injury (MEI) is common in traumatic brain injury (TBI) patients, but the effect on outcome is controversial. OBJECTIVE: To assess the prognostic value of MEI on mortality after TBI in an individual patient data meta-analysis of 3 observational TBI studies (International Mission on Prognosis and Clinical Trial Design in TBI [IMPACT]), a randomized controlled trial (Corticosteroid Randomization After Significant Head Injury [CRASH]), and a trauma registry (Trauma Audit and Research Network [TARN]). METHODS: MEI (extracranial injury with an Abbreviated Injury Scale ≥ 3 or requiring hospital admission) was related to mortality with logistic regression analysis, adjusted for age, Glasgow Coma Scale motor score, and pupil reactivity and stratified by TBI severity. We pooled odds ratios (ORs) with random-effects meta-analysis. RESULTS: We included 39,274 patients. Mortality was 25%, and 32% had MEI. MEI was a strong predictor for mortality in TARN, with adjusted odds ratios of 2.81 (95% confidence interval [CI], 2.44-3.23) in mild, 2.18 (95% CI, 1.80-2.65) in moderate, and 2.14 (95% CI, 1.95-2.35) in severe TBI patients. The prognostic effect was smaller in IMPACT and CRASH, with pooled adjusted odds ratios of 2.14 (95% CI, 0.93-4.91) in mild, 1.46 (95% CI, 1.14-1.85) in moderate, and 1.18 (95% CI, 1.03-1.55) in severe TBI. When patients who died within 6 hours after injury were excluded from TARN, the effect of MEI was comparable with IMPACT and CRASH. CONCLUSION: MEI is an important prognostic factor for mortality in TBI patients. However, the effect varies by population, which explains the controversy in the literature. The strength of the effect is smaller in patients with more severe brain injury and depends on time of inclusion in a study.
Alvarado, JC; Dewan, Y; Elsayed, HF; Gogichaishvili, T; Gupta, S; Hunt, BJ; Iribhogbe, P; Izurieta, M; Khamis, H; Komolafe, EO; Mejía-Mantilla, JH; Miranda, J; Uribe, CH Morales; Olaomi, O; Olldashi, F; Perel, P; Ramana, PV; Ravi, RR; Roberts, IR; Shakur-Still, Haleema
Tranexamic acid in trauma: we need stronger global health policy Journal Article
In: BMJ, vol. 347, no. 4593, 2012.
@article{lshtm1082615,
title = {Tranexamic acid in trauma: we need stronger global health policy},
author = {JC Alvarado and Y Dewan and HF Elsayed and T Gogichaishvili and S Gupta and BJ Hunt and P Iribhogbe and M Izurieta and H Khamis and EO Komolafe and JH Mejía-Mantilla and J Miranda and CH Morales Uribe and O Olaomi and F Olldashi and P Perel and PV Ramana and RR Ravi and IR Roberts and Haleema Shakur-Still},
url = {http://researchonline.lshtm.ac.uk/id/eprint/1082615/},
year = {2012},
date = {2012-01-01},
journal = {BMJ},
volume = {347},
number = {4593},
abstract = {Tranexamic acid substantially reduces death in bleeding trauma patients. So why are the World Health Organization, the United Nations, the World Bank, and Unicef not ensuring global implementation, ask Ian Roberts and colleagues},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Tranexamic acid substantially reduces death in bleeding trauma patients. So why are the World Health Organization, the United Nations, the World Bank, and Unicef not ensuring global implementation, ask Ian Roberts and colleagues
Jarrett, James; Woodcock, James; Griffiths, Ulla K; Chalabi, Zaid; Edwards, Phil; Roberts, Ian; Haines, Andy
Effect of increasing active travel in urban England and Wales on costs to the National Health Service. Journal Article
In: Lancet, vol. 379, no. 9832, pp. 2198–2205, 2012.
@article{lshtm30344,
title = {Effect of increasing active travel in urban England and Wales on costs to the National Health Service.},
author = {James Jarrett and James Woodcock and Ulla K Griffiths and Zaid Chalabi and Phil Edwards and Ian Roberts and Andy Haines},
url = {http://researchonline.lshtm.ac.uk/id/eprint/30344/},
year = {2012},
date = {2012-01-01},
journal = {Lancet},
volume = {379},
number = {9832},
pages = {2198--2205},
publisher = {Elsevier},
abstract = {Increased walking and cycling in urban areas and reduced use of private cars could have positive effects on many health outcomes. We estimated the potential effect of increased walking and cycling in urban England and Wales on costs to the National Health Service (NHS) for seven diseases--namely, type 2 diabetes, dementia, cerebrovascular disease, breast cancer, colorectal cancer, depression, and ischaemic heart disease--that are associated with physical inactivity. Within 20 years, reductions in the prevalences of type 2 diabetes, dementia, ischaemic heart disease, cerebrovascular disease, and cancer because of increased physical activity would lead to savings of roughly UKpounds17 billion (in 2010 prices) for the NHS, after adjustment for an increased risk of road traffic injuries. Further costs would be averted after 20 years. Sensitivity analyses show that results are invariably positive but sensitive to assumptions about time lag between the increase in active travel and changes in health outcomes. Increasing the amount of walking and cycling in urban settings could reduce costs to the NHS, permitting decreased government expenditure on health or releasing resources to fund additional health care.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Increased walking and cycling in urban areas and reduced use of private cars could have positive effects on many health outcomes. We estimated the potential effect of increased walking and cycling in urban England and Wales on costs to the National Health Service (NHS) for seven diseases--namely, type 2 diabetes, dementia, cerebrovascular disease, breast cancer, colorectal cancer, depression, and ischaemic heart disease--that are associated with physical inactivity. Within 20 years, reductions in the prevalences of type 2 diabetes, dementia, ischaemic heart disease, cerebrovascular disease, and cancer because of increased physical activity would lead to savings of roughly UKpounds17 billion (in 2010 prices) for the NHS, after adjustment for an increased risk of road traffic injuries. Further costs would be averted after 20 years. Sensitivity analyses show that results are invariably positive but sensitive to assumptions about time lag between the increase in active travel and changes in health outcomes. Increasing the amount of walking and cycling in urban settings could reduce costs to the NHS, permitting decreased government expenditure on health or releasing resources to fund additional health care.
Ker, Katharine; Edwards, Phil; Perel, Pablo; Shakur-Still, Haleema; Roberts, Ian
Effect of tranexamic acid on surgical bleeding: systematic review and cumulative meta-analysis. Journal Article
In: BMJ (Clinical research ed), vol. 344, no. may17, pp. e3054–, 2012.
@article{lshtm21145,
title = {Effect of tranexamic acid on surgical bleeding: systematic review and cumulative meta-analysis.},
author = {Katharine Ker and Phil Edwards and Pablo Perel and Haleema Shakur-Still and Ian Roberts},
url = {http://researchonline.lshtm.ac.uk/id/eprint/21145/},
year = {2012},
date = {2012-01-01},
journal = {BMJ (Clinical research ed)},
volume = {344},
number = {may17},
pages = {e3054--},
publisher = {BMJ Publishing Group},
abstract = {OBJECTIVE: To assess the effect of tranexamic acid on blood transfusion, thromboembolic events, and mortality in surgical patients. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Cochrane central register of controlled trials, Medline, and Embase, from inception to September 2011, the World Health Organization International Clinical Trials Registry Platform, and the reference lists of relevant articles. STUDY SELECTION: Randomised controlled trials comparing tranexamic acid with no tranexamic acid or placebo in surgical patients. Outcome measures of interest were the number of patients receiving a blood transfusion; the number of patients with a thromboembolic event (myocardial infarction, stroke, deep vein thrombosis, and pulmonary embolism); and the number of deaths. Trials were included irrespective of language or publication status. RESULTS: 129 trials, totalling 10,488 patients, carried out between 1972 and 2011 were included. Tranexamic acid reduced the probability of receiving a blood transfusion by a third (risk ratio 0.62, 95% confidence interval 0.58 to 0.65; Pensuremath<0.001). This effect remained when the analysis was restricted to trials using adequate allocation concealment (0.68, 0.62 to 0.74; Pensuremath<0.001). The effect of tranexamic acid on myocardial infarction (0.68, 0.43 to 1.09; P = 0.11), stroke (1.14, 0.65 to 2.00; P = 0.65), deep vein thrombosis (0.86, 0.53 to 1.39; P = 0.54), and pulmonary embolism (0.61, 0.25 to 1.47; P=0.27) was uncertain. Fewer deaths occurred in the tranexamic acid group (0.61, 0.38 to 0.98; P = 0.04), although when the analysis was restricted to trials using adequate concealment there was considerable uncertainty (0.67, 0.33 to 1.34; P = 0.25). Cumulative meta-analysis showed that reliable evidence that tranexamic acid reduces the need for transfusion has been available for over 10 years. CONCLUSIONS: Strong evidence that tranexamic acid reduces blood transfusion in surgery has been available for many years. Further trials on the effect of tranexamic acid on blood transfusion are unlikely to add useful new information. However, the effect of tranexamic acid on thromboembolic events and mortality remains uncertain. Surgical patients should be made aware of this evidence so that they can make an informed choice.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE: To assess the effect of tranexamic acid on blood transfusion, thromboembolic events, and mortality in surgical patients. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Cochrane central register of controlled trials, Medline, and Embase, from inception to September 2011, the World Health Organization International Clinical Trials Registry Platform, and the reference lists of relevant articles. STUDY SELECTION: Randomised controlled trials comparing tranexamic acid with no tranexamic acid or placebo in surgical patients. Outcome measures of interest were the number of patients receiving a blood transfusion; the number of patients with a thromboembolic event (myocardial infarction, stroke, deep vein thrombosis, and pulmonary embolism); and the number of deaths. Trials were included irrespective of language or publication status. RESULTS: 129 trials, totalling 10,488 patients, carried out between 1972 and 2011 were included. Tranexamic acid reduced the probability of receiving a blood transfusion by a third (risk ratio 0.62, 95% confidence interval 0.58 to 0.65; Pensuremath<0.001). This effect remained when the analysis was restricted to trials using adequate allocation concealment (0.68, 0.62 to 0.74; Pensuremath<0.001). The effect of tranexamic acid on myocardial infarction (0.68, 0.43 to 1.09; P = 0.11), stroke (1.14, 0.65 to 2.00; P = 0.65), deep vein thrombosis (0.86, 0.53 to 1.39; P = 0.54), and pulmonary embolism (0.61, 0.25 to 1.47; P=0.27) was uncertain. Fewer deaths occurred in the tranexamic acid group (0.61, 0.38 to 0.98; P = 0.04), although when the analysis was restricted to trials using adequate concealment there was considerable uncertainty (0.67, 0.33 to 1.34; P = 0.25). Cumulative meta-analysis showed that reliable evidence that tranexamic acid reduces the need for transfusion has been available for over 10 years. CONCLUSIONS: Strong evidence that tranexamic acid reduces blood transfusion in surgery has been available for many years. Further trials on the effect of tranexamic acid on blood transfusion are unlikely to add useful new information. However, the effect of tranexamic acid on thromboembolic events and mortality remains uncertain. Surgical patients should be made aware of this evidence so that they can make an informed choice.
Ker, Katharine; Kiriya, Junko; Perel, Pablo; Edwards, Phil; Shakur-Still, Haleema; Roberts, Ian
In: BMC emergency medicine, vol. 12, no. 1, pp. 3–, 2012.
@article{lshtm20758,
title = {Avoidable mortality from giving tranexamic acid to bleeding trauma patients: an estimation based on WHO mortality data, a systematic literature review and data from the CRASH-2 trial.},
author = {Katharine Ker and Junko Kiriya and Pablo Perel and Phil Edwards and Haleema Shakur-Still and Ian Roberts},
url = {http://researchonline.lshtm.ac.uk/id/eprint/20758/},
year = {2012},
date = {2012-01-01},
journal = {BMC emergency medicine},
volume = {12},
number = {1},
pages = {3--},
publisher = {BMC},
abstract = {BACKGROUND: The CRASH-2 trial showed that early administration of tranexamic acid (TXA) safely reduces mortality in bleeding in trauma patients. Based on data from the CRASH-2 trial, global mortality data and a systematic literature review, we estimated the number of premature deaths that might be averted every year worldwide through the use of TXA. METHODS: We used CRASH-2 trial data to examine the effect of TXA on death due to bleeding by geographical region. We used WHO mortality data (2008) and data from a systematic review of the literature to estimate the annual number of in-hospital trauma deaths due to bleeding. We then used the relative risk estimates from the CRASH-2 trial to estimate the number of premature deaths that could be averted if all hospitalised bleeding trauma patients received TXA within one hour of injury, and within three hours of injury. Sensitivity analyses were used to explore the effect of uncertainty in the parameter estimates and the assumptions made in the model. RESULTS: There is no evidence that the effect of TXA on death due to bleeding varies by geographical region (heterogeneity p = 0.70). Based on WHO data and our systematic literature review, we estimate that each year worldwide there are approximately 400,000 in-hospital trauma deaths due to bleeding. If patients received TXA within one hour of injury then approximately 128,000 (uncertainty range [UR] $approx$ 72,000 to 172,000) deaths might be averted. If patients received TXA within three hours of injury then approximately 112,000 (UR $approx$ 68,000 to 148,000) deaths might be averted. Country specific estimates show that the largest numbers of deaths averted would be in India and China. CONCLUSIONS: The use of TXA in the treatment of traumatic bleeding has the potential to prevent many premature deaths every year. A large proportion of the potential health gains are in low and middle income countries.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: The CRASH-2 trial showed that early administration of tranexamic acid (TXA) safely reduces mortality in bleeding in trauma patients. Based on data from the CRASH-2 trial, global mortality data and a systematic literature review, we estimated the number of premature deaths that might be averted every year worldwide through the use of TXA. METHODS: We used CRASH-2 trial data to examine the effect of TXA on death due to bleeding by geographical region. We used WHO mortality data (2008) and data from a systematic review of the literature to estimate the annual number of in-hospital trauma deaths due to bleeding. We then used the relative risk estimates from the CRASH-2 trial to estimate the number of premature deaths that could be averted if all hospitalised bleeding trauma patients received TXA within one hour of injury, and within three hours of injury. Sensitivity analyses were used to explore the effect of uncertainty in the parameter estimates and the assumptions made in the model. RESULTS: There is no evidence that the effect of TXA on death due to bleeding varies by geographical region (heterogeneity p = 0.70). Based on WHO data and our systematic literature review, we estimate that each year worldwide there are approximately 400,000 in-hospital trauma deaths due to bleeding. If patients received TXA within one hour of injury then approximately 128,000 (uncertainty range [UR] $approx$ 72,000 to 172,000) deaths might be averted. If patients received TXA within three hours of injury then approximately 112,000 (UR $approx$ 68,000 to 148,000) deaths might be averted. Country specific estimates show that the largest numbers of deaths averted would be in India and China. CONCLUSIONS: The use of TXA in the treatment of traumatic bleeding has the potential to prevent many premature deaths every year. A large proportion of the potential health gains are in low and middle income countries.
Pealing, Louise; Perel, Pablo; Prieto-Merino, David; Roberts, Ian; Collaborators, CRASH-2 Trial
Risk factors for vascular occlusive events and death due to bleeding in trauma patients; an analysis of the CRASH-2 cohort. Journal Article
In: PloS one, vol. 7, no. 12, pp. e50603–, 2012.
@article{lshtm585226,
title = {Risk factors for vascular occlusive events and death due to bleeding in trauma patients; an analysis of the CRASH-2 cohort.},
author = {Louise Pealing and Pablo Perel and David Prieto-Merino and Ian Roberts and CRASH-2 Trial Collaborators},
url = {http://researchonline.lshtm.ac.uk/id/eprint/585226/},
year = {2012},
date = {2012-01-01},
journal = {PloS one},
volume = {7},
number = {12},
pages = {e50603--},
publisher = {Public Library of Science},
abstract = {BACKGROUND: Vascular occlusive events can complicate recovery following trauma. We examined risk factors for venous and arterial vascular occlusive events in trauma patients and the extent to which the risk of vascular occlusive events varies with the severity of bleeding. METHODS AND FINDINGS: We conducted a cohort analysis using data from a large international, double-blind, randomised, placebo-controlled trial (The CRASH-2 trial) [1]. We studied the association between patient demographic and physiological parameters at hospital admission and the risk of vascular occlusive events. To assess the extent to which risk of vascular occlusive events varies with severity of bleeding, we constructed a prognostic model for the risk of death due to bleeding and assessed the relationship between risk of death due to bleeding and risk of vascular occlusive events. There were 20,127 trauma patients with outcome data including 204 (1.01%) patients with a venous event (pulmonary embolism or deep vein thrombosis) and 200 (0.99%) with an arterial event (myocardial infarction or stroke). There were 81 deaths due to vascular occlusive events. Increasing age, decreasing systolic blood pressure, increased respiratory rates, longer central capillary refill times, higher heart rates and lower Glasgow Coma Scores (all pensuremath<0.02) were strong risk factors for venous and arterial vascular occlusive events. Patients with more severe bleeding as assessed by predicted risk of haemorrhage death had a greatly increased risk for all types of vascular occlusive event (all pensuremath<0.001). CONCLUSIONS: Patients with severe traumatic bleeding are at greatly increased risk of venous and arterial vascular occlusive events. Older age and blunt trauma are also risk factors for vascular occlusive events. Effective treatment of bleeding may reduce venous and arterial vascular occlusive complications in trauma patients.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Vascular occlusive events can complicate recovery following trauma. We examined risk factors for venous and arterial vascular occlusive events in trauma patients and the extent to which the risk of vascular occlusive events varies with the severity of bleeding. METHODS AND FINDINGS: We conducted a cohort analysis using data from a large international, double-blind, randomised, placebo-controlled trial (The CRASH-2 trial) [1]. We studied the association between patient demographic and physiological parameters at hospital admission and the risk of vascular occlusive events. To assess the extent to which risk of vascular occlusive events varies with severity of bleeding, we constructed a prognostic model for the risk of death due to bleeding and assessed the relationship between risk of death due to bleeding and risk of vascular occlusive events. There were 20,127 trauma patients with outcome data including 204 (1.01%) patients with a venous event (pulmonary embolism or deep vein thrombosis) and 200 (0.99%) with an arterial event (myocardial infarction or stroke). There were 81 deaths due to vascular occlusive events. Increasing age, decreasing systolic blood pressure, increased respiratory rates, longer central capillary refill times, higher heart rates and lower Glasgow Coma Scores (all pensuremath<0.02) were strong risk factors for venous and arterial vascular occlusive events. Patients with more severe bleeding as assessed by predicted risk of haemorrhage death had a greatly increased risk for all types of vascular occlusive event (all pensuremath<0.001). CONCLUSIONS: Patients with severe traumatic bleeding are at greatly increased risk of venous and arterial vascular occlusive events. Older age and blunt trauma are also risk factors for vascular occlusive events. Effective treatment of bleeding may reduce venous and arterial vascular occlusive complications in trauma patients.
Perel, P; Salman, Al-Shahi R; Kawahara, T; Morris, Z; Prieto-Merino, D; Roberts, I; Sandercock, P; Shakur-Still, Haleema; Wardlaw, J
In: Health technology assessment (Winchester, England), vol. 16, no. 13, pp. iii–54, 2012.
@article{lshtm24858,
title = {CRASH-2 (Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage) intracranial bleeding study: the effect of tranexamic acid in traumatic brain injury--a nested randomised, placebo-controlled trial.},
author = {P Perel and Al-Shahi R Salman and T Kawahara and Z Morris and D Prieto-Merino and I Roberts and P Sandercock and Haleema Shakur-Still and J Wardlaw},
url = {http://researchonline.lshtm.ac.uk/id/eprint/24858/},
year = {2012},
date = {2012-01-01},
journal = {Health technology assessment (Winchester, England)},
volume = {16},
number = {13},
pages = {iii--54},
publisher = {NIHR Journals Library},
abstract = {BACKGROUND: Tranexamic acid (TXA) has been shown to reduce blood loss in surgical patients and the risk of death in patients with traumatic bleeding, with no apparent increase in vascular occlusive events. These findings raise the possibility that it might also be effective in traumatic brain injury (TBI). OBJECTIVE: The Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage Intracranial Bleeding Study (CRASH-2 IBS) was conducted to quantify the effect of an early short course of TXA on intracranial haemorrhage and new focal cerebral ischaemic lesions in patients with TBI. DESIGN: CRASH-2 IBS was a prospective randomised controlled trial nested within the CRASH-2 trial. Randomisation was balanced by centre, with an allocation sequence based on a block size of eight. We used a local pack system that selected the lowest numbered treatment pack from a box containing eight numbered packs. Apart from the pack number, the treatment packs were identical. The pack number was recorded on the entry form, which was sent to the international trial co-ordinating centre in London, UK. Once the treatment pack number was recorded, the patient was included in the trial whether or not the treatment pack was opened or the allocated treatment started. All site investigators and trial co-ordinating centre staff were masked to treatment allocation. SETTING: Ten hospitals: (India) Aditya Neuroscience Centre, Sanjivani Hospital, CARE Hospital, Christian Medical College, Medical Trust Hospital, Jeevan Jyoti Hospital and (Colombia) Hospital Universitario San Vicente de Paul, Hospital Pablo Tobón Uribe, Hospital Universitario San José de Popayán and Fundación Valle del Lili. PARTICIPANTS: The trial was conducted in a subset of 270 CRASH-2 trial participants. Patients eligible for inclusion in the CRASH-2 IBS fulfilled the inclusion criteria for the CRASH-2 trial, and also had TBI [Glasgow Coma Scale score of $łeq$ 14 and a brain computerised tomography (CT) scan compatible with TBI]. Pregnant women and patients for whom a second brain CT scan was not possible were excluded. INTERVENTIONS: Participants were randomly allocated to receive either a loading dose of 1 g of TXA infused over 10 minutes followed by an intravenous infusion of 1 g over 8 hours or matching placebo. MAIN OUTCOME MEASURE: The primary outcome was the increase in size of intracranial haemorrhage growth between a CT scan at hospital admission and a second scan 24-48 hours later. RESULTS: One hundred and thirty-three patients were allocated to TXA and 137 to placebo, of whom information on the primary (imaging) outcome was available for 123 (92%) and 126 (92%) respectively. The analysis suggested that TXA was likely to be associated with a reduction in haemorrhage growth [adjusted difference -3.8 ml, 95% credibility interval (CrI) -11.5 ml to 3.9 ml], fewer focal ischaemic lesions [adjusted odds ratio (OR) 0.54, 95% CrI 0.20 to 1.46] and fewer deaths (adjusted OR 0.49, 95% CrI 0.22 to 1.06). CONCLUSIONS: This was the first randomised controlled study to evaluate the effect of TXA in TBI patients and it found that neither moderate benefits nor moderate harmful effects can be excluded. However, although uncertainty remains, our analyses suggest that TXA administration might improve outcome in TBI patients and provide grounds for evaluating this hypothesis in future research. TRIAL REGISTRATION: Current Controlled Trials ISRCTN86750102. SOURCE OF FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 16, No. 13. See the HTA programme website for further project information.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Tranexamic acid (TXA) has been shown to reduce blood loss in surgical patients and the risk of death in patients with traumatic bleeding, with no apparent increase in vascular occlusive events. These findings raise the possibility that it might also be effective in traumatic brain injury (TBI). OBJECTIVE: The Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage Intracranial Bleeding Study (CRASH-2 IBS) was conducted to quantify the effect of an early short course of TXA on intracranial haemorrhage and new focal cerebral ischaemic lesions in patients with TBI. DESIGN: CRASH-2 IBS was a prospective randomised controlled trial nested within the CRASH-2 trial. Randomisation was balanced by centre, with an allocation sequence based on a block size of eight. We used a local pack system that selected the lowest numbered treatment pack from a box containing eight numbered packs. Apart from the pack number, the treatment packs were identical. The pack number was recorded on the entry form, which was sent to the international trial co-ordinating centre in London, UK. Once the treatment pack number was recorded, the patient was included in the trial whether or not the treatment pack was opened or the allocated treatment started. All site investigators and trial co-ordinating centre staff were masked to treatment allocation. SETTING: Ten hospitals: (India) Aditya Neuroscience Centre, Sanjivani Hospital, CARE Hospital, Christian Medical College, Medical Trust Hospital, Jeevan Jyoti Hospital and (Colombia) Hospital Universitario San Vicente de Paul, Hospital Pablo Tobón Uribe, Hospital Universitario San José de Popayán and Fundación Valle del Lili. PARTICIPANTS: The trial was conducted in a subset of 270 CRASH-2 trial participants. Patients eligible for inclusion in the CRASH-2 IBS fulfilled the inclusion criteria for the CRASH-2 trial, and also had TBI [Glasgow Coma Scale score of $łeq$ 14 and a brain computerised tomography (CT) scan compatible with TBI]. Pregnant women and patients for whom a second brain CT scan was not possible were excluded. INTERVENTIONS: Participants were randomly allocated to receive either a loading dose of 1 g of TXA infused over 10 minutes followed by an intravenous infusion of 1 g over 8 hours or matching placebo. MAIN OUTCOME MEASURE: The primary outcome was the increase in size of intracranial haemorrhage growth between a CT scan at hospital admission and a second scan 24-48 hours later. RESULTS: One hundred and thirty-three patients were allocated to TXA and 137 to placebo, of whom information on the primary (imaging) outcome was available for 123 (92%) and 126 (92%) respectively. The analysis suggested that TXA was likely to be associated with a reduction in haemorrhage growth [adjusted difference -3.8 ml, 95% credibility interval (CrI) -11.5 ml to 3.9 ml], fewer focal ischaemic lesions [adjusted odds ratio (OR) 0.54, 95% CrI 0.20 to 1.46] and fewer deaths (adjusted OR 0.49, 95% CrI 0.22 to 1.06). CONCLUSIONS: This was the first randomised controlled study to evaluate the effect of TXA in TBI patients and it found that neither moderate benefits nor moderate harmful effects can be excluded. However, although uncertainty remains, our analyses suggest that TXA administration might improve outcome in TBI patients and provide grounds for evaluating this hypothesis in future research. TRIAL REGISTRATION: Current Controlled Trials ISRCTN86750102. SOURCE OF FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 16, No. 13. See the HTA programme website for further project information.
Perel, P; Salman, RAS; Kawahara, T; Morris, Z; Prieto-Merino, D; Roberts, I; Sandercock, P; Shakur-Still, Haleema; Wardlaw, J
In: Health technology assessment (Winchester, England), vol. 16, no. 13, pp. 1–+, 2012.
@article{lshtm20633,
title = {CRASH-2 (Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage) intracranial bleeding study: the effect of tranexamic acid in traumatic brain injury - a nested, randomised, placebo-controlled trial},
author = {P Perel and RAS Salman and T Kawahara and Z Morris and D Prieto-Merino and I Roberts and P Sandercock and Haleema Shakur-Still and J Wardlaw},
url = {http://researchonline.lshtm.ac.uk/id/eprint/20633/},
year = {2012},
date = {2012-01-01},
journal = {Health technology assessment (Winchester, England)},
volume = {16},
number = {13},
pages = {1--+},
publisher = {NIHR Health Technology Assessment Programme},
abstract = {Background: Tranexamic acid (TXA) has been shown to reduce blood loss in surgical patients and the risk of death in patients with traumatic bleeding, with no apparent increase in vascular occlusive events. These findings raise the possibility that it might also be effective in traumatic brain injury (TBI). Objective: The Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage Intracranial Bleeding Study (CRASH-2 IBS) was conducted to quantify the effect of an early short course of TXA on intracranial haemorrhage and new focal cerebral ischaemic lesions in patients with TBI. Design: CRASH-2 IBS was a prospective randomised controlled trial nested within the CRASH-2 trial. Randomisation was balanced by centre, with an allocation sequence based on a block size of eight. We used a local pack system that selected the lowest numbered treatment pack from a box containing eight numbered packs. Apart from the pack number, the treatment packs were identical. The pack number was recorded on the entry form, which was sent to the international trial co-ordinating centre in London, UK. Once the treatment pack number was recorded, the patient was included in the trial whether or not the treatment pack was opened or the allocated treatment started. All site investigators and trial co-ordinating centre staff were masked to treatment allocation. Setting: Ten hospitals: (India) Aditya Neuroscience Centre, Sanjivani Hospital, CARE Hospital, Christian Medical College, Medical Trust Hospital, Jeevan Jyoti Hospital and (Colombia) Hospital Universitario San Vicente de Paul, Hospital Pablo Tobon Uribe, Hospital Universitario San Jose de Popayan and Fundacion Valle del Lili. Participants: The trial was conducted in a subset of 270 CRASH-2 trial participants. Patients eligible for inclusion in the CRASH-2 IBS fulfilled the inclusion criteria for the CRASH-2 trial, and also had TBI [Glasgow Coma Scale score of ensuremath<= 14 and a brain computerised tomography (CT) scan compatible with TBI]. Pregnant women and patients for whom a second brain CT scan was not possible were excluded. Interventions: Participants were randomly allocated to receive either a loading dose of 1g of TXA infused over 10 minutes followed by an intravenous infusion of 1g over 8 hours or matching placebo. Main outcome measure: The primary outcome was the increase in size of intracranial haemorrhage growth between a CT scan at hospital admission and a second scan 24-48 hours later. Results: One hundred and thirty-three patients were allocated to TXA and 137 to placebo, of whom information on the primary (imaging) outcome was available for 123 (92%) and 126 (92%) respectively. The analysis suggested that TXA was likely to be associated with a reduction in haemorrhage growth [adjusted difference -3.8 ml, 95% credibility interval (CrI) -11.5 ml to 3.9 ml], fewer focal ischaemic lesions [adjusted odds ratio (OR) 0.54, 95% CrI 0.20 to 1.46] and fewer deaths (adjusted OR 0.49, 95% CrI 0.22 to 1.06). Conclusions: This was the first randomised controlled study to evaluate the effect of TXA in TBI patients and it found that neither moderate benefits nor moderate harmful effects can be excluded. However, although uncertainty remains, our analyses suggest that TXA administration might improve outcome in TBI patients and provide grounds for evaluating this hypothesis in future research.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background: Tranexamic acid (TXA) has been shown to reduce blood loss in surgical patients and the risk of death in patients with traumatic bleeding, with no apparent increase in vascular occlusive events. These findings raise the possibility that it might also be effective in traumatic brain injury (TBI). Objective: The Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage Intracranial Bleeding Study (CRASH-2 IBS) was conducted to quantify the effect of an early short course of TXA on intracranial haemorrhage and new focal cerebral ischaemic lesions in patients with TBI. Design: CRASH-2 IBS was a prospective randomised controlled trial nested within the CRASH-2 trial. Randomisation was balanced by centre, with an allocation sequence based on a block size of eight. We used a local pack system that selected the lowest numbered treatment pack from a box containing eight numbered packs. Apart from the pack number, the treatment packs were identical. The pack number was recorded on the entry form, which was sent to the international trial co-ordinating centre in London, UK. Once the treatment pack number was recorded, the patient was included in the trial whether or not the treatment pack was opened or the allocated treatment started. All site investigators and trial co-ordinating centre staff were masked to treatment allocation. Setting: Ten hospitals: (India) Aditya Neuroscience Centre, Sanjivani Hospital, CARE Hospital, Christian Medical College, Medical Trust Hospital, Jeevan Jyoti Hospital and (Colombia) Hospital Universitario San Vicente de Paul, Hospital Pablo Tobon Uribe, Hospital Universitario San Jose de Popayan and Fundacion Valle del Lili. Participants: The trial was conducted in a subset of 270 CRASH-2 trial participants. Patients eligible for inclusion in the CRASH-2 IBS fulfilled the inclusion criteria for the CRASH-2 trial, and also had TBI [Glasgow Coma Scale score of ensuremath<= 14 and a brain computerised tomography (CT) scan compatible with TBI]. Pregnant women and patients for whom a second brain CT scan was not possible were excluded. Interventions: Participants were randomly allocated to receive either a loading dose of 1g of TXA infused over 10 minutes followed by an intravenous infusion of 1g over 8 hours or matching placebo. Main outcome measure: The primary outcome was the increase in size of intracranial haemorrhage growth between a CT scan at hospital admission and a second scan 24-48 hours later. Results: One hundred and thirty-three patients were allocated to TXA and 137 to placebo, of whom information on the primary (imaging) outcome was available for 123 (92%) and 126 (92%) respectively. The analysis suggested that TXA was likely to be associated with a reduction in haemorrhage growth [adjusted difference -3.8 ml, 95% credibility interval (CrI) -11.5 ml to 3.9 ml], fewer focal ischaemic lesions [adjusted odds ratio (OR) 0.54, 95% CrI 0.20 to 1.46] and fewer deaths (adjusted OR 0.49, 95% CrI 0.22 to 1.06). Conclusions: This was the first randomised controlled study to evaluate the effect of TXA in TBI patients and it found that neither moderate benefits nor moderate harmful effects can be excluded. However, although uncertainty remains, our analyses suggest that TXA administration might improve outcome in TBI patients and provide grounds for evaluating this hypothesis in future research.
Perel, Pablo; Prieto-Merino, David; Shakur-Still, Haleema; Clayton, Tim; Lecky, Fiona; Bouamra, Omar; Russell, Rob; Faulkner, Mark; Steyerberg, Ewout W; Roberts, Ian
Predicting early death in patients with traumatic bleeding: development and validation of prognostic model. Journal Article
In: BMJ (Clinical research ed), vol. 345, no. aug15, pp. e5166–, 2012.
@article{lshtm174920,
title = {Predicting early death in patients with traumatic bleeding: development and validation of prognostic model.},
author = {Pablo Perel and David Prieto-Merino and Haleema Shakur-Still and Tim Clayton and Fiona Lecky and Omar Bouamra and Rob Russell and Mark Faulkner and Ewout W Steyerberg and Ian Roberts},
url = {http://researchonline.lshtm.ac.uk/id/eprint/174920/},
year = {2012},
date = {2012-01-01},
journal = {BMJ (Clinical research ed)},
volume = {345},
number = {aug15},
pages = {e5166--},
publisher = {BMJ Publishing Group},
abstract = {OBJECTIVE: To develop and validate a prognostic model for early death in patients with traumatic bleeding. DESIGN: Multivariable logistic regression of a large international cohort of trauma patients. SETTING: 274 hospitals in 40 high, medium, and low income countries PARTICIPANTS: Prognostic model development: 20,127 trauma patients with, or at risk of, significant bleeding, within 8 hours of injury in the Clinical Randomisation of an Anti?brinolytic in Signi?cant Haemorrhage (CRASH-2) trial. External validation: 14,220 selected trauma patients from the Trauma Audit and Research Network (TARN), which included mainly patients from the UK. OUTCOMES: In-hospital death within 4 weeks of injury. RESULTS: 3076 (15%) patients died in the CRASH-2 trial and 1765 (12%) in the TARN dataset. Glasgow coma score, age, and systolic blood pressure were the strongest predictors of mortality. Other predictors included in the final model were geographical region (low, middle, or high income country), heart rate, time since injury, and type of injury. Discrimination and calibration were satisfactory, with C statistics above 0.80 in both CRASH-2 and TARN. A simple chart was constructed to readily provide the probability of death at the point of care, and a web based calculator is available for a more detailed risk assessment (http://crash2.lshtm.ac.uk). CONCLUSIONS: This prognostic model can be used to obtain valid predictions of mortality in patients with traumatic bleeding, assisting in triage and potentially shortening the time to diagnostic and lifesaving procedures (such as imaging, surgery, and tranexamic acid). Age is an important prognostic factor, and this is of particular relevance in high income countries with an aging trauma population.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE: To develop and validate a prognostic model for early death in patients with traumatic bleeding. DESIGN: Multivariable logistic regression of a large international cohort of trauma patients. SETTING: 274 hospitals in 40 high, medium, and low income countries PARTICIPANTS: Prognostic model development: 20,127 trauma patients with, or at risk of, significant bleeding, within 8 hours of injury in the Clinical Randomisation of an Anti?brinolytic in Signi?cant Haemorrhage (CRASH-2) trial. External validation: 14,220 selected trauma patients from the Trauma Audit and Research Network (TARN), which included mainly patients from the UK. OUTCOMES: In-hospital death within 4 weeks of injury. RESULTS: 3076 (15%) patients died in the CRASH-2 trial and 1765 (12%) in the TARN dataset. Glasgow coma score, age, and systolic blood pressure were the strongest predictors of mortality. Other predictors included in the final model were geographical region (low, middle, or high income country), heart rate, time since injury, and type of injury. Discrimination and calibration were satisfactory, with C statistics above 0.80 in both CRASH-2 and TARN. A simple chart was constructed to readily provide the probability of death at the point of care, and a web based calculator is available for a more detailed risk assessment (http://crash2.lshtm.ac.uk). CONCLUSIONS: This prognostic model can be used to obtain valid predictions of mortality in patients with traumatic bleeding, assisting in triage and potentially shortening the time to diagnostic and lifesaving procedures (such as imaging, surgery, and tranexamic acid). Age is an important prognostic factor, and this is of particular relevance in high income countries with an aging trauma population.
Roberts, I
The truth about road traffic accidents. Journal Article
In: The British journal of surgery, vol. 99 Sup, no. S1, pp. 8–9, 2012.
@article{lshtm20762,
title = {The truth about road traffic accidents.},
author = {I Roberts},
url = {http://researchonline.lshtm.ac.uk/id/eprint/20762/},
year = {2012},
date = {2012-01-01},
journal = {The British journal of surgery},
volume = {99 Sup},
number = {S1},
pages = {8--9},
publisher = {Wiley},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Roberts, I; Vieceli, E; Duffield, P
TXA Comic Strip Miscellaneous
2012.
@misc{lshtm333704,
title = {TXA Comic Strip},
author = {I Roberts and E Vieceli and P Duffield},
url = {http://researchonline.lshtm.ac.uk/id/eprint/333704/},
year = {2012},
date = {2012-01-01},
keywords = {},
pubstate = {published},
tppubtype = {misc}
}
Roberts, Ian
Tranexamic Acid: a recipe for saving lives in traumatic bleeding. Journal Article
In: Nigerian journal of surgery, vol. 18, no. 1, pp. 1–, 2012.
@article{lshtm1217020,
title = {Tranexamic Acid: a recipe for saving lives in traumatic bleeding.},
author = {Ian Roberts},
url = {http://researchonline.lshtm.ac.uk/id/eprint/1217020/},
year = {2012},
date = {2012-01-01},
journal = {Nigerian journal of surgery},
volume = {18},
number = {1},
pages = {1--},
publisher = {Medknow Publications},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Roberts, Ian; Perel, Pablo; Prieto-Merino, David; Shakur-Still, Haleema; Coats, Tim; Hunt, Beverley J; Lecky, Fiona; Brohi, Karim; Willett, Keith; Collaborators, CRASH-2
Effect of tranexamic acid on mortality in patients with traumatic bleeding: prespecified analysis of data from randomised controlled trial. Journal Article
In: BMJ (Clinical research ed), vol. 345, no. sep11, pp. e5839–, 2012.
@article{lshtm333680,
title = {Effect of tranexamic acid on mortality in patients with traumatic bleeding: prespecified analysis of data from randomised controlled trial.},
author = {Ian Roberts and Pablo Perel and David Prieto-Merino and Haleema Shakur-Still and Tim Coats and Beverley J Hunt and Fiona Lecky and Karim Brohi and Keith Willett and CRASH-2 Collaborators},
url = {http://researchonline.lshtm.ac.uk/id/eprint/333680/},
year = {2012},
date = {2012-01-01},
journal = {BMJ (Clinical research ed)},
volume = {345},
number = {sep11},
pages = {e5839--},
publisher = {BMJ Publishing Group},
abstract = {OBJECTIVES: To examine whether the effect of tranexamic acid on the risk of death and thrombotic events in patients with traumatic bleeding varies according to baseline risk of death. To assess the extent to which current protocols for treatment with tranexamic acid maximise benefits to patients. DESIGN: Prespecified stratified analysis of data from an international multicentre randomised controlled trial (the CRASH-2 trial) with an estimation of the proportion of premature deaths that could potentially be averted through the administration of tranexamic acid. PARTICIPANTS: 13,273 trauma patients in the CRASH-2 trial who were treated with tranexamic acid or placebo within three hours of injury and trauma patients enrolled in UK Trauma and Audit Research Network, stratified by risk of death at baseline (ensuremath<6%, 6-20%, 21-50%, ensuremath>50%). INTERVENTION: Tranexamic acid (1 g over 10 minutes followed by 1 g over eight hours) or matching placebo. MAIN OUTCOME MEASURE: Odds ratios and 95% confidence intervals for death in hospital within four weeks of injury, deaths from bleeding, and fatal and non-fatal thrombotic events associated with the use of tranexamic acid according to baseline risk of death. Unless there was strong evidence against the null hypothesis of homogeneity of effects (Pensuremath<0.001), the overall odds ratio was used as the most reliable guide to the odds ratios in all strata. RESULTS: Tranexamic acid was associated with a significant reduction in all cause mortality and deaths from bleeding. In each stratum of baseline risk, there were fewer deaths among patients treated with tranexamic acid. There was no evidence of heterogeneity in the effect of tranexamic acid on all cause mortality (P=0.96 for interaction) or deaths from bleeding (P=0.98) by baseline risk of death. In those treated with tranexamic acid there was a significant reduction in the odds of fatal and non-fatal thrombotic events (odds ratio 0.69, 95% confidence interval 0.53 to 0.89; P=0.005) and a significant reduction in arterial thrombotic events (0.58, 0.40 to 0.83; P=0.003) but no significant reduction in venous thrombotic events (0.83, 0.59 to 1.17; P=0.295). There was no evidence of heterogeneity in the effect of tranexamic acid on the risk of thrombotic events (P=0.74). If the effect of tranexamic acid is assumed to be the same in all risk strata (ensuremath<6%, 6-20%, 21-50%, ensuremath>50% risk of death at baseline), the percentage of deaths that could be averted by administration of tranexamic acid within three hours of injury in each group is 17%, 36%, 30%, and 17%, respectively. CONCLUSIONS: Tranexamic acid can be administered safely to a wide spectrum of patients with traumatic bleeding and should not be restricted to the most severely injured. TRIAL REGISTRATION: ISRCTN86750102.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVES: To examine whether the effect of tranexamic acid on the risk of death and thrombotic events in patients with traumatic bleeding varies according to baseline risk of death. To assess the extent to which current protocols for treatment with tranexamic acid maximise benefits to patients. DESIGN: Prespecified stratified analysis of data from an international multicentre randomised controlled trial (the CRASH-2 trial) with an estimation of the proportion of premature deaths that could potentially be averted through the administration of tranexamic acid. PARTICIPANTS: 13,273 trauma patients in the CRASH-2 trial who were treated with tranexamic acid or placebo within three hours of injury and trauma patients enrolled in UK Trauma and Audit Research Network, stratified by risk of death at baseline (ensuremath<6%, 6-20%, 21-50%, ensuremath>50%). INTERVENTION: Tranexamic acid (1 g over 10 minutes followed by 1 g over eight hours) or matching placebo. MAIN OUTCOME MEASURE: Odds ratios and 95% confidence intervals for death in hospital within four weeks of injury, deaths from bleeding, and fatal and non-fatal thrombotic events associated with the use of tranexamic acid according to baseline risk of death. Unless there was strong evidence against the null hypothesis of homogeneity of effects (Pensuremath<0.001), the overall odds ratio was used as the most reliable guide to the odds ratios in all strata. RESULTS: Tranexamic acid was associated with a significant reduction in all cause mortality and deaths from bleeding. In each stratum of baseline risk, there were fewer deaths among patients treated with tranexamic acid. There was no evidence of heterogeneity in the effect of tranexamic acid on all cause mortality (P=0.96 for interaction) or deaths from bleeding (P=0.98) by baseline risk of death. In those treated with tranexamic acid there was a significant reduction in the odds of fatal and non-fatal thrombotic events (odds ratio 0.69, 95% confidence interval 0.53 to 0.89; P=0.005) and a significant reduction in arterial thrombotic events (0.58, 0.40 to 0.83; P=0.003) but no significant reduction in venous thrombotic events (0.83, 0.59 to 1.17; P=0.295). There was no evidence of heterogeneity in the effect of tranexamic acid on the risk of thrombotic events (P=0.74). If the effect of tranexamic acid is assumed to be the same in all risk strata (ensuremath<6%, 6-20%, 21-50%, ensuremath>50% risk of death at baseline), the percentage of deaths that could be averted by administration of tranexamic acid within three hours of injury in each group is 17%, 36%, 30%, and 17%, respectively. CONCLUSIONS: Tranexamic acid can be administered safely to a wide spectrum of patients with traumatic bleeding and should not be restricted to the most severely injured. TRIAL REGISTRATION: ISRCTN86750102.
Roberts, Ian; Shakur-Still, Haleema; Ker, Katharine; Coats, Tim; collaborators, CRASH-2 Trial
Antifibrinolytic drugs for acute traumatic injury. Journal Article
In: The Cochrane database of systematic reviews, vol. 12, no. 1, pp. CD004896–, 2012.
@article{lshtm616545,
title = {Antifibrinolytic drugs for acute traumatic injury.},
author = {Ian Roberts and Haleema Shakur-Still and Katharine Ker and Tim Coats and CRASH-2 Trial collaborators},
url = {http://researchonline.lshtm.ac.uk/id/eprint/616545/},
year = {2012},
date = {2012-01-01},
journal = {The Cochrane database of systematic reviews},
volume = {12},
number = {1},
pages = {CD004896--},
publisher = {Cochrane Collaboration},
abstract = {BACKGROUND: Uncontrolled bleeding is an important cause of death in trauma victims. Antifibrinolytic treatment has been shown to reduce blood loss following surgery and may also be effective in reducing blood loss following trauma. OBJECTIVES: To quantify the effect of antifibrinolytic drugs in reducing blood loss, transfusion requirement and mortality after acute traumatic injury. SEARCH STRATEGY: We searched the Cochrane Injuries Group's Specialised Register, CENTRAL, MEDLINE, PubMed, EMBASE, Science Citation Index, National Research Register, Zetoc, SIGLE, Global Health, LILACS, and Current Controlled Trials. The Cochrane Injuries Group Specialised Register, CENTRAL, MEDLINE and EMBASE searches were updated in July 2010. SELECTION CRITERIA: We included all randomised controlled trials of antifibrinolytic agents (aprotinin, tranexamic acid [TXA] and epsilon-aminocaproic acid) following acute traumatic injury. DATA COLLECTION AND ANALYSIS: The titles and abstracts identified in the electronic searches were screened by two independent authors to identify studies that had the potential to meet the inclusion criteria. The full reports of all such studies were obtained. From the results of the screened electronic searches, bibliographic searches, and contacts with experts, two authors independently selected trials meeting the inclusion criteria, with any disagreements resolved by consensus. MAIN RESULTS: Four trials met the inclusion criteria. Two trials with a combined total of 20,451 patients assessed the effects of TXA on mortality; TXA reduced the risk of death by 10% (RR=0.90, 95% CI 0.85 to 0.97; p=0.0035). Data from one trial involving 20,211 patients found that TXA reduced the risk of death due to bleeding by 15% (RR=0.85, 95% CI 0.76 to 0.96; p=0.0077). There was no evidence that TXA increased the risk of vascular occlusive events or need for surgical intervention. There was no substantial difference in the receipt of blood transfusion between the TXA and placebo groups. The two trials of aprotinin provided no reliable data. AUTHORS' CONCLUSIONS: TXA safely reduces mortality in bleeding trauma patients without increasing the risk of adverse events. Further trials are needed to determine the effects of TXA in patients with isolated traumatic brain injury.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Uncontrolled bleeding is an important cause of death in trauma victims. Antifibrinolytic treatment has been shown to reduce blood loss following surgery and may also be effective in reducing blood loss following trauma. OBJECTIVES: To quantify the effect of antifibrinolytic drugs in reducing blood loss, transfusion requirement and mortality after acute traumatic injury. SEARCH STRATEGY: We searched the Cochrane Injuries Group's Specialised Register, CENTRAL, MEDLINE, PubMed, EMBASE, Science Citation Index, National Research Register, Zetoc, SIGLE, Global Health, LILACS, and Current Controlled Trials. The Cochrane Injuries Group Specialised Register, CENTRAL, MEDLINE and EMBASE searches were updated in July 2010. SELECTION CRITERIA: We included all randomised controlled trials of antifibrinolytic agents (aprotinin, tranexamic acid [TXA] and epsilon-aminocaproic acid) following acute traumatic injury. DATA COLLECTION AND ANALYSIS: The titles and abstracts identified in the electronic searches were screened by two independent authors to identify studies that had the potential to meet the inclusion criteria. The full reports of all such studies were obtained. From the results of the screened electronic searches, bibliographic searches, and contacts with experts, two authors independently selected trials meeting the inclusion criteria, with any disagreements resolved by consensus. MAIN RESULTS: Four trials met the inclusion criteria. Two trials with a combined total of 20,451 patients assessed the effects of TXA on mortality; TXA reduced the risk of death by 10% (RR=0.90, 95% CI 0.85 to 0.97; p=0.0035). Data from one trial involving 20,211 patients found that TXA reduced the risk of death due to bleeding by 15% (RR=0.85, 95% CI 0.76 to 0.96; p=0.0077). There was no evidence that TXA increased the risk of vascular occlusive events or need for surgical intervention. There was no substantial difference in the receipt of blood transfusion between the TXA and placebo groups. The two trials of aprotinin provided no reliable data. AUTHORS' CONCLUSIONS: TXA safely reduces mortality in bleeding trauma patients without increasing the risk of adverse events. Further trials are needed to determine the effects of TXA in patients with isolated traumatic brain injury.
Schierhout, Gillian; Roberts, Ian
WITHDRAWN: Antiepileptic drugs for preventing seizures following acute traumatic brain injury. Journal Article
In: Cochrane database of systematic reviews (Online), vol. 6, no. 6, pp. CD000173–, 2012.
@article{lshtm21082,
title = {WITHDRAWN: Antiepileptic drugs for preventing seizures following acute traumatic brain injury.},
author = {Gillian Schierhout and Ian Roberts},
url = {http://researchonline.lshtm.ac.uk/id/eprint/21082/},
year = {2012},
date = {2012-01-01},
journal = {Cochrane database of systematic reviews (Online)},
volume = {6},
number = {6},
pages = {CD000173--},
publisher = {Cochrane Collaboration},
abstract = {BACKGROUND: Seizure activity in the early post-traumatic period following head injury may cause secondary brain damage as a result of increased metabolic demands, raised intracranial pressure and excess neurotransmitter release. OBJECTIVES: To determine the effects of prophylactic anti-epileptic agents for acute traumatic head injury. SEARCH METHODS: We searched the Cochrane Injuries Group specialised register, MEDLINE and the registers of the Cochrane Stroke Group and Cochrane Epilepsy Group. We contacted pharmaceutical companies who manufacture anti-epileptic agents, the National Institute of Neurological Disorders and Stroke, Epilepsy Division, and the United States' National Institute of Health. SELECTION CRITERIA: All randomised trials of anti-epileptic agents, in which study participants had a clinically defined acute traumatic head injury of any severity. Trials in which the intervention was started more than eight weeks after injury were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed the trial quality. Relative risks and 95% confidence intervals (95%CI) were calculated for each trial on an intention-to-treat basis, which included pre-drug loading exclusions. As long as statistical heterogeneity did not exist, for dichotomous data, summary relative risks and 95% confidence intervals were calculated using a fixed effects model. Where the source of heterogeneity could obviously be related to allocation concealment, drug type, or drug dose, we stratified the analyses on that dimension. MAIN RESULTS: We identified 10 eligible randomised controlled trials, including 2036 participants, but data was unavailable for four unpublished trials, representing 631 participants and they were excluded. For the remaining six trials, the pooled relative risk (RR) for early seizure prevention was 0.34 (95%CI 0.21, 0.54); based on this estimate, for every 100 patients treated, 10 would be kept seizure free in the first week. Seizure control in the acute phase was not accompanied by a reduction in mortality (RR = 1.15; 95%CI 0.89, 1.51), a reduction in death and neurological disability (RR = 1.49; 95%CI 1.06, 2.08 for carbamazepine and RR = 0.96; 95%CI 0.72, 1.26 for phenytoin) or a reduction in late seizures (pooled RR = 1.28; 95%CI 0.90, 1.81). The pooled relative risk for skin rashes was 1.57 (95%CI 0.57, 39.88). AUTHORS' CONCLUSIONS: Prophylactic anti-epileptics are effective in reducing early seizures, but there is no evidence that treatment with prophylactic anti-epileptics reduces the occurrence of late seizures, or has any effect on death and neurological disability. Insufficient evidence is available to establish the net benefit of prophylactic treatment at any time after injury.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Seizure activity in the early post-traumatic period following head injury may cause secondary brain damage as a result of increased metabolic demands, raised intracranial pressure and excess neurotransmitter release. OBJECTIVES: To determine the effects of prophylactic anti-epileptic agents for acute traumatic head injury. SEARCH METHODS: We searched the Cochrane Injuries Group specialised register, MEDLINE and the registers of the Cochrane Stroke Group and Cochrane Epilepsy Group. We contacted pharmaceutical companies who manufacture anti-epileptic agents, the National Institute of Neurological Disorders and Stroke, Epilepsy Division, and the United States' National Institute of Health. SELECTION CRITERIA: All randomised trials of anti-epileptic agents, in which study participants had a clinically defined acute traumatic head injury of any severity. Trials in which the intervention was started more than eight weeks after injury were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed the trial quality. Relative risks and 95% confidence intervals (95%CI) were calculated for each trial on an intention-to-treat basis, which included pre-drug loading exclusions. As long as statistical heterogeneity did not exist, for dichotomous data, summary relative risks and 95% confidence intervals were calculated using a fixed effects model. Where the source of heterogeneity could obviously be related to allocation concealment, drug type, or drug dose, we stratified the analyses on that dimension. MAIN RESULTS: We identified 10 eligible randomised controlled trials, including 2036 participants, but data was unavailable for four unpublished trials, representing 631 participants and they were excluded. For the remaining six trials, the pooled relative risk (RR) for early seizure prevention was 0.34 (95%CI 0.21, 0.54); based on this estimate, for every 100 patients treated, 10 would be kept seizure free in the first week. Seizure control in the acute phase was not accompanied by a reduction in mortality (RR = 1.15; 95%CI 0.89, 1.51), a reduction in death and neurological disability (RR = 1.49; 95%CI 1.06, 2.08 for carbamazepine and RR = 0.96; 95%CI 0.72, 1.26 for phenytoin) or a reduction in late seizures (pooled RR = 1.28; 95%CI 0.90, 1.81). The pooled relative risk for skin rashes was 1.57 (95%CI 0.57, 39.88). AUTHORS' CONCLUSIONS: Prophylactic anti-epileptics are effective in reducing early seizures, but there is no evidence that treatment with prophylactic anti-epileptics reduces the occurrence of late seizures, or has any effect on death and neurological disability. Insufficient evidence is available to establish the net benefit of prophylactic treatment at any time after injury.
Subaiya, Saleena; Roberts, Ian; Komolafe, Edward; Perel, Pablo
In: BMC emergency medicine, vol. 12, no. 1, pp. 17–, 2012.
@article{lshtm1462947,
title = {Predicting intracranial hemorrhage after traumatic brain injury in low and middle-income countries: a prognostic model based on a large, multi-center, international cohort.},
author = {Saleena Subaiya and Ian Roberts and Edward Komolafe and Pablo Perel},
url = {http://researchonline.lshtm.ac.uk/id/eprint/1462947/},
year = {2012},
date = {2012-01-01},
journal = {BMC emergency medicine},
volume = {12},
number = {1},
pages = {17--},
publisher = {BMC},
abstract = {BACKGROUND: Traumatic brain injury (TBI) affects approximately 10 million people annually, of which intracranial hemorrhage is a devastating sequelae, occurring in one-third to half of cases. Patients in low and middle-income countries (LMIC) are twice as likely to die following TBI as compared to those in high-income countries. Diagnostic capabilities and treatment options for intracranial hemorrhage are limited in LMIC as there are fewer computed tomography (CT) scanners and neurosurgeons per patient as in high-income countries. METHODS: The Medical Research Council CRASH-1 trial was utilized to build this model. The study cohort included all patients from LMIC who received a CT scan of the brain (n = 5669). Prognostic variables investigated included age, sex, time from injury to randomization, pupil reactivity, cause of injury, seizure and the presence of major extracranial injury. RESULTS: There were five predictors that were included in the final model; age, Glasgow Coma Scale, pupil reactivity, the presence of a major extracranial injury and time from injury to presentation. The model demonstrated good discrimination and excellent calibration (c-statistic 0.71). A simplified risk score was created for clinical settings to estimate the percentage risk of intracranial hemorrhage among TBI patients. CONCLUSION: Simple prognostic models can be used in LMIC to estimate the risk of intracranial hemorrhage among TBI patients. Combined with clinical judgment this may facilitate risk stratification, rapid transfer to higher levels of care and treatment in resource-poor settings.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Traumatic brain injury (TBI) affects approximately 10 million people annually, of which intracranial hemorrhage is a devastating sequelae, occurring in one-third to half of cases. Patients in low and middle-income countries (LMIC) are twice as likely to die following TBI as compared to those in high-income countries. Diagnostic capabilities and treatment options for intracranial hemorrhage are limited in LMIC as there are fewer computed tomography (CT) scanners and neurosurgeons per patient as in high-income countries. METHODS: The Medical Research Council CRASH-1 trial was utilized to build this model. The study cohort included all patients from LMIC who received a CT scan of the brain (n = 5669). Prognostic variables investigated included age, sex, time from injury to randomization, pupil reactivity, cause of injury, seizure and the presence of major extracranial injury. RESULTS: There were five predictors that were included in the final model; age, Glasgow Coma Scale, pupil reactivity, the presence of a major extracranial injury and time from injury to presentation. The model demonstrated good discrimination and excellent calibration (c-statistic 0.71). A simplified risk score was created for clinical settings to estimate the percentage risk of intracranial hemorrhage among TBI patients. CONCLUSION: Simple prognostic models can be used in LMIC to estimate the risk of intracranial hemorrhage among TBI patients. Combined with clinical judgment this may facilitate risk stratification, rapid transfer to higher levels of care and treatment in resource-poor settings.
Turner, Elizabeth L; Perel, Pablo; Clayton, Tim; Edwards, Phil; á, Adrian Hern V; Roberts, Ian; Shakur-Still, Haleema; Steyerberg, Ewout W; trial collaborators, CRASH
Covariate adjustment increased power in randomized controlled trials: an example in traumatic brain injury. Journal Article
In: Journal of clinical epidemiology, vol. 65, no. 5, pp. 474–481, 2012.
@article{lshtm20592,
title = {Covariate adjustment increased power in randomized controlled trials: an example in traumatic brain injury.},
author = {Elizabeth L Turner and Pablo Perel and Tim Clayton and Phil Edwards and Adrian Hern V á and Ian Roberts and Haleema Shakur-Still and Ewout W Steyerberg and CRASH trial collaborators},
url = {http://researchonline.lshtm.ac.uk/id/eprint/20592/},
year = {2012},
date = {2012-01-01},
journal = {Journal of clinical epidemiology},
volume = {65},
number = {5},
pages = {474--481},
publisher = {Elsevier},
abstract = {OBJECTIVE: We aimed to determine to what extent covariate adjustment could affect power in a randomized controlled trial (RCT) of a heterogeneous population with traumatic brain injury (TBI). STUDY DESIGN AND SETTING: We analyzed 14-day mortality in 9,497 participants in the Corticosteroid Randomization After Significant Head Injury (CRASH) RCT of corticosteroid vs. placebo. Adjustment was made using logistic regression for baseline covariates of two validated risk models derived from external data (International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury [IMPACT]) and from the CRASH data. The relative sample size (RESS) measure, defined as the ratio of the sample size required by an adjusted analysis to attain the same power as the unadjusted reference analysis, was used to assess the impact of adjustment. RESULTS: Corticosteroid was associated with higher mortality compared with placebo (odds ratio=1.25, 95% confidence interval=1.13-1.39). RESS of 0.79 and 0.73 were obtained by adjustment using the IMPACT and CRASH models, respectively, which, for example, implies an increase from 80% to 88% and 91% power, respectively. CONCLUSION: Moderate gains in power may be obtained using covariate adjustment from logistic regression in heterogeneous conditions such as TBI. Although analyses of RCTs might consider covariate adjustment to improve power, we caution against this approach in the planning of RCTs.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE: We aimed to determine to what extent covariate adjustment could affect power in a randomized controlled trial (RCT) of a heterogeneous population with traumatic brain injury (TBI). STUDY DESIGN AND SETTING: We analyzed 14-day mortality in 9,497 participants in the Corticosteroid Randomization After Significant Head Injury (CRASH) RCT of corticosteroid vs. placebo. Adjustment was made using logistic regression for baseline covariates of two validated risk models derived from external data (International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury [IMPACT]) and from the CRASH data. The relative sample size (RESS) measure, defined as the ratio of the sample size required by an adjusted analysis to attain the same power as the unadjusted reference analysis, was used to assess the impact of adjustment. RESULTS: Corticosteroid was associated with higher mortality compared with placebo (odds ratio=1.25, 95% confidence interval=1.13-1.39). RESS of 0.79 and 0.73 were obtained by adjustment using the IMPACT and CRASH models, respectively, which, for example, implies an increase from 80% to 88% and 91% power, respectively. CONCLUSION: Moderate gains in power may be obtained using covariate adjustment from logistic regression in heterogeneous conditions such as TBI. Although analyses of RCTs might consider covariate adjustment to improve power, we caution against this approach in the planning of RCTs.
2011
Roberts, Ian; Blackhall, Karen; Alderson, Phil; Bunn, Frances; Schierhout, Gillian
Human albumin solution for resuscitation and volume expansion in critically ill patients. Journal Article
In: The Cochrane database of systematic reviews, vol. 11, no. 11, pp. CD001208–, 2011.
@article{lshtm20452,
title = {Human albumin solution for resuscitation and volume expansion in critically ill patients.},
author = {Ian Roberts and Karen Blackhall and Phil Alderson and Frances Bunn and Gillian Schierhout},
url = {http://researchonline.lshtm.ac.uk/id/eprint/20452/},
year = {2011},
date = {2011-11-01},
journal = {The Cochrane database of systematic reviews},
volume = {11},
number = {11},
pages = {CD001208--},
publisher = {Cochrane Collaboration},
abstract = {BACKGROUND: Human albumin solutions are used for a range of medical and surgical problems. Licensed indications are the emergency treatment of shock and other conditions where restoration of blood volume is urgent, such as in burns and hypoproteinaemia. Human albumin solutions are more expensive than other colloids and crystalloids. OBJECTIVES: To quantify the effect on mortality of human albumin and plasma protein fraction (PPF) administration in the management of critically ill patients. SEARCH METHODS: We searched the Cochrane Injuries Group Specialised Register (searched 31 May 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2), MEDLINE (Ovid) (1948 to week 3 May 2011), EMBASE (Ovid) (1980 to Week 21 2011), CINAHL (EBSCO) (1982 to May 2011), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) (1970 to May 2011), ISI Web of Science: Conference Proceedings Citation Index - Science (CPCI-S) (1990 to May 2011), PubMed (www.ncbi.nlm.nih.gov/sites/entrez/) (searched 10 June 2011, limit: last 60 days). Reference lists of trials and review articles were checked, and authors of identified trials were contacted. SELECTION CRITERIA: Randomised controlled trials comparing albumin or PPF with no albumin or PPF or with a crystalloid solution in critically ill patients with hypovolaemia, burns or hypoalbuminaemia. DATA COLLECTION AND ANALYSIS: We collected data on the participants, albumin solution used, mortality at the end of follow up, and quality of allocation concealment. Analysis was stratified according to patient type. MAIN RESULTS: We found 38 trials meeting the inclusion criteria and reporting death as an outcome. There were 1,958 deaths among 10,842 trial participants.For hypovolaemia, the relative risk of death following albumin administration was 1.02 (95% confidence interval (CI) 0.92 to 1.13). This estimate was heavily influenced by the results of the SAFE trial, which contributed 75.2% of the information (based on the weights in the meta-analysis). For burns, the relative risk was 2.93 (95% CI 1.28 to 6.72) and for hypoalbuminaemia the relative risk was 1.26 (95% CI 0.84 to 1.88). There was no substantial heterogeneity between the trials in the various categories (Chi(2) = 26.66},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Human albumin solutions are used for a range of medical and surgical problems. Licensed indications are the emergency treatment of shock and other conditions where restoration of blood volume is urgent, such as in burns and hypoproteinaemia. Human albumin solutions are more expensive than other colloids and crystalloids. OBJECTIVES: To quantify the effect on mortality of human albumin and plasma protein fraction (PPF) administration in the management of critically ill patients. SEARCH METHODS: We searched the Cochrane Injuries Group Specialised Register (searched 31 May 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2), MEDLINE (Ovid) (1948 to week 3 May 2011), EMBASE (Ovid) (1980 to Week 21 2011), CINAHL (EBSCO) (1982 to May 2011), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) (1970 to May 2011), ISI Web of Science: Conference Proceedings Citation Index - Science (CPCI-S) (1990 to May 2011), PubMed (www.ncbi.nlm.nih.gov/sites/entrez/) (searched 10 June 2011, limit: last 60 days). Reference lists of trials and review articles were checked, and authors of identified trials were contacted. SELECTION CRITERIA: Randomised controlled trials comparing albumin or PPF with no albumin or PPF or with a crystalloid solution in critically ill patients with hypovolaemia, burns or hypoalbuminaemia. DATA COLLECTION AND ANALYSIS: We collected data on the participants, albumin solution used, mortality at the end of follow up, and quality of allocation concealment. Analysis was stratified according to patient type. MAIN RESULTS: We found 38 trials meeting the inclusion criteria and reporting death as an outcome. There were 1,958 deaths among 10,842 trial participants.For hypovolaemia, the relative risk of death following albumin administration was 1.02 (95% confidence interval (CI) 0.92 to 1.13). This estimate was heavily influenced by the results of the SAFE trial, which contributed 75.2% of the information (based on the weights in the meta-analysis). For burns, the relative risk was 2.93 (95% CI 1.28 to 6.72) and for hypoalbuminaemia the relative risk was 1.26 (95% CI 0.84 to 1.88). There was no substantial heterogeneity between the trials in the various categories (Chi(2) = 26.66
Perel, Pablo; Roberts, Ian
Colloids versus crystalloids for fluid resuscitation in critically ill patients. Journal Article
In: The Cochrane database of systematic reviews, vol. 3, no. 3, pp. CD000567–, 2011.
@article{lshtm1191,
title = {Colloids versus crystalloids for fluid resuscitation in critically ill patients.},
author = {Pablo Perel and Ian Roberts},
url = {http://researchonline.lshtm.ac.uk/id/eprint/1191/},
year = {2011},
date = {2011-03-01},
journal = {The Cochrane database of systematic reviews},
volume = {3},
number = {3},
pages = {CD000567--},
publisher = {Cochrane Collaboration},
abstract = {BACKGROUND: Colloid solutions are widely used in fluid resuscitation of critically ill patients. There are several choices of colloid and there is ongoing debate about the relative effectiveness of colloids compared to crystalloid fluids. OBJECTIVES: To assess the effects of colloids compared to crystalloids for fluid resuscitation in critically ill patients. SEARCH STRATEGY: We searched the Cochrane Injuries Group Specialised Register, CENTRAL (The Cochrane Library 2008, Issue 3), MEDLINE, EMBASE, ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED), ISI Web of Science: Conference Proceedings Citation Index-Science (CPCI-S), and The Controlled Trials metaRegister (www.controlled-trials.com). Reference lists of relevant studies and review articles were searched for further trials. The searches were last updated in September 2008. SELECTION CRITERIA: Randomised controlled trials (RCTs) of colloids compared to crystalloids, in patients requiring volume replacement. We excluded cross-over trials and trials in pregnant women and neonates. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and rated quality of allocation concealment. We analysed trials with a 'double-intervention', such as those comparing colloid in hypertonic crystalloid to isotonic crystalloid, separately. We stratified the analysis according to colloid type and quality of allocation concealment. MAIN RESULTS: We identified 65 eligible trials; 56 of these presented mortality data.Colloids compared to crystalloidsAlbumin or plasma protein fraction - 23 trials reported data on mortality, including a total of 7754 patients. The pooled relative risk (RR) from these trials was 1.01 (95% confidence interval (95% CI) 0.92 to 1.10). When we excluded the trial with poor quality allocation concealment, pooled RR was 1.00 (95% CI 0.91 to 1.09). Hydroxyethyl starch - 17 trials compared hydroxyethyl starch with crystalloids},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Colloid solutions are widely used in fluid resuscitation of critically ill patients. There are several choices of colloid and there is ongoing debate about the relative effectiveness of colloids compared to crystalloid fluids. OBJECTIVES: To assess the effects of colloids compared to crystalloids for fluid resuscitation in critically ill patients. SEARCH STRATEGY: We searched the Cochrane Injuries Group Specialised Register, CENTRAL (The Cochrane Library 2008, Issue 3), MEDLINE, EMBASE, ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED), ISI Web of Science: Conference Proceedings Citation Index-Science (CPCI-S), and The Controlled Trials metaRegister (www.controlled-trials.com). Reference lists of relevant studies and review articles were searched for further trials. The searches were last updated in September 2008. SELECTION CRITERIA: Randomised controlled trials (RCTs) of colloids compared to crystalloids, in patients requiring volume replacement. We excluded cross-over trials and trials in pregnant women and neonates. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and rated quality of allocation concealment. We analysed trials with a 'double-intervention', such as those comparing colloid in hypertonic crystalloid to isotonic crystalloid, separately. We stratified the analysis according to colloid type and quality of allocation concealment. MAIN RESULTS: We identified 65 eligible trials; 56 of these presented mortality data.Colloids compared to crystalloidsAlbumin or plasma protein fraction - 23 trials reported data on mortality, including a total of 7754 patients. The pooled relative risk (RR) from these trials was 1.01 (95% confidence interval (95% CI) 0.92 to 1.10). When we excluded the trial with poor quality allocation concealment, pooled RR was 1.00 (95% CI 0.91 to 1.09). Hydroxyethyl starch - 17 trials compared hydroxyethyl starch with crystalloids
Edwards, P; Durand, MA; Hollister, M; Green, J; Lutchmun, S; Kessel, A; Roberts, I
Scald risk in social housing can be reduced through thermostatic control system without increasing Legionella risk: a cluster randomised trial. Journal Article
In: Archives of disease in childhood, vol. 96, no. 12, pp. 1097–1102, 2011.
@article{lshtm64,
title = {Scald risk in social housing can be reduced through thermostatic control system without increasing Legionella risk: a cluster randomised trial.},
author = {P Edwards and MA Durand and M Hollister and J Green and S Lutchmun and A Kessel and I Roberts},
url = {http://researchonline.lshtm.ac.uk/id/eprint/64/},
year = {2011},
date = {2011-01-01},
journal = {Archives of disease in childhood},
volume = {96},
number = {12},
pages = {1097--1102},
publisher = {BMJ Publishing Group},
abstract = {OBJECTIVE: To quantify the effects of a thermostatic control system in social (public) housing on the prevalence of dangerous (>60°C) water temperatures and on fuel consumption. DESIGN: Pair-matched double-blind cluster randomised controlled trial. SETTING: Social housing in a deprived inner-London borough. PARTICIPANTS: 150 households recruited as clusters from 22 social housing estates. Four small estates were combined into two clusters (resulting in a total of 10 pairs of clusters). INTERVENTION: Social housing estate boiler houses were randomised to a thermostatic control sterilisation programme (heating water to 65°C during 00:00-06:00 h and to 50°C from 06:00 to 00:00 h daily) or to standard control (constant temperature 65°C). MAIN OUTCOME MEASURES: Water temperature over 60°C ('dangerous') after running taps for 1 min and daily fuel consumption (cubic feet of gas). RESULTS: 10 clusters (80 households) were allocated to the sterilisation programme and 10 clusters (70 households) to control, of which 73 and 67 households, respectively, were analysed. Prevalence of dangerous (>60°C) hot water temperatures at 1 min was significantly reduced with the sterilisation programme (mean of cluster prevalence 1% in sterilisation programme group vs 34% in control group; absolute difference 33%, 95% CI 12% to 54%; p=0.006). Prevalence of high (>55°C) hot water temperatures at 1 min was significantly reduced (31% sterilisation vs 59% control; absolute difference 28%, 95% CI 9% to 47%; p=0.009). Gas consumption per day reduced more in the control group than in the sterilisation programme group, although not statistically significantly (p=0.125). CONCLUSIONS: The thermostatic control with daily sterilisation was effective in capping hot water temperatures and therefore reduced scald risk. Although expected to save energy, fuel consumption was increased relative to the control group. Trial registration ClinicalTrials.gov ID: NCT00874692.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE: To quantify the effects of a thermostatic control system in social (public) housing on the prevalence of dangerous (>60°C) water temperatures and on fuel consumption. DESIGN: Pair-matched double-blind cluster randomised controlled trial. SETTING: Social housing in a deprived inner-London borough. PARTICIPANTS: 150 households recruited as clusters from 22 social housing estates. Four small estates were combined into two clusters (resulting in a total of 10 pairs of clusters). INTERVENTION: Social housing estate boiler houses were randomised to a thermostatic control sterilisation programme (heating water to 65°C during 00:00-06:00 h and to 50°C from 06:00 to 00:00 h daily) or to standard control (constant temperature 65°C). MAIN OUTCOME MEASURES: Water temperature over 60°C ('dangerous') after running taps for 1 min and daily fuel consumption (cubic feet of gas). RESULTS: 10 clusters (80 households) were allocated to the sterilisation programme and 10 clusters (70 households) to control, of which 73 and 67 households, respectively, were analysed. Prevalence of dangerous (>60°C) hot water temperatures at 1 min was significantly reduced with the sterilisation programme (mean of cluster prevalence 1% in sterilisation programme group vs 34% in control group; absolute difference 33%, 95% CI 12% to 54%; p=0.006). Prevalence of high (>55°C) hot water temperatures at 1 min was significantly reduced (31% sterilisation vs 59% control; absolute difference 28%, 95% CI 9% to 47%; p=0.009). Gas consumption per day reduced more in the control group than in the sterilisation programme group, although not statistically significantly (p=0.125). CONCLUSIONS: The thermostatic control with daily sterilisation was effective in capping hot water temperatures and therefore reduced scald risk. Although expected to save energy, fuel consumption was increased relative to the control group. Trial registration ClinicalTrials.gov ID: NCT00874692.
Free, Caroline; Knight, Rosemary; Robertson, Steven; Whittaker, Robyn; Edwards, Phil; Zhou, Weiwei; Rodgers, Anthony; Cairns, John; Kenward, Michael G; Roberts, Ian
Smoking cessation support delivered via mobile phone text messaging (txt2stop): a single-blind, randomised trial. Journal Article
In: Lancet, vol. 378, no. 9785, pp. 49–55, 2011.
@article{lshtm303b,
title = {Smoking cessation support delivered via mobile phone text messaging (txt2stop): a single-blind, randomised trial.},
author = {Caroline Free and Rosemary Knight and Steven Robertson and Robyn Whittaker and Phil Edwards and Weiwei Zhou and Anthony Rodgers and John Cairns and Michael G Kenward and Ian Roberts},
url = {http://researchonline.lshtm.ac.uk/id/eprint/303/},
year = {2011},
date = {2011-01-01},
journal = {Lancet},
volume = {378},
number = {9785},
pages = {49--55},
publisher = {Elsevier},
abstract = {BACKGROUND: Smoking cessation programmes delivered via mobile phone text messaging show increases in self-reported quitting in the short term. We assessed the effect of an automated smoking cessation programme delivered via mobile phone text messaging on continuous abstinence, which was biochemically verified at 6 months. METHODS: In this single-blind, randomised trial, undertaken in the UK, smokers willing to make a quit attempt were randomly allocated, using an independent telephone randomisation system, to a mobile phone text messaging smoking cessation programme (txt2stop), comprising motivational messages and behavioural-change support, or to a control group that received text messages unrelated to quitting. The system automatically generated intervention or control group texts according to the allocation. Outcome assessors were masked to treatment allocation. The primary outcome was self-reported continuous smoking abstinence, biochemically verified at 6 months. All analyses were by intention to treat. This study is registered, number ISRCTN 80978588. FINDINGS: We assessed 11,914 participants for eligibility. 5800 participants were randomised, of whom 2915 smokers were allocated to the txt2stop intervention and 2885 were allocated to the control group; eight were excluded because they were randomised more than once. Primary outcome data were available for 5524 (95%) participants. Biochemically verified continuous abstinence at 6 months was significantly increased in the txt2stop group (10·7% txt2stop vs 4·9% control, relative risk [RR] 2·20, 95% CI 1·80-2·68; p<0·0001). Similar results were obtained when participants that were lost to follow-up were treated as smokers (268 [9%] of 2911 txt2stop vs 124 [4%] of 2881 control [RR 2·14, 95% CI 1·74-2·63; p<0·0001]), and when they were excluded (268 [10%] of 2735 txt2stop vs 124 [4%] of 2789 control [2·20, 1·79-2·71; p<0·0001]). No significant heterogeneity was shown in any of the prespecified subgroups. INTERPRETATION: The txt2stop smoking cessation programme significantly improved smoking cessation rates at 6 months and should be considered for inclusion in smoking cessation services. FUNDING: UK Medical Research Council, Primary Care Research Networks.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Smoking cessation programmes delivered via mobile phone text messaging show increases in self-reported quitting in the short term. We assessed the effect of an automated smoking cessation programme delivered via mobile phone text messaging on continuous abstinence, which was biochemically verified at 6 months. METHODS: In this single-blind, randomised trial, undertaken in the UK, smokers willing to make a quit attempt were randomly allocated, using an independent telephone randomisation system, to a mobile phone text messaging smoking cessation programme (txt2stop), comprising motivational messages and behavioural-change support, or to a control group that received text messages unrelated to quitting. The system automatically generated intervention or control group texts according to the allocation. Outcome assessors were masked to treatment allocation. The primary outcome was self-reported continuous smoking abstinence, biochemically verified at 6 months. All analyses were by intention to treat. This study is registered, number ISRCTN 80978588. FINDINGS: We assessed 11,914 participants for eligibility. 5800 participants were randomised, of whom 2915 smokers were allocated to the txt2stop intervention and 2885 were allocated to the control group; eight were excluded because they were randomised more than once. Primary outcome data were available for 5524 (95%) participants. Biochemically verified continuous abstinence at 6 months was significantly increased in the txt2stop group (10·7% txt2stop vs 4·9% control, relative risk [RR] 2·20, 95% CI 1·80-2·68; p<0·0001). Similar results were obtained when participants that were lost to follow-up were treated as smokers (268 [9%] of 2911 txt2stop vs 124 [4%] of 2881 control [RR 2·14, 95% CI 1·74-2·63; p<0·0001]), and when they were excluded (268 [10%] of 2735 txt2stop vs 124 [4%] of 2789 control [2·20, 1·79-2·71; p<0·0001]). No significant heterogeneity was shown in any of the prespecified subgroups. INTERPRETATION: The txt2stop smoking cessation programme significantly improved smoking cessation rates at 6 months and should be considered for inclusion in smoking cessation services. FUNDING: UK Medical Research Council, Primary Care Research Networks.
Free, Caroline; Roberts, Ian G; Abramsky, Tanya; Fitzgerald, Molly; Wensley, Frances
A systematic review of randomised controlled trials of interventions promoting effective condom use. Journal Article
In: Journal of epidemiology and community health, vol. 65, no. 2, pp. 100–110, 2011.
@article{lshtm1299,
title = {A systematic review of randomised controlled trials of interventions promoting effective condom use.},
author = {Caroline Free and Ian G Roberts and Tanya Abramsky and Molly Fitzgerald and Frances Wensley},
url = {http://researchonline.lshtm.ac.uk/id/eprint/1299/},
year = {2011},
date = {2011-01-01},
journal = {Journal of epidemiology and community health},
volume = {65},
number = {2},
pages = {100--110},
publisher = {BMJ Publishing Group},
abstract = {BACKGROUND: Effective condom use can prevent sexually transmitted infections (STIs) and unwanted pregnancy. We conducted a systematic review and methodological appraisal of randomised controlled trials (RCTs) of interventions to promote effective condom use. METHODS: We searched for all RCTs of interventions to promote effective condom use using the Cochrane Infectious Diseases Group's trials register (Oct 2006), CENTRAL (Issue 4, 2006), MEDLINE (1966 to Oct 2006), EMBASE (1974 to Oct 2006), LILACS (1982 to Oct 2006), IBSS (1951 to Oct 2006) and Psychinfo (1996 to Oct 2006). We extracted data on allocation sequence, allocation concealment, blinding, loss to follow-up and measures of effect. Effect estimates were calculated. RESULTS: We identified 139 trials. Seven out of ten trials reported reductions in ány STI' with five statistically significant results. Three out of four trials reported reductions in pregnancy, although none was statistically significant. Only four trials met all the quality criteria. Trials reported a median of 11 (IQR 7-17) outcome measures. Few trials used the same outcome measure. Altogether, 10 trials (7%) used the outcome ány STI', 4 (3%) self-reported pregnancy and 22 (16%) used 'condom use at last sex'. CONCLUSIONS: The results are generally consistent with modest benefits but there is considerable potential for bias due to poor trial quality. Because of the low proportion of trials using the same outcome the potential for bias from selective reporting of outcomes is considerable. Despite the public health importance of increasing condom use there is little reliable evidence on the effectiveness of condom promotion interventions.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Effective condom use can prevent sexually transmitted infections (STIs) and unwanted pregnancy. We conducted a systematic review and methodological appraisal of randomised controlled trials (RCTs) of interventions to promote effective condom use. METHODS: We searched for all RCTs of interventions to promote effective condom use using the Cochrane Infectious Diseases Group's trials register (Oct 2006), CENTRAL (Issue 4, 2006), MEDLINE (1966 to Oct 2006), EMBASE (1974 to Oct 2006), LILACS (1982 to Oct 2006), IBSS (1951 to Oct 2006) and Psychinfo (1996 to Oct 2006). We extracted data on allocation sequence, allocation concealment, blinding, loss to follow-up and measures of effect. Effect estimates were calculated. RESULTS: We identified 139 trials. Seven out of ten trials reported reductions in ány STI' with five statistically significant results. Three out of four trials reported reductions in pregnancy, although none was statistically significant. Only four trials met all the quality criteria. Trials reported a median of 11 (IQR 7-17) outcome measures. Few trials used the same outcome measure. Altogether, 10 trials (7%) used the outcome ány STI', 4 (3%) self-reported pregnancy and 22 (16%) used 'condom use at last sex'. CONCLUSIONS: The results are generally consistent with modest benefits but there is considerable potential for bias due to poor trial quality. Because of the low proportion of trials using the same outcome the potential for bias from selective reporting of outcomes is considerable. Despite the public health importance of increasing condom use there is little reliable evidence on the effectiveness of condom promotion interventions.
Guerriero, Carla; Cairns, John; Perel, Pablo; Shakur-Still, Haleema; Roberts, Ian; trial collaborators, CRASH 2
Cost-effectiveness analysis of administering tranexamic acid to bleeding trauma patients using evidence from the CRASH-2 trial. Journal Article
In: PloS one, vol. 6, no. 5, pp. e18987–, 2011.
@article{lshtm767,
title = {Cost-effectiveness analysis of administering tranexamic acid to bleeding trauma patients using evidence from the CRASH-2 trial.},
author = {Carla Guerriero and John Cairns and Pablo Perel and Haleema Shakur-Still and Ian Roberts and CRASH 2 trial collaborators},
url = {http://researchonline.lshtm.ac.uk/id/eprint/767/},
year = {2011},
date = {2011-01-01},
journal = {PloS one},
volume = {6},
number = {5},
pages = {e18987--},
publisher = {Public Library of Science},
abstract = {OBJECTIVE: To assess the cost effectiveness of giving tranexamic acid (TXA) to bleeding trauma patients in low, middle and high income settings. METHODS: The CRASH-2 trial showed that TXA administration reduces the risk of death in bleeding trauma patients with a small but statistically significant increase in non-intensive care stay. A Markov model was used to assess the cost effectiveness of TXA in Tanzania, India and the United Kingdom (UK). The health outcome was the number of life years gained (LYs). Two costs were considered: the cost of administering TXA and the cost of additional days in hospital. Cost data were obtained from hospitals, World Health Organization (WHO) database and UK reference costs. Cost-effectiveness was measured in international dollars ($) per LY. Both deterministic and probabilistic sensitivity analyses were performed to test the robustness of the results to model assumptions. FINDINGS: Administering TXA to bleeding trauma patients within three hours of injury saved an estimated 372, 315 and 755 LYs per 1,000 trauma patients in Tanzania, India and the UK respectively. The cost of giving TXA to 1,000 patients was $17,483 in Tanzania, $19,550 in India and $30,830 in the UK. The incremental cost of giving TXA versus not giving TXA was $18,025 in Tanzania, $20,670 in India and $48,002 in the UK. The estimated incremental cost per LY gained of administering TXA is $48, $66 and $64 in Tanzania, India and the UK respectively. CONCLUSION: Early administration of TXA to bleeding trauma patients is likely to be highly cost effective in low, middle and high income settings. TRIAL REGISTRATION: This paper uses data collected by the CRASH 2 trial: Controlled-Trials.com ISRCTN86750102, Clinicaltrials.govNCT00375258 and South African Clinical Trial Register DOH-27-0607-1919.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE: To assess the cost effectiveness of giving tranexamic acid (TXA) to bleeding trauma patients in low, middle and high income settings. METHODS: The CRASH-2 trial showed that TXA administration reduces the risk of death in bleeding trauma patients with a small but statistically significant increase in non-intensive care stay. A Markov model was used to assess the cost effectiveness of TXA in Tanzania, India and the United Kingdom (UK). The health outcome was the number of life years gained (LYs). Two costs were considered: the cost of administering TXA and the cost of additional days in hospital. Cost data were obtained from hospitals, World Health Organization (WHO) database and UK reference costs. Cost-effectiveness was measured in international dollars ($) per LY. Both deterministic and probabilistic sensitivity analyses were performed to test the robustness of the results to model assumptions. FINDINGS: Administering TXA to bleeding trauma patients within three hours of injury saved an estimated 372, 315 and 755 LYs per 1,000 trauma patients in Tanzania, India and the UK respectively. The cost of giving TXA to 1,000 patients was $17,483 in Tanzania, $19,550 in India and $30,830 in the UK. The incremental cost of giving TXA versus not giving TXA was $18,025 in Tanzania, $20,670 in India and $48,002 in the UK. The estimated incremental cost per LY gained of administering TXA is $48, $66 and $64 in Tanzania, India and the UK respectively. CONCLUSION: Early administration of TXA to bleeding trauma patients is likely to be highly cost effective in low, middle and high income settings. TRIAL REGISTRATION: This paper uses data collected by the CRASH 2 trial: Controlled-Trials.com ISRCTN86750102, Clinicaltrials.govNCT00375258 and South African Clinical Trial Register DOH-27-0607-1919.
Ker, Katharine; Edwards, Phil; Roberts, Ian
Misadventures to patients during surgical and medical care in England and Wales: an analysis of deaths and hospital episodes. Journal Article
In: Journal of the Royal Society of Medicine, vol. 104, no. 7, pp. 292–298, 2011.
@article{lshtm80,
title = {Misadventures to patients during surgical and medical care in England and Wales: an analysis of deaths and hospital episodes.},
author = {Katharine Ker and Phil Edwards and Ian Roberts},
url = {http://researchonline.lshtm.ac.uk/id/eprint/80/},
year = {2011},
date = {2011-01-01},
journal = {Journal of the Royal Society of Medicine},
volume = {104},
number = {7},
pages = {292--298},
publisher = {SAGE Publications},
abstract = {Objectives To estimate incidence of injury to patients attributed to misadventures during surgical and medical care by age group and to examine recent trends. Design Analysis of routine morbidity and mortality data categorized by the 9th and 10th revisions of the International Classification of Diseases. Participants Children 0-14 years and adults ≥15 years. Setting England and Wales during 1999 to 2008 (hospital episodes) and 1979 to 2009 (deaths). Main outcome measures We calculated deaths per million person-years and per 1000 hospital episodes; hospital episodes per 100,000 person-years and per 100,000 procedures performed. Results The rate of death attributed to misadventures during surgical and medical care in patients aged 75 years and older was over 50 times (rate ratio 57.2; 95% confidence interval 38.3-85.3) higher than in children aged 1-14 years. Estimated hospital episode rates were 20 times (RR 20.0; 18.9-21.2) higher in patients aged 75 years and older. Mortality attributed to misadventures declined from 1.1 (0.9-1.4) deaths per million person-years in 1979 to 0.4 (0.2-0.6) in 2009. Hospital episodes of misadventures decreased between 1999 and 2008 from 30.8 (29.9-31.8) episodes per 100,000 procedures to 23.25 (22.5-24.1), but increased from 7.8 (7.6-8.1) per 100,000 person-years to 9.8 (9.5-10.1). Conclusions Misadventures during surgical and medical care are an important cause of avoidable injury. Older patients appear to be at higher risk of experiencing and dying from misadventure. Interpretation of recent trends is limited by uncertainties regarding the consistency and coverage of coding.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Objectives To estimate incidence of injury to patients attributed to misadventures during surgical and medical care by age group and to examine recent trends. Design Analysis of routine morbidity and mortality data categorized by the 9th and 10th revisions of the International Classification of Diseases. Participants Children 0-14 years and adults ≥15 years. Setting England and Wales during 1999 to 2008 (hospital episodes) and 1979 to 2009 (deaths). Main outcome measures We calculated deaths per million person-years and per 1000 hospital episodes; hospital episodes per 100,000 person-years and per 100,000 procedures performed. Results The rate of death attributed to misadventures during surgical and medical care in patients aged 75 years and older was over 50 times (rate ratio 57.2; 95% confidence interval 38.3-85.3) higher than in children aged 1-14 years. Estimated hospital episode rates were 20 times (RR 20.0; 18.9-21.2) higher in patients aged 75 years and older. Mortality attributed to misadventures declined from 1.1 (0.9-1.4) deaths per million person-years in 1979 to 0.4 (0.2-0.6) in 2009. Hospital episodes of misadventures decreased between 1999 and 2008 from 30.8 (29.9-31.8) episodes per 100,000 procedures to 23.25 (22.5-24.1), but increased from 7.8 (7.6-8.1) per 100,000 person-years to 9.8 (9.5-10.1). Conclusions Misadventures during surgical and medical care are an important cause of avoidable injury. Older patients appear to be at higher risk of experiencing and dying from misadventure. Interpretation of recent trends is limited by uncertainties regarding the consistency and coverage of coding.
Lingsma, Hester F; Roozenbeek, Bob; Perel, Pablo; Roberts, Ian; Maas, Andrew IR; Steyerberg, Ewout W
Between-centre differences and treatment effects in randomized controlled trials: a case study in traumatic brain injury. Journal Article
In: Trials, vol. 12, no. 1, pp. 201–, 2011.
@article{lshtm18749,
title = {Between-centre differences and treatment effects in randomized controlled trials: a case study in traumatic brain injury.},
author = {Hester F Lingsma and Bob Roozenbeek and Pablo Perel and Ian Roberts and Andrew IR Maas and Ewout W Steyerberg},
url = {http://researchonline.lshtm.ac.uk/id/eprint/18749/},
year = {2011},
date = {2011-01-01},
journal = {Trials},
volume = {12},
number = {1},
pages = {201--},
publisher = {BMC},
abstract = {BACKGROUND: In Traumatic Brain Injury (TBI), large between-centre differences in outcome exist and many clinicians believe that such differences influence estimation of the treatment effect in randomized controlled trial (RCTs). The aim of this study was to assess the influence of between-centre differences in outcome on the estimated treatment effect in a large RCT in TBI. METHODS: We used data from the MRC CRASH trial on the efficacy of corticosteroid infusion in patients with TBI. We analyzed the effect of the treatment on 14 day mortality with fixed effect logistic regression. Next we used random effects logistic regression with a random intercept to estimate the treatment effect taking into account between-centre differences in outcome. Between-centre differences in outcome were expressed with a 95% range of odds ratios (OR) for centres compared to the average, based on the variance of the random effects (tau2). A random effects logistic regression model with random slopes was used to allow the treatment effect to vary by centre. The variation in treatment effect between the centres was expressed in a 95% range of the estimated treatment ORs. RESULTS: In 9978 patients from 237 centres, 14-day mortality was 19.5%. Mortality was higher in the treatment group (OR = 1.22, p = 0.00010). Using a random effects model showed large between-centre differences in outcome (95% range of centre effects: 0.27- 3.71), but did not substantially change the estimated treatment effect (OR = 1.24, p = 0.00003). There was limited, although statistically significant, between-centre variation in the treatment effect (OR = 1.22, 95% treatment OR range: 1.17-1.26). CONCLUSION: Large between-centre differences in outcome do not necessarily affect the estimated treatment effect in RCTs, in contrast to current beliefs in the clinical area of TBI.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: In Traumatic Brain Injury (TBI), large between-centre differences in outcome exist and many clinicians believe that such differences influence estimation of the treatment effect in randomized controlled trial (RCTs). The aim of this study was to assess the influence of between-centre differences in outcome on the estimated treatment effect in a large RCT in TBI. METHODS: We used data from the MRC CRASH trial on the efficacy of corticosteroid infusion in patients with TBI. We analyzed the effect of the treatment on 14 day mortality with fixed effect logistic regression. Next we used random effects logistic regression with a random intercept to estimate the treatment effect taking into account between-centre differences in outcome. Between-centre differences in outcome were expressed with a 95% range of odds ratios (OR) for centres compared to the average, based on the variance of the random effects (tau2). A random effects logistic regression model with random slopes was used to allow the treatment effect to vary by centre. The variation in treatment effect between the centres was expressed in a 95% range of the estimated treatment ORs. RESULTS: In 9978 patients from 237 centres, 14-day mortality was 19.5%. Mortality was higher in the treatment group (OR = 1.22, p = 0.00010). Using a random effects model showed large between-centre differences in outcome (95% range of centre effects: 0.27- 3.71), but did not substantially change the estimated treatment effect (OR = 1.24, p = 0.00003). There was limited, although statistically significant, between-centre variation in the treatment effect (OR = 1.22, 95% treatment OR range: 1.17-1.26). CONCLUSION: Large between-centre differences in outcome do not necessarily affect the estimated treatment effect in RCTs, in contrast to current beliefs in the clinical area of TBI.
Roberts, I
Crash-2: Antifibrinolytic Treatment in Traumatic Brain Injury Inproceedings
In: pp. A33–A34, Mary Ann Liebert, 2011.
@inproceedings{lshtm707,
title = {Crash-2: Antifibrinolytic Treatment in Traumatic Brain Injury},
author = {I Roberts},
url = {http://researchonline.lshtm.ac.uk/id/eprint/707/},
year = {2011},
date = {2011-01-01},
journal = {Journal of neurotrauma},
volume = {28},
number = {5},
pages = {A33--A34},
publisher = {Mary Ann Liebert},
keywords = {},
pubstate = {published},
tppubtype = {inproceedings}
}
Roberts, Ian
Fat chance for Cancun. Journal Article
In: Journal of the Royal Society of Medicine, vol. 104, no. 1, pp. 43–44, 2011.
@article{lshtm1810,
title = {Fat chance for Cancun.},
author = {Ian Roberts},
url = {http://researchonline.lshtm.ac.uk/id/eprint/1810/},
year = {2011},
date = {2011-01-01},
journal = {Journal of the Royal Society of Medicine},
volume = {104},
number = {1},
pages = {43--44},
publisher = {SAGE Publications},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Roberts, Ian
Tranexamic Acid - a recipe for saving lives in traumatic bleeding. Journal Article
In: The journal of Tehran Heart Center, vol. 6, no. 4, pp. 178–, 2011.
@article{lshtm354869,
title = {Tranexamic Acid - a recipe for saving lives in traumatic bleeding.},
author = {Ian Roberts},
url = {http://researchonline.lshtm.ac.uk/id/eprint/354869/},
year = {2011},
date = {2011-01-01},
journal = {The journal of Tehran Heart Center},
volume = {6},
number = {4},
pages = {178--},
publisher = {Tehran University of Medical Sciences},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Roberts, Ian
Tranexamic acid--a recipe for saving lives in traumatic bleeding. Journal Article
In: International journal of epidemiology, vol. 40, no. 5, pp. 1145–, 2011.
@article{lshtm20330,
title = {Tranexamic acid--a recipe for saving lives in traumatic bleeding.},
author = {Ian Roberts},
url = {http://researchonline.lshtm.ac.uk/id/eprint/20330/},
year = {2011},
date = {2011-01-01},
journal = {International journal of epidemiology},
volume = {40},
number = {5},
pages = {1145--},
publisher = {Oxford University Press (OUP)},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Roberts, Ian
Tranexamic acid--a recipe for saving lives in traumatic bleeding. Journal Article
In: Journal of primary health care, vol. 3, no. 4, pp. 331–, 2011.
@article{lshtm60540,
title = {Tranexamic acid--a recipe for saving lives in traumatic bleeding.},
author = {Ian Roberts},
url = {http://researchonline.lshtm.ac.uk/id/eprint/60540/},
year = {2011},
date = {2011-01-01},
journal = {Journal of primary health care},
volume = {3},
number = {4},
pages = {331--},
publisher = {Royal New Zealand College of General Practitioners},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Roberts, Ian
Why petrol tanks and stomachs are competing to be filled. Journal Article
In: Journal of public health (Oxford, England), vol. 33, no. 2, pp. 170–171, 2011.
@article{lshtm693,
title = {Why petrol tanks and stomachs are competing to be filled.},
author = {Ian Roberts},
url = {http://researchonline.lshtm.ac.uk/id/eprint/693/},
year = {2011},
date = {2011-01-01},
journal = {Journal of public health (Oxford, England)},
volume = {33},
number = {2},
pages = {170--171},
publisher = {Oxford University Press (OUP)},
keywords = {},
pubstate = {published},
tppubtype = {article}
}