Publications

@article{lshtm3364155,

title = {Effects of tranexamic acid on platelet function and thrombin generation (ETAPlaT): WOMAN trial sub-study.},

author = {Kastriot Dallaku and Haleema Shakur-Still and Ian Roberts and Phil Edwards and Danielle Beaumont and Maria Delius and Braun Siegmund and Orion Gliozheni and Ilir Tasha and Saimir Cenameri and Ulrich Mansmann},

url = {http://researchonline.lshtm.ac.uk/id/eprint/3364155/},

year  = {2016},

date = {2016-12-01},

journal = {Scientific reports},

volume = {1},

pages = {29--},

publisher = {Nature Research (part of Springer Nature)},

abstract = {Background. Postpartum haemorrhage (PPH) is a leading cause of maternal death. Tranexamic acid (TXA) has the potential to reduce bleeding and a large randomized placebo controlled trial of its effect in women with PPH (The WOMAN trial) is underway. TXA might also affect coagulation factors and platelets. Objectives. To examine the effect of TXA on thrombin generation, platelet function, fibrinogen, D-dimer and coagulation factors in women with PPH. Methods. We will conduct a sub-study within the WOMAN trial. Women with clinically diagnosed primary PPH after vaginal or caesarean delivery are eligible for inclusion. Blood samples will be collected at baseline and 30 minutes after the first dose of study treatment. Using platelet poor plasma we will measure thrombin generation, fibrinogen, D-dimer, factor V and VIII, and Von Willebrand factor. Platelet function will be evaluated in whole blood using Multiplate? tests. Outcomes. The primary outcome is the effect of TXA on thrombin generation. Secondary outcomes include the effect of TXA on platelet function, fibrinogen, D-dimer and coagulation factors.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm2997151,

title = {How do children travel to school in urban India? A cross-sectional study of 5,842 children in Hyderabad.},

author = {Shailaja Tetali and P Edwards and GVS Murthy I Roberts},

url = {http://researchonline.lshtm.ac.uk/id/eprint/2997151/},

year  = {2016},

date = {2016-10-01},

journal = {BMC public health},

volume = {16},

number = {1},

pages = {1099--},

publisher = {BMC},

abstract = {BACKGROUND: Millions of children travel to school every day in India, yet little is known about this journey. We examined the distribution and determinants of school travel in Hyderabad, India. METHODS: We conducted a cross-sectional survey using a two-stage stratified cluster sampling design. School travel questionnaires were used to collect data from children aged 11-14 years, attending private, semi-private and government funded schools in Hyderabad. We used Google Earth to estimate the distance from home to school for each child and modelled the relationship between distance to school and mode of travel, adjusting for confounders. RESULTS: Forty five of the 48 eligible schools that were selected agreed to participate, providing a total sample of 5842 children. The response rate was 99 %. Most children walked (57 %) or cycled (6 %) to school but 36 % used motorised transport (mostly bus). The proportion using motorised transport was higher in children attending private schools (41 %) than in those attending government schools (24 %). Most (90 %) children lived within 5km of school and 36 % lived within 1km. Greater distance to school was strongly associated with the use of motorised transport. Children living close to school were much more likely to walk or cycle. CONCLUSIONS: Most children in Hyderabad walk (57 %) or cycle (6 %) to school. If these levels are to be maintained, there is an urgent need to ensure that walking and cycling are safe and pleasant. Social policies that decrease distances to school could have a large impact on road traffic injuries, air pollution, and physical activity levels.},

keywords = {},

pubstate = {published},

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}

@article{lshtm4650019,

title = {Erratum to: Simple steps to develop trial follow-up procedures.},

author = {Ona McCarthy and Rebecca S French and Ian Roberts and Caroline Free},

url = {http://researchonline.lshtm.ac.uk/id/eprint/4650019/},

year  = {2016},

date = {2016-10-01},

journal = {TRIALS},

volume = {17},

number = {1},

pages = {484--},

publisher = {BIOMED CENTRAL LTD},

abstract = {Unfortunately, the original version of this article [1] contained an error. There were errors in the reference numbers in Additional file 1. This has now been corrected and Additional file 1 is included here with the correct reference numbers.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm2997194,

title = {Does tranexamic acid improve outcomes in traumatic brain injury?},

author = {Abda Mahmood and Ian Roberts and Haleema Shakur-Still and Tim Harris and Antonio Belli},

url = {http://researchonline.lshtm.ac.uk/id/eprint/2997194/},

year  = {2016},

date = {2016-09-01},

journal = {BMJ (Clinical research ed)},

volume = {354},

pages = {i4814--},

publisher = {BMJ Publishing Group},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm2997183,

title = {Land use, transport, and population health: estimating the health benefits of compact cities.},

author = {Mark Stevenson and Jason Thompson and Thiago Hérick de Sá and Reid Ewing and Dinesh Mohan and Rod McClure and Ian Roberts and Geetam Tiwari and Billie Giles-Corti and Xiaoduan Sun and Mark Wallace and James Woodcock},

url = {http://researchonline.lshtm.ac.uk/id/eprint/2997183/},

year  = {2016},

date = {2016-09-01},

journal = {Lancet},

volume = {388},

number = {10062},

pages = {2925--2935},

publisher = {Elsevier},

abstract = {Using a health impact assessment framework, we estimated the population health effects arising from alternative land-use and transport policy initiatives in six cities. Land-use changes were modelled to reflect a compact city in which land-use density and diversity were increased and distances to public transport were reduced to produce low motorised mobility, namely a modal shift from private motor vehicles to walking, cycling, and public transport. The modelled compact city scenario resulted in health gains for all cities (for diabetes, cardiovascular disease, and respiratory disease) with overall health gains of 420-826 disability-adjusted life-years (DALYs) per 100 000 population. However, for moderate to highly motorised cities, such as Melbourne, London, and Boston, the compact city scenario predicted a small increase in road trauma for cyclists and pedestrians (health loss of between 34 and 41 DALYs per 100 000 population). The findings suggest that government policies need to actively pursue land-use elements-particularly a focus towards compact cities-that support a modal shift away from private motor vehicles towards walking, cycling, and low-emission public transport. At the same time, these policies need to ensure the provision of safe walking and cycling infrastructure. The findings highlight the opportunities for policy makers to positively influence the overall health of city populations.},

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pubstate = {published},

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}

@article{lshtm2884467,

title = {Interpretation of the evidence for the efficacy and safety of statin therapy.},

author = {R Collins and C Reith and J Emberson and J Armitage and C Baigent and L Blackwell and R Blumenthal and J Danesh and GD Smith and D DeMets and S Evans and M Law and S MacMahon and S Martin and B Neal and N Poulter and D Preiss and P Ridker and I Roberts and A Rodgers and P Sandercock and K Schulz and P Sever and J Simes and L Smeeth and N Wald and S Yusuf and R Peto},

url = {http://researchonline.lshtm.ac.uk/id/eprint/2884467/},

year  = {2016},

date = {2016-09-01},

journal = {Lancet},

publisher = {Elsevier},

abstract = {This Review is intended to help clinicians, patients, and the public make informed decisions about statin therapy for the prevention of heart attacks and strokes. It explains how the evidence that is available from randomised controlled trials yields reliable information about both the efficacy and safety of statin therapy. In addition, it discusses how claims that statins commonly cause adverse effects reflect a failure to recognise the limitations of other sources of evidence about the effects of treatment. Large-scale evidence from randomised trials shows that statin therapy reduces the risk of major vascular events (ie, coronary deaths or myocardial infarctions, strokes, and coronary revascularisation procedures) by about one-quarter for each mmol/L reduction in LDL cholesterol during each year (after the first) that it continues to be taken. The absolute benefits of statin therapy depend on an individual's absolute risk of occlusive vascular events and the absolute reduction in LDL cholesterol that is achieved. For example, lowering LDL cholesterol by 2 mmol/L (77 mg/dL) with an effective low-cost statin regimen (eg, atorvastatin 40 mg daily, costing about pounds2 per month) for 5 years in 10 000 patients would typically prevent major vascular events from occurring in about 1000 patients (ie, 10% absolute benefit) with pre-existing occlusive vascular disease (secondary prevention) and in 500 patients (ie, 5% absolute benefit) who are at increased risk but have not yet had a vascular event (primary prevention). Statin therapy has been shown to reduce vascular disease risk during each year it continues to be taken, so larger absolute benefits would accrue with more prolonged therapy, and these benefits persist long term. The only serious adverse events that have been shown to be caused by long-term statin therapy-ie, adverse effects of the statin-are myopathy (defined as muscle pain or weakness combined with large increases in blood concentrations of creatine kinase), new-onset diabetes mellitus, and, probably, haemorrhagic stroke. Typically, treatment of 10 000 patients for 5 years with an effective regimen (eg, atorvastatin 40 mg daily) would cause about 5 cases of myopathy (one of which might progress, if the statin therapy is not stopped, to the more severe condition of rhabdomyolysis), 50-100 new cases of diabetes, and 5-10 haemorrhagic strokes. However, any adverse impact of these side-effects on major vascular events has already been taken into account in the estimates of the absolute benefits. Statin therapy may cause symptomatic adverse events (eg, muscle pain or weakness) in up to about 50-100 patients (ie, 0?5-1?0% absolute harm) per 10 000 treated for 5 years. However, placebo-controlled randomised trials have shown definitively that almost all of the symptomatic adverse events that are attributed to statin therapy in routine practice are not actually caused by it (ie, they represent misattribution). The large-scale evidence available from randomised trials also indicates that it is unlikely that large absolute excesses in other serious adverse events still await discovery. Consequently, any further findings that emerge about the effects of statin therapy would not be expected to alter materially the balance of benefits and harms. It is, therefore, of concern that exaggerated claims about side-effect rates with statin therapy may be responsible for its under-use among individuals at increased risk of cardiovascular events. For, whereas the rare cases of myopathy and any muscle-related symptoms that are attributed to statin therapy generally resolve rapidly when treatment is stopped, the heart attacks or strokes that may occur if statin therapy is stopped unnecessarily can be devastating.},

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pubstate = {published},

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}

@article{lshtm2821097,

title = {Does tranexamic acid prevent postpartum haemorrhage? A systematic review of randomised controlled trials.},

author = {K Ker and Haleema Shakur-Still and I Roberts},

url = {http://researchonline.lshtm.ac.uk/id/eprint/2821097/},

year  = {2016},

date = {2016-08-01},

journal = {BJOG},

volume = {123},

number = {11},

pages = {1745--52},

publisher = {Wiley},

abstract = {: Postpartum haemorrhage is the leading cause of maternal mortality. Tranexamic acid (TXA) reduces surgical haemorrhage and the risk of death in bleeding trauma patients.ensuremath
 : To assess the effects of TXA on risk of postpartum haemorrhage and other clinically relevant outcomes.ensuremath
 : We searched the MEDLINE, CENTRAL, EMBASE, PubMed, ClinicalTrials.gov and WHO ICTRP electronic databases to May 2015.ensuremath
 : Randomised controlled trials comparing TXA with no TXA or placebo in women giving birth vaginally or by caesarean section.ensuremath
 : Two authors extracted data and assessed the risk of bias for each trial. Because of data concerns we did not conduct a meta-analysis.ensuremath
 : We found 26 trials including a total of 4191 women. Examination of the trial reports raised concerns about the quality of the data. Eight trial reports contained identical or similar text and there were important data inconsistencies in several trials. Two trials did not have ethics committee approval. Meta-analysis of baseline variables suggested that randomisation was inadequate in many trials.ensuremath
 : There is no reliable evidence that TXA prevents postpartum haemorrhage during childbirth. Many of the trials conducted to date are small, low quality and contain serious flaws.ensuremath
 : No evidence that TXA prevents postpartum haemorrhage. Existing trials are unreliable, with serious flaws.ensuremath
},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm2728832,

title = {Cochrane: the unfinished symphony of research synthesis.},

author = {Ian Roberts and Katharine Ker},

url = {http://researchonline.lshtm.ac.uk/id/eprint/2728832/},

year  = {2016},

date = {2016-07-01},

journal = {Systematic reviews},

volume = {5},

number = {1},

pages = {115--},

publisher = {BMC},

abstract = {The NHS needs valid information on the safety and effectiveness of healthcare interventions. Cochrane systematic reviews are an important source of this information. Traditionally, Cochrane has attempted to identify and include all relevant trials in systematic reviews on the basis that if all trials are identified and included, there should be no selection bias. However, a predictable consequence of the drive to include all trials is that some studies are included that are not trials (false positives). Including such studies in reviews might increase bias. More effort is needed to authenticate trials to be included in reviews, but this task is bedevilled by the enormous increase in the number of 'trials' conducted each year. We argue that excluding small trials from reviews would release resources for more detailed appraisal of larger trials. Conducting fewer but broader reviews that contain fewer but properly validated trials might better serve patients' interests.},

keywords = {},

pubstate = {published},

tppubtype = {article}

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@article{lshtm2551664,

title = {The effect of tranexamic acid on the risk of death and hysterectomy in women with post-partum haemorrhage: statistical analysis plan for the WOMAN trial.},

author = {Haleema Shakur-Still and Ian Roberts and Philip Edwards and Diana Elbourne and Zarko Alfirevic and Carine Ronsmans},

url = {http://researchonline.lshtm.ac.uk/id/eprint/2551664/},

year  = {2016},

date = {2016-05-01},

journal = {Trials},

volume = {17},

number = {1},

pages = {249--},

publisher = {BMC},

abstract = {BACKGROUND: Severe haemorrhage is a leading cause of maternal death worldwide. Most haemorrhage deaths occur soon after childbirth. Severe post-partum bleeding is sometimes managed by the surgical removal of the uterus (hysterectomy). Death and hysterectomy are important health consequences of post-partum haemorrhage, and clinical trials of interventions aimed at preventing these outcomes are needed. METHODS: The World Maternal Antifibrinolytic trial aims to determine the effect of tranexamic acid on death, hysterectomy and other health outcomes in women with post-partum haemorrhage. It is an international, multicentre, randomised trial. Approximately 20,000 women with post-partum haemorrhage will be randomly allocated to receive an intravenous injection of either tranexamic acid or matching placebo in addition to usual care. The primary outcome measure is a composite of death in hospital or hysterectomy within 42 days of delivery. The cause of death will be described. Secondary outcomes include death, death due to bleeding, hysterectomy, thromboembolic events, blood transfusion, surgical and radiological interventions, complications, adverse events and quality of life. The health status and occurrence of thromboembolic events in breastfed babies will also be reported. We will conduct subgroup analyses for the primary outcome by time to treatment, type of delivery and cause of haemorrhage. We will conduct an analysis of treatment effect adjusted for baseline risk. DISCUSSION: The World Maternal Antifibrinolytic trial should provide reliable evidence for the efficacy of tranexamic acid in the prevention of death, hysterectomy and other outcomes that are important to patients. We present a protocol update and the statistical analysis plan for the trial. TRIAL REGISTRATION: Current Controlled Trials ISRCTN76912190 (Registration date 08 December 2008), Clinicaltrials.gov NCT00872469 (Registration date 30 March 2009) and Pan African Clinical Trials Registry: PACTR201007000192283 (Registration date 02 September 2010).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm2572485,

title = {Time for sharing data to become routine: the seven excuses for not doing so are all invalid.},

author = {Richard Smith and Ian Roberts},

url = {http://researchonline.lshtm.ac.uk/id/eprint/2572485/},

year  = {2016},

date = {2016-04-01},

journal = {F1000Research},

volume = {5},

pages = {781--},

publisher = {F1000Research},

abstract = {Data are more valuable than scientific papers but researchers are incentivised to publish papers not share data. Patients are the main beneficiaries of data sharing but researchers have several incentives not to share: others might use their data to get ahead in the academic rat race; they might be scooped; their results might not be replicable; competitors may reach different conclusions; their data management might be exposed as poor; patient confidentiality might be breached; and technical difficulties make sharing impossible. All of these barriers can be overcome and researchers should be rewarded for sharing data. Data sharing must become routine.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm2545312,

title = {Fibrinolytic shutdown: fascinating theory but randomized controlled trial data are needed.},

author = {Ian Roberts},

url = {http://researchonline.lshtm.ac.uk/id/eprint/2545312/},

year  = {2016},

date = {2016-04-01},

journal = {Transfusion},

volume = {56 Sup},

pages = {S115--S118},

publisher = {Wiley},

abstract = {Administration of tranexamic acid (TXA) to bleeding trauma patients who are within 3 hours of injury has been shown to safely reduce mortality in bleeding trauma patients. However, some believe that thromboelastography (TEG or ROTEM) can be used to subdivide these patients into those that will benefit from TXA and those that will be harmed by it. If thromboelastography can be used in this way there could be important patient benefits. However, if the approach is misguided, patients could be denied a lifesaving treatment. I believe that rather than debate the theoretical basis of this hypothesis, it should be tested by conducting a randomized controlled trial. Bleeding trauma patients who are within 3 hours of injury should be randomly allocated to receive TXA treatment or thromboelastometry-guided TXA treatment with the risk of death and complications compared between the groups. An adequately powered clinical trial would better serve patient interest than ongoing debate.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm4241824,

title = {Intravenous tranexamic acid for hyperacute primary intracerebral hemorrhage: Protocol for a randomized, placebo-controlled trial.},

author = {Nikola Sprigg and Katie Robson and Philip Bath and Robert Dineen and Ian Roberts and Tom Robinson and Christine Roffe and David Werring and Rustam Al-Shahi Salman and Stuart Pocock and Lelia Duley and Tim England and David Whynes and Alfonso Ciccone and Ann Charlotte Laska and Hanne Christensen and Serefnur Ozturk and Ronan Collins and Daniel Bereczki and Juan Jose Egea-Guerrero and Zhe Kang Law and Anna Czlonkowska and David Seiffge and Maia Beredzie and TICH-2 Investigators},

url = {http://researchonline.lshtm.ac.uk/id/eprint/4241824/},

year  = {2016},

date = {2016-04-01},

journal = {International journal of stroke},

volume = {11},

number = {6},

pages = {683--694},

publisher = {SAGE Publications},

abstract = {RATIONALE: Outcome after intracerebral hemorrhage remains poor. Tranexamic acid is easy to administer, readily available, inexpensive, and effective in other hemorrhagic conditions. AIM: This randomized trial aims to test the hypothesis that intravenous tranexamic acid given within 8 h of spontaneous intracerebral hemorrhage reduces death or dependency. DESIGN: Phase III prospective double-blind randomized placebo-controlled trial. Participants within 8 h of spontaneous intracerebral hemorrhage are randomized to receive either intravenous tranexamic acid 1 g 10 min bolus followed by 1 g 8 h infusion, or placebo. SAMPLE SIZE ESTIMATES: A trial of 2000 participants (300 from start-up phase and 1700 from main phase) will have 90% power to detect an ordinal shift of the modified Rankin Scale with odds ratio 0.79. STUDY OUTCOMES: The primary outcome is death or dependency measured by ordinal shift analysis of the 7 level mRS at day 90. Secondary outcomes are neurological impairment at day 7 and disability, quality of life, cognition, and mood at day 90. Safety outcomes are death, serious adverse events, thromboembolic events, and seizures. Cost outcomes are length of stay in hospital, readmission, and institutionalization. DISCUSSION: This pragmatic trial is assessing efficacy of tranexamic acid after spontaneous intracerebral hemorrhage. Recruitment started in 2013; as of 15th January 2016 1355 participants have been enrolled, from 95 centers in seven countries. Recruitment is due to end in 2017. TICH-2 Trial is registered as ISRCTN93732214.},

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pubstate = {published},

tppubtype = {article}

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@article{lshtm2534175,

title = {Simple steps to develop trial follow-up procedures.},

author = {Ona McCarthy and Rebecca S French and Ian Roberts and Caroline Free},

url = {http://researchonline.lshtm.ac.uk/id/eprint/2534175/},

year  = {2016},

date = {2016-01-01},

journal = {Trials},

volume = {17},

number = {1},

pages = {28--},

publisher = {BMC},

abstract = {BACKGROUND: Loss to follow-up in randomised controlled trials reduces statistical power and increases the potential for bias. Almost half of all trials fail to achieve their follow-up target. Statistical methods have been described for handling losses to follow-up and systematic reviews have identified interventions that increase follow-up. However, there is little guidance on how to develop practical follow-up procedures. This paper describes the development of follow-up procedures in a pilot randomised controlled trial of a sexual health intervention that required participants to provide and return questionnaires and chlamydia test samples in the post. We identified effective methods to increase follow-up from systematic reviews. We developed and tested prototype procedures to identify barriers to follow-up completion. We asked trial participants about their views on our follow-up procedures and revised the methods accordingly. RESULTS: We identified 17 strategies to increase follow-up and employed all but five. We found that some postal test kits do not fit through letterboxes and that that the test instructions were complicated. After identifying the appropriate sized test kit and simplifying the instructions, we obtained user opinions. Users wanted kits to be sent in coloured envelopes (so that they could identify them easily), with simple instructions and questionnaires and wanted to be notified before we sent the kits. We achieved 92 % (183/200) overall follow-up for the postal questionnaire at 1 month and 82 % (163/200) at 12 months. We achieved 86 % (171/200) overall follow-up for the postal chlamydia test at 3 months and 80 % (160/200) at 12 months. CONCLUSIONS: By using established methods to increase follow-up, testing prototype procedures and seeking user opinions, we achieved higher follow-up than previous sexual health trials. However, it is not possible to determine if the increase in response was due to our follow-up procedures. TRIAL REGISTRATION: Current Controlled Trials ISRCTN02304709 Date of registration: 27 March 2013.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm2699469,

title = {Can text messages increase safer sex behaviours in young people? Intervention development and pilot randomised controlled trial.},

author = {Caroline Free and Ona McCarthy and Rebecca S French and Kaye Wellings and Susan Michie and Ian Roberts and Karen Devries and Sujit Rathod and Julia Bailey and Jonathan Syred and Phil Edwards and Graham Hart and Melissa Palmer and Paula Baraitser},

url = {http://researchonline.lshtm.ac.uk/id/eprint/2699469/},

year  = {2016},

date = {2016-01-01},

journal = {Health technology assessment (Winchester, England)},

volume = {20},

number = {57},

pages = {1--82},

publisher = {NIHR Journals Library},

abstract = {BACKGROUND: Younger people bear the heaviest burden of sexually transmitted infections (STIs). Partner notification, condom use and STI testing can reduce infection but many young people lack the knowledge, skills and confidence needed to carry out these behaviours. Text messages can provide effective behavioural support. The acceptability and feasibility of a randomised controlled trial of safer sex support delivered by text message are not known. OBJECTIVES: To assess the acceptability and feasibility of a randomised controlled trial of a safer sex intervention delivered by text message for young people aged 16-24 years. DESIGN: (1) Intervention development; (2) follow-up procedure development; (3) a pilot, parallel-arm randomised controlled trial with allocation via remote automated randomisation (ratio of 1 : 1) (participants were unmasked, whereas researchers analysing samples and data were masked); and (4) qualitative interviews. SETTING: Participants were recruited from sexual health services in the UK. PARTICIPANTS: Young people aged 16-24 years diagnosed with chlamydia or reporting unprotected sex with more than one partner in the last year. INTERVENTIONS: A theory- and evidence-based safer sex intervention designed, with young people's input, to reduce the incidence of STIs by increasing the correct treatment of STIs, partner notification, condom use and STI testing before unprotected sex with a new partner. The intervention was delivered via automated mobile phone messaging over 12 months. The comparator was a monthly text message checking contact details. MAIN OUTCOME MEASURES: (1) Development of the intervention based on theory, evidence and expert and user views; (2) follow-up procedures; (3) pilot trial primary outcomes: full recruitment within 3 months and follow-up rate for the proposed primary outcomes for the main trial; and (4) participants' views and experiences regarding the acceptability of the intervention. RESULTS: In total, 200 participants were randomised in the pilot trial, of whom 99 were allocated to the intervention and 101 were allocated to the control. We fully recruited early and achieved an 81% follow-up rate for our proposed primary outcome of the cumulative incidence of chlamydia at 12 months. There was no differential follow-up between groups. In total, 97% of messages sent were successfully delivered to participants' mobile phones. Recipients reported that the tone, language, content and frequency of messages were appropriate. Messages reportedly increased knowledge of and confidence in how to use condoms and negotiate condom use and reduced stigma about STIs, enabling participants to tell a partner about a STI. CONCLUSIONS: Our research shows that the intervention is acceptable and feasible to deliver. Our pilot trial demonstrated that a main trial is feasible. It remains unclear which behaviour change techniques and elements of the intervention or follow-up procedures are associated with effectiveness. A further limitation is that in the trial one person entering data and the participants were unmasked. A randomised controlled trial to establish the effects of the intervention on STIs at 12 months is needed. TRIAL REGISTRATION: Current Controlled Trials ISRCTN02304709. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 57. See the NIHR Journals Library website for further project information.},

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@article{lshtm2478703,

title = {Road traffic injuries to children during the school commute in Hyderabad, India: cross-sectional survey.},

author = {Shailaja Tetali and P Edwards and GVS Murthy and I Roberts},

url = {http://researchonline.lshtm.ac.uk/id/eprint/2478703/},

year  = {2015},

date = {2015-12-01},

journal = {Injury prevention},

volume = {22},

number = {3},

pages = {171--175},

publisher = {BMJ Publishing Group},

abstract = {BACKGROUND: India is motorising rapidly. With increasing motorisation, road traffic injuries are predicted to increase. A third of a billion children travel to school every day in India, but little is known about children's safety during the school commute. We investigated road traffic injury to children during school journeys. METHODS: We conducted a cross-sectional survey in Hyderabad using a two-stage stratified cluster sampling design. We used school travel questionnaires to record any road injury in the past 12 months that resulted in at least 1 day of school missed or required treatment by a doctor or nurse. We estimated the prevalence of road injury by usual mode of travel and distance to school. RESULTS: The total sample was 5842 children, of whom 5789 (99.1%) children answered the question on road injury. The overall prevalence of self-reported road injury in the last 12 months during school journeys was 17% (95% CI 12.9% to 21.7%). A higher proportion of boys (25%) reported a road injury than girls (11%). There was a strong association between road injury, travel mode and distance to school. Children who cycled to school were more likely to be injured compared with children who walked (OR 1.5; 95% CI 1.2 to 2.0). Travel by school bus was safer than walking (OR 0.5; 95% CI 0.3 to 0.9). CONCLUSIONS: A sixth of the children reported a road traffic injury in the past 12 months during school journeys in Hyderabad. Injury prevention interventions should focus on making walking and cycling safer for children.},

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pubstate = {published},

tppubtype = {article}

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@article{lshtm2338133,

title = {Development and validation of a self-administered questionnaire to estimate the distance and mode of children's travel to school in urban India.},

author = {Shailaja Tetali and Phil Edwards and GVS Murthy and I Roberts},

url = {http://researchonline.lshtm.ac.uk/id/eprint/2338133/},

year  = {2015},

date = {2015-10-01},

journal = {BMC medical research methodology},

volume = {15},

number = {1},

pages = {92--},

publisher = {BMC},

abstract = {BACKGROUND: Although some 300 million Indian children travel to school every day, little is known about how they get there. This information is important for transport planners and public health authorities. This paper presents the development of a self-administered questionnaire and examines its reliability and validity in estimating distance and mode of travel to school in a low resource urban setting. METHODS: We developed a questionnaire on children's travel to school. We assessed test re-test reliability by repeating the questionnaire one week later (n = 61). The questionnaire was improved and re-tested (n = 68). We examined the convergent validity of distance estimates by comparing estimates based on the nearest landmark to children's homes with a 'gold standard' based on one-to-one interviews with children using detailed maps (n = 50). RESULTS: Most questions showed fair to almost perfect agreement. Questions on usual mode of travel (ensuremathkappa 0.73- 0.84) and road injury (ensuremathkappa 0.61- 0.72) were found to be more reliable than those on parental permissions (ensuremathkappa 0.18- 0.30), perception of safety (ensuremathkappa 0.00- 0.54), and physical activity (ensuremathkappa -0.01- 0.07). The distance estimated by the nearest landmark method was not significantly different than the in-depth method for walking , 52 m [95 % CI -32 m to 135 m], 10 % of the mean difference, and for walking and cycling combined, 65 m [95 % CI -30 m to 159 m], 11 % of the mean difference. For children who used motorized transport (excluding private school bus), the nearest landmark method under-estimated distance by an average of 325 metres [95 % CI -664 m to 1314 m], 15 % of the mean difference. CONCLUSIONS: A self-administered questionnaire was found to provide reliable information on the usual mode of travel to school, and road injury, in a small sample of children in Hyderabad, India. The 'nearest landmark' method can be applied in similar low-resource settings, for a reasonably accurate estimate of the distance from a child's home to school.},

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tppubtype = {article}

}

@article{lshtm2287469,

title = {Exploring redundant research into the effect of tranexamic acid on surgical bleeding: further analysis of a systematic review of randomised controlled trials.},

author = {Katharine Ker and Ian Roberts},

url = {http://researchonline.lshtm.ac.uk/id/eprint/2287469/},

year  = {2015},

date = {2015-08-01},

journal = {BMJ open},

volume = {5},

number = {8},

pages = {e009460--},

publisher = {BMJ Publishing Group},

abstract = {OBJECTIVES: We examined whether apparent redundancy in a cumulative meta-analysis of trials is justified by concern about bias, random error or generalisability of the results. DESIGN: Cumulative meta-analysis, risk of bias assessment, trial sequential analysis, description of study participants over time and a review of rationales for conducting trials. DATA SOURCE: 126 randomised trials included in a systematic review assessing of tranexamic acid on blood transfusion in surgery. RESULTS: The cumulative meta-analysis including all trials shows that the pooled estimate first reached statistical significance after the second trial in 1993. When the analysis was limited to the 38 high-quality trials and adjusted to account for potential systematic and random errors, the uncertainty was resolved after the 22nd trial in 2008. When the analysis was restricted to the two high-quality, prospectively registered trials, the cumulative z-curve crossed p=0.05 but not the monitoring boundary, suggesting an early potentially spurious statistically significant result. As precision of the pooled estimate increased, the number of trials initiated increased, although trial activity appeared to move to other surgery types. Most (62%) reports cited at least one systematic review. Of 118 reports examined, concern about generalisability was the reason for initiating the trial in 60%. Other reasons were to address a question other than the effect on bleeding (26%) and to confirm previously observed results (4%). Unawareness of previous research was apparent in 4% trials, while the rationale was unclear in 3%. CONCLUSIONS: Our results indicate that poor quality is a more important cause of redundant research than the failure to review existing evidence. Concerns about generalisability of results is the main motivation for new trials. Contrary to previous claims, our results suggest that systematic reviews showing treatment effects can stimulate an increase in trial activity rather than reduce it.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm2212609,

title = {Extending evidence for the use of tranexamic acid from traumatic haemorrhage to other patients with major bleeding: do we need more than one haemorrhage protocol? The case of gastrointestinal bleeding.},

author = {SJ Stanworth and D Manno and Haleema Shakur-Still and T Coats and P Edwards and I Gilmore and V Jairath and A Veitch and I Roberts},

url = {http://researchonline.lshtm.ac.uk/id/eprint/2212609/},

year  = {2015},

date = {2015-06-01},

journal = {Transfusion medicine (Oxford, England)},

volume = {25},

number = {3},

pages = {198--200},

publisher = {Wiley},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm2210686,

title = {The knowledge system underpinning healthcare is not fit for purpose and must change.},

author = {Ian Roberts and Katharine Ker and Phil Edwards and Deirdre Beecher and Daniela Manno and Emma Sydenham},

url = {http://researchonline.lshtm.ac.uk/id/eprint/2210686/},

year  = {2015},

date = {2015-06-01},

journal = {BMJ (Clinical research ed)},

volume = {350},

number = {jun02},

pages = {h2463--},

publisher = {BMJ Publishing Group},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm2167436,

title = {Antifibrinolytic drugs for acute traumatic injury.},

author = {Katharine Ker and Ian Roberts and Haleema Shakur-Still and Tim J Coats},

url = {http://researchonline.lshtm.ac.uk/id/eprint/2167436/},

year  = {2015},

date = {2015-05-01},

journal = {The Cochrane database of systematic reviews},

volume = {5},

number = {5},

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 assess the effect of antifibrinolytic drugs in patients with acute traumatic injury. SEARCH METHODS: We ran the most recent search in January 2015. We searched the Cochrane Injuries Group's Specialised Register, The Cochrane Library, Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), Embase Classic+Embase (OvidSP), PubMed and clinical trials registries. SELECTION CRITERIA: Randomised controlled trials of antifibrinolytic agents (aprotinin, tranexamic acid [TXA], epsilon-aminocaproic acid and aminomethylbenzoic acid) following acute traumatic injury. DATA COLLECTION AND ANALYSIS: From the results of the screened electronic searches, bibliographic searches, and contacts with experts, two authors independently selected trials meeting the inclusion criteria, and extracted data. One review author assessed the risk of bias for key domains.Outcome measures included: mortality at end of follow-up (all-cause); adverse events (specifically vascular occlusive events [myocardial infarction, stroke, deep vein thrombosis or pulmonary embolism] and renal failure); number of patients undergoing surgical intervention or receiving blood transfusion; volume of blood transfused; volume of intracranial bleeding; brain ischaemic lesions; death or disability.We rated the quality of the evidence as 'high', 'moderate', 'low' or 'very low' according to the GRADE approach. MAIN RESULTS: Three trials met the inclusion criteria.Two trials (n = 20,451) assessed the effect of TXA. The larger of these (CRASH-2},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm2162890,

title = {Comparison of routes for achieving parenteral access with a focus on the management of patients with Ebola virus disease.},

author = {Katharine Ker and Gavin Tansley and Deirdre Beecher and Anders Perner and Haleema Shakur-Still and Tim Harris and Ian Roberts},

url = {http://researchonline.lshtm.ac.uk/id/eprint/2162890/},

year  = {2015},

date = {2015-02-01},

journal = {The Cochrane database of systematic reviews},

volume = {2},

number = {2},

pages = {CD011386--},

publisher = {Cochrane Collaboration},

abstract = {BACKGROUND: Dehydration is an important cause of death in patients with Ebola virus disease (EVD). Parenteral fluids are often required in patients with fluid requirements in excess of their oral intake. The peripheral intravenous route is the most commonly used method of parenteral access, but inserting and maintaining an intravenous line can be challenging in the context of EVD. Therefore it is important to consider the advantages and disadvantages of different routes for achieving parenteral access (e.g. intravenous, intraosseous, subcutaneous and intraperitoneal). OBJECTIVES: To compare the reliability, ease of use and speed of insertion of different parenteral access methods. SEARCH METHODS: We ran the search on 17 November 2014. We searched the Cochrane Injuries Group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily, Ovid MEDLINE(R) and Ovid OLDMEDLINE(R), Embase Classic + Embase (OvidSP), CINAHL (EBSCOhost), clinicaltrials.gov and screened reference lists. SELECTION CRITERIA: Randomised controlled trials comparing different parenteral routes for the infusion of fluids or medication. DATA COLLECTION AND ANALYSIS: Two review authors examined the titles and abstracts of records obtained by searching the electronic databases to determine eligibility. Two review authors extracted data from the included trials and assessed the risk of bias. Outcome measures of interest were success of insertion; time required for insertion; number of insertion attempts; number of dislodgements; time period with functional access; local site reactions; clinicians' perception of ease of administration; needlestick injury to healthcare workers; patients' discomfort; and mortality. For trials involving the administration of fluids we also collected data on the volume of fluid infused, changes in serum electrolytes and markers of renal function. We rated the quality of the evidence as 'high', 'moderate', 'low' or 'very low' according to the GRADE approach for the following outcomes: success of insertion, time required for insertion, number of dislodgements, volume of fluid infused and needlestick injuries. MAIN RESULTS: We included 17 trials involving 885 participants. Parenteral access was used to infuse fluids in 11 trials and medications in six trials. None of the trials involved patients with EVD. Intravenous and intraosseous access was compared in four trials; intravenous and subcutaneous access in 11; peripheral intravenous and intraperitoneal access in one; saphenous vein cutdown and intraosseous access in one; and intraperitoneal with subcutaneous access in one. All of the trials assessing the intravenous method involved peripheral intravenous access.We judged few trials to be at low risk of bias for any of the assessed domains.Compared to the intraosseous group, patients in the intravenous group were more likely to experience an insertion failure (risk ratio (RR) 3.89, 95% confidence interval (CI) 2.39 to 6.33; n = 242; GRADE rating: low). We did not pool data for time to insertion but estimates from the trials suggest that inserting intravenous access takes longer (GRADE rating: moderate). Clinicians judged the intravenous route to be easier to insert (RR 0.15, 95% CI 0.04 to 0.61; n = 182). A larger volume of fluids was infused via the intravenous route (GRADE rating: moderate). There was no evidence of a difference between the two routes for any other outcomes, including adverse events.Compared to the subcutaneous group, patients in the intravenous group were more likely to experience an insertion failure (RR 14.79, 95% CI 2.87 to 76.08; n = 238; GRADE rating: moderate) and dislodgement of the device (RR 3.78, 95% CI 1.16 to 12.34; n = 67; GRADE rating: low). Clinicians also judged the intravenous route as being more difficult to insert and patients were more likely to be agitated in the intravenous group. Patients in the intravenous group were more likely to develop a local infection and phlebitis, but were less likely to develop erythema, oedema or swelling than those in the subcutaneous group. A larger volume of fluids was infused into patients via the intravenous route. There was no evidence of a difference between the two routes for any other outcome.There were insufficient data to reliably determine if the risk of insertion failure differed between the saphenous vein cutdown (SVC) and intraosseous method (RR 4.00, 95% CI 0.51 to 31.13; GRADE rating: low). Insertion using SVC took longer than the intraosseous method (MD 219.60 seconds, 95% CI 135.44 to 303.76; GRADE rating: moderate). There were no data and therefore there was no evidence of a difference between the two routes for any other outcome.There were insufficient data to reliably determine the relative effects of intraperitoneal or central intravenous access relative to any other parenteral access method. AUTHORS' CONCLUSIONS: There are several different ways of achieving parenteral access in patients who are unable meet their fluid requirements with oral intake alone. The quality of the evidence, as assessed using the GRADE criteria, is somewhat limited because of the lack of adequately powered trials at low risk of bias. However, we believe that there is sufficient evidence to draw the following conclusions: if peripheral intravenous access can be achieved easily, this allows infusion of larger volumes of fluid than other routes; but if this is not possible, the intraosseous and subcutaneous routes are viable alternatives. The subcutaneous route may be suitable for patients who are not severely dehydrated but in whom ongoing fluid losses cannot be met by oral intake.A film to accompany this review can be viewed here (http://youtu.be/ArVPzkf93ng).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm2124254,

title = {Good clinical practice in trauma care research: considerations for inter-hospital patient transfers.},

author = {Catriona Bryceland and Sophie Ellis and Danielle Beaumont and Haleema Shakur-Still and Timothy J Coats},

url = {http://researchonline.lshtm.ac.uk/id/eprint/2124254/},

year  = {2015},

date = {2015-01-01},

journal = {International emergency nursing},

volume = {23},

number = {1},

pages = {42--44},

publisher = {Elsevier},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm2124273,

title = {The science of clinical practice: disease diagnosis or patient prognosis? Evidence about "what is likely to happen" should shape clinical practice.},

author = {Peter Croft and Douglas G Altman and Jonathan J Deeks and Kate M Dunn and Alastair D Hay and Harry Hemingway and Linda LeResche and George Peat and Pablo Perel and Steffen E Petersen and Richard D Riley and Ian Roberts and Michael Sharpe and Richard J Stevens and Danielle Van Der A Windt and Michael Von Korff and Adam Timmis},

url = {http://researchonline.lshtm.ac.uk/id/eprint/2124273/},

year  = {2015},

date = {2015-01-01},

journal = {BMC medicine},

volume = {13},

number = {1},

pages = {20--},

publisher = {BMC},

abstract = {BACKGROUND: Diagnosis is the traditional basis for decision-making in clinical practice. Evidence is often lacking about future benefits and harms of these decisions for patients diagnosed with and without disease. We propose that a model of clinical practice focused on patient prognosis and predicting the likelihood of future outcomes may be more useful. DISCUSSION: Disease diagnosis can provide crucial information for clinical decisions that influence outcome in serious acute illness. However, the central role of diagnosis in clinical practice is challenged by evidence that it does not always benefit patients and that factors other than disease are important in determining patient outcome. The concept of disease as a dichotomous 'yes' or 'no' is challenged by the frequent use of diagnostic indicators with continuous distributions, such as blood sugar, which are better understood as contributing information about the probability of a patient's future outcome. Moreover, many illnesses, such as chronic fatigue, cannot usefully be labelled from a disease-diagnosis perspective. In such cases, a prognostic model provides an alternative framework for clinical practice that extends beyond disease and diagnosis and incorporates a wide range of information to predict future patient outcomes and to guide decisions to improve them. Such information embraces non-disease factors and genetic and other biomarkers which influence outcome. SUMMARY: Patient prognosis can provide the framework for modern clinical practice to integrate information from the expanding biological, social, and clinical database for more effective and efficient care.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm2121365,

title = {Comparison of routes for achieving parenteral access with a focus on the management of patients with Ebola virus disease.},

author = {K Ker and G Tansley and D Beecher and A Perner and Haleema Shakur-Still and T Harris and I Roberts},

url = {http://researchonline.lshtm.ac.uk/id/eprint/2121365/},

year  = {2015},

date = {2015-01-01},

journal = {The Cochrane database of systematic reviews},

volume = {2},

pages = {CD011386},

publisher = {Cochrane Collaboration},

abstract = {Dehydration is an important cause of death in patients with Ebola virus disease (EVD). Parenteral fluids are often required in patients with fluid requirements in excess of their oral intake. The peripheral intravenous route is the most commonly used method of parenteral access, but inserting and maintaining an intravenous line can be challenging in the context of EVD. Therefore it is important to consider the advantages and disadvantages of different routes for achieving parenteral access (e.g. intravenous, intraosseous, subcutaneous and intraperitoneal). 

 

 To compare the reliability, ease of use and speed of insertion of different parenteral access methods. 

 

 We ran the search on 17 November 2014. We searched the Cochrane Injuries Group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily, Ovid MEDLINE(R) and Ovid OLDMEDLINE(R), Embase Classic + Embase (OvidSP), CINAHL (EBSCOhost), clinicaltrials.gov and screened reference lists. 

 

 Randomised controlled trials comparing different parenteral routes for the infusion of fluids or medication. 

 

 Two review authors examined the titles and abstracts of records obtained by searching the electronic databases to determine eligibility. Two review authors extracted data from the included trials and assessed the risk of bias. Outcome measures of interest were success of insertion; time required for insertion; number of insertion attempts; number of dislodgements; time period with functional access; local site reactions; clinicians' perception of ease of administration; needlestick injury to healthcare workers; patients' discomfort; and mortality. For trials involving the administration of fluids we also collected data on the volume of fluid infused, changes in serum electrolytes and markers of renal function. We rated the quality of the evidence as 'high', 'moderate', 'low' or 'very low' according to the GRADE approach for the following outcomes: success of insertion, time required for insertion, number of dislodgements, volume of fluid infused and needlestick injuries. 

 We included 17 trials involving 885 participants. Parenteral access was used to infuse fluids in 11 trials and medications in six trials. None of the trials involved patients with EVD. Intravenous and intraosseous access was compared in four trials; intravenous and subcutaneous access in 11; peripheral intravenous and intraperitoneal access in one; saphenous vein cutdown and intraosseous access in one; and intraperitoneal with subcutaneous access in one. All of the trials assessing the intravenous method involved peripheral intravenous access.We judged few trials to be at low risk of bias for any of the assessed domains.Compared to the intraosseous group, patients in the intravenous group were more likely to experience an insertion failure (risk ratio (RR) 3.89, 95% confidence interval (CI) 2.39 to 6.33; n = 242; GRADE rating: low). We did not pool data for time to insertion but estimates from the trials suggest that inserting intravenous access takes longer (GRADE rating: moderate). Clinicians judged the intravenous route to be easier to insert (RR 0.15, 95% CI 0.04 to 0.61; n = 182). A larger volume of fluids was infused via the intravenous route (GRADE rating: moderate). There was no evidence of a difference between the two routes for any other outcomes, including adverse events.Compared to the subcutaneous group, patients in the intravenous group were more likely to experience an insertion failure (RR 14.79, 95% CI 2.87 to 76.08; n = 238; GRADE rating: moderate) and dislodgement of the device (RR 3.78, 95% CI 1.16 to 12.34; n = 67; GRADE rating: low). Clinicians also judged the intravenous route as being more difficult to insert and patients were more likely to be agitated in the intravenous group. Patients in the intravenous group were more likely to develop a local infection and phlebitis, but were less likely to develop erythema, oedema or swelling than those in the subcutaneous group. A larger volume of fluids was infused into patients via the intravenous route. There was no evidence of a difference between the two routes for any other outcome.There were insufficient data to reliably determine if the risk of insertion failure differed between the saphenous vein cutdown (SVC) and intraosseous method (RR 4.00, 95% CI 0.51 to 31.13; GRADE rating: low). Insertion using SVC took longer than the intraosseous method (MD 219.60 seconds, 95% CI 135.44 to 303.76; GRADE rating: moderate). There were no data and therefore there was no evidence of a difference between the two routes for any other outcome.There were insufficient data to reliably determine the relative effects of intraperitoneal or central intravenous access relative to any other parenteral access method. 

 

 There are several different ways of achieving parenteral access in patients who are unable meet their fluid requirements with oral intake alone. The quality of the evidence, as assessed using the GRADE criteria, is somewhat limited because of the lack of adequately powered trials at low risk of bias. However, we believe that there is sufficient evidence to draw the following conclusions: if peripheral intravenous access can be achieved easily, this allows infusion of larger volumes of fluid than other routes; but if this is not possible, the intraosseous and subcutaneous routes are viable alternatives. The subcutaneous route may be suitable for patients who are not severely dehydrated but in whom ongoing fluid losses cannot be met by oral intake.A film to accompany this review can be viewed here (http://youtu.be/ArVPzkf93ng).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm2235979,

title = {Tranexamic acid in trauma: how should we use it?},

author = {I Roberts},

url = {http://researchonline.lshtm.ac.uk/id/eprint/2235979/},

year  = {2015},

date = {2015-01-01},

journal = {Journal of thrombosis and haemostasis},

volume = {13 Sup},

pages = {S195--S199},

publisher = {Wiley},

abstract = {Tranexamic acid (TXA) reduces blood loss by inhibiting the enzymatic breakdown of fibrin. It is often used in surgery to decrease bleeding and the need for blood transfusion. In 2011, results from a multi-center, randomized, and placebo-controlled trial (CRASH-2 trial) showed that TXA (1 g loading dose over 10 min followed by an infusion of 1 g over 8 h) safely reduces mortality in bleeding trauma patients. Initiation of TXA treatment within 3 h of injury reduces the risk of hemorrhage death by about one-third, regardless of baseline risk. Because it does not have any serious adverse effects, TXA can be administered to a wide spectrum of bleeding trauma patients. Limiting its use to the most severely injured or those with a diagnosis of 'hyperfibrinolysis' would result in thousands of avoidable deaths. A clinical trial (CRASH-3 trial) of TXA in patients with traumatic brain injury is now in progress.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm2344767,

title = {How systematic reviews cause research waste.},

author = {Ian Roberts and Katharine Ker},

url = {http://researchonline.lshtm.ac.uk/id/eprint/2344767/},

year  = {2015},

date = {2015-01-01},

journal = {Lancet},

volume = {386},

number = {10003},

pages = {1536--},

publisher = {Elsevier},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm4398482,

title = {Mechanism of action of tranexamic acid in bleeding trauma patients: an exploratory analysis of data from the CRASH-2 trial.},

author = {Ian Roberts and David Prieto-Merino and Daniela Manno},

url = {http://researchonline.lshtm.ac.uk/id/eprint/4398482/},

year  = {2014},

date = {2014-12-01},

journal = {Critical care (London, England)},

volume = {18},

number = {6},

pages = {685--},

publisher = {BMC},

abstract = {INTRODUCTION: To investigate the mechanism of action of tranexamic acid (TXA) in bleeding trauma patients, we examined the timing of its effect on mortality. We hypothesised that if TXA reduces mortality by decreasing blood loss, its effect should be greatest on the day of the injury when bleeding is most profuse. However, if TXA reduces mortality via an anti-inflammatory mechanism its effect should be greater over the subsequent days. METHODS: Exploratory analysis, including per-protocol analyses, of data from the CRASH-2 trial, a randomised placebo controlled trial of the effect of TXA on mortality in 20,211 trauma patients with, or at risk of, significant bleeding. We examined hazard ratios (HR) and 95% confidence intervals for all-cause mortality, deaths due to bleeding and non-bleeding deaths, according to the day since injury. The CRASH-2 trial is registered as ISRCTN86750102 and ClinicalTrials.gov NCT00375258. RESULTS: The effect of TXA on mortality is greatest for deaths occurring on the day of the injury (HR all-cause mortality = 0.83, 0.73 to 0.93). This survival benefit is only evident in patients in whom treatment is initiated within 3 hours of their injury (HR $łeq$ 3 hours = 0.78, 0.68 to 0.90; HR ensuremath> 3 hours = 1.02, 0.76 to 1.36). Initiation of TXA treatment within 3 hours of injury reduced the hazard of death due to bleeding on the day of the injury by 28% (HR = 0.72, 0.60 to 0.86). TXA treatment initiated beyond 3 hours of injury appeared to increase the hazard of death due to bleeding, although the estimates were imprecise. CONCLUSIONS: Early administration of tranexamic acid appears to reduce mortality primarily by preventing exsanguination on the day of the injury.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm2167252,

title = {The tens of thousands of lives saved by randomized clinical trials in critical care.},

author = {Gordon S Doig and Ian Roberts and Rinaldo Bellomo},

url = {http://researchonline.lshtm.ac.uk/id/eprint/2167252/},

year  = {2014},

date = {2014-12-01},

journal = {Intensive care medicine},

volume = {41},

number = {4},

pages = {701--704},

publisher = {Springer (part of Springer Nature)},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm2124334,

title = {Ebola care and research protocols.},

author = {Anders Perner and Robert A Fowler and Rinaldo Bellomo and Ian Roberts},

url = {http://researchonline.lshtm.ac.uk/id/eprint/2124334/},

year  = {2014},

date = {2014-11-01},

journal = {Intensive care medicine},

volume = {41},

number = {1},

pages = {111--114},

publisher = {Springer (part of Springer Nature)},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm2026593,

title = {HALT-IT--tranexamic acid for the treatment of gastrointestinal bleeding: study protocol for a randomised controlled trial.},

author = {Ian Roberts and Timothy Coats and Phil Edwards and Ian Gilmore and Vipul Jairath and Katharine Ker and Daniela Manno and Haleema Shakur-Still and Simon Stanworth and Andrew Veitch},

url = {http://researchonline.lshtm.ac.uk/id/eprint/2026593/},

year  = {2014},

date = {2014-11-01},

journal = {Trials},

volume = {15},

number = {1},

pages = {450--},

publisher = {BMC},

abstract = {BACKGROUND: Gastrointestinal bleeding is a common emergency that causes substantial mortality worldwide. Acute upper and lower gastrointestinal bleeding accounts for about 75,000 hospital admissions each year in the UK and causes the death of about 10% of these patients. Tranexamic acid has been shown to reduce the need for blood transfusion in surgical patients and to reduce mortality in bleeding trauma patients, with no apparent increase in thromboembolic events. A systematic review of clinical trials of upper gastrointestinal bleeding shows a reduction in the risk of death with tranexamic acid but the quality of the trials was poor and the estimates are imprecise. The trials were also too small to assess the effect of tranexamic acid on thromboembolic events. METHODS: HALT-IT is a pragmatic, randomised, double-blind, placebo-controlled trial which will determine the effect of tranexamic acid on mortality, morbidity (re-bleeding, non-fatal vascular events), blood transfusion, surgical intervention, and health status in patients with acute gastrointestinal bleeding. Eight thousand adult patients who fulfil the eligibility criteria will be randomised to receive tranexamic acid or placebo. Adults with significant acute upper or lower gastrointestinal bleeding can be included if the responsible doctor is substantially uncertain as to whether or not to use tranexamic acid in that particular patient. Trial treatment consists of a loading dose of tranexamic acid (1 g by intravenous injection) or placebo (sodium chloride 0.9%) given as soon as possible after randomisation, followed by an intravenous infusion of 3 g tranexamic acid or placebo (sodium chloride 0.9%) over 24 hours. The main analyses will compare those allocated tranexamic acid with those allocated placebo, on an intention-to-treat basis. Results will be presented as effect estimates with a measure of precision (95% confidence intervals). Subgroup analyses for the primary outcome will be based on time to treatment, source of bleeding (upper versus lower), suspected variceal bleeding and severity of bleeding. A study with 8,000 patients will have over 90% power to detect a 25% reduction in mortality from 10% to 7.5%. TRIAL REGISTRATION: Current Controlled Trials ISRCTN11225767 (registration date: 3 July 2012); Clinicaltrials.gov NCT01658124 (registration date: 26 July 2012).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm2026646,

title = {Blood pressure lowering and cardiovascular risk.},

author = {Ian Roberts and David Prieto-Merino},

url = {http://researchonline.lshtm.ac.uk/id/eprint/2026646/},

year  = {2014},

date = {2014-11-01},

journal = {Lancet},

volume = {384},

number = {9956},

pages = {1745--},

publisher = {Elsevier},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm2121354,

title = {Applying results from clinical trials: tranexamic acid in trauma patients.},

author = {Ian Roberts and David Prieto-Merino},

url = {http://researchonline.lshtm.ac.uk/id/eprint/2121354/},

year  = {2014},

date = {2014-10-01},

journal = {Journal of intensive care},

volume = {2},

number = {1},

pages = {56--},

publisher = {BMC},

abstract = {This paper considers how results from clinical trials should be applied in the care of patients, using the results of the Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage (CRASH-2) trial of tranexamic acid in bleeding trauma patients as a case study. We explain why an understanding of the mechanisms of action of the trial treatment, and insight into the factors that might be relevant to this mechanism, is critical in order to properly apply (generalise) trial results and why it is not necessary that the trial population is representative of the population in which the medicine will be used. We explain why cause (mechanism)-specific mortality is more generalizable than all-cause mortality and why the risk ratio is the generalizable measure of the effect of the treatment. Overall, we argue that a biological insight into how the treatment works is more relevant when applying research results to patient care than the application of statistical reasoning.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm1883893,

title = {Tranexamic acid for surgical bleeding.},

author = {Katharine Ker and Ian Roberts},

url = {http://researchonline.lshtm.ac.uk/id/eprint/1883893/},

year  = {2014},

date = {2014-08-01},

journal = {BMJ (Clinical research ed)},

volume = {349},

number = {aug12},

pages = {g4934--},

publisher = {BMJ Publishing Group},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm1848687,

title = {Guide to the design and review of emergency research when it is proposed that consent and consultation be waived.},

author = {Hugh Davies and Haleema Shakur-Still and Andrew Padkin and Ian Roberts and Anne-Marie Slowther and Gavin D Perkins},

url = {http://researchonline.lshtm.ac.uk/id/eprint/1848687/},

year  = {2014},

date = {2014-07-01},

journal = {Emergency medicine journal},

volume = {31},

number = {10},

pages = {794--795},

publisher = {BMJ Publishing Group},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm1785941,

title = {Red blood cell transfusion and mortality in trauma patients: risk-stratified analysis of an observational study.},

author = {Pablo Perel and Tim Clayton and Doug G Altman and Peter Croft and Ian Douglas and Harry Hemingway and Aroon Hingorani and Katherine I Morley and Richard Riley and Adam Timmis and Danielle Van der Windt and Ian Roberts and PROGRESS Partnership},

url = {http://researchonline.lshtm.ac.uk/id/eprint/1785941/},

year  = {2014},

date = {2014-06-01},

journal = {PLoS medicine},

volume = {11},

number = {6},

pages = {e1001664--},

publisher = {Public Library of Science},

abstract = {BACKGROUND: Haemorrhage is a common cause of death in trauma patients. Although transfusions are extensively used in the care of bleeding trauma patients, there is uncertainty about the balance of risks and benefits and how this balance depends on the baseline risk of death. Our objective was to evaluate the association of red blood cell (RBC) transfusion with mortality according to the predicted risk of death. METHODS AND FINDINGS: A secondary analysis of the CRASH-2 trial (which originally evaluated the effect of tranexamic acid on mortality in trauma patients) was conducted. The trial included 20,127 trauma patients with significant bleeding from 274 hospitals in 40 countries. We evaluated the association of RBC transfusion with mortality in four strata of predicted risk of death: ensuremath<6%, 6%-20%, 21%-50%, and ensuremath>50%. For this analysis the exposure considered was RBC transfusion, and the main outcome was death from all causes at 28 days. A total of 10,227 patients (50.8%) received at least one transfusion. We found strong evidence that the association of transfusion with all-cause mortality varied according to the predicted risk of death (p-value for interaction ensuremath<0.0001). Transfusion was associated with an increase in all-cause mortality among patients with ensuremath<6% and 6%-20% predicted risk of death (odds ratio [OR] 5.40, 95% CI 4.08-7.13, pensuremath<0.0001, and OR 2.31, 95% CI 1.96-2.73, pensuremath<0.0001, respectively), but with a decrease in all-cause mortality in patients with ensuremath>50% predicted risk of death (OR 0.59, 95% CI 0.47-0.74, pensuremath<0.0001). Transfusion was associated with an increase in fatal and non-fatal vascular events (OR 2.58, 95% CI 2.05-3.24, pensuremath<0.0001). The risk associated with RBC transfusion was significantly increased for all the predicted risk of death categories, but the relative increase was higher for those with the lowest (ensuremath<6%) predicted risk of death (p-value for interaction ensuremath<0.0001). As this was an observational study, the results could have been affected by different types of confounding. In addition, we could not consider haemoglobin in our analysis. In sensitivity analyses, excluding patients who died early; conducting propensity score analysis adjusting by use of platelets, fresh frozen plasma, and cryoprecipitate; and adjusting for country produced results that were similar. CONCLUSIONS: The association of transfusion with all-cause mortality appears to vary according to the predicted risk of death. Transfusion may reduce mortality in patients at high risk of death but increase mortality in those at low risk. The effect of transfusion in low-risk patients should be further tested in a randomised trial. TRIAL REGISTRATION: www.ClinicalTrials.gov NCT01746953.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm1682447,

title = {Importance of äcknowledging and reducing treatment uncertainty" in appraisal and revalidation.},

author = {Ian Roberts and Brigitte Chaudhry and Iain Chalmers},

url = {http://researchonline.lshtm.ac.uk/id/eprint/1682447/},

year  = {2014},

date = {2014-04-01},

journal = {BMJ (Clinical research ed)},

volume = {348},

number = {apr29},

pages = {g2851--},

publisher = {BMJ Publishing Group},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm1592717,

title = {Treatment for primary postpartum haemorrhage.},

author = {Hatem A Mousa and Jennifer Blum and Ghada Abou El Senoun and Haleema Shakur-Still and Zarko Alfirevic},

url = {http://researchonline.lshtm.ac.uk/id/eprint/1592717/},

year  = {2014},

date = {2014-02-01},

journal = {The Cochrane database of systematic reviews},

volume = {2},

number = {2},

pages = {CD003249--},

publisher = {Cochrane Collaboration},

abstract = {BACKGROUND: Primary postpartum haemorrhage (PPH) is one of the top five causes of maternal mortality in both developed and developing countries. OBJECTIVES: To assess the effectiveness and safety of any intervention used for the treatment of primary PPH. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2013). SELECTION CRITERIA: Randomised controlled trials comparing any interventions for the treatment of primary PPH. DATA COLLECTION AND ANALYSIS: We assessed studies for eligibility and quality and extracted data independently. We contacted authors of the included studies to request more information. MAIN RESULTS: Ten randomised clinical trials (RCTs) with a total of 4052 participants fulfilled our inclusion criteria and were included in this review.Four RCTs (1881 participants) compared misoprostol with placebo given in addition to conventional uterotonics. Adjunctive use of misoprostol (in the dose of 600 to 1000 mcg) with simultaneous administration of additional uterotonics did not provide additional benefit for our primary outcomes including maternal mortality (risk ratio (RR) 6.16, 95% confidence interval (CI) 0.75 to 50.85), serious maternal morbidity (RR 0.34, 95% CI 0.01 to 8.31), admission to intensive care (RR 0.79, 95% CI 0.30 to 2.11) or hysterectomy (RR 0.93, 95% CI 0.16 to 5.41). Two RCTs (1787 participants) compared 800 mcg sublingual misoprostol versus oxytocin infusion as primary PPH treatment; one trial included women who had received prophylactic uterotonics, and the other did not. Primary outcomes did not differ between the two groups, although women given sublingual misoprostol were more likely to have additional blood loss of at least 1000 mL (RR 2.65, 95% CI 1.04 to 6.75). Misoprostol was associated with a significant increase in vomiting and shivering.Two trials attempted to test the effectiveness of estrogen and tranexamic acid, respectively, but were too small for any meaningful comparisons of pre-specified outcomes.One study compared lower segment compression but was too small to assess impact on primary outcomes.We did not identify any trials evaluating surgical techniques or radiological interventions for women with primary PPH unresponsive to uterotonics and/or haemostatics. AUTHORS' CONCLUSIONS: Clinical trials included in the current review were not adequately powered to assess impact on the primary outcome measures. Compared with misoprostol, oxytocin infusion is more effective and causes fewer side effects when used as first-line therapy for the treatment of primary PPH. When used after prophylactic uterotonics, misoprostol and oxytocin infusion worked similarly. The review suggests that among women who received oxytocin for the treatment of primary PPH, adjunctive use of misoprostol confers no added benefit.The role of tranexamic acid and compression methods requires further evaluation. Furthermore, future studies should focus on the best way to treat women who fail to respond to uterotonic therapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm1559947,

title = {How effective is tranexamic acid for acute gastrointestinal bleeding?},

author = {Daniela Manno and Katharine Ker and Ian Roberts},

url = {http://researchonline.lshtm.ac.uk/id/eprint/1559947/},

year  = {2014},

date = {2014-02-01},

journal = {BMJ (Clinical research ed)},

volume = {348},

number = {feb17},

pages = {g1421--},

publisher = {BMJ Publishing Group},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm1462957,

title = {Biomedical research: increasing value, reducing waste.},

author = {Malcolm R Macleod and Susan Michie and Ian Roberts and Ulrich Dirnagl and Iain Chalmers and John PA Ioannidis and Rustam Al-Shahi Salman and An-Wen Chan and Paul Glasziou},

url = {http://researchonline.lshtm.ac.uk/id/eprint/1462957/},

year  = {2014},

date = {2014-01-01},

journal = {Lancet},

volume = {383},

number = {9912},

pages = {101--104},

publisher = {Elsevier},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm1701199,

title = {Is road safety being driven in the wrong direction?},

author = {Gareth R Davies and Ian Roberts},

url = {http://researchonline.lshtm.ac.uk/id/eprint/1701199/},

year  = {2014},

date = {2014-01-01},

journal = {International journal of epidemiology},

volume = {43},

number = {5},

pages = {1615--1623},

publisher = {Oxford University Press (OUP)},

abstract = {BACKGROUND: Road traffic crashes are a major cause of death and injury worldwide and are set to increase as low- and middle-income countries motorize. United Nations (UN)and World Health Organization (WHO) road traffic injury prevention efforts depend on support from external organizations, many of which have commercial interests in increasing car use. Because of concerns about conflict of interest, this study objectively assessed the activities of a key WHO collaborator, the Global Road Safety Partnership (GRSP). METHODS: We conducted a quantitative content analysis comparing GRSP publications and the 2004 WHO World Report on Road Traffic Injury Prevention. Dictionaries of terms were constructed for each of the evidence-based interventions detailed in the World REPORT. Text analysis software was used to generate word frequency counts of those terms to compare the World Report and GRSP documents. RESULTS: Education, information and publicity featured far more commonly in the GRSP publications than in the WHO World Report [word frequency ratios and 95% confidence intervals: GRSP Newsletter 3.09, 2.53 to 3.78; Around GRSPs World 4.69, 3.76 to 5.87;GRSP Project summaries 3.42, 2.59 to 4.51] On the other hand, compared with the World Report, reducing car use [GRSP Newsletter 0.36, 0.27 to 0.48], minimizing exposure to high-risk scenarios [GRSP Newsletter 0.04, 0.02 to 0.09] and encouraging the use of safer modes of travel [GRSP Newsletter 0.02, 0.01 to 0.08] rarely featured in GRSP publications. CONCLUSIONS: The GRSP focuses on educational interventions, for which there is no evidence of effectiveness. Furthermore, the GRSP does not appear to consider the full range of WHO interventions. As motorization growth has serious negative implications for health, including those associated from physical inactivity, climate change and air and noise pollution, it is imperative that the UN and WHO do not allow business interests to dominate public health interests.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm1829337,

title = {PTU-185 Update On The Halt-it Trial Progress: Tranexamic Acid For The Treatment Of Gastrointestinal Haemorrhage ? An International, Randomised, Double Blind Placebo Controlled Trial},

author = {V Jairath and Haleema Shakur-Still and P Edwards and K Ker and D Manno and I Gilmore and A Veitch and S Stanworth and T Coats and I Roberts},

url = {http://researchonline.lshtm.ac.uk/id/eprint/1829337/},

year  = {2014},

date = {2014-01-01},

journal = {Gut},

volume = {63},

number = {Suppl},

pages = {A120.1--A120},

publisher = {BMJ Publishing Group},

abstract = {INTRODUCTION Gastrointestinal (GI) bleeding is a common medical emergency and an important cause of morbidity and mortality in high, middle and low income countries. Despite advances in resuscitative, pharmacological and endoscopic therapy, re-bleeding occurs in 10% of patients with non-variceal bleeding and up to 25% of those with variceal bleeding and is an important predictor of death. Excessive fibrinolysis may play an important role both in the failure to control initial bleeding and in the precipitation of re-bleeding through premature breakdown of blood clots at sites of vascular injury. This raises the possibility that an antifibrinolytic drug administered following GI bleeding could limit severity of bleeding and transfusion requirements. 

 

METHODS HALT-IT has been designed as a large, pragmatic randomised controlled trial which aims to quantify the efficacy and safety of tranexamic acid (TXA) in adults with significant acute upper or lower gastrointestinal bleeding. The trial will determine the effect of early administration of TXA on mortality, morbidity, blood transfusion, surgical intervention and health status in patients with GI bleeding. The primary outcome is death in hospital within 28 days of randomisation. Secondary outcomes include re-bleeding, need for surgery or radiological intervention, blood product transfusion and thromboembolic events. 

 

RESULTS UK recruitment began in August 2013. By January 2014, a total of 507 patients were randomised across 26 actively recruiting sites, averaging a recruitment rate of 20 patients per week. Centralised and statistical data monitoring ensures trial participants meet inclusion criteria and allows real time monitoring of event rates for the primary and secondary outcomes. The results will be presented by intention to treat and a pre-specified subgroup analysis will also determine the treatment effect in patients with liver cirrhosis and variceal bleeding. 

 

CONCLUSION HALT-IT aims to recruit 8000 participants in hospitals worldwide and recruitment is ahead of schedule based upon a strong performance in the UK. The success of the trial to date has been dependent upon multi-disciplinary and societal engagement as well as infrastructural support provided by NIHR research networks. The results will add to our expanding knowledge about the role of tranexamic acid as an agent for patients with significant bleeding. It is anticipated that the full trial results will be available in 2017. 

 

DISCLOSURE OF INTEREST None Declared.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm1823786,

title = {Wie wirksam ist Tranexamsäure bei akuten gastrointestinalen Blutungen?},

author = {Daniela Manno and Katharine Ker and Ian Roberts},

url = {http://researchonline.lshtm.ac.uk/id/eprint/1823786/},

year  = {2014},

date = {2014-01-01},

journal = {Praxis},

volume = {103},

number = {14},

pages = {845--848},

publisher = {Hogrefe},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm2030892,

title = {Ebola virus disease: clinical care and patient-centred research.},

author = {Ian Roberts and Anders Perner},

url = {http://researchonline.lshtm.ac.uk/id/eprint/2030892/},

year  = {2014},

date = {2014-01-01},

journal = {Lancet},

volume = {384},

number = {9959},

pages = {2001--2002},

publisher = {Elsevier},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm1621956,

title = {Tranexamic acid and trauma.},

author = {Ian Roberts},

url = {http://researchonline.lshtm.ac.uk/id/eprint/1621956/},

year  = {2013},

date = {2013-12-01},

journal = {The Medical journal of Australia},

volume = {200},

number = {5},

pages = {254--255},

publisher = {Australasian Medical Publishing Company Ltd},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm1367727,

title = {Dangers of non-specific composite outcome measures in clinical trials.},

author = {David Prieto-Merino and Liam Smeeth and Tjeerd P van Staa and Ian Roberts},

url = {http://researchonline.lshtm.ac.uk/id/eprint/1367727/},

year  = {2013},

date = {2013-11-01},

journal = {BMJ (Clinical research ed)},

volume = {347},

number = {nov22},

pages = {f6782--},

publisher = {BMJ Publishing Group},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm1229897,

title = {The importance of health co-benefits in macroeconomic assessments of UK Greenhouse Gas emission reduction strategies.},

author = {Henning Tarp Jensen and Marcus R Keogh-Brown and Richard D Smith and Zaid Chalabi and Alan D Dangour and Mike Davies and Phil Edwards and Tara Garnett and Moshe Givoni and Ulla Griffiths and Ian Hamilton and James Jarrett and Ian Roberts and Paul Wilkinson and James Woodcock and Andy Haines},

url = {http://researchonline.lshtm.ac.uk/id/eprint/1229897/},

year  = {2013},

date = {2013-11-01},

journal = {Climatic Change},

volume = {121},

number = {2},

pages = {223--237},

publisher = {Springer Netherlands},

abstract = {We employ a single-country dynamically-recursive Computable General Equilibrium model to make health-focussed macroeconomic assessments of three contingent UK Greenhouse Gas (GHG) mitigation strategies, designed to achieve 2030 emission targets as suggested by the UK Committee on Climate Change. In contrast to previous assessment studies, our main focus is on health co-benefits additional to those from reduced local air pollution. We employ a conservative cost-effectiveness methodology with a zero net cost threshold. Our urban transport strategy (with cleaner vehicles and increased active travel) brings important health co-benefits and is likely to be strongly cost-effective; our food and agriculture strategy (based on abatement technologies and reduction in livestock production) brings worthwhile health co-benefits, but is unlikely to eliminate net costs unless new technological measures are included; our household energy efficiency strategy is likely to breakeven only over the long term after the investment programme has ceased (beyond our 20 year time horizon). We conclude that UK policy makers will, most likely, have to adopt elements which involve initial net societal costs in order to achieve future emission targets and longer-term benefits from GHG reduction. Cost-effectiveness of GHG strategies is likely to require technological mitigation interventions and/or demand-constraining interventions with important health co-benefits and other efficiency-enhancing policies that promote internalization of externalities. Health co-benefits can play a crucial role in bringing down net costs, but our results also suggest the need for adopting holistic assessment methodologies which give proper consideration to welfare-improving health co-benefits with potentially negative economic repercussions (such as increased longevity).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm4646184,

title = {The importance of health co-benefits in macroeconomic assessments of UK Greenhouse Gas emission reduction strategies.},

author = {HT Jensen and MR Keogh-Brown and RD Smith and Z Chalabi and AD Dangour and M Davies and P Edwards and T Garnett and M Givoni and U 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/4646184/},

year  = {2013},

date = {2013-09-01},

journal = {Climatic change},

volume = {121},

number = {2},

pages = {223--237},

publisher = {Springer Verlag},

abstract = {We employ a single-country dynamically-recursive Computable General Equilibrium model to make health-focussed macroeconomic assessments of three contingent UK Greenhouse Gas (GHG) mitigation strategies, designed to achieve 2030 emission targets as suggested by the UK Committee on Climate Change. In contrast to previous assessment studies, our main focus is on health co-benefits additional to those from reduced local air pollution. We employ a conservative cost-effectiveness methodology with a zero net cost threshold. Our urban transport strategy (with cleaner vehicles and increased active travel) brings important health co-benefits and is likely to be strongly cost-effective; our food and agriculture strategy (based on abatement technologies and reduction in livestock production) brings worthwhile health co-benefits, but is unlikely to eliminate net costs unless new technological measures are included; our household energy efficiency strategy is likely to breakeven only over the long term after the investment programme has ceased (beyond our 20 year time horizon). We conclude that UK policy makers will, most likely, have to adopt elements which involve initial net societal costs in order to achieve future emission targets and longer-term benefits from GHG reduction. Cost-effectiveness of GHG strategies is likely to require technological mitigation interventions and/or demand-constraining interventions with important health co-benefits and other efficiency-enhancing policies that promote internalization of externalities. Health co-benefits can play a crucial role in bringing down net costs, but our results also suggest the need for adopting holistic assessment methodologies which give proper consideration to welfare-improving health co-benefits with potentially negative economic repercussions (such as increased longevity).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm1037027,

title = {Systematic review, meta-analysis and meta-regression of the effect of tranexamic acid on surgical blood loss.},

author = {K Ker and D Prieto-Merino and I Roberts},

url = {http://researchonline.lshtm.ac.uk/id/eprint/1037027/},

year  = {2013},

date = {2013-08-01},

journal = {The British journal of surgery},

volume = {100},

number = {10},

pages = {1271--1279},

publisher = {Wiley},

abstract = {BACKGROUND: Tranexamic acid (TXA) reduces blood transfusion in surgery but the extent of the reduction in blood loss and how it relates to the dose of TXA is unclear. METHODS: A systematic review of randomized trials was performed. Data were extracted on blood loss from trials comparing intravenous TXA with no TXA or placebo in surgical patients. A Bayesian linear regression was used to describe the relationship between the reduction in blood loss with TXA and the extent of bleeding as measured by the mean blood loss in the control group. A meta-analysis of the log-transformed data was conducted to quantify the effect of TXA on blood loss, stratified by type of surgery, timing of TXA administration and trial quality. Meta-regression was used to explore the effect of TXA dosage. RESULTS: Data from 104 trials were examined. Although the absolute reduction in blood loss with TXA increased as surgical bleeding increased, the percentage reduction was similar. TXA reduced blood loss by 34 per cent (pooled ratio 0?66, 95 per cent confidence interval 0?65 to 0?67; P ensuremath< 0?001). The percentage reduction in blood loss with TXA differed by type of surgery, timing of TXA administration and trial quality, but the differences were small. The effect of TXA on blood loss did not vary over the range of doses assessed (5?5-300 mg/kg). CONCLUSION: TXA reduces blood loss in surgical patients by about one-third. A total dose of 1 g appears to be sufficient for most adults. There is no evidence to support the use of high doses.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm989935,

title = {New GMC guidance takes a major, ethically flawed, backward step.},

author = {Ian Roberts and Brigitte Chaudhry and Iain Chalmers},

url = {http://researchonline.lshtm.ac.uk/id/eprint/989935/},

year  = {2013},

date = {2013-06-01},

journal = {BMJ (Clinical research ed)},

volume = {346},

number = {jun18},

pages = {f3879--},

publisher = {BMJ Publishing Group},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lshtm638999,

title = {Colloids versus crystalloids for fluid resuscitation in critically ill patients.},

author = {Pablo Perel and Ian Roberts and Katharine Ker},

url = {http://researchonline.lshtm.ac.uk/id/eprint/638999/},

year  = {2013},

date = {2013-02-01},

journal = {The Cochrane database of systematic reviews},

volume = {2},

number = {2},

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 (17 October 2012), the Cochrane Central Register of Controlled Trials (The Cochrane Library) (Issue 10, 2012), MEDLINE (Ovid) 1946 to October 2012, EMBASE (Ovid) 1980 to October 2012, ISI Web of Science: Science Citation Index Expanded (1970 to October 2012), ISI Web of Science: Conference Proceedings Citation Index-Science (1990 to October 2012), PubMed (October 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 involving pregnant women and neonates. DATA COLLECTION AND ANALYSIS: Two review 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 78 eligible trials; 70 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 risk ratio (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 - 25 trials compared hydroxyethyl starch with crystalloids and included 9147 patients. The pooled RR was 1.10 (95% CI 1.02 to 1.19). Modified gelatin - 11 trials compared modified gelatin with crystalloid and included 506 patients. The pooled RR was 0.91 (95% CI 0.49 to 1.72). (When the trials by Boldt et al were removed from the three preceding analyses, the results were unchanged.) Dextran - nine trials compared dextran with a crystalloid and included 834 patients. The pooled RR was 1.24 (95% CI 0.94 to 1.65). COLLOIDS IN HYPERTONIC CRYSTALLOID COMPARED TO ISOTONIC CRYSTALLOID: Nine trials compared dextran in hypertonic crystalloid with isotonic crystalloid, including 1985 randomised participants. Pooled RR for mortality was 0.91 (95% CI 0.71 to 1.06). AUTHORS' CONCLUSIONS: There is no evidence from randomised controlled trials that resuscitation with colloids reduces the risk of death, compared to resuscitation with crystalloids, in patients with trauma, burns or following surgery. Furthermore, the use of hydroxyethyl starch might increase mortality. As colloids are not associated with an improvement in survival and are considerably more expensive than crystalloids, it is hard to see how their continued use in clinical practice can be justified.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}