The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trialThe CRASH-2 collaborators* SummaryBackground The aim of the CRASH-2 trial was to assess the eff ects of early administration of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with signifi cant haemorrhage. Tranexamic acid signifi cantly reduced all-cause mortality. Because tranexamic acid is thought to exert its eff ect through inhibition of fi brinolysis, we undertook exploratory analyses of its eff ect on death due to bleeding.Methods The CRASH-2 trial was undertaken in 274 hospitals in 40 countries. 20 211 adult trauma patients with, or at risk of, signifi cant bleeding were randomly assigned within 8 h of injury to either tranexamic acid (loading dose 1 g over 10 min followed by infusion of 1 g over 8 h) or placebo. Patients were randomly assigned by selection of the lowest numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Both participants and study staff (site investigators and trial coordinating centre staff ) were masked to treatment allocation. We examined the eff ect of tranexamic acid on death due to bleeding according to time to treatment, severity of haemorrhage as assessed by systolic blood pressure, Glasgow coma score (GCS), and type of injury. All analyses were by intention to treat. The trial is registered as ISRCTN86750102, ClinicalTrials.gov NCT00375258, and South African Clinical Trial Register/Department of Health DOH-27-0607-1919.Findings 10 096 patients were allocated to tranexamic acid and 10 115 to placebo, of whom 10 060 and 10 067, respectively, were analysed. 1063 deaths (35%) were due to bleeding. We recorded strong evidence that the eff ect of tranexamic acid on death due to bleeding varied according to the time from injury to treatment (test for interaction p<0·0001). Early treatment (≤1 h from injury) signifi cantly reduced the risk of death due to bleeding (198 Interpretation Tranexamic acid should be given as early as possible to bleeding trauma patients. For trauma patients admitted late after injury, tranexamic acid is less eff ective and could be harmful.Funding UK NIHR Health Technology Assessment programme, Pfi zer, BUPA Foundation, and J P Moulton Charitable Foundation. IntroductionThe CRASH-2 trial showed that administration of tranexamic acid to adult trauma patients with, or at risk of, signifi cant haemorrhage, within 8 h of injury, signi fi cantly reduces all-cause mortality (relative risk [RR] 0·91, 95% CI 0·85-0·97; p=0·0035) with no apparent increase in vascular occlusive events.1 As a consequence of this trial, tranexamic acid has been incorporated into trauma treatment protocols worldwide.Results from the CRASH-2 trial raise some important questions. The trial was motivated by the evidence that tranexamic acid reduces bleeding in patients undergoing elective surgery, and the hypothesised mechanism was inhi...

Background Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0•9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0•9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124.

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Consistent with other observations in the literature, residents' clinical teaching skills were suboptimal, particularly in their ability to promote understanding and retention. To enhance these skills, we recommend the integration of appropriately tailored programs to teach pedagogic skills programs in residency training.

Introduction: Oncologic surgical extirpation, the mainstay of loco-regional disease control in breast cancer, is aimed at achieving negative margins and lymph node clearance. Even though axillary lymph nodal metastasis is a critical index of prognostication, establishing the impact of lymph node ratio (LNR) and adequate surgical margins on diseasespecific survivorship would be key to achieving longer survival. This study examines the prognostic role of pN (lymph nodes positive for malignancy), LNR and resection margin on breast cancer survival in a tertiary hospital in Ibadan, Nigeria. Methods: We conducted a longitudinal cohort study of 225 patients with breast carcinoma, documented clinico-pathologic parameters and 5-year follow up outcomes-distant metastasis and survival. Chi-square test and logistic regression analysis were used to evaluate the interaction of resection margin and proportion of metastatic lymph nodes with patients' survival. The receiver operating characteristic curve was plotted to determine the proportion of metastatic lymph nodes which predicted survival. The survival analysis was done using Kaplan-Meier method. Results: Sixty (26.7%) patients of the patients had positive resection margins, with the most common immuno-histochemical type being Lumina A. 110 (49%) patients had more than 10 axillary lymph nodes harvested. The mean age was 48.6 + 11.8 years. Tumour size (p = 0.018), histological type (p = 0.015), grade (p = 0.006), resection margin (p = 0.023), number of harvested nodes (p < 0.01), number of metastatic nodes (p < 0.001) and loco-regional recurrence (p < 0.01) are associated with survival. The overall 5-year survival was 65.3%. Conclusion: Unfavourable survival outcomes following breast cancer treatment is multifactorial, including the challenges faced in the multimodal treatment protocol received by our patients.