There is a paucity of data on incidence, prevalence and mortality associated with non-cystic fibrosis bronchiectasis.

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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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BackgroundThe CRASH-2 trial showed that tranexamic acid (TXA) administration reduces mortality in bleeding trauma patients. However, the effect appeared to depend on how soon after injury TXA treatment was started. Treatment within 3 h reduced bleeding deaths whereas treatment after 3 h increased the risk. We examine how patient characteristics vary by time to treatment and explore whether any such variations explain the time-dependent treatment effect.MethodsExploratory analysis were carried out, 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 examine how patient characteristics (age, type of injury, presence or absence of head injury, Glasgow coma scale (GCS), systolic blood pressure and capillary refill time) vary with time to treatment and use univariable (restriction) and multivariable methods to examine whether any such variations explain the time-dependent effect of TXA. If not explained by differences in patient characteristics, we planned to conduct separate prespecified subgroup analyses for the early benefit and late harm.ResultsThere was no substantial variation in age or capillary refill by time to treatment. However, the proportion of patients with blunt trauma, the proportion with head injury and mean systolic blood pressure increased as time to treatment increased. Mean GCS decreased as time to treatment increased. Analyses restricted to patients with blunt trauma, those without head injury and those with a systolic blood pressure <100 mmHg showed that these characteristics did not explain the time-dependent treatment effect. In a multivariable analysis the interaction with time to treatment remained highly significant (p < 0.0001). Separate subgroup analyses that examine how the benefits of early TXA treatment and the harms of late TXA treatment vary by systolic blood pressure (≤75, 76–89, >89 mmHg); GCS (severe 3–8, moderate 9–12, mild 13–15); and type of injury (penetrating versus blunt) showed no significant heterogeneity.ConclusionsThe time-dependent effect of TXA in bleeding trauma patients is not explained by the type of injury, the presence or absence of head injury or systolic blood pressure. When given within 3 h of injury, TXA reduces death due to bleeding regardless of type of injury, GCS or blood pressure.Trial registrationClinicalTrials.gov, NCT00375258. Registered on 11 September 2006.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1750-1) contains supplementary material, which is available to authorized users.

Conflict of Interest DisclosuresJKQ reports grants from the Medical Research Council (MRC), GlaxoSmithKline (GSK), British Lung Foundation (BLF), Wellcome Trust, during the conduct of the study, and personal fees from AstraZeneca and Boehringer Ingelheim, outside of the submitted work. MS reports other current research grants from Arthritis Research UK, Public Health England and the EU EITHealth Programme, with no conflicts of interest. SS reports grants from the National Institute for Health Research (NIHR), GlaxoSmithKline (GSK), Boehringer Ingelheim and Novartis and personal fees from Novartis and AstraZeneca. All other authors report no other conflicts of interest. 2 AbstractBackground: In previous systematic reviews, predominantly of randomised controlled trials,

A review of riluzole in MND by NICE concluded that riluzole was modestly effective. NICE however suggested that further studies were needed to gain further insights into its clinical effectiveness. As these studies have not been carried out we audited outcomes in our use of riluzole. Median survival of 148 MND patients receiving riluzole was 3.07 years (2.25 years for 327 patients not given riluzole), hazard ratio 1.66, 95% confidence interval (CI) 1.32-2.12; 3.61 years in 103 limb onset patients given riluzole (2.62 years for 124 limb onset patients not given riluzole), hazard ratio 1.50, 95% CI 1.09-2.05; 2.19 years in 43 bulbar onset patients receiving riluzole (1.84 years for 103 bulbar onset patients not given riluzole), hazard ratio 1.34, 95% CI 0.89-2.07 and 3.80 years in 87 patients with a PEG given riluzole (2.21 years for 261 patients with a PEG not given riluzole), hazard ratio 1.86, 95% CI 1.44-2.39. These findings are comparable with the results of similar analyses from other groups. The uncertainties they raise emphasize the importance of adequate randomized studies being completed prior to licensing of new drugs. They further illustrate the desirability of controlled introduction of new drugs into clinical practice when RCTs have only suggested a modest level of efficacy.