SummaryBackgroundPost-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage.MethodsIn this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283.FindingsBetween March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus ...

To determine the diagnostic accuracy of state, minimally invasive clinical and physical signs (or sets of signs) to be used as screening tests for detecting impending or current water-loss dehydration, or both, in older people by systematically reviewing studies that have measured a reference standard and at least one index test in people aged 65 years and over. 1 Clinical and physical signs for identification of impending and current water-loss dehydration in older people (Protocol)

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.

ObjectivesWe aimed to assess the association between long-term use of inhaled corticosteroids (ICS) and bone adverse effects in patients with asthma.DesignSystematic review and meta-analysis of fracture risk and changes in bone mineral density with long-term ICS use in asthma.MethodsWe initially searched MEDLINE and EMBASE in July 2013, and performed an updated PubMed search in December 2014. We selected randomised controlled trials (RCTs) and controlled observational studies of any ICS (duration at least 12 months) compared to non-ICS use in patients with asthma. We conducted meta-analysis of ORs for fractures, and mean differences in bone mineral density. Heterogeneity was assessed using the I2 statistic.ResultsWe included 18 studies (7 RCTs and 11 observational studies) in the systematic review. Meta-analysis of observational studies did not demonstrate any significant association between ICS and fractures in children (pooled OR 1.02, 95% CI 0.94 to 1.10, two studies), or adults (pooled OR 1.09, 95% CI 0.45 to 2.62, four studies). Three RCTs and three observational studies in children reported on bone mineral density at the lumbar spine, and our meta-analysis did not show significant reductions with ICS use. Three RCTs and four observational studies in adults reported on ICS use and bone mineral density at the lumbar spine and femur, with no significant reductions found in the meta-analysis compared to control.ConclusionsICS use for ≥12 months in adults or children with asthma was not significantly associated with harmful effects on fractures or bone mineral density.

In view of the dose-response relationship seen between ICS use and important adverse effects such as fractures and pneumonia, clinicians needs to carefully balance the benefits of ICS versus the harms in older patients receiving long-term high-dose ICS.

To determine the diagnostic accuracy of state, minimally invasive clinical and physical signs (or sets of signs) to be used as screening tests for detecting impending or current water-loss dehydration, or both, in older people by systematically reviewing studies that have measured a reference standard and at least one index test in people aged 65 years and over. Clinical and physical signs for identification of impending and current water-loss dehydration in older people (Protocol)

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