Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-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. Methods In 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. Findings Between 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 placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation

Simultaneous determination of silver and other heavy metals in aquatic environment receiving wastewater from industrial area, applying an enrichment method

In the present study, silver (Ag), cadmium (Cd), nickel (Ni), cobalt (Co) and lead (Pb) were simultaneously determined in water samples of fresh water canal receiving untreated effluents from an industrial area, of Sindh Pakistan. The analytes in the water sample were determined by CPE using ammonium pyrrolidinedithiocarbamate (APDC) as a complexing agent and then entrapped in non-ionic surfactant, octylphenoxypolyethoxyethanol (Triton X-114). The surfactant rich phase was diluted with acidic ethanol prior to analysis by flame atomic absorption spectrometry. The variables affecting the complexation and extraction steps such as pH of sample solution, concentration of oxine and Triton X-114, equilibration temperature and time period for shaking were investigated in detail. The validation of the procedure was carried out by analysis of a certified reference sample of water (CRM1634e). Reliability of the proposed method was also checked by the standard addition method in a real sample at three concentration levels of all metals. Under the optimum conditions, the preconcentration of 10 mL sample solutions, allowed preconcentration factor of 20-fold. The lower limit of detection obtained for Ag, Cd, Ni, Co and Pb was 0.42, 0.48, 0.92, 0.62, and 1.42 μg L−1, respectively. The proposed procedure was successfully applied to waste and fresh water samples for simultaneous determination of different metals. The concentration of Ag, Cd, Ni, Co and Pb has shown a decreased trend from 46.5–6.96, 23.0–8.92, 30.2–12.8, 14.2–4.45 and 15.3–5.32 μg L−1, respectively from initial entrance of waste water along the downstream of canal

Assessment of Lead in Blood Samples of Children Residing in the Vicinity of Industries

The aim of present study was to determine the lead (Pb) distributions in blood and prevalence of elevated Pb exposure among children, age ranged (5–10 years), residing near industrialized region of Hyderabad city, Pakistan. For comparison, biological samples of children of same age group from non-industrial area were also analyzed. The Pb concentration in blood samples was determined by electrothermal atomic absorption spectrometry, prior to microwave assisted acid digestion. The results showed that significantly higher proportion of children living in the vicinity of industrial area, had blood Pb levels (BLL) in the range of 15.4-35.6 µg/dL, and 8.51-16.7 µg/dL for those of non-industrial area. The blood Pb level was higher in boys of both groups as compared to girls of same age group, but the difference was not significant (p=0.178). Negative correlation was observed between BLL and hemoglobin levels (p<0.001), while positive correlation was observed between BLL and age