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

Levels of Awareness on Safety and Health in Use of Agro-Chemicals among Large Scale Flower Farm Workers in Uasin Gishu County. Kenya

Flower farms play an important role in the horticulture industry which contributes about 10% of agricultural produce in Kenya. They create employment, earn foreign exchange through exports and improve infrastructure in the world. Despite these achievements agro-chemicals used in these farms to increase production pose a great danger to the health of the farm workers and the surrounding environment. The broad objective of this study sought to reduce the health impact of unsafe handling of agro-chemicals by assessing compliance with legal requirements by large scale flower farm workers in Uasin Gishu County. This study was guided by the following objectives, to assess knowledge, attitude safe handling and disposal of agro-chemicals as well as assess frequencies of self-reported health symptoms related to pesticide exposure among large scale private farm workers. The study employed cross sectional survey design, purposive sampling was used to get the sample from four large scale flower farms in Uasin Gishu County. Data was collected by administering questionnaires and analyzed using SPSS version 20 using descriptive and inferential statistics (percentages means and medians). The study findings have revealed that some of the agro-chemicals used are acephate, tetradifon, aldicarb and piperophos. Though majority of the respondents have participated in training courses related to the safe handling, a significant percentage of the respondents do not safe practice to reduce pesticide exposure. Despite this, the respondents were aware of other ways of pest control such as fostering beneficial organisms and disrupting pest’s life cycle. The results indicate that agro-chemicals can have negative impacts on health. Therefore, both men and women should put on personal protective devices and ensure proper storage, handling and disposal of agro-chemicals. Workers that handled agro-chemicals had symptoms of skin rash, itch, running nose, burns, eye itching, excessive sweating, chest pains and pregnancy complications. Workers should undergo training on safe handling of agro-chemicals so that they can read and understand the information written on agro-chemicals; undergo medical checkups before and during work periods and have a positive attitude towards safe handling of agro-chemicals. There is also need for effective diagnosis and treatment of the symptoms brought by agro-chemicals in order to reduce fatality of acute poisoning. Keywords: Agro-chemicals, awareness, safe-handling, attitude, health and safety, Uasin Gishu county- Kenya