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

Etude sur l’utilisation de Primolut N comme un comprimé contraceptif dans la métropole de Kumasi au Ghana.

This study investigated the use of Primolut N tablet which contains norethisterone 5mg popularly called N- tablet by users as a precoital contraceptive by women in the Kumasi metropolis of Ghana. Clients who called at any of the twenty (20) selected Pharmacies in residential areas within the Kumasi metropolis demanding the drug, with or without valid prescriptions were interviewed using a guide. Of the two hundred and twenty (220) users interviewed, 94% demanded the drug for contraception and 6% for menstrual disorders. Sixty one percent of those demanding it for contraception were between the ages 20-25 years. Respondents preferred the use of norethisterone tablets as a contraceptive to other methods because it worked for them and they also found it easy and convenient taking a tablet just before coitus than taking daily oral contraceptive pills. Norethisterone is being used as a pre-coital contraceptive, though the efficacy, safety and reliability of the drug for that purpose is unknown. Until these are known, women must be discouraged from using the drugCette étude a examiné l’utilisation de Primolut N (comprimé) qui contient la noréthistérone 5mg et qui est communément connue comme le comprimé N par les usagers comme un contraceptif pré coïtal dans la métropole au Ghana. Les clients qui se sont présentées à n’importe quelle pharmacie parmi les vingt (20) pharmacies dans les quartiers résidentiels au sein de la métropole de Kumasi pour chercher le médicament avec ou sans l’ordonnance valable, ont été interrogées à l’aide d’un guide. Sur les deux cent vingt (220) usagères interrogées, 94% ont demandé le médicament pour la contraception et 6% pour les troubles menstruels. Soixante et un pour cent de celles qui le demandaient pour la contraception étaient âgées d’entre 20 et 25 ans. Les interrogées préféraient utiliser les comprimés de la noréthistérone comme contraceptif par rapport aux autres méthodes parce qu’il a marché pour elles et elles le trouvaient facile et plus convenable de prendre des pilules contraceptives orales tous les jours. La noréthistérone est utilisée comme un contraceptif pré coïtal, bien que l’efficacité, la sureté et la fiabilité du médicament ne soient pas connues. Il faut décourager les femmes d’utiliser le médicament jusqu’à ce qu’on se renseigne sur ces détail

Assessment of â freshâ versus â maceratedâ as accurate markers of time since intrauterine fetal demise in lowâ income countries

ObjectiveTo compare provider assessment of fetal maceration with deathâ toâ delivery interval to evaluate the reliability of appearance as a proxy for time of death.MethodsCohort chart abstraction was performed for all stillbirth deliveries at or above 28 weeks of gestation during a 1â year period in a teaching hospital in Ghana.ResultsOf 470 stillborn infants, 337 had adequate data for analysis. Of 47 fetuses alive on admission with deathâ toâ delivery intervals estimated to be less than 8 hours (expected to be reported as fresh), 14 (30%) were actually reported as macerated. Of 94 cases in which the fetus was deceased on admission with deathâ toâ delivery interval of more than 8 hours (expected to be macerated), 17 (18%) were described as fresh.ConclusionProvider description of fetal appearance may be an unreliable indicator for time since fetal death. The findings have significant implications for stillbirth prevention and assessment.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135680/1/ijgo223.pd