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

Obstetric anal sphincter injuries before and after the introduction of the Episcissors-60: A multi-centre time series analysis.

Abstract Obstetric anal sphincter injuries before and after the introduction of the Episcissors-60: A multi-centre time series analysis. Paul Ayuk , Allison Farnworth , Jon Rees , Aethele Khunda , Dawn Edmundson , Vinita Raheja , Aarti Ullal , Velauthapillai Ravimohan , Ena Lu , S C Robson Objective To investigate the impact of the Episcissors-60 on obstetric anal sphincter injury (OASI) rates. Study design Observational multi-centre time series analysis at four maternity units in the North-East of England. The main outcome measures were obstetric anal sphincter injury rates and delivery blood loss Results Data were analysed for women who had a vaginal birth of a singleton pregnancy before (11,192) and after (8,064) the introduction of the Episcissors-60. There were 2115 episiotomies before and 1498 after the introduction of the Episcissors-60, of which 1311 (87.5%) were undertaken with the Episcissors-60, 114 (7.6%) with other scissors and the scissors used were not stated in 73 (4.8%) women. There was no significant association between the introduction of Episcissors-60 and the performance of an episiotomy (χ2 = 0.006, p = 0.94). Episiotomy was associated with a significant reduction in OASI rates (1.9% Vs 2.8%, odds ratio = 0.67 [0.51 – 0.86]; p = 0.001). There was no significant association between the introduction of the Episcissors-60 and the occurrence of OASIs in all women (χ2 = 0.6, p= 0.46) or in women who had an episiotomy (χ2 = 0.20, p = 0.71). In women who had an episiotomy, the mean estimated delivery blood loss was 550.3 ± 8.2 ml before and 598.8 ± 10.9 ml after the introduction of the Episcissors-60 (p < 0.001). Conclusion Introduction of the Episcissors-60 was not associated with a change in OASI or episiotomy rates but may be associated with a small increase in delivery blood loss. Key words: Episcissors-60, obstetric anal sphincter injur

A Preliminary Test of a Student-Centered Intervention on Increasing Physical Activity in Underserved Adolescents

Background—Previous studies have shown that choice and self-initiated behavior change are important for increasing intrinsic motivation and physical activity (PA), however, little of this research has focused on underserved adolescents. Purpose—This study examined the effects of a 4-week student-centered intervention on increasing PA in underserved adolescents. Methods—Twenty-eight students in the intervention school were matched (on race, percentage on free or reduced-price lunch program, gender, and age) with 20 students from another school who served as the comparison group (30 girls, 18 boys; ages 10–12 years; 83% African American; 83% on free or reduced-price lunch). The student-centered intervention was consistent with selfdetermination (motivation) theory and social cognitive theory in that it emphasized increasing intrinsic motivation and behavioral skills for PA. Intervention adolescents took ownership in selecting a variety of PA activities in which to participate, and they generated coping strategies for making effective PA behavior changes. Results—Intervention participants showed greater increases in accelerometer estimates of time spent in moderate PA, moderate-to-vigorous PA, and vigorous PA from baseline to Week 4 of the intervention than the comparison group. Intervention participants also showed greater increases in PA motivation and positive self-concept for PA than comparison adolescents. Conclusions—This study provides preliminary evidence that increasing adolescent involvement and choice of activities may be important in developing future PA interventions for underserved adolescents

A randomized trial of planned cesarean or vaginal delivery for twin pregnancy

Background: Twin birth is associated with a higher risk of adverse perinatal outcomes than singleton birth. It is unclear whether planned cesarean section results in a lower risk of adverse outcomes than planned vaginal delivery in twin pregnancy.\ud \ud Methods: We randomly assigned women between 32 weeks 0 days and 38 weeks 6 days of gestation with twin pregnancy and with the first twin in the cephalic presentation to planned cesarean section or planned vaginal delivery with cesarean only if indicated. Elective delivery was planned between 37 weeks 5 days and 38 weeks 6 days of gestation. The primary outcome was a composite of fetal or neonatal death or serious neonatal morbidity, with the fetus or infant as the unit of analysis for the statistical comparison.\ud \ud Results: A total of 1398 women (2795 fetuses) were randomly assigned to planned cesarean delivery and 1406 women (2812 fetuses) to planned vaginal delivery. The rate of cesarean delivery was 90.7% in the planned-cesarean-delivery group and 43.8% in the planned-vaginal-delivery group. Women in the planned-cesarean-delivery group delivered earlier than did those in the planned-vaginal-delivery group (mean number of days from randomization to delivery, 12.4 vs. 13.3; P = 0.04). There was no significant difference in the composite primary outcome between the planned-cesarean-delivery group and the planned-vaginal-delivery group (2.2% and 1.9%, respectively; odds ratio with planned cesarean delivery, 1.16; 95% confidence interval, 0.77 to 1.74; P = 0.49).\ud \ud Conclusion: In twin pregnancy between 32 weeks 0 days and 38 weeks 6 days of gestation, with the first twin in the cephalic presentation, planned cesarean delivery did not significantly decrease or increase the risk of fetal or neonatal death or serious neonatal morbidity, as compared with planned vaginal delivery