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Background Postpartum haemorrhage (PPH) is a leading cause of maternal mortality worldwide. Maternal anaemia greatly increases the risk of PPH, and over a third of all pregnant women are anaemic. Because anaemia reduces the oxygen-carrying capacity of the blood, anaemic women cannot tolerate the same volume of blood loss as healthy women. Yet the same blood loss threshold is used to define PPH in all women. The lack of an established PPH definition in anaemic women means the most appropriate outcome measures for use in clinical trials are open to question. We used data from the WOMAN-2 trial to examine different definitions of PPH in anaemic women and consider their appropriateness as clinical trial outcome measures. Main body The WOMAN-2 trial is assessing tranexamic acid (TXA) for PPH prevention in women with moderate or severe anaemia at baseline. To obtain an accurate, precise estimate of the treatment effect, outcome measures should be highly specific and reasonably sensitive. Some outcome misclassification is inevitable. Low sensitivity reduces precision, but low specificity biases the effect estimate towards the null. Outcomes should also be related to how patients feel, function, or survive. The primary outcome in the WOMAN-2 trial, a ‘clinical diagnosis of PPH’, is defined as estimated blood loss > 500 ml or any blood loss within 24 h sufficient to compromise haemodynamic stability. To explore the utility of several PPH outcome measures, we analysed blinded data from 4521 participants. For each outcome, we assessed its: (1) frequency, (2) specificity for significant bleeding defined as shock index ≥1.0 and (3) association with fatigue (modified fatigue symptom inventory [MFSI]), physical endurance (six-minute walk test) and breathlessness. A clinical diagnosis of PPH was sufficiently frequent (7%), highly specific for clinical signs of early shock (95% specificity for shock index ≥1) and associated with worse maternal functioning after childbirth. Conclusion Outcome measures in clinical trials of interventions for PPH prevention should facilitate valid and precise estimation of the treatment effect and be important to women. A clinical diagnosis of PPH appears to meet these criteria, making it an appropriate primary outcome for the WOMAN-2 trial. Trial registration ClinicalTrials.gov NCT03475342, registered on 23 March 2018; ISRCTN62396133, registered on 7 December 2017; Pan African Clinical Trial Registry PACTR201909735842379, registered on 18 September 2019.

Background Tranexamic acid reduces blood loss in surgery and the risk of death in trauma patients. Meta-analyses of small trials suggest that tranexamic acid decreases the number of deaths from gastrointestinal bleeding, but these meta-analyses are prone to selection bias. Objective The trial provides reliable evidence of the effect of tranexamic acid on mortality, rebleeding and complications in significant acute gastrointestinal bleeding. Design A multicentre, randomised, placebo-controlled trial and economic analysis. Patients were assigned by selecting one treatment pack from a box of eight, which were identical apart from the pack number. Patients, caregivers and outcome assessors were masked to allocation. The main analyses were by intention to treat. Setting The setting was 164 hospitals in 15 countries, co-ordinated from the London School of Hygiene & Tropical Medicine. Participants Adults with significant upper or lower gastrointestinal bleeding (n = 12,009) were eligible if the responsible clinician was substantially uncertain about whether or not to use tranexamic acid. The clinical diagnosis of significant bleeding implied a risk of bleeding to death, including hypotension, tachycardia or signs of shock, or urgent transfusion, endoscopy or surgery. Intervention Tranexamic acid (a 1-g loading dose over 10 minutes, then a 3-g maintenance dose over 24 hours) or matching placebo. Main outcome measures The primary outcome was death due to bleeding within 5 days of randomisation. Secondary outcomes were all-cause and cause-specific mortality; rebleeding; need for endoscopy, surgery or radiological intervention; blood product transfusion; complications; disability; and days spent in intensive care or a high-dependency unit. Results A total of 12,009 patients were allocated to receive tranexamic acid (n = 5994, 49.9%) or the matching placebo (n = 6015, 50.1%), of whom 11,952 (99.5%) received the first dose. Death due to bleeding within 5 days of randomisation occurred in 222 (3.7%) patients in the tranexamic acid group and in 226 (3.8%) patients in the placebo group (risk ratio 0.99, 95% confidence interval 0.82 to 1.18). Thromboembolic events occurred in 86 (1.4%) patients in the tranexamic acid group and 72 (1.2%) patients in the placebo group (risk ratio 1.20, 95% confidence interval 0.88 to 1.64). The risk of arterial thromboembolic events (myocardial infarction or stroke) was similar in both groups (0.7% in the tranexamic acid group vs. 0.8% in the placebo group; risk ratio 0.92, 95% confidence interval 0.60 to 1.39), but the risk of venous thromboembolic events (deep-vein thrombosis or pulmonary embolism) was higher in tranexamic acid-treated patients than in placebo-treated patients (0.8% vs. 0.4%; risk ratio 1.85, 95% confidence interval 1.15 to 2.98). Seizures occurred in 38 patients who received tranexamic acid and in 22 patients who received placebo (0.6% vs. 0.4%, respectively; risk ratio 1.73, 95% confidence interval 1.03 to 2.93). In the base-case economic analysis, tranexamic acid was not cost-effective and resulted in slightly poorer health outcomes than no tranexamic acid. Conclusions Tranexamic acid did not reduce death from gastrointestinal bleeding and, although inexpensive, it is not cost-effective in adults with acute gastrointestinal bleeding. Future work These results caution against a uniform approach to the management of patients with major haemorrhage and highlight the need for randomised trials targeted at specific pathophysiological processes. Limitations Although this is one of the largest randomised trials in gastrointestinal bleeding, we cannot rule out a modest increase or decrease in death due to bleeding with tranexamic acid. Trial registration Current Controlled Trials ISRCTN11225767, ClinicalTrials.gov NCT01658124 and EudraCT 2012-003192-19. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 58. See the NIHR Journals Library website for further project information.

Objectives: To understand the acceptability and feasibility of sexually transmitted infection (STI) testing during antenatal care, along with the prevalence of STIs, in Rawalpindi, Pakistan. Methods: We enrolled pregnant women seeking antenatal care and performed STI testing using Cepheid GeneXpert® CT/NG and TV kits and Alere Determine™ HIV and syphilis tests. We used interviewer-administered surveys to collect medical, social, and sexual histories. Participants testing positive for STIs and their partners were treated. Results: We enrolled 1001 women from September to December 2019. Nearly all women offered to participate in this study enrolled. Most women understood the effects an STI can have on their pregnancy (99.6%) and valued STI screening during pregnancy (98.1%). 11 women tested positive for any STI: ( Chlamydia trachomatis = 4, Neisseria gonorrhoeae = 1, and Trichomonas vaginalis = 6). Of those, six presented for a test-of-cure, and two were positive for Trichomonas vaginalis. None tested positive for HIV infection or syphilis ( n = 503). Conclusions: STI testing during antenatal care in Rawalpindi was acceptable, valued, understood, and feasible. The prevalence of STIs in pregnant women was low. Continued prevalence monitoring is warranted.

Background Early administration of the antifibrinolytic drug tranexamic acid reduces death from bleeding in trauma and postpartum haemorrhage. We examined how the effectiveness and safety of antifibrinolytic drugs varies by the baseline risk of death as a result of bleeding. Methods We performed an individual patient-level data meta-analysis of randomised trials including more than 1000 patients that assessed antifibrinolytics in acute severe bleeding. We identified trials performed between January 1, 1946 and July 5, 2018 (PROSPERO, number 42016052155). Results Two randomised trials were selected where 28 333 patients received tranexamic acid treatment within 3 h after the onset of acute bleeding. Baseline characteristics to estimate the risk of death as a result of bleeding were divided into four categories: Low (0–5%), intermediate (6–10%), high (11–20%), and very high (>20%). Most patients had a low baseline risk of death as a result of bleeding (23 008 [81%]). Deaths as a result of bleeding occurred in all baseline risk categories with 240 (1%), 202 (8%), 232 (14%), and 357 (30%) deaths in the low-, intermediate-, high-, and very high-risk categories, respectively. The effectiveness of tranexamic acid did not vary by baseline risk when given within 3 h after bleeding onset (P=0.51 for interaction term). There was no increased risk of vascular occlusive events with tranexamic acid and it did not vary by baseline risk categories (P=0.25). Conclusions Tranexamic acid appears to be safe and effective regardless of baseline risk of death. Because many deaths are in patients at low and intermediate risk, tranexamic acid use should not be restricted to the most severely injured or bleeding patients.

Background Acute gastrointestinal (GI) bleeding is an important cause of mortality worldwide. Bleeding can occur from the upper or lower GI tract, with upper GI bleeding accounting for most cases. The main causes include peptic ulcer/erosive mucosal disease, oesophageal varices and malignancy. The case fatality rate is around 10% for upper GI bleeding and 3% for lower GI bleeding. Rebleeding affects 5–40% of patients and is associated with a four-fold increased risk of death. Tranexamic acid (TXA) decreases bleeding and the need for blood transfusion in surgery and reduces death due to bleeding in patients with trauma and postpartum haemorrhage. It reduces bleeding by inhibiting the breakdown of fibrin clots by plasmin. Due to the methodological weaknesses and small size of the existing trials, the effectiveness and safety of TXA in GI bleeding is uncertain. The Haemorrhage ALleviation with Tranexamic acid – Intestinal system (HALT-IT) trial aims to provide reliable evidence about the effects of TXA in acute upper and lower GI bleeding. Methods The HALT-IT trial is an international, randomised, double-blind, placebo-controlled trial of tranexamic acid in 12,000 adults (increased from 8000) with acute upper or lower GI bleeding. Eligible patients are randomly allocated to receive TXA (1-g loading dose followed by 3-g maintenance dose over 24 h) or matching placebo. The main analysis will compare those randomised to TXA with those randomised to placebo on an intention-to-treat basis, presenting the results as effect estimates (relative risks) and confidence intervals. The primary outcome is death due to bleeding within 5 days of randomisation and secondary outcomes are: rebleeding; all-cause and cause-specific mortality; thromboembolic events; complications; endoscopic, radiological and surgical interventions; blood transfusion requirements; disability (defined by a measure of patient’s self-care capacity); and number of days spent in intensive care or high-dependency units. Subgroup analyses for the primary outcome will consider time to treatment, location of bleeding, cause of bleed and clinical Rockall score. Discussion We present the statistical analysis of the HALT-IT trial. This plan was published before the treatment allocation was unblinded. Trial registration Current Controlled Trials, ID: ISRCTN11225767. Registered on 3 July 2012; Clinicaltrials.gov, ID: NCT01658124. Registered on 26 July 2012. Electronic supplementary material The online version of this article (10.1186/s13063-019-3561-7) contains supplementary material, which is available to authorized users.

BACKGROUND: Antifibrinolytics reduce death from bleeding in trauma and post-partum haemorrhage. We examined the effect of treatment delay on the effectiveness of antifibrinolytics. METHODS: We did an individual patient-level data meta-analysis of randomised trials done with more than 1000 patients that assessed antifibrinolytics in acute severe bleeding. We identified trials done between Jan 1, 1946, and April 7, 2017, from MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, PubMed, Popline, and the WHO International Clinical Trials Registry Platform. The primary measure of treatment benefit was absence of death from bleeding. We examined the effect of treatment delay on treatment effectiveness using logistic regression models. We investigated the effect of measurement error (misclassification) in sensitivity analyses. This study is registered with PROSPERO, number 42016052155. FINDINGS: We obtained data for 40 138 patients from two randomised trials of tranexamic acid in acute severe bleeding (traumatic and post-partum haemorrhage). Overall, there were 3558 deaths, of which 1408 (40%) were from bleeding. Most (884 [63%] of 1408) bleeding deaths occurred within 12 h of onset. Deaths from post-partum haemorrhage peaked 2-3 h after childbirth. Tranexamic acid significantly increased overall survival from bleeding (odds ratio [OR] 1·20, 95% CI 1·08-1·33; p=0·001), with no heterogeneity by site of bleeding (interaction p=0·7243). Treatment delay reduced the treatment benefit (p

To compare the safety and efficacy of 10 units of intravenous syntocinon alone with 10 units intravenous syntocinon and 0.25 mg intramuscular ergometrine in the prevention of atonic uterine haemorrhage during caesarean section.The quasi-experimental study was conducted at the Maternal and Child Health Centre, Unit I, Pakistan Institute of Medical Sciences, Islamabad, from November 1, 2010 to February 28, 2011. All women undergoing caesarean section were included in the study. Patients were given intravenous 10 units syntocinon alone intraoperatively from November 1 to December 31,2010, while 0.25 mg ergometrine intramuscular was added to 10 units intravenous syntocinon from January 1 to February 28, 2011. Frequency of postpartum haemorrhage, adverse effects of drugs and maternal morbidity and mortality were assessed by using chi square test. P0.05 was taken as statistically significant.Of the total number of 701 subjects, 378 (54%) women were given 10 units syntocinon and 323 (46%) were given 0.25 mg ergometrine in addition to 10 units syntocinon. The mean age in the syntocinon group was 28 +/- 3.5 yrs with gestational age of 37.5 +/- 2 wks, while that in syntocinon-ergometrine group was 29 +/- 3.4 years and 38 +/- 2 weeks respectively. Postpartum haemorrhage in the syntocinon group was found in 38 (10%) women versus 05 (1.5%) women) in the other group (p0.001). Adverse effects like nausea, vomiting and raised blood pressure were slightly more with syntocinon-ergometrine than syntocinon alone (n = 56; 15.3% vs n = 35; 9.2%), but it was not statistically significant. Post partum haemorrhage was responsible for 40% of maternal mortality during the study period and that was in the syntocinon group.Prophylactic ergometrine in addition to syntocinon is superior to syntocinon alone in decreasing frequency of postpartum haemorrhage in caesarean section and associated maternal morbidity and mortality. Regarding safety profile, the two groups showed no statistically significant change.