Postpartum haemorrhage (PPH), defined as a blood loss of 500 mL or more after birth, is the leading cause of maternal death worldwide. The World Health Organization (WHO) recommends that all women ...giving birth should receive a prophylactic uterotonic agent. Despite the routine administration of a uterotonic agent for prevention, PPH remains a common complication causing one-quarter of all maternal deaths globally. When prevention fails and PPH occurs, further administration of uterotonic agents as 'first-line' treatment is recommended. However, there is uncertainty about which uterotonic agent is best for the 'first-line' treatment of PPH.
To identify the most effective uterotonic agent(s) with the least side-effects for PPH treatment, and generate a meaningful ranking among all available agents according to their relative effectiveness and side-effect profile.
We searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (5 May 2020), and the reference lists of all retrieved studies.
All randomised controlled trials or cluster-randomised trials comparing the effectiveness and safety of uterotonic agents with other uterotonic agents for the treatment of PPH were eligible for inclusion.
Two review authors independently assessed all trials for inclusion, extracted data and assessed each trial for risk of bias. Our primary outcomes were additional blood loss of 500 mL or more after recruitment to the trial until cessation of active bleeding and the composite outcome of maternal death or severe morbidity. Secondary outcomes included blood loss-related outcomes, morbidity outcomes, and patient-reported outcomes. We performed pairwise meta-analyses and indirect comparisons, where possible, but due to the limited number of included studies, we were unable to conduct the planned network meta-analysis. We used the GRADE approach to assess the certainty of evidence.
Seven trials, involving 3738 women in 10 countries, were included in this review. All trials were conducted in hospital settings. Randomised women gave birth vaginally, except in one small trial, where women gave birth either vaginally or by caesarean section. Across the seven trials (14 trial arms) the following agents were used: six trial arms used oxytocin alone; four trial arms used misoprostol plus oxytocin; three trial arms used misoprostol; one trial arm used Syntometrine® (oxytocin and ergometrine fixed-dose combination) plus oxytocin infusion. Pairwise meta-analysis of two trials (1787 participants), suggests that misoprostol, as first-line treatment uterotonic agent, probably increases the risk of blood transfusion (risk ratio (RR) 1.47, 95% confidence interval (CI) 1.02 to 2.14, moderate-certainty) compared with oxytocin. Low-certainty evidence suggests that misoprostol administration may increase the incidence of additional blood loss of 1000 mL or more (RR 2.57, 95% CI 1.00 to 6.64). The data comparing misoprostol with oxytocin is imprecise, with a wide range of treatment effects for the additional blood loss of 500 mL or more (RR 1.66, 95% CI 0.69 to 4.02, low-certainty), maternal death or severe morbidity (RR 1.98, 95% CI 0.36 to 10.72, low-certainty, based on one study n = 809 participants, as the second study had zero events), and the use of additional uterotonics (RR 1.30, 95% CI 0.57 to 2.94, low-certainty). The risk of side-effects may be increased with the use of misoprostol compared with oxytocin: vomiting (2 trials, 1787 participants, RR 2.47, 95% CI 1.37 to 4.47, high-certainty) and fever (2 trials, 1787 participants, RR 3.43, 95% CI 0.65 to 18.18, low-certainty). According to pairwise meta-analysis of four trials (1881 participants) generating high-certainty evidence, misoprostol plus oxytocin makes little or no difference to the use of additional uterotonics (RR 0.99, 95% CI 0.94 to 1.05) and to blood transfusion (RR 0.95, 95% CI 0.77 to 1.17) compared with oxytocin. We cannot rule out an important benefit of using the misoprostol plus oxytocin combination over oxytocin alone, for additional blood loss of 500 mL or more (RR 0.84, 95% CI 0.66 to 1.06, moderate-certainty). We also cannot rule out important benefits or harms for additional blood loss of 1000 mL or more (RR 0.76, 95% CI 0.43 to 1.34, moderate-certainty, 3 trials, 1814 participants, one study reported zero events), and maternal mortality or severe morbidity (RR 1.09, 95% CI 0.35 to 3.39, moderate-certainty). Misoprostol plus oxytocin increases the incidence of fever (4 trials, 1866 participants, RR 3.07, 95% CI 2.62 to 3.61, high-certainty), and vomiting (2 trials, 1482 participants, RR 1.85, 95% CI 1.16 to 2.95, high-certainty) compared with oxytocin alone. For all outcomes of interest, the available evidence on the misoprostol versus Syntometrine® plus oxytocin combination was of very low-certainty and these effects remain unclear. Although network meta-analysis was not performed, we were able to compare the misoprostol plus oxytocin combination with misoprostol alone through the common comparator of oxytocin. This indirect comparison suggests that the misoprostol plus oxytocin combination probably reduces the risk of blood transfusion (RR 0.65, 95% CI 0.42 to 0.99, moderate-certainty) and may reduce the risk of additional blood loss of 1000 mL or more (RR 0.30, 95% CI 0.10 to 0.89, low-certainty) compared with misoprostol alone. The combination makes little or no difference to vomiting (RR 0.75, 95% CI 0.35 to 1.59, high-certainty) compared with misoprostol alone. Misoprostol plus oxytocin compared to misoprostol alone are compatible with a wide range of treatment effects for additional blood loss of 500 mL or more (RR 0.51, 95% CI 0.20 to 1.26, low-certainty), maternal mortality or severe morbidity (RR 0.55, 95% CI 0.07 to 4.24, low-certainty), use of additional uterotonics (RR 0.76, 95% CI 0.33 to 1.73, low-certainty), and fever (RR 0.90, 95% CI 0.17 to 4.77, low-certainty).
The available evidence suggests that oxytocin used as first-line treatment of PPH probably is more effective than misoprostol with less side-effects. Adding misoprostol to the conventional treatment of oxytocin probably makes little or no difference to effectiveness outcomes, and is also associated with more side-effects. The evidence for most uterotonic agents used as first-line treatment of PPH is limited, with no evidence found for commonly used agents, such as injectable prostaglandins, ergometrine, and Syntometrine®.
The Medical Certificate of Stillbirth (MCS) records data about a baby's death after 24 weeks of gestation but before birth. Major errors that could alter interpretation of the MCS were widespread in ...two UK-based regional studies.
A multicentre evaluation was conducted, examining MCS issued 1 January 2018 to 31 December 2018 in 76 UK obstetric units. A systematic case-note review of stillbirths was conducted by Obstetric and Gynaecology trainees, generating individual 'ideal MCSs' and comparing these to the actual MCS issued. Anonymized central data analysis described rates and types of error, agreement and factors associated with major errors.
There were 1120 MCSs suitable for assessment, with 126 additional submitted data sets unsuitable for accuracy analysis (total 1246 cases). Gestational age demonstrated 'substantial' agreement K = 0.73 (95% CI 0.70-0.76). Primary cause of death (COD) showed 'fair' agreement K = 0.26 (95% CI 0.24-0.29). Major errors 696/1120; 62.1% (95% CI 59.3-64.9%) included certificates issued for fetal demise at <24 weeks' gestation 23/696; 3.3% (95% CI 2.2-4.9%) or neonatal death 2/696; 0.3% (95% CI 0.1-1.1%) or incorrect primary COD 667/696; 95.8% (95% CI 94.1-97.1%). Of 540/1246 43.3% (95% CI 40.6-46.1%) 'unexplained' stillbirths, only 119/540 22.0% (95% CI 18.8-25.7%) remained unexplained; the majority were redesignated as either fetal growth restriction FGR: 195/540; 36.1% (95% CI 32.2-40.3%) or placental insufficiency 184/540; 34.1% (95% CI 30.2-38.2). Overall, FGR 306/1246; 24.6% (95% CI 22.3-27.0%) was the leading primary COD after review, yet only 53/306 17.3% (95% CI 13.5-22.1%) FGR cases were originally attributed correctly.
This study demonstrates widespread major errors in MCS completion across the UK. MCS should only be completed following structured case-note review, with particular attention on the fetal growth trajectory.
IntroductionSurgical repair of congenital heart defects often requires the use of cardiopulmonary bypass (CPB) and cardioplegic arrest. Cardioplegia is used during cardiac surgery requiring CPB to ...keep the heart still and to reduce myocardial damage as a result of ischaemia–reperfusion injury. Cold cardioplegia is the prevalent method of myocardial protection in paediatric patients; however, warm cardioplegia is used as part of usual care throughout the UK in adults. We aim to provide evidence to support the use of warm versus cold blood cardioplegia on clinical and biochemical outcomes during and after paediatric congenital heart surgery.Methods and analysisWe are conducting a single-centre randomised controlled trial in paediatric patients undergoing operations requiring CPB and cardioplegic arrest at the Bristol Royal Hospital for Children. We will randomise participants in a 1:1 ratio to receive either ‘cold-blood cardioplegia’ or ‘warm-blood cardioplegia’. The primary outcome will be the difference between groups with respect to Troponin T levels over the first 48 postoperative hours. Secondary outcomes will include measures of cardiac function; renal function; cerebral function; arrythmias during and postoperative hours; postoperative blood loss in the first 12 hours; vasoactive-inotrope score in the first 48 hours; intubation time; chest and wound infections; time from return from theatre until fit for discharge; length of postoperative hospital stay; all-cause mortality to 3 months postoperative; myocardial injury at the molecular and cellular level.Ethics and disseminationThis trial has been approved by the London – Central Research Ethics Committee. Findings will be disseminated to the academic community through peer-reviewed publications and presentation at national and international meetings. Patients will be informed of the results through patient organisations and newsletters to participants.Trial registration numberISRCTN13467772; Pre-results.
Background
Colorectal cancer (CRC) is rising in incidence in young adults, and this observation is currently unexplained. We investigated whether having a personal history of type 2 diabetes mellitus ...(T2D) was a potential risk factor for young‐onset colorectal cancer (YOCRC).
Methods
The South Australian Young Onset (SAYO) CRC study is a series of young adults with CRC below age 55. Ninety unrelated YOCRC cases were recruited to the study. Personal history and detailed family history of T2D were obtained at face‐to‐face interview and confirmed from medical records. Whole exome sequencing was conducted on germline DNA from each CRC case. Controls for personal history studies of T2D were 240 patients with proven clear colonoscopies and no known CRC predispositions.
Results
The median age of YOCRC cases was 44 years (18–54) and of controls was 45 years (18–54), and 53% of both cases and controls were females (P = 0.99). Left‐sided (distal) CRC was seen in 67/89 (75%) of cases. A personal history of T2D was confirmed in 17/90 (19%) YOCRC patients compared with controls (12/240, 5%; P < 0.001; odds ratio = 4.4; 95% confidence interval, 2.0–9.7). YOCRC patients frequently reported at least one first‐degree relative with T2D (32/85, 38%). Ten of 87 (12%) of YOCRC cases had CRC‐related pathogenic germline variants, however, no pathogenic variants in familial diabetes‐associated genes were seen.
Conclusions
Though the mechanism remains unclear, our observations suggest that there is enrichment for personal history of T2D in YOCRC patients.
Impact
A diagnosis of T2D could therefore potentially identify a subset of young adults at increased risk for CRC and in whom early screening might be appropriate.
There is an enrichment for personal history of type 2 diabetes in young‐onset colorectal cancer (YOCRC) patients, and this feature could therefore potentially identify a subset of young adults at increased risk for CRC and in whom early screening might be appropriate.
Aquaculture is currently the fastest expanding global animal food production sector and is a key future contributor to food security. An increase in food security will be dependent upon the ...development and improvement of sustainable practices. A prioritization exercise was undertaken, focusing on the future knowledge needs to underpin UK sustainable aquaculture (both domestic and imported products) using a ‘task force’ group of 36 ‘practitioners’ and 12 ‘research scientists’ who have an active interest in sustainable aquaculture. A long list of 264 knowledge needs related to sustainable aquaculture was developed in conjunction with the task force. The long list was further refined through a three stage process of voting and scoring, including discussions of each knowledge need. The top 25 knowledge needs are presented, as scored separately by ‘practitioners’ or ‘research scientists’. There was similar agreement in priorities identified by these two groups. The priority knowledge needs will provide guidance to structure ongoing work to make science accessible to practitioners and help to prioritize future science policy needs and funding. The process of knowledge exchange, and the mechanisms by which this can be achieved, effectively emerged as the top priority for sustainable aquaculture. Viable alternatives to wild fish‐based aquaculture feeds, resource constraints that will potentially limit expansion of aquaculture, sustainable offshore aquaculture and the treatment of sea lice also emerged as strong priorities. Although the exercise was focused on UK needs for sustainable aquaculture, many of the emergent issues are considered to have global application.
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