Endothelin-Dependent Vasoconstriction in Human Uterine Artery: Application to Preeclampsia

BACKGROUND: Reduced uteroplacental perfusion, the initiating event in preeclampsia, is associated with enhanced endothelin-1 (ET-1) production which feeds the vasoconstriction of uterine artery. Whether the treatments of preeclampsia were effective on ET-1 induced contraction and could reverse placental ischemia is the question addressed in this study. We investigated the effect of antihypertensive drugs used in preeclampsia and of ET receptor antagonists on the contractile response to ET-1 on human uterine arteries. METHODOLOGY/PRINCIPAL FINDINGS: Experiments were performed, ex vivo, on human uterine artery samples obtained after hysterectomy. We studied variations in isometric tension of arterial rings in response to the vasoconstrictor ET-1 and evaluated the effects of various vasodilators and ET-receptor antagonists on this response. Among antihypertensive drugs, only dihydropyridines were effective in blocking and reversing the ET-1 contractile response. Their efficiency, independent of the concentration of ET-1, was only partial. Hydralazine, alpha-methyldopa and labetalol had no effect on ET-1 induced contraction which is mediated by both ET(A) and ET(B) receptors in uterine artery. ET receptors antagonists, BQ-123 and BQ-788, slightly reduced the amplitude of the response to ET-1. Combination of both antagonists was more efficient, but it was not possible to reverse the maximal ET-1-induced contraction with antagonists used alone or in combination. CONCLUSION: Pharmacological drugs currently used in the context of preeclampsia, do not reverse ET-1 induced contraction. Only dihydropyridines, which partially relax uterine artery previously contracted with ET-1, might offer interesting perspectives to improve placental perfusion

Identification of pregnancies at increased risk of brachial plexus birth palsy - the construction of a weighted risk score

Objective: Since it is difficult to identify women at increased risk of fetal brachial plexus birth palsy (BPBP) during labor and delivery, we aimed to construct and validate a risk score. Methods: A retrospective case-control study was undertaken in 2001 and 2006 in an urban context in Malmo, Sweden. A risk score was constructed for all women who had received routine municipal maternal health care at Skane University Hospital (n = 10 459). The model was validated among all pregnant women with BPBP and controls in Sweden between 2006 and 2007. Results: The likelihood of BPBP increased as the risk score rose: 3.1% of the women studied had a risk score >= 5, including 32.1% of the BPBP cases, where the risk showed a 38-fold increase, as compared to those with a risk score <= 1 (2/3 of the population). Conclusion: Our findings indicate that it is possible to identify women at increased risk of having a child with BPBP by using variables observable in advance of delivery

One Plus One Equals Two—will that do? A trial protocol for a Swedish multicentre randomised controlled trial to evaluate a clinical practice to reduce severe perineal trauma {1}

Background: Severe perineal trauma sustained during childbirth is a serious complication since it can lead to both short- and long-term consequences for women. Some of the methods used to prevent perineal injuries have been evaluated in clinical trials, but there are still gaps in the evidence. A new clinical practice has been introduced, adopted by more than half of the maternity wards in Sweden with the aim of reducing severe perineal trauma. This procedure involves two midwives assisting the woman during the second stage of labour. Methods/design: In this multicentre randomised controlled trial, 2946 women will be randomised to be assisted by one or two midwives during the second stage of labour. Women age 18–47, who plan for their first vaginal birth, with a singleton pregnancy in cephalic presentation, will be asked to participate when admitted to the maternity ward. Five maternity wards comprising 19,500 births/year in different parts of Sweden will participate in this study. The sample size is powered to demonstrate a 50% reduction (from 4.1–2.0%) in primary outcome, which is the prevalence of severe perineal trauma (3rd and 4th degree). Secondary outcomes will include maternal and neonatal outcomes, women’s experiences, midwives’ experiences of the intervention, incontinence, and pelvic floor symptoms. The primary analysis is intention to treat. Questionnaires will be sent to the women at 1 month and 1 year after the birth to assess women’s experiences, pain, incontinence, pelvic floor symptoms, sexual function, and mental health. Discussion: It is important for care during labour and birth to be evidence based. There is a strong desire among midwives to reduce the risk of severe perineal trauma. This may lead to new strategies and practices being implemented into practice without scientific evidence. The intervention might have negative side effects or unintended consequences. On the other hand, there is a possibility of the intervention improving care for women. Trial registration {2a}: ClinicalTrials.gov NCT03770962. Registered on 10 December 201

Probabilistic Progress Bars

Predicting the time at which the integral over a stochastic process reaches a target level is a value of interest in many applications. Often, such computations have to be made at low cost, in real time. As an intuitive example that captures many features of this problem class, we choose progress bars, a ubiquitous element of computer user interfaces. These predictors are usually based on simple point estimators, with no error modelling. This leads to fluctuating behaviour confusing to the user. It also does not provide a distribution prediction (risk values), which are crucial for many other application areas. We construct and empirically evaluate a fast, constant cost algorithm using a Gauss-Markov process model which provides more information to the user

The Effect of Two Midwives During the Second Stage of Labour to Reduce Severe Perineal Trauma (Oneplus) : A Multicentre, Randomized Controlled Trial in Sweden

In many high-income countries, severe perinatal trauma (SPT), affecting the anal sphincter muscle complex, has been on the rise over the last decade. However, effective strategies to prevent SPT are scarce. In randomized controlled trials, only perineal warm compresses and massage have shown benefit. Other cohort studies have shown that prevention models involving several components can decrease the occurrence of SPT, including a stepped-wedge design that reduced SPT from 3.3% to 3.0%. In Scandinavia, a preventive strategy called collegial assistance has been used to help prevent SPT. This strategy involves 2 midwiveswho assist thewoman in the second stage of labor, with the second midwife primarily focused on preventing SPT. The aim of this study was to compare the rate of SPT in pregnancies managed by collegial assistance versus a single midwife. This Oneplus study was a randomized, controlled, unmasked trial, conducted at 5 obstetric units in Sweden between December 10, 2018, and March 21, 2020. Included were adult women with uncomplicated singleton pregnancies at >37 weeks of gestation, who were carrying their first child or having their first vaginal birth after cesarean delivery. Excluded were women who had multiple pregnancies, had intrauterine fetal demise, were undergoing a planned cesarean section, or were at <37 weeks' gestation.Women were randomly assigned to either the intervention group with 2 midwives in attendance during active second stage labor or standard care with 1 midwife. All midwives were asked to document the preventive methods used in case report forms. A total of 3750 women were included in the final analysis-with 1879 women receiving collegial assistance and 1871 women receiving standard care. Of the women who gave birth spontaneously, 1546 were in the intervention group and 1513 in the standard care group. Severe perinatal trauma occurred less frequently in the intervention group than the standard care group (3.9% vs 5.7%; odds ratio, 0.68; 95% confidence interval, 0.49-0.97; P = 0.025). In the intervention group, 0.2% had fourth-degree tears compared with 0.5% in the standard care group. The median time for collegial assistance was 15 minutes (interquartile range, 10-20 minutes). The use of perineal warm compresses was similar in the intervention group and standard care group (86.4% vs 85.7%, respectively). No differences were observed in birth positions, manual perineal protection, neonatal outcomes, or secondary maternal outcomes. In conclusion, the attendance of a second midwife dedicated to preventing SPT during the second stage of labor significantly reduced the risk of injury

The effect of two midwives during the second stage of labour to reduce severe perineal trauma (Oneplus): a multicentre, randomised controlled trial in Sweden

BackgroundSevere perineal trauma (SPT) affecting the anal sphincter muscle complex is a serious complication following childbirth, associated with short-term and long-term maternal morbidity. Effective preventive strategies are still scarce. The aim of the Oneplus trial was to test the hypothesis that the presence of a second midwife during the second stage of labour, with the purpose of preventing SPT, would result in fewer injuries affecting the anal sphincter than if attended by one midwife.MethodsIn this multicentre, randomised, controlled parallel group, unmasked trial done at five obstetric units in Sweden, women were randomly assigned to be assisted by either one or two midwives in late second stage. Nulliparous women and women planning the first vaginal birth after caesarean section who were age 18–47 years were randomly assigned to an intervention when reaching the second stage of labour. Further inclusion criteria were gestational week 37+0, carrying a singleton live fetus in vertex presentation, and proficiency in either Swedish, English, Arabic, or Farsi. Exclusion criteria were a multiple pregnancy, intrauterine fetal demise, a planned caesarean section, or women who were less than 37 weeks pregnant. Randomisation to the intervention group of two midwives or standard care group of one midwife (1:1) was done using a computer-based program and treatment groups were allocated by use of sealed opaque envelopes. All women and midwives were aware of the group assignment, but the statistician from Clinical Studies Forum South, who did the analyses, was masked to group assignment. Midwives were instructed to implement existing prevention models and the second midwife was to assist on instruction of the primary midwife, when asked. Midwives were also instructed to complete case report forms detailing assistance techniques and perineal trauma prevention techniques. The primary outcome was the proportion of women who had SPT, for which odds ratios (ORs) and 95% CIs were calculated, and logistic regression was done to adjust for study site. All analyses were done according to intention to treat. The trial is registered with ClinicalTrials.gov, NCT0377096.FindingsBetween Dec 10, 2018, and March 21, 2020, 8866 women were assessed for eligibility, and 4264 met the inclusion criteria and agreed to participate. 3776 (88·5%) of 4264 women were randomly assigned to an intervention after reaching the second stage of labour. 1892 women were assigned to collegial assistance (two midwives) during the second stage of labour and 1884 women were assigned to standard care (one midwife). 13 women in each group did not meet the inclusion criteria and were excluded. After further exclusions, 1546 women spontaneously gave birth in the intervention group and 1513 in the standard care group. 1546 women in the intervention group and 1513 in the standard care group were included in the intention-to-treat analysis of the primary outcome. There was a significant reduction in SPT in the intervention group (3·9% [61 of 1546] vs 5·7% [86 of 1513]; adjusted OR 0·69 (0·49–0·97).InterpretationThe presence of two midwives during the active second stage can reduce SPT in women giving birth for the first time

Transmission of stimulus-locked responses in two coupled phase oscillators

A model of two n:m coupled phase oscillators is studied, where both oscillators are subject to random forces, but only one oscillator is repetitively stimulated with a pulsatile stimulus. The focus of the paper is on transmission of transient responses as well as transient synchronization and desynchronization, which are stimulus locked, i.e., tightly time locked to the stimulus. A bistability or multistability of stable synchronized states of the two-phase oscillators (modulo 2pi) occurs due to the n:m coupling. Accordingly, after stimulation the two oscillators may tend to qualitatively different stable states, which leads to a cross-trial (CT) response clustering (i.e., a switching between qualitatively different poststimulus responses across trials) of either one of the oscillators or both. A stochastic CT phase resetting analysis allows one to detect such transient responses and provides a reliable estimation of the transmission time. In contrast, CT averaging (averaging over an ensemble of responses), CT standard deviation, and CT cross correlation fail in studying the transmission of such stimulus-locked responses, even in the simpler case of 1:1 coupling. In particular, even though being used as golden standard for the analysis of evoked responses in medicine and neuroscience, CT averaging typically causes severe artifacts and misinterpretations