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Oxytocin is the principal drug and the primary choice for labor induction and postpartum hemorrhage prevention and treatment. The problems associated with oxytocin are not usually from its effectiveness, but they are from its compromised quality which may occur at the point of manufacturing, transportation, and storage. The main objective of this study was to assess the status of oxytocin injection quality and associated factors in the health facilities located in Addis Ababa city, Ethiopia. A laboratory based instrumental quality testing alongside a cross sectional study design was used to evaluate oxytocin injection quality in Addis Ababa city administration from January to June, 2022 according to United States Pharmacopeia (USP 20), and the World Health Organization guideline of post-market medicine quality assessment. Binary logistic regression and cross tabulation analysis were conducted using SPSS 26. Significance was considered at p ≤ 0.05. Out of 107 tested oxytocin injection samples, 92.5% met the limit for oxytocin content, 81.3% for sterility test, and 91.6% for pH value. Overall, quality failure rate was 23.4%, while sterility test failure rate was 18.7%. Lack of reliable refrigerated storage condition [(AOR = 5.62, 95% CI: (1.87, 16.88)], lack of effective cold chain system during distribution [(AOR = 5.5, 95% CI: (1.53, 19.74)], and weak national medicine regulatory system [(AOR = 3.23, 95% CI: (1.13, 9.23)] were among the significantly associated factors for the failure of some of the brands. The study demonstrated that oxytocin injection quality failure rate, failing to meet at least one quality test requirement, is demonstrated in the health facilities of Addis Ababa. The determinant factors for the reported failures are related to storage, distribution, and regulatory system. Hence, these should be addressed by strictly adhering in to the national regulation and providing a comprehensive health promotion on rational use of oxytocin injection should be implemented to assure its quality and safety. [ABSTRACT FROM AUTHOR]

Objectives: At our center, natural home‐like delivery settings have been established in or near conventional labor wards, for the care of pregnant women who prefer little or no medical intervention during labor and birth. We compared obstetrical and neonatal outcomes of women in active spontaneous labor, between those who chose to deliver in a natural‐delivery setup and those who chose a conventional setting. Methods: This retrospective study included low‐risk women who delivered at term between March 1, 2020 and December 31, 2022, in a single tertiary university affiliated medical center. Birth outcomes were compared between 124 women who delivered by natural birth (the study group) and 244 who gave birth in a conventional setting (the control group). Results: No cesarean deliveries were performed in the study group, compared to 18 (7.4%) of the control group, p = 0.004. Intrapartum fever, postpartum hemorrhage, and uterotonic administration were similar between the groups. For the study compared to the control group, breastfeeding was more common (71.3% vs. 12.3%, p < 0.001), analgesia administration within 48 h delivery was lower (4.1% vs. 10.7%, p = 0.033), and maternal and neonatal length of hospitalization were shorter. Of the women initially admitted to the natural‐delivery room, 14 (11.5%) were transferred to a conventional‐delivery room. Conclusions: Birth in a hospital natural‐delivery setting was associated with increased likelihood of vaginal birth, increased immediate breastfeeding and breastfeeding at discharge, and lower postpartum pain. [ABSTRACT FROM AUTHOR]

Introduction: GLP-1 receptor agonists are the number one drug prescribed for the treatment of obesity and type 2 diabetes. These drugs are not, however, without side effects, and in an effort to maximize therapeutic effect while minimizing adverse effects, gut hormone co-agonists received considerable attention as new drug targets in the fight against obesity. Numerous previous reports identified the neuropeptide oxytocin (OXT) as a promising anti-obesity drug. The aims of this study were to evaluate OXT as a possible co-agonist for GLP-1 and examine the effects of its co-administration on food intake (FI) and body weight (BW) in mice. Methods: FI and c-Fos levels were measured in the feeding centers of the brain in response to an intraperitoneal injection of saline, OXT, GLP-1, or OXT/GLP-1. The action potential frequency and cytosolic Ca2+ ([Ca2+]i) in response to OXT, GLP-1, or OXT/GLP-1 were measured in ex vivo paraventricular nucleus (PVN) neuronal cultures. Finally, FI and BW changes were compared in diet-induced obese mice treated with saline, OXT, GLP-1, or OXT/GLP-1 for 13 days. Results: Single injection of OXT/GLP-1 additively decreased FI and increased c-Fos expression specifically in the PVN and supraoptic nucleus. Seventy percent of GLP-1 receptor-positive neurons in the PVN also expressed OXT receptors, and OXT/GLP-1 co-administration dramatically increased firing and [Ca2+]i in the PVN OXT neurons. The chronic OXT/GLP-1 co-administration decreased BW without changing FI. Conclusion: Chronic OXT/GLP-1 co-administration decreases BW, possibly via the activation of PVN OXT neurons. OXT might be a promising candidate as an incretin co-agonist in obesity treatment. [ABSTRACT FROM AUTHOR]

Background: Optimizing care during labor protraction is a key strategy for reducing cesareans, especially among people with obesity. The pathophysiology of labor dystocia remains poorly understood, limiting precise interventions targeting the cause of protraction. Methods: In this secondary analysis of nulliparas (n = 92) with obesity (BMI ≥ 30 kg/m2) and spontaneous labor onset, we classified labor into four phenotypes based on duration of protraction and birth route: (1) no protraction, (2) short protraction and vaginal birth, (3) extended protraction meeting criteria for labor arrest, but with eventual progression and vaginal birth, and (4) extended protraction meeting criteria for labor arrest and cesarean birth. Across these phenotypes, we compared MVU, oxytocin dose, and novel measures of uterine responsiveness to oxytocin augmentation (MVU to oxytocin dose ratios). Results: In our sample, phenotype group 1 comprised 14.1% (n = 13); group 2 comprised 30.4% (n = 28); group 3 comprised 34.8% (n = 32); and group 4 comprised 20.7% (n = 19). Uterine responsiveness to oxytocin, but not MVU, decreased with each labor phenotype. Participants with cesarean birth had the lowest uterine responsiveness to oxytocin. Conclusion: Labor and birth outcomes were associated with measures of uterine responsiveness to oxytocin rather than MVU alone, and thus these may be more clinically appropriate measures for guiding clinical decision‐making. Current criteria for labor arrest are likely too stringent for nulliparas with obesity, many of whom appear to progress to safe vaginal birth after longer labor durations. Differences in uterine responsiveness to oxytocin augmentation across the groups suggests underlying physiologic differences in the labor phenotypes, which should drive future research targeting pathophysiology. [ABSTRACT FROM AUTHOR]

Severe post-partum hemorrhage (PPH) is a major cause of maternal mortality worldwide. Recombinant activated factor VII (rFVIIa) has recently been approved by the European Medicines Agency for the treatment of severe PPH if uterotonics fail to achieve hemostasis. Although large randomized controlled trials are lacking, accumulated evidence from smaller studies and international registries supports the efficacy of rFVIIa alongside extended standard treatment to control severe PPH. Because rFVIIa neither substitutes the activity of a missing coagulation factor nor bypasses a coagulation defect in this population, it is not immediately evident how it exerts its beneficial effect. Here, we discuss possible mechanistic explanations for the efficacy of rFVIIa and the published evidence in patients with severe PPH. Recombinant FVIIa may not primarily increase systemic thrombin generation, but may promote local thrombin generation through binding to activated platelets at the site of vascular wall injury. This explanation may also address safety concerns that have been raised over the administration of a procoagulant molecule in a background of increased thromboembolic risk due to both pregnancy-related hemostatic changes and the hemorrhagic state. However, the available safety data for this and other indications are reassuring and the rates of thromboembolic events do not appear to be increased in women with severe PPH treated with rFVIIa. We recommend that the administration of rFVIIa be considered before dilutional coagulopathy develops and used to support the current standard treatment in certain patients with severe PPH. [ABSTRACT FROM AUTHOR]

Background: Healthcare costs are a major burden on the society of developing countries like India. Countries like India try to limit healthcare costs in support of generic medicine. So, the Indian government initiated the Jan Aushadhi scheme in 2008 to provide high-quality generic medication at a low cost. Aim: The aim of the study was to compare the cost difference between Jan Aushadhi generic pharmaceutical formulations and branded medications in Tamil Nadu. Settings and Design: Pharmaco economic - Cost minimization observational study. Methods and Material: Study Duration: Five months, from February 2023 to June 2023. Study Place: 10 Jan Aushadhi outlets from various districts of Tamil Nadu. Sampling technique: Convenience sampling technique Statistical analysis used: Mean median, mode and Percentage. Results: A total of 729 medications were available in 10 Jan Aushadhi outlets. The Jan Aushadhi outlet has the most cardiovascular medications and the fewest antimalarial medications among different categories of drugs. Erythropoietin has the biggest cost difference between the average cost of branded medications and Jan Aushadhi drug costs, while Digoxin has the lowest cost difference. Antitubercular drugs, Oxytocics, Antileprosy drugs, Antiparkinsonism categories of drugs also delisted in Jan Aushadhi outlet. Conclusions: Compared to branded drugs, Jan Aushadhi's generic drugs are 64.65 % less costly on an average as observed in our study. The manufacturer of Jan Aushadhi shops is a WHO and GMO-certified company, and they manufacture branded drugs. So, there will be no quality compromise in Jan Aushadhi's generic drugs. [ABSTRACT FROM AUTHOR]

Introduction: Since the 1970s, fetal scalp blood sampling (FSBS) has been used as a second‐line test of the acid–base status of the fetus to evaluate fetal well‐being during labor. The commonly employed thresholds that delineate normal pH (>7.25), subnormal (7.20–7.25), and pathological pH (<7.20) guide clinical decisions. However, these experienced‐based thresholds, based on observations and common sense, have yet to be confirmed. The aim of the study was to investigate if pH drop rate accelerates at the common thresholds (7.25 and 7.20) and to explore the possibility of identifying more accurate thresholds. Material and methods: A retrospective study was conducted at a tertiary maternity hospital between June 2017 and July 2021. Patients with at least one FSBS during labor for category II fetal heart rate and delivery of a singleton cephalic infant were included. The rate of change in pH value between consecutive samples for each patient was calculated and plotted as a function of pH value. Linear regression models were used to model the evolution of the pH drop rate estimating slope and standard errors across predefined pH intervals. Exploration of alternative pH action thresholds was conducted. To explore the independence of the association between pH value and pH drop rate, multiple linear regression adjusted on age, body mass index, parity, oxytocin stimulation and suspected small for gestational age was performed. Results: We included 2047 patients with at least one FSBS (total FSBS 3467); with 2047 umbilical cord blood pH, and a total of 5514 pH samples. Median pH values were 7.29 1 h before delivery, 7.26 30 min before delivery. The pH drop was slow between 7.40 and 7.30, then became more pronounced, with median rates of 0.0005 units/min at 7.25 and 0.0013 units/min at 7.20. Out of the alternative pH thresholds, 7.26 and 7.20 demonstrated the best alignment with our dataset. Multiple linear regression revealed that only pH value was significantly associated to the rate of pH change. Conclusions: Our study confirms the validity and reliability of current guideline thresholds for fetal scalp pH in category II fetal heart rate. [ABSTRACT FROM AUTHOR]

Oxytocin is a reproductive hormone implicated in the process of parturition and widely used during labor. Oxytocin is produced within the supraoptic nucleus and paraventricular nucleus of the hypothalamus and released from the posterior pituitary lobe into the circulation. Oxytocin is released in pulses with increasing frequency and amplitude in the first and second stages of labor, with a few pulses released in the third stage of labor. During labor, the fetus exerts pressure on the cervix of the uterus, which activates a feedforward reflex—the Ferguson reflex—which releases oxytocin. When myometrial contractions activate sympathetic nerves, it decreases oxytocin release. When oxytocin binds to specific myometrial oxytocin receptors, it induces myometrial contractions. High levels of circulating estrogen at term make the receptors more sensitive. In addition, oxytocin stimulates prostaglandin synthesis and release in the decidua and chorioamniotic membranes by activating a specific type of oxytocin receptor. Prostaglandins contribute to cervical ripening and uterine contractility in labor. The oxytocin system in the brain has been implicated in decreasing maternal levels of fear, pain, and stress, and oxytocin release and function during labor are stimulated by a social support. Moreover, studies suggest, but have not yet proven, that labor may be associated with long-term, behavioral and physiological adaptations in the mother and infant, possibly involving epigenetic modulation of oxytocin production and release and the oxytocin receptor. In addition, infusions of synthetic oxytocin are used to induce and augment labor. Oxytocin may be administered according to different dose regimens at increasing rates from 1 to 3 mIU/min to a maximal rate of 36 mIU/min at 15- to 40-minute intervals. The total amount of synthetic oxytocin given during labor can be 5 to 10 IU, but lower and higher amounts of oxytocin may also be given. High-dose infusions of oxytocin may shorten the duration of labor by up to 2 hours compared with no infusion of oxytocin; however, it does not lower the frequency of cesarean delivery. When synthetic oxytocin is administered, the plasma concentration of oxytocin increases in a dose-dependent way: at infusion rates of 20 to 30 mIU/min, plasma oxytocin concentration increases approximately 2- to 3-fold above the basal level. Synthetic oxytocin administered at recommended dose levels is not likely to cross the placenta or maternal blood-brain barrier. Synthetic oxytocin should be administered with caution as high levels may induce tachystole and uterine overstimulation, with potentially negative consequences for the fetus and possibly the mother. Of note, 5 to 10 IU of synthetic oxytocin is often routinely given as an intravenous or intramuscular bolus administration after delivery to induce uterine contractility, which, in turn, induces uterine separation of the placenta and prevents postpartum hemorrhage. Furthermore, it promotes the expulsion of the placenta. [ABSTRACT FROM AUTHOR]

Investigation of the mechanism of neuronal communication underlies the fundamental discoveries that promote health. The studies of oxytocin signaling in neurons from or within different brain areas are directed to explore the role of this neurohormonal modulator in the regulation of synaptic transmission and plasticity, neuronal excitability that contributes to the reproduction, social behavior and learning capacity, anxiety, inflammation and differentiation in the brain. Oxytocin is synthesized in supraoptic and paraventricular nuclei of the hypothalamus and when secreted into the bloodstream from the posterior pituitary, it produces a significant effect on uterine contraction and lactation. At the same time this nonapeptide being released within the limbic system and brain cortex modulates neuronal activity by affecting ion channels on their membranes. The oxytocin receptor is primarily coupled to Gq/11 proteins causing phospholipase C activation, Ca2+ release and store-operated Ca2+ entry. These pathways are central for the regulation of the activity of different types of TRP channels, especially of the canonical subfamily (TRPC). Here we highlight the link between oxytocin signaling, which is particularly well investigated in the myometrium, and receptor-operated TRPC4 and multimodal TRPV4 ion channels that participate in oxytocin-dependent regulation of the uterine smooth muscle contractility under various conditions. Importantly, similarly to oxytocin, these channels have been implicated in neuropathic pain behavior, anxiety, fear and depression. Since similar signal transduction pathways are likely to be functional in neuronal cells, we propose that future studies of oxytocin effects in the CNS should also consider the role of these Ca2+-permeable channels. [ABSTRACT FROM AUTHOR]

Phloroglucinol is commonly used to alleviate dysmenorrhoea and stomach cramps. However, there is little evidence of phloroglucinol in the mechanism of primary dysmenorrhoea (PD) development. In this study, a PD rat model was established. The effects of phloroglucinol on the contraction of rat gastric circular muscle and uterine smooth muscle induced by oxytocin (OT) were investigated. The writhing response, and levels of oestradiol (E2), prostaglandin e2 (PGE2), and prostaglandin f2α (PGF2α) were determined. The protein and mRNA levels of OT receptor (OTR) were detected. OT showed a significant promoting effect on gastric circular muscle and uterine smooth muscle contraction. However, phloroglucinol strongly inhibited the contraction induced by 10−6 mol/L of OT. We also found that phloroglucinol reduced writhing response and attenuated uterine damage. Compared to the blank group, E2 and PGF2α were significantly increased, but PGE2 was significantly decreased in the PD model group. Phloroglucinol was found to reverse the changes of E2, PGF2α and PGE2. Moreover, phloroglucinol reduced the protein and mRNA levels of OTR. In conclusion, phloroglucinol could attenuate PD and inhibit the contraction of rat gastric circular muscle and uterine smooth muscle induced by OT. The mechanism might be related with the regulation of OTR expression. What is already known on this subject? Phloroglucinol is commonly used to alleviate dysmenorrhoea and stomach cramps. However, there is little evidence of phloroglucinol in the mechanism of primary dysmenorrhoea (PD) development. What do the results of this study add? Phloroglucinol could attenuate PD and inhibit the contraction of rat gastric circular muscle and uterine smooth muscle induced by OT. The underlying mechanisms of phloroglucinol for PD treatment may be associated with OTR. What are the implications of these findings for clinical practice and/or further research? These findings provide novel ideas for the role of phloroglucinol in PD development. [ABSTRACT FROM AUTHOR]

Background: Adverse effects can be produced by carbetocin and oxytocin during management of postpartum hemorrhage after caesarean section. Objective: The purpose of the present study was to compare the adverse effects among women with post-partum hemorrhage after caesarean section. Methodology: This randomized controlled trial was conducted in the Department of Obstetrics and Gynaecology at Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from July 2015 to December 2015 for a period of six months. Pregnant women diagnosed on the standard criteria admitted in BSMMU, Dhaka, Bangladesh were selected as study population by consecutive type of sampling. Randomization was performed according to computer generated simple random sampling method. An Uterotonic was an agent used to induce contraction or greater tonicity of the uterus. Then the patients were monitored per operatively and post operatively. All the information was recorded in data collection sheet. Main outcome variables were estimated blood loss. Results: A total number of 96 pregnant women were recruited for this study of which 48 cases were enrolled in group I and the rest of 48 case were enrolled in group II. The mean age with SD of the group I and group II were 24.4±4.7 years and 24.7±3.7 years. In blood transfusion of the study patients, 2(4.2%) patients need blood transfusion in group I and 5(10.4%) in group II (p>0.05). One (2.1%) patients had anaemia in group I and 5(10.4%) in group II. Forty-six (95.8%) patients had average menstrual flow in group I and 40(83.3%) in group II (p>0.05). Considering the side effect, 1(2.1%) patients had nausea in group I and 4(8.3%) in group II. Two (4.2%) patients had vomiting in group I and 5(10.4%) in group II. One (2.1%) patients had headache in group I and 4(8.3%) in group II. Four (8.3%) patients had infection rate in group I and 5(10.4%) in group II (p>0.05). Conclusion: In conclusion blood transfusion, anaemia, vomiting and infection rate are found less in group I than group II. [ABSTRACT FROM AUTHOR]

Background: In this meta-analysis, we aimed to update the clinical evidence regarding the efficacy and safety of TXA in the prevention of PPH. Methods: A literature search of PubMed, Scopus, Web of Science, Google Scholar, and Cochrane Library from inception until December 2022 was conducted. We included randomized controlled trials (RCTs) comparing TXA with a placebo among pregnant women. All relevant outcomes, such as total blood loss, the occurrence of nausea and/or vomiting, and changes in hemoglobin, were combined as odds ratios (OR) or mean differences (MD) in the meta-analysis models using STATA 17 MP. Results: We included 59 RCTs (18,649 patients) in this meta-analysis. For cesarean birth, TXA was favored over the placebo in reducing total blood loss (MD= -2.11 mL, 95%CI [-3.09 to -1.14], P < 0.001), and occurrence of nausea or/and vomiting (OR = 1.36, 95%CI [1.07 to 1.74], P = 0.01). For vaginal birth, the prophylactic use of TXA was associated with lower total blood loss, and higher occurrence of nausea and/or vomiting (MD= -0.89 mL, 95%CI [-1.47 to -0.31], OR = 2.36, 95%CI [1.32 to 4.21], P = 0.02), respectively. However, there were no differences between the groups in changes in hemoglobin during vaginal birth (MD = 0.20 g/dl, 95%CI [-0.07 to 0.48], P = 0.15). The overall risk of bias among the included studies varies from low to high risk of bias using ROB-II tool for RCTs. Conclusions: This meta-analysis suggested that TXA administration is effective among women undergoing cesarean birth or vaginal birth in lowering total blood loss and limiting the occurrence of PPH. Further clinical trials are recommended to test its efficacy on high-risk populations. [ABSTRACT FROM AUTHOR]

The article focuses on the mechanisms responsible for uterine contraction and relaxation, exploring topics such as the pathways involved, physiological changes during pregnancy and labor, and the pharmacology of drugs affecting the myometrium. It discusses how drugs like oxytocin, carbetocin, ergot alkaloids, prostaglandins, antiprogestins, and various tocolytics exert their effects on uterine contraction and relaxation.

Objective: Our study's primary objective was to examine the effects of four different prophylactic protocols on the prevention of postpartum hemorrhage following vaginal birth, including carbetocin only, oxytocin only, and a combination of carbetocin or oxytocin with tranexamic acid. Design: A multicentric randomized controlled trial. Participants/Materials, Setting, and Methods: This multicentric center prospective randomized controlled trial was conducted at the Department of Obstetrics and Gynecology of Bezmialem University and Van Health Teaching and Research Hospital from August 2022 to January 2023. The collected data included age, gravidity, parity, gestational age at birth, duration of delivery stages, prepartum hemoglobin and hematocrit concentrations, changes in hemoglobin and hematocrit concentrations, intrapartum blood loss, estimated blood loss after 2 h of vaginal delivery, Apgar scores at 1 and 5 min, birth weight, and neonatal intensive care unit (NICU) admission. Intrapartum blood loss was objectively measured in milliliters using a postpartum drape with a calibrated bag. The amount of bleeding was measured by subtracting the empty weight of the pads placed under the patient in the patient's bed within 2 h after delivery. Group I: carbetocin 100 μg/mL (n = 75), group II: oxytocin 5 IU/mL (n = 75), group III: carbetocin and tranexamic acid 50 mg/mL (n = 75), group IV: oxytocin and tranexamic acid (n = 75). Results: The hemoglobin concentration decrease significantly differed between groups (1.03 ± 1.04, 1.3 ± 0.85, 1.4 ± 0.85, 1.41 ± 0.87, respectively; p < 0.001). Group 4 has the highest decrease in hemoglobin and hematocrit concentrations. When we investigated the subgroup differences, the decrease in hemoglobin concentration was significantly higher in group 2 than group 1 (1.30 ± 0.85 vs. 1.03 ± 1.04; p = 0.023), in group 2 than group 3 (1.3 ± 0.85 vs. 1.04 ± 0.9; p = 0.013), and in group 4 than group 3 (1.41 ± 0.87 vs. 1.04 ± 0.9; p < 0.001). The decrease in hematocrit level was significantly different between groups (3.07 ± 3.23, 3.55 ± 2.44, 2.13 ± 3.09, 4.25 ± 2.52; p < 0.001, respectively). No significant differences were observed in terms of mean blood loss between the four groups (277.19 ± 208.10, 294.13 ± 198.64, 274.33 ± 199.57, and 283.97 ± 178.11; p = 0.445, respectively). Furthermore, there was no significant difference between the groups in the rate of need for blood transfusion (1.3%, 5.4%, 4%, and 4%, respectively; p = 0.6). Limitations: The most important limitation of the study is a relatively small number of participants. Conclusion: In conclusion, our findings suggest that carbetocin may be more successful than oxytocin and oxytocin plus tranexamic acid regimens in terms of postpartum hemoglobin reduction, and there is no difference in terms of the need for blood transfusion when it is used for postpartum hemorrhage prophylaxis after vaginal delivery. [ABSTRACT FROM AUTHOR]

Background: Peripartum haemorrhage (PPH) is a potentially life-threatening complication. Although still rare, the incidence of peripartal haemorrhage is rising in industrialised countries and refractory bleeding remains among the leading causes of death in the peripartal period. Summary: The interdisciplinary German, Austrian, and Swiss guideline on "Peripartum Haemorrhage: Diagnostics and Therapies" has reviewed the evidence for the diagnostics and medical, angiographic, haemostatic, and surgical treatment and published an update in September 2022. This article reviews the updated recommendations regarding the early diagnosis and haemostatic treatment of PPH. Keystones of the guideline recommendations are the early diagnosis of the bleeding by measuring blood loss using calibrated collector bags, the development of a multidisciplinary treatment algorithm adapted to the severity of bleeding, and the given infrastructural conditions of each obstetric unit, the early and escalating use of uterotonics, the therapeutic, instead of preventative, use of tranexamic acid, the early diagnostics of progressive deficiencies of coagulation factors or platelets to facilitate a tailored and guided haemostatic treatment with coagulation factors, platelets as well as packed red blood cells and fresh frozen plasma when a massive transfusion is required. Key Messages: Essential for the effective and safe treatment of PPH is the timely diagnosis. The diagnosis of PPH requires the measurement rather than estimation of blood loss. Successful treatment of PPH consists of a multidisciplinary approach involving surgical and haemostatic treatments to stop the bleeding. Haemostatic treatment of PPH starts early after diagnosis and combines tranexamic acid, an initially ratio-driven transfusion with RBC:plasma:PC = 4:4:1 (when using pooled or apheresis PC) and finally a goal-directed substitution with coagulation factor concentrates for proven deficiencies. Early monitoring of coagulation either by standard parameters or viscoelastic methods facilitates goal-directed haemostatic treatment. [ABSTRACT FROM AUTHOR]

Introduction: There are numerous pharmacologic treatments for opioid use disorder (OUD), but none that directly target the underlying addictive effects of opioids. Oxytocin, a peptide hormone produced in the paraventricular nucleus (PVN) of the hypothalamus, has been investigated as a potential therapeutic for OUD. Promising preclinical and clinical results have been reported, but the brain region(s) and mechanism(s) by which oxytocin impacts reward processes remain undetermined. Methods: Here, we assess peripherally administered oxytocin's impacts on cued reinstatement of heroin seeking following forced abstinence and its effects on neuronal activation in the PVN and key projection regions. We also examine how designer receptors exclusively activated by designer drug (DREADD)-mediated activation or inhibition of oxytocinergic PVN neurons alters cued heroin seeking and social interaction. Results: As predicted, peripheral oxytocin administration successfully decreased cued heroin seeking on days 1 and 30 of abstinence. Oxytocin administration also led to increased neuronal activity within the PVN and the central amygdala (CeA). Activation of oxytocinergic PVN neurons with an excitatory (Gq) DREADD did not impact cued reinstatement or social interaction. In contrast, suppression with an inhibitory (Gi) DREADD reduced heroin seeking on abstinence day 30 and decreased time spent interacting with a novel conspecific. Discussion: These findings reinforce oxytocin's therapeutic potential for OUD, the basis for which may be driven in part by increased PVN-CeA circuit activity. Our results also suggest that oxytocin has distinct signaling and/or other mechanisms of action to produce these effects, as inhibition, but not activation, of oxytocinergic PVN neurons did not recapitulate the suppression in heroin seeking. [ABSTRACT FROM AUTHOR]

Background The clinical debut of schizophrenia is frequently a first episode of psychosis (FEP). As such, there is considerable interest in identifying associations between biological markers and clinical or cognitive characteristics that help predict the progression and outcome of FEP patients. Previous studies showed that high prolactin, low oxytocin, and high homocysteine are factors associated with FEP 6 months after diagnosis, at which point plasma levels were correlated with some clinical and cognitive characteristics. Methods We reexamined 75 patients at 12 months after diagnosis to measure the evolution of these molecules and assess their association with clinical features. Results At follow-up, FEP patients had lower prolactin levels than at baseline, and patients treated with risperidone or paliperidone had higher prolactin levels than patients who received other antipsychotic agents. By contrast, no changes in oxytocin and homocysteine plasma levels were observed between the baseline and follow-up. In terms of clinical features, we found that plasma prolactin and homocysteine levels were correlated with the severity of the psychotic symptoms in male FEP patients, suggesting that they might be factors associated with psychotic symptomatology but only in men. Together with oxytocin, these molecules may also be related to sustained attention, verbal ability, and working memory cognitive domains in FEP patients. Conclusion This study suggests that focusing on prolactin, oxytocin, and homocysteine at a FEP may help select adequate pharmacological treatments and develop new tools to improve the outcome of these patients, where sex should also be borne in mind. [ABSTRACT FROM AUTHOR]

Background & Objective: To determine the safety and adequacy of intravenous (IV) carbetocin compared to IV tranexamic acid (TA) plus sublingual misoprostol in reducing hemorrhage during and following cesarean delivery (CD) in women with at least one risk factor for postpartum hemorrhage. Materials & Methods: This clinical study was randomized. We randomly assigned 400 term pregnant women who were candidates for elective CD to receive either a 100 μg intravenous infusion of carbetocin or 1gm. IV TA along with 400 μg of sublingual misoprostol after delivery. Comparing the quantity of blood loss at and six hours following a CD was the primary result. We also disclosed the necessity for any extra medications and any adverse drug reactions. Results: When compared to the misoprostol plus tranexamic acid group, the carbetocin group's total mean blood loss was considerably higher (829.7 293.3 mL vs. 609.33 211.5 mL; P = 0.0001). Following the administration of carbetocin and misoprostol with TA, respectively, 9.5% and 26.5% of patients required further uterotonics treatment (P = 0.0001). When compared to the carbetocin group, the misoprostol group's side effects, such as a bad taste in the mouth and fever, were much greater (P = 0.0001). Conclusion: When it comes to minimizing overall blood loss during and after CD, IV tranexamic acid combined with sublingual misoprostol is superior to IV carbetocin. [ABSTRACT FROM AUTHOR]

Oxytocin (OXT), a pro-social peptide, is increasingly recognized as a potential protective substance against drug addiction. In the context of ethanol, previous research has shown OXT's properties in reducing self-administration, alleviating motor impairment in rodents, and reducing craving in humans. However, its role in behavioral sensitization, a neuroadaptive response resulting from repeated drug exposure linked to an increased drug incentive, remains unexplored. OXT is recognized for its role in regulating the hypothalamic–pituitary–adrenal (HPA) axis, in which corticosterone is acknowledged as a significant factor in the development of behavioral sensitization. This study aimed to investigate the effects of carbetocin (CBT), an analogue of OXT, on the expression of behavioral sensitization to ethanol and the concurrent alterations in plasma corticosterone levels in male and female Swiss mice. We also aimed to confirm previous studies on OXT's impact on ethanol consumption in male mice, but with a focus on CBT, using the two-bottle choice model and the drinking in the dark (DID) methodology. For the sensitization study, the mice received either ethanol (1.8 g/kg, i.p.) or saline treatments daily for 15 consecutive days, followed by treatment with carbetocin (0.64 mg/kg, i.p.) or a vehicle for 6 days. Subsequently, on day 22, all the animals underwent an ethanol challenge to assess the expression of behavioral sensitization. The plasma corticosterone levels were measured on days 21 and 22. The CBT effectively prevented the expression of ethanol-induced behavioral sensitization in both male and female subjects, with no alterations having been detected in their corticosterone levels. In the ethanol consumption study, following an initial phase of ethanol acquisition, the male mice underwent a 6-day treatment with CBT i.p. or saline before being re-exposed to ethanol. We also found a reduction in their ethanol consumption due to the CBT treatment. In conclusion, carbetocin emerges as a promising and effective intervention for mitigating ethanol-induced behavioral sensitization and reducing ethanol intake, highlighting its potential significance in alcohol addiction treatment. [ABSTRACT FROM AUTHOR]

Objective: The complications associated with miscarriages have surfaced as a major concern in maintaining women's physical and mental health. The present study evaluated the efficacy of three medication regimes for the complete expulsion of retained intrauterine tissues in patients who underwent a miscarriage. Methods: In this randomized clinical trial, 90 patients participated with their gestational age below 12 weeks, each having undergone a recent miscarriage. After being screened for underlying diseases and coagulative blood disorders, they were randomly allocated into three groups. For the first group, labeled as the control group, misoprostol was administered alone. In contrast, the combination of misoprostol plus methylergometrine and misoprostol plus oxytocin was prescribed for the second and third groups, respectively. Further, the data obtained were analyzed by descriptive and inferential statistics using Stata software version 14. Results: The mean age of participants and gestational age were 29.76 ± 5.53 years and 8.23 ± 2.29 weeks, respectively. There was no significant difference between the three treatment groups regarding the amount of bleeding after the abortion(P = 0.627). Regarding pain severity, the group that received Misoprostol plus Methylergometrine had less pain intensity than the other two groups(p = 0.004). The mean rate of RPOC expulsion was in the Misoprostol plus Oxytocin (9.68 ± 10.36) group, Misoprostol plus Methylergometrine (11.73 ± 12.86), and Misoprostol groups (19.07 ± 14.31)(p = 0.013). The success rate in outpatient medical abortion in the misoprostol plus oxytocin and misoprostol plus methylergonovine group was 93.33%, but in patients treated by misoprostol alone was 83.33%. Conclusion: The effectiveness of the drugs in the two drug groups combined with oxytocin and methylergometrine is higher than the misoprostol group alone. An outpatient approach was deemed more satisfactory against surgical maneuvers and hospitalizations by patients since family support influenced their pain coping mechanism. Trial registration: The trial was registered in the Iranian registry of clinical trials on 04/10/2019. (https://fa.irct.ir/trial/34519; registration number: IRCT20150407021653N19). [ABSTRACT FROM AUTHOR]

Background: Africa is a developing continent with a high maternal mortality rate. It is beneficial to implement interventions that alleviate the problem. As a result, this systematic review and meta-analysis was carried out to summarize evidence that will assist concerned bodies in proposing strategies to reduce maternal mortality due to post-partum hemorrhage. Methods: This systematic review and meta-analysis includes randomized control trials (RCT) studies searched from various databases (PubMed, Web of Sciences, SCOPUS, African Journal Online, Clinical trials, and African indexes Medics). Data synthesis and statistical analysis were conducted using a combination of review manager 5.3 and STATA Version 14 software. The effect measure utilized was the standardized mean difference for estimated mean blood loss and mean hemoglobin level. Results: This systematic review and meta-analysis includes a total of 3308 women. The pooled standardized mean difference showed that tranexamic acid statistical significantly reduced the estimated amount of blood loss after vaginal delivery (standardized mean difference with 95% CI − 0.93 [− 1.45, − 0.41]) and during and after cesarean delivery (standardized mean difference with 95% CI − 1.93 [− 2.40, − 1.47]). Conclusion: Tranexamic acid has been found to be a good choice for reducing blood loss during and after delivery in Africa regardless of the mode of delivery. Tranexamic acid had no effect on hemoglobin levels before and after delivery. To reduce maternal mortality due to post-partum hemorrhage, it is critical to implement and strengthen interventions aimed at increasing tranexamic acid uptake in Africa. [ABSTRACT FROM AUTHOR]

Backgrounds: Outpatient induction of labor (IOL) is an alternative choice offered to pregnant women requiring cervical ripening. Outpatient IOL can provide solutions in terms of women empowerment, but most importantly promotes as normal labor as possible, within the medical context of the IOL. The objectives of this systematic review were to assess safety and effectiveness of cervical ripening performed with a slow‐release dinoprostone vaginal insert in term pregnancies in two settings: the outpatient (home) versus the inpatient (hospital). Methods: The electronic databases Cinahl, Embase, Medline and Maternity and Infant Care were searched to detect studies that met the inclusion criteria. Both reviewers collected the data and assessed the quality of the studies and assessed the pooled odds ratio using a 95% confidence interval and a random‐effects model. Primary outcomes were linked to maternal and neonatal morbidity. Secondary outcomes were related to birth outcomes. Results: No statistical difference was seen between the outpatient and inpatient setting in terms of maternal complications, neonatal morbidity, cesarean section, and labor onset <24 h. Women in the outpatient setting were significantly less likely to experience uterine hyperstimulation, and they were also significantly more likely to require oxytocin to augment or induce their labor than the women in the inpatient setting. Women in the outpatient setting were more satisfied with the cervical ripening experience. Conclusions: Cervical ripening with a slow‐release dinoprostone vaginal insert in term pregnancies in the outpatient setting appears as safe as the inpatient setting in terms of maternal, neonatal, and birth outcomes. [ABSTRACT FROM AUTHOR]

Background: In clinical obstetrics, many guidelines recommended the use of Doppler fetal ductus venosus blood flow to monitor and to manage fetal growth restriction (FGR). The ductus venosus and the pulmonary venous flow pattern of fetuses are similar. Umbilical artery pH (UA pH) is essential in identifying adverse pregnancy outcomes, particularly in fetal growth restriction cases. Nevertheless, the literature indicates that the relationship between pulmonary vein pulsatility index (PVPI) and UA pH in FGR cases has not been well investigated. This study aimed to identify the alteration in PVPI in FGR cases and evaluate the correlation between PVPI and UA pH in FGR newborns. Methods: This matched cohort study of singleton pregnancies from 28+ 0 to 40+ 0 weeks of gestation without congenital abnormalities included 135 cases of FGR (disease group) and 135 cases of normal growth (control group). The PVPI was measured at the proximal segment of the right or left pulmonary vein, approximately 5 mm from the left atrium wall. The umbilical artery pulsatility index (UAPI) was measured on the free umbilical cord. An elective cesarean section or labor induction are both options for ending the pregnancy, depending on the condition of the mother or fetus. Umbilical artery blood samples were collected within 5 min of delivery for UA pH measurement. SPSS version 20 and Medcalc version 20.1 were used for data analysis. Results: FGR cases had a significantly higher mean fetal PVPI than the control group (1.16 ± 0.26 vs. 0.84 ± 0.16; p < 0.01), and PVPI and UAPI were positively correlated (r = 0.63; p < 0.001). PVPI and UA pH were negatively correlated in FGR patients, with r = -0.68; p < 0.001. The PVPI value on the 95th percentile had a prognostic value of UA pH < 7.20 with a sensitivity of 88.2%, specificity of 66.3%, positive predictive value of 46.9%, and negative predictive value of 94.3%. Conclusions: There was a statistically significant difference in PVPI values in FGR cases compared to the normal growth group, a positive correlation between PVPI and UAPI, and a negative correlation between PVPI and UA pH. PVPI might have a prognostic meaning in predicting UA pH at birth. [ABSTRACT FROM AUTHOR]

Objective: This study compares the effectiveness of administering sublingual misoprostol combined with oxytocin to that of IV tranexamic acid combined with oxytocin to reduce intra and post-operative blood loss in high-risk women for postpartum haemorrhage (PPH) following cesarean section (CS). Methods: About 315 high-risk pregnant women undergoing CS participated in this trial. They were randomly assigned into three groups; tranexamic group, misoprostol group, and control group, according to the medication given in the operative theatre. All patients received oxytocin intraoperatively. They were assessed regarding intraoperative blood loss, the incidence of PPH, and the reduction in haemoglobin and hematocrit values. Results: Both tranexamic and misoprostol groups had similar results in reducing intra and post-operative blood loss. However, the reduction in haemoglobin and hematocrit were significantly lower in tranexamic and misoprostol groups compared to the control group (-0.78 ± 0.57 vs. -0.83 ± 0.52 vs. -1.32 ± 0.57 gm/dl, P < 0.001 and − 3.05 ± 1.28 vs. -3.06 ± 1.13 vs. -4.94 ± 1.82%, P < 0.001 respectively). In addition, the estimated blood loss was significantly lower in the tranexamic and misoprostol groups compared to the control group (641.6 ± 271.9 vs. 617.9 ± 207.4 vs. 1002.4 ± 340.7 ml, P < 0.001). Conclusion: Both tranexamic acid and misoprostol are equally capable of reducing blood loss, but the results were significantly better compared to using oxytocin alone in high-risk patients. Clinical Trial Registration: Registered at www.clinicaltrials.govon07/10/2019 with registration number NCT04117243. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness of tranexamic acid (TXA) in reducing blood loss during elective caesarean sections in women with and without risk factors for postpartum haemorrhage (PPH). Design: A double‐blind, randomised placebo‐controlled trial. Setting: An academic tertiary referral centre in Singapore. Population: Multiethnic women aged 21 years or older undergoing elective caesarean section. Methods: Randomisation to intravenous TXA or normal saline (placebo) 10 minutes before skin incision. Main outcome measures: Calculated estimated blood loss (cEBL), derived from blood volume and haematocrit levels. Results: Between June 2020 and October 2021, 200 women were randomised to the placebo or TXA groups. Women who received prophylactic TXA had a significantly lower mean cEBL compared with those receiving placebo (adjusted mean difference −126.4 mL, 95% CI −243.7 to −9.1, p = 0.035). The effect was greatest in those at high risk for PPH, with a reduction in cEBL (mean difference −279.6 mL, 95% CI −454.8 to −104.3, p = 0.002) and a lower risk of cEBL ≥500 mL (risk ratio [RR] 0.54, 95% CI 0.36–0.83, p = 0.007) and cEBL ≥1000 mL (RR 0.44, 95% CI 0.20–0.98, p = 0.016). Subgroup analysis showed benefit for women with preoperative haemoglobin <10.5 g/dL (mean difference −281.9 mL, 95% CI −515.0 to −48.8, p = 0.019). There was no significant difference in need for additional medical or surgical interventions. There were no maternal or neonatal adverse outcomes. Conclusion: Prophylactic TXA should be considered in women with risk factors for PPH, and those most likely to benefit are those with preoperative haemoglobin <10.5 g/dL. [ABSTRACT FROM AUTHOR]

BACKGROUND: Delays in the detection or treatment of postpartum hemorrhage can result in complications or death. A blood-collection drape can help provide objective, accurate, and early diagnosis of postpartum hemorrhage, and delayed or inconsistent use of effective interventions may be able to be addressed by a treatment bundle. METHODS: We conducted an international, cluster-randomized trial to assess a multicomponent clinical intervention for postpartum hemorrhage in patients having vaginal delivery. The intervention included a calibrated blood-collection drape for early detection of postpartum hemorrhage and a bundle of first-response treatments (uterine massage, oxytocic drugs, tranexamic acid, intravenous fluids, examination, and escalation), supported by an implementation strategy (intervention group). Hospitals in the control group provided usual care. The primary outcome was a composite of severe postpartum hemorrhage (blood loss, >1000 ml), laparotomy for bleeding, or maternal death from bleeding. Key secondary implementation outcomes were the detection of postpartum hemorrhage and adherence to the treatment bundle. RESULTS: A total of 80 secondary-level hospitals across Kenya, Nigeria, South Africa, and Tanzania, in which 210,132 patients underwent vaginal delivery, were randomly assigned to the intervention group or the usual-care group. Among hospitals and patients with data, a primary-outcome event occurred in 1.6°/o of the patients in the intervention group, as compared with 4.3°/o of those in the usual-care group (risk ratio, 0.40; 95% confidence interval [CI], 0.32 to 0.50; P<0.001). Postpartum hemorrhage was detected in 93.1% of the patients in the intervention group and in 51.1% of those in the usual-care group (rate ratio, 1.58; 95% CI, 1.41 to 1.76), and the treatment bundle was used in 91.2% and 19.4%, respectively (rate ratio, 4.94; 95% CI, 3.88 to 6.28). CONCLUSIONS: Early detection of postpartum hemorrhage and use of bundled treatment led to a lower risk of the primary outcome, a composite of severe postpartum hemorrhage, laparotomy for bleeding, or death from bleeding, than usual care among patients having vaginal delivery. (Funded by the Bill and Melinda Gates Foundation; E-MOTIVE ClinicalTrials.gov number, NCT04341662.). [ABSTRACT FROM AUTHOR]

Objective: To find the efficacy of prophylactic tranexamic acid and Oxytocin in preventing postpartum hemorrhage during cesarean section as compared to uterotonic alone. Materials and Methods: A randomized clinical trial that was single-center, double-blind placebo-controlled was conducted in the Department of Obstetrics and Gynaecology, Khyber Teaching Hospital, between 1st July 2021 to 31st December 2021. A total of 280 patients undergoing cesarean section were randomized to group A receiving tranexamic acid and uterotonic (oxytocin) and control group B having placebo and uterotonic(oxytocin) within three minutes of delivery of the baby. Blood loss after the cesarean section was calculated from blood volume and pre and post-operative hematocrit. The main outcome of the study was to establish the efficacy of tranexamic acid in decreasing the number of women with calculated estimated blood loss> 1000 ml. Secondary outcomes included differences in mean calculated blood loss, peripartum change in hematocrit, and postoperative blood transfusion in both groups. Data was analyzed by statistical package for social sciences(SPSS) version 23.0. Mean and standard deviation were calculated for numerical data and percentages, and frequencies for categorical variables. To see the effects of modifiers, post stratified t-test was used. P-value <0.05 was considered statistically significant. Results: Both the groups were comparable for maternal age (28.4±4.5, 28.8±4.9) gestational age (37.71±1.61, 37.70±1.56), and parity (1.79±1.5, 2±1.6). Tranexamic acid significantly reduced the number of women with estimated calculated blood loss of > 1000 ml in group A to 10%(n=14) as compared to 18.6%(n=26) in group B (p-value<0.005). Secondary outcomes like mean calculated blood loss and postoperative blood transfusion were statistically insignificant between the two groups. Conclusion: Pregnant women who received prophylactic uterotonic agents and tranexamic acid treatment within three minutes of cesarean delivery, resulted in a lesser number of women with calculated estimated blood loss > 1000 ml than placebo. [ABSTRACT FROM AUTHOR]

Patients and methods: This was a prospective double-blinded multi-center randomized controlled trial conducted from April 2022 till September 2022 involving one hundred eighty women categorized into three categories, each involving 60 females who received either tranexamic acid, etamsylate or placebo just after birth of the baby. Results: Loss of blood in tranexamic acid was the same as the blood loss in etamsylate and both wer e lower than the placebo group. The difference in hemoglobin after delivery in tranexamic acid individuals was the same as etamsylate group and both of them were lower than placebo group. The occurrence of postpartum hemorrhage and blood transfusion in tranexamic acid category and etamsylate category were significantly less than placebo. Conclusions: Etamsylate is an efficiently alternative agent for tranexamic acid in decreasing blood loss with lower side effects, therefore, it can be used instead of tranexamic acid in women with contraindications or anticipated to be have higher risk to develop tranexamic acid side effects. [ABSTRACT FROM AUTHOR]

Maternal separation is a widely used animal model to study early life adversity in offspring. However, only a few studies have focused on the impact of disrupting the maternal bond from the mother's perspective. Such studies reveal alterations in behavior, whereas the underlying neuroendocrine mechanisms remain largely unknown. In this study, we compared the consequences of daily brief maternal separation (BMS; 15 min) versus long maternal separation (LMS; 180 min) during the first week postpartum with respect to behavioral and neuroendocrine changes in lactating Sprague–Dawley dams. Mothers were tested for their maternal care before and after separation, maternal motivation to retrieve pups, as well as anxiety‐related and stress‐coping behaviors. In addition, we analyzed their basal plasma corticosterone levels and oxytocin receptor binding in selected brain regions of the limbic system and maternal network. LMS dams showed higher levels of behavioral alterations compared to BMS and non‐maternally separated (NMS) dams, including increased licking and grooming of the pups and decreased maternal motivation. Anxiety‐related behavior was not affected by either separation paradigm, whereas passive stress‐coping behavior tended to increase in the LMS group. Plasma corticosterone concentrations were not different between groups. Oxytocin receptor binding was higher in the medial preoptic area and tended to be higher in the prelimbic cortex of LMS dams, only. Our results demonstrate that especially daily prolonged maternal separation impacts on the mothers' behavior and oxytocin system, which suggests that enhanced oxytocin receptor binding could be a compensatory mechanism for potentially decreased central oxytocin release due to limited pup contact. [ABSTRACT FROM AUTHOR]

We explored a possible role of oxytocin (OXT) for the onset and maintenance of rabbit maternal behavior by: (a) confirming that a selective oxytocin receptor antagonist (OTA) widely used in rodents selectively binds to OXT receptors (OXTR) in the rabbit brain and (b) determining the effect of daily intracerebroventricular (icv) injections of OTA to primiparous and multiparous does from gestation day 29 to lactation day 3. OTA efficiently displaced the high affinity, selective oxytocin receptor (OXTR) radioligand, 125I‐labeled ornithine vasotocin analog (125I‐OVTA), but was much less effective at displacing the selective V1a vasopressin receptor radioligand, 125I‐labeled linear vasopressin, thus showing high affinity and selectivity of OTA for rabbit OXTR as in rodents. Further, ICV OTA injections did not modify nest‐building, latency to enter the nest box, time spent nursing or the amount of milk produced, relative to vehicle‐injected does. The percentage of mothers suckling the litter was also similar between both groups, regardless of parity. Together, our results do not support a role of OXT for the initiation or maintenance of rabbit maternal behavior. Future studies are warranted to determine if OXT participates in fine‐tuning additional aspects of the maternal ethogram, for example, circadian periodicity of nursing and nest defense. [ABSTRACT FROM AUTHOR]

Objective: To investigate the compatibility of oxytocin and tranexamic acid injection products when mixed for the purpose of co‐administration by intravenous infusion. Design: Compatibility testing. Setting: Hospitals taking part in a multicentre postpartum haemorrhage treatment (E‐MOTIVE) trial in Kenya, Nigeria, Tanzania and South Africa. Sample: Oxytocin and tranexamic acid products. Methods: The compatibility of two sentinel products of oxytocin injection and tranexamic acid injection in 200‐mL infusion bags of both 0.9% w/v saline and Ringer's lactate solution was assessed. We analysed all tranexamic acid–oxytocin combinations, and each evaluation was conducted for up to 3 h. Subsequently, the compatibility of multiple tranexamic acid products with reference oxytocin products when mixed in 0.9% w/v saline over a period of 1 h was investigated. Main outcome measures: Concentration of oxytocin over time after mixing with tranexamic acid products. Results: We found significant interaction between certain oxytocin and tranexamic acid products after mixing them in vitro and observing for 1 h. The interaction substantially impacted oxytocin content leading to reduction in concentration (14.8%–29.0%) immediately on mixing (t = 0 min). In some combinations, the concentration continued to decline throughout the stability assessment period. Oxytocin loss was observed in 7 out of 22 (32%) of combinations tested. Conclusions: In a clinical setting, mixing certain oxytocin and tranexamic acid products before administration may result in an underdosing of oxytocin, compromising care in an emergency life‐threatening situation. The mixing of oxytocin and tranexamic acid injection products for co‐administration with intravenous infusion fluids should be avoided until the exact nature of the observed interaction and its implications are understood. [ABSTRACT FROM AUTHOR]

Oxytocin (OXT) plays a significant role during pregnancy, especially toward the end of pregnancy. Some studies have reported that OXT is involved in the stimulation of steroidogenesis in several organs. However, the effects of OXT on placental steroidogenesis have not yet been established. In this study, we investigated the regulation of steroid hormones and steroidogenic enzymes by OXT-associated signaling in vitro and in vivo. OXT increased the gene expression of steroidogenic enzymes, which convert pregnenolone to progesterone and dehydroepiandrosterone (DHEA) in vitro. In OXT-administered pregnant rats, pregnenolone and DHEA levels were significantly enhanced in the plasma and the expression of the enzymes synthesizing DHEA, testosterone, and estradiol (E2) was increased in placental tissues. Furthermore, OXT was found to affect placental cell differentiation, which is closely related to steroid hormone synthesis. After treatment of the pregnant rats with atosiban, an antagonist of the OXT receptor, the concentration of E2 in the plasma and the expression of E2-synthesizing enzyme were reduced. This regulation may be due to OXT-mediated differentiation, because OXT increases the expression of corticotropin-releasing hormone, which is a biomarker of placental cell differentiation. Our findings suggest that OXT contributes to maintaining pregnancy by regulating the differentiation of placental cells and steroidogenesis during pregnancy. [ABSTRACT FROM AUTHOR]

Electronic fetal monitoring, particularly in the form of cardiotocography, forms the centerpiece of labor management. Initially successfully designed for stillbirth prevention, there was hope to also include prediction and prevention of fetal acidosis and its sequelae. With the routine use of electronic fetal monitoring, the cesarean delivery rate increased from <5% in the 1970s to >30% at present. Most at-risk cases produced healthy babies, resulting in part from considerable confusion as to the differences between diagnostic and screening tests. Electronic fetal monitoring is clearly a screening test. Multiple attempts have aimed at enhancing its ability to accurately distinguish babies at risk of in utero injury from those who are not and to do this in a timely manner so that appropriate intervention can be performed. Even key electronic fetal monitoring opinion leaders admit that this goal has yet to be achieved. Our group has developed a modified approach called the "Fetal Reserve Index" that contextualizes the findings of electronic fetal monitoring by formally including the presence of maternal, fetal, and obstetrical risk factors and increased uterine contraction frequencies and breaking up the tracing into 4 quantifiable components (heart rate, variability, decelerations, and accelerations). The result is a quantitative 8-point metric, with each variable being weighted equally in version 1.0. In multiple previously published refereed papers, we have shown that in head-to-head studies comparing the fetal reserve index with the American College of Obstetricians and Gynecologists' fetal heart rate categories, the fetal reserve index more accurately identifies babies born with cerebral palsy and could also reduce the rates of emergency cesarean delivery and vaginal operative deliveries. We found that the fetal reserve index scores and fetal pH and base excess actually begin to fall earlier in the first stage of labor than was commonly appreciated, and the fetal reserve index provides a good surrogate for pH and base excess values. Finally, the last fetal reserve index score before delivery combined with early analysis of neonatal heart rate and acid/base balance shows that the period of risk for neonatal neurologic impairment can continue for the first 30 minutes of life and requires much closer neonatal observation than is currently being done. [ABSTRACT FROM AUTHOR]

Growing evidence pointed out that guanine-based purines are able to modulate smooth muscle contractile activity of blood vessels and gastrointestinal tract. Since, so far, possible guanine-based purine modulation of uterine musculature is unknown, the aim of the present study was to investigate in vitro, using organ bath technique, guanosine and guanine effects on spontaneous uterine contraction, and uterine contraction induced by K+-depolarization and oxytocin in a non-pregnant rat. Guanosine, but not guanine, reduced the amplitude of spontaneous contraction of the uterine muscle in a dose-dependent manner. The inhibitory response was antagonized by S-(4-nitrobenzyl)-6-thioinosine (NBTI), a membrane nucleoside transporter inhibitor, but persisted in the presence of theophylline, a nonselective adenosine receptor antagonist, or propanolol, β1/β2 adrenoreceptor antagonist or blockers of a nitrergic pathway. In addition, potassium channel blockers did not influence guanosine-induced effects. Guanosine was able to inhibit the external calcium (Ca2+) influx-induced contraction, but it did not affect the contraction induced by high-KCl solution, indicating that guanosine does not interact with L-type voltage-gated calcium channel. Guanosine prevented/reduced uterine contractions induced by oxytocin, even in the absence of external calcium. In conclusion, guanosine is able to reduce both spontaneous and oxytocin-induced contractions of rat myometrium, likely subsequently to its intracellular intake. The blockade of extracellular Ca2+ influx and reduction of Ca2+ release from the intracellular store are the mechanisms involved in the guanosine-induced tocolytic effects. [ABSTRACT FROM AUTHOR]

Background: Few data are available on the intensity of pain that women experience during the first five days after vaginal childbirth. Moreover, it is unknown if the use of neuraxial labor analgesia has any impact on the level of postpartum pain. Methods: We performed a retrospective cohort study based on chart review of all women who delivered vaginally at an urban teaching hospital between April 2017 and April 2019. The primary outcome was the area under the curve of pain score on numeric rating scale (NRS) documented in electronic medical records for five days postpartum (NRS-AUC5days). Secondary outcomes included peak NRS score, doses of oral and intravenous analgesics consumed during the first five days postpartum, and relevant obstetric outcomes. Logistic regression was used to examine the associations between the use of neuraxial labor analgesia and pain-related outcomes adjusting for potential confounders. Results: During the study period, 778 women (38.6%) underwent vaginal delivery with neuraxial analgesia and 1240 women (61.4%) delivered without neuraxial analgesia. Median (Interquartile range) of NRS-AUC5days was 0.17 (0.12–0.24) among women who received neuraxial analgesia and 0.13 (0.08–0.19) among women who did not (p<0.001). Women who received neuraxial analgesia were more likely to require the first- and second-line analgesics postpartum than women who did not: diclofenac (87.9% vs. 73.0%, p< 0.001, respectively); acetaminophen (40.7% vs. 21.0%, p< 0.001, respectively). The use of neuraxial labor analgesia was independently associated with increased odds of having NRS-AUC5days in the highest 20 percentile (adjusted odds ratio [aOR] 2.03; 95% confidence interval [CI] 1.55–2.65), having peak NRS ≥ 4 (aOR 1.54; 95% CI 1.25–1.91) and developing hemorrhoids during the postpartum hospitalization (aOR 2.13; 95% CI 1.41–3.21) after adjusting for relevant confounders. Conclusion: Although women who used neuraxial labor analgesia had slightly higher pain scores and increased analgesic requirement during postpartum hospitalization, pain after vaginal childbirth was overall mild. The small elevation in the pain burden in neuraxial group does not seem to be clinically relevant and should not influence women's choice to receive labor analgesia. [ABSTRACT FROM AUTHOR]

Background: The incidence of gestational diabetes mellitus (GDM) is increasing worldwide. GDM patients have a significantly higher rate of cesarean section and postpartum hemorrhage, suggesting changes in uterine contractility. TWIK-1-related potassium channel (TREK1) expressed in the pregnant uterus and its role in uterine contraction. In this study, we examined the expression of HIF-1a and TREK1 proteins in GDM uterine and investigated whether high glucose levels are involved in the regulation of human uterine smooth muscle cells (HUSMCs) contraction through TREK1, and verified the role of HIF-1α in this process. Methods: Compared the uterine contractility between GDM and normal patients undergoing elective lower segment cesarean section. The HUSMCs were divided into normal glucose group, high glucose group, normal glucose with CoCl2 group, CoCl2 with echinomycin/L-Methionine group, and high glucose with echinomycin/LMethionine group; Compare the cell contractility of each group. Compared the expression of hypoxia-inducible factor-1α (HIF-1α) and TREK1 protein in each group. Results: The contractility of human uterine strips induced by both KCl and oxytocin was significantly lower in patients with GDM compared with that in normal individuals, with increased TREK1 and HIF-1α protein expression. The contractility of cultured HUSMCs was significantly decreased under high glucose levels, which was consistent with increased expression of HIF-1α and TREK1 proteins. The contractility of HUSMCs was decreased when hypoxia was induced by CoCl2 and increased when hypoxia was inhibited by echinomycin. The TREK1 inhibitor Lmethionine also recovered the decreased contractility of HUSMCs under high glucose levels or hypoxia. Discussion: The high glucose levels decreased the contractility of the myometrium, and increased expression of HIF-1α and TREK1 proteins play a role in changes in uterus contractility. [ABSTRACT FROM AUTHOR]

Problem: Premature birth is a common obstetric complication but its pathogenesis is unclear. Inflammation at the maternal‐fetal interface in preterm labor leads to the infiltration of neutrophils, which promotes inflammatory responses and induces the degradation of extracellular matrix and cell apoptosis, thus contributing to preterm labor. It is unclear whether neutrophil extracellular traps (NETs), a functional form of neutrophils, are involved in preterm labor. Methods of Study: After collecting amniotic membranes from research objects, we localized NETs by immunofluorescence and evaluated the expression of matrix metalloproteinase (MMP)‐9 and MMP‐2 by western blotting. Primary human amniotic epithelial cells (hAECs) subjected to treatment with NETs, 5‐ethynyl‐20‐deoxyuridine cell proliferation assay, lactate dehydrogenase (LDH) assay, western blotting, and flow cytometry apoptosis assay were used to determine the effects of NETs on hAECs. We also elucidated possible mechanisms underlying the effects. Results: Compared with normal term women, NETs infiltration and MMP‐9 expression in the amniotic membrane from preterm women had increased. Thereafter, NETs might suppress the proliferation and promote the apoptosis of hAECs. Furthermore, after NETs treatment, the mitochondrial membrane potential was significantly decreased, ERK1/2 phosphorylation expression was upregulated and reactive oxygen species (ROS) production was increased in hAECs. Changes in cell proliferation, LDH release, and cell apoptosis level due to NETs could be reversed by ROS inhibitor or ERK phosphorylation inhibitors. Conclusions: NETs can promote the apoptosis of hAECs via ERK1/2 pathways dependent on ROS release. [ABSTRACT FROM AUTHOR]

Background: Placenta previa is a common cause of postpartum hemorrhage (PPH) that contributes substantively to maternal morbidity and mortality rates. Tranexamic acid is an antifibrinolytic drug that is useful for the treatment of PPH. The recommendation from many guidelines is to start giving tranexamic acid as soon as PPH is diagnosed to reduce postpartum blood loss. Furthermore, some studies report the beneficial use of tranexamic acid given as a prophylactic before Cesarean section to decrease intraoperative blood loss and prevent PPH. To the authors' knowledge, in high-risk obstetrics case such as placenta previa, there was insufficient data to support recommendations of the use of tranexamic acid for prevent PPH. Objective: To evaluate the efficacy of supplementary intravenous tranexamic acid before cesarean section versus prophylactic intravenous oxytocin after placenta delivery alone to decrease intraoperative blood loss and prevent PPH in placenta previa. Material and Methods: The present study conducted a double blinded placebo control trial comparing adjunct 1 g tranexamic acid given intravenously before skin incision with prophylactic intravenous oxytocin after placenta delivery alone before cesarean section for placenta previa. The study recruited 60 women who were diagnosed with placenta previa at gestational age (GA) of more than 28 completed weeks undergoing emergency cesarean section due to active bleeding or scheduled for elective cesarean section at 37 completed weeks at Chonburi Hospital between July 2021 and July 2022. The primary outcome was intraoperative blood loss. Results: Sixty diagnosed placenta previa women were recruited, with 30 patients per group. Group I patients were given 1 g tranexamic acid and Group II were given a placebo of 100 ml NSS before skin incision. Both groups received intravenous oxytocin 20 units after placenta delivery. The main outcome showed that preoperative tranexamic acid intravenous reduced intraoperative blood loss significantly compared with the placebo at 349.5 ml (range of 168 to 2,200) versus 619 ml (range of 288 to 3,243), p<0.001. The secondary outcome showed a significant decrease in the incidence of PPH at 4 (13.33%) versus 10 (33.33%), p=0.030 and decreased in the incidence of blood transfusion of more than one unit from 5 (16.67%) versus 13 (43.33%), p=0.047. Conclusion: Prophylactic supplementary 1 g tranexamic acid intravenously before cesarean section to prophylactic intravenous oxytocin after placental delivery was found to effectively reduce intraoperative blood loss and PPH. [ABSTRACT FROM AUTHOR]

Oxytocin is used in approximately half of all births in the United States during labor induction and/or augmentation. However, the effects of maternal oxytocin administration on offspring development have not been fully characterized. Here, we used the socially monogamous prairie vole to examine the hypothesis that oxytocin exposure at birth can have long-term developmental consequences. Maternally administered oxytocin increased methylation of the oxytocin receptor (Oxtr) in the fetal brain. As adults, oxytocin-exposed voles were more gregarious, with increased alloparental caregiving toward pups and increased close social contact with other adults. Cross-fostering indicated that these effects were the result of direct action on the offspring, rather than indirect effects via postnatal changes in maternal behavior. Male oxytocin-exposed offspring had increased oxytocin receptor density and expression in the brain as adults. These results show that long-term effects of perinatal oxytocin may be mediated by an epigenetic mechanism.

BACKGROUND: Mozambique has a high maternal mortality ratio, and postpartum hemorrhage (PPH) is a leading cause of maternal deaths. In 2015, the Mozambican Ministry of Health (MOH) commenced a program to distribute misoprostol at the community level in selected districts as a strategy to reduce PPH. This case study uses the ExpandNet/World Health Organization (WHO) scale-up framework to examine the planning, management, and outcomes of the early expansion phase of the scale-up of misoprostol for the prevention of PPH in 2 provinces in Mozambique. METHODS: Qualitative semistructured interviews were conducted between February and October 2017 in 5 participating districts in 2 provinces. Participants included program stakeholders, health staff, community health workers (CHWs), and traditional birth attendants (TBAs). Interviews were analyzed using the ExpandNet/WHO framework alongside national policy and planning documents and notes from a 2017 national Ministry of Health maternal, newborn, and child health workshop. Outcomes were estimated using misoprostol coverage and access in 2017 for both provinces. RESULTS: The study revealed a number of barriers and facilitators to scale-up. Facilitators included a supportive political and legal environment; a clear, credible, and relevant innovation; early expansion into some Ministry of Health systems and a strong network of CHWs and TBAs. Barriers included a reduction in reach due to a shift from universal distribution to application of eligibility criteria; fear of misdirecting misoprostol for abortion or labor induction; limited communication and understanding of the national PPH prevention strategy; inadequate monitoring and evaluation; challenges with logistics systems; and the inability to engage remote TBAs. Lower coverage was found in Inhambane province than Nampula province, possibly due to NGO support and political champions. CONCLUSION: This study identified the need for a formal review of the misoprostol program to identify adaptations and to develop a systematic scale-up strategy to guide national scale-up.

The investigation studied the enkephalinergic neuro fibers (En) contained in the Lower Uterine Segment (LUS) during the prolonged dystocic labor (PDL) with Labor Neuraxial Analgesia (LNA). PDL is generally caused by fetal head malpositions in the Occiput Posterior Position (OPP), Persistent Occiput Posterior Position (POPP), in a transverse position (OTP), and asynclitism (A), and it is detected by Intrapartum Ultrasonography (IU). The En were detected in the LUS samples picked up during cesarean section (CS) of 38 patients undergoing urgent CS in PDL, compared to 37 patients submitted to elective CS. Results were statistically evaluated to understand the differences in En morphological analysis by scanning electron microscopy (SEM) and by fluorescence microscopy (FM). The LUS samples analysis showed an important reduction in En in LUS of CS for the PDL group, in comparison with the elective CS group. The LUS overdistension, by fetal head malpositions (OPP, OTP, A) and malrotations, lead to dystocia, modification of vascularization, and En reduction. The En reduction in PDL suggests that drugs used during the LNA, usually local anesthetics and opioids, cannot control the "dystocic pain", that differs from normal labor pain. The IU administration in labor and the consequent diagnosis of dystocia suggest stopping the numerous and ineffective top-up drug administration during LNA, and to shift the labor to operative vaginal delivery or CS. [ABSTRACT FROM AUTHOR]

Background: Secondary postpartum haemorrhage (PPH) complicates ~1% of pregnancies and can cause serious maternal morbidity. However, evidence guiding optimal management is scarce and often based on case series and expert opinion. Aims: To measure the success of primary medical therapy in managing secondary PPH and to identify factors associated with need for surgical management. Materials and methods: Postpartum patients presenting to a tertiary women's hospital emergency department between July 2020 and October 2021 with secondary PPH were recruited. Data from the acute presentation were prospectively collected. Antenatal and intrapartum data were collected from medical record review. The primary outcome was the success of medical management for secondary PPH, defined by the implementation of medical or expectant measures without subsequent need for surgical intervention. Results: One‐hundred and twenty patients underwent primary medical management for secondary PPH. Ninety‐eight (82%) were managed successfully with medical management and 22 (18%) required surgery. Medical management involved misoprostol (n = 33; 27.5%), antibiotics (n = 108; 90%), and less commonly other uterotonics (n = 6; 5%). Factors associated with lower rates of successful medical management included: antecedent manual removal of placenta (MROP) (odds ratio (OR) 0.2, P = 0.047), primary PPH ≥500 mL (OR 0.39, P = 0.048) or ≥1 L (OR 0.24, P = 0.009), >200 mL blood loss at presentation (OR 0.17, P = 0.015), increasing time post‐delivery (OR 0.84, P = 0.044), retained products of conception (RPOC) on ultrasound (OR 0.024, P = 0.001) and vaginal birth (OR 0.27, P = 0.027). Conclusion: Medical management was highly successful. Vaginal birth, MROP, primary PPH, RPOC on ultrasound and increasing time post‐delivery were associated with increased need for surgical management. [ABSTRACT FROM AUTHOR]

The article discusses the uterotonics drugs that could induce uterine contraction like prostaglandins, ergot alkaloids, and oxytocin. Other topics include the use of said drugs in preventing and treating postpartum hemorrhage (PPH), the studies on the potential effects of oxytocin in elective cesarean procedures, as well as the effects of carbetocin and other uterotonic agents like ergometrine and methylergometrine.

The use of tranexamic acid for postpartum hemorrhage has entered obstetrical practice globally with the evidence‐based expectation of saving lives. This improvement in the care of women with postpartum hemorrhage has come at a price. For the anesthetist, having tranexamic acid ampoules close at hand would seem an obvious strategy to facilitate its use during cesarean delivery, an important setting for severe hemorrhage. Tragically, we have identified a number of recent instances of inadvertent intrathecal administration of tranexamic acid instead of local anesthetic for spinal anesthesia. Reported cases of this catastrophic error seem to be increasing. The profound neurotoxicity of tranexamic acid causes rapid‐onset convulsions, with mortality of 50%. How can these tragic errors be averted? Drug safety alerts have been issued by the US Food and Drug Administration and the World Health Organization, but that is not enough. We recommend extensive dissemination of information to raise awareness of this potential hazard, and local hospital protocols to ensure that tranexamic acid is stored separately from anesthetic drugs, preferably outside the operating room and with an auxiliary warning label. Implementation of safety strategies on a very large scale will be needed to ensure that the life‐saving potential of tranexamic acid is not eclipsed by drug‐error mortality. [ABSTRACT FROM AUTHOR]

Purpose: The global rise in frequency of cesarean delivery raises the concern to minimize the post-operative complications, in order to improve the maternal and neonatal health. Closure of subcutaneous tissue following cesarean section closes dead space, hence reduces the wound complications. No previous study has compared the clinical equivalence of polyglycolic acid suture with polyglactin 910 suture for subcutaneous tissue closure following cesarean section. Therefore, this study compared the incidence of subcutaneous abdominal wound disruptions within the first 6 weeks of subcutaneous tissue closure with either of the sutures. Patients and Methods: A single-blind, prospective, randomized study was conducted in two centres between February and November, 2021. Primiparous or multiparous women (18– 40 years) with a singleton pregnancy requiring cesarean section were randomized to polyglycolic acid suture (Truglyde®) (n=54) and polyglactin 910 suture (Vicryl®) (n=54) group. The primary endpoint, incidence of subcutaneous abdominal wound disruptions within 6 weeks of cesarean delivery was evaluated. In addition, the secondary endpoints, incidence of post-operative subcutaneous abdominal wound disruptions for the study period, skin disruption, surgical site infection (SSI), seroma, hematoma, intraoperative handling, operative time, hospital stay, suture removal, microbial deposits on sutures, pain, time taken to resume normal activities, and adverse events were recorded. Results: Non-significant difference in the incidence of subcutaneous abdominal wound disruptions, skin disruption, SSI, seroma, hematoma, intraoperative handling characteristics, operative time, pain, duration of hospital stay, suture removal, microbial deposits, time taken to return to day-to-day activities, and adverse events were observed between the two treatment groups. Conclusion: Following cesarean section, subcutaneous tissue closure using polyglycolic acid suture or polyglactin 910 suture was not associated with incidence of subcutaneous abdominal wound disruptions. Additionally, non-significant differences regarding secondary endpoints between the groups suggested the clinical equivalence of the sutures. CTRI Registration Number: CTRI/2020/12/029737; Registration date: 11/12/2020. [ABSTRACT FROM AUTHOR]

Purpose: Vitamin D deficiency is common during pregnancy and may cause complications such as preterm labor (PTL). This study was aimed to investigate the effect of the vitamin D-binding protein (VDBP) rs7041 genotype, which has a significant effect on vitamin D metabolism and PTL. Methods: This cross-sectional study was conducted with 32 pregnant women who had spontaneous PTL and 54 pregnant women who had no specific findings as a control group. Serum total vitamin D 25-hydroxy vitamin D (25(OH)D) levels were measured using the Elecsys Vitamin D Total Kit. VDBP was measured using a VDBP Quantikine ELISA Kit. The levels of bioavailable 25(OH)D were calculated based on the total 25(OH)D and VDBP concentrations. DNA was extracted using the DNeasy Blood and Tissue Kit. Single nucleotide polymorphisms (rs7041) in GC were analyzed using a TaqMan SNP Genotyping Assay Kit. The unpaired t-test, Chi-squared, and ANCOVA tests were performed. Firth’s penalized logistic regression was applied. The area under the curve (AUC) was calculated and the cutoff value was determined. All statistical analyses were performed using R version 4.0.3 (R Foundation for Statistical Computing, Vienna, Austria). Results: Total 25(OH)D levels were not significantly different between the two groups. Bioavailable 25(OH)D was significantly decreased in PTL women (p= .011), and VDBP was significantly increased in PTL women (p= .004) compared to the controls. Bioavailable 25(OH)D was lower in women with GT/TG and TT rs7041 genotypes than in those with GG, with statistical significance in women with the TT allele (p= .048). VDBP was higher in women with GT/TG and TT than those with GG, but there was no statistical significance. In PTL prevalence, bioavailable 25(OH)D and VDBP, the odds ratio increased by 1.463 times in GT/TG (p= .728) and increased by 1.675 times in TT compared to the GG allele (p= .640). In receiver operating characteristic (ROC) analysis for bioavailable 25(OH)D and VDBP, the AUC was 0.665 and 0685, respectively. The optimum cutoff of bioavailable 25(OH)D and VDBP levels for the diagnosis of PTL was calculated as 0.6 ng/mL and 523 µg/mL, respectively. Conclusions: Pregnant women with the VDBP rs7041(c.1296 T > G) T allele genotype had reduced serum levels of bioavailable 25(OH)D and were more likely to develop PTL. Therefore, if the T allele is found in the VDBP rs7041 SNP genotyping test before or during pregnancy, more careful prenatal care may be required because of the increased risk of PTL. [ABSTRACT FROM AUTHOR]

The use of tranexamic acid for postpartum hemorrhage has entered obstetrical practice globally with the evidence-based expectation of saving lives. This improvement in the care of women with postpartum hemorrhage has come at a price. For the anesthetist, having tranexamic acid ampoules close at hand would seem an obvious strategy to facilitate its use during cesarean delivery, an important setting for severe hemorrhage. Tragically, we have identified a number of recent instances of inadvertent intrathecal administration of tranexamic acid instead of local anesthetic for spinal anesthesia. Reported cases of this catastrophic error seem to be increasing. The profound neurotoxicity of tranexamic acid causes rapid-onset convulsions, with mortality of 50%. How can these tragic errors be averted? Drug safety alerts have been issued by the US Food and Drug Administration and the World Health Organization, but that is not enough. We recommend extensive dissemination of information to raise awareness of this potential hazard, and local hospital protocols to ensure that tranexamic acid is stored separately from anesthetic drugs, preferably outside the operating room and with an auxiliary warning label. Implementation of safety strategies on a very large scale will be needed to ensure that the life-saving potential of tranexamic acid is not eclipsed by drug-error mortality. [ABSTRACT FROM AUTHOR]

Receiving help can be a "mixed blessing." Despite the many psychosocial benefits it can carry, it sometimes has negative psychological consequences, such as loss in self-esteem or enhanced guilt. It is, therefore, important to understand the factors that modify responses to receiving help from others. We explored the role of the hormone oxytocin (OT) on affective and social responses to receiving help, given the putative role of OT in social bonding and attunement. To this end, we manipulated whether help was received from a same-sex interaction partner (confederate) versus a control condition, crossed with a double-blind administration of intranasal OT (vs. placebo), and examined subjective and observer-rated participant responses to help. We observed significant interactions between OT and the help manipulation. In the placebo condition, receiving help from the interaction partner compared with the control condition had negative consequences, such that participants reported greater negative affect and came to view themselves and their interaction partners more negatively after interacting together on several tasks. What is important, however, is that OT administration buffered against these negative subjective responses to receiving help. Further, outside observers rated participants who received OT administration as expressing greater happiness and gratitude in response to help, relative to those who received placebo. In sum, in the context of receiving help from a stranger, oxytocin administration fostered more positive affective and social responses. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Background: Induction of labour is one of the most common obstetric interventions globally. Balloon catheters and vaginal prostaglandins are widely used to ripen the cervix in labour induction. We aimed to compare the effectiveness and safety profiles of these two induction methods.Methods: We did an individual participant data meta-analysis comparing balloon catheters and vaginal prostaglandins for cervical ripening before labour induction. We systematically identified published and unpublished randomised controlled trials that completed data collection between March 19, 2019, and May 1, 2021, by searching the Cochrane Library, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and PubMed. Further trials done before March 19, 2019, were identified through a recent Cochrane review. Data relating to the combined use of the two methods were not included, only data from women with a viable, singleton pregnancy were analysed, and no exclusion was made based on parity or membrane status. We contacted authors of individuals trials and participant-level data were harmonised and recoded according to predefined definitions of variables. Risk of bias was assessed with the ROB2 tool. The primary outcomes were caesarean delivery, indication for caesarean delivery, a composite adverse perinatal outcome, and a composite adverse maternal outcome. We followed the intention-to-treat principle for the main analysis. The primary meta-analysis used two-stage random-effects models and the sensitivity analysis used one-stage mixed models. All models were adjusted for maternal age and parity. This meta-analysis is registered with PROSPERO (CRD42020179924).Findings: Individual participant data were available from 12 studies with a total of 5460 participants. Balloon catheters, compared with vaginal prostaglandins, did not lead to a significantly different rate of caesarean delivery (12 trials, 5414 women; crude incidence 27·0%; adjusted OR [aOR] 1·09, 95% CI 0·95-1·24; I2=0%), caesarean delivery for failure to progress (11 trials, 4601 women; aOR 1·20, 95% CI 0·91-1·58; I2=39%), or caesarean delivery for fetal distress (10 trials, 4441 women; aOR 0·86, 95% CI 0·71-1·04; I2=0%). The composite adverse perinatal outcome was lower in women who were allocated to balloon catheters than in those allocated to vaginal prostaglandins (ten trials, 4452 neonates, crude incidence 13·6%; aOR 0·80, 95% CI 0·70-0·92; I2=0%). There was no significant difference in the composite adverse maternal outcome (ten trials, 4326 women, crude incidence 22·7%; aOR 1·02, 95% CI 0·89-1·18; I2=0%).Interpretation: In induction of labour, balloon catheters and vaginal prostaglandins have comparable caesarean delivery rates and maternal safety profiles, but balloon catheters lead to fewer adverse perinatal events.Funding: Australian National Health and Medical Research Council and Monash Health Emerging Researcher Fellowship. [ABSTRACT FROM AUTHOR]

Background: In 2019, WHO prioritized updating recommendations relating to three labour induction topics: labour induction at or beyond term, mechanical methods for labour induction, and outpatient labour induction. As part of this process, we aimed to review the evidence addressing factors beyond clinical effectiveness (values, human rights and sociocultural acceptability, health equity, and economic and feasibility considerations) to inform WHO Guideline Development Group decision-making using the WHO-INTEGRATE evidence-to-decision framework, and to reflect on how methods for identifying, synthesizing and integrating this evidence could be improved.Methods: We adapted the framework to consider the key criteria and sub-criteria relevant to our intervention. We searched for qualitative and other evidence across a variety of sources and mapped the eligible evidence to country income setting and perspective. Eligibility assessment and quality appraisal of qualitative evidence syntheses was undertaken using a two-step process informed by the ENTREQ statement. We adopted an iterative approach to interpret the evidence and provided both summary and detailed findings to the decision-makers. We also undertook a review to reflect on opportunities to improve the process of applying the framework and identifying the evidence.Results: Using the WHO-INTEGRATE framework allowed us to explore health rights and equity in a systematic and transparent way. We identified a lack of qualitative and other evidence from low- and middle-income settings and in populations that are most impacted by structural inequities or traditionally excluded from research. Our process review highlighted opportunities for future improvement, including adopting more systematic evidence mapping methods and working with social science researchers to strengthen theoretical understanding, methods and interpretation of the evidence.Conclusions: Using the WHO-INTEGRATE evidence-to-decision framework to inform decision-making in a global guideline for induction of labour, we identified both challenges and opportunities relating to the lack of evidence in populations and settings of need and interest; the theoretical approach informing the development and application of WHO-INTEGRATE; and interpretation of the evidence. We hope these insights will be useful for primary researchers as well as the evidence synthesis and health decision-making communities, and ultimately contribute to a reduction in health inequities. [ABSTRACT FROM AUTHOR]