Alternative routes for tranexamic acid treatment in obstetric bleeding (WOMAN-PharmacoTXA trial): a randomised trial and pharmacological study in caesarean section births.

OBJECTIVE: To examine the safety, efficacy and pharmacology of intravenous (IV), intramuscular (IM) and oral tranexamic acid (TXA) use in pregnant women. DESIGN: Randomised, open-label trial. SETTING: Hospitals in Pakistan and Zambia. POPULATION: Women giving birth by caesarean section. METHODS: Women were randomised to receive 1 g IV, 1 g IM, 4 g oral TXA or no TXA. Adverse events in women and neonates were recorded. TXA concentration in whole blood was measured and the concentrations over time were examined with population pharmacokinetics. The relationship between drug exposure and D-dimer was explored. The trial registration is NCT04274335. MAIN OUTCOME MEASURES: Concentration of TXA in maternal blood. RESULTS: Of the 120 women included in the randomised safety study, there were no serious maternal or neonatal adverse events. TXA concentrations in 755 maternal blood and 87 cord blood samples were described by a two-compartment model with one effect compartment linked by rate transfer constants. Maximum maternal concentrations were 46.9, 21.6 and 18.1 mg/L for IV, IM and oral administration, respectively, and 9.5, 7.9 and 9.1 mg/L in the neonates. The TXA response was modelled as an inhibitory effect on the D-dimer production rate. The half-maximal inhibitory concentration (IC50 ) was 7.5 mg/L and was achieved after 2.6, 6.4 and 47 minutes with IV, IM and oral administration of TXA, respectively. CONCLUSIONS: Both IM and oral TXA are well tolerated. Oral TXA took about 1 hour to reach minimum therapeutic concentrations and would not be suitable for emergency treatment. Intramuscular TXA inhibits fibrinolysis within 10 minutes and may be a suitable alternative to IV

Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation

Propolis to curb lifestyle related disorders: an overview

The natural products are gaining immense importance in the domain of nutrition to prevent various maladies and improve the quality of life. Among these, natural exudates are of significant worth as these biochemical compounds are released by various living entities having pharmacological properties for utilization in various drug developments. These natural exudates are the promising source for the discovery of new medications. Numerous bioactive moieties collected by honeybees from exudates and buds of particular trees and plants, considered to be utilized as defensive barrier with special reference to propolis. It generally contains numerous biochemical components, i.e., polyphenols, steroids, terpenoids, and amino acids. They also contain isoferulic acid, sinapinic acid, caffeic acid, and chrysin responsible for antibacterial perspectives. With special attention to propolis, it has been utilized in folk medicines due to several of its therapeutic activities, i.e., antioxidant, antidiabetic, anti-inflammatory, antiviral, and anticancer properties. In this context, it is extensively used in foodstuffs and beverages to improve health related disorders like inflammation, diabetes, heart disease, protects injured gums, and cancer insurgence. Moreover, it has been used to curtail stomatology, gastroenterology, skin lesions, and otorhinolaryngologic and respiration diseases

Enhanced Bioaccessibility of Microencapsulated Puerarin Delivered by Pickering Emulsions Stabilized with OSA-Modified Hydrolyzed <i>Pueraria montana</i> Starch: In Vitro Release, Storage Stability, and Physicochemical Properties

Puerarin is a bioactive flavonoid isolated from Kudzu roots that possesses numerous health benefits. However, its poor bioavailability and existing complex delivery systems with safety issues are challenging tasks for its incorporation into functional foods. Preparing modified-starch-stabilized Pickering emulsions containing microencapsulated puerarin with improved bioaccessibility was the key objective of the present research work. Acid-hydrolyzed high-amylose Pueraria montana starch (PMS) was modified with octenyl succinic anhydride (OSA) and evaluated as an emulsifier to prepare emulsions. The FTIR, SEM, and XRD results showed that PMS was successfully modified. Furthermore, the emulsification index (EI), mean droplet size, and ζ-potential values showed that modified starch with a higher degree of substitution (DS) enhanced the storage stability of emulsions. Similarly, the retention degree and encapsulation efficiency results of puerarin proved the assumption after storage of 16 d. The Pickering emulsions also helped in the controlled release of microencapsulated puerarin in vitro. The study outcomes proved that Pickering emulsions stabilized with OSA-modified PMS have promising applicability in functional foods as efficient food-grade delivery systems, enhancing oral supplementation and accessibility of puerarin