Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

European Society of Cardiology: Cardiovascular Disease Statistics 2019

Aims The 2019 report from the European Society of Cardiology (ESC) Atlas provides a contemporary analysis of cardiovascular disease (CVD) statistics across 56 member countries, with particular emphasis on international inequalities in disease burden and healthcare delivery together with estimates of progress towards meeting 2025 World Health Organization (WHO) non-communicable disease targets. Methods and results In this report, contemporary CVD statistics are presented for member countries of the ESC. The statistics are drawn from the ESC Atlas which is a repository of CVD data from a variety of sources including the WHO, the Institute for Health Metrics and Evaluation, and the World Bank. The Atlas also includes novel ESC sponsored data on human and capital infrastructure and cardiovascular healthcare delivery obtained by annual survey of the national societies of ESC member countries. Across ESC member countries, the prevalence of obesity (body mass index ≥30 kg/m2) and diabetes has increased two- to three-fold during the last 30 years making the WHO 2025 target to halt rises in these risk factors unlikely to be achieved. More encouraging have been variable declines in hypertension, smoking, and alcohol consumption but on current trends only the reduction in smoking from 28% to 21% during the last 20 years appears sufficient for the WHO target to be achieved. The median age-standardized prevalence of major risk factors was higher in middle-income compared with high-income ESC member countries for hypertension {23.8% [interquartile range (IQR) 22.5–23.1%] vs. 15.7% (IQR 14.5–21.1%)}, diabetes [7.7% (IQR 7.1–10.1%) vs. 5.6% (IQR 4.8–7.0%)], and among males smoking [43.8% (IQR 37.4–48.0%) vs. 26.0% (IQR 20.9–31.7%)] although among females smoking was less common in middle-income countries [8.7% (IQR 3.0–10.8) vs. 16.7% (IQR 13.9–19.7%)]. There were associated inequalities in disease burden with disability-adjusted life years per 100 000 people due to CVD over three times as high in middle-income [7160 (IQR 5655–8115)] compared with high-income [2235 (IQR 1896–3602)] countries. Cardiovascular disease mortality was also higher in middle-income countries where it accounted for a greater proportion of potential years of life lost compared with high-income countries in both females (43% vs. 28%) and males (39% vs. 28%). Despite the inequalities in disease burden across ESC member countries, survey data from the National Cardiac Societies of the ESC showed that middle-income member countries remain severely under-resourced compared with high-income countries in terms of cardiological person-power and technological infrastructure. Under-resourcing in middle-income countries is associated with a severe procedural deficit compared with high-income countries in terms of coronary intervention, device implantation and cardiac surgical procedures. Conclusion A seemingly inexorable rise in the prevalence of obesity and diabetes currently provides the greatest challenge to achieving further reductions in CVD burden across ESC member countries. Additional challenges are provided by inequalities in disease burden that now require intensification of policy initiatives in order to reduce population risk and prioritize cardiovascular healthcare delivery, particularly in the middle-income countries of the ESC where need is greatest

Fully Developed Liquid Layer Flow Over a Convex Corner Considering Surface Tension Effects Using Numerical Methods

In this paper, liquid layer flow considering surface tension effect, encountering a convex corner has been discussed. The flow profile far upstream is fully developed. Half-Poiseuille gives exact solution far upstream. Due to small disturbance of 0(δ), matched asymptotic technique has been opted to get the linearized solutions far downstream. The obtained equations have been solved numerically using Chebyshev Collocation method in collaboration with finite difference scheme. These results have been verified via computational work. The aforementioned method is beneficial, as we have successfully plotted graphs for the cases s = 0.1 and 0.2. Eventually, we have compared obtained results with the Gajjar’s results [3

Analysis of Leachate and Water Resource Quality Surrounding Municipal Solid Waste Landfill of Tamellast (Agadir, Morocco)

The aim of this work was to study the physicochemical characterization and heavy metal testing results carried out for leachate generated by the landfilling of household and similar waste in the Tamellast landfill of Agadir. The surface and groundwater resource (often used as drinking source) samples collected from Tamellast and different water sources wells surrounding the landfill were used to find out the impact of leachate percolation on surface and groundwater quality. The Physico-chemical parameters analyzed were, pH, Electrical Conductivity (EC), Dissolved oxygen, Sodium, Potassium, while biological parameters tested were Biological Oxygen Demand (BOD), Chemical Oxygen Demand (COD), E.Coli and Coliform tot. The contamination was investigated by measuring the concentration of heavy metals (Pb, Zn, Cr, Ni, As, and Fe). The Electrical Conductivity (EC), COD, BOD, Sodium, Potassium, in leachate were found to be 13180 µs/cm, 3150 mgO2/l, 1000 mgO2/l, 2000 mg/L, and 10700 mg/L, respectively. The concentration in the surrounding dug wells varied from 8.33 – 9.13 mg/L for Dissolved Oxygen, 9.8 – 18 mg/L for potassium, 0.22 – 0.6 mg/L for Fe, and 0.012 – 0.1 mg/L for total Mn. The concentration of Mn, Fe, and other parameters decreased with increasing distance between the landfill and wells

Surface tension effects on fully developed liquid layer flow over a convex corner

This investigation deals with the study of fully developed liquid layer flow along with surface tension effects, confronting a convex corner in the direction of fluid flow. At the point of interaction, the related equations are formulated using double deck structure and match asymptotic techniques. Linearized solutions for small angle are obtained analytically. The solutions corresponding to similar flow neglecting surface tension effects are also recovered as special case of our general solutions. Finally, the influence of pertinent parameters on the flow, as well as a comparison between models, are shown by graphical illustration

The geological and hydrogeological characteristics of Tamelast landfill site in Agadir, Morocco

The Grand Agadir is confronting with huge production of solid waste. Due to the fact of changes in habits of consumption, the increase of production, and demographic evolution. This production is buried in the controlled discharge of Tamelast. This landfill faces many environmental issues. Our work aims to evaluate the environmental characteristics based on the geological and hydrogeological properties of the site of the Tamelast landfill in Grand Agadir (Morocco). To evaluate the geological and hydrogeological characteristics of the Tamelast landfill, we have generated geological, hydrogeological maps, stratigraphic vertical sections, and cross-sections of the landfill area that have been prepared for further assessment of environmental geological factors. Besides, we also focused on other measures of permeability, and field data we could define the probability and importance of contamination by leachate. The Tamelast landfill is installed on the marl-limestone and carbonate ranges of the Campanian and Maastrichtian. Geologically, the site consists essentially of carbonate deposits, limestones, and Cretaceous marls. These geological outcrops that can play the role of a potential aquifer are the fractured Campanian marl-limestone formations. These soils have a permeability of 5.10-4 to 10-3m/s and transmissivity of 10-2 to 5.10-2 m2/s

Assesment of polyphenolic compounds against biofilms produced by clinical Acinetobacter baumannii strains using in silico and in vitro models

Several types of microbial infections are caused by Acinetobacter baumanii that has developed resistance to antimicrobial agents. We therefore investigated the role of plant polyphenols against A. baumannii using in silico and in vitro models. The clinical strains of A. baumannii were investigated for determination of resistance pattern and resistance mechanisms including efflux pump, extended spectrum beta lactamase, phenotype detection of AmpC production, and Metallo-β-lactamase. The polyphenolic compounds were docked against transcription regulator BfmR (PDB ID 6BR7) and antimicrobial, antibiofilm, and anti-quorum sensing activities were performed. The antibiogram studies showed that all isolated strains were resistant. Strain A77 was positive in Metallo-β-lactamase production. Similarly, none of strains were producers of AmpC, however, A77, A76, A75 had active efflux pumps. Molecular docking studies confirmed a strong binding affinity of Rutin and Catechin towards transcription regulator 6BR7. A significant antimicrobial activity was recorded in case of quercetin and syringic acid (MIC 3.1 µg/mL) followed by vanillic acid and caffeic acid (MIC 12.5 µg/mL). All tested compounds presented a strong antibiofilm activity against A. baumanii strain A77 (65 to 90%). It was concluded that all tested polyphenols samples posess antimicrobial and antibiofilm activities, and hence they may be utilized to treat multidrug resistance A. baumannii infections