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

Usability and Performance Measure of a Consumer-grade Brain Computer Interface System for Environmental Control by Neurological Patients

With the increasing incidence and prevalence of chronic brain injury patients and the current financial constraints in healthcare budgets, there is a need for a more intelligent way to realise the current practice of neuro-rehabilitation service provision. Brain-computer Interface (BCI) systems have the potential to address this issue to a certain extent only if carefully designed research can demonstrate that these systems are accurate, safe, cost-effective, are able to increase patient/carer satisfaction and enhance their quality of life. Therefore, one of the objectives of the proposed study was to examine whether participants (patients with brain injury and a sample of reference population) were able to use a low cost BCI system (Emotiv EPOC) to interact with a computer and to communicate via spelling words. Patients participated in the study did not have prior experience in using BCI headsets so as to measure the user experience in the first-exposure to BCI training. To measure emotional arousal of participants we used an ElectroDermal Activity Sensor (Qsensor by Affectiva). For the signal processing and feature extraction of imagery controls the Cognitive Suite of Emotiv's Control Panel was used. Our study reports the key findings based on data obtained from a group of patients and a sample reference population and presents the implications for the design and development of a BCI system for communication and control. The study also evaluates the performance of the system when used practically in context of an acute clinical environment

Crystal structure of M^pro (PDB ID: 6W63) representing Domain I, II and III with the co-crystalized ligand (PDB code: X77).

Crystal structure of Mpro (PDB ID: 6W63) representing Domain I, II and III with the co-crystalized ligand (PDB code: X77).</p

Native ligand (X77)-protein (PDB structure 6W63) 2D interactions plot: Representation of intermolecular interaction between native ligand and the active site amino acid residue of the target protein.

Native ligand (X77)-protein (PDB structure 6W63) 2D interactions plot: Representation of intermolecular interaction between native ligand and the active site amino acid residue of the target protein.</p

Fig 5 -

3D and 2D interaction profiles for SARS-CoV-2 Mpro- compounds (a-b) Mpro-CHEMBL1940602 (c-d) Mpro-CHEMBL2036486 (e-f) Mpro-CHEMBL3628485 (g-h) Mpro-CHEMBL200972 (i-j) Mpro-CHEMBL2036488, and (k-l) Mpro-X77 (control).</p

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