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.
Background: Several cardiovascular pathologies cause heart failure. Heart failure with reduced ejection fraction (HFrEF) is deteriorated by neurohormonal activation, so neurohormonal antagonists are recommended in HFrEF patients. They improve morbidity, mortality, and quality of life and reduce hospital admissions. Heart failure treatment guidelines recommend achieving target doses of those drugs. However, many clinicians prescribe suboptimal doses for the fear of inducing hypotension. The aim of this systematic review and meta-analysis is to understand whether it is still beneficial to uptitrate the doses of those drugs even if the patient is at the risk of developing hypotension. Methods: The primary outcome is symptomatic or asymptomatic hypotension in patients on neurohormonal antagonist drugs for HFrEF. Secondary outcomes are blood pressure reduction, New Yok Heart Association functional class deterioration, non-fatal cardiovascular events, cardiovascular mortality, all-cause mortality, heart failure hospitalizations, and adverse events. Randomized controlled trials involving adults with HFrEF will be included. Comprehensive literature search will be done in MEDLINE, Scopus, Web of Science, WHO Global Index Medicus, and the Cochrane Central Register of Controlled Trials. MEDLINE will be searched first using controlled vocabulary and free text terms and then adapted to other databases. Linear and nonlinear dose-response metaanalyses will be conducted. Publication bias and statistical heterogeneity will be tested by Egger's regression and Cochran's Q tests, respectively. Sensitivity, subgroup, and meta-regression analyses will be performed. Grading of Recommendations Assessment, Development and Evaluation approach will be used to judge the quality of evidence.
Postinfectious immune-mediated brainstem encephalitis associated with herpes simplex virus infection is believed to be rare. We report a seven-year-old previously healthy boy who developed brainstem encephalitis with excellent response to acyclovir and methylprednisolone, after herpetic gingivostomatitis. No relapse was noted during a 24-month follow-up period.
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