33 research outputs found
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
Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19
IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19.
Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19.
DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022).
INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days.
MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes.
RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively).
CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes.
TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570
Reparations for Historical Human Rights Violations: The International and Historical Dimensions of the Alien Torts Claims Act Genocide Case of the Herero of Namibia
T-DNA tagging of a flowering-time gene and improved gene transfer by in planta transformation of Arabidopsis
Improved knockdown from artificial microRNAs in an enhanced miR-155 backbone: a designer's guide to potent multi-target RNAi
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Terricolous lichens as indicators of nitrogen deposition: evidence from national records
Large areas of Great Britain currently receive nitrogen (N) deposition at rates which exceed the thresholds above which there is risk of damage to sensitive components of the ecosystem (critical loads for nutrient nitrogen and critical levels for ammonia), and are predicted to continue to do so. Excess N can damage semi-natural ecosystems. Lichens are potentially sensitive to air quality because they directly utilise nutrients deposited from the atmosphere thus may be good indicators of air quality. We used data from the British Lichen Society (BLS) database, which records the presence of all lichen taxa growing in Britain at 10 km resolution. The probability of presence of a taxa at a given level of N deposition was analysed together with driver data for climate, change in sulphur deposition, land-use and N deposition using generalised additive models (GAMs). Many taxa showed negative responses to N deposition with reductions in the probability of presence as N deposition increased. In all of the habitats, there were a mix of terricolous taxa which showed negative or no significant relationship with N deposition. Most of the taxa with negative relationships with N deposition started to decline in prevalence at the lowest levels of deposition found in this study. Levels of deposition over which a negative response apparently occurs are lower than those at which critical loads have been set for some habitats. These findings suggest that some terricolous lichen taxa are sensitive to atmospheric N deposition and even low levels of nitrogen deposition could be damaging terricolous lichen communities making then potentially good indicators of N deposition