Fostamatinib for Hospitalized Adults With COVID-19 and Hypoxemia: A Randomized Clinical Trial.

Importance: Fostamatinib, a spleen tyrosine kinase inhibitor, has been reported to improve outcomes of COVID-19.

Objective: To evaluate the efficacy and safety of fostamatinib in adults hospitalized with COVID-19 and hypoxemia.

Design, Setting, And Participants: This multicenter, phase 3, placebo-controlled, double-blinded randomized clinical trial was conducted at 41 US sites and 21 international sites between November 17, 2021, and September 27, 2023; the last follow-up visit was December 31, 2023.

Preparing better: Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) therapeutics trials lessons learned: A call to the future.

The Accelerating COVID-19 Therapeutic Interventions and Vaccines Therapeutic-Clinical Working Group members gathered critical recommendations in follow-up to lessons learned manuscripts released earlier in the COVID-19 pandemic. Lessons around agent prioritization, preclinical therapeutics testing, master protocol design and implementation, drug manufacturing and supply, data sharing, and public-private partnership value are shared to inform responses to future pandemics.

Biomarkers and cardiovascular events in patients with stable coronary disease in the ISCHEMIA Trials.

Importance: Biomarkers may improve prediction of cardiovascular events for patients with stable coronary artery disease (CAD), but their importance in addition to clinical tests of inducible ischemia and CAD severity is unknown.

Objectives: To evaluate the prognostic value of multiple biomarkers in stable outpatients with obstructive CAD and moderate or severe inducible ischemia.

Design And Setting: The ISCHEMIA and ISCHEMIA CKD trials randomized 5,956 participants with CAD to invasive or conservative management from July 2012 to January 2018; 1,064 participated in the biorepository.

Impact of Complete Revascularization in the ISCHEMIA Trial.

Background: Anatomic complete revascularization (ACR) and functional complete revascularization (FCR) have been associated with reduced death and myocardial infarction (MI) in some prior studies. The impact of complete revascularization (CR) in patients undergoing an invasive (INV) compared with a conservative (CON) management strategy has not been reported.

Objectives: Among patients with chronic coronary disease without prior coronary artery bypass grafting randomized to INV vs CON management in the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial, we examined the following: 1) the outcomes of ACR and FCR compared with incomplete revascularization; and 2) the potential impact of achieving CR in all INV patients compared with CON management.

The impact of solvents on the toxicity of the banned parathion insecticide.

The aerial crop dusting and spraying of fields with the phosphorothioate insecticide parathion in the late 1900s, significantly improved crop yields but resulted in high levels of occupational toxicity in handlers and agricultural workers, as well as cases of intentional self-harm poisoning, culminating in its banning in many western countries by early 2000s. However because of the low solubility and volatility of parathion, most available products were formulated using organic solvents e.g.

Best medical treatment in patients with PAD.

Guidelines recommend comprehensive lifestyle change in patients with peripheral arterial disease (PAD) to prevent cardiovascular events and death. When compared with other populations, patients with PAD are less likely to receive best medical therapies (BMT). The aim of this pilot study was to integrate all aspects of BMT in an intervention program and to determine the feasibility of such an approach by highlighting strengths and obstacles of a multi-aspect intervention.

Renin-Angiotensin System Modulation With Synthetic Angiotensin (1-7) and Angiotensin II Type 1 Receptor-Biased Ligand in Adults With COVID-19: Two Randomized Clinical Trials.

Importance: Preclinical models suggest dysregulation of the renin-angiotensin system (RAS) caused by SARS-CoV-2 infection may increase the relative activity of angiotensin II compared with angiotensin (1-7) and may be an important contributor to COVID-19 pathophysiology.

Objective: To evaluate the efficacy and safety of RAS modulation using 2 investigational RAS agents, TXA-127 (synthetic angiotensin [1-7]) and TRV-027 (an angiotensin II type 1 receptor-biased ligand), that are hypothesized to potentiate the action of angiotensin (1-7) and mitigate the action of the angiotensin II.

Design, Setting, And Participants: Two randomized clinical trials including adults hospitalized with acute COVID-19 and new-onset hypoxemia were conducted at 35 sites in the US between July 22, 2021, and April 20, 2022; last follow-up visit: July 26, 2022.

Evidence for the Role of a Second Fc-Binding Receptor in Placental IgG Transfer in Nonhuman Primates.

Transplacental transfer of maternal antibodies provides the fetus and newborn with passive protection against infectious diseases. While the role of the highly conserved neonatal Fc receptor (FcRn) in transfer of IgG in mammals is undisputed, recent reports have suggested that a second receptor may contribute to transport in humans. We report poor transfer efficiency of plant-expressed recombinant HIV-specific antibodies, including engineered variants with high FcRn affinity, following subcutaneous infusion into rhesus macaques close to parturition.

The global biomass of wild mammals.

Wild mammals are icons of conservation efforts, yet there is no rigorous estimate available for their overall global biomass. Biomass as a metric allows us to compare species with very different body sizes, and can serve as an indicator of wild mammal presence, trends, and impacts, on a global scale. Here, we compiled estimates of the total abundance (i.

A single post-exposure oxime RS194B treatment rapidly reactivates acetylcholinesterase and reverses acute symptoms in macaques exposed to diethylphosphorothioate parathion and chlorpyrifos insecticides.

Millions of individuals globally suffer from inadvertent, occupational or self-harm exposures from organophosphate (OP) insecticides, significantly impacting human health. Similar to nerve agents, insecticides are neurotoxins that target and inhibit acetylcholinesterase (AChE) in central and peripheral synapses in the cholinergic nervous system. Post-exposure therapeutic countermeasures generally include administration of atropine with an oxime to reactivate the OP-inhibited AChE.

The global biomass and number of terrestrial arthropods.

Insects and other arthropods are central to terrestrial ecosystems. However, data are lacking regarding their global population abundance. We synthesized thousands of evaluations from around 500 sites worldwide, estimating the absolute biomass and abundance of terrestrial arthropods across different taxa and habitats.

Survival After Invasive or Conservative Management of Stable Coronary Disease.

Background: The ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) compared an initial invasive versus an initial conservative management strategy for patients with chronic coronary disease and moderate or severe ischemia, with no major difference in most outcomes during a median of 3.2 years. Extended follow-up for mortality is ongoing.

Use of pragmatic and explanatory trial designs in acute care research: lessons from COVID-19.

Unique challenges arise when conducting trials to evaluate therapies already in common clinical use, including difficulty enrolling patients owing to widespread open-label use of trial therapies and the need for large sample sizes to detect small but clinically meaningful treatment effects. Despite numerous successes in trials evaluating novel interventions such as vaccines, traditional explanatory trials have struggled to provide definitive answers to time-sensitive questions for acutely ill patients with COVID-19. Pragmatic trials, which can increase efficiency by allowing some or all trial procedures to be embedded into clinical care, are increasingly proposed as a means to evaluate therapies that are in common clinical use.

Enhanced HIV SOSIP Envelope yields in plants through transient co-expression of peptidyl-prolyl isomerase B and calreticulin chaperones and ER targeting.

High yield production of recombinant HIV SOSIP envelope (Env) trimers has proven elusive as numerous disulfide bonds, proteolytic cleavage and extensive glycosylation pose high demands on the host cell machinery and stress imposed by accumulation of misfolded proteins may ultimately lead to cellular toxicity. The present study utilized the Nicotiana benthamiana/p19 (N.b.

Patient Onboarding and Engagement to Build a Digital Study After Enrollment in a Clinical Trial (TAILOR-PCI Digital Study): Intervention Study.

Background: The Tailored Antiplatelet Initiation to Lessen Outcomes Due to Decreased Clopidogrel Response After Percutaneous Coronary Intervention (TAILOR-PCI) Digital Study is a novel proof-of-concept study that evaluated the feasibility of extending the TAILOR-PCI randomized controlled trial (RCT) follow-up period by using a remote digital platform.

Objective: The aim of this study is to describe patients' onboarding, engagement, and results in a digital study after enrollment in an RCT.

Methods: In this intervention study, previously enrolled TAILOR-PCI patients in the United States and Canada within 24 months of randomization were invited by letter to download the study app.