Building global collaborative research networks in paediatric critical care: a roadmap.

Paediatric critical care units are designed for children at a vulnerable stage of development, yet the evidence base for practice and policy in paediatric critical care remains scarce. In this Health Policy, we present a roadmap providing strategic guidance for international paediatric critical care trials. We convened a multidisciplinary group of 32 paediatric critical care experts from six continents representing paediatric critical care research networks and groups.

Long-term follow-up of patients with a first clinical demyelinating event (clinically isolated syndrome) who received cladribine tablets in CLASSIC-MS: Findings for the ORACLE-MS cohort.

Background: CLASSIC-MS explored long-term outcomes of patients treated with cladribine tablets.

Objective: Assess long-term efficacy in patients previously enrolled in ORACLE-MS, a Phase III parent trial.

Methods: ORACLE-MS included patients with a first clinical demyelinating event (FCDE or clinically isolated syndrome) who received ⩾1 course of cladribine tablets or placebo.

Factors Influencing Nerinetide Effect on Infarct Volume in Patients Without Alteplase in the Randomized ESCAPE-NA1 Trial.

Background: In the ESCAPE-NA1 trial (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke), treatment with nerinetide was associated with a smaller infarct volume among patients who did not receive intravenous alteplase. We assessed the effect of nerinetide on the surrogate imaging outcome of final infarct volume in patients who did not receive intravenous alteplase and explored predictors of outcome and modifiers of nerinetide's effect on infarct volume.

Methods: ESCAPE-NA1 was a multicenter, randomized trial in which patients with acute stroke with a baseline Alberta Stroke Program Early CT Score >4, undergoing endovascular thrombectomy, were randomized to receive intravenous nerinetide or placebo.

Mucosal SARS-CoV-2 S1 adenovirus-based vaccine elicits robust systemic and mucosal immunity and protects against disease in animals.

Unlabelled: The COVID-19 pandemic has emphasized the importance and need for accessible safe, effective, and versatile vaccine platforms. While approved SARS-CoV-2 vaccines have been instrumental in saving lives and reducing healthcare and economic burdens, the induction of mucosal immunity remains an unmet need. Here, we engineered and evaluated a non-replicating adenovirus 5 (rAd5)-based vaccine expressing the SARS-CoV-2 S1 subunit (rAd5-SARS2-S1).

The AMPK allosteric activator MK-8722 improves the histology and spliceopathy in myotonic dystrophy type 1 (DM1) skeletal muscle.

Multiple signaling pathways have been reported to be altered in Myotonic Dystrophy type 1 (DM1) skeletal muscle, contributing to pathogenicity. In particular, previous work established that AMPK signaling, a key sensor of energy metabolism, is repressed in DM1 mouse muscle and that activating AMPK through exercise and/or with pharmacological activators is beneficial for the DM1 muscle phenotype. Here, we explored the effects of a newer, more specific allosteric AMPK activator acting directly on AMPK.

Computational Investigation of the Therapeutic Potential of in the Management of Erectile Dysfunction.

Erectile dysfunction (ED) is a multifactorial social problem affecting men worldwide. While phosphodiesterase type 5 inhibitors (PDE5) like sildenafil are commonly used, they often present side effects, underscoring the need for alternative therapies. Therefore, this study investigated the potential of phytochemicals from in the management of ED.

International Comparison of Quality Indicators for Adults Hospitalized for Heart Failure: A Systematic Review.

Background: There is limited international agreement on defining care quality for the millions of people hospitalized with heart failure worldwide. Our objective was to compare and measure agreement across existing internationally published quality indicators (QIs) for the care of adults hospitalized for heart failure.

Methods: Systematic review and evidence gap map of internationally published articles reporting on QIs for adults hospitalized for heart failure, using PubMed, MEDLINE, EMBASE, and TRIP from inception to July 18, 2022.

Catheter Ablation or Antiarrhythmic Drugs for Ventricular Tachycardia.

Background: Patients with ventricular tachycardia and ischemic cardiomyopathy are at high risk for adverse outcomes. Catheter ablation is commonly used when antiarrhythmic drugs do not suppress ventricular tachycardia. Whether catheter ablation is more effective than antiarrhythmic drugs as a first-line therapy in patients with ventricular tachycardia is uncertain.

Clinical Tools to Assess Functional Capacity During Risk Assessment Before Elective Noncardiac Surgery : A Scoping Review.

Background: Functional capacity is critical to preoperative risk assessment, yet guidance on its measurement in clinical practice remains lacking.

Purpose: To identify functional capacity assessment tools studied before surgery and characterize the extent of evidence regarding performance, including in populations where assessment is confounded by noncardiopulmonary reasons.

Data Sources: MEDLINE, EMBASE, and EBM Reviews (until July 2024).

Consent-Related Outcomes in the Alteplase Compared to Tenecteplase Trial.

Background And Objectives: In recent years, researchers have sought to address the challenges of obtaining informed consent for participation in acute stroke trials. We studied outcomes related to the use of deferral of consent in the phase 3 Alteplase Compared to Tenecteplase (AcT) trial.

Methods: As part of our protocol, we captured methods of consent, participant withdrawals, door-to-randomization times, and door-to-needle times.

Targeted Genome Mining Facilitates the Discovery of a Promiscuous, Hyperthermostable Amidase from Thermovenabulum Gondwanense with Notable Nylon-Degrading Capacity.

Plastics are ubiquitous in our ecosystems, and microplastic accumulation in the environment is an emerging global health concern. Since available recycling technologies are not economically competitive with primary plastic production, global use is expected to reach 1231 megatons by 2060, with 493 megatons leeching into the environment each year. To identify new nylon-recycling biotechnologies, targeted genome mining was used to identify thermostable enzymes capable of degrading polyamides.

Rapid normalization of vitamin D deficiency in PICU (VITdALIZE-KIDS): study protocol for a phase III, multicenter randomized controlled trial.

Background: The rate of vitamin D deficiency (VDD) in critically ill children worldwide has been estimated at 50%. These children are at risk of multiple organ dysfunction, chronic morbidity, and decreased health related quality of life (HRQL). Pediatric and adult ICU clinical trials suggest that VDD is associated with worse clinical outcomes, although data from supplementation trials are limited and inconclusive.

Anticoagulation in device-detected atrial fibrillation with or without vascular disease: a combined analysis of the NOAH-AFNET 6 and ARTESiA trials.

Background And Aims: The optimal antithrombotic therapy in patients with device-detected atrial fibrillation (DDAF) is unknown. Concomitant vascular disease can modify the benefits and risks of anticoagulation.

Methods: These pre-specified analyses of the NOAH-AFNET 6 (n = 2534 patients) and ARTESiA (n = 4012 patients) trials compared anticoagulation with no anticoagulation in patients with DDAF with or without vascular disease, defined as prior stroke/transient ischaemic attack, coronary or peripheral artery disease.

A Randomized Trial Comparing Concurrent versus Sequential Radiation and Endocrine Therapy in Early-Stage, Hormone-Responsive Breast Cancer.

Concerns exist regarding increased toxicities, including endocrine therapy toxicity, with concurrent radiation and endocrine therapy in early breast cancer (EBC). We present a pragmatic, randomized trial comparing concurrent versus sequential endocrine and radiotherapy in hormone-responsive EBC. In this multicenter trial, patients were randomized to receive adjuvant endocrine therapy concurrent with, or sequential to, radiotherapy.

Hepatic Sinusoidal Disorders.

Hepatic sinusoids are highly specialized microcirculatory conduits within the hepatic lobules that facilitate liver functions. The sinusoids can be affected by various disorders, including sinusoidal dilatation, sinusoidal obstruction syndrome (SOS), sinusoidal cellular infiltration, perisinusoidal infiltration, and endothelial neoplasms, such as hemangioendothelioma and angiosarcoma. While these disorders, particularly SOS and neoplasms, can be life threatening, their clinical manifestation is often nonspecific.