Using a novel in-mask non-invasive ventilator microphone to improve talker intelligibility in healthy and hospitalised adults.

Non-invasive ventilation (NIV) provides respiratory support without invasive endotracheal intubation but can hinder patients' ability to communicate effectively. The current study presents preliminary results using a novel in-mask ventilator microphone to enhance talker intelligibility while receiving NIV. A proof-of-concept study assessed sentence intelligibility of five healthy adult talkers using a prototype model of the microphone under continuous positive airway pressure (CPAP; 5/5 cm HO) and bilevel positive airway pressure (BiPAP; 8/4 cm HO) ventilator conditions.

Modifiable in-hospital factors for 12-month global cognition, post-traumatic stress disorder symptoms, and depression symptoms in adults hospitalized with COVID-19.

Background: We sought to identify potentially modifiable in-hospital factors associated with global cognition, post-traumatic stress disorder (PTSD) symptoms, and depression symptoms at 12 months.

Methods: This was a multi-center prospective cohort study in adult hospitalized patients with acute COVID-19. The following in-hospital factors were assessed: delirium; frequency of in-person and virtual visits by friends and family; and hydroxychloroquine, corticosteroid, and remdesivir administration.

Implementation of coordinated spontaneous awakening and breathing trials using telehealth-enabled, real-time audit and feedback for clinician adherence (TEACH): a type II hybrid effectiveness-implementation cluster-randomized trial.

Background: Intensive care unit (ICU) patients on mechanical ventilation often require sedation and analgesia to improve comfort and decrease pain. Prolonged sedation and analgesia, however, may increase time on mechanical ventilation, risk for ventilator associated pneumonia, and delirium. Coordinated interruptions in sedation [spontaneous awakening trials (SATs)] and spontaneous breathing trials (SBTs) increase ventilator-free days and improve mortality.

Awakening and Breathing Coordination: A Mixed-Methods Analysis of Determinants of Implementation.

Routine spontaneous awakening and breathing trial coordination (SAT/SBT) improves outcomes for mechanically ventilated patients, but adherence varies. Understanding barriers to and facilitators of consistent daily use of SAT/SBT (implementation determinants) can guide the development of implementation strategies to increase adherence to these evidence-based interventions. We conducted an explanatory, sequential mixed-methods study to measure variation in the routine daily use of SAT/SBT and to identify implementation determinants that might explain variation in SAT/SBT use across 15 intensive care units (ICUs) in urban and rural locations within an integrated, community-based health system.

Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial.

Background: There is a clinical need for therapeutics for COVID-19 patients with acute hypoxemic respiratory failure whose 60-day mortality remains at 30-50%. Aviptadil, a lung-protective neuropeptide, and remdesivir, a nucleotide prodrug of an adenosine analog, were compared with placebo among patients with COVID-19 acute hypoxaemic respiratory failure.

Methods: TESICO was a randomised trial of aviptadil and remdesivir versus placebo at 28 sites in the USA.

Implementation of Lung-Protective Ventilation in Patients With Acute Respiratory Failure.

Objectives: We implemented a computerized protocol for low tidal volume ventilation (LTVV) to improve management and outcomes of mechanically ventilated patients with, and without, the acute respiratory distress syndrome (ARDS).

Design: Pragmatic, nonrandomized stepped wedge type II hybrid implementation/effectiveness trial.

Setting: Twelve hospitals in an integrated healthcare system over a 2-year period.

Delivery of Lung-protective Ventilation for Acute Respiratory Distress Syndrome: A Hybrid Implementation-Effectiveness Trial.

Lung-protective ventilation (LPV) improves outcomes for patients with acute respiratory distress syndrome (ARDS), but adherence remains inadequate. To measure the process and clinical impacts of implementation of a science-based intervention to improve LPV adherence for patients with ARDS, in part by increased use of clinical decision support (CDS). We conducted a type III hybrid implementation/effectiveness pilot trial enrolling adult patients with ARDS admitted to three hospitals before and after the launch of a multimodal implementation intervention to increase the use of mechanical ventilation CDS and improve LPV adherence.

Care of the Seriously Ill Patient with SARS-CoV-2.

In late 2019, SARS-CoV-2 caused the greatest global health crisis in a century, impacting all aspects of society. As the COVID-19 pandemic evolved throughout 2020 and 2021, multiple variants emerged, contributing to multiple surges in cases of COVID-19 worldwide. In 2021, highly effective vaccines became available, although the pandemic continues into 2022.

Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19 : A Randomized Controlled Trial.

Background: Ensovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection.

Objective: To investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standard care alone.

Design: Double-blind, randomized, placebo-controlled, clinical trial.

New-Onset Systemic Capillary Leak Syndrome in an Adult Patient with COVID-19.

Systemic capillary leak syndrome (SCLS) is a rare disorder manifesting as shock, hemoconcentration, and hypoalbuminemia, which may be either idiopathic or secondary to an underlying disease process. We report a case of an adult with COVID-19 infection associated with new onset SCLS. Our case joins only two other cases of new SCLS associated with COVID-19 infection reported in the literature.

Hydroxychloroquine vs. Azithromycin for Hospitalized Patients with COVID-19 (HAHPS): Results of a Randomized, Active Comparator Trial.

Rationale: The COVID-19 pandemic struck an immunologically naïve, globally interconnected population. In the face of a new infectious agent causing acute respiratory failure for which there were no known effective therapies, rapid, often pragmatic trials were necessary to evaluate potential treatments, frequently starting with medications that are already marketed for other indications. Early in the pandemic, hydroxychloroquine and azithromycin were two such candidates.

Rationale and Design of ORCHID: A Randomized Placebo-controlled Clinical Trial of Hydroxychloroquine for Adults Hospitalized with COVID-19.

The ORCHID (Outcomes Related to COVID-19 treated with Hydroxychloroquine among In-patients with symptomatic Disease) trial is a multicenter, blinded, randomized trial of hydroxychloroquine versus placebo for the treatment of adults hospitalized with coronavirus disease (COVID-19). This document provides the rationale and background for the trial and highlights key design features. We discuss five novel challenges to the design and conduct of a large, multicenter, randomized trial during a pandemic, including ) widespread, off-label use of the study drug before the availability of safety and efficacy data; ) the need to adapt traditional procedures for documentation of informed consent during an infectious pandemic; ) developing a flexible and robust Bayesian analysis incorporating significant uncertainty about the disease, outcomes, and treatment; ) obtaining indistinguishable drug and placebo without delaying enrollment; and ) rapidly obtaining administrative and regulatory approvals.

Hydroxychloroquine versus Azithromycin for Hospitalized Patients with Suspected or Confirmed COVID-19 (HAHPS). Protocol for a Pragmatic, Open-Label, Active Comparator Trial.

Coronavirus disease (COVID-19) is a potentially fatal illness with no proven therapy beyond excellent supportive care. Treatments are urgently sought. Adaptations to traditional trial logistics and design to allow rapid implementation, evaluation of trials within a global trials context, flexible interim monitoring, and access outside traditional research hospitals (even in settings where formal placebos are unavailable) may be helpful.