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☐ ☆ ✇ BMJ Open

Sedating with volatile anaesthetics for COVID-19 and non-COVID-19 acute hypoxaemic respiratory failure patients in ICU (SAVE-ICU): protocol for a randomised clinical trial

Por: Jerath · A. · Slessarev · M. · Martin · C. · DAragon · F. · Carrier · F. M. · Senaratne · J. · Meggison · H. · Hooper · J. · Alexandros Cavayas · Y. · Goligher · E. C. · Couture · E. J. · Randall · I. · Hatzakorzian · R. · Jacka · M. · Wiener-Kronish · J. · Xie · Z. · Pinto · R. L. · Cut — Octubre 13th 2025 at 16:51
Introduction

Inhaled anaesthetics can be used in mechanically ventilated critically ill patients to provide sedation. This approach to sedation potentially improves patient and health system outcomes, but further supportive evidence is needed. The objective of the SAVE-ICU clinical trial is to compare the effectiveness of inhaled versus intravenous sedation in ventilated adults with acute hypoxaemic respiratory failure.

Methods and analysis

SAVE-ICU is a multicentre, open-label, pragmatic, randomised controlled trial conducted in 15 intensive care units (ICUs) in Canada and the USA. Eligible patients include mechanically ventilated and sedated adults with acute hypoxemic respiratory failure from COVID-19 or non-COVID causes with PaO2/FIO2 ratio 12 hour). A hierarchy of outcomes was identified at the time of trial design, as the trial was launched during the COVID-19 pandemic when study drug shortages, staffing challenges and healthcare system pressures were prevalent and there was a requirement for rapid evidence generation and implementation on this topic. The primary outcome and highest in the hierarchy is hospital mortality (requiring 758 participants). Secondary and lower hierarchical outcomes are ventilator-free days at day 30 (200 patients), quality of life at 3 months (144 participants) and ICU-free days at day 30 (128 participants). Additional secondary outcomes include median daily oxygenation at day 3 (PaO2/FIO2 ratio), need for adjunctive acute respiratory distress syndrome therapies (prone positioning, inhaled nitric oxide, paralysis with a neuromuscular blocking agent and extracorporeal membrane oxygenation) during ICU stay, days alive and free from delirium and coma at day 14, hospital-free days at day 60 and disability score at 3 months and 12 months after enrolment.

Ethics and dissemination

The protocol was approved by all hospital ethics committees and by Health Canada. Informed consent will be obtained from substitute decision makers or deferred consent (as permitted by site ethics board). Trial findings will be shared at the end of the study using peer-review publications, conference presentations and social media as part of the trial knowledge translation plan.

Trial registration number

NCT04415060.

☐ ☆ ✇ PLOS ONE Medicine&Health

Environment and weight class linked to skin microbiome structure of juvenile Eastern hellbenders (<i>Cryptobranchus alleganiensis alleganiensis</i>) in human care

by Andrea C. Aplasca, Peter B. Johantgen, Christopher Madden, Kilmer Soares, Randall E. Junge, Vanessa L. Hale, Mark Flint

Amphibian skin is integral to promoting normal physiological processes in the body and promotes both innate and adaptive immunity against pathogens. The amphibian skin microbiota is comprised of a complex assemblage of microbes and is shaped by internal host characteristics and external influences. Skin disease is a significant source of morbidity and mortality in amphibians, and increasing research has shown that the amphibian skin microbiota is an important component in host health. The Eastern hellbender (Cryptobranchus alleganiensis alleganiensis) is a giant salamander declining in many parts of its range, and captive-rearing programs are important to hellbender recovery efforts. Survival rates of juvenile hellbenders in captive-rearing programs are highly variable, and mortality rates are overall poorly understood. Deceased juvenile hellbenders often present with low body condition and skin abnormalities. To investigate potential links between the skin microbiota and body condition, we collected skin swab samples from 116 juvenile hellbenders and water samples from two holding tanks in a captive-rearing program. We used 16s rRNA gene sequencing to characterize the skin and water microbiota and observed significant differences in the skin microbiota by weight class and tank. The skin microbiota of hellbenders that were housed in tanks in close proximity were generally more similar than those housed physically distant. A single taxa, Parcubacteria, was differentially abundant by weight class only and observed in higher abundance in low weight hellbenders. These results suggest a specific association between this taxa and Low weight hellbenders. Additional research is needed to investigate how husbandry factors and potential pathogenic organisms, such as Parcubacteria, impact the skin microbiota of hellbenders and ultimately morbidity and mortality in the species.
☐ ☆ ✇ PLOS ONE Medicine&Health

Testing learning as alternative to the blank slate hypothesis in the honey bee, <i>Apis mellifera</i>

Por: Olav Rueppell · Kayla De Jong · Jacob J. Herman · Cleo Randall — Junio 9th 2025 at 16:00

by Olav Rueppell, Kayla De Jong, Jacob J. Herman, Cleo Randall

Reliable recognition of nestmates and discrimination against non-nestmates is key to the integrity of social insect colonies. Cuticular hydrocarbon profiles play a key role in this recognition process in many species, including honey bees. Newly emerged worker bees are largely devoid of cuticular hydrocarbons and therefore believed to represent a “blank slate” that is not discriminated against and instead accepted into other colonies regardless of colony origin. However, instead of being unrecognizable, the absence of cuticular hydrocarbons may also represent a recognizable “Gestalt”. Thus, an alternative hypothesis for the universal acceptance of newly emerged workers may be that older workers in every colony learn the absence of cuticular hydrocarbons as a familiar stimulus that belongs to their colony because other such workers are constantly emerging under normal circumstances. Here, we tested this hypothesis by comparing the response to newly emerged workers between bees that matured in colonies with and without newly emerging bees. Contrary to our prediction, we found no significant difference between these two experimental groups in an aggression bioassay towards newly emerged workers. We thus failed to provide empirical evidence against the blank slate hypothesis. However, the groups displayed significant differences in aggression towards foragers from their own respective colonies, indicating that the emergence of new workers in a colony can affect group discriminatory behavior in honey bees. Furthermore, we identified a negative effect of temperature on aggressive behavior toward newly emerged workers.
☐ ☆ ✇ PLOS ONE Medicine&Health

Patient-Selection of a Clinical Trial Primary Outcome: The ENHANCE-AF Outcomes Survey

by Randall S. Stafford, Eli N. Rice, Rushil Shah, Mellanie T. Hills, Julio C. Nunes, Katie DeSutter, Amy Lin, Karma Lhamo, Bryant Lin, Ying Lu, Paul J. Wang

Introduction

Before the initiation of the ENHANCE-AF clinical trial, which tested a novel digital shared decision-making tool to guide the use of anticoagulants in stroke prevention for patients with atrial fibrillation, this study aimed to identify the most appropriate, patient-selected primary outcome and to examine whether outcome selection varied by demographic and clinical characteristics.

Methods

Our cross-sectional survey asked 100 participants with atrial fibrillation to rank two alternative scales based on the scales’ ability to reflect their experiences with decision-making for anticoagulation. The Decisional Conflict Scale (DCS), a 16-item scale, measures perceptions of uncertainty in choosing options. The 5-item Decision Regret Scale (DRS) focuses on remorse after a healthcare decision. We included adults with non-valvular AFib and CHA2DS2VASc scores of at least 2 for men and 3 for women. Multivariable logistic regression with backward selection identified characteristics independently associated with scale choice.

Results

The DCS was chosen over the DRS by 77% [95% confidence interval (CI) 68 to 85%] of participants. All subgroups designated a preference for the DCS. Those with higher CHA2DS2VASc scores (≥5, n = 26) selected the DCS 54% of the time compared with 86% of those with lower scores (p =  0.002). Multiple logistic regression confirmed a weaker preference for the DCS among those with higher CHA2DS2VASc scores.

Conclusions

Individuals with atrial fibrillation preferred the DCS over the DRS for measuring their decision-making experiences. As a result of this survey, the DCS was designated as the ENHANCE-AF clinical trial’s primary endpoint.

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