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Frailty and the risk of ICU-acquired infections in a randomised trial: a protocol and statistical analysis plan

Por: Fernando · S. M. · Muscedere · J. · Rochwerg · B. · Johnstone · J. · Daneman · N. · Marshall · J. C. · Lauzier · F. · Rudkowski · J. C. · Arabi · Y. M. · Heels-Ansdell · D. · Sligl · W. · Kristof · A. S. · Duan · E. · Dionne · J. C. · St-Arnaud · C. · Reynolds · S. · Khwaja · K. · Cook
Introduction

Dysregulated immunity may account for an increased risk of infection and other adverse outcomes among frail hospitalised persons. The primary objective of this study is to examine whether baseline frailty is associated with the risk of developing ventilator-associated pneumonia (VAP) or other intensive care unit (ICU)-acquired infections among invasively ventilated adults. Additional objectives are to examine the relationship between frailty and hospital length of stay, discharge to a long-term care facility and vital status. We hypothesise that persons with frailty compared with others would have an increased risk of VAP and other infections, a longer hospital stay, higher probability of discharge to a long-term care facility and higher mortality.

Methods and analysis

This is a preplanned secondary analysis of the PROSPECT trial (Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial) which enrolled patients across 44 ICUs in three countries. We will use Cox proportional hazards regression analysis to assess the association of frailty with the clinical outcomes of interest, adjusting for other baseline variables. Baseline demographic and descriptive outcome data will be reported using descriptive statistics. Regression results will be presented as adjusted HRs or ORs with 95% CIs for the associations of each independent variable with the primary, secondary and tertiary outcomes.

Ethics and dissemination

Participating hospital research ethics board approved the PROSPECT trial and data collection. The protocol for this study was approved by the Hamilton Integrated Research Ethics Board on 20 August 2015 (Project ID:19128). This study will identify whether frailty is associated with risk of VAP and other healthcare-associated infections in invasively ventilated patients, adjusted for other baseline factors. Results may be useful to patients, their caregivers, clinicians and the design of future research. Findings will be disseminated to investigators at a meeting of the Canadian Critical Care Trials Group. We will present study results at an international conference in the fields of critical care and infectious diseases, to coincide with or precede open-access peer-review publication. To aid knowledge dissemination, we will use a variety of formats. For example, for traditional and social media, we will create two different visual abstracts and infographics of our results suitable to share on clinician-facing and public-facing platforms.

Trial registration number

NCT02462590.

Protocol for an economic evaluation alongside the Re-Evaluating the Inhibition of Stress Erosions (E-REVISE) trial

Por: Humphries · B. · Zytaruk · N. · Heels-Ansdell · D. · Lau · V. · Rochwerg · B. · Fowler · R. · Yao · Y. · Cook · D. J. · Xie · F.
Introduction

Economic evaluations in healthcare can guide practice and inform policy. The objective of this paper is to present the protocol for a health economic evaluation comparing the cost-effectiveness of prophylactic treatment using pantoprazole 40 mg daily compared with no pantoprazole to prevent upper gastrointestinal (GI) bleed among invasively ventilated patients.

Methods and analysis

This is an economic evaluation conducted alongside the Re-Evaluating the Inhibition of Stress Erosions (REVISE) trial (ClinicalTrials.gov NCT03374800). The primary outcome is the incremental cost per clinically important upper GI bleed prevented. The base-case analysis will focus on the entire international cohort of 4821 REVISE patients. The analysis will be conducted from a healthcare payer perspective over a time horizon of ICU admission to hospital discharge or death. To facilitate comparisons across countries given the international scope of the REVISE trial, costs will be presented in United States dollars. The study protocol was developed following the Professional Society for Health Economics and Outcomes Research guidelines.

Ethics and dissemination

The trial was approved by each participating institution; this economic evaluation was approved by the Hamilton Integrated Research Ethics Board. Given widespread daily use of proton pump inhibitors for critically ill patients, the results of this economic evaluation will be of high relevance to patients, family members, physicians, pharmacists, policymakers and guideline developers. Integrated knowledge translation will involve periodic progress reports to collaborators. End-of-study knowledge translation will include rounds, videoconferences, abstracts and slide-decks for intensive care unit quality councils and healthcare organisations, and open-access publications. Patient and family partners will co-create lay language summaries for traditional and social media to help inform all interest groups.

High-flow nasal Oxygen with or without alternating helmet Non-invasive ventilation for Oxygenation sUpport in acute Respiratory failure (HONOUR): a protocol for a pilot randomised controlled trial

Por: Angriman · F. · Ferreyro · B. L. · Rochwerg · B. · Sklar · M. · Adhikari · N. · Bagshaw · S. M. · Brochard · L. · Cuthbertson · B. · Del Sorbo · L. · Fowler · R. · Geagea · A. · Granton · J. T. · Mehta · S. · Munshi · L. · Muscedere · J. · Nardi · J. · Parhar · K. · Pinto · R. L. · Piquett
Introduction

Acute hypoxaemic respiratory failure is a common reason for intensive care unit (ICU) admission. Non-invasive respiratory support strategies such as high-flow nasal oxygen (HFNO) and helmet non-invasive ventilation may reduce the need for invasive mechanical ventilation and death. The High-flow nasal Oxygen with or without alternating helmet Non-invasive ventilation for Oxygenation sUpport in acute Respiratory failure pilot trial is designed to compare helmet non-invasive ventilation combined with HFNO vs HFNO alone in patients with acute hypoxaemic respiratory failure and to determine the feasibility of a larger randomised controlled trial.

Methods and analysis

This is a pragmatic, open-label, multicentre randomised controlled pilot trial enrolling 200 critically ill adults with acute hypoxaemic respiratory failure across 12 Canadian ICUs. Participants are randomised 1 to 1 to receive either helmet non-invasive ventilation plus HFNO or HFNO alone for at least 48 hours. The primary aim is to assess feasibility metrics including recruitment rate, protocol adherence and fidelity to pre-specified intubation criteria. Secondary outcomes include rates of intubation, all-cause mortality, ventilator-free days, ICU length of stay and quality of life at 6 months. Primary and secondary outcomes will be analysed using Bayesian methods.

Ethics and dissemination

Ethics approval has been obtained at all participating centres. Findings will inform the feasibility and design of a future full-scale trial and be disseminated through peer review publications and conference presentations.

Trial registration number

ClinicalTrials.gov Identifier: NCT05078034.

Exploring the use of physical rehabilitation for sepsis survivors: a scoping review

Por: Smith-Turchyn · J. · Farley · C. · Hvizd · J. L. · Newman · A. N. L. · OGrady · H. · Werdens Abram · S. · Nannapaneni · N. · McKenney · S. · Rochwerg · B. · Kho · M. E.
Objectives

To explore the use, parameters, safety and outcomes of physical rehabilitation for adults with sepsis.

Design

We conducted a scoping review following the Joanna Briggs Institute framework.

Participants

Studies were eligible for inclusion in the study if they included: (1) adults 18 and older, (2) with a previous diagnosis of sepsis, (3) using a physical rehabilitation intervention at any point of sepsis management, (4) published in English or French.

Procedure

We searched seven databases and screened titles and abstracts, reviewed full texts and performed data extraction independently and in duplicate. We summarised findings narratively using the "population, context, concept" framework and used descriptive statistics where appropriate. End-users reviewed and commented on study findings.

Results

We included 58 studies, representing 77 434 participants, with the majority (79%) being published in the last decade. A large proportion (36%) of physical rehabilitation interventions included exercise and were overseen by a physical therapist (41%). The parameters of the interventions varied widely. However, all interventions (100%) were hospital based and the interventions implemented appeared safe. Of the 28 studies evaluating effectiveness of the intervention, function improved in most studies (78%) following physical rehabilitation.

Conclusion

Research addressing physical rehabilitation for patients with sepsis is increasing. Physical rehabilitation appears safe and may improve functional outcomes in those with sepsis. Future research should report details of intervention parameters and evaluate rehabilitation post-hospital discharge to maximise impact on function and quality of life for sepsis survivors.

Registration

The protocol was registered on Open Science Framework Registries (Registration DOI: https://doi.org/10.17605/OSF.IO/2EPJ6).

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