Target trial emulation in paediatric research: how can causal effects be estimated from observational data?

Conducting randomised controlled trials (RCTs) in rare paediatric diseases is often impractical or prohibitively expensive. Observational data from longitudinal cohort studies, disease registries, and population-based databases exist for children and adolescents, but standard observational analyses are typically limited by bias. Target trial emulation methods can improve the quality of observational analysis, address common sources of bias, and help fill evidence gaps in paediatric clinical practice.

Low-Tidal-Volume Ventilation and Mortality in Patients With Acute Brain Injury: A Secondary Analysis of an International Observational Study.

Background: Low-tidal-volume ventilation (LTVV) improves outcomes in critically ill patients, but its impact in patients with acute brain injuries (ABIs) is less certain.

Research Question: What is the association between LTVV and mortality in mechanically ventilated patients with ABI?

Study Design And Methods: We did a secondary analysis of a prospective observational study (NCT03400904; https://clinicaltrials.gov/study/NCT03400904).

Evidence-based personalised medicine in critical care: a framework for quantifying and applying individualised treatment effects in patients who are critically ill.

Clinicians aim to provide treatments that will result in the best outcome for each patient. Ideally, treatment decisions are based on evidence from randomised clinical trials. Randomised trials conventionally report an aggregated difference in outcomes between patients in each group, known as an average treatment effect.

The Association Between Mechanical Power Within the First 24 Hours and ICU Mortality in Mechanically Ventilated Adult Patients With Acute Hypoxemic Respiratory Failure: A Registry-Based Cohort Study.

Background: Despite the widespread adoption of lung-protective ventilation strategies, mortality among patients receiving invasive mechanical ventilation (IMV) remains high. Mechanical power (MP) integrates various variables responsible for ventilator-induced lung injury and has been associated with mortality in patients with ARDS. However, the impact of MP on ICU mortality in the larger group of patients with acute hypoxemic respiratory failure (AHRF) has not been well established, and previous studies have reported inconsistent thresholds for predicting outcomes.

One-Year Mortality and Hospital Readmission in Survivors of COVID-19 Critical Illness-A Population-Based Cohort Study.

Objectives: To evaluate 1-year outcomes (mortality, and recurrent hospital and ICU readmission) in adult survivors of COVID-19 critical illness compared with survivors of critical illness from non-COVID-19 pneumonia.

Design: Population-based retrospective observational cohort study.

Setting: Province of Ontario, Canada.

Early reduction in gut microbiota diversity in critically ill patients is associated with mortality.

Background: Critical illness is associated with an altered gut microbiota, yet its association with poor outcomes remains unclear. This study evaluates the early gut microbiota diversity changes in intensive care unit patients and its association with mortality. Additionally, it explores fecal pH as a potential biomarker for these changes.

Understanding ventilator-induced lung injury: The role of mechanical power.

Mechanical ventilation stands as a life-saving intervention in the management of respiratory failure. However, it carries the risk of ventilator-induced lung injury. Despite the adoption of lung-protective ventilation strategies, including lower tidal volumes and pressure limitations, mortality rates remain high, leaving room for innovative approaches.

Designing a Bayesian adaptive clinical trial to evaluate novel mechanical ventilation strategies in acute respiratory failure using integrated nested Laplace approximations.

Background: Adaptive trials usually require simulations to determine values for design parameters, demonstrate error rates, and establish the sample size. We designed a Bayesian adaptive trial comparing ventilation strategies for patients with acute hypoxemic respiratory failure using simulations. The complexity of the analysis would usually require computationally expensive Markov Chain Monte Carlo methods but this barrier to simulation was overcome using the Integrated Nested Laplace Approximations (INLA) algorithm to provide fast, approximate Bayesian inference.

Effects of sevoflurane and its metabolite hexafluoroisopropanol on hypoxia/reoxygenation-induced injury and mitochondrial bioenergetics in murine cardiomyocytes.

Background: The volatile anaesthetic sevoflurane protects cardiac tissue from reoxygenation/reperfusion. Mitochondria play an essential role in conditioning. We aimed to investigate how sevoflurane and its primary metabolite hexafluoroisopropanol (HFIP) affect necrosis, apoptosis, and reactive oxygen species formation in cardiomyocytes upon hypoxia/reoxygenation injury.

Outcomes of patients with respiratory failure declined for extracorporeal membrane oxygenation: a prospective observational study.

Purpose: Descriptive information on referral patterns and short-term outcomes of patients with respiratory failure declined for extracorporeal membrane oxygenation (ECMO) is lacking.

Methods: We conducted a prospective single-centre observational cohort study of ECMO referrals to Toronto General Hospital (receiving hospital) for severe respiratory failure (COVID-19 and non-COVID-19), between 1 December 2019 and 30 November 2020. Data related to the referral, the referral decision, and reasons for refusal were collected.

Mechanical Ventilation after Traumatic Spinal Cord Injury-A Multicentric Cohort Study-based Prediction Model for Weaning Success: The BICYCLE Score.

Limited information exists about the epidemiology, outcomes, and predictors of weaning from mechanical ventilation in patients with spinal cord injury. Our aim was to investigate predictors of weaning outcomes for patients with traumatic spinal cord injury (tSCI) and develop and validate a prognostic model and score for weaning success. This was a registry-based, multicentric cohort study including all adult patients with tSCI requiring mechanical ventilation (MV) and admitted to one of the intensive care units (ICUs) of the Trauma Registry at St.

Limiting Dynamic Driving Pressure in Patients Requiring Mechanical Ventilation.

Objectives: Previous studies reported an association between higher driving pressure (∆P) and increased mortality for different groups of mechanically ventilated patients. However, it remained unclear if sustained intervention on ∆P, in addition to traditional lung-protective ventilation, improves outcomes. We investigated if ventilation strategies limiting daily static or dynamic ∆P reduce mortality compared with usual care in adult patients requiring greater than or equal to 24 hours of mechanical ventilation.

Linking Acute Physiology to Outcomes in the ICU: Challenges and Solutions for Research.

ICU clinicians rely on bedside physiological measurements to inform many routine clinical decisions. Because deranged physiology is usually associated with poor clinical outcomes, it is tempting to hypothesize that manipulating and intervening on physiological parameters might improve outcomes for patients. However, testing these hypotheses through mathematical models of the relationship between physiology and outcomes presents a number of important methodological challenges.

Hexafluoroisopropanol decreases liver ischemia-reperfusion injury by downregulation of high mobility group box-1 protein.

Liver ischemia-reperfusion (IR) injury is associated with poor outcome after liver transplantation and liver resections. Hexafluoroisopropanol (HFIP) is a tri-fluorinated metabolites of volatile anesthetics and has modulatory effects on inflammation that have been observed mainly in cell culture experiments. In this survey, we investigated the effects of HFIP in a rat model of normothermic hepatic ischemia-reperfusion injury.

Transesophageal Echocardiography-Guided Extracorporeal Membrane Oxygenation Cannulation in COVID-19 Patients.

Objectives: A paucity of data supports the use of transesophageal echocardiography (TEE) for bedside extracorporeal membrane oxygenation (ECMO) cannulation. Concerns have been raised about performing TEEs in patients with COVID-19. The authors describe the use and safety of TEE guidance for ECMO cannulation for COVID-19.

Point-of-Care Ultrasound: A Case Series of Potential Pitfalls.

• Integration of POCUS findings in the clinical context is crucial. • Valvular abnormalities may not be identified by POCUS. • Valvular disease should not be excluded based solely on a POCUS.

Evaluation of an advanced critical care echocardiography program: a mixed methods study.

Purpose: Limited data exist on advanced critical care echocardiography (CCE) training programs for intensivists. We sought to describe a longitudinal echocardiography program and investigate the effect of distributed conditional supervision vs predefined en-bloc supervision, as well as the effect of an optional echocardiography laboratory rotation, on learners' engagement.

Methods: In this mixed methods study, we enrolled critical care fellows and faculty from five University of Toronto-affiliated intensive care units (ICU) between July 2015 and July 2018 in an advanced training program, comprising theoretical lectures and practical sessions.