Clinical trials in critical care: can a Bayesian approach enhance clinical and scientific decision making?

Recent Bayesian reanalyses of prominent trials in critical illness have generated controversy by contradicting the initial conclusions based on conventional frequentist analyses. Many clinicians might be sceptical that Bayesian analysis, a philosophical and statistical approach that combines prior beliefs with data to generate probabilities, provides more useful information about clinical trials than the frequentist approach. In this Personal View, we introduce clinicians to the rationale, process, and interpretation of Bayesian analysis through a systematic review and reanalysis of interventional trials in critical illness.

Concordance of Identified Cases of Pediatric HA-VTE with American College of Physicians and Cincinnati Children's Hospital HA-VTE Prophylaxis Guidelines Over a 10-Year Period.

: Our aim is to (1) ascertain the proportion of pediatric patients at a tertiary hospital in Western Massachusetts over a 10-year period with hospital-acquired venous thromboembolism (VTE) of particular characteristics and (2) determine whether ACCP or Cincinnati Children's guidelines would have recommended VTE prophylaxis in these patients. : Urban teaching hospital in the United States. : Data from 98 477 pediatric hospital admissions (roughly 10 000 admission per year) from 2008 to 2017 were reviewed.

Extracorporeal life support for adults with acute respiratory distress syndrome.

Extracorporeal life support (ECLS) can support gas exchange in patients with the acute respiratory distress syndrome (ARDS). During ECLS, venous blood is drained from a central vein via a cannula, pumped through a semipermeable membrane that permits diffusion of oxygen and carbon dioxide, and returned via a cannula to a central vein. Two related forms of ECLS are used.

Critically Ill Patients with COVID-19: A Narrative Review on Prone Position.

Introduction: Prone position is known to improve mortality in patients with acute respiratory distress syndrome (ARDS). The impact of prone position in critically ill patients with coronavirus disease of 2019 (COVID-19) remains to be determined. In this review, we describe the mechanisms of action of prone position, systematically appraise the current experience of prone position in COVID-19 patients, and highlight unique considerations for prone position practices during this pandemic.

Effect of Driving Pressure Change During Extracorporeal Membrane Oxygenation in Adults With Acute Respiratory Distress Syndrome: A Randomized Crossover Physiologic Study.

Objectives: Venovenous extracorporeal membrane oxygenation is an effective intervention to improve gas exchange in patients with severe acute respiratory distress syndrome. However, the mortality of patients with severe acute respiratory distress syndrome supported with venovenous extracorporeal membrane oxygenation remains high, and this may be due in part to a lack of standardized mechanical ventilation strategies aimed at further minimizing ventilator-induced lung injury. We tested whether a continuous positive airway pressure ventilation strategy mitigates ventilator-induced lung injury in patients with severe acute respiratory distress syndrome on venovenous extracorporeal membrane oxygenation, compared with current ventilation practice that employs tidal ventilation with limited driving pressure.

Barriers and Facilitators to Early Rehabilitation in the ICU: A Theory Driven Delphi Study.

Objectives: There is conflicting evidence for the effectiveness of early rehabilitation in the intensive care and marked variation in rates of implementation in practice. We aimed to identify barriers and facilitators to early rehabilitation in mechanically ventilated patients and their relevance to practice, as perceived by key ICU clinicians across North America.

Design: A Delphi study using the Theoretical Domains Framework, consisting of an initial qualitative round and subsequent quantitative rounds, was conducted to gather clinician agreement and perceived importance of barriers and facilitators to early rehabilitation.

Extracorporeal membrane oxygenation support in COVID-19: an international cohort study of the Extracorporeal Life Support Organization registry.

Background: Multiple major health organisations recommend the use of extracorporeal membrane oxygenation (ECMO) support for COVID-19-related acute hypoxaemic respiratory failure. However, initial reports of ECMO use in patients with COVID-19 described very high mortality and there have been no large, international cohort studies of ECMO for COVID-19 reported to date.

Methods: We used data from the Extracorporeal Life Support Organization (ELSO) Registry to characterise the epidemiology, hospital course, and outcomes of patients aged 16 years or older with confirmed COVID-19 who had ECMO support initiated between Jan 16 and May 1, 2020, at 213 hospitals in 36 countries.

Lung-Protective Ventilation and Associated Outcomes and Costs Among Patients Receiving Invasive Mechanical Ventilation in the ED.

Background: Invasive mechanical ventilation is often initiated in the ED, and mechanically ventilated patients may be kept in the ED for hours before ICU transfer. Although lung-protective ventilation is beneficial, particularly in ARDS, it remains uncertain how often lung-protective tidal volumes are used in the ED, and whether lung-protective ventilation in this setting impacts patient outcomes.

Research Question: What is the association between the use of lung-protective ventilation in the ED and outcomes among invasively ventilated patients?

Study Design And Methods: A retrospective analysis (2011-2017) of a prospective registry from eight EDs enrolling consecutive adult patients (≥ 18 years) who received invasive mechanical ventilation in the ED was performed.

TBK1/IKKε Negatively Regulate LPS-Induced Neutrophil Necroptosis and Lung Inflammation.

Cell necroptosis, a form of regulated inflammatory cell death, is one of the mechanisms that controls cell release of inflammatory mediators from innate immune cells, such as polymorphonuclear neutrophils (PMNs), and critically regulates the progress of inflammation. Cell necroptosis features receptor-interacting protein (RIPK) 1 activation and necroptosome formation. This leads to loss of plasma membrane integrity, the release of cell contents into the extracellular space, and subsequent increased inflammation.

Comparing the Effects of Tidal Volume, Driving Pressure, and Mechanical Power on Mortality in Trials of Lung-Protective Mechanical Ventilation.

Background: The unifying goal of lung-protective ventilation strategies in ARDS is to minimize the strain and stress applied by mechanical ventilation to the lung to reduce ventilator-induced lung injury (VILI). The relative contributions of the magnitude and frequency of mechanical stress and the end-expiratory pressure to the development of VILI is unknown. Consequently, it is uncertain whether the risk of VILI is best quantified in terms of tidal volume (V), driving pressure (ΔP), or mechanical power.

Time-varying intensity of mechanical ventilation and mortality in patients with acute respiratory failure: a registry-based, prospective cohort study.

Unlabelled: Background Mortality in acute respiratory failure remains high despite the use of lung-protective ventilation. Recent studies have shown an association between baseline ventilation parameters (driving pressure or mechanical power) and outcomes for patients with acute respiratory distress syndrome. Strategies focused on limiting these parameters have been proposed to further improve outcomes.

Comparative assessment of the effects of bumped kinase inhibitors on early zebrafish embryo development and pregnancy in mice.

Bumped kinase inhibitors (BKIs) are effective against a variety of apicomplexan parasites. Fifteen BKIs with promising in vitro efficacy against Neospora caninum tachyzoites, low cytotoxicity in mammalian cells, and no toxic effects in non-pregnant BALB/c mice were assessed in pregnant mice. Drugs were emulsified in corn oil and were applied by gavage for 5 days.

Cell-Cell Interaction Mechanisms in Acute Lung Injury.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are caused by an exaggerated inflammatory response arising from a wide variety of pulmonary and systemic insults. Lung tissue is composed of a variety of cell populations, including parenchymal and immune cells. Emerging evidence has revealed that multiple cell populations in the lung work in concert to regulate lung inflammation in response to both direct and indirect stimulations.

Glucose oxidase-based biocatalytic acid-leaching process for recovering valuable metals from spent lithium-ion batteries.

An environmentally benign leaching process for recovering valuable metals from the cathodes of spent lithium-ion batteries was developed. Glucose oxidase produced by Aspergillus niger can oxidize glucose to give the leaching agent gluconic acid. The presence of gluconic acid was proven by mass spectrometry.

Long-term mortality and costs following use of Impella® for mechanical circulatory support: a population-based cohort study.

Purpose: The Impella® device is a form of mechanical circulatory support (MCS) used in critically ill adults with cardiogenic shock. We sought to evaluate short- and long-term outcomes following the use of Impella, including mortality, healthcare utilization, and costs.

Methods: Population-based, retrospective cohort study of adult patients (≥ 16 yr) receiving Impella in Ontario, Canada (1 April 2012-31March 2019).

COVID-19-associated acute respiratory distress syndrome: is a different approach to management warranted?

The COVID-19 pandemic has seen a surge of patients with acute respiratory distress syndrome (ARDS) in intensive care units across the globe. As experience of managing patients with COVID-19-associated ARDS has grown, so too have efforts to classify patients according to respiratory system mechanics, with a view to optimising ventilatory management. Personalised lung-protective mechanical ventilation reduces mortality and has become the mainstay of treatment in ARDS.

Transfusion Thresholds for Adult Respiratory Extracorporeal Life Support: An Expert Consensus Document.

Severe acute respiratory distress syndrome (ARDS) can complicate novel pandemic coronavirus disease (COVID-19). Extracorporeal life support (ECLS) represents the final possible rescue strategy. Variations in practice, combined with a paucity of rigourous guidelines, may complicate blood-product resource availability and allocation during a pandemic.

Intracranial hemorrhage on extracorporeal membrane oxygenation: an international survey.

Introduction: Intracranial hemorrhage is one of the most dreaded complications associated with extracorporeal membrane oxygenation. However, robust data to guide clinical practice are lacking. We aimed to describe the current perceptions and practices surrounding the risk, prevention, diagnosis, management, and prognosis of intracranial hemorrhage in patients on extracorporeal membrane oxygenation.

Lung- and Diaphragm-Protective Ventilation.

Mechanical ventilation can cause acute diaphragm atrophy and injury, and this is associated with poor clinical outcomes. Although the importance and impact of lung-protective ventilation is widely appreciated and well established, the concept of diaphragm-protective ventilation has recently emerged as a potential complementary therapeutic strategy. This Perspective, developed from discussions at a meeting of international experts convened by PLUG (the Pleural Pressure Working Group) of the European Society of Intensive Care Medicine, outlines a conceptual framework for an integrated lung- and diaphragm-protective approach to mechanical ventilation on the basis of growing evidence about mechanisms of injury.

Fluid management and deresuscitation practices: A survey of critical care physicians.

Accumulation of a positive fluid balance is common in critically ill patients, and is associated with adverse outcomes, including mortality. However, there are few randomised clinical trials to guide clinicians as to the most appropriate fluid strategy following initial resuscitation and on the use of deresuscitation (removal of accumulated fluid using diuretics and/or renal replacement therapy). To inform the design of randomised trials, we surveyed critical care physicians with regard to perceptions of fluid overload in critical care, self-reported practice, acceptability of a variety of approaches to deresuscitation, appropriate safety parameters, and overall acceptability of a randomised trial of deresuscitation.