Effects of yperoxa on ulmonary nflammation and organ injury in a human in vivo model (HIPI): study protocol of a randomised, double-blind, placebo-controlled trial.

Introduction: Liberal administration of supplemental oxygen (O) is ubiquitous across numerous healthcare settings. However, appropriate O titration targets remain controversial and despite numerous large-scale randomised trials, there is an ongoing lack of consensus regarding optimal oxygenation strategies and the absence of high-quality mechanistic data pertaining to the potential proinflammatory effects of hyperoxia.

Methods And Analysis: We hypothesise that (1) short-term exposure to hyperoxia will induce mild pulmonary inflammation and cellular injury and that (2) hyperoxia will accentuate pulmonary inflammation and cellular injury in the setting of inhaled lipopolysaccharide challenge.

The Effect of Lower Tidal Volume Ventilation Facilitated by Extracorporeal Carbon Dioxide Removal Compared With Conventional Lung Protective Ventilation on Cardiac Function.

Objectives: Lower tidal volume ventilation (targeting 3 mL/kg predicted body weight, PBW) facilitated by extracorporeal carbon dioxide removal (ECCOR) has been investigated as a potential therapy for acute hypoxemic respiratory failure (AHRF) in the pRotective vEntilation with veno-venouS lung assisT in respiratory failure (REST) trial. We investigated the effect of this strategy on cardiac function, and in particular the right ventricle.

Design: Substudy of the REST trial.

Elevated ferritin, mediated by IL-18 is associated with systemic inflammation and mortality in acute respiratory distress syndrome (ARDS).

Background: Inflammatory subphenotypes have been identified in acute respiratory distress syndrome (ARDS). Hyperferritinaemia in sepsis is associated with hyperinflammation, worse clinical outcomes, and may predict benefit with immunomodulation. Our aim was to determine if raised ferritin identified a subphenotype in patients with ARDS.

Effect of total cholesterol and statin therapy on mortality in ARDS patients: a secondary analysis of the SAILS and HARP-2 trials.

Background: Two acute respiratory distress syndrome (ARDS) trials showed no benefit for statin therapy, though secondary analyses suggest inflammatory subphenotypes may have a differential response to simvastatin. Statin medications decrease cholesterol levels, and low cholesterol has been associated with increased mortality in critical illness. We hypothesized that patients with ARDS and sepsis with low cholesterol could be harmed by statins.

Baseline plasma IL-18 may predict simvastatin treatment response in patients with ARDS: a secondary analysis of the HARP-2 randomised clinical trial.

Background: Interleukin (IL)-18 is a marker of inflammasome activation, and high baseline plasma IL-18 is associated with increased mortality in patients with sepsis-induced ARDS. The aim of this analysis was to determine if simvastatin was associated with benefit in patients with ARDS and high plasma IL-18.

Methods: In this secondary analysis of the HARP-2 study, we compared 28-day mortality and response to simvastatin according to baseline plasma IL-18 using cox proportional hazards analysis.

Transepithelial nasal potential difference in patients with, and at risk of acute respiratory distress syndrome.

Background: Impaired alveolar fluid clearance, determined in part by alveolar sodium transport, is associated with acute respiratory distress syndrome (ARDS). Nasal sodium transport may reflect alveolar transport. The primary objective of this prospective, observational study was to determine if reduced nasal sodium transport, as measured by nasal potential difference (NPD), was predictive of the development of and outcome from ARDS.

Central effects of trout tachykinins on heart rate variability in trout.

Recent studies in trout have shown that tachykinins might be selectively implicated in important neuroregulatory functions related to the central control of ventilation. In teleost fish, cardiorespiratory coupling probably contributes to heart rate variability (HRV), and the hypoventilatory effects observed after central injection of tachykinins suggest that these peptides also may produce changes in HRV. Consequently, the present study was undertaken to compare the central actions of picomolar doses (25-250 pmol) of trout neuropeptide gamma (NPgamma), substance P (SP), and neurokinin A (NKA) on HRV in unanesthetized rainbow trout.

Use of simulation to compare the performance of minimization with stratified blocked randomization.

Minimization is an alternative method to stratified permuted block randomization, which may be more effective at balancing treatments when there are many strata. However, its use in the regulatory setting for industry trials remains controversial, primarily due to the difficulty in interpreting conventional asymptotic statistical tests under restricted methods of treatment allocation. We argue that the use of minimization should be critically evaluated when designing the study for which it is proposed.

Burden and health care resource utilization in neovascular age-related macular degeneration: findings of a multicountry study.

Objective: To describe the burden of bilateral neovascular age-related macular degeneration (NV-AMD) on patient-reported functioning and health resource utilization.

Methods: A cross-sectional study of 401 patients with bilateral NV-AMD and 471 elderly control subjects without AMD was conducted in 5 countries. Subjects completed a telephone survey, including the National Eye Institute 25-Item Visual Function Questionnaire, the EuroQol instrument, the Hospital Anxiety and Depression Scale, and history of falls, fractures, and health care resource utilization.

Regionally specific occurrence of an active sodefrin variant in the red-bellied newt.

Sodefrin (SIPSKDALLK) is a female-attracting pheromone that is secreted by the abdominal gland of the male red-bellied newt. We found that mRNA encoding a sodefrin variant, [Val(8)] sodefrin, is expressed exclusively in specimens captured in the Nara area of Japan. The synthetic peptide was tested for its activity.