Increased Hospital-Based Physical Rehabilitation and Information Provision After Intensive Care Unit Discharge: The RECOVER Randomized Clinical Trial.

Importance: Critical illness results in disability and reduced health-related quality of life (HRQOL), but the optimum timing and components of rehabilitation are uncertain.

Objective: To evaluate the effect of increasing physical and nutritional rehabilitation plus information delivered during the post-intensive care unit (ICU) acute hospital stay by dedicated rehabilitation assistants on subsequent mobility, HRQOL, and prevalent disabilities.

Design, Setting, And Participants: A parallel group, randomized clinical trial with blinded outcome assessment at 2 hospitals in Edinburgh, Scotland, of 240 patients discharged from the ICU between December 1, 2010, and January 31, 2013, who required at least 48 hours of mechanical ventilation.

Measuring Hospital-Wide Mortality-Pitfalls and Potential.

Risk-adjusted hospital-wide mortality has been proposed as a key indicator of system-level quality. Several risk-adjusted measures are available, and one-the hospital standardized mortality ratio (HSMR) - is publicly reported in a number of countries, but not in the United States. This paper reviews potential uses of such measures.

A rehabilitation intervention to promote physical recovery following intensive care: a detailed description of construct development, rationale and content together with proposed taxonomy to capture processes in a randomised controlled trial.

Background: Increasing numbers of patients are surviving critical illness, but survival may be associated with a constellation of physical and psychological sequelae that can cause ongoing disability and reduced health-related quality of life. Limited evidence currently exists to guide the optimum structure, timing, and content of rehabilitation programmes. There is a need to both develop and evaluate interventions to support and expedite recovery during the post-ICU discharge period.

A randomised controlled trial evaluating a rehabilitation complex intervention for patients following intensive care discharge: the RECOVER study.

Introduction: Patients who survive an intensive care unit admission frequently suffer physical and psychological morbidity for many months after discharge. Current rehabilitation pathways are often fragmented and little is known about the optimum method of promoting recovery. Many patients suffer reduced quality of life.

Diagnostic importance of pulmonary interleukin-1beta and interleukin-8 in ventilator-associated pneumonia.

Background: Ventilator-associated pneumonia (VAP) is the most commonly fatal nosocomial infection. Clinical diagnosis of VAP remains notoriously inaccurate. The hypothesis was tested that significantly augmented inflammatory markers distinguish VAP from conditions closely mimicking VAP.

C5a mediates peripheral blood neutrophil dysfunction in critically ill patients.

Rationale: Critically ill patients are highly susceptible to hospital-acquired infection. Neutrophil function in critical illness remains poorly understood.

Objectives: To characterize and define mechanisms of peripheral blood neutrophil (PBN) dysfunction in critically ill patients.

Rhodanine derivatives as novel inhibitors of PDE4.

The discovery, synthesis and in vitro activity of a novel series of rhodanine based phosphodiesterase-4 (PDE4) inhibitors is described. Structure-activity relationship studies directed toward improving potency led to the development of submicromolar inhibitors 2n and 3i (IC(50)=0.89 & 0.

2-Aryl-3,3,3-trifluoro-2-hydroxypropionic acids: a new class of protein tyrosine phosphatase 1B inhibitors.

A new series of non-peptidic, mono-acid protein tyrosine phosphatase 1B (PTP1B) inhibitors has been identified by structure-based design. Compounds with 2-(indol-3-yl)- and 2-phenyl-3,3,3-trifluoro-2-hydroxypropionic acid core units targeted at the enzyme's primary site and a hydrophobic chlorophenylthiazole extension in its 2 degrees site exhibit 3-60microM IC(50)s for PTP1B inhibition in an Sf9 cell-based assay.

The inhibitory profile of Ibudilast against the human phosphodiesterase enzyme family.

Ibudilast is widely used in Japan to treat ischemic stroke and bronchial asthma. Its mode of action is through the inhibition of cyclic nucleotide phosphodiesterases (PDEs). Growing evidence suggests this compound has utility in a range of neurological conditions linked to its ability to elevate cellular cyclic nucleotide concentrations, however limited data exists on Ibudilast's action on individual PDE families.

The effect of selective phosphodiesterase inhibitors, alone and in combination, on a murine model of allergic asthma.

Background: The anti-inflammatory effects of the selective phosphodiesterase (PDE) inhibitors cilostazol (PDE 3), RO 20-1724 (PDE 4) and sildenafil (PDE 5) were examined in a murine model of allergic asthma. These compounds were used alone and in combination to determine any potential synergism, with dexamethasone included as a positive control.

Methods: Control and ovalbumin sensitised Balb/C mice were administered orally with each of the possible combinations of drugs at a dose of 3 mg/Kg for 10 days.

Long PDE4 cAMP specific phosphodiesterases are activated by protein kinase A-mediated phosphorylation of a single serine residue in Upstream Conserved Region 1 (UCR1).

1. Challenge of COS1 cells with the adenylyl cyclase activator forskolin led to the activation of recombinant PDE4A8, PDE4B1, PDE4C2 and PDE4D5 cAMP-specific phosphodiesterase long isoforms. 2.