Effect of the a7nAChR agonist GTS-21 on inflammation during human endotoxemia

Abstract

IntroductionThere is considerable uncertainty about the reproducibility of the various instruments used to measure dyspnea, their ability to reflect changes in symptoms, whether they accurately reflect the patient's experience and if its evolution is similar between acute heart failure syndrome patients and nonacute heart failure syndrome patients. URGENT was a prospective multicenter trial designed to address these issues. Methods Patients were interviewed within 1 hour of first physician evaluation, in the emergency department or acute care setting, with dyspnea assessed by the patient using both a five-point Likert scale and a 10-point visual analog scale (VAS) in the sitting (60º) and then supine (20º) position if dyspnea had not been considered severe or very severe by the sitting versus decubitus dyspnea measurement. Results Very good agreements were found between the five-point Likert and VAS at baseline (0.891, P <0.0001) and between changes (from baseline to hour 6) in the five-point Likert and in VAS (0.800, P <0.0001) in acute heart failure (AHF) patients. Lower agreements were found when changes from baseline to H6 measured by Likert or VAS were compared with the seven-point comparative Likert (0.512 and 0.500 respectively) in AHF patients. The worse the dyspnea at admission, the greater the amplitude of improvement in the first 6 hours; this relationship is stronger when dyspnea is measured with VAS (Spearman's rho coefficient = 0.672) than with the five-point Likert (0.272) (both P <0.0001) in AHF patients. By the five-point Likert, only nine patients (3% (1% to 5%)) reported an improvement in their dyspnea, 177 (51% (46% to 57%)) had no change, and 159 (46% (41% to 52%)) reported worse dyspnea supine compared with sitting up in AHF patients. The PDA test with VAS was markedly different between AHF and non-AHF patients. Conclusions Both clinical tools five-point Likert and VAS showed very good agreement at baseline and between changes from baseline to tests performed 6 hours later in AHF patients. The PDA test with VAS was markedly different between AHF and non-AHF patients. Dyspnea is improved within 6 hours in more than threequarters of the patients regardless of the tool used to measure the change in dyspnea. The greater the dyspnea at admission, the greater the amplitude of improvement in the first 6 hours. Introduction Endotracheal intubation (ETI) engages the patient's life and demands a good experience. A preliminary prospective study has shown in one hospital that emergency physicians (EPs) rarely performed ETI. Do the EPs in Ile de France (Paris region) have sufficient experience and regular training to realise this procedure safely in the emergency room (ER)? Methods We conducted a descriptive telephone-based questionnaire study to assess EPs' endotracheal intubation skills through all ERs in Ile de France public hospitals. A questionnaire was completed by the investigator during a 10-minute telephone call with at least one EP in each ER. The structure of hospitals, number of ETIs perform...

Modulation of preeclampsia by the cholinergic anti-inflammatory pathway: Therapeutic perspectives

“…Despite promising preclinical reports, clinical studies on the therapeutic potential of α7-nAChR modulators in inflammatory disorders are limited. Interestingly, the activation of α7-nAChR by GTS-21 in healthy human subjects reduces TNF-α and elevates IL-10 plasma levels during endotoxemia indicating a shift to an upregulated anti-inflammatory state [78]. Besides, a recent clinical trial has been conducted to evaluate the efficiency of vagal nerve stimulation, an activator of CAP and α7-nAChR, in alleviating inflammatory and immune insults in osteoarthritis [79].…”