Chronic cough and esomeprazole: A double-blind placebo-controlled parallel study

Background and objective: Gastro-oesophageal reflux has been implicated in the pathogenesis of chronic cough. Guidelines on management suggest a therapeutic trial of anti-reflux medication. Esomeprazole is a proton pump inhibitor licensed for the long-term treatment of acid reflux in adults and we compared the effects of esomeprazole and placebo on patients with chronic cough. Methods: This was a prospective, single-centre, randomized, double-blind, placebo-controlled, parallel group study conducted over 8 weeks. Fifty adult non-smokers with chronic cough and normal spirometry were randomized. Patients completed cough-related quality-of-life and symptom questionnaires and subjective scores of cough frequency and severity at the beginning and end of the study. They also kept a daily diary of symptom scores. Citric acid cough challenge and laryngoscopic examination were performed at baseline and the end of the study. The primary outcome was improvement in cough score. Results: There were no differences in cough scores in the placebo and treatment arms of the study although some significant improvements were noted when compared to baseline. In the cough diary scores there was a trend towards greater improvement in the treatment arm in patients with dyspepsia. Conclusions: Esomeprazole did not have a clinically important effect greater than placebo in patients with cough. It suggests a marked placebo effect in the treatment of cough. There is paucity of evidence on which to base the treatment of reflux-associated cough. We demonstrate that acid suppressive therapy does not lead to a significant clinical effect in these patients. There may be some improvement in those with coexisting dyspeptic symptoms and therapy should be restricted to this group. © 2011 Asian Pacific Society of Respirology

La Charente

20 août 18941894/08/20 (A23,N10440)-1894/08/20.Appartient à l’ensemble documentaire : PoitouCh

Additional file 1: Table S1. of Effectiveness of current and future regimens for treating genotype 3 hepatitis C virus infection: a large-scale systematic review

Search terms in PubMed (Medline in Process). Table summarising search terms used in PubMed and Medline in Process. (DOCX 13 kb

Additional file 7: Figure S4. of Effectiveness of current and future regimens for treating genotype 3 hepatitis C virus infection: a large-scale systematic review

Real-world pooled SVR12 rates for (a) patients with cirrhosis and (b) patients without cirrhosis. Forest plot showing SVR12 rates from real-world datasets stratified by the presence or absence of cirrhosis. (PDF 22 kb

Correction: Accelerating Influenza Research: Vaccines, Antivirals, Immunomodulators and Monoclonal Antibodies. The Manufacture of a New Wild-Type H3N2 Virus for the Human Viral Challenge Model.

[This corrects the article DOI: 10.1371/journal.pone.0145902.]

Accelerating Influenza Research: Vaccines, Antivirals, Immunomodulators and Monoclonal Antibodies. The Manufacture of a New Wild-Type H3N2 Virus for the Human Viral Challenge Model

<div><p>Background</p><p>Influenza and its associated diseases are a major cause of morbidity and mortality. The United States Advisory Committee on Immunization Practices recommends influenza vaccination for everyone over 6 months of age. The failure of the flu vaccine in 2014–2015 demonstrates the need for a model that allows the rapid development of novel antivirals, universal/intra-seasonal vaccines, immunomodulators, monoclonal antibodies and other novel treatments. To this end we manufactured a new H3N2 influenza virus in compliance with Good Manufacturing Practice for use in the Human Viral Challenge Model.</p><p>Methods and Strain Selection</p><p>We chose an H3N2 influenza subtype, rather than H1N1, given that this strain has the most substantial impact in terms of morbidity or mortality annually as described by the Centre for Disease Control. We first subjected the virus batch to rigorous adventitious agent testing, confirmed the virus to be wild-type by Sanger sequencing and determined the virus titres appropriate for human use via the established ferret model. We built on our previous experience with other H3N2 and H1N1 viruses to develop this unique model.</p><p>Human Challenge and Conclusions</p><p>We conducted an initial safety and characterisation study in healthy adult volunteers, utilising our unique clinical quarantine facility in London, UK. In this study we demonstrated this new influenza (H3N2) challenge virus to be both safe and pathogenic with an appropriate level of disease in volunteers. Furthermore, by inoculating volunteers with a range of different inoculum titres, we established the minimum infectious titre required to achieve reproducible disease whilst ensuring a sensitive model that can be translated to design of subsequent field based studies.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT02525055?term=NCT02525055&rank=1" target="_blank">NCT02525055</a></p></div