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Research questions Patients with severe pulmonary hypertension associated with chronic lung disease have a poor prognosis. Targeted pulmonary arterial hypertension therapies might improve exercise capacity and outcome, but there are no guidelines on treatments which are not recommended because of an unproven benefit, with discordant results from few studies in this context. The aim of our study was to evaluate targeted pulmonary arterial hypertension therapies for severe group 3 pulmonary hypertension patients. Study design and methods We conducted an observational retrospective monocentre study on patients with severe group 3 pulmonary hypertension diagnosed on right heart catheterisation treated with targeted therapies. Primary outcome was an improvement of the distance on 6-min walk test of ≥30 m. Secondary end-points included changes in haemodynamics (pulmonary vascular resistance (PVR) and mean pulmonary arterial pressure (mPAP)) and identification of potential predictive factors of therapeutic response. Results 139 patients were enrolled. Most patients had monotherapy with phosphodiesterase 5 inhibitors (n=128; 92%). Mean change in 6-min walk distance was +1.5 m after treatment (p=0.59). Forced expiratory volume in 1 s and forced vital capacity were not predictive factors for response. We found a significant improvement of PVR and mPAP of −1.0 Wood Units (p

Abstract The SARS-CoV-2 pandemic has disrupted clinical trials worldwide. The European Cystic Fibrosis Society-Clinical Trials Network (ECFS-CTN) has tracked clinical trial disruption by surveying its 58 trial sites across 17 European countries and collated information on measures to mitigate the impact of the pandemic and ensure trial continuity. Here, we present recommendations on how to reduce the risk of SARS-CoV-2 exposure to patients and trial staff by implementing remote trial visits where possible, using home assessments, video and phone calls, electronic consent, and home delivery of study drugs. We discuss the practicalities of remote source data verification, protocol amendments, changing trial site location, and staff absences and home working. We outline recommendations on how to protect trial outcomes, including home assessments, safety reporting, protocol deviations, and recruitment challenges. Finally, we discuss the importance of continued access to study drugs via extension trials for some patients. This guidance was co-created from the shared knowledge and experience of sites in our network and was re-distributed directly to all ECFS-CTN sites to help mitigate the impact of further waves of the SARS-CoV-2 pandemic. We will also use this guidance to assist companies, academia, and consortia with future protocol design and risk mitigation plans. This guidance can be applied to clinical trials in other diseases and could help sites that are not supported by clinical trial networks.

Abstract Background Chronic Lung Allograft Dysfunction (CLAD) is the main cause of morbidity and mortality after the first year following lung transplantation (LTx). Risk factors of CLAD have been extensively studied, but the association between gram-negative bacteria (GNB) bronchial colonization and the development of CLAD is controversial. The purpose of our study was to investigate the association between post-transplant recolonization with the same species or de-novo colonization with a new GNB species and CLAD. The same analysis was performed on a sub-group of patients at the strain level using Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry technique. Results Forty adult cystic fibrosis (CF) patients who underwent a first bilateral LTx in the University Hospital of Marseille, between January 2010 and December 2014, were included in the study. Patients with GNB de-novo colonization had a higher risk of developing CLAD (OR = 6.72, p = 0.04) and a lower rate of CLAD-free survival (p = 0.005) compared to patients with GNB recolonization. No conclusion could be drawn from the subgroup MALDI-TOF MS analysis at the strain level. Conclusion Post-LTx GNB airway recolonization seems to be a protective factor against CLAD, whereas de-novo colonization with a new species of GNB seems to be a risk factor for CLAD.