New and conventional strategies for lung recruitment in acute respiratory distress syndrome

Mechanical ventilation is a supportive and life saving therapy in patients with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Despite advances in critical care, mortality remains high. During the last decade, the fact that mechanical ventilation can produce morphologic and physiologic alterations in the lungs has been recognized. In this context, the use of low tidal volumes (VT) and limited inspiratory plateau pressure (Pplat) has been proposed when mechanically ventilating the lungs of patients with ALI/ARDS, to prevent lung as well as distal organ injury. However, the reduction in VT may result in alveolar derecruitment, cyclic opening and closing of atelectatic alveoli and distal small airways leading to ventilator-induced lung injury (VILI) if inadequate low positive end-expiratory pressure (PEEP) is applied. On the other hand, high PEEP levels may be associated with excessive lung parenchyma stress and strain and negative hemodynamic effects, resulting in systemic organ injury. Therefore, lung recruitment maneuvers have been proposed and used to open up collapsed lung, while PEEP counteracts alveolar derecruitment due to low VT ventilatio

A Delphi-method-based consensus guideline for definition of treatment-resistant depression for clinical trials

Criteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if conducted for regulatory purposes. We reviewed the literature and brought together a group of international experts (including clinicians, academics, researchers, employees of pharmaceutical companies, regulatory bodies representatives, and one person with lived experience) to evaluate the state-of-the-art and main controversies regarding the current classification. We then provided recommendations on how to design clinical trials, and on how to guide research in unmet needs and knowledge gaps. This report will feed into one of the main objectives of the EUropean Patient-cEntric clinicAl tRial pLatforms, Innovative Medicines Initiative (EU-PEARL, IMI) MDD project, to design a protocol for platform trials of new medications for TRD/PRD. © 2021, The Author(s).EU/EFPIA/Innovative Medicines Initiative 2 Joint Undertaking

A Delphi-method-based consensus guideline for definition of treatment-resistant depression for clinical trials

Criteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if conducted for regulatory purposes. We reviewed the literature and brought together a group of international experts (including clinicians, academics, researchers, employees of pharmaceutical companies, regulatory bodies representatives, and one person with lived experience) to evaluate the state-of-the-art and main controversies regarding the current classification. We then provided recommendations on how to design clinical trials, and on how to guide research in unmet needs and knowledge gaps. This report will feed into one of the main objectives of the EUropean Patient-cEntric clinicAl tRial pLatforms, Innovative Medicines Initiative (EU-PEARL, IMI) MDD project, to design a protocol for platform trials of new medications for TRD/PRD