Dynamic flow synthesis of porous organic cages

The dynamic covalent synthesis of two imine-based porous organic cages was successfully transferred from batch to continuous flow. The same flow reactor was then used to scramble the constituents of these two cages in differing ratios to form cage mixtures. Preparative HPLC purification of one of these mixtures allowed rapid access to a desymmetrised cage molecule.We thank the Engineering and Physical Sciences Research Council (EPSRC) for financial support under the Grants EP/H000925/1 (AIC), EP/K009494/1 (SVL) and EP/M004120/1 (SVL), and Pfizer Worldwide Research & Development (CB). The authors would like to thank EPSRC Dial-a-Molecule Grand Challenge Network (EP/K004840/1) for funding a placement with SVL via the Interdisciplinary Mobility Funding scheme (AGS).This is the author accepted manuscript. The final version is available from RSC via http://dx.doi.org/10.1039/C5CC07447

Levosimendan beyond inotropy and acute heart failure: Evidence of pleiotropic effects on the heart and other organs: An expert panel position paper

Peer reviewe

Rationale and design of the multicentre randomized trial investigating the efficacy and safety of pulsed infusions of levosimendan in outpatients with advanced heart failure (LevoRep study)

Advanced chronic heart failure (CHF) is a clinical syndrome with high morbidity and mortality that often requires inotropic support for the alleviation of symptoms and congestion. There are no definite evidence-based data on the safety and efficacy of intermittent infusions of inotropic agents in this severe clinical condition. The purpose of the LevoRep study is to clarify whether pulsed infusions of the new inotropic agent levosimendan administered in an outpatient setting can safely improve exercise capacity, quality-of-life (QoL), and outcome in advanced CHF patients. The LevoRep study is a prospective, randomized, double-blind, placebo-controlled, two-armed, parallel-group, multicentre trial. The study is designed to investigate the effects of pulsed infusions of levosimendan (6 h administration at 0.2 mu g/kg/min every 2 weeks) on the composite endpoint (primary endpoint) comprising changes in functional capacity and QoL (20% or greater improvement in the 6 min walk test and 15% or higher score on the Kansas City Cardiomyopathy Questionnaire) at the end of the 24 week study period. In addition, short-term (8 weeks from randomization) and long-term (24 weeks from randomization) event-free survival (secondary endpoint) will be assessed. The LevoRep study aims to include 120 outpatients with advanced CHF. LevoRep is the first prospective randomized trial to assess the effects of pulsed infusions of an inotrope on hard endpoints as well as on the safety in patients with advanced CHF on an outpatient basis. The results are expected to promote the development of evidence-based recommendations for the ambulatory management of patients with end-stage heart failure