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Background Fresh frozen plasma (FFP) is the accepted standard treatment for clotting factor replacement in bleeding patients during or immediately after cardiac surgery. In the United Kingdom prothrombin complex concentrate (PCC) is not licensed in this setting, although it is being used in Europe because it has a higher concentration of clotting factor levels, and it can be administered rapidly and in small volume, resulting in less volume overload during cardiac surgery. Methods PROPHESY is a pragmatic, single-centre, open-label, randomised, controlled pilot trial that will assess whether it is feasible to perform a large trial in the future that will compare PCC versus FFP in patients who are bleeding (not on warfarin) and who require blood transfusion. Over a 15-month period, 50 patients will be randomised to PCC versus FFP if they develop active bleeding within 24 h of cardiac surgery and for whom the clinician has decided to administer FFP for treatment of bleeding. Standard laboratory and point-of-care assessments will be performed as per routine practice, and additional research blood samples will be taken at three time points to assess haemostasis. Subjects will be assessed daily up to hospital discharge or 30 days or death (whichever occurs first) and will be seen in follow-up for 90 days after surgery to assess for thromboembolic complications and hospital re-admission since discharge. Quality-of-life assessment will be performed pre-surgery and at 90 days post-surgery. We will also perform qualitative research with clinical experts and patients to explore the understanding of and experience with the interventions, as well as adherence to study procedures and protocol. Discussion There have been no randomised controlled trials that have compared the safety and efficacy of FFP versus PCC in cardiac surgery patients who are bleeding. This pilot study will assess if individual components of a large trial are deliverable to assess the safety and efficacy of the two blood products in the future. Trial registration EudraCT, 2018-003041-41; ClinicalTrials.gov, NCT03715348. Registered on 29 July 2018.

Background Out-of-hospital cardiac arrest carries a poor prognosis with survival less than 10% in many patient cohorts. Survival is inversely associated with duration of resuscitation as external chest compressions do not provide sufficient blood flow to prevent irreversible organ damage during a prolonged resuscitation. Extracorporeal membrane oxygenation (ECMO) instituted during cardiac arrest can provide normal physiological blood flows and is termed Extracorporeal Cardio-Pulmonary Resuscitation (ECPR). ECPR may improve survival when used with in-hospital cardiac arrests. This possible survival benefit has not been replicated in trials of out-of-hospital cardiac arrests, possibly because of the additional time it takes to transport the patient to hospital and initiate ECPR. Pre-hospital ECPR may shorten the time between cardiac arrest and physiological blood flows, potentially improving survival. It may also mitigate some of the neurological injury that many survivors suffer. Methods Sub30 is a prospective six patient feasibility study. The primary aim is to test whether it is possible to institute ECPR within 30 ​min of collapse in adult patients with refractory out of hospital cardiac arrest (OHCA). The secondary aims are to gather preliminary data on clinical outcomes, resource utilisation, and health economics associated with rapid ECPR delivery in order to plan any subsequent clinical investigation or clinical service. On study days a dedicated fast-response vehicle with ECPR capability will be tasked to out-of-hospital cardiac arrests in an area of London served by Barts Heart Centre. If patients suffer a cardiac arrest refractory to standard advanced resuscitation and meet eligibility criteria, ECPR will be started in the pre-hospital environment. Discussion Delivering pre-hospital ECPR within 30 ​min of an out-of-hospital cardiac arrest presents significant ethical, clinical, governance and logistical challenges. Prior to conducting an efficacy study of ECPR the feasibility of timely and safe application must be demonstrated first. Extensive planning, multiple high-fidelity multiagency simulations and a unique collaboration between pre-hospital and in-hospital institutions will allow us to test the feasibility of this intervention in London. The study has been reviewed, refined and endorsed by the International ECMO Network (ECMONet). Trial registration Clinicaltrials. gov NCT03700125 , prospectively registered October 9, 2018.

Background Fresh Frozen Plasma (FFP) is the accepted standard treatment for clotting factor replacement in bleeding patients during, or immediately after cardiac surgery. In the United Kingdom (UK) prothrombin complex concentrate (PCC) is not licensed in this setting although it is being used in Europe, because it has a higher concentration of clotting factor levels, and it can be administered rapidly and in small volume, resulting in less volume overload during cardiac surgery. Methods PROPHESY is a pragmatic single-centre, open-label, randomized, controlled pilot trial that will assess whether it is feasible to perform a large trial in the future that will compare PCC versus FFP in patients who are bleeding (not on warfarin) and who require blood transfusion. Over a 15-month period, 50 patients will be randomized to PCC versus FFP if they develop active bleeding within 24 hours of cardiac surgery, and for whom the clinician has decided to administer FFP for treatment of bleeding. Standard laboratory and Point-of-Care assessments will be performed as per routine practice, and additional research blood samples will be taken at three time-points to assess haemostasis. Subjects will be assessed daily up to hospital discharge or 30 days or death (whichever occurs first) and will be followed up for 90 days after surgery to assess for thromboembolic complications, and hospital re-admission since discharge. Quality of life assessment will be performed pre-surgery and at 90 days. We will also perform qualitative research with clinical experts and patients to explore the understanding and experience with the interventions, and adherence to study procedures and protocol. Discussion There have been no randomized control trials that have compared the safety and efficacy of FFP versus PCC in cardiac surgery in patients who are bleeding. This pilot study will assess if individual components of a large trial are deliverable to assess the safety and efficacy of the two blood products in the future.

Background Air pollution may increase the incidence of ventricular cardiac arrhythmias. We investigated this in patients with implantable cardioverter defibrillators attending London clinics. Method We explored associations between dates of activation of defibrillators and daily concentrations of various metrics of particulate matter and of pollutant gases at lags from 0 to 5 days, using a fixed-stratum case-crossover analysis controlling for confounding factors. Results Over an average of 1200 days of observation, 705 patients experienced 5462 activation days. Of 11 pollutants considered, we found positive associations with particle sulfate, particulate matter with aerodynamic diameter less than 10 microm and less than 2.5 microm, ozone, and sulfur dioxide. Only the association for particle sulfate was not easily explainable by chance (for 1 microg/m, lag 0-1 day, odds ratio = 1.025 [95% confidence interval = 1.003 to 1.047]). There was little or no evidence of associations with markers of primary vehicle emissions (particle number concentration, black smoke, nitrogen oxides, and carbon monoxide). There was little evidence of interactions with clinical factors such as ischemic heart disease, frequency of activation, or cardiac drugs. Conclusion Overall there was little evidence of an association between air pollution and activation of implantable cardioverter defibrillators. The pollutants with positive associations tended to be those of secondary origin with a regional distribution, rather than primary pollutants emitted from transport sources.