Remote ischaemic preconditioning versus sham procedure for abdominal aortic aneurysm repair: An external feasibility randomized controlled trial

© 2015 Mouton et al. Background: Despite advances in perioperative care, elective abdominal aorta aneurysm (AAA) repair carries significant morbidity and mortality. Remote ischaemic preconditioning (RIC) is a physiological phenomenon whereby a brief episode of ischaemia-reperfusion protects against a subsequent longer ischaemic insult. Trials in cardiovascular surgery have shown that RIC can protect patients' organs during surgery. The aim of this study was to investigate whether RIC could be successfully introduced in elective AAA repair and to obtain the information needed to design a multi-centre RCT. Methods: Consecutive patients presenting for elective AAA repair, using an endovascular (EVAR) or open procedure, in a single large city hospital in the UK were assessed for trial eligibility. Patients who consented to participate were randomized to receive RIC (three cycles of 5 min ischaemia followed by 5 min reperfusion in the upper arm immediately before surgery) or a sham procedure. Patients were followed up for 6 months. We assessed eligibility and consent rates, the logistics of RIC implementation, randomization, blinding, data capture, patient and staff opinion, and variability and frequency of clinical outcome measures. Results: Between January 2010 and December 2012, 98 patients were referred for AAA repair, 93 were screened, 85 (91 %) were eligible, 70 were approached for participation and 69 consented to participate; 34 were randomized to RIC and 35 to the sham procedure. There was a greater than expected variation in the complexity of EVAR that impacted the outcomes. Acute kidney injury occurred in 28 (AKIN 1: 23 %; AKIN 2: 15 % and AKIN 3: 3 %) and 7 (10 %) had a perioperative myocardial infarction. Blinding was successful, and interviews with participants and staff indicated that the procedure was acceptable. There were no adverse events secondary to the intervention in the 6 months following the intervention. Conclusions: This study provided essential information for the planning and design of a multi-centre RCT to assess effectiveness of RIC for improving clinical outcomes in elective AAA repair. Patient consent was high, and the RIC intervention was carried out with minimal disruption to clinical care. The allocation scheme for a definite trial should take into account both the surgical procedure and its complexity to avoid confounding the effect of the RIC, as was observed in this study. Trial registration: Current Controlled Trials ISRCTN19332276(date of registration: 16 March 2012). The trial protocol is available from the corresponding author

Reablement : supporting older people towards independence

As the overwhelming majority of older people prefer to remain in their own homes and communities, innovative service provision aims to promote independence of older people despite incremental age associated frailty. Reablement is one such service intervention that is rapidly being adopted across high-income countries and projected to result in significant cost-savings in public health expenditure by decreasing premature admission to acute care settings and long-term institutionalisation. It is an intensive, time-limited intervention provided in people's homes or in community settings, often multi-disciplinary in nature, focussing on supporting people to regain skills around daily activities. It is goal-orientated, holistic and person-centred irrespective of diagnosis, age and individual capacities. Reablement is an inclusive approach that seeks to work with all kinds of frail people but requires skilled professionals who are willing to adapt their practise, as well as receptive older people, families and care staff. Although reablement may just seem the right thing to do, studies on the outcomes of this knowledge-based practice are inconsistent-yet there is an emerging evidence and practice base that suggests that reablement improves performance in daily activities. This innovative service however may lead to hidden side effects such as social isolation and a paradoxical increase in hospital admissions. Some of the necessary evaluative research is already underway, the results of which will help fill some of the evidence gaps outlined here

The p85 subunit of phosphatidylinositol 3-kinase associates with the Fc receptor gamma-chain and linker for activitor of T cells (LAT) in platelets stimulated by collagen and convulxin.

There is extensive evidence to show that phosphatidylinositol 3-kinase plays an important role in signaling by the immune family of receptors, which has recently been extended to include the platelet collagen receptor, glycoprotein VI. In this report we present two potential mechanisms for the regulation of this enzyme on stimulation of platelets by collagen. We show that on stimulation with collagen, the regulatory subunit of phosphatidylinositol 3-kinase associates with the tyrosine-phosphorylated form of the adapter protein linker for activator of T Cells (LAT) and the tyrosine-phosphorylated immunoreceptor tyrosine-based activation motif of the Fc receptor gamma-chain (a component of the collagen receptor complex that includes glycoprotein VI). The associations of the Fc receptor gamma-chain and LAT with p85 are rapid and supported by the Src-homology 2 domains of the regulatory subunit. We did not obtain evidence to support previous observations that the regulatory subunit of phosphatidylinositol 3-kinase is regulated through association with the tyrosine kinase Syk. The present results provide a molecular basis for the regulation of the p85/110 form of phosphatidylinositol 3-kinase by GPVI, the collagen receptor that underlies activation