BJA/RCoA Project Grant

The successful applicants for the BJA & RCoA Project Grant were:

Principal Applicants
Dr Jonathan Coles
University of Cambridge

Title
Imaging NMDA (N-methyl-D-aspartate) receptor activation following head injury using positron emission tomography

Amount
£52,856

Scientific Abstract

Traumatic brain injury (TBI) is a major cause of death and disability. Experimental studies following TBI  demonstrate  increases  in  excitatory  neurotransmission,  and  glutamate  mediated  activation  of  the N-­‐methyl-­‐D-­‐aspartate (NMDA) receptor is associated with epilepsy and neuronal death. Clinical trials of NMDA receptor antagonists have not shown benefit, probably due to poor understanding of the  temporal  and  spatial  profile  of  metabolic  derangements  following  TBI.  Such  spatial  heterogeneity is shown by bedside microdialysis measurements of high glutamate levels typically surrounding contusions, and such derangements are associated with poor outcome.

The aim of this research is to obtain pilot positron emission tomography data regarding the temporal profile of NMDA receptor activation with 18F-­‐GE-­‐179, a novel tracer, following TBI and compare this with  clinical  microdialysis  monitoring  of  glutamate  levels.  Magnetic  resonance  imaging  (MRI)  and  spectroscopy (MRS) will be used to identify structural lesions (contusions), and significant metabolic derangements  around  such  regions  will  be  examined.  Clinical  monitoring,  incidence  of  post-­‐traumatic epilepsy and outcome will be assessed using the Glasgow Outcome Scale and neurocognitive outcome assessments. We expect that these data will allow us to refine our imaging techniques, and provide information that will guide the development and use of novel therapeutic interventions.



Principal Applicants
Professor Helen Galley & Professor Nigel Webster
University of Aberdeen

Title
Transcriptome changes induced by shift working and the effect of administered melatonin

Amount
£65,000

Scientific Abstract
Poor cognitive performance and increased time to undertake tasks have been reported in people working night shifts, including anaesthetists, compared to day shifts. Adaptation to night shifts requires sleeping patterns and endogenous melatonin secretion to be 'in phase'. Melatonin has effects on genes, and changes to the human transcriptome in healthy subjects when their sleep pattern is out of phase with melatonin secretion has been reported. There are no reports of the effects of exogenous melatonin on transcripts in night shift workers. The aim of this study is to determine the effects of exogenous melatonin administration compared with placebo in medical staff working night shifts. This pragmatic pilot study will assess, in a double blinded randomised cross-over trial, whether melatonin given before sleep time can improve sleep and psychomotor vigilance and modulate transcript changes. In the placebo phase we will be able to determine if the transcriptome changes described when sleep is out of phase with melatonin secretion are also seen in actual night shift workers. Changes in gene transcripts may explain the health disadvantages of shift working and melatonin may be useful intervention. This study is part of an MPhil/PhD project studying the effects of melatonin.



Principal Applicants
Dr Simon Howell
University of Leeds

Title
Pilot Study of the Diagnosis and Impact of Frailty in Patients Undergoing Elective Colorectal Surgery

Amount
£56,409.15

Scientific Abstract
As the population ages frailty is becoming increasingly common within the surgical population. There is evidence from both the non-surgical and surgical settings that interventions may to some extent reverse functional decline. It would be rational to integrate the primary and secondary care of frail surgical patients so that interventions to improve function and decrease surgical risk could be delivered from the point of referral for surgery and maintained through rehabilitation and beyond. This application requests funding for pilot work for a study to assess such an intervention. We will compare the context validity and concordance of three clinical measures and an electronic frailty index in an elective colorectal surgical population. We will collect pilot data on objective measures of clinical outcome in frail and non-frail patients including quality of life outcomes. We will conduct focus group studies with patients and staff to establish expectations of recovery and outcomes of relevance to patients. We will hold a consensus conference to define appropriate pre-assessment frailty tools and outcome measures for the study of a joint primary-secondary care intervention in frail elderly surgical patients and we will apply for funding for this study.



Principal Applicants
Dr Iain Moppett
University of Nottingham

Title
Hip Fracture Intervention Study for Prevention of Hypotension (HIP-HOP) Trial: Pilot Study

Amount
£52,290

Scientific Abstract

The annual cost of inpatient care for the 75,000 patients that sustain a hip fracture in the UK and Ireland consumes 1% of the NHS annual budget. Ninety-eight percent of hip fractures are fixed surgically, after which 30-day mortality is around 8%, with significant attendant morbidity, reduced level of independent mobility and increased risk of dependence.

Recent national data (ASAP) have shown that regardless of anaesthetic technique, hypotension during hip fracture is both common and severe, with around 30% of patients having a lowest recorded mean arterial pressure (MAP) < 55 mmHg. MAP below this is associated with increased mortality compared to patients whose lowest MAP remained >55mmHg (6.0% v 4.6%, p=0.002). This is consistent with data from non-hip fracture patients.

We hypothesise that tighter intraoperative control of blood pressure (SBP fall < 20% from pre-induction value, MAP > 75mmHg) using vasopressors during hip fracture surgery under either general or spinal anaesthesia improves outcomes after hip fracture surgery compared with standard treatment (at the anaesthetist's discretion) only. We propose a pilot, feasibility study enrolling the first 75 patients in a multi-centre trial.