BJA/RCoA Project Grants

University of Manchester

Title
Ventilating circadian rhythms: a novel cause of circadian disruption?

Amount
£69,929

Scientific Abstract
We have discovered that ventilation is a novel cause of circadian disruption. We now propose to investigate whether mechanical force generated by ventilation results in circadian disruption causing increased pulmonary inflammation and injury.

Aim 1: Identify ventilator conditions which cause maximal circadian disruption
Using real time reporters (PER2::luc) it is possible to view circadian oscillations in real time, therefore we will use this technology to investigate what happens in the lung with different modes of ventilation (volume CMV, pressure CMV and spontaneous). Experiments will also be repeated at different times of day to generate a phase response curve and evaluate pulmonary damage and inflammation.

Aim 2: Use ventilator conditions which cause maximal circadian disruption to identify the responsible cell type, relevant biochemical pathways and promising therapeutic targets
We will then investigate the effect of ventilation in specific cell types, identifying the key cell causing circadian disruption. This cell will then be used in an in vitro model of ventilation to elucidate key mechanisms (MAPK, ROS or mechanotransduction). Then the efficacy of existing compounds in ameliorating circadian disruption or the downstream effects will be investigated.

Royal Surrey County Hospital NHS Foundation Trust

Title
Muscle wasting in major abdominal surgery (MAMAS) 2

Amount
£24,970

Scientific Abstract
Perioperative muscle wasting impairs patient recovery and can contribute towards persistent functional disability. Prevention of ICU-acquired weakness is difficult to study, and perioperative muscle wasting may be a useful model to explore potential therapies. Muscle wasting and recovery from surgery have been identified as priorities from James Lind Alliance Priority Setting Partnerships in ICU (How can the physical consequences of critical illness, such as muscle wasting, weakness, nerve damage, be prevented and what is the best way to support recovery from these after intensive care?) and anaesthesia (How can we improve recovery from surgery for elderly patients?)

We have demonstrated significant muscle wasting occurs during the first week after major abdominal surgery (unpublished data, MAMAS study). To facilitate the design of interventional studies to prevent perioperative muscle wasting - we need further information about the nadir of muscle dimensions (and associated muscle measures).

Quadriceps femoris muscle morphological parameters and diaphragm muscle thickness measure using ultrasound, and muscle strength, will be assessed pre surgery; day 1 post surgery; thereafter alternate days until hospital discharge and 6 weeks post hospital discharge. In addition, physical function assessments will be performed. The outcome of our study will directly inform design of future interventional studies.

Queen Mary University of London

Title
Post-operative Carer Led Monitoring (P-CALM): An intervention to train family carers to measure and document basic vital signs for surgical in-patients in a resource limited hospital in Uganda: A stepped-wedge cluster randomised trial

Amount
£49,820

Scientific Abstract
Surgical patients in Africa are younger and fitter than the global average, they develop fewer complications but are twice as likely to die. These high rates of death following post-operative complications (termed failure to rescue) suggest many lives could be saved through routine postoperative surveillance for deteriorating patients. Data collected at Mbale Regional Referral Centre in Uganda reveal a critical shortage of nursing staff on post-operative wards with highly variable rates of vital signs monitoring. In some wards, basic vital signs such as heart rate and respiratory rate are not monitored at all. In many African hospitals, family members provide much of the basic personal care. We propose a simple but novel intervention, designed in accordance with the MRC complex intervention framework, to teach family carers to measure and document vital signs for patients after surgery. They will be taught a simple method to recognise abnormal values, and how to escalate these findings to nursing staff. We will evaluate this intervention in a stepped-wedge cluster randomised trial, recruiting 2000 patients over a six-month period. The trial will provide explanatory, feasibility and pilot data to inform the design of a subsequent international trial providing definitive evidence for this intervention across Africa.