ARS Heath Family Grant

The successful applicants for the ARS Heath Family Grant were:

Principal Applicant
Dr Simon Scott
Honorary Lecturer & Specialty Registrar, Leicester Royal Infirmary

Title
Differential expression of nociceptin receptor (NOP) and pre-pro nociceptin / orphanin FQ (pp-N/OFQ) amongst leucoctyes and their subpopulations.

Amount
£12,815

Scientific Abstract

Main research question: Is there differential expression of nociceptin receptor (NOP) and its precursor (pp-N/OFQ) from subpopulations of leucocytes in a model of sepsis?
Plan of investigation: Leucocytes extracted from healthy blood will be stimulated with lipopolysaccharide or Staphyloccal enterotoxin B, or remain as a control. N/OFQ levels will be measured. Leucocyte subpopulations will be isolated, RNA extracted and expression measured for NOP and pp-N/OFQ. Specific equipment is required to confirm purity and mass of extracted RNA.
Methodology: 50 blood samples of 30ml each will be taken from volunteers and healthy patients recruited into the study. Samples will be divided into stimulated and unstimulated groups. Leucocytes will be extracted from whole blood, stimulated as appropriate and analysed for N/OFQ peptide via enzymelinked immunosorbent assay. Samples will then be separated into subpopulations. Granulocytes will be further separated into basophils, eosinophils and neutrophils. Separation will be achieved through the use of fluorescence-activated cell sorting. RNA will be extracted from these subpopulations and analysed by quantitative PCR for expression of NOP and pp-N/OFQ.

Outcome measures:

  • N/OFQ peptide concentration from stimulated and unstimulated leucocytes
  • NOP / pp-N/OFQ mRNA expression measured by qPCR in leucocyte sub-populations expressed as Î�Ct (difference between NOP or pp-N/OFQ and GAPDH cycle threshold, where one cycle is a doubling of start material).
     Final report from Dr Simon Scott (297 KB)

Principal Applicant
Dr Samantha Wilson
SpR Anaesthesia -Research Fellow, University College Hospital, London

Title
Determining the relationships between perioperative risk, socioeconomic characteristics, short term postoperative morbidity, and long term patient reported health gain and survival after joint replacement surgery

Amount
£5,288

Scientific Abstract

Main research questions:

  • What is the precision of a previously validated perioperative risk score (orthopaedic POSSUM) for predicting a novel outcome measure (health gain as defined by changes in Oxford hip & knee scores and EQ5D) after joint replacement surgery?
  • What is the precision of O-POSSUM for short-term postoperative morbidity and long-term survival in a modern NHS cohort?
  • What is the relationship between postoperative morbidity and longer term patient outcomes (health gain and long term survival) and how much of this relationship is explained by variation in perioperative risk and socioeconomic characteristics?
  • Is there is a socioeconomic gradient in the size of treatment effect (health gain or long-term survival) from joint replacement surgery?

Plan of investigation and methodology:

Linkage between data collected internally at two London hospitals (patient demographics, O-POSSUM, Post-Operative Morbidity Scores) and centrally held PROMs and mortality data for patients undergoing hip and knee replacement surgery.

Main outcome measures:
Predictive precision of continuous variables for continuous outcomes: scatter plots and regression modelling with calculation of goodness of fit (R2). Predictive precision of continuous variables for dichotomous outcomes: ROC curve analyses. Identification of independent predictors of short and long term outcomes: multiple regression analyses.