Pre-clinical evaluation of the forces during limb lengthening using manual and automated devices

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.Limb lengthening procedures use fixation devices to extend the constantly regenerating bone and surrounding soft tissues. Automated devices have been developed that aim to provide a more gradual tissue extension, resulting in better quality of treatment for the patient. Benefits include pain reduction and probable enhanced tissue outcomes. The development of one such new smart lengthening device is described. An integrated numerical model of tissue mechanics during lengthening is presented. It represents the mechanical environment in which the devices extend. The mechanism of the automated device is also modelled using Matlab software and validation was achieved through experimental testing. Validation of the tissue model includes the design of an experimental hydraulic system with the ability to control the peak loads and relaxation over time. A simplified mechanobiological model for the longer term healing effects is proposed. Calibration of the tissue model to clinical data allows for direct comparison of the load and extension of identical tissues, one being lengthened by a traditional device, the other an automated device. This simulation can be extended to include a range of lengthening rates and frequencies of distraction alongside various patient dependent tissue properties. The models also provide the opportunity to assess the effects of iterative changes to the device parameters (such as stiffness) on its performance as well as analyse the effect that these changes have on tissue extension and loading. Use of these models to optimise the device design alongside optimisation of the extension regime can result in improved device design and consequently improved patient outcomes

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Rapid sequence induction

Rapid sequence induction (RSI) is an established method of inducing anaesthesia in patients who are at risk of aspiration of gastric contents into the lungs. It involves loss of consciousness during cricoid pressure followed by intubation without face mask ventilation. The aim is to intubate the trachea as quickly and as safely as possible. This technique is employed daily during emergency surgery

Exploring factors influencing uptake and adherence to a home-based prehabilitation physical activity and exercise intervention for patients undergoing chemotherapy before major surgery (ChemoFit):A qualitative study

OBJECTIVES: Preoperative exercise training can improve cardiorespiratory fitness before major surgery. However, little is known about what influences participation and adherence in high-risk patient groups. We identified barriers and facilitators to uptake, engagement and adherence to a presurgical, home-based physical activity and exercise intervention called ChemoFit delivered during chemotherapy and before major oesophagogastric surgery. DESIGN: A qualitative study using focus group discussions and individual semi-structured interviews was conducted. All were audio-recorded, transcribed verbatim and data thematically analysed. SETTING: Northern Oesophagogastric Unit, Royal Victoria Infirmary, Newcastle upon Tyne NHS Hospitals Foundation Trust. PARTICIPANTS: Patients with oesophagogastric cancer who participated in the ChemoFit intervention recruited between March 2020 and January 2021. INTERVENTION: A home-based physical activity and exercise intervention involving cardiovasular and strength exercise using resistance bands and pedometers to monitor step count. Weekly telephone calls provided feedback, support and positive reinforcement. RESULTS: Twenty-two participants (18 men, 4 women; aged 67±8 years old) took part in a focus group discussion (n=17) or a semi-structured interview (n=5). Fifteen themes were identified from the data generated. Participants reported that the intervention was physically and mentally beneficial, and data highlighted features of the intervention that influenced uptake and adherence. An opportunity to increase the likelihood of surviving the pending operation was reported by participants as the most salient factor to engagement, and using the intervention as a distraction from illness and taking steps to positively influence the situation were the most salient factors to adherence. CONCLUSIONS: Uptake to the ChemoFit intervention was encouraged by provision of information that participation could reduce surgical risk and that participants could play an active role in risk reduction. Adherence was facilitated by the intervention being considered a positive distraction and participants being able to do something that could ultimately provide benefit. While participants reported difficulties and avoidance with some of the exercises recommended, understanding the importance of physical activity and exercise as part of their treatment regimen led to individual adaptations to intervention components to reach individual goals. TRIAL REGISTRATION NUMBER: NCT0419446