The demand for affordable and realistic phantoms for training, in particular for functional endoscopic sinus surgery (FESS), has continuously increased in recent years. Conventional training methods, such as current physical models, virtual simulators and cadavers may have restrictions, including fidelity, accessibility, cost and ethics. In this investigation, the potential of three-dimensional printing for the manufacture of biologically representative simulation materials for surgery training phantoms has been investigated. A characterisation of sinus anatomical elements was performed through CT and micro-CT scanning of a cadaveric sinus portion. In particular, the relevant constituent tissues of each sinus region have been determined. Secondly, feedback force values experienced during surgical cutting have been quantified with an actual surgical instrument, specifically modified for this purpose. Force values from multiple post-mortem subjects and different areas of the paranasal sinuses have been gathered and used as a benchmark for the optimisation of 3D-printing materials. The research has explored the wide range of properties achievable in 3DP through post-processing methods and variation of printing parameters. For this latter element, a machine-vision system has been developed to monitor the 3DP in real time. The combination of different infiltrants allowed the reproduction of force values comparable to those registered from cadaveric human tissue. The internal characteristics of 3D printed samples were shown to influence their fracture behaviour under resection. Realistic appearance under endoscopic conditions has also been confirmed. The utilisation of some of the research has also been demonstrated in another medical (non-surgical) training application. This investigation highlights a number of capabilities, and also limitations, of 3DP for the manufacturing of representative materials for application in surgical training phantoms.

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Background: Enhanced Recovery After Surgery (ERAS) is a perioperative programme to accelerate recovery. Nutrition ERAS components include preoperative carbohydrate loading and reduced preoperative/postoperative fasting. Postoperative chewing gum (CG) may be a useful nutrition-related practice to reduce ileus duration/onset through sham feeding. Patient involvement is central to ERAS, and studies indicate that patients perceive nutrition as an important ERAS component requiring improvement. Current adherence to, and predictors of, ERAS nutrition practices are uncertain. Aims: This thesis aims to: Systematically review the evidence for CG for postoperative recovery, Explore patient perioperative nutrition experiences, Investigate postoperative feeding practices in colorectal surgical patients. Findings will be synthesised to provide an overall investigation into the current role of nutrition practices in perioperative care. Methods: Three studies were conducted: a systematic review (SR)/meta-analysis assessing evidence from randomised-controlled trials for the effects of CG on postoperative recovery; a qualitative interview study exploring patient experiences of perioperative nutrition; and a secondary data analysis observational study investigating current adherence to, and predictors/outcomes associated with, early postoperative feeding. Results: SR results (from 81 RCTs) suggested that CG may reduce time to first flatus (l0.4h), bowel movement (TBM) (12.7h), and length of hospital stay (LOHS) (0.7d). In the qualitative study, four themes affecting perioperative nutrition experiences were identified (preparation/autonomy/relationship with food/hospital environment), from which barriers/facilitators to perioperative nutrition practices were observed. In the observational study 66% and 33% of participants respectively consumed and tolerated solid food early. Opiate analgesics and open/converted-to-open surgery were associated with delayed food tolerance. Early postoperative feeding was associated with reduced TBM/LOHS. Conclusions: Findings suggest that postoperative CG may be useful clinically. Patients' perioperative nutrition experiences could be improved by addressing patient-perceived barriers/facilitators, and vulnerable patients could be characterised from predictors of delayed postoperative feeding. Future research may be warranted exploring CG use alongside ERAS, and targeting patient-perceived barriers to nutrition practices and vulnerable patients.

Postoperative nausea and vomiting (PONV) is one of the most common complications following surgery. Despite better anaesthetic techniques, and the availability of newer generations of antiemetics, the incidence of PONV is still as high as 60-70% in high-risk subjects. Patients rated symptoms of nausea and vomiting as highly undesirable and are willing to pay out of pocket a substantial amount for an effective antiemetic. PONV also has major economic implications, prolonging recovery room and hospital stay, and in some cases, increases patient morbidity. Propofol is an intravenous anaesthetic which gained rapid popularity due to its favourable pharmacokinetic and pharmacodynamic profile. In particular, it is associated with rapid recovery, making it the intravenous anaesthetic agent of choice especially in ambulatory anaesthesia. Previous studies have demonstrated that total intravenous anaesthesia with propofol is associated with a lower incidence of PONV when compared with inhalational anaesthetic. However, it is unclear regarding the dose response of propofol when used as an antiemetic, and how propofol should be administered in the perioperative period for its antiemetic effects. The over arching goal of this MD thesis is to examine the use of propofol for its antiemetic properties. First, we assessed the extent of clinical practice of using propofol for its antiemetic effects among US anaesthesiologists. Next, we determine the dose response of propofol for its antiemetic effects. We examined the efficacy of propofol when used as antiemetic prophylaxis as well as for the treatment of established PONV. Different regimens of propofol administration were assessed for its prophylactic antiemetic effects. Treatment of established PONV was assessed using a patient controlled antiemetic system. We also determined the use of propofol in a multimodal PONV prevention strategy as well as its use in paediatric population. The main objective of these series of investigations was to systematically determine the antiemetic effects of propofol and recommend how propofol should be used in clinical practice.

Objective: There have been calls from health professional organisations and advocacy groups to regulate and ban cosmetic surgery advertising due to concerns about increasing uptake of elective cosmetic surgical procedures that are often accompanied by substantial financial, medical and psychological costs. To date, the impact of cosmetic surgery advertisements on body image and intentions to undergo cosmetic surgery has not been examined experimentally. Method: A community sample of British women (N=193) were randomly assigned to view one of four conditions: cosmetic surgery advertisements with models, cosmetic surgery advertisements without models, beauty product advertisements with models, and beauty advertisements without models. Participants completed validated measures of state body dissatisfaction, intentions to undergo cosmetic surgery, internalisation of cultural beauty ideals and appearance comparisons. Results: Women exposed to advertisements featuring models reported significantly greater body dissatisfaction post exposure compared to women exposed to advertisements without models. No differences in body dissatisfaction emerged post-exposure between cosmetic surgery and beauty product advertisements with, and without, models. There were also no differences between conditions on intentions to undergo cosmetic surgery. Internalisation of cultural beauty ideals and appearance comparison tendency did not moderate these effects. Conclusion: Compared to exposure to beauty product advertising, exposure to cosmetic surgery advertising did not result in increased state body dissatisfaction and intentions to undergo cosmetic surgery. The effect of cumulative, longer-term exposure to cosmetic surgery advertising and the inclusion of models in advertisements should be examined in order to guide policy makers towards the most effective strategies involving this form of advertising.

The patient safety ‘movement’ has relied largely on formal, explicit structures in attempting to promote principles and practices from safety-critical industries within the healthcare sector. The ‘craft’ nature of medical practice is however, predicated on the interplay of formal and tacit experiential knowledge. The specialty of anaesthesia is a branch of medicine and yet the nature of anaesthetic practice resembles operational work within e.g. aviation and nuclear power, sharing with them the characteristics of time pressure, complex human-machine interactions, uncertainty and risk. This thesis takes the form of an interpretive meta-synthesis of six published journal articles to examine how patient safety is constructed and enacted through the transmission and co-creation of professional knowledge. After delineating the forms of knowledge used in anaesthetic work, it describes how abstract notions of safety are expressed within a number of specific aspects of practice: the use of electronic monitoring equipment; communication between actors on induction of, and emergence from, general anaesthesia; the definition and analysis of adverse incidents; postoperative handover of care in the recovery room and in the performance of regional anaesthesia as an exemplar technical procedure. Anaesthetists draw both on informal logics and routines of practice and on codified safety knowledge and tools. How, and when, to reconcile these two approaches relies on a dynamic combination of cognitive, affective and normative influences, which seem to be embedded in anaesthetists’ professional identity. Paradoxically, much of this seems to be learned through contact with the very failure and error that the routines are designed to avoid and prevent; It is developed through dealing with the many perturbations and threats to the safety of their patients, whether through personal experience, the ‘cautionary tales’ of others, or imagining what might go wrong. The interpretive synthesis thus provides empirical support for theoretical notions of how resilience to error is created in everyday work in safety-critical settings.

Background: Each year approximately 11% of infants who are born will require extra care, which often results in admission to a Neonatal Intensive Care Unit (NICU). For some of these infants extra care will include surgery. Research to date has focused on the experiences of parents of infants in the NICU, with less known about parents’ experiences of infant surgery. NICU admission is often characterised as a time of significant stress and distress for parents. For parents of surgical infants there may be additional stressors, including the required transfer between the maternity and children’s hospitals for surgery. The management of transfers between hospitals for this vulnerable population is increasingly topical in view of the establishment of the neonatal managed clinical networks in the United Kingdom, which will result in increased movement of infants between hospitals providing neonatal care at different levels. Aims: To explore the experiences of parents who have an infant that requires surgery and transfer between hospitals. To explore how parents cope with this experience. Methods: This qualitative study was conducted and analysed using Interpretative Phenomenological Analysis (IPA) approach. Purposive sampling was used to recruit a relatively homogenous sample. Semi-structured interviews were conducted with five parents. Results: The results of this study suggest that the experience of having an infant who requires surgery is particularly challenging for parents. Five superordinate themes were identified that represented parents’ experiences: being told – the psychological impact of diagnosis; living on the ward; becoming a parent to a critically ill baby; coping and facing the future. Conclusions: The findings of this study have implications for clinicians, policy makers and service managers who are involved in the delivery and design of services that care for infants who require surgery and their families. In light of the limited research that has been conducted in this area, suggestions are made for future research that will enhance service provision for these families.

The lymphatic system plays an important role in both tissue homeostasis and inflammation. During the surgical procedure there is complete disruption of lymphatic drainage of the allograft kidney. The time course and nature of lymphatic reconnection following transplantation is poorly understood. In addition to the extra-renal lymphangiogenesis required for lymphatic reconnection, some patients may develop de novo lymphatic vessels within the renal parenchyma during acute rejection or chronic allograft damage. This work sought to examine the time course and mechanism of lymphangiogenesis and the role of macrophages in this process. Injection of carbon black and Evan’s blue into the rat kidney resulted in rapid transit to the draining hilar renal lymph node. Surgical disruption of the lymphatic drainage of the kidney prevented trafficking of carbon black to the renal lymph node at 24 hours. At day 6 there was macroscopic and microscopic evidence of carbon black localisation in the renal lymph node suggesting functional reconnection. Careful histological analysis of hilar renal tissue indicated that the large lymphatic trunks were replaced by a network of small proliferating lymphatic vessels. Assessment of intra-renal lymphangiogenesis was undertaken in 2 distinct experimental models of renal transplantation. In a murine model of acute allograft rejection there was no evidence of increased lymphatic vessel number at day 7. In a collaboration with Sheffield University, tissue from a rat model of interstitial fibrosis and tubular atrophy was examined. The rat tissue exhibited a prominent macrophage and T-cell infiltration at 12 months but there was no difference in the number of perivascular lymphatic vessels. In contrast, there were numerous lymphatic vessels evident in the interstitium that were absent in control isograft tissue. Interestingly, the number of lymphatic vessels correlated with the extent of fibrosis. Analysis of vascular endothelial cell growth factor-C (VEGF-C) mRNA expression did not show any increase in allografts. The model of unilateral ureteric obstruction (UUO) was employed as a model of rapidly progressive inflammatory fibrosis. UUO was associated with rapid and prominent interstitial lymphangiogenesis. This was associated with a marked increase in macrophage and T-lymphocyte infiltration and increased whole kidney mRNA expression of VEGF-C. The role of macrophages in lymphangiogenesis was explored by administration of macrophage depleting liposomal clodronate. No effect upon lymphangiogenesis was found but liposomal clodronate failed to deplete ED-1 positive macrophages in the kidney. A macrophage isolation strategy was thus employed using the myeloid CD11b marker cells and flow cytometric cell sorting and immunomagnetic bead sorting. Although gene expression studies demonstrated increased ED1 mRNA expression by CD11b enriched cells, no difference in VEGF-C mRNA expression between CD11b cells obtained from obstructed kidneys versus cells from sham controls was evident. Lastly, despite extensive efforts, immunostaining for VEGF-C was unsuccessful. In summary, lymphangiogenesis can reconstitute the lymphatic drainage of the kidney and is prominent in both chronic allograft injury and the acutely obstructed kidney in the rat. Although VEGF-C is the likely driver of lymphangiogenesis direct evidence of macrophage VEGF-C production was not found.

Sepsis is a life threatening progression of a trauma or pathogen initiated systemic inflammatory response. Current treatment is supportive and depends mainly on antibiotics, fluids, and the careful administration of oxygen therapy. As sepsis progresses, it becomes a dysregulated inflammatory response, characterised by oxidative stress and excessive production of inflammatory cytokines, mitochondrial dysfunction and loss of antioxidant protection. Previous work on cells and animals has shown that novel antioxidants targeted to mitochondria may have a beneficial effect. To induce an inflammatory response and mitochondrial dysfunction, a human umbilical vein endothelial cell (HUVEC) in vitro mixed sepsis model with 0.2 μg/ml lipopolysaccharide (LPS) plus 20 μg/ml peptidoglycan (PepG) was used in the presence of a mitochondrially targeted vitamin E derivative, MitoVit E, and compared to the non-targeted vitamin E forms, Trolox and DL α-tocopherol acetate. Gene expression analysis was performed by quantitative polymerase chain reaction (qPCR) of the Toll-like receptor (TLR) 2 and 4 pathways from cells treated with the antioxidant +/- LPS/PepG for 4 h. Results showed that MitoVit E differentially regulated 11 genes compared to just four genes for the non-targeted forms of vitamin E. MitoVit E, Trolox and vitamin E were able to blunt IL-6 and IL-8 cytokine response in a dose-dependent manner. Inhibition of NFĸB gene and accessory protein expression was different for each antioxidant investigated along with effects on other inflammatory signalling proteins STAT 3 and MyD88. In addition, the antioxidants regulated radical production to similar extents, but had different effects on the reduced glutathione/oxidised glutathione, mitochondrial metabolic activity, mitochondrial membrane potential, oxygen consumption and mitochondrial number. In conclusion, MitoVit E showed encouraging effects in preventing dysregulation of the inflammatory response, maintaining mitochondrial membrane potential and radical production and normal cell function.

The operating room (OR) within a hospital environment is one of the most expensive functional areas, yet the use of the OR also provides hospitals with an essential source of income. However, at present, there are variations on how to evaluate the performance of ORs, since there is no clear and full explanation of the concept and methods used for evaluation. The overall aim of this thesis is to develop an evidence based Operating Room Assessment Framework (ORAF) to evaluate Operating Room performance with clear and complete guidelines that can be used by operating room managers, directors or any other medical professionals to evaluate operating room performance, determine OR planning and scheduling efficiency, OR workload and OR utilization. The resulting Operating Room Assessment Framework will assist targeted healthcare professionals in their quest to evaluate, monitor and improve overall Operating Room efficiency. The OR management systems of eight tertiary and teaching hospitals in three countries (Japan, Canada and Saudi Arabia) have been examined from 2010 to 2012, which include more than 98,500 procedures. The Operating Room Assessment Framework (ORAF) involves three important elements of Operating Room performance, namely: OR scheduling level, the type of OR workload, and OR utilization. These elements can simply be read to reach the end result, which includes three types of scheduling levels: under scheduling, ideal scheduling and over scheduling; five types of OR workload: OR total workload (the gross workload), OR actual workload, over workload, unnecessary workload and unexpected workload; and three types of OR utilization: underutilization, ideal utilization, and 100% utilization with over workload. Through the validation process in different hospital contexts, the ORAF has proven its ability to perform satisfactorily, with accuracy, in line within the research’s objectives.