Background Proper management of pain is necessary to help patients recover quickly during postoperative care. Failure to promptly assess and manage pain could lead to complications in postoperative situations and can also increase the length of required hospital stays, create or add to elements of chronic post-surgical pain and overall poor health outcomes for the patients. Nurses play crucial roles in assessing postoperative pain, however despite advances in nursing care, there is evidence from a range of research which suggests that patients still suffer considerable levels of postoperative pain. In Kuwait’s healthcare setting, there is a paucity of literature on how nurses perform pain assessment and whether this leads to significant pain relief amongst patients. This research addressed this apparent vacuum in current research literature by exploring the experiences of nurses and patients in Kuwait in postoperative scenarios – focusing in particular on postoperative pain. This work also utilised the findings to help to provide a suggested framework through which the quality of care received by patients in surgical wards in Kuwait could be improved. Aims and Objectives This study aimed to explore how Kuwaiti nurses assess pain in postoperative patients in hospital settings in Kuwait and also to examine postoperative patients’ self-reported experiences of pain. Specifically, this study aimed to address the following objectives: - To explore the roles and responsibilities of surgical nurses in postoperative pain assessment; - To determine the knowledge and perceptions of nurses working in Kuwait on pain assessment; - To investigate the postoperative pain experiences of patients in surgical wards; and identify potential factors that could affect how patients respond to postoperative pain. This was intended to help to provide a framework for dealing with the main aim of this thesis which was to look at how nurses assess postoperative pain in Kuwait, and whether the current methods for doing so represented best practice when compared to other regions or institutions. Methodology This study utilises a qualitative methodology based on a Grounded Theory (GT) approach to social research. This encourages theory building throughout the work and is used to explore concepts relating to pain and how this is influenced by a range of socio-economic and cultural factors. In addressing these issues the experiences of nurses and patients in a hospital ward in a Kuwaiti hospital was established as the research case study. Ten nurses and ten patients were invited to take part in the study through purposive sampling techniques outlined within a grounded theory approach. Inclusion and exclusion criteria were established to ensure that only adult patients aged 18 years old and above who will give their informed consent to participate in the study would be included. Nurses who have at least one-year experience in a surgical ward were also invited to take part in the study. Data Analysis Data was analysed through a grounded theory approach based on key elements of the models espoused by Strauss and Corbin (2008) and Charmaz (2006). This began with a process of data familiarisation once the interviews had taken place, followed by processes of axial and open coding, selective coding, and the generation of categories and themes. In accordance with the grounded theory methodology data analysis and collection of data occurred simultaneously. The main aim of the data analysis was to help generate theories that explain the nurses and patients’ experiences in pain assessment during postoperative care in Kuwait’s healthcare setting. Results and Recommendations The research found evidence to suggest that many patients in the Kuwaiti healthcare system in postoperative scenarios are experiencing difficulties in addressing issues relating to postoperative pain. This was evidenced by patient participants in the study who felt de-legitimised and an undercurrent of distrust between the nurses and the patients. This was mirrored in the responses of some nurses, who also expressed concern that some patients were exaggerating their pain - determining their own opinions and perhaps devaluing the direct experiences of the patients themselves. In addition the research suggests that there are ongoing social power issues in Kuwait and an apparent lack of autonomy which is creating a culture of blame. Although there are clear resource issues, it is apparent that this lack of autonomy and the levels of distrust between patients, nurses and doctors need to be addressed urgently to ensure that postoperative pain care in Kuwaiti hospitals is improved. In Kuwait these issues of a lack of autonomy and an apparent lack of focus on the subjective nature of pain in relation to robust assessment methods has manifested as a cultural norm. As a result there is a need to begin to address formal education of nurses, the level of power and autonomy given to nurses and the establishment of standardised pain assessment procedures more rigorously and definitively. This can be achieved by ensuring that the nurse-doctor professional relationship is improved through better communication structures, more effective training programmes in treating pain, and by challenging a culture where patient’s opinions and feelings on pain are not addressed by medical professionals. This study has provided evidence based data sets which can be utilised in further developing the nursing curricula in Kuwait across both undergraduate and postgraduate nursing programmes and also across many aspects of in-service education within the hospital units themselves.

Orthotopic liver transplantation (OLT) remains the only proven treatment for end-stage liver disease. However the waiting list for OLT far exceeds the supply of donor organs. Hepatocyte transplantation may offer an alternative for these patients either as a bridge to OLT or replacing OLT altogether. Unfortunately efforts so far have failed to result in long term benefit despite initial promising results. The mechanisms regulating engraftment of transplanted hepatocytes into host liver, in particular the nature of their interaction with hepatic sinusoidal endothelial cells (HSEC), remain poorly understood. I have significantly improved the outcome of human hepatocyte isolation from liver tissue and shown that human hepatocytes express a range of adhesion molecules including β1-integrin. Rather than reducing adhesion, β1-integrin blockade significantly improves hepatocyte adhesion to HSEC under flow, increases transmigration across HSEC and leads to greater engraftment in a murine model of hepatocyte transplantation. Furthermore, I have shown that blocking β1-integrin on human hepatocytes leads to activation of the PKB/Akt signalling pathway, resulting in suppression of anoikis and improved viability, and promotion of cytoskeletal reorganisation that may lead to a more migratory phenotype. This work therefore demonstrates a possible target to improve hepatocyte engraftment and thus the outcome of hepatocyte transplantation.

This thesis provides an overview of the design, conduct and analysis of a multicentre phase III trial exploring the clinical effectiveness of a novel in-theatre intervention to try to reduce rates of post-operative surgical site infection (SSI). The pitfalls inherent in the conduct of research into SSI are discussed, along with measures to try and overcome these. The wound-edge protection device (WEPD) intervention is defined and the published evidence assessing its clinical effectiveness systematically appraised. Clinical surgical research and its difficulties are described, and the paradigm-shift bought about by the new trainee-led research collaborative model introduced. The design considerations involved creating a pragmatic and simple trial within the complex intervention that is surgery are explored in the context of the creation of the ROSSINI trial. This trial successfully recruited ahead of time and target and robustly proved that WEPDs are not clinically effective in reducing SSI. It also demonstrated the power and ability of this new collaborative model, as witnessed by both the citations of the results paper and the exponential growth in similar collaborative ventures. Finally, lessons learned about SSI research and clinical surgical research are summarised, and plans for future research presented.

The use of sedation for diagnostic and therapeutic procedures in children is common and leads to considerable debate. Evaluating this subject is complicated by differences in the methods and the outcomes used for sedation assessment in children reported in the literature which are large. This thesis used systematic literature reviews, a prospective study and a national survey to evaluate several aspects of paediatric sedation. A systematic review of the safety and effectiveness of chloral hydrate in three categories of procedural sedation was conducted. For painless procedural sedation, chloral hydrate was more effective for shorter imaging procedures, such as CT scanning. The incidence of adverse events was 1,951 occurring in 14439 patients (13.5%), with hypoxia the most frequent. Moderate hypoxia (SpO2 85%–90%) was seen in 281 cases of 14439 patients (1.9%) of children. For painful procedural sedation, the success rate of chloral hydrate was variable (35%–100%). Hypoxia was the most common adverse event, occurring in 95 of 1810 patients (5.2%). Most (66 cases/1810 patients, 3.6%) were mild however moderate hypoxia occurred in 29 of 1810 patients (1.6%). The incidence of adverse events was higher during painful procedures than during painless procedures: 313AEs/1810 patients (17.3%) versus 1,951AEs/14439 patients (13.5%). The most frequent use of chloral hydrate as a treatment was to reduce agitation during mechanical ventilation, followed by treatment of neonatal diseases and treatment of neurological disorders. The reported success rate was high throughout all treatment procedures (86%–100%). The incidence of hypoxia was found to be the highest, when it was used for the treatment of agitation 71 cases/438 patients (16.2%). Due to the heterogeneity between the studies it was not possible to perform meaningful statistical analysis. The effectiveness and safety of triclofos (a chloral hydrate derivative) was evaluated for procedural sedation in children, in a systematic review of the literature. The success rate was variable (ranging from 50 to 100%), shorter procedures such as CT scanning were more likely to be successful. Vomiting and hypoxia were the most frequently reported adverse events, 10% (62/613) and 7.8% (48/613) respectively. A systematic literature review of the safety and effectiveness of paraldehyde as a sedative agent for children was performed, as it was named as a second line agent in the sedation policy of the Derbyshire Children's Hospital. The literature is scant; only five studies were located and involved 157 patients. The reported effectiveness of paraldehyde ranged from 75- 93%. Vomiting was the most commonly reported adverse event (2 cases/8 patients, 25%). Due to the small numbers of patients and poor methodology of studies, its clinical use cannot be supported. A further systematic literature review of 29 studies involving 6342 children on the safety and effectiveness of midazolam for imaging procedures was conducted. The procedural success rate was variable (0%–100%, median 82%). Hypoxia was the most commonly reported adverse event (74 cases/2046 patients, 3.6%) with (32 cases/2046 patients) 1.6% of cases being reported as moderate hypoxia. Palatability of the two most commonly used sedative agents, chloral hydrate and midazolam, was evaluated by conducting a literature review and a prospective study at the Derbyshire Children's Hospital. Only 9 studies were identified during the literature review. Of these, 8 studies evaluated the palatability of midazolam, while only 2 evaluated the palatability of chloral hydrate. Midazolam was reported as more acceptable to patients than chloral hydrate. The prospective study supported this, and showed that patient acceptance of midazolam was good, while it was poor for chloral hydrate. The success rate of procedures was lower with midazolam, then chloral hydrate. A further literature review evaluated the use of sedation in Middle Eastern countries. Limited numbers of reports were found. Of the 37 studies, the majority (43%) were conducted in Turkey, within single centres and only examined a single procedure. Very limited evidence on the use of sedation guidelines was reported. Further exploration of the current sedation practice in the Kingdom of Saudi Arabia was done using a national survey. The questionnaires were completed by 81 health care professionals. Only 61% documented the use of sedation guidelines, although 91% reported monitoring of patients during procedural sedation. The most commonly reported agents for both painless and painful procedures were chloral hydrate and midazolam. This research aimed to add to the evidence base for paediatric sedation. The results suggest a need for future research to cover further areas, including the safety and effectiveness of other drugs, worldwide practice and patient monitoring.

The use of anaesthetic rooms as the standard site of anaesthetic induction in the United Kingdom has been criticised and debated over several decades, and yet practice has remained largely unchanged. The impacts of the anaesthetic room on cost, efficiency, patient experience, and patient safety are either conflicting or unknown. This research utilised a systems approach to evaluate the efficacy of anaesthetic rooms and make recommendations for the improvement of both the design and practice of surgical suites in the UK. The study incorporated mixed methods to investigate the qualitative and quantitative benefits of anaesthetic rooms for all stakeholders. A survey of consultant anaesthetists investigated current practice and attitudes regarding the use of anaesthetic rooms and the importance of various types of ‘evidence’ for affecting change in practice. This study revealed the wide diversity of current anaesthetic practice and the factors that influence the selection of the site of induction. A second study, which used interviews with anaesthetists and perioperative managers explored the decision making surrounding the continued use of anaesthetic rooms and the relationship between design and practice. Factors influencing the perpetuation of anaesthetic rooms were shown to exist systemically across individual, organisational, and external levels. Willingness to change and the relevance of evidence for decision making is discussed. In a third study, a modified participatory design Delphi was used to investigate the decision making priorities of multiple anaesthetic room stakeholders to reach a consensus for the design of theatres in a new fictional hospital. The novel Delphi technique presented conflicting research findings to participants in order to require them to evaluate and come to agreement regarding the incorporation of anaesthetic rooms. A critique of this method is presented along with suggestions for future application. A cost-benefit analysis of anaesthetic rooms was then conducted in one NHS Trust. This was supplemented by ethnographic observations of its surgical suites to provide context to the historical timing data gathered retrospectively for financial and productive evaluations. The cost-benefit analysis revealed that there are missed opportunities associated with anaesthetic rooms, as downtime and delay mean that the potential financial gain and return on investment of anaesthetic rooms cannot be realised. An investigation of patient experience with surgical anaesthesia was conducted through a multi-part questionnaire evaluating patients’ expectations, anxiety, and satisfaction with their anaesthetic care. The study focused on the impact of the site of induction on patient experience and revealed that anaesthetic rooms do not appear to have a significant effect on patient anxiety and satisfaction. Opportunities for improving patient experience were identified, with the majority of these being unrelated to the site of induction of anaesthesia. Through a number of separate studies, this research provides a complete evaluation of anaesthetic rooms. It has identified the contradictions between stated priorities for anaesthetic rooms that stakeholders report and the actual choices that they make for the use and design of surgical suites. The human factors methods and systems approach that has been taken to this thesis has shown that it is a valuable way of investigating deeply embedded practices in healthcare. In addition, this research has set forth a novel method for integrating four dominant paradigms of healthcare improvement. The integration of participatory ergonomics and evidence-based practice may provide a useful method for reaching consensus of contentious issues, aligning systems design with individual and organisational priorities, and encouraging evidence evaluation as a part of the decision making process.

Brachial plexus block (BPB) techniques provide significant benefits including better pain control, faster discharge and reduced adverse effects compared to general anaesthesia. Prior to 2005 BPBs were performed using landmark, paraesthesia or electrical nerve stimulation (PNS) methods and were associated with reasonable success (70-80%) but were still associated with risk of failure and complications. Use of ultrasound (US) to guide local anaesthetic injection was first reported in 1989 but until 2004 remained unexplored. From 2004 we aimed to explore the feasibility, success and safety of ultrasound-guided brachial plexus block (USBPB) compared to techniques guided by anatomical landmarks or peripheral nerve stimulation. We hypothesized that USBPB would be feasible, have greater success and safety compared to standard methods. In 2004 we identified the possibility of using US to place infraclavicular block (ICB) and identified a pattern of local anaesthetic spread that predicated successful block. A subsequent randomized trial found improved success of US compared to existing methods. We examined success of US-guided axillary brachial plexus block (ABPB) and found that performance time and success were improved. In a large retrospective review of ABPB techniques we identified that US techniques were faster to perform, had a higher success and were safer compared to standard methods. We also assessed existing nerve localization methods in an observational study and found that both have poor sensitivity and specificity possibly explaining some of the limitations of these techniques. A bench study examining local anaesthetic injection using ultrasound found that both novices and experts could accurately determine local anaesthetic spread. In practice this is a useful marker for safe injection and could explain findings of increased safety with ultrasound methods. we systematically reviewed the literature for studies examining USBPB and this demonstrated that US improved block success and performance time. Subsequent pilot work indicated that US, in addition to improves block success and performance time. Subsequent pilot work indicated that US, in addition to improving quality, could also reduce volume of local anaesthetic required for successful block and we hypothesized that for certain techniques such as interscalene block this may improve safely. we compared US-guided interscalene block (ISB) using traditional volumes (20ml) and compared with a low volume (5ml) of ropivacaine 0.5%. Results demonstrated no difference in efficacy or duration but significant reduction in respiratory (and other) complications with lower volumes. We then compared US-guide ISB to PNS using and Up and Down Sequential Allocation design to estimate the minimum effective anaesthetic volume (MEAV50) for ropivavaine 0.5% for major shoulder surgery. Our findings indicated that volumes of local anaesthetic could be dramatically reduced with US (0.9 vs 5.4ml) whilst still providing effective pain relief. In the last ten years the cases and studies described have demonstrated that US improves BPB success and safety. For ISB US reduces volumes of local anaesthetic required for success whilst also reducing respiratory and other complications.

This PhD thesis contains five chapters. The first chapter of the thesis reviews the achievement of proficiency in procedural skills, common principles regarding the educational theory behind assessment. It further examines the literature about the diverse methods that is currently being used for the assessment of procedural skills in anaesthesia and also makes important implications from the literature in other fields of medicine. The second chapter identifies that visuospatial ability can predict technical performance of an ultrasound – guided needle task by novice operators, and also describes how emotional state, intelligence and fear of failure can have impact on this. This is an original, prospective, observational study, which is organized in four phases and participants complete all four phases of the study. The study concludes that mental rotation test predicts novice performance of an ultrasound – guided needling task. In addition, this novice performance is adversely affected by anxiety. Therefore both may prove useful in directing targeted training in ultrasound – guided regional anesthesia (UGRA). The third chapter validates a new assessment tool for the performance of UGRA, by examining whether it can adequately differentiate between performance levels in anaesthetists across the spectrum of expertise. It is a qualitative, observational study, which takes place during routine operating lists. We observe single performance of any UGRA by the participant anaesthetist, which formed part of the planned anaesthetic management of their patients. The study successfully validates the new assessment tool. The fourth chapter explores the association of video game experience with UGRA skills. This is another original, prospective, observational study, which involves three elements and the participants complete all three elements of the study. The study concludes that ‘gamers’ perform significantly better than ‘non – gamers’, and predicts psychomotor performance of an ultrasound – guided needle task. The last chapter summarizes conclusions, which are drawn at the end of each chapter concerning the investigations performed and the results obtained. It also indicates the possible future implications.

Early-onset spinal deformity (EOSD) is characterised by detection of spinal deformity (scoliosis, kyphosis or multi-planar) in children at aged less than five years. The common causes could be classified under congenital, neuromuscular, syndromic and idiopathic etiologies. Early treatment is paramount in preventing rigid, severe and progressive deformities that can cause pulmonary compromise. The inability of lungs and thoracic cage to support normal ventilation at rest constitutes the pathophysiology in manifestation of thoracic insufficiency syndrome (TIS). The treatment options have evolved from observation, serial casting, bracing to surgery. Early definitive spinal fusion is now obsolete and contra-indicated for EOSD. Growing rods (submuscular or subfascial) continues to be the standard of care in treating these challenging deformities. Vertebral expandable prosthetic titanium rib (VEPTR) continues to be an attractive option for TIS but is fraught with high complication rate. I hereby present a theme on EOSD with a set of thirty three peer reviewed indexed publications and one surgical patent in treating such challenging conditions highlighting my original contribution as Consultant spinal surgeon spanning over two decades. My pioneering and ground-breaking research that has shaped the surgical management of EOSD and helped define 'standard of care' is presented. My novel and innovative concept of treating EOSD using magnet driven growing rod (MdGR) along with its preliminary results is discussed. MdGRs are an attractive alternative in eliminating need for repetitive anaesthesia facilitating normal cognitive development in comparison to growing rods (CGRs). They also improve pulmonary function in neuromuscular scoliosis. A brief one page summary of all my indexed publications with comments on originality and how they contributed to spinal surgery is enclosed at the end of each chapter. My current research update on MdGR project at Royal National Orthopaedic Hospital (Stanmore), my surgical patent National institute of clinical excellence (NICE) position statement on MdGRs and clinical guidance documents are attached appendices I - III.

The number of clinical procedures performed in the USA using bone graft substitutes was estimated at 1.1 million in 2010 and is projected to reach 1.3 million in 2015. This increasing demand for bone graft substitutes is a result of an ever-ageing population coupled with recent reports in the clinical literature of concerns regarding the safety of allograft and recombinant bone morphogenetic proteins such as rh- BMP-2 and the supply of autograft, which has led to an increased clinical interest in synthetic alternatives to allograft; autograft; and recombinant growth factors. One such synthetic material is silicate-substituted hydroxyapatite (SiCaP). Mechanical testing revealed SiCaP to have similar mechanical behaviour to morcellised cancellous bone. In computated spinal and hip models the simulated stresses in SiCaP were determined to be low when in situ, indicating a stressshielding effect from the implanted metalwork and surrounding bone. We also found an inverse relationship between porosity and Young's Modulus. Our results indicated that the strut-porosity of a material substrate should be increased to maximise the potential for formation of a precursor to bone-like apatite after implantation in osseous defects and further confirmed previous reports that betatricalcium phosphate is less bioactive than hydroxyapatite. We demonstrated a direct link between the amount of strut-porosity and the osteoinductivity of SiCaP. We learned that adding a resorbable carrier phase did not impair the osteoinductive potential of SiCaP, suggesting that osteoinductivity is not necessarily determined in the first 24-48 hours post implantation. Most notably from our studies we determined that the osteoinductivity of SiCaP correlated with its performance in orthotopic defects. Our research confirmed our hypothesis that modifying the micron-scale physical structure of a hierarchical porous SiCaP based biomaterial influences its functional performance in vitro and such modifications can be applied to improve its performance outcomes in ectopic and orthotopic treatment sites in vivo.

For the past fifteen months, I have been attached to the Third Australian General Hospital as Anaesthetist, and now record my experiences gleaned from somewhere over a thousand cases of anaesthesia in war surgery. I may conveniently divide up the time in question into three equal periods of four months each. During the transfer of the hospital from England to France, and its subsequent establishment as a base hospital on the lines of communication, no surgery was possible for a period of about three months. During my first four months with this unit we existed as a General Hospital at Brighton in England, where practically all our patients arrived from the Base Hospitals in France. From the end of July to the end of November, 1917, I was attached to a Casualty Clearing Station in Flanders, where I gave anaesthetics for one of our own hospital surgeons, working together as "a team" all through the Flanders offensive. There remains a period of four months during which I have either been giving anaesthetics or instructing others in their use, at our Base. Although it is not my intention to quote figures extensively, it may be of interest to give the number of anaesthetics given by me in those three periods. I find at Brighton I gave just under 300 anaesthetics. At the Casualty Clearing Station (c.c.s.) exactly 660. At the Base Hospital upwards of 150, so that my experience of war anaesthesia is derived from a variety of operations in 1100 cases. In considering the experience gained by those anaesthetics, I think my object will be best attained by considering.- 1. The type of Patient. 2. The type of Anaesthetic given. 3. The type of wound and operation for which the anaesthetic was required.