Introduction. Previous investigations that have attempted to relate mechanical parameters to NSLBP groups are often contradictory of each other, and currently clear mechanical markers for LBP remain elusive. In order to move forward in this area, it may be necessary to take a step back, and improve understanding of ‘normal’ spinal biomechanics (i.e. in low back pain free populations). Indeed, Peach et al. (1998) stated “By knowing what is “normal” and what is “abnormal” it may be possible to provide objective evaluation of rehabilitation protocols, and possibly classify different low back pathologies” (Peach et al. 1998). Therefore, an improved understanding of biomechanical behaviours in groups of back pain free people is desirable, particularly at an inter-vertebral level, an area where clear knowledge gaps still exist. Control of the spine during voluntary movement requires finely-tuned coordination of numerous trunk muscles. This dynamic control is believed to be achieved via communication between three sub-systems, the passive (vertebrae, discs and ligaments), the active (muscles and tendons) and the control (central and peripheral nervous system) systems. Investigating the interplay between these sub-systems however is difficult, as the spine is a complex structure with a hidden kinematic chain. Quantitative fluoroscopy (QF) is an imaging technology capable of measuring continuous spinal kinematics at the inter-vertebral level, and surface electromyography (sEMG) provides a non-invasive means of objectively quantifying muscle activity. This study used QF and sEMG technologies concurrently to investigate relationships between and amongst lumbar kinematic (QF determined) and muscle activity (sEMG determined) variables, during weight-bearing active forward flexion. This was the first time such technologies have been combined to investigate the biomechanics of the lumbar spine in vivo. An improved understanding of normal lumbar kinematic and myoelectric behaviour, will assist in the interpretation of what is abnormal in terms of inter-vertebral spinal mechanics. Methods. Contemporaneous lumbar sEMG and QF motion sequences were recorded during controlled active flexion of 60° in 20 males with no history of low back pain in the previous year. Electrodes were placed adjacent to the spinous processes of T9, L2 and L5 bilaterally, to record the myoelectric activity of the thoracic and lumbar erector spinae (TES and LES) and lumbar multifidus (LMU) respectively. QF was used concurrently to measure the maximum inter-vertebral rotation during flexion (IV-RoMmax) and initial attainment rate for the inter-vertebral levels between L2 and S1, as well as each participant’s lordotic angle. The sEMG amplitude data were expressed as a percentage of a sub-maximal voluntary contraction (sMVC). Ratios were calculated between the mean sEMG amplitudes of all three muscles examined. Each flexion cycle was also divided into five epochs, and the changes in mean sEMG amplitude between epochs were calculated. This was repeated to determine changes between all epochs for each muscle group. Relationships between IV-RoMmax and all other kinematic, morphological (i.e. lordosis) and muscle activity variables were determined using correlation coefficients, and simple linear regression was used to determine the effects of any significant relationships. The reliability and agreement of the IV-RoMmax, initial attainment rate, and normalised RMS sEMG measurements were also assessed. Results. The reliability and agreement of IV-RoMmax, initial attainment rate and sEMG amplitude measurements were high. There were significant correlations between the IV-RoMmax at specific levels and the IV-RoMmax at other lumbar motion segments (r = -0.64 to 0.65), lordosis (r = -0.52 to 0.54), initial attainment rate (-0.64 to 0.73), sEMG amplitude ratios (r = -0.53) and sEMG amplitude changes (r = -0.48 to 0.59). Simple linear regression analysis of all significant relationships showed that these variables predict between 18% and 42% of the variance in IV-RoMmax. Conclusion. The study found moderately strong relationships between kinematic, morphological and muscle activity amplitude variables and the IV-RoMmax of lumbar motion segments. The effects of individual parameters, when combined, may be important when such inter-vertebral levels are considered to be sources of pain generation or targets for therapy. This is an important consideration for future non-specific low back pain (NSLBP) research, as any attempts to associate these parameters with low back pain (LBP), should also now take in to account the normal biomechanical behaviour of an individual’s lumbar spine. Indeed, consideration should be given to the interactions that exists between such parameters, and they should not be considered in isolation. Multivariate investigations in larger samples are warranted to determine the relative independent contribution of these variables to the IV-RoMmax.

No description available.

Systemic neuromodulatory medications (NMs) are the conventional management modality of neuropathic orofacial pain (NOP). Topical administration of NMs such as amitriptyline, carbamazepine and gabapentin have been reported to show promising results when used with NOP, however, the effect of exposure of oral mucosa and skin to topical NMs has not been examined and is therefore unlicensed. The aims of the research contained within this thesis were to: a) investigate the effects of the aforementioned NMs on cell lines and 3D tissue relevant to the orofacial tissue in vitro; b) conduct a preliminary study using RNA extracted from human gingival tissue to investigate whether the potential therapeutic targets for these NMs were expressed. Cellular viability was measured using alamarBlue®, testing the effects of NMs on monolayer cell culture (2D): human skin and oral keratinocytes and mouse fibroblasts. Effects on cell counts were investigated by a CCK-8 assay. Morphological changes and cytokine expression were investigated using scanning electron microscopy and antibody array, respectively. Human gingival tissue biopsy was used to investigate the expression of receptors at the mRNA level using PCR. Amitriptyline exposure was found to decrease cellular viability and count, along with morphological changes as opposed to carbamazepine and gabapentin which had little demonstrable effects. Amitriptyline’s cytotoxic effect was confirmed using 3D oral mucosa models. Amitriptyline’s effect on 3D models was then further examined using immunohistochemistry (H&E, anti-caspase 3 antibodies) and immunofluorescence (anti-amitriptyline antibody). In the 3D model, amitriptyline caused apoptosis after repeated exposure, but was able to traverse tissue barriers, which was also confirmed by High Performance Liquid Chromatography (HPLC). The results of preliminary genetic investigations suggested the expression of the most receptors analysed, this suggests that further studies are required to investigate the efficacy of the topical route as a treatment for NOP. The overall results demonstrate amitriptyline toxicity and avoiding topical amitriptyline is therefore likely to be advisable. Carbamazepine and gabapentin exposure were less harmful and possibly more suitable topical choices, but further studies need to be conducted.

Title: BOS Orthognathic DVD: RCT assessing patients’ knowledge and satisfaction Objectives: To compare patients’ knowledge of orthognathic treatment and satisfaction with their multi-disciplinary clinic consultation, after receiving information in a standard format versus standard format plus BOS Orthognathic DVD. Design: Multi-centred, randomised controlled trial. Setting: Multi-disciplinary orthognathic clinics at four hospitals in Merseyside, UK. Participants and Methods: 106 participants, age > 16 years, attending their first multi-disciplinary orthognathic clinic, were given information on orthognathic treatment in either the standard format – verbal and written or the standard format plus the BOS Orthognathic DVD. Primary outcome measures were participants’ knowledge of orthognathic treatment and satisfaction with their multi-disciplinary clinic consultation and information provided. Validated knowledge questionnaires were given prior to the multi-disciplinary clinic consultation and 4-6 weeks later. Satisfaction was assessed from participants’ response to 16 questions using visual analogue scale. Results of knowledge scores were analysed using ANCOVA at p < 0.05, and satisfaction using non-parametric Mann Whitney Wilcoxon test. Results: Knowledge scores improved from baseline in both groups. Baseline knowledge had a statistically significant effect on participants’ follow-up score. No significant difference in knowledge score was found between groups at follow-up once the baseline score had been accounted for. No difference in general satisfaction was found between groups. However, satisfaction with the DVD was significantly less than general satisfaction (p=0.015). Conclusions: There was no difference in participants’ knowledge of orthognathic treatment or satisfaction when given information in the standard format or standard format plus the BOS Orthognathic DVD.

The use of total ankle replacement (TAR) for treatment of arthritis is rapidly increasing, but survival rates are of major concern. The primary indication for TAR revision is implant loosening, which is linked with inadequate primary stability manifested in higher levels of initial implant-bone micromotion. Finite-element (FE) modelling has been utilised to assess micromotion of arthroplasty implants, but not TAR. Additionally, the biomechanical consequences of TAR malpositioning during surgery – previously linked with higher failure rates – remain unexplored. The aim of this thesis was therefore to apply FE modelling to estimate implant-bone micromotion and peri-implant bone strains of current TAR designs under optimally-positioned and malpositioned cases, and thereby identify fixation features and malpositioning scenarios that place the reconstructed ankle at risk of early loosening. Computational models simulating commonly-used TAR designs (BOX®, Mobility® and Salto®) implanted into the tibia and talus were developed; the loads applied were the contact forces acting in the ankle during gait, as calculated using a previously-validated musculoskeletal model, while implementing muscle-architecture data obtained through dissections of cadaveric legs. Micromotion and strain outcomes were larger for the tibial compared with the talar components, in agreement with previous clinical observations. The tibial Mobility® and talar Salto® components demonstrated the largest micromotion. A gap between the tibia/talus and implant component resulted in a considerable increase in implant-bone micromotion and peri-implant bone strains; the Salto® design was relatively ‘forgiving’ for such malpositioning. It was concluded that better primary stability can be achieved through fixation nearer to the joint line, while relying on more than a single fixation peg, and preserving more of the cortical sidewalls of the bone; incomplete seating of the implant on the bone increases the risk for TAR failure. The models presented in this thesis may assist implant designers and surgeons in improving TAR designs and surgical techniques.

The last decade saw a resurgence in the use of large diameter metal on metal (MoM) hip arthroplasties. Some of these devices have reported an unacceptably high failure rate secondary to the development of soft tissue lesions. Multiple sources have reported that patients with total hip replacement (THRs) with taper junction experience greater failure rates. Using the facilities of a national explant retrieval unit, a prospective study was conducted to investigate the relationships between the wear of MoM devices, the corresponding blood, serum and synovial fluid cobalt (Co) and chromium (Cr) concentrations, and the host aseptic lymphocyte dominated vasculitis associated lesion (ALVAL) response and soft tissue damage as noted during revision surgery. Investigation of the role of blood metal ions in identifying poorly performing bearing surfaces revealed linear regression analysis demonstrated a powerful relationship between total volumetric wear rates and blood Co and Cr concentrations, with R2 values greater than 85% (p<0.001). Examining the source of metal debris and its relationship to blood/joint fluid metal ions and periprosthetic tissue metal particle sizes revealed greater wear rates were associated with larger particle sizes in excised tissues (p<0.001). Greater source contribution of wear debris from the taper junction was associated with significantly lower synovial fluid Cr concentrations and smaller particle sizes (p<0.001). Examining the soft tissue damage and ALVAL response revealed, the extent of soft tissue injury observed at revision surgery was more strongly associated with the presence of fluid and the ALVAL grade than the synovial fluid concentrations of Co and Cr or total volumetric wear. The higher grade ALVAL was associated with increasing age and joint fluid Co concentrations (p<0.001). While adverse reactions occurred more frequently in the presence of abnormally wearing devices, soft tissue injury does not appear to be mediated by a direct toxic effect of metal.

Total hip replacement is a human surgical intervention with the aim of pain relief and function restoration, with a survival rate of ≥ 90% at ten years. Currently, imaging techniques are the primary diagnostic and follow-up method, but are unreliable for early loosening detection. Vibrometry has been proposed as an alternative, more sensitive method for loosening diagnosis. Despite the fact that acetabular cups have a higher revision rate over femoral components, most of the existing vibrometry literature is stem related. A limited number of studies have examined cup loosening without defining the loosening level detected. Hence, the present study aimed to investigate the feasibility of detecting acetabular cup loosening using vibrometry, and to define the earliest loosening phase that could be accurately detected. Three objectives were devised to address this aim. Firstly, a simplified set-up with minimal boundary conditions utilising Sawbones blocks. Secondly, a complex bone geometry was examined by utilising a Sawbones hemi-pelvis, and thirdly a more clinically relevant experiment was tested by using a composite femur and hemi-pelvis. Loosening was demonstrated by a reduction in the fundamental frequency and an increase in the magnitude of the related harmonics. By quantifying the magnitude of the harmonics in relation to the fundamental frequency, it was found that the harmonic ratio would increase, corresponding to the degree of loosening. These findings support the existing vibrometry literature. In the first objective the minimum detected simulated loosening was 1mm zone 2 loosening within the frequency range 2000-2500Hz. For the second and third objectives this was 1mm spherical acetabular cup loosening within the range 500-1500Hz. Hence, the study suggests that vibrometry has the potential to diagnose early acetabular cup loosening. This study is therefore novel because it has defined the minimum acetabular cup loosening level that can be reliably detected, alongside the favourable frequency range.

The hip joint is subjected to cyclic loading and motion during activities of daily living, which can induce micromotion of total hip replacements. High levels of micromotion inhibit bone formation, and hence osseointegration of cementless implants. Initial stability is therefore crucial to ensure successful osseointegration of cementless acetabular cups. Hence, it is important to be able to measure the micromotion of acetabular cups in vitro in order to predict if they will survive once implanted. There are no standardised methods to measure cup micromotion however there are numerous studies available in the literature. These studies have two main limitations: they only measure cup micromotion in the assumed dominant direction(s) of motion rather than in six degrees of freedom; and they overlook the effect of dynamic hip motion as the hip joint is held in a fixed position. Finally, most of these studies either use cadaveric pelvic bones or synthetic foam blocks with a hemispherical cavity, both of which have their advantages and limitations. A new robust methodology capable of measuring cup micromotion in six degrees of freedom under cyclic loading and hip motion was developed, as well as a more representative synthetic acetabular model which replicated the structural support in the acetabulum. A number of investigations were carried out using this protocol. The results indicated that hemispherical cavities used to model the acetabulum overestimate cup stability compared to the more representative model which replicated the natural acetabulum; there was a significant increase in cup micromotion under dynamic hip motion; and clinically relevant micromotions were present in all translations. This novel protocol provides a better understanding of the behaviour of an implanted press-fit cup and the basis for more representative protocol for future pre-clinical evaluations of new design features that can improve cup fixation, and hence its longevity.

Osteoarthritis of the knee is one of the most prevalent diseases. The primary treatment for young patients is regenerative cartilage repair. The best treatment for the middle aged group is cartilage substitution material. Although in the worst case scenario, knee replacement becomes an option, giving proper treatment in advance, most patients can postpone or even avoid the irreversible replacement procedure. Since the surface varies in size and shape among patients, the conventional standard sized instruments are not appropriate for these novel treatments. The existing preparation technique used by surgeons is freehand debridement, which relies on highly skilful and experienced surgeons to yield good results. Although there are some patient-specific instrumentations on the market, the majority of them are designed to assist the conventional knee replacement implants, and are not applicable on curved surfaces. The aim of this study was to develop effective, simple and standardized patient-specific instrumentations for large joint surface preparation. The study started from verifying the accuracy of experimental equipment and proposed patient-specific techniques and instruments. Then, an experiment on plastic bone samples was performed. The outcomes showed that the errors of repairing surface, depth, and position were less than ±0.5 mm, ±0.5 mm and ±1.0 mm respectively. This is regarded as sufficiently accurate to prepare the knee surface. Then, some improvements were made on the surgical jigs and procedures for the later cadaveric experiment. Eight cadaveric samples were tested. The outcomes showed that the 5% and 95% percentiles of errors in repairing surface, position errors and depth errors were -0.22 mm to 0.56 mm, -1.40 mm to 1.04 mm, and -0.58 mm to 0.20 mm respectively. Furthermore, patient-specific instrumentations were designed for arthroscopic procedures, which is the only patient-specific guide that can be used arthroscopically for orthopaedic surgeries. A tibial preparation guide was also designed, but further tests are needed for this device.

Aims The aim of this thesis was to investigate, for supervised training in laparoscopic colorectal surgery (LCS); clinical safety, proficiency gain, training quality and programme structure. The specific objectives were (1) define national learning curves for LCS and analyse the clinical safety of supervised LCS training (2) assess the performance of supervised LCS trainees and define their proficiency gain (3) evaluate the impact of training quality and programme structure. Methods Objective 1: National data was used to create national proficiency gain curves and define the national clinical outcomes for LCS. Clinical data and proficiency gain curves from the National Training Programme (NTP) and laparoscopic fellowships were compared against this. Objective 2: The formative Global Assessment Scale (GAS) scores were used to assess the performance and define the competency proficiency gain for supervised LCS training. Summative Competency Assessment Tool (CAT) scores were used to assess trainee performance on completion of training. Objective 3: Mini-Structured Training Trainer Assessment Report (mini-STTAR) scores were used to measure training quality and the impact of the Lapco-TT course. A survey study was used to evaluate the structural and organisational quality of the NTP. Results There has been a national learning curve for mortality associated with the introduction of LCS. Supervised training in LCS flattened the clinical learning curve and prevented unnecessary patient harm. The supervised competency proficiency gain curve for LCS was around 30 cases. Increased training volume improved technical performance in objective summative competency assessment, which in turn improved clinical outcomes. The quality of the training, structure and organisation was high and Lapco-TT course augmented training. Conclusion The introduction of novel surgical techniques is associated with patient harm. LCS was learnt safely, efficiently and effectively within the NTP. The NTP model, including the structure, organisation, competency assessment and audit provides a template for future training programmes.