The eight refereed publications and four abstracts of presentations which form the basis of this PhD each deal with patient health outcomes. The publications are drawn predominantly from practice based research in chiropractic services. In a systematic review of the impact of Patient Reported Outcome Measures (PROMs) on the process and outcomes of care for a single patient, Paper 1 describes this occurring across four domains; patient assessment and initial clinical decision making, tracking progress and evaluating current treatment efficacy, influencing the patient / clinician relationship and there is weak evidence to suggest they directly influence patient outcomes. Paper two is a descriptive review of the utility of PROMs to include their ability to improve communication and shared decision making in the patient / clinician relationship. Care Response is a novel, free to use multilingual electronic PROM system developed by the author. It has had significant impact in the chiropractic profession in Europe and Canada and has contributed data to 11 peer reviewed papers and four post graduate degrees (Abstract 1) Electronic PROM systems suffer from lower response rates than paper based systems. Abstract 2 reports a study looking at the impact of this missing information on the generalisability of the overall data collected. Non respondents to an emailed assessment 30 days after starting care were less likely to have had >30 days pain in the last year but were not otherwise significantly different from those returning electronic assessments. In a telephone survey comparing respondents and non respondents, patients global impression of change (PGIC) scores were identical and there was no statistical difference in pain scores. Paper 3 sought to ascertain if patient less likely to do well with chiropractic care could be identified from data routinely collected at baseline in chiropractic practice. Longer duration of symptoms at presentation, females with higher social disability scores and males with more adverse scores for depression were found less likely to describe themselves as much improved a month after starting care. In investigating for a relationship between outcome and components of the fear-avoidance model for chronicity in lower back pain, paper 4 found only a week relationship with catastrophisation at baseline however patient’s scores of catastrophisation, fear avoidance beliefs and low self efficacy just before their second visit were significantly associated with a poorer outcome. Paper 5 looking into a relationship between the risk category patients were placed into by the STarT Back Tool reported that whilst HIGH risk patients has more adverse scores for pain at presentation this rapidly faded and at 30 and 90 days there was no significant difference between the risk groups and patients reports of their recovery (PGIC) . Comparing the health outcomes of 8222 patients accessing chiropractic services either via the NHS or privately Paper 6 described those accessing a NHS route to have had symptoms for longer and more adverse scores across a range of health domains at presentation and to be less well 30 & 90 days later. However both NHS and private patient groups improved well and differences between the two disappeared when controlling for differences at baseline. Paper 7 sought to explore the ability of chiropractic clinicians working from 5 linked practices to identify those patients less likely to do well with care at the time of their initial assessment. It concluded that they generally failed to reliably predict outcomes with most practitioners doing no better than chance. The STarT Back Tool is increasingly being recommended to guide decisions as to care pathway for patients with spinal pain. Paper 8 looked to see if the timing of when this assessment was made had any impact on its ability to detect groups of patients responding differently when undergoing a course of chiropractic care. In the assessed population (n=749) attending 1 of 11 clinics in the UK there was a significant difference with ranking at the time of presentation being unrelated to outcome. When repeated a few days post initial visit over one third of patients had changed risk group with this subsequent group being found to be an independent predictor of improvement in multivariate analysis.

Working wrist splints are commonly used in the management of rheumatoid arthritis (RA), yet evidence for their effectiveness is inconclusive. A mixed methods, systematic review was conducted and found strong quantitative evidence, supported by qualitative literature, that working wrist splints reduce pain. The review also found moderate evidence that grip strength is improved and dexterity impaired. Insufficient evidence was found of their effect on function. The literature review exposed limited exploration of occupational therapists’ and users’ experiences and perceptions of the use and effectiveness of working wrist splints. Three focus groups were conducted with occupational therapists and revealed that therapists believed they provided a person-centred, customised service. Person- centred practice was exposed as being challenged at organisational and scope of practice levels. Focus groups identified opportunities in the field of work rehabilitation and measurement and use of activation levels to individualise self-management techniques. To explore patient perceptions and experiences of working wrist splints, a focus group and focused telephone interviews were conducted. Participants reported that splints relieved pain and improved some functional tasks while impeding others. Occupational identity influenced splint use for social and work purposes and the need for therapists to help assimilate splint use into a new occupational self-image was highlighted. Tailored patient education to maximise self-management techniques and outcomes was also highlighted. This work has strengthened the evidence for the effectiveness of working wrist splints for people with RA and variations across individuals and tasks in improving functional ability was exposed. Factors influencing splint effectiveness and implications for practice have been identified. There is scope to improve person-centred practice through enhanced training and inclusion of interventions tailored to individual activation levels. Those with RA should be supported to remain in work and increased choice of splint and improvements in design could also aid engagement and outcomes for users.

By the end of 2012, Zimbabwe had enrolled more than half a million patients on free antiretroviral treatment (ART). Reviews of ART programmes in sub-Saharan Africa revealed that one third of the patients drop out of the programme during the first three years of treatment. I explored reasons for programme attrition in an NGO-supported ART programme in rural Zimbabwe. In a mixed-methods design, I combined a retrospective cohort study among 8425 adult patients who initiated ART from 2005 to 2012, with a qualitative inquiry including 44 interviews, 8 focus group discussions with 78 participants, and participant observation during two months of field work. Programme retention at three years was 75%. Tracing of patients lost to follow-up revealed that mortality at 12 months was 1.8 times higher than reported before tracing: corrected mortality was 11.5%, 18.8% and 21.3% after 12, 36 and 60 months. 574/1055 (54.4%) deaths occurred before the next ART appointment, 481/1055 (45.6%) after missing the appointment. Programme retention did not imply consistent adherence to ART: 1780/6291 (28.3%) retained patients temporarily interrupted ART at least once for more than seven days. Qualitative data showed that patients temporarily interrupted ART for different reasons rooted in social, cultural and gender conflicts and related to mobility. ART restart was facilitated by social capital in family and kinship networks, decentralised access to ART and trusting patient-health worker relationships. Social isolation and discrimination of HIV-positive women by partner and in-laws, health workers blaming patients for missing an ART appointment and distance to the initiation site were the main reasons for prolonged and potentially fatal ART discontinuation. Our findings suggest that ART re-engagement after interruption is key for long-term retention. Programmes can prevent attrition from ART by decentralising their services, supportive management by health workers, and early tracing of medically- and socially vulnerable treatment interrupters.

This thesis explores how fluctuating, ambiguous, and medically unexplained illnesses might be quintessentially postmodern conditions that disrupt taken-for-granted medical and socio-cultural classifications. Drawing on qualitative interviews with people with the “contested” diagnosis of Fibromyalgia Syndrome (FMS), I offer the concept of embodying liminality to describe the disruptive possibilities of embodiment that resists containment and instead resides in the liminal space in-between health/illness, dis/ability, in/visibility, and absence/presence. Situating this analysis within a broader context of neoliberalism and disablism/ableism, I argue that the liminal embodied experiences of people with unexplained, contested, and in/visible illnesses might provide a critique of the increasing pressure we are all under to embody and enact narrow cultural ideals of healthiness, fitness, and competence. Ultimately, this thesis hopes to contribute to the deconstruction of damaging dichotomous categories and the harmful illusion of the invulnerable and perfect(able) body, and to reveal the liberating potentialities of embracing the fluid spectrum of embodiment.

The prevalence of musculoskeletal disorders is a major burden for modern societies. Due to the increasing aging population and the lifestyle changes, a significant number of people are severely affected worldwide. The important issue with these diseases is the fact that they cause pain and disability on a person's physical functioning for long time, thus diminishing the quality of life of the individual. Moreover, they are accompanied by a high financial cost for the society and the healthcare system. Current ways of treatment do not provide optimum therapy. They employ high concentration of growth factors and they are expensive, inefficient and many times exhibit various side effects. For this reason, an alternative solution is needed. Tissue engineering (TE) strategies offer a novel approach to the problem. The combination of the appropriate cell source with the essential scaffold leads to the formation of three-dimensional (3D) constructs, which can be subsequently, cultured within a bioreactor, with the employment of proper osteoinductive factors. This process leads to the generation of high number of efficiently differentiated cells, which are needed for cellular therapies. In this project, the generation of 3D mineralised cellular constructs was performed using mouse Embryonic Stem Cells (mESCs) encapsulated in alginate hydrogels. The novelty of this project lied on two components; the employment of a custom-made rotating wall vessel (RWV) perfusion bioreactor, which had been shown previously to exhibit advantageous properties regarding the efficient differentiation of high cell numbers needed for potential therapeutic applications and the use of simvastatin (Sim) in the culture media, acting as an osteoinductive substance in very low concentration of the nanomolar scale. Sim had been previously employed to induce osteoblast differentiation. The novelty lied on the total combined configuration with the low concentration of Sim and the perfusion bioreactor used for cell culture and differentiation. Evaluation of cell proliferation and osteogenic differentiation was performed through several analyses. Extended gene expression was tested and obtained results were also compared with those acquired previously by the currently used protocol with dexamethasone (Dex). Acquired results indicated that the favorable environment of the perfusion bioreactor culture could support higher cell number sand more efficient osteogenic differentiation in comparison to static configuration. Sim was more efficient when supplied in the culture at the appropriate time point, after two weeks of initiation of the experiment. Sim and Dex indicated similar outcome in biochemical analysis. Osteogenic gene expression was strongly induced after Dex treatment while Sim supported the generation of higher cell numbers. These findings suggested the generation of a more progenitor cell type after Sim treatment and a more mature phenotype after Dex treatment.

The overall aim of this thesis is to develop prediction models to identify key predictors of poor outcome in people with osteoarthritis (OA) and examine the cost effectiveness of two approaches to delivering primary care interventions for OA compared to current primary care. This thesis is comprised of two parts – the first part concerns the development of prediction models to identify the combination of factors that predicts poor outcome of OA in relation to pain and functional limitation at three year follow up for participants aged 50 years or more. The strongest baseline predictors of pain and functional disability were having pain in the previous year and poor physical function at baseline respectively. The models developed showed good internal validity and hence may be further tested for external validity in community-based adults with similar characteristics as those in this study. The second part involves a summary of evidence on the effectiveness of four primary care interventions (information and advice, simple analgesia, topical NSAIDs and exercise) in reducing pain and improving function at one or more joint sites among osteoarthritis patients in primary care. The results showed significant small to moderate improvements in pain and functional disability for advice/information, topical NSAIDs and exercise interventions compared to their controls, whilst simple analgesia failed to demonstrate significant improvements in either measures. This evidence was used to populate the economic (decision) model developed in this thesis. The decision model examined the cost effectiveness of two approaches to delivering primary care interventions for OA - stepped care and one-stop-shop care were compared with current primary care. The primary results were robust to changes in the input v variables with stepped care emerging as the most cost-effective option ahead of one-stop-shop care and current care in that order. These findings need to be confirmed in samples of primary care consulters.

Musculoskeletal (MSK) pain is a major reason why people consult their general practitioner. Analgesia plays a central role in its treatment but do not always work, resulting in the need to switch amongst analgesia potency levels. Stronger analgesia is however associated with increased adverse effects. The aim was to investigate the use of robust statistical approaches to determine socio-demographic and clinical factors associated with receiving and switching, prescribed analgesia in primary care management of MSK pain. The first phase reviewed statistical methods previously used in modelling medication switching, and established that Cox proportional hazards and logistic regression models were predominantly used. The second phase investigated the prevalence of prescribed analgesia, factors associated with being prescribed analgesia, and prescription patterns in the management of new MSK conditions using a general practice database. In 3236 incident consulters, 42% were prescribed analgesia, NSAIDs being most prescribed. In a 5 year follow-up period, three prescription patterns were identified: no analgesia or basic analgesia only, use of NSAIDs, and multiple-potency analgesia combinations. The main baseline factors associated with being prescribed analgesia, and stronger analgesia were increasing age and having been previously prescribed analgesia. The third phase used Cox and Weibull frailty models to identify factors associated with switching analgesia and switching to stronger analgesia. The main factors identified were age, gender and initially prescribed analgesia. The fourth phase used a prevalent cohort of 1610 patients aged 50+ with linked self-reported and medical record data. Patient-reported factors such as level of physical function and pain interference were also associated with switching of analgesia. Using a propensity score approach to modelling outcomes suggested those who switched analgesia did not have better three year outcomes, but further research is required to establish if switching analgesia is beneficial in reducing pain and improving function.

Objectives: The primary aim of this UK-based study was to identify core clinical competencies (skills, knowledge, attitudes, and behaviours) for primary-care-based extended-scope physiotherapists (ESPs) working in the field of adult musculoskeletal (MSK) medicine. Although the musculoskeletal (MSK) ESP role in the UK has been in existence for over 10 years, there is no competency and curriculum framework supporting these posts. This study used a consensus-building methodology with a multidisciplinary panel of MSK experts to identify core clinical competencies for MSK ESP practice. Methods: Purposive sampling was used to recruit MSK ESPs and MSK medical experts from six specialist fields within medicine: rheumatology, neurology, neurosurgery, general practice, orthopaedic surgery, and rehabilitation medicine. Seventy-two experts volunteered to take part in a three-round online Delphi survey and fifty-six experts completed all three rounds. Qualitative data from the first and second questionnaire rounds were analysed using content analysis, and descriptive statistics facilitated the presentation of quantitative data. Principal findings: The expert Delphi panellists identified 104 core clinical competencies for primary-care-based MSK ESP practice and they reached a consensus view on 85 competency items. Importance and Relevance: This is the first study to have identified core clinical competencies for primary-care-based MSK ESPs. Although further work is required to validate the results of this Delphi survey, they represent a contribution to knowledge in the field of MSK ESP practice and they should assist the professional body and the health care regulator with their development of a nationally agreed competency and curriculum framework for MSK ESP practice.

Background: Osteoarthritis (OA) is the commonest long term condition in primary care. Current guidance suggests that much can be done to improve outcomes but existing research suggests doctors and patients are pessimistic about OA treatment. An important question concerns the role of the primary care consultation in this incongruity. This study used a combination of video recorded consultations and post consultation interviews using video-stimulated recall (VSR), to uncover what happens when patients discuss OA with their general practitioners (GPs). Methods: With ethical approval, GP consultations with 190 consenting patients aged ≥ 45 were recorded. Twenty consultations contained reference to OA, and 17 of these patients and their GPs (n=13) participated in post consultation interviews. Analysis involved thematic analysis of videotapes and comparisons of patient and GP interviews with the consultation findings. Results: Osteoarthritis arises in the consultation in complex contexts of multi-morbidity, multiple and varied patient agendas which are often not explicit, and against a background of clinician agendas including time pressures, multiple guidelines and service requirements. Dissonance between doctors and patients was observed and was often underpinned by patient perception of lack of empathy and symptom validation. Doctors and patients often adopt a ‘lay’ construct of OA where joint pain is seen as a normal part of life; this influences doctor and patient behaviour and acts as a significant barrier to formal recognition and hence treatment of the condition. Conclusions: The design of interventions to improve outcomes of patients with OA must take account of the complexity and heterogeneity of presentations in primary care. Osteoarthritis appears to be experiencing an identity crisis, with doctors and patients uncertain of what constitutes OA and when to use the term ‘osteoarthritis’. Further work is needed to identify effective ways of translating best evidence about OA management into effective primary care strategies.