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Inhaled administration is the mainstay of asthma and chronic obstructive pulmonary disease (COPD) management using either a pressurised metered dose inhaler (pMDI) or a dry powder inhaler (DPI). Poor disease control and increased hospitalisations is linked to poor inhaler technique. Previous studies to assess inhaler technique have used subjective measures and there is very limited data about the inhalation characteristics used by patients when they use their inhalers. Inhalation flow profiles when patients use their pMDI and inhalation pressure profiles when they use DPIs have been measured using 659 subjects (106 children with asthma [CHILD], 361 adults with asthma [ADULT], 142 COPD [COPD] and 50 healthy volunteers [HEALTHY]) in 5 separate studies. All patient studies used their real life inhaler technique. One of the studies also evaluated the value of using a pMDI co-ordination aid and training these patients to prolong their inhalation whilst a different one investigated the impact of using enhanced training when using a DPI. The first study, 20 CHILD, 57 ADULT and 32 COPD subjects, revealed that the mean (SD) inhalation flows through a pMDI were 108.9 (40.4), 146.0 (58.8) and 107 (50.6) L/min, respectively and only 7, 10 and 10 used a slow flow. In the second pMDI study involving, 20 CHILD, 130 ADULTS, 31 COPD patients, their flows were 70.5 (36.4), 131.4 (60.8) and 70.9 (28.1) L/min and 5, 53 and 10 used their pMDI with good co-ordination. However only 3, 6 and 9 patients had good co-ordination and slow flow. In the third study, 71 ADULT patients, the mean (SD) pMDI inhalation flow was 155.6 (61.5) L/min which decreased (p<0.001) to 112.3 (48.4) when the pMDI was fitted with a co-ordination aid. This was due to the increased resistance to airflow from the aid. Inhalation flow further reduced (p<0.001) to 73.9 (34.9) L/min when patients were trained to prolong their inhalations. Their inhaled volumes did not change whereas mean (SD) inhalation times were 1.60 (0.21), 1.92 (0.80) and 2.66 (1.03) seconds (p< 0.001) respectively. There was a good correlation between their inhaled volume and forced vital capacity with a ratio of 0.7 suggesting that the patient used a full inhalation. A DPI study, involving 16 CHILD, 53 ADULT and 29 COPD patients, measured inhalation characteristics through different DPIs (low to high resistance) when patients used their real life DPI inhalation manoeuvres. The inhalation characteristics were lower in CHILD and highest in ADULT. Overall flows were higher when using low resistance DPIs but the pressure changes and the acceleration of the inhalation flow were significantly higher with high resistance DPIs which suggest more efficient de-aggregation of the formulation. There was a tendency for more problems with low resistance DPIs than high resistance DPIs. The last study involved CHILD, ADULT, COPD and HEALTHY subjects (50 of each) when they inhaled through a Spiromax and a Turbuhaler (similar resistance) after standard verbal inhalation technique training and when using enhanced training with an IN-Check Dial. The order of inhalation characteristics was HEALTHY > ADULT > COPD > CHILD. Significant (p<0.001) improvements in the inhalation flows, pressure changes and acceleration of the flow were achieved in all groups after the enhanced training. The studies provide an insight into the inhalation characteristics of patients when they use different inhalers. The main problem with pMDI use was short inhalation times and when patients were trained to prolong their inhalation then flows reduced. Enhanced training when using a DPI significantly improved the technique of all patients.

Background to the study: Cochlear implants (CI) can help to suppress tinnitus and often make existing tinnitus more bearable. However, a number of patients still suffer from tinnitus afterwards. In some cases the implantation makes existing tinnitus worse, or tinnitus may occur as a result of cochlear implantation. Because of the inconclusive aetiology of tinnitus it is difficult to treat its effects. So far, one of the most popular treatments for tinnitus is the widely used Cognitive Behavioural Therapy (CBT), which aims to influence dysfunctional emotions, behaviours and cognitions though a goal-orientated, systematic procedure. CBT aims to minimize the side-effects of tinnitus and help to manage it in a more efficient way. CBT has been investigated in several studies and shows promising results in reducing the debilitating effect of tinnitus. CBT has not yet been used specifically for, or investigated in, relation to treating CI users suffering from tinnitus. Aims and outline of the study: Our research aimed to investigate CBT’s effectiveness for cochlear implant users. Using a randomized control trial, we investigated whether two-hour Tinnitus Workshops for the control group were as equally as effective as CBT for the research group. We also explored if either type of treatment for cochlear implant users needed any modifications to make them more suitable for this group of tinnitus sufferers. Using Open Questions, we investigated tinnitus in cochlear implant users. We analysed the Open Questions from both groups, creating a profile of a typical cochlear implant user who suffers from tinnitus, and we also explored whether both interventions (Tinnitus Workshop or CBT) were suitable for this kind of patient. Data was gathered, pre- and post-interventions, by questionnaires; these were Tinnitus Questionnaires (TQ), Visual Analogue Scale (VAS), Quality of Life Short Form 36 Health Survey (SF-36) and Hospital Anxiety and Depression Scale (HADS). Results: In the control group, we found no significant differences between the TQ scores pre- and post-intervention. VAS scores post-intervention were lower than pre-intervention, indicating some improvement in individual tinnitus perception; however, the difference was not significant. In the research group, we found small, but not significant, differences in both TQ pre- and post-intervention (z =1.83, p>.05) and in VAS (z=0.14, p>.05). No significant differences were found between the control and the research group pre- and post-intervention. Conclusions: The questionnaires used in this study, such as TQ or VAS, showed a decrease in general tinnitus distress, but a larger-sized sample group may be needed for greater statistical certainty. The results from the Open Questions showed that cochlear implant users were affected by tinnitus in a similar way to non-cochlear implant users. Overall, both interventions need further, small modifications and adjustments to their protocols in order to be more effective for this type of tinnitus sufferer.

Personality disorders (PDs) are common, chronic, mental health problems. The majority of treatment outcome research, which has focused specifically on Borderline PD, has provided substantial empirical support for Dialectical Behaviour Therapy (DBT; Linehan, 1993), particularly in terms of self-harm reduction. Nevertheless, DBT graduates can continue to experience poor personality functioning across PD diagnostic categories, Axis I disorders, and restricted lives. Acceptance and Commitment Therapy (ACT; Hayes, Strosahl, & Wilson, 1999), might be suitable as a follow-up intervention for DBT graduates, to address their continued difficulties: to date, however, there has been little empirical investigation of its utility in relation to PD. This thesis was therefore designed to examine theoretical underpinnings of ACT relevant to the development of an ACT intervention for DBT graduates. Study 1 tested the performance of a new self-report measure of cognitive fusion (CF), the Cognitive Fusion Questionnaire (CFQ), with a mental health sample, including individuals with PD. CF is a key ACT concept, and the CFQ proved to be a psychometrically sound measure of CF with people with mental health problems. Study 2 used cross-sectional modelling to show that CF fully mediated the relationships between two PD risk factors, negative affectivity and childhood trauma, and personality functioning in adulthood. Study 3 used the CFQ to investigate the behavioural correlates of CF. These findings strengthened the possibility that an ACT-based intervention might prove effective in improving outcomes for DBT graduates. To explore this further, Studies 4 and 5 were designed as very small-scale uncontrolled treatment development trials for this population. Study 4 suggested that ACT had a positive impact on engagement in life, but produced little improvement in psychiatric symptomology. Study 5 tested a revised protocol, which yielded more consistently positive findings, with improvements in both engagement in life and psychiatric symptoms. These findings tentatively suggest that ACT may have a role to play as a DBT follow-up intervention.

Stroke represents the second leading cause of global mortality. Despite improvements in acute stroke management in recent years, many patients suffer a poor outcome and stroke represents a leading cause of adult disability. Beyond the human impact of disease, societal costs are huge. Stroke is principally a disease of the elderly population, which is increasing in size. Incidence is increasing in the younger population and the developing world. Accordingly, the global burden of stroke is anticipated to increase substantially in the coming decades. Fatal and disabling strokes are frequently preceded by either a milder, non-disabling stroke or a transient ischaemic attack (TIA). The optimised implementation of effective preventative strategies and the evaluation of potentially novel therapeutic agents, both represent crucial strategies in reducing the burden of cerebrovascular disease. This thesis addresses two aspects of secondary prevention following ischaemic stroke: Firstly, improved identification and optimised use of anticoagulant based secondary prevention for an established but frequently occult risk factor for recurrent stroke; paroxysmal atrial fibrillation (PAF). Secondly, the evaluation of xanthine oxidase inhibition (XOI), as a potential therapeutic strategy for the prevention of stroke and cardiovascular disease. Chapter 1 highlights the importance of optimising secondary preventative strategies following ischaemic stroke and TIA. The anticipated increase in the global burden of cerebrovascular disease is described, together with review of stroke outcomes in the context of contemporary acute stroke management. The risk of stroke recurrence following ischaemic stroke and TIA is reviewed, followed by discussion of available secondary preventative strategies. In Chapter 2, the role of AF in the aetiology of stroke disease is reviewed in greater detail. The early and subsequent risk of stroke recurrence in patients with AF is considered, together with review of the evidence for antithrombotic therapy. The potential for increased detection of paroxysmal AF in the ischaemic stroke and TIA population is discussed, with particular reference to the therapeutic implications and potential for reduced stroke recurrence. In Chapter 3, details of a randomised, open-label trial with objective outcome assessment, in patients with recent (< 7 days) ischaemic stroke or TIA, are presented. This study evaluated the use of non-invasive cardiac event monitoring to detect AF, in patients with ischaemic stroke or TIA presenting with sinus rhythm, an area of management for which a robust evidence base is lacking. The primary endpoint was the difference in AF detection at 14 days, between patients randomised to receive supplemental cardiac event monitoring of 7 days duration, compared to those receiving standard guideline based investigation alone. Detection of AF was defined as evidence of “sustained” PAF and “any duration” PAF episodes. Secondary endpoints were the difference in AF detection at 90 days and the difference in AF-thromboembolic prophylaxis-related anticoagulation (e.g. warfarin) at 14 & 90 days. 100 patients were enrolled and completed 90 day follow up. “Sustained” and “any duration” PAF episodes were detected, respectively, in 16% (95% CI, 7.2 – 29.1%) and 42% (95% CI, 28.2 – 56.8%) of patients through 7 days non-invasive cardiac event monitoring. Supplementation of standard guideline based investigation with 7 days’ cardiac event monitoring resulted in detection of “sustained” and “any duration” PAF episodes in an additional 16% (4.7 – 27.3%) and 40% (25.2 – 54.8%) of patients, respectively, at 14 days follow up. These differences persisted at 90 days. Anticoagulant therapy was commenced within 14 days in 16% of the group randomised to receive supplemental monitoring, versus none randomised to standard investigation alone (p<0.01). This difference persisted to 90 days (22% versus 6%, p<0.05). This study provided the first randomised controlled evidence for a specific investigation strategy for the detection of occult PAF in unselected patients with ischaemic stroke and TIA. These data should support guidelines regarding the management of this patient group. In addition, the study provided evidence that this strategy is not reliant on specialist electrocardiological service support, with very good agreement [(96%; 95% CI, 86.3 – 99.5%), Fleiss’ Kappa 0.86, p < 0.00001] observed between non-cardiology trained stroke clinicians and the independent reporting electrocardiology laboratory for “sustained” PAF detection. In a related observational study, the predictive value of detection of AF in the period immediately following ischaemic stroke or TIA was examined, relative to interval evaluation for AF by non-invasive cardiac event monitoring, performed 90 days following the index event. This study demonstrated that identification of AF immediately following stroke holds strong positive predictive value for subsequent AF detection following a 90 day interval, supporting treatment decisions being based on the findings of early monitoring. Negative predictive value of failure to identify AF through early monitoring was only modest, suggesting that repeated investigation may be of value. In Chapter 4, the hypothetical role of uric acid (UA) in the pathogenesis of cardiovascular disease is reviewed. Conflicting data are discussed, including those which support the hypothesis that serum UA represents a surrogate marker of elevated cardiovascular risk attributable to either its association with established cardiovascular risk factors or, alternatively, as a surrogate marker for a novel mechanism of vascular injury: harmful oxidative stress produced by the xanthine oxidase enzymatic system. XOI is discussed as a potential novel therapeutic strategy in the prevention and management of cardiovascular disease. In chapter 5 a systematic review and meta-analysis of studies evaluating the effect of XOI on cardiovascular health in humans are presented. This study identified a body of heterogeneous studies, reporting largely positive results. In meta-analysis, improvement in brachial artery flow mediated dilatation, [2.50% increase (95% CI, 0.15 – 4.84%)] and venous occlusion plethysmography derived forearm blood flow response to acetylcholine, [69% increase relative to control arm (95% CI, 18 – 119%)], indicated that XOI improves endothelial function amongst patients with, or at risk of, cardiovascular disease. In addition, XOI reduces vascular oxidative stress, Malondialdehyde reducing by 0.56 nmol/ml (95% CI 0.26 – 0.87 nmol/ml). Several studies indicated that the benefits of treatment may be limited to patients with hyperuricaemia. Definitive clinical endpoint studies were lacking. The study confirmed that XOI has beneficial effects within the cardiovascular system, providing supportive evidence for further study in the stroke patient population and in relation to more definitive clinical endpoints. In Chapter 6, three surrogate measures of cardiovascular risk: Carotid intima media thickness (CIMT); blood pressure pulse wave analysis (BP-PWA); and endothelial function are reviewed. Each is considered with respect to their independent predictive value for risk of cardiovascular disease, and utility as surrogate outcome measures in clinical trials. Together with chapter 4 and the systematic review reported in chapter 5, this chapter provides additional background to the randomised controlled trial reported in chapter 7. In Chapter 7, the details of a double blind, randomised placebo-controlled trial, evaluating XOI (with Allopurinol 300 mg once daily) in a population with recent (< 12 months) ischaemic stroke or TIA, are presented. Patients were followed up at 1, 3, 6 & 12 months in relation to several prognostically important surrogate measures of cardiovascular function.

Emergency Departments (EDs) deliver urgent treatment at the ‘front-door' of acute hospitals. In Scotland, occupational therapists have had an increasing presence in EDs, an emerging role with limited evidence to guide its development. There are no predetermined philosophies or existing theories of ED occupational therapy. Therefore, this exploratory study examined the lived experience of ED occupational therapists in order to make an original contribution to knowledge, and to inform practice. Ethical approval was granted from Glasgow Caledonian University. Research methods were framed by Interpretative Phenomenological Analysis (IPA), and purposive sampling was used to recruit nine ED occupational therapists from across Scotland. Individual, semi-structured interviews were audio-recorded and transcribed verbatim. Interview transcripts were analysed line-by-line and interpreted using IPA methods. Two over-arching themes emerged from the data. Theme 1: 'On the Factory Floor' captured the experience of working in an ED. EDs are highly organised, likened to factory production-lines, but also unpredictable, even chaotic. The participants contributed their professional skills to make sense of both the order and the chaos. Theme 2: 'A Stranger in a Strange Land' encapsulated what it was like to enter the ED environment, and the participants were still discovering how they might acculturate. They experienced EDs as challenging environments, which potentially threatened the delivery of occupational therapy in terms of its core-constructs. However, they were able to maintain the values of occupational therapy, though they applied them with constraints. In addition, challenges placed clinicians at high risk of burn-out. Despite this, there were personal and professional rewards, especially enjoyment, being valued and being recognised. Occupational therapy is still emerging in the ED context, professional identity is forming and models of practice are not fully developed. Implications arising from the study are discussed in relation to health policy, future research, occupational therapy practice and occupational therapy education.

The aim of this thesis was to develop and evaluate methodologies to assess the impact of medicines use review (MUR), a new service introduced under the new Community Pharmacy Contract in April 2005. A cohort study utilised a prospective active group of 120 patients recruited from 7 pharmacies across Kent with a retrospective control cohort matched for age, sex, GP practice and number of medicines. The primary outcome measure was a reduction in drug therapy problems (DTPs) with a 64% resolution observed in the active group compared to only 3% in the control group over the six month period of the study. The effect size was significant (p<0.0001) with an absolute risk reduction of 61% and a number needed to treat of 1.6. This means for every 16 DTPs receiving an intervention, 10 DTPs would be resolved over and above standard care at 6 months. There were no significant differences in secondary outcome measures (number of repeat medicines and use of health services) between the two groups. A focus group of 6 patients not involved in the main study confirmed that MUR was well received by patients with overarching themes of awareness and trust. In addition a semi-structured questionnaire completed by 72 study participants confirmed that MUR was well received by patients. Two further focus groups of 6 pharmacists (providers and non-providers of MUR) were also conducted which raised contrasting views regarding the New Pharmacy Contract but showed an overwhelming consensus between both groups that MUR was a beneficial service. On the basis of these results, one can conclude that the hypothesis 'MUR will reduce drug therapy problems and will be well accepted by both patients and pharmacists' can be accepted. These findings make an original contribution to the literature and represent a significant contribution to the evidence base in support of MUR services.

Medical products based on nanomaterials can revolutionise disease diagnosis and management modalities via faster, non-invasive diagnostic techniques and targeted therapeutic delivery and will be used extensively in coming years. The central goal of this thesis was to understand environmental risks that could potentially arise from mass production and wider use of nanotechnology enabled medical products and to gather insights from experts’ perceptions on “Responsible Innovation”. The research presented here uses a mixed methods approach to answer the research questions. By applying probabilistic mass flow modelling concept, prospective environmental concentrations of nanomedicine was estimated and a preliminary environmental risk assessment was done using gold nanoparticles in medical applications (potential of commercialisation and marketed) as a case study. This demonstrated that environmental risks from gold nanoparticles for the two major compartments (sludge applied soil and water) is likely to be minimal in the near future. The second component of the research involved 38 interviews with academics and 28 interviews with representatives from regulatory bodies, industry and funding bodies to understand their perceptions on environmental hazards and risks from nanomedicine and their views on the meaning of the concept of “Responsible Innovation”. This revealed that risks from nanomedicine can be compared with risks from existing chemicals and that “Responsible Innovation” is a phrase which can be discussed based on an individual’s experience and discipline.