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The aim of the study was to investigate the assessment and treatment of stance symmetry and sway after stroke and was divided into 3 parts. Stage 1. Sway and stance symmetry were surveyed with the Nottingham Balance Platform (NBP), a computerised limb load monitor. Over 400 volunteers of both sexes and a wide age range were recruited. There were significant differences between the sexes for both sway (p<0.05) and stance symmetry (p<O.Ol) and significant correlations between age and sway (p<O.OOl) and stance symmetry (p<O.OOl). Thus, normative data was provided. Stage 2. Patients were surveyed to examine these variables after stroke and their relationships with age, falls and motor and ADL function. A consecutive sample of 92 patients underwent 2 assessments, 4 months apart, between 2 and 9 months post-stroke. Abnormal stance symmetry was seen, which improved with time (p<O.01) and correlated with functional measures (p<.001), length of stay and age. Abnormal sway values also present, improved with time (p<O.Ol). A significant relationship existed between sway values and falls frequency (p<O.01), but there was no significant association with functional abilities, age or sex. Stage 3. A single-blind randomised-controlled trial was conducted with 26 stroke patients to assess the value of visual feedback training. Patients demonstrating asymmetry were randomly allocated to two groups. Group A received visual feedback and Group B a placebo program, incorporated into 12 physiotherapy sessions. Independent assessments of motor and ADL function were completed at the start (0 weeks) and end of treatment (4 weeks) and at 8 weeks. Initially, there were no significant differences between the groups. At 4 weeks, stance symmetry and measures of function were significantly better for the treatment group than controls (p<0.05), but not at the final assessment. The improvement, although maintained, did not continue after treatment. The results support the further use of feedback techniques to improve standing posture after stroke.

Poor pain assessment contributes to inadequate postoperative pain relief. Studies in the US suggest that nurse education might make students less sensitive to patients' experience of pain. This research set out to examine this process in the United Kingdom and to explore the experience of the students during their common foundation programme (CFP). 217 students completed the Standard Measure of Inferences of Suffering Questionnaire (SMIS) before and after their CFP. Their inferences of psychological distress increased as studies in the US had found but unlike these studies no change was found in their inferences of pain. Inferences of pain and psychological distress were affected by the age of the cases, while gender affected only the latter. None of the characteristics of the students were related to their inferences Of 51 qualified nurses who completed the SMIS, 5 with high inferences and 5 with low inferences, rated patients for whom they were caring. Over half of their ratings were different from those of the patients' and there was no relationship between their SMIS scores and the tendency to over or under estimate patients' pain casting doubt on the validity of the SMIS. Interviews with 15 students following their CFP showed that they experienced a wide range of strong emotions when caring for patients in pain. Their relatively junior status in the wards seemed to place them in difficult positions and provided them with little support. Theories of desensitisation, cognitive dissonance and acculturation have been proposed to explain decreasing sensitivity to pain. The lack of a significant change in students' inferences of pain and the analysis of their interviews suggest that their experiences are more varied than these theories suggest. These findings have important implications for both nurse education and the mechanisms to support student nurses in clinical practice.

Perceptual problems are common following stroke and affect the patients' functional ability, suggesting that these problems should be treated. Eighty patients admitted to the Nottingham Stroke Unit, were assessed for perceptual and functional abilities, using standardised assessments (Rivermead Perceptual Assessment Battery, Barthel ADL Index and Edmans ADL index). Each patient identified as having perceptual problems, was randomly allocated to one of two groups for perceptual treatment. One group followed the transfer of training approach and one group followed the functional approach. The study compared the effectiveness of the two approaches in improving perceptual and functional abilities. Treatment was given for 2.5 hours per week for six weeks. On completion of the six weeks treatment, each patient was reassessed for perceptual and functional abilities. There was no significant difference between the treatment groups on patient characteristics or impairments. The results also showed no significant difference between the treatment groups before and after treatment on perceptual ability total scores, individual perceptual subtest scores, or functional ability total scores (Mann Whitney U 642.5-798.0, p > 0.05). Wilcoxon Matched Pairs Signed Ranks Tests showed a significant improvement after treatment, on perceptual and functional abilities, (perceptual z = 6.02, p<0.001, functional z = 6.72, p<0.001). These results indicated the improvement in perceptual abilities was equivalent using either of the two approaches. Therefore, a no treatment group of 20 patients was studied. The results showed similar results between the treatment and no treatment groups, suggesting that neither treatment approach improved outcome. However, these results may have been influenced by spontaneous recovery or the effects of the Stroke Unit.

Not all stroke patients are admitted to hospital. The literature indicates that between 22% and 60% of stroke patients remain in the community, often with little or no rehabilitation. Occupational therapy is commonly used in the treatment of stroke patients and aims to promote recovery through purposeful activity. Several small trials have suggested that this approach may be effective in reducing disability but none has examined the effect of occupational therapy on stroke patients not admitted to hospital. Therefore the aim of this study was to evaluate the effect of occupational therapy on the disability and handicap experienced by stroke patients who remain in the community. Patients were recruited to the study from a community stroke register. This register covered a geographical area of Nottingham and Southern Derbyshire, incorporating 73 general practitioner practices, covering 494,000 patients. Patients were included in the study if they fulfilled the WHO definition of stroke and had not been admitted to hospital. Patients were excluded if they lived in a nursing or residential home, could not speak or understand English prior to their stroke or had a previous history of dementia. At one month after stroke patients were assessed on a series of physical and cognitive assessments. Patients were then randomly allocated to a treatment group or a control group. Patients allocated to the treatment group received visits from a research occupational therapist for up to five months. The main aim of treatment was independence in personal and extended activities of daily living. Patients were also encouraged to participate in leisure activities. Two hundred and forty patients were notified to the study and of these, 55 patients were excluded. Of the remaining 185 patients, 94 were randomly allocated to the treatment group and 91 to the control group. All baseline assessments and demographic data were well matched between the groups. Twenty-two patients could not be assessed at six months; 13 patients had died during follow up and nine withdrew from the study. Significant differences were found between the groups at six months after stroke on the Barthel Index (p=0.002, 95% CI 0 to 1), Nottingham Extended Activities of Daily Living (p=0.009, 95% CI 1 to 4), Rivermead Gross Function (p=0.004, 95% CI 0 to 2), Caregiver Strain Index (p= 0.02, 95% CI 0 to 2) and the London Handicap Scale (p=0.03, 95% CI 0.3 to 13.5). There were no significant differences between the groups on the Hospital Anxiety and Depression scale. General Health Questionnaire 28 for either the patient or the carer or on the Nottingham Leisure Questionnaire. This study demonstrated that occupational therapy significantly reduced the level of disability and handicap experienced by stroke patients who remained in the community and also significantly reduced the strain of the carer. NB. This ethesis has been created by scanning the typescript original and may contain inaccuracies. In case of difficulty, please refer to the original text.

Until recently, meta-analyses have usually been performed based on summary data methods. Individual patient data methods are becoming more popular, but the advantages of using these methods have not been fully investigated with regards to assessing and exploring heterogeneity. This thesis has assessed whether there are any clinically important differences in the results from analysing data from three meta-analyses of randomised controlled trials in the area of stroke medicine, using summary and individual patient data methodologies. Blood pressure ill Acute Stroke Collaboration (BASC) The management of blood pressure during the acute phase of stroke remains an enigma, therefore a systematic review and meta-analysis of existing randomised controlled trials was conducted to assess the effects of vasoactive drugs on outcome. Trends towards an increase in the risk of death, and death or dependency at the end of trial were found in patients randomised to a vasoactive drug as compared to those randomised to control. When baseline systolic blood pressure was taken into account in the analyses, patients randomised to a vasoactive drug had a significantly higher risk of death at the end of trial. Analyses also indicated that patients recruited early and within 48 hours has significant increases in the risk of death at the end of trial. However, no significant effects were seen for early change in systolic blood pressure. Community occupational therapy in stroke patients An evaluation of the efficacy of occupational therapy given in the community to stroke patients was performed using a systematic review and meta-analysis of randomised controlled trials. At the end of intervention, patient randomised to occupational therapy had significantly higher scores for extended and personal activities of daily living, and non-significantly higher scores for leisure participation. These effects appeared to be maintained over time. No effects were seen between the groups for death or minor psychiatric disorders as measured in patients or their carers. Subgroup analyses revealed that the benefits of occupational therapy were greatest when targeted interventions were used. Also, being male or independent at baseline was found to be important predictor of extended activities of daily living scores. Dipyridamole in Stroke Collaboration (DISC) Results from randomised controlled trials of dipyridamole, given with and without aspirin, for secondary prevention after stroke or transient ischaemic attack have given conflicting results; therefore, we performed a systematic review and meta-analysis. The risk of subsequent fatal or non-fatal stroke was reduced using the dual treatment of aspirin and dipyridamole as compared to either aspirin alone, dipyridamole alone, or control. Additionally, the dual treatment lowered the risk of non-fatal stroke, and subsequent vascular events defined by a composite outcome (non-fatal stroke, non fatal myocardial infarction, or vascular death). Analyses indicated that these results were independent of method of formulation of dipyridamole, dose of aspirin, type of qualifying event, and gender of the patients. However, increasing age was found to be an important predictor of subsequent stroke. These systematic reviews demonstrate that collaborations within the area of stroke medicine can be successful and much data can be shared. The findings from meta-analyses can be informative about the effectiveness of particular treatment and about which patients should be targeted for treatment; and may help steer the direction of future trials. Although summary data meta-analyses are practically easier to perform, it is important that assessments and explorations of heterogeneity should always be performed. Meta-analyses based on individual patient data may be needed to allow for more in depth investigations of heterogeneity, especially of patient characteristics. However, they themselves are not the panacea to all difficulties since they are subject to particular problems, mainly related to obtaining individual patient data to enable these in depth analyses to be performed.

People who have suffered a stroke can become housebound and miserable because they cannot access suitable transport. They can have difficulty getting to the shops, doctors and hospital and this can have an effect on their quality of life. Occupational therapists routinely aim to help these people overcome their outdoor mobility problems by providing information and verbal instructions but these interventions do not appear to be effective. The aim of this research was to design and evaluate a new occupational therapy outdoor mobility intervention. The intervention was modeled on travel training that is provided for other conditions and the outdoor mobility experiences and needs of people with stroke. Qualitative semi structured interviews were used to investigate 24 peoples experiences of both using transport and their outdoor mobility after they had suffered a stroke. It was found that people wanted to travel for a variety of reasons; shopping, work, getting to the doctors, social reasons, meeting friends, visiting family and just for the sake of traveling. People were prevented from traveling because of physical difficulties such as stepping onto the bus, psychological problems such as confidence and environmental barriers such as the weather or lack of information. The results were used to define the main components of an Occupational Therapy Outdoor Mobility Intervention. A randomised controlled trial was used to evaluate the effects of this Occupational Therapy Outdoor Mobility Intervention (OTOMI) by comparing it to the routine occupational therapy intervention. Participants with stroke in the last 36 months were recruited from primary care services and randomly allocated to receive either the OTOMI or the routine occupational therapy. Participants in the OTOMI received up to seven individualised occupational therapy sessions. The sessions aimed to increase confidence, encourage use of different types of transport and provided tailor-made information. Outcomes were measured by postal assessment 4 and 10 months after recruitment. The primary outcome measure was a yes/ no question, Do you get out of the house as much as you would like? Secondary outcomes included the number of journeys, mood, performance of activities of daily living and leisure. 168 participants who had had a stroke in the last 36 months were recruited into the study over eighteen months, 82 in the control group and 86 to the OTOMI group. 10 people were unable to provide follow-up information at the four month assessment and 21 people at the ten month assessment. Intention-to-treat analyses were undertaken. For the principal outcome measure, participants who were dead at the point of assessment were allocated the worst outcome, and for others lost to follow up their baseline or last recorded responses were used. For the other analyses all missing values were imputed using baseline values. Participants in the treatment group were more likely to get out of their house as often as they wanted at 4 months (RR 1.72,95% CI 1.25 to 2.37) and at 10 months (RR 1.74,95 Cl 1.24 to 2.44). The treatment group recorded more journeys outdoors in the month prior to assessment at 4 months (intervention group median 37, control group median 14, Mann-Whitney p<0.01) and at 10 months (intervention group median 42, control group median 14, Mann-Whitney: p<0.01). At 4 months the NEADL mobility scores were significantly higher in the intervention group, but there were no significant differences in the other secondary outcomes. There were no significant differences in these measures at 10 months. The interview study demonstrated that participating in outdoor mobility is a major problem for people who have had a stroke. The randomised controlled trial demonstrated that a relatively simple and feasible, individualized, properly organised, focused and adequately resourced occupational therapy outdoor mobility intervention can increase participation in outdoor mobility activities, allowing people to get out of the house as much as they wish.

The aims of this study were to investigate (i) the levels of catecholamines, indoleamines, substance P and thyrotrophin-releasing hormone (TRH) in the post-mortem spinal cord of subjects who had died with Parkinson's disease and to compare them with those of control subjects (ii) adrenergic and serotonergic receptors in the post-mortem Parkinsonian and control spinal cord and (iii) the effects of subject age and sex and the interval between death and post-mortem (PMI) on the levels of neurotransmitters and neuropeptides and on receptor binding in post-mortem tissue. To perform these investigations (i) a sensitive radioimmunoassay which is specific for substance P and has low cross-reactivity with other similar peptides and (ii) a common extraction medium for the concomitant extraction of catecholamines, indoleamines, substance P and TRH from CNS tissue were developed. The main findings were: There were significant correlations between the levels of 5HT, TRH and α2-adrenoceptor binding and both subject age and the PMI. In Parkinson's disease compared with control subjects: (i) the levels of noradrenaline were significantly reduced in the thoracic ventral region of the spinal cord,(ii) dopamine levels were higher in the thoracic ventral and dorsal spinal cord,(iii) in the lumbar spinal cord 5HT levels were significantly reduced in the dorsal horn with an increase in the ratio of 5HIAA/5HT, (iv) noradrenaline levels were reduced in both dorsal and ventral horns of the lumbar spinal cord and (v) there were no differences between the levels of substance P and TRH in any spinal cord region. There were no measurable 5HT1A or 5HT2 binding sites in the human spinal cord under the conditions used. However, specific α2-adrenoceptor binding was defined in terms of binding affinity and number of receptors in the spinal cord.

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