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INTRODUCTION Trauma is the main cause of death in working-age adults in the UK. Multiple organ failure (MOF) is associated with a high proportion of late trauma deaths, and MOF survivors have poor long-term outcomes. Early prediction of patients at risk of MOF would assist treatment decisions and allow targeted interventions. METHODS A cohort of major trauma patients requiring intensive care unit (ICU) treatment at the John Radcliffe Hospital was identified. Data were obtained from the two national databases of the Trauma Audit Research Network and the Intensive Care National Audit and Research Centre, and from a local ICU database with hourly data recording. Literature review and questionnaire analysis of trauma clinicians identified candidate predictors of MOF, grouped into patient, injury, physiological, laboratory and management variables. MOF scoring systems were reviewed to determine the most appropriate for use in trauma patients. Prediction models of post-trauma MOF were developed using logistic regression at a range of times from 0 to 48 hours after injury. Models were internally validated using bootstrapping. RESULTS 517 adult trauma patients were identified from 2003-2011. Overall mortality was 14.9%, with 491 patients surviving more than 48 hours, and therefore being at risk of MOF development. For these 491 patients, MOF incidence depended on the definition, and ranged from 23% (Denver score) to 58% (SOFA score). MOF was associated with mortality, time to ICU admission, and length of ICU and hospital stay. MOF could be predicted with an accuracy of up to 81.3% at 2 hours post-injury, and 84.2% at 12 hours post-injury using small numbers of clinical variables. Age, head injury, abdominal injury, maximum heart rate and the need for vasopressors were strong predictors of all definitions of MOF. CONCLUSIONS Post-trauma MOF can be predicted early after injury using combinations of clinical variables. Further validation of the identified variables on external populations would allow development of a clinical score to assist clinicians in trauma management.

The aim of this thesis was to develop yoga as a complex intervention in health care for the improvement of health-related quality of life (HRQoL) in adult cancer. As the Indian tradition of practising yoga increases in popularity worldwide, populations in the West are beginning to see yoga as an opportunity to prevent and treat health conditions. The Medical Research Council’s framework has provided a methodology to address a paucity of coherent evidence for the myriad of unsupported health claims made by yoga enthusiasts. The thesis structure included a step-by-step approach to investigate biomedical theories of how yoga might work to improve health, to synthesise evidence of yoga interventions, to model their process and outcomes, and to test evaluation procedures in the context of a randomised controlled trial (RCT). The results of a bibliometric analysis indicated an overall increase in the publication rate of yoga research in health care, and in 2005 this research began to focus on cancer. A component analysis, semi-structured patient interviews (n=10) and oncologist surveys (n=29) were successively designed, implemented and analysed to advance a model of yoga intervention specific to adult cancer. The cumulative results were applied to design three yoga interventions randomly allocated to men and women receiving treatment for cancer (n=15). Outcomes of the feasibility study demonstrated that yoga intervention is appropriate for adult patients and can be administered safely in a clinical setting. In its conclusion, this thesis produces evidence-based support for the optimisation of yoga intervention in the context of a large-scale RCT for HRQoL in adult cancer, and it provides recommendations to improve research methodology and reporting of complex interventions in health care.

Background Midwifery units (MUs) provide midwife-led care for women at low risk of complications. They may be located on the same site as an obstetric unit (OU), in a hospital without obstetric services or separate from any hospital. In MUs, if unforeseen complications arise, transfer to an OU may be necessary. Aim To provide evidence to contribute to the improvement of the transfer process, help make transfer safer and less distressing for women, thereby improving the care and experience of women planning to give birth in MUs. Methods A structured literature review of existing evidence was followed by three integrated component studies using different methods. The content and quality of local NHS transfer guidelines were evaluated. Data from the Birthplace national prospective cohort study were analysed to estimate transfer rates, describe the transfer process and identify factors associated with transfer. The experiences of women transferred were explored in qualitative interviews. Findings Transfer is a common event, affecting around 25% of women planning birth in MUs, although rates in different units vary. Primiparous women are more likely to be transferred than women having a second or subsequent baby. The risk of transfer for primiparous women increases with increasing age; around 50% of women having their first baby aged 40 years or over are transferred. Local NHS transfer guidelines are generally of poor quality and pay little attention to women’s experience. Women interviewed after transfer report feeling unprepared for transfer. Sensitive care and clear communication from midwives during labour facilitate feelings of control in women and help women accept transfer as the right decision and not a 'negative' event. Transfer that is perceived by women as “too late” can have potentially serious and long-lasting negative effects. Women’s experience of the transfer journey could be improved by the offer of choice in a number of areas which would help women feel 'cared for' rather than 'transported'. Having the MU midwife continue to care for the woman after transfer should be considered 'best practice'; where this is not possible a good handover is essential. Women who have experienced transfer should be offered the opportunity to talk to a midwife about their experience.

Objectives To determine whether providing an information sheet to patients with acute chest pain reduces anxiety, improves health related quality of life, improves satisfaction with care, or alters subsequent symptoms or actions. Design Single centre, non-blinded, randomised controlled trial. Setting Chest pain unit of an emergency department. Participants 700 consecutive patients with acute chest pain and no clear diagnosis at initial presentation. Interventions After a diagnostic assessment patients were randomised to receive either standard verbal advice or verbal advice followed by an information sheet. Main outcome measures The primary outcome was anxiety (hospital anxiety and depression scale). Secondary outcomes were depression (hospital anxiety and depression scale), health related quality of life (SF-36), patient satisfaction, presentation with further chest pain within one month, lifestyle change (smoking cessation, diet, exercise), further information sought from other sources, and planned healthcare seeeking behaviour in response to further pain. Results 494 of 700 (70.6%) patients responded. Compared with those receiving standard verbal advice those receiving advice and an information sheet had lower mean hospital anxiety and depression scale scores for anxiety (7.61 v 8.63, difference 1.02, 95% confidence interval 0.20 to 1.84) and depression (4.14 v 5.28, difference 1.14, 0.41 to 1.86) and higher scores for mental health and perception of general health on the SF-36. The information sheet had no significant effect on satisfaction with care, subsequent symptoms, lifestyle change, information seeking, or planned actions in the event of further pain. Conclusions Provision of an information sheet to patients with acute chest pain can reduce anxiety and depression and improve mental health and perception of general health but does not alter satisfaction with care or other outcomes. Trial registration Current Controlled Trials ISRCTN85248020.

The overall aim of this thesis is to define a candidate set of quality indicators that are evidence-based, feasible to implement, and have the potential to improve the quality of care provided for children in UK general practice. The indicators were developed using a three-stage process. First, the areas and aspects of care of highest priority for quality indicator development were identified. This was achieved by seeking the views of primary care clinicians and by undertaking a formal analysis of unplanned hospital admissions for ambulatory care sensitive conditions. Then, the evidence-base to underpin indicator development was identified through an overview of Cochrane systematic reviews of interventions relevant to the primary care of children. A search of SIGN and NICE national guidelines was also conducted to inform the evidence-base. Lastly, an expert panel determined the formulation and selection of indicators by applying the RAND appropriateness methodology. This process created a final set of 26 quality indicators in six priority areas: early recognition of potentially serious illness (n=7); child protection and safeguarding (n=4); mental health (n=4); health promotion (n=1); routinely managed conditions (n=6); and general practice management (n=4). The main strength of these indicators is that they reflect a strong professional consensus on their validity and feasibility. The main weakness is that the indicators are underpinned by evidence mainly derived from expert opinion rather than formal research; the requirement for professional consensus means that they do not challenge existing models of care delivery.

This investigation systematically assesses the quality and effectiveness of risk:benefit appraisal methodologies implemented in the analysis of published randomised controlled trials for pre-licensure biomedical innovations – therapeutics, devices and surgical procedures. The key finding is that, to date, reported applications of risk:benefit methodologies are highly heterogeneous and poorly reflective of the stakeholder needs assessed in the investigation. [Abstract continues in thesis]

No abstract.

This thesis evaluates the cost-effectiveness of eight policies expanding human immunodeficiency virus (HIV) testing in South Africa. All policies entail provider-initiated test offers for primary healthcare users and one of two options across three policy components: (i) consent method, opt-in or opt-out; (ii) test protocol, rapid only or rapid plus acute infection testing; and (iii) linkage-to-care, standard or enhanced. This thesis highlights four methodological issues. First is the challenge of conducting a population-level analysis, projecting the cost-effectiveness of expanded testing for each member of South Africa’s adult African population. To this end, I conducted a retrospective, descriptive study to measure current population-level testing rates and epidemic descriptors in an African community near Cape Town, South Africa. Second, the effects of testing expansion on current testing uptake were estimated by distinguishing testing in the study community likely to cease after testing expansion (baseline testing) from that likely to continue (background testing). Third, because testing alone is an outcome of less interest than health benefits following treatment, study community linkage-to-care probabilities were estimated and models utilized to estimate the efficacy of treatment. Fourth, the methods to convert the study community testing data into inputs for these models’ parameters are outlined. The enhanced linkage-to-care policies proved the most cost-effective, with opt-in testing and a rapid-only test protocol the least expensive cost-effective option at $848 per life year gained (LYG). Adding an opt-out consent method or acute infection test protocol to this policy increased the LYGs, but at higher cost-effectiveness ratios.

Neurodegeneration is a progressive loss of neuron function or structure, including death of neurons, and occurs at many different levels of neuronal circuitry. In this thesis I discuss Parkinson’s Disease (PD), the second most common neurodegenerative disease (NDD). PD is a devastating progressive NDD often with delayed diagnosis due to detection methods that depend on the appearance of visible motor symptoms. By the time cardinal symptoms manifest, 60 to 80 percent or more of the dopamine-producing cells in the substantia nigra are irreversibly lost. Although there is currently no cure, earlier detection would be highly beneficial to manage treatment and track disease progression. However, today’s clinical diagnosis methods are limited to subjective evaluations and observation. Onset, symptoms and progression significantly vary from patient to patient across stages and subtypes that exceed the scope of a standardized diagnosis. The goal of this thesis is to provide the basis of a more general approach to study the brain, investigating early detection method for NDD with focus on PD. It details the preliminary development, testing and validation of tools and methods to objectively quantify and extrapolate motor and non-motor features of PD from behavioral and cognitive output during everyday life. Measures of interest are categorized within three domains: the motor system, cognitive function, and brain activity. This thesis describes the initial development of non-intrusive tools and methods to obtain high-resolution movement and speech data from everyday life and feasibility analysis of facial feature extraction and EEG for future integration. I tested and validated a body sensor system and wavelet analysis to measure complex movements and object interaction in everyday living situations. The sensor system was also tested for differentiating between healthy and impaired movements. Engineering and design criteria of the sensor system were tested for usability during everyday life. Cognitive processing was quantified during everyday living tasks with varying loaded conditions to test methods for measuring cognitive function. Everyday speech was analyzed for motor and non-motor correlations related to the severity of the disease. A neural oscillation detection (NOD) algorithm was tested in pain patients and facial expression was analyzed to measure both motor and non-motor aspects of PD. Results showed that the wearable sensor system can measure complex movements during everyday living tasks and demonstrates sensitivity to detect physiological differences between patients and controls. Preliminary engineering design supports clothing integration and development of a smartphone sensor platform for everyday use. Early results from loaded conditions suggest that attentional processing is most affected by cognitive demands and could be developed as a method to detect cognitive decline. Analysis of speech symptoms demonstrates a need to collect higher resolution spontaneous speech from everyday living to measure speech motor and non-motor speech features such as language content. Facial expression classifiers and the NOD algorithm indicated feasibility for future integration with additional validation in PD patients. Thus this thesis describes the initial development of tools and methods towards a more general approach to detecting PD. Measuring speech and movement during everyday life could provide a link between motor and cognitive domains to characterize the earliest detectable features of PD. The approach represents a departure from the current state of detection methods that use single data entities (e.g.one-off imaging procedures), which cannot be easily integrated with other data streams, are time consuming and economically costly. The long-term vision is to develop a non-invasive system to measure and integrate behavioral and cognitive features enabling early detection and progression tracking of degenerative disease.

Proponents of evidence-based medicine (EBM) have argued convincingly for applying this scientific method to medicine. However, the current methodological framework of the EBM movement has recently been called into question, especially in epidemiology and the philosophy of science. The debate has focused on whether the methodology of randomized controlled trials provides the best evidence available. This paper attempts to shift the focus of the debate by arguing that clinical reasoning involves a patchwork of evidential approaches and that the emphasis on evidence hierarchies of methodology fails to lend credence to the common practice of corroboration in medicine. I argue that the strength of evidence lies in the evidence itself, and not the methodology used to obtain that evidence. Ultimately, when it comes to evaluating the effectiveness of medical interventions, it is the evidence obtained from the methodology rather than the methodology that should establish the strength of the evidence.

Factorial randomised controlled trials (RCTs) evaluate two or more interventions simultaneously, enabling assessment of interactions between treatments. This thesis presents literature reviews, methodological reviews, simulation studies and applied case studies that explore methods for assessing cost-effectiveness based on factorial RCTs. My systematic review suggests that factorial RCTs account for around 3% of trial-based economic evaluations, although there is currently no guidance or methodological work indicating the most appropriate methods. Around 40% of published studies assumed no interaction between treatments and many were poorly-reported. Various mechanisms are likely to produce large interactions within economic endpoints such as costs, quality-adjusted life-years (QALYs) and net benefits. Failing to take account of interactions can introduce bias and prevent efficient allocation of healthcare resources. I developed the opportunity cost of ignoring interactions as a measure of the implications of this bias. However, allowing for small, chance interactions is inefficient, potentially leading to over-investment in research if trial-based evaluations are used to inform decisions about subsequent research. Nonetheless, analyses on simulated trial data suggest that the opportunity cost of adopting a treatment that will not maximise health gains from the healthcare budget is minimised by including all interactions regardless of magnitude or statistical significance. Different approaches for conducting economic evaluations of factorial RCTs (including regression techniques, extrapolation using patient-level simulation, and considering different components of net benefit separately) are evaluated within three applied studies, including both full and partial factorials with 2x2 and 2x2x2 designs. I demonstrate that within both trial-based and model-based economic evaluation, efficient allocation of healthcare resources requires consideration of interactions between treatments, and joint decisions about interacting treatments based on incremental cost-effectiveness evaluated “inside-the-table” on a natural scale. I make recommendations for the design, analysis and reporting of factorial trial-based economic evaluations based on the results of this thesis.

Objective To elicit women's preferences for attributes of alternative management options for first-trimester miscarriage. Methods A stated preference discrete-choice experiment was conducted among 1198 women with a confirmed pregnancy of less than 13 weeks gestation, who had been diagnosed with either an incomplete miscarriage or missed miscarriage/early fetal demise and who had been recruited as part of a randomized controlled trial (miscarriage treatment [MIST] trial) comparing expectant, medical, and surgical miscarriage. Six attributes, each with three or four levels, were used in the statistical design. An orthogonal main effects design was generated (i.e., a design where the attributes are independent of each other) and the choice sets devised according to the principles of minimum overlap and level balance. A cost attribute was included to allow estimation of willingness to pay (WTP) values. Three different questionnaires were designed such that women were asked their preferences for attributes of the two management options they had not been allocated to in the trial. Results A total of 630 women completed the stated preference discrete-choice survey questionnaires: 189 out of 398 women (47.5%) allocated to expectant management, 223 out of 398 women (56.0%) allocated to medical management, and 218 out of 402 women (54.2%) allocated to surgical management. For each of the three discrete-choice survey questionnaires, women expressed a clear preference for decreased levels of all six attributes (time spent at the hospital receiving treatment, level of pain experienced, number of days of bleeding after treatment, time taken to return to normal activities after treatment, cost of treatment to women, and chance of complications requiring more time or readmission to hospital). For each of the three discrete-choice survey questionnaires, the highest valued attribute in terms of WTP was for a reduction in pain levels followed by time taken to return to normal activities after treatment. On aggregate, surgical management was valued more highly than expectant and medical management by women allocated to medical and expectant management, respectively, and medical management was valued more highly than expectant management by women allocated to surgical management. This held true regardless of the application of either hypothetical data for each attribute generated by the pretrial-designed discrete-choice experiment questionnaires or actual data for each attribute observed in the MIST trial. ConclusionsThe preference results generated by this study suggest that many women undergoing management of first-trimester miscarriage would value being offered alternatives to expectant management. The data from this study should be considered by decision-makers in conjunction with the clinical and cost-effectiveness evidence base in this area as well as consideration of the budgets available to them for such services.

This investigation systematically assesses the quality and effectiveness of risk:benefit appraisal methodologies implemented in the analysis of published randomised controlled trials for pre-licensure biomedical innovations – therapeutics, devices and surgical procedures. The key finding is that, to date, reported applications of risk:benefit methodologies are highly heterogeneous and poorly reflective of the stakeholder needs assessed in the investigation. [Abstract continues in thesis]

The aim of this thesis was to develop yoga as a complex intervention in health care for the improvement of health-related quality of life (HRQoL) in adult cancer. As the Indian tradition of practising yoga increases in popularity worldwide, populations in the West are beginning to see yoga as an opportunity to prevent and treat health conditions. The Medical Research Council’s framework has provided a methodology to address a paucity of coherent evidence for the myriad of unsupported health claims made by yoga enthusiasts. The thesis structure included a step-by-step approach to investigate biomedical theories of how yoga might work to improve health, to synthesise evidence of yoga interventions, to model their process and outcomes, and to test evaluation procedures in the context of a randomised controlled trial (RCT). The results of a bibliometric analysis indicated an overall increase in the publication rate of yoga research in health care, and in 2005 this research began to focus on cancer. A component analysis, semi-structured patient interviews (n=10) and oncologist surveys (n=29) were successively designed, implemented and analysed to advance a model of yoga intervention specific to adult cancer. The cumulative results were applied to design three yoga interventions randomly allocated to men and women receiving treatment for cancer (n=15). Outcomes of the feasibility study demonstrated that yoga intervention is appropriate for adult patients and can be administered safely in a clinical setting. In its conclusion, this thesis produces evidence-based support for the optimisation of yoga intervention in the context of a large-scale RCT for HRQoL in adult cancer, and it provides recommendations to improve research methodology and reporting of complex interventions in health care.

Objective To investigate whether placebo controls should be used in the evaluation of surgical interventions. Design Systematic review. Data sources We searched Medline, Embase, and the Cochrane Controlled Trials Register from their inception to November 2013. Study selection Randomised clinical trials comparing any surgical intervention with placebo. Surgery was defined as any procedure that both changes the anatomy and requires a skin incision or use of endoscopic techniques. Data extraction Three reviewers (KW, BJFD, IR) independently identified the relevant trials and extracted data on study details, outcomes, and harms from included studies. Results In 39 out of 53 (74%) trials there was improvement in the placebo arm and in 27 (51%) trials the effect of placebo did not differ from that of surgery. In 26 (49%) trials, surgery was superior to placebo but the magnitude of the effect of the surgical intervention over that of the placebo was generally small. Serious adverse events were reported in the placebo arm in 18 trials (34%) and in the surgical arm in 22 trials (41.5%); in four trials authors did not specify in which arm the events occurred. However, in many studies adverse events were unrelated to the intervention or associated with the severity of the condition. The existing placebo controlled trials investigated only less invasive procedures that did not involve laparotomy, thoracotomy, craniotomy, or extensive tissue dissection. Conclusions Placebo controlled trial is a powerful, feasible way of showing the efficacy of surgical procedures. The risks of adverse effects associated with the placebo are small. In half of the studies, the results provide evidence against continued use of the investigated surgical procedures. Without well designed placebo controlled trials of surgery, ineffective treatment may continue unchallenged.

Neurodegeneration is a progressive loss of neuron function or structure, including death of neurons, and occurs at many different levels of neuronal circuitry. In this thesis I discuss Parkinson’s Disease (PD), the second most common neurodegenerative disease (NDD). PD is a devastating progressive NDD often with delayed diagnosis due to detection methods that depend on the appearance of visible motor symptoms. By the time cardinal symptoms manifest, 60 to 80 percent or more of the dopamine-producing cells in the substantia nigra are irreversibly lost. Although there is currently no cure, earlier detection would be highly beneficial to manage treatment and track disease progression. However, today’s clinical diagnosis methods are limited to subjective evaluations and observation. Onset, symptoms and progression significantly vary from patient to patient across stages and subtypes that exceed the scope of a standardized diagnosis. The goal of this thesis is to provide the basis of a more general approach to study the brain, investigating early detection method for NDD with focus on PD. It details the preliminary development, testing and validation of tools and methods to objectively quantify and extrapolate motor and non-motor features of PD from behavioral and cognitive output during everyday life. Measures of interest are categorized within three domains: the motor system, cognitive function, and brain activity. This thesis describes the initial development of non-intrusive tools and methods to obtain high-resolution movement and speech data from everyday life and feasibility analysis of facial feature extraction and EEG for future integration. I tested and validated a body sensor system and wavelet analysis to measure complex movements and object interaction in everyday living situations. The sensor system was also tested for differentiating between healthy and impaired movements. Engineering and design criteria of the sensor system were tested for usability during everyday life. Cognitive processing was quantified during everyday living tasks with varying loaded conditions to test methods for measuring cognitive function. Everyday speech was analyzed for motor and non-motor correlations related to the severity of the disease. A neural oscillation detection (NOD) algorithm was tested in pain patients and facial expression was analyzed to measure both motor and non-motor aspects of PD. Results showed that the wearable sensor system can measure complex movements during everyday living tasks and demonstrates sensitivity to detect physiological differences between patients and controls. Preliminary engineering design supports clothing integration and development of a smartphone sensor platform for everyday use. Early results from loaded conditions suggest that attentional processing is most affected by cognitive demands and could be developed as a method to detect cognitive decline. Analysis of speech symptoms demonstrates a need to collect higher resolution spontaneous speech from everyday living to measure speech motor and non-motor speech features such as language content. Facial expression classifiers and the NOD algorithm indicated feasibility for future integration with additional validation in PD patients. Thus this thesis describes the initial development of tools and methods towards a more general approach to detecting PD. Measuring speech and movement during everyday life could provide a link between motor and cognitive domains to characterize the earliest detectable features of PD. The approach represents a departure from the current state of detection methods that use single data entities (e.g.one-off imaging procedures), which cannot be easily integrated with other data streams, are time consuming and economically costly. The long-term vision is to develop a non-invasive system to measure and integrate behavioral and cognitive features enabling early detection and progression tracking of degenerative disease.

Sepsis remains the second largest killer in the Intensive Care Unit (ICU), giving rise to a significant economic burden ($17b per annum in the US, 0.3% of the gross domestic product). The aim of the work described in this thesis is to improve the estimation of severity in this population, with a view to improving the allocation of resources. A cohort of 2,143 adult patients with sepsis and hypotension was identified from the MIMIC-II database (v2.26). The implementation of state-of-the-art models confirms the superiority of the APACHE-IV model (AUC=73.3%) for mortality prediction using ICU admission data. Using the same subset of features, state-of-the art machine learning techniques (Support Vector Machines and Random Forests) give equivalent results. More recent mortality prediction models are also implemented and offer an improvement in discriminatory power (AUC=76.16%). A shift from expert-driven selection of variables to objective feature selection techniques using all available covariates leads to a major gain in performance (AUC=80.4%). A framework allowing simultaneous feature selection and parameter pruning is developed, using a genetic algorithm, and this offers similar performance. The model derived from the first 24 hours in the ICU is then compared with a “dynamic” model derived over the same time period, and this leads to a significant improvement in performance (AUC=82.7%). The study is then repeated using data surrounding the hypotensive episode in an attempt to capture the physiological response to hypotension and the effects of treatment. A significant increase in performance (AUC=85.3%) is obtained with the static model incorporating data both before and after the hypotensive episode. The equivalent dynamic model does not demonstrate a statistically significant improvement (AUC=85.6%). Testing on other ICU populations with sepsis is needed to validate the findings of this thesis, but the results presented in it highlight the role that data mining will increasingly play in clinical knowledge generation.

INTRODUCTION Trauma is the main cause of death in working-age adults in the UK. Multiple organ failure (MOF) is associated with a high proportion of late trauma deaths, and MOF survivors have poor long-term outcomes. Early prediction of patients at risk of MOF would assist treatment decisions and allow targeted interventions. METHODS A cohort of major trauma patients requiring intensive care unit (ICU) treatment at the John Radcliffe Hospital was identified. Data were obtained from the two national databases of the Trauma Audit Research Network and the Intensive Care National Audit and Research Centre, and from a local ICU database with hourly data recording. Literature review and questionnaire analysis of trauma clinicians identified candidate predictors of MOF, grouped into patient, injury, physiological, laboratory and management variables. MOF scoring systems were reviewed to determine the most appropriate for use in trauma patients. Prediction models of post-trauma MOF were developed using logistic regression at a range of times from 0 to 48 hours after injury. Models were internally validated using bootstrapping. RESULTS 517 adult trauma patients were identified from 2003-2011. Overall mortality was 14.9%, with 491 patients surviving more than 48 hours, and therefore being at risk of MOF development. For these 491 patients, MOF incidence depended on the definition, and ranged from 23% (Denver score) to 58% (SOFA score). MOF was associated with mortality, time to ICU admission, and length of ICU and hospital stay. MOF could be predicted with an accuracy of up to 81.3% at 2 hours post-injury, and 84.2% at 12 hours post-injury using small numbers of clinical variables. Age, head injury, abdominal injury, maximum heart rate and the need for vasopressors were strong predictors of all definitions of MOF. CONCLUSIONS Post-trauma MOF can be predicted early after injury using combinations of clinical variables. Further validation of the identified variables on external populations would allow development of a clinical score to assist clinicians in trauma management.

The overall aim of this thesis is to define a candidate set of quality indicators that are evidence-based, feasible to implement, and have the potential to improve the quality of care provided for children in UK general practice. The indicators were developed using a three-stage process. First, the areas and aspects of care of highest priority for quality indicator development were identified. This was achieved by seeking the views of primary care clinicians and by undertaking a formal analysis of unplanned hospital admissions for ambulatory care sensitive conditions. Then, the evidence-base to underpin indicator development was identified through an overview of Cochrane systematic reviews of interventions relevant to the primary care of children. A search of SIGN and NICE national guidelines was also conducted to inform the evidence-base. Lastly, an expert panel determined the formulation and selection of indicators by applying the RAND appropriateness methodology. This process created a final set of 26 quality indicators in six priority areas: early recognition of potentially serious illness (n=7); child protection and safeguarding (n=4); mental health (n=4); health promotion (n=1); routinely managed conditions (n=6); and general practice management (n=4). The main strength of these indicators is that they reflect a strong professional consensus on their validity and feasibility. The main weakness is that the indicators are underpinned by evidence mainly derived from expert opinion rather than formal research; the requirement for professional consensus means that they do not challenge existing models of care delivery.

Vascular disease is the leading cause of death and disability worldwide. Incidence, risk factors, and outcome of coronary artery disease have been extensively studied, but there are fewer data on other forms of arterial disease, including carotid, aortic, visceral, and peripheral arterial disease. Although the burden of these diseases may be increasing due to the ageing population, we lack the most basic epidemiological data on which to base clinical decisions on individual patients (short and long-term prognosis); local service provision (current incidence and projected future burden); public health / screening initiatives (age and sex-specific incidence, risk factors, and outcome); and with which to assess current levels of primary prevention (pre-morbid risk factor control). Indeed, it is this lack of data, rather than a lack of treatments that is the greatest barrier to effective prevention. I have contributed to, cleaned, and analysed data from the Oxford Vascular Study, a prospective, population-based study (n=92,728) of all acute vascular events (2002-2012), and the Oxford Plaque Study, a carotid atherosclerosis biobank of over 1000 carotid plaques, in order to study these conditions. For acute aortic disease, I aimed to assess the risk factors associated with acute abdominal aortic aneurysms (AAA) and the population impact of the current UK AAA screening programme; and the incidence, risk factors, outcome, and projected future burden of acute aortic dissection. For acute peripheral arterial disease, I assessed the risk factors associated with premature onset and poor outcome, together with current levels of primary prevention. For symptomatic carotid artery disease, I studied the timing and benefits of surgical intervention in the current era; and went on to assess whether underlying carotid plaque morphology can be used to improve stroke risk stratification and help explain why ocular and cerebral stroke types have vast differences in future ipsilateral stroke risk. I found that compared with the current UK AAA screening strategy (one-off scan for men aged 65), screening of male smokers at 65 and all men at 75 would prevent nearly four-times as many deaths and three-times as many life-years lost with 21% fewer annual scans. I have also shown that incidence of acute aortic dissection is higher than previous estimates, a third of cases are out-of-hospital deaths, and uncontrolled hypertension is the most significant treatable risk factor for this condition. For acute peripheral arterial disease, the presence of multiple atherosclerotic risk factors are associated with premature onset, and severity of ischaemia, pre-morbid renal dysfunction, cardiac failure, and diabetes mellitus are predictive of future limb loss and survival. A significant proportion of acute peripheral events are AF-related in high risk patients who were not pre-morbidly anticoagulated despite having no contraindications and being at low risk of bleeding. Symptomatic carotid artery disease currently accounts for

Background Midwifery units offer care to women with straightforward pregnancies, but unforeseen complications can arise during labour or soon after birth, necessitating transfer to a hospital obstetric unit. In England, 21% of women planning birth in freestanding midwifery units are transferred; in alongside units, the transfer rate is 26%. There is little high quality contemporary evidence on women’s experience of transfer. Methods We carried out a qualitative interview study, using semi-structured interviews, with women who had been transferred from a midwifery unit (freestanding or alongside) in England up to 12 months prior to interview. Maximum variation sampling was used. Interviews with 30 women took place between March 2009 and March 2010. Thematic analysis using constant comparison and exploration of deviant cases was carried out. Results Most women hoped for or expected a natural birth and did not expect to be transferred. Transfer was disappointing for many; sensitive and supportive care and preparation for the need for transfer helped women adjust to their changing circumstances. A small number of women, often in the context of prolonged labour, described transfer as a relief. For women transferred from freestanding units, the ambulance journey was a “limbo” period. Women wondered, worried or were fearful about what was to come and could be passive participants who felt like they were being “transported” rather than cared for. For many this was a direct contrast with the care they experienced in the midwifery unit. After transfer, most women appreciated the opportunity to talk about their experience to make sense of what happened and help them plan for future pregnancies, but did not necessarily seek this out if it was not offered. Conclusions Transfer affects a significant minority of women planning birth in midwifery units and is therefore a concern for women and midwives. Transfer is not expected by women, but sensitive care and preparation can help women adjust to changing circumstances. Particular sensitivity around decision-making may be required by midwives caring for women during prolonged labour. Some apparently straightforward changes to practice have the potential to make an important difference to women’s experience of ambulance transfer.

Background Children make up about 20% of the UK population and caring for them is an important part of a general practitioner’s (GP’s) workload. However, the UK Quality Outcomes Framework (pay-for-performance system) largely ignores children – less than 3% of the quality markers relate to them. As no previous research has investigated whether GPs would support or oppose the introduction of child-specific quality markers, we sought their views on this important question. Methods Qualitative interview study with 20 GPs from four primary care trusts in Thames Valley, England. Semi-structured interviews explored GPs’ viewpoints on quality markers and childhood conditions that could be developed into markers in general practice. Interviews were audiotaped and transcribed verbatim. Analysis was thematic and used constant comparative method to look for anticipated and emergent themes as the analysis progressed. Results All the GPs interviewed supported the development of ‘benchmarks’ or ‘standards’ to measure and improve quality of care for children. However no consensus was expressed about the clinical conditions for which quality markers should be developed. Many participants reflected on their concerns about unmet health care needs and felt there may be opportunities to improve proactive care in ‘at risk’ groups. Some expressed feelings of powerlessness that important child-relevant outcomes such as emergency department visits and emergency admissions were out of their control and more directly related to public health, school and parents/carers. The importance of access was a recurrent theme; access to urgent general practice appointments for children and GP access to specialists when needed. Conclusion The GPs expressed support for the development of quality markers for the care of children in UK general practice. However, they flagged up a number of important challenges which need to be addressed if markers are to be developed that are measureable, targeted and within the direct control of primary care. Easy access to primary and secondary care appointments may be an important benchmark for commissioners of care.

Background Despite the importance of continuity of care [COC] in contemporary mental health service provision, COC lacks a clearly agreed definition. Furthermore, whilst there is broad agreement that definitions should include service users’ experiences, little is known about this. This paper aims to explore a new construct of service user-defined COC and its relationship to a range of health and social outcomes. Methods In a cross sectional study design, 167 people who experience psychosis participated in structured interviews, including a service user-generated COC measure (CONTINU-UM) and health and social assessments. Constructs underlying CONTINU-UM were explored using factor analysis in order to understand service user-defined COC. The relationships between the total/factor CONTINU-UM scores and the health and social measures were then explored through linear regression and an examination of quartile results in order to assess whether service user-defined COC is related to outcome. Results Service user-defined COC is underpinned by three sub-constructs: preconditions, staff-related continuity and care contacts, although internal consistency of some sub-scales was low. High COC as assessed via CONTINU-UM, including preconditions and staff-related COC, was related to having needs met and better therapeutic alliances. Preconditions for COC were additionally related to symptoms and quality of life. COC was unrelated to empowerment and care contacts unrelated to outcomes. Service users who had experienced a hospital admission experienced higher levels of COC. A minority of service users with the poorest continuity of care also had high BPRS scores and poor quality of life. Conclusions Service-user defined continuity of care is a measurable construct underpinned by three sub-constructs (preconditions, staff-related and care contacts). COC and its sub-constructs demonstrate a range of relationships with health and social measures. Clinicians have an important role to play in supporting service users to navigate the complexities of the mental health system. Having experienced a hospital admission does not necessarily disrupt the flow of care. Further research is needed to test whether increasing service user-defined COC can improve clinical outcomes. Using CONTINU-UM will allow researchers to assess service users’ experiences of COC based on the elements that are important from their perspective.

Background Midwifery units (MUs) provide midwife-led care for women at low risk of complications. They may be located on the same site as an obstetric unit (OU), in a hospital without obstetric services or separate from any hospital. In MUs, if unforeseen complications arise, transfer to an OU may be necessary. Aim To provide evidence to contribute to the improvement of the transfer process, help make transfer safer and less distressing for women, thereby improving the care and experience of women planning to give birth in MUs. Methods A structured literature review of existing evidence was followed by three integrated component studies using different methods. The content and quality of local NHS transfer guidelines were evaluated. Data from the Birthplace national prospective cohort study were analysed to estimate transfer rates, describe the transfer process and identify factors associated with transfer. The experiences of women transferred were explored in qualitative interviews. Findings Transfer is a common event, affecting around 25% of women planning birth in MUs, although rates in different units vary. Primiparous women are more likely to be transferred than women having a second or subsequent baby. The risk of transfer for primiparous women increases with increasing age; around 50% of women having their first baby aged 40 years or over are transferred. Local NHS transfer guidelines are generally of poor quality and pay little attention to women’s experience. Women interviewed after transfer report feeling unprepared for transfer. Sensitive care and clear communication from midwives during labour facilitate feelings of control in women and help women accept transfer as the right decision and not a 'negative' event. Transfer that is perceived by women as “too late” can have potentially serious and long-lasting negative effects. Women’s experience of the transfer journey could be improved by the offer of choice in a number of areas which would help women feel 'cared for' rather than 'transported'. Having the MU midwife continue to care for the woman after transfer should be considered 'best practice'; where this is not possible a good handover is essential. Women who have experienced transfer should be offered the opportunity to talk to a midwife about their experience.

Background Research has investigated whether communication technologies (e.g. mobile telephony, forums, email) can be used to transfer digital information between healthcare professionals and young people who live with diabetes. The systematic review evaluates the effectiveness and impact of these technologies on communication. Methods Nine electronic databases were searched. Technologies were described and a narrative synthesis of all studies was undertaken. Results Of 20,925 publications identified, 19 met the inclusion criteria, with 18 technologies assessed. Five categories of communication technologies were identified: video-and tele-conferencing (n = 2); mobile telephony (n = 3); telephone support (n = 3); novel electronic communication devices for transferring clinical information (n = 10); and web-based discussion boards (n = 1). Ten studies showed a positive improvement in HbA1c following the intervention with four studies reporting detrimental increases in HbA1c levels. In fifteen studies communication technologies increased the frequency of contact between patient and healthcare professional. Findings were inconsistent of an association between improvements in HbA1c and increased contact. Limited evidence was available concerning behavioural and care coordination outcomes, although improvement in quality of life, patient-caregiver interaction, self-care and metabolic transmission were reported for some communication technologies. Conclusions The breadth of study design and types of technologies reported make the magnitude of benefit and their effects on health difficult to determine. While communication technologies may increase the frequency of contact between patient and health care professional, it remains unclear whether this results in improved outcomes and is often the basis of the intervention itself. Further research is needed to explore the effectiveness and cost effectiveness of increasing the use of communication technologies between young people and healthcare professionals.

© 2009 Wagai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background: Case management guidelines use a limited set of clinical features to guide assessment and treatment for common childhood diseases in poor countries. Using video records of clinical signs we assessed agreement among experts and assessed whether Kenyan health workers could identify signs defined by expert consensus. Methodology: 104 videos representing 11 clinical sign categories were presented to experts using a web questionnaire. Proportionate agreement and agreement beyond chance were calculated using kappa and the AC1 statistic. 31 videos were selected and presented to local health workers, 20 for which experts had demonstrated clear agreement and 11 for which experts could not demonstrate agreement. Principal Findings: Experts reached very high level of chance adjusted agreement for some videos while for a few videos no agreement beyond chance was found. Where experts agreed Kenyan hospital staff of all cadres recognised signs with high mean sensitivity and specificity (sensitivity: 0.897-0.975, specificity: 0.813-0.894); years of experience, gender and hospital had no influence on mean sensitivity or specificity. Local health workers did not agree on videos where experts had low or no agreement. Results of different agreement statistics for multiple observers, the AC1 and Fleiss' kappa, differ across the range of proportionate agreement. Conclusion: Videos provide a useful means to test agreement amongst geographically diverse groups of health workers. Kenyan health workers are in agreement with experts where clinical signs are clear-cut supporting the potential value of assessment and management guidelines. However, clinical signs are not always clear-cut. Video recordings offer one means to help standardise interpretation of clinical signs.

This thesis evaluates the cost-effectiveness of eight policies expanding human immunodeficiency virus (HIV) testing in South Africa. All policies entail provider-initiated test offers for primary healthcare users and one of two options across three policy components: (i) consent method, opt-in or opt-out; (ii) test protocol, rapid only or rapid plus acute infection testing; and (iii) linkage-to-care, standard or enhanced. This thesis highlights four methodological issues. First is the challenge of conducting a population-level analysis, projecting the cost-effectiveness of expanded testing for each member of South Africa’s adult African population. To this end, I conducted a retrospective, descriptive study to measure current population-level testing rates and epidemic descriptors in an African community near Cape Town, South Africa. Second, the effects of testing expansion on current testing uptake were estimated by distinguishing testing in the study community likely to cease after testing expansion (baseline testing) from that likely to continue (background testing). Third, because testing alone is an outcome of less interest than health benefits following treatment, study community linkage-to-care probabilities were estimated and models utilized to estimate the efficacy of treatment. Fourth, the methods to convert the study community testing data into inputs for these models’ parameters are outlined. The enhanced linkage-to-care policies proved the most cost-effective, with opt-in testing and a rapid-only test protocol the least expensive cost-effective option at $848 per life year gained (LYG). Adding an opt-out consent method or acute infection test protocol to this policy increased the LYGs, but at higher cost-effectiveness ratios.

Background although there is a wealth of information available about quality improvement tools and techniques in healthcare there is little understanding about overcoming the challenges of day-to-day implementation in complex organisations like hospitals. The 'Quality and Safety in Europe by Research' (QUASER) study will investigate how hospitals implement, spread and sustain quality improvement, including the difficulties they face and how they overcome them. The overall aim of the study is to explore relationships between the organisational and cultural characteristics of hospitals and how these impact on the quality of health care; the findings will be designed to help policy makers, payers and hospital managers understand the factors and processes that enable hospitals in Europe to achieve-and sustain-high quality services for their patients. Methods/design in-depth multi-level (macro, meso and micro-system) analysis of healthcare quality policies and practices in 5 European countries, including longitudinal case studies in a purposive sample of 10 hospitals. The project design has three major features: • a working definition of quality comprising three components: clinical effectiveness, patient safety and patient experience • a conceptualisation of quality as a human, social, technical and organisational accomplishment • an emphasis on translational research that is evidence-based and seeks to provide strategic and practical guidance for hospital practitioners and health care policy makers in the European Union. Throughout the study we will adopt a mixed methods approach, including qualitative (in-depth, narrative-based, ethnographic case studies using interviews, and direct non-participant observation of organisational processes) and quantitative research (secondary analysis of safety and quality data, for example: adverse incident reporting; patient complaints and claims). Discussion the protocol is based on the premise that future research, policy and practice need to address the sociology of improvement in equal measure to the science and technique of improvement, or at least expand the discipline of improvement to include these critical organisational and cultural processes. We define the 'organisational and cultural characteristics associated with better quality of care' in a broad sense that encompasses all the features of a hospital that might be hypothesised to impact upon clinical effectiveness, patient safety and/or patient experience.

BACKGROUND: The Electronic Prescription Service release Two (EPS2) is a new national healthcare information and communication technology in England that aims to deliver effective prescription writing, dispensing and reimbursement service to benefit patients. The aim of the study was to explore initial user experiences of Community Pharmacists (CPs) using EPS2. METHODS: We conducted nonparticipant observations and interviews in eight EPS2 early adopter community pharmacies classified as 'first-of-type' in midlands and northern regions in England. We interviewed eight pharmacists and two dispensers in addition to 56 hours recorded nonparticipant observations as field notes. Line-by-line coding and thematic analysis was conducted on the interview transcripts and field notes. RESULTS: CPs faced two types of challenge. The first was to do with missing electronic prescriptions. This was sometimes very disrupting to work practice, but pharmacists considered it a temporary issue resolvable with minor modifications to the system and user familiarity. The second was to do with long term design-specific issues. Pharmacists could only overcome these by using the system in ways not intended by the developers. Some felt that these issues would not exist had 'real' users been involved in the initial development. The issues were: 1) printing out electronic prescriptions (tokens) to dispense from for safe dispensing practices and to free up monitors for other uses, 2) logging all dispensing activities with one user's Smartcard for convenience and use all human resources in the pharmacy, and, 3) problematic interface causing issues with endorsing prescriptions and claiming reimbursements. CONCLUSIONS: We question if these unintended uses and barriers would have occurred had a more rigorous user-centric principles been applied at the earlier stages of design and implementation of EPS. We conclude that, since modification can occur at the evaluation stage, there is still scope for some of these barriers to be corrected to address the needs, and enhance the experiences, of CPs using the service, and make recommendations on how current challenges could be resolved.