Research Question: What are patients’ experiences of technology in adult intensive care? Research Objectives: -To explore patients’ perceptions of receiving care in a technological environment -To explore patients’ perceptions of how technology has influenced their experience of care Background: Technology is fundamental to the physical recovery of critically ill patients in intensive care (ICU), however, there is a suggestion in the literature that its presence may dehumanise patient care and distract the nurse from attending to patients’ psychosocial needs. Little attention has been paid to patients’ perceptions of receiving care in a technological environment. The purpose of this research, therefore, was to explore patients’ experiences of technology and care within ICU. Methods: This study was informed by Heideggerian phenomenology. The research took place in a university hospital in England. Nineteen participants who had been a patient in ICU were interviewed using a semi-structured approach. Interviews were transcribed verbatim and analysed utilising Van Manen’s framework. Findings: Resulting themes were ‘My Useless Body’ which describes how participants experienced their body as dysfunctional, disconnected and invaded by technology, ‘Making Sense of It’, which describes how participants rationalised their experiences by constructing a story, and ‘Technology and Care’, which describes how and why participants endured technologies in ICU. Conclusions: The disintegrated body is central to the critically ill’s experiences in ICU. Families play an important role in helping patients make sense of their experiences by filling in gaps in memory and helping them to sort the real from unreal memories. Families therefore require support and information resources in fulfilling this role. Patients experience technology and care as a series of paradoxical relationships: alienating yet reassuring, uncomfortable yet comforting, impersonal yet personal. Nurses maintaining a close and supportive presence and providing personal comfort and care may minimise the invasive and isolating potential of technology

This research study evaluated the use of Personal Development Planning (PDP) as a strategy to help a group of ten doctoral and fourteen postdoctoral research scientists, based in eight developing countries in Africa, enhance and progress their career development. To achieve this, a PDP system, with built-in tools and support systems was developed specifically for this purpose. Using an Action Research approach, within a framework adapted from Kirkpatrick’s “Four Levels of Evaluation” the research study evaluated the PDP system, tools and processes; and from lessons learned developed a transferable system and tools for future use with research scientists based in these and other developing countries in Africa. The study explored the following questions: (1) How do these research scientists feel about using PDP, the system and tools? (2) What is being done differently as a result of engaging with PDP – are there any learning gains, and are they applied in practice? (3) To what extent has PDP helped these research scientists feel confident about planning and managing their career development? (4) How far is it feasible to implement PDP more widely with other research scientists in Africa? Using both quantitative and qualitative data from the Group’s PDP documentation, questionnaires, nominal group technique, an online focus group discussion, and semi-structured interviews, the main study findings showed that overall the majority of the group felt that PDP made a positive contribution to helping them enhance and progress their career development; and was successful in helping them to feel confident about planning and managing their career development and progression. Given the focus and limited time, the study does not evaluate the broader impact that engagement with PDP might have on career progression. A longitudinal, follow up study would be needed to evaluate this aspect of PDP in relation to career development in Africa. The data showed that PDP is a concept that can be transferred successfully to developing country settings in Africa. It also indicated that, with the essential support elements of personal support, financial support, time and institutional support built into a PDP programme, it would be feasible to implement PDP with a similar group of research scientists in Africa. Further studies are needed to evaluate feasibility of implementing this strategy more widely in countries in Sub-Saharan Africa.

Due to increasing awareness of potential Cr toxicity, there is a pressing need to establish sensitive and robust Cr fractionation and speciation methodologies that will be enable separation of the two redox Cr species (CrIII and CrVI) from different environmental phases and their quantification. The intention of this work was to assess the behaviour of Cr species, especially CrVI, in soils and the factors controlling Cr solubility, fractionation, redox transformation rates and uptake by plants. The analysis methods relied on alkaline extraction in TMAH, liquid chromatography (LC) to separate the chromium species and inductively couple plasma mass spectrometry (ICP-MS) for quantification of chromium. The interference of 40Ar12C+ background peak at mass 52 was reduced by using the CCT-KED facility of the ICP-MS. A solution of 50 mM TRIS buffer, 40 mM NH4NO3, 10-5 M ammonium-EDTA at pH 7.0 was used as the chromatographic eluent. The method developed is suitable for determining CrVI in soil, following alkaline extraction in TMAH, but not for CrIII due to poor recovery, redox transformation and strong binding of CrIII with humic acid despite attempts to preserve the trivalent species using EDTA and heating. The extraction method was applied to assessing Cr speciation and fractionation in a wide range of soil ecosystems collected from urban sites in Wolverhampton, Nottingham, London and a historical sewage sludge disposal farm in Nottinghamshire. To predict soil CrVI content the use of TMAH-extractable Cr (CrTMAH) was better (R=0.911) compared to total soil Cr content (Crtotal; R=0.554). The same analytical approaches were also applied to the development of a method to determine isotopically exchangeable CrVI in soils. This employed isotopically enriched 50CrVI as a ‘spike’ isotope added to soils suspended in varying concentrations of TMAH in an attempt to resolve a consistent fraction of isotopically exchangeable, or ‘labile’, CrVIO42- in soil. It was apparent that, because of the slow exchange kinetics of CrVI in soils, it was difficult to determine a consistent isotopically exchangeable fraction. Nevertheless, the investigation did suggest a refinement of the simple TMAH extraction protocol could enable direct determination of labile soil CrVI. The kinetics of CrVI interaction with a geocolloid (humic acid) was assessed and humic acid was found capable of both reducing CrVI and binding with the resulting CrIII species. Finally, Cr uptake by maize grown on a historical sewage sludge disposal farm was assessed with several approaches to finding a correlation between Cr in soil and Cr uptake by plants. The concentration of CrVI in soil, and its solubility, could be reasonably well predicted from Crtotal or CrTMAH and soil properties. However, restricted uptake of CrVI by the maize plants, and probably reduction of CrVI to CrIII in the root system, made it impossible to predict Cr transfer to shoots or the speciation of the Cr in maize shoots. Overall, due mainly to the apparent ability of the maize plants to control uptake and speciation of CrVI, the produce was considered safe to be consumed by ruminants as regards CrVI content.

Objectives To develop an alcohol intervention model that predicts life years (LYs), quality adjusted life years (QALYs), and healthcare costs classified by the Alcohol Use Disorder Identification Test (AUDIT) screening tool and other various risk factors related to alcohol consumption. Furthermore, the developed model was transferred to the Thai setting. Methods Eight Scottish Health Surveys from 1995-2012 were linked to Scottish morbidity records and death records for the period 1981 to the end of 2013. Parametric survival analysis was used to estimate the hazard risks of first alcohol-related and non-alcohol related hospitalisations and deaths. For men and women, multivariate data analyses were applied separately for each gender in modelling the utility score, risks of subsequent hospitalisation and annual healthcare costs within the follow-up period. Risk profiles were used for the covariates of the models as follows: age, socio-economic status, health condition, alcohol drinking (i.e. AUDIT and binge drinking), smoking, body mass index, and physical activity. According to the under-reporting bias of alcohol consumption among the survey population, this study adjusted the reported alcohol consumption using alcohol sales data. Multiple imputation approach was applied to deal with missing data. A health-state transition model with annual cycle length was developed to predict LYs, QALYs, lifetime costs, and cost-effectiveness. Probabilistic sensitivity analysis was also performed to deal with parameter uncertainty. Moreover, a methodological transferability protocol of the Thai study was detailed. Results The sample size of the cohort was 46,230. The developed model showed the association between drinking and alcohol-related and non-alcohol related hospitalisations and deaths which were calculated as LYs and QALYs. Other risk factors were also taken into account that would likely affect the outcomes of interest. The modelling showed that an increasing AUDIT score and the number of cigarettes per day were associated with an increased risk of first alcohol-attributable hospitalisation. Predicted outcomes for a male aged 30 year with high-risk drinking levels (AUDIT >7) were worse than males with low risk drinking (AUDIT ≤7), with approximately 5 LY gained and 7 QALY gained. The same results for females were obtained for high-risk drinking (AUDIT >4) compared to low-risk drinking (AUDIT ≤4), with approximately 10 LY gained and 12 QALY gained. Furthermore, an economic evaluation was performed to compare the no-intervention situation with a hypothetical health promotion intervention - which aimed to stop drinking (measured by the AUDIT) and smoking (measured by the number of cigarettes per day) behaviours. To compare the costs and benefits of the hypothetical intervention and no intervention over the lifetime period, a within-trial analysis combined with the developed model was able to capture both short- and longer-term consequences (i.e. LYs, QALYs, and healthcare costs) of the intervention. Finally, the model was able to compare cost-effectiveness ratio between risk behaviours without the new intervention and the modified risk behaviours when the new intervention is implemented. Conclusions The study highlights the potential and importance of developing health economic models utilising data from routine national health surveys linked to national hospitalisation and death records. The developed framework can be used for further economic evaluation of alcohol interventions and other health behaviour change interventions. The framework can further be transferred to other country settings.

For the most part, diagnostic clinical microbiology still relies on 19th century ideas and techniques, particularly microscopy and laboratory culture. In this thesis I investigate the utility of a new approach, whole-genome sequencing (WGS), to tackle current issues in infectious disease. I present four studies. The first demonstrates the utility of WGS in a hospital outbreak of Acinetobacter baumannii. The second study uses WGS to examine the evolution of drug resistance following antibiotic treatment. I then explore the use of WGS prospectively during an international outbreak of food-borne Escherichia coli infection, which caused over 50 deaths. The final study compares the performance of benchtop sequencers applied to the genome of this outbreak strain and touches on the issue of whether WGS is ready for routine use by clinical and public health laboratories. In conclusion, through this programme of work, I provide ample evidence that whole-genome sequencing of bacterial pathogens has great potential in clinical and public health microbiology. However, a number of technical and logistical challenges have yet to be addressed before such approaches can become routine.

Delirium is an acute neuropsychiatric syndrome commonly affecting older people in general hospital. Dementia is common in older people in hospital with a distinct phenotype. Delirium and dementia commonly co-exist and are associated with adverse outcomes. The aims of the thesis were to developed pragmatic methods to screen for dementia in patients with delirium and to examine the outcomes of people with delirium. A prospective cohort study of older people admitted to hospital with delirium was carried out. Cognitive impairment was common among older people with delirium, with 3 in five having dementia and 1 in 5 having unrecognized dementia. Previously published dementia screening tools are scarce and not valid in people with delirium. Informant tools (the IQCODE and AD8) are highly sensitive and specific to detect dementia and combined cognitive impairment (MCI or dementia) in delirium. Delirium duration, severity, the hypoactive subtype and dysregulated inflammation were predictors of adverse outcomes in older people with delirium. This thesis confirms the close relationship between delirium and dementia in general hospitals. It offers pragmatic solutions to both screening for dementia in older people with delirium, and improving follow-up by detailing predictions of adverse outcome.

China is an emerging force in undertaking randomised clinical trials. The quality of trials from China may affect not only its own substantial population but also potentially contribute to health policy throughout the world. However, little is known about the quality of clinical trials conducted there. In this thesis, I will evaluate the quality of published Chinese randomised controlled trials (RCTs) by comparing them with Indian RCTs as well as a set of ‘gold standard’ trials reported in leading European and North American journals. I will also describe and contrast the quality and biases within Chinese RCTs. I then explore the reasons for these differences from the point of view of the major RCT stakeholders: Chinese clinicians and patients. The potential influences from Chinese traditional culture is also evaluated. Chinese medical journal editors need to undertake more training on the reporting of RCTs; all medical societies should take more concern about doctors’ research work; the Chinese public media should help the general population to understand more about RCT principles.

This PhD submission focuses on issues arising from the recent expansion of medical education in England, including widening access to medicine. It presents 11 papers published over the last 9 years which are the product of academic collaborations with colleagues and students at the University of Birmingham. The work includes outputs from local and national evaluations that have examined the expansion policy, process, and outcomes. Three research themes are identified from this body of papers; the first around predicted and observed impacts of expansion policy at local and national levels; the second concentrating on students’ and clinical teachers’ experiences of education amidst expanding provision; and finally issues relevant to widening access to medicine policy. The findings complement and add to existing knowledge in these research areas and give the basis to draw overarching conclusions about the significance of recent policy shifts for policy makers, medical schools, educators and students. In turn this work allows us to identify the need for further lines of enquiry and argues for a broad approach and conceptualisation for medical education research that is able to track macro policy changes, through meso level organisational and institutional influences, to micro level experience of educational policy and delivery.

The aim of this thesis is to help the RM industry avoid misguidedly investing in technologies that are unlikely to be cost-effective and reimbursed by healthcare providers. Health economics provides the tools to demonstrate value for money. These tools are typically used by healthcare providers to drive demand side decisions. However, they can be used by manufacturers to inform the supply side. I propose a simple approach, termed the headroom method. This ‘back of the envelope’ calculation is based on estimates of effectiveness of the proposed treatment towards the upper end of the plausible range. The method can be used either to inform an intuitive decision to continue or abandon development, or as a screening test to decide if more elaborate models are justified. One problem I encountered was the development of technologies without clearly defining the clinical problem. In particular, the marginal gain in benefit over alternative treatments is frequently overlooked. A large part of this thesis is therefore concerned with the clinical epidemiology of the conditions at which treatment is targeted. In this way, it was found, for example, the headroom for health gain from new treatment for inguinal hernia was much smaller than that for incisional hernias.

Computational toxicology is an emerging, multidisciplinary field that uses in-silico modelling techniques to predict and understand how biological organisms interact with pollutants and environmental stressors. Genome-wide metabolic reconstruction (GWMR) is an in-silico modelling technique that aims to represent the metabolic capabilities of an organism. Daphnia is an emerging model species for environmental omics whose underlying biology is still being uncovered. Creating a metabolic reconstruction of Daphnia and applying it in an environmental computational toxicology setting has the potential to aid in understanding its interaction with environmental stressors. Here, the fist GWMR of D. magna is presented, which is built using METRONOME, a newly developed tool for automated GWMR of new genome sequences. Active module identification allows for omics data sets to be integrated into in-silico models and uses optimisation algorithms to find hot-spots within networks that represent areas that are significantly impacted based on a toxicogenomic transcriptomics dataset. Here, a method that uses the active modules approach in a predictive capacity for computational hypothesis generation is introduced to predict unknown metabolic responses to environmentally relevant human-induced stressors. A computational workflow is presented that takes a new genome sequence, builds a GWMR and integrates gene expression data to make predictions of metabolic effects. The aim is to introduce an element of hypothesis generation into the untargeted metabolomics experimental workflow. A study to validate this approach using D. magna as the target organism is presented, which uses untargeted Liquid-Chromatography Mass Spectrometry (LC-MS) to make metabolomics measurements. A software tool MUSCLE is presented that uses multi-objective closed-loop evolutionary optimisation to automatically develop LC-MS instrument methods and is used here to develop the analytical method.