Hand hygiene is considered a key infection prevention strategy against the challenge of healthcare associated infections, as it prevents cross-transmission of microorganisms which may cause harm. Despite this, compliance amongst healthcare professionals is often poor. Considerable attention has been placed on developing interventions to increase hand hygiene, however known problems with measurement make determining improvement from established baselines difficult. This thesis addresses measurement through three research themes: The importance of meaningful data (Study 1), the potential for technology (Study 2), and the influence of human behaviour (Study 3). These are considered in relation to guidelines developed by the World Health Organisation (WHO) (My 5 Moments for Hand Hygiene). The thesis output provides recommendations for the healthcare setting, technology industry and research community by forming a new conceptual and integrated way of considering the measurement of hand hygiene compliance. A mixed methods approach was applied using a single case study methodology comprising three studies (two qualitative, one quantitative), based at a UK acute National Health Service Trust. Healthcare professionals involved in the current hand hygiene measurement process participated in all three studies (N=47). Methods included structured literature reviews, participant observation, one-to-one and group interviews, nonparticipant observation and analysis of existing case study site data. In Study 1 healthcare professionals identified a lack of clarity regarding feedback, and a lack of synergy between hand hygiene training and measurement. Combined with data accuracy flaws, their view was that the current hand hygiene measurement process produced meaningless data. Study 2 investigated healthcare professional views regarding the potential of technology to measure hand hygiene. It found that whilst current innovations are unable to detect all the WHO 5 Moments, healthcare professionals are interested in their potential to aid measurement and compliance. However they raised concerns about Fit for Purpose, anonymity and resistance, and over-reliance on technology and habituation. Interestingly participants suggested that hand hygiene across all WHO 5 Moments is not equal, expecting higher levels of adherence to Moments 2 and 3 than Moments 1, 4 and 5. Study 3 explored this, investigating the theory of Inherent and Elective hand hygiene behaviour. Inherent can be linked to Moments 2 and 3, through activities likely to stimulate an automatic “disgust” reaction within humans. Hand hygiene was significantly lower when healthcare professionals performed Elective rather than Inherent activities. The research developed Inherent and Elective theory further by proposing it as a lens with which to view the WHO 5 Moments and develop strategies for improved compliance. Understanding that hand hygiene is less likely at Elective activities, linked to Moments 1, 4 and 5 suggests these as key areas of focus for technology development. Acknowledging that hand hygiene may be more instinctive at Moment 2 and 3 may be useful when planning education, leading to reduced healthcare professional apathy towards hand hygiene. Involvement of healthcare professionals in exploring measurement processes and developing technologies for hand hygiene is proposed as key to ensure data produced by future methods of measurement is meaningful, vital to ensure desired behaviour change.

Waiting environments often represent the first interaction point of the healthcare journey and as such contribute to end-user overall experience. The design of these spaces should therefore make the experience as positive as possible. The body of evidence about the relationship between healthcare built-environments and end-user outcomes has grown rapidly in recent years. However, as opposed to inpatient and longterm care, few studies have focused on the design of outpatient settings and their waiting environments. In order to improve the waiting experience, it is necessary to understand how end-users perceive the design of the healthcare waiting environments. This research therefore aims to understand how end-users in the United Kingdom perceive the design of outpatient healthcare waiting environments (OHCWEs). A mixed methods research consisting of quantitative and qualitative techniques was developed to address key research objectives in four studies. In Study 1, end-user perceptions were explored through 24 photo-elicitation interviews. Content analysis of the data revealed that end-users described their perception of the design of OHCWEs using design descriptors and/or emotional, cognitive and associative terms. This contributed to the understanding of the content and language that participants used to describe the design. In Study 2a, 66 participants rated images on semantic differential scales. Using Principal Component Analysis, the level of pleasantness and typical healthcare appearance were extracted as two end-user main perceptions. As these two perceptions were found uncorrelated, a direct causal effect relationship between them could not be assumed. This challenged existing knowledge suggesting a positive effect on end-users related to untypical healthcare appearance. In Study 2b, learning from the review of the literature and from the studies 1 and 2a were consolidated to form a theoretical foundation for the research design of Study 3 to assess design attributes. In Study 3, participants (N=116) evaluated seven design attributes and their sub-attributes on perceived level of pleasantness using photo-realistic renderings which were specifically created. Conjoint Analysis revealed that wooden flooring, an open reception area, upholstered, single chairs that are arranged in rows, clear signage and additional features e.g. indoor plants or refreshment facilities were perceived most pleasant. The quantifiable measures about the contribution of each design attribute to perceived level of pleasantness extend existing knowledge in evidence-based design and hence represent conceptual contributions. In addition to the conceptual contributions, this research also contributes to the practical and methodological development of evidence-based design. The methodological framework provides a novel way of measuring end-user perceptions of the design in OHCWEs. The developed method allowed a more complete view on end-user insights which would not have been possible using traditional, pure methods. Additional learning about the design enabled the formulation of practical design recommendations to improve end-user perceptions of OHCWEs. Being able to assess the pleasantness of healthcare environments has the potential to improve the well-being of end-users.

Patient safety measurement methods are dominated by outcome measurement, reducing them to counts of harm or adverse events. Performance measurement recognises the limitations of the sole use of outcome indicators and proposes the use of measures throughout the system, in particular the determinants of the desired outcomes. Furthermore, it promotes stakeholder engagement in the design of measures in order to understand their expectations and how they contribute. This is particularly important in healthcare services, such as the NHS case management programme, where patient contribution is growing. This programme is a response to the ageing population and the subsequent increase in complex long term conditions, aiming to deliver care in the home to empower patients so they are able to care for themselves to a greater extent. In comparison to the institutionalised setting, the home setting is relatively unexplored. Therefore, this research has provided an opportunity to examine the concept of safety in a care service with an increasing demand from a vulnerable population. The research aimed to develop a conceptual framework for safety measurement that was: 1) reflective of key stakeholders; 2) able to incorporate the system; and 3) representative of the home-delivered healthcare of the case management programme. An exploratory, sequential mixed method design within the critical realist philosophy, which was guided by the principles of performance measurement, was adopted. A case study utilising 13 interviews with nine patients and six carers (two interviews were held jointly) and three focus groups with 17 case management nurses was deployed. This enabled in-depth exploration of their perspectives regarding safety, including: their definitions of safety, who was involved, the contributing factors, and which outcomes were most important. Intriguing, important or contradictory findings were further examined using a survey (patient n=35, carer n=19 and case management nurse n=26), which aimed to determine the level of agreement with these qualitative findings and identify any statistically significant differences between the stakeholder groups. Through engagement with stakeholders, this research has established a definition of safety that represents the type of care provided by the case management programme. In particular, it recognises the importance of meeting the care needs of this patient population, acknowledging that the alternative would facilitate disease progression, exposing patients to unnecessary harm. Understanding the patient perspective has proven to be particularly important because of the level of control asserted by patients on the structure, processes and outcomes of care. This level of control is an integral component of the proposed conceptual framework. Of greatest significance is the incorporation of the patients' living environments and their resources into the structure of care, as well as the involvement of their daily self-care activities in the processes of care. Consequently, the framework is inclusive of non-traditional safety outcomes, such as functional health status, because they help sustain patient controlled structures and processes, which in turn influence traditional measures of harm. The conceptual framework is a guide to the assessment of safety in case management that specifies a range of factors that facilitate the condition of safety, providing a holistic overview of the complex, nested system of care required to manage long term conditions.

This thesis describes a series of observational studies that examine the relationship between the systemic inflammatory response, glucose, micronutrients concentrations and outcomes in patients with critical illness with reference to a large nutrition screen cohort. Data and stored samples were available from cohorts which had been defined previously. The critical illness cohort comprised of medical or surgical patients ≥ 18 years admitted to the Intensive Care Unit (ICU) of the Glasgow Royal Infirmary (GRI) between September 2006 and December 2008. The nutrition screen cohort comprised samples and associated information which had been processed by the Pathological Biochemistry Department of the GRI. The samples had been received for vitamin and / or trace element assessment of patients from both GRI and other Scottish hospitals between January 2006 and March 2013. Samples had been referred to the lab for analysis of a number of variables related to nutrition, including glucose, albumin, C-reactive protein (CRP), lutein, lycopene, vitamins A, B1, B2, B6, C, D and E, and zinc, selenium, copper, and manganese. Data was not available for all variables for all samples, hence studies varied in the number of observations. plasma glucose was measured in sodium floride blood sample whole-blood samples underwent for routine analysis of concentrations of lutein, lycopene, α-carotene and β-carotene, 25-hydroxyvitamin D (25 (OH) D), ascorbic acid (vitamin C), α-tocopherol (vitamin E) in plasma, zinc, selenium, copper, B1, B2, B6 in plasma and red cells. In Chapter 2 the relationship between glucose and markers of the systemic inflammatory response was examined in detail in patients from the critical illness cohort (n=100). The results of this study showed that plasma glucose concentration - even within the context of tight insulin protocol - was influenced by many factors. Surgical and medical patients differed in their requirements for insulin; medical patients have higher plasma glucose and insulin administration accordingly compared with surgical patients. However, catecholamine and steroid administration were also associated with higher insulin requirements. In Chapter 3 the relationship between plasma asymmetric dimethylarginine (ADMA) and related arginine metabolism (homoarginine, arginine, symmetric dimethylarginine (SDMA)) and outcome was examined in patients from critical illness cohort (n=104). Patients with critical illness experience metabolic disorders including catabolism and hyperglycaemia and these were associated with poor outcome. Plasma ADMA and SDMA concentrations were higher in patients with critical illness and were also associated with disease severity and mortality. In contrast, plasma homoarginine concentrations were lower in patients with critical illness and were also associated with disease severity and mortality. These results suggest that ADMA metabolism is perturbed with likely knock on effects on nitric oxide synthase (NOS) and endothelial function. There is a need for further work on in vivo dimethylaminohydrolase (DDAH) activity in critical illness and the effect of critical illness on the cationic amino acid transporters (CAT)-mediated exchange of ADMA between intra and extra-cellular compartments. It was proposed that ADMA and SDMA may not only be indicators of the severity of illness and may even contribute to adverse events in patients with critical illness. In Chapter 4 the relationship between markers of the systemic inflammatory response, as evidenced by CRP and albumin, and mortality, in patients from critical illness cohort (n=261) was examined. In this cohort, the combination of CRP and albumin predicted ICU and hospital mortality as effectively as APACHE II. In Chapter 5 the relationship between markers of the systemic inflammatory response and plasma glucose was examined in a nutrition screen cohort (n=5248). The results of this study showed that plasma concentrations of glucose were independently positive and negative associated with both CRP and albumin respectively, and were consistent with the systemic inflammatory response as having an impact on glucose concentrations. However, such relationships were not apparent in patients with critical illness (n=116). It was concluded that plasma concentrations of glucose were independently associated with both CRP and albumin, and were consistent with the systemic inflammatory response as a determinant of its concentrations. In Chapter 6 the relationship between markers of the systemic inflammatory response and plasma concentrations of carotenoids was examined in a nutrition screen cohort (n=1074). The results of this study showed that the clinical interpretation of plasma carotenoids requires knowledge of the magnitude of the systemic inflammatory response, even after adjustment for cholesterol. It was concluded that a reliable clinical interpretation can be made only for plasma lutein, lycopene and β-carotene if the CRP is less than 20 mg/L. In Chapter 7 the relationship between markers of the systemic inflammatory response and plasma 25-hydroxyvitamin D (25(OH) D) was examined in a nutrition screen cohort (n=5327, and in patients from critical illness cohort n=117). The results of this study showed that plasma concentrations of 25(OH) D were independently associated with both CRP and albumin. It was concluded that the systemic inflammatory response was a major confounding factor in determining vitamin D status. In Chapter 8 the relationship between markers of the systemic inflammatory response and plasma vitamin E (α-tocopherol) and vitamin C (ascorbic acid) was examined in a nutrition screen cohort (n=359, n=494 respectively and in patients from critical illness cohort n= 82). The results of this study showed that α-tocopherol/ cholesterol ratio and ascorbic acid were independently associated with both CRP and albumin. It was concluded that the systemic inflammatory response was a major confounding factor in determining vitamin E and C status. In Chapter 9 the relationship between markers of the systemic inflammatory response and plasma zinc, selenium was examined in a nutrition screen cohort (n=743, n=833, respectively and in patients from the critical illness cohort n= 114). The results of this study showed that plasma concentrations of zinc were associated with both CRP and albumin. However, the impact of the systemic inflammatory response (as evidenced by elevation of CRP concentrations) on plasma zinc concentrations could be largely adjusted by albumin concentrations. Plasma concentrations of selenium were associated with both CRP and albumin. However, the impact of the systemic inflammatory response on plasma selenium concentrations could not be reasonably adjusted by albumin concentrations. It was concluded that plasma zinc and selenium concentrations were independently associations with CRP and albumin as markers of systemic inflammatory response. In Chapter 10 the relationship between markers of the systemic inflammatory response and red cell zinc, selenium and copper was examined in patients from critical illness cohort (n= 125). The results of this study showed that altered red cell concentrations of zinc, selenium and copper were likely to be more reliable measures of status in the presence of a systemic inflammatory response. In Chapter 11 the relationship between markers of the systemic inflammatory response and red cell vitamins B1, B2 and B6 was examined in nutrition screen cohort (n= 553, n=251, n= 313, respectively and in patients from critical illness cohort n=94). The results of this study showed that in contrast to plasma concentrations of B1, B2 and B6, red cell concentrations do not fall as a part of the systemic inflammatory response. It was concluded that red cell concentrations of B1, B2 and B6 were likely to be more reliable measures of status in the presence of a systemic inflammatory response. In summary, studies in the present thesis showed that, during the systemic inflammatory response, plasma concentration of glucose had multiple determinants other than insulin. Furthermore, in the presence of systemic inflammatory response, plasma lutein, lycopene, α-carotene and β-carotene, 25 (OH) D, C, E, zinc, selenium, and copper were unreliable, and that intracellular micronutrients concentrations such as red cell zinc, selenium, copper, B1, B2 and B6, were more reliable as indicators of vitamin and trace element status in patients subject to nutrition screen and in patients with critical illness. These results have implications for the assessment of glucose and micronutrient status in the general population and for treatment in patients with critical illness.

This thesis presents an investigation into the personal constructs that people with type 2 diabetes use, to live and manage their condition. The approach adopted was underpinned by personal construct psychology, utilising qualitative and dependency grid methods to determine individual personal constructs in a multiple case series design. In the thesis a critical discussion is presented of current UK national policy and clinical guidelines in diabetes care. This found that gaps exist in the current evidence base, particularly in individual approaches and interventions provided by healthcare professional services. The synthesis of research literature in the experience of adults with type 2 diabetes showed that some common themes exist; achieving balance, normalising and psychological alterations. Furthermore the synthesis revealed that self-efficacy and personal model research studies in diabetes have found that these issues are influential in how people live and cope with their condition. Using a convenience sample of adults with type 2 diabetes, predominantly cared for in the community, a series of interviews were conducted in a sample of 23 participants. Ten participants completed all the stages of the research data collection and these are presented in the results as a case study series. The dependency grid technique required each participant to complete a series of grid ratings of constructs and elements associated with their living with type 2 diabetes. The results of the exploratory qualitative interviews were five major themes of family, relationships and interactions; social-life/activity; emotional changes/support; meaningful work/sense of worth; and making adiustments/diabetes functional activity. The themes were translated into the dependency grids as constructs and participants then rated people as elements against these constructs. The analysis of the ten case studies showed personal constructs associated with interdependence with family, friends and healthcare professionals. The interdependence identified had strong or weak associations with diabetes related constructs depending on how each individual participant had rated them. The findings suggest that people with type 2 diabetes do not always consider primary care services as appropriate for their needs and contrast this with the value they previously made to secondary care services. Each individual has developed their own level of interdependence with some type 2 patients with diabetes being self reliant or using family members/friends more than professional health services. Recommendations include further exploration of interdependence in type 2 diabetes. Limitations of the study include sample issues, and a methodological approach that is educative and lengthy in implementation.

Detailed within this thesis are the synthetic studies performed on the preparation of lipase catalysed activated esters and their subsequent use in the synthesis of pharmaceutically relevant amides. It also includes the application of activated esters in chemoselective amide formation reactions. The introduction summarizes the significance and use of activating agents in lipase catalysed reactions over the classical methods of amides synthesis. Additionally, a detailed review on some currently available chemoselective N-acylating agents along with their applications is also mentioned. A separate chapter is given to the application of related amides in the designing of biological probes to ultimately detect enzymes which are over-expressed in disease. The discussion begins with the lipase-catalysed synthesis of acetone oxime activated esters and their role in the one-pot synthesis of acetanilides. Further discussion continues with the synthesis of activated esters from ethylene glycol and haloalcohols. The use of a lipase in the synthesis of glycol esters prevented the formation of dimers which indicates its potential usefulness in the future. Unfortunately, these activated esters could not be applied to a synthesis of amides in the same manner as acetone oxime. Thereafter the section focuses on the investigation and synthesis a novel chemoselective N-acylating agent and its subsequent applications in the synthesis of pharmaceutically important amides, in particular, those involving chemoselective reactions between anilines and N-substituted anilines. Additionally, the chemoselective agent was also used in preparation of pharmaceutically important compounds. To round off the thesis the application of one of the target compounds-benzanilide-was used to develop and synthesise a novel biological probe and to scope out its potential for application in the detection of enzyme-controlled disease. The preliminary utility of the probe was demonstrated using HPLC and NMR. The thesis concludes with the experimental encompassing experimental details, spectroscopic and analytical analysis of all the compounds described.

Between the years 1852 and 1860 six voluntary hospitals were opened in Great Britain to provide medical care for children who would previously have been considered too young to be admitted to hospital. This thesis argues that the process was shaped by the public health movement which was ascendant at that time. The literature review shows that while historians of nineteenth-century childhood have been aware that child health was a problem, especially for working-class children, they have tended to view this through the prism of industrial and urban history, and there is little work available relating specifically to the provision of health care for younger children. Chapters two and three demonstrate the emergence of a new understanding of the nature of childhood which came about as a result of the great inquiries into child labour, the health of towns, and the condition of the labouring classes, and the impact of the emerging science of statistics. At a time of crisis in traditional British medicine, the new approaches combined with French clinical and German laboratory techniques to open British physicians to the possibility of working with young children as a serious proposition for the first time. Chapters four to six follow the various ways in which six children’s hospitals were opened in London, Norwich, Liverpool, Manchester, and Edinburgh. Influences which are analysed include the desire to rectify the acknowledged ignorance among physicians concerning children’s diseases, the recognition of environmental management as a fruitful means for improving children’s health, and a new willingness to emulate Continental practices. This thesis departs from the existing historiography in challenging the underlying assumption as to the operating model of a hospital. Histories of children’s hospitals are written in terms of the extent to which they succeeded in applying the allopathic model of health, with the administration of medicines and surgical procedures at the centre, however ineffectually. What actually distinguished the new institutions was their emphasis on promoting healing not by manipulating children’s bodies but, drawing on the insights of the public health movement, by providing a therapeutic environment.

This thesis describes the impact of high energy density nutritional supplement drinks (HENSDs) on appetite regulation, energy intake and cardiovascular risk factors in lean healthy females. It also explores the impact of Solid Ready-To-Use Foods (RTUF) and a milk based Liquid Ready-To-Use proprietary Supplement (LRUS) on weight gain and appetite in mild to moderate underweight children from Pakistan. The thesis consists of a literature review (Chapter 1), general methods (Chapter 2), three experimental chapters (Chapter 3- Chapter 5), each describing an independent research study, and a general discussion and conclusion chapter (Chapter 6). Accumulating evidence suggests that oral HENSDs increases energy intake and are beneficial for the treatment of malnutrition. Their effectiveness however, may be diminished by acute suppression of appetite. Therefore, the first experimental study aimed to investigate the extent to which the consumption of the HENSD in the fasted state reduces energy intake during a consecutive breakfast and lunch and whether this reduction relates to changes in appetite and metabolic appetite regulators. Twenty three young females with BMI of 18.2 ± 0.8 kg/m2 consumed either a HENSD or a low energy drink (PLACEBO) after fasting, in a single blind randomized cross-over study. Appetite was tracked, and blood taken, prior to the intake of the supplement and 240 minutes afterwards. Energy intake was recorded during an ad libitum buffet breakfast served 60 minutes and an ad libitum buffet lunch served 240 minutes post supplementation. Energy intake during the breakfast was significantly higher in the PLACEBO than in the HENSD trial. No significant difference was found in energy intake during the lunch between the two trials. When energy provided by supplements was added to energy intake during breakfast and lunch, the energy intake in the HENSD trial was significantly higher. The net effect was that total energy intake was increased by 1.07 ± 0.34 MJ in the HENSD trial. During the pre-breakfast, feelings of hunger and a desire to eat were significantly lower; satiety and fullness were significantly higher in the HENSD trial. After breakfast, none of the appetite measures differed between the trials regardless of plasma PYY, CCK, and insulin concentrations being significantly higher in the HENSD trial. The second experimental study investigated the time scale of compensation after HENSD supplementation. Over a five day period, energy intake was measured after the supplementation during the evening meal, and during the ad libitum breakfast, lunch and dinner consumed on the consecutive day. Since, consumption of HENSD due to the promotion of energy was expected to promote positive energy balance, this study also aimed to investigate the impact of HENSD supplementation on cardio-metabolic risk factors. Twenty-three young healthy females with a BMI of 18.7 ± 1.2 kg/m2 participated in a single blind randomised, controlled, crossover study. Participants consumed either HENSD or a PLACEBO for five days in the evening. Participants were asked to record their dietary intake during the days of supplementation. On the sixth day plasma lipids, insulin and glucose concentrations were measured in the fasted state and at 30, 60, 90 and 120 minutes after the ad libitum buffet breakfast and lunch. The findings showed that the average daily energy intake was significantly higher in HENSD trial and that consumption of HENSDs in the evening induced immediate and short-lasting reduction in energy intake. Fasting plasma concentrations of insulin and HOMA (IR) were significantly higher in the HENSD as compared to the PLACEBO trial. No significant differences were detected in fasting plasma concentrations of TAG, total-, HDL- and LDL-cholesterol between the HENSD and the PLACEBO trials. The third experimental study explored the efficacy of RTUFs and LRUS in promoting weight gain and their effect on appetite regulation in mild to moderate malnourished children. An open labelled randomized controlled trial was conducted in primary schools of Pakistan. Sixty eight mild to moderate underweight children aged 8.2 ± 1.2 years were randomly allocated to receive either RTUF or LRUS providing 500 kcal/ day in addition to regular diet in their school for four weeks. The children’s height, weight, and skinfolds were measured before supplementation and at the end of the supplementation. The children marked visual analogue scale questionnaires before the provision of the first and the last supplement. The findings from this study indicated that after four weeks of supplementation the average weight gain, change from the baseline in weight-for-age Z score (WAZ), height-for-age Z score (HAZ) in the RTUF and LRUS were not significantly different between the two groups. The difference in the appetite measures before the provision of the first and the last supplement between the two groups were also not significantly different. The total extra energy supplied for 4 weeks would have been expected to lead to an excess gain of 2kg. Thus, at least 2/3 of the energy ingested appeared to have been compensated by less intake at other times. Based on the data obtained the following conclusions have been drawn: • Following oral intake of HENSDs, the appetite suppressive action of the metabolic and hormonal appetite modulators is short lived. • HENSDs consumption for five consecutive days in the evening induced compensation, which happens immediately, disappears quickly and is short-lived which allows only partial compensation for the energy provided by HENSD. • Short-term supplementation with HENSD is safe in relation to the impact on cardiometabolic risk factors such as plasma concentration of fasting and postprandial lipids but can be expected to reduce insulin sensitivity. • RTUF and LRUS given to the community has similar impact on improving the nutritional status in mild of moderate underweight children but the overall rate of weight gain was lower than expected.

Comorbidity is defined as experiencing an ‘index’ health condition with one or more other conditions at the same time. The prevalence of comorbidity, in particular chronic disease comorbidity, is set to rise in ageing Western populations and negatively influences patient health and health care services. However, our understanding of how specific comorbid chronic disease combinations (such as cardiovascular disease and osteoarthritis) interact, the subsequent outcomes and how severity influences these remains limited. The aim of this thesis was to investigate the consequences of cardiovascular disease and osteoarthritis comorbidity on short and long-term physical health change in general practice populations.

In response to long waiting lists and problems with access to primary care physiotherapy, several Primary Care Trusts (PCTs) developed physiotherapy-led telephone assessment and treatment services. The MRC-funded PhysioDirect trial was a randomised trial in four PCTs, with a total of 2252 patients that compared this approach with usual physiotherapy care. This nested qualitative study aimed to explore and understand the key issues that determine the acceptability of PhysioDirect services from the perspectives of patients, physiotherapists, physiotherapy managers, (General Practitioners) GPs and commissioners.