Applying quantitative methods in the assessment of outcomes of pharmacotherapy of psoriasis

Healthcare providers and policy makers are faced with an ever-increasing number of medical publications. Searching for relevant information and keeping up to date with new research findings remains a constant challenge. It has been widely acknowledged that narrative reviews of the literature are susceptible to several types of bias and a systematic approach may protect against these biases. The aim of this thesis was to apply quantitative methods in the assessment of outcomes of topical therapies for psoriasis. In particular, to systematically examine the comparative efficacy, tolerability and cost-effectiveness of topical calcipotriol in the treatment of mild-to-moderate psoriasis. Over the years, a wide range of techniques have been used to evaluate the severity of psoriasis and the outcomes from treatment. This lack of standardisation complicates the direct comparison of results and ultimately the pooling of outcomes from different clinical trials. There is a clear requirement for more comprehensive tools for measuring drug efficacy and disease severity in psoriasis. Ideally, the outcome measures need to be simple, relevant, practical, and widely applicable, and the instruments should be reliable, valid and responsive. The results of the meta-analysis reported herein show that calcipotriol is an effective antipsoriatic agent. In the short-tenn, the pooled data found calcipotriol to be more effective than calcitriol, tacalcitol, coal tar and short-contact dithranol. Only potent corticosteroids appeared to have comparable efficacy, with less short-term side-effects. Potent corticosteroids also added to the antipsoriatic effect of calcipotriol, and appeared to suppress the occurrence of calcipotriol-induced irritation. There was insufficient evidence to support any large effects in favour of improvements in efficacy when calcipotriol is used in combination with systemic therapies in patients with severe psoriasis. However, there was a total absence of long-term morbidity data on the effectiveness of any of the interventions studied. Decision analysis showed that, from the perspective of the NHS as payer, the relatively small differences in efficacy between calcipotriol and short-contact dithranol lead to large differences in the direct cost of treating patients with mildto-moderate plaque psoriasis. Further research is needed to examine the clinical and economic issues affecting patients under treatment for psoriasis in the UK. In particular, the maintenance value and cost/benefit ratio for the various treatment strategies, and the assessment of patient's preferences has not yet been adequately addressed for this chronic recurring disease.

Cell surface analysis of the basidiomycete yeast cryptococcus neoformans

Cell surface properties of the basidiomycete yeast Cryptococcus neoformans were investigated with a combination of novel and well proven approaches. Non-specific cell adhesion forces, as well as exposed carbohydrate and protein moieties potentially associated with specific cellular interaction, were analysed. Experimentation and analysis employed cryptococcal cells of different strains, capsular status and culture age. Investigation of cellular charge by particulate microelectrophoresis revealed encapsulated yeast forms of C. neoformans manifest a distinctive negative charge regardless of the age of cells involved; in turn, the neutral charge of acapsulate yeasts confirmed that the polysaccharide capsule, and not the cell wall, was responsible for this occurrence. Hydrophobicity was measured by MATH and HICH techniques, as well as by the attachment of polystyrene microspheres. All three techniques, where applicable, found C. neoformans yeast to be consistently hydrophilic; this state varied little regardless of strain and culture age. Cell surface carbohydrates and protein were investigated with novel fluorescent tagging protocols, flow cytometry and confocal microscopy. Cell surface carbohydrate was identified by controlled oxidation in association with biotin hydrazide and fluorescein-streptavidin tagging. Marked amounts of carbohydrate were measured and observed on the cell wall surface of cryptococcal yeasts. Furthermore, tagging of carbohydrates with selective fluorescent lectins supported the identification, measurement and observation of substantial amounts of mannose, glucose and N-acetyl-glucosamine. Cryptococcal cell surface protein was identified using sulfo-NHS-biotin with fluorescein-streptavidin, and then readily quantified by flow cytometry. Confocal imaging of surface exposed carbohydrate and protein revealed common localised areas of vivid fluorescence associated with buds, bud scars and nascent daughter cells. Carbohydrate and protein fluorescence often varied between strains, culture age and capsule status of cells examined. Finally, extension of protein tagging techniques resulted in the isolation and extraction of two biotinylated proteins from the yeast cell wall surface of an acapsulate strain of C.neoformans.

Development and validaton of an indicator to compare antibiotic usage in secondary care in England

The use of antibiotics was investigated in twelve acute hospitals in England. Data was collected electronically and by questionnaire for the financial years 2001/2, 2002/3 and 2003/4. Hospitals were selected on the basis of their Medicines Management Self-Assessment Scores (MMAS) and included a cohort of three hospitals with integrated electronic prescribing systems. The total sample size was 6.65% of English NHS activity for 2001/2 based on Finished Consultant Episode (FCE) numbers. Data collected included all antibiotics dispensed (ATC category J01), hospital activity FCE's and beddays, Medicines Management Self-assessment scores, Antibiotic Medicines Management scores (AMS), Primary Care Trust (PCT) of origin of referral populations, PCT antibiotic prescribing rates, Index of Multiple Deprivation for each PCT. The DDD/FCE (Defined Daily Dose/FCE) was found to correlate with the DDD 100beddays (r = 0.74 p

An examination of adverse drug reaction reporting to the yellow card scheme

Chief pharmacists in 209 hospitals were surveyed about ADR reporting schemes, the priority given to ADR reporting, and attitudes towards ADR reporting. ADR reporting had a low managerial priority. Local reporting schemes were found to be operating in 37% trusts, but there were few plans to start new schemes. Few problems were discovered by the introduction of pharmacist ADR reporting. Chief pharmacists had concerns about the competence of hospital pharmacists to detect ADRs and were in favour of increased training. Lack of time on wards, and recruitment difficulties were suggested as reasons for hospital pharmacist under-reporting. Teaching hospitals appeared to have an increased interest in ADR reporting. A retrospective analysis of reporting trends within the West Midlands region from 1994, showed increasing or stable reporting rates for most sectors of reporters, except for general practitioners (GPs). The West Midlands region maintained higher ADR reporting rates than the rest of the UK. National reporting figures showed a worrying decline in ADR reports from healthcare professionals. Variation was found in the ADR reporting rates of Acute NHS Hospital Trusts and Primary Care Trusts (PCTs) in the West Midlands region, including correlations with prescribing rates and other PCT characteristics. Qualitative research into attitudes of GPs towards the Yellow Card scheme was undertaken. A series of qualitative interviews with GPs discovered barriers and positive motivators for their involvement in the Yellow Card scheme. A grounded theory of GP involvement in the Yellow Card scheme was developed to explain GP behaviour, and which could be used to inform potential solutions to halt declining rates of reporting. Under-reporting of ADRs continues to be a major concern to those who administer spontaneous reporting schemes.

Sensing and control of adipocyte function

Obesity has become a global epidemic. Approximately 15% of the world population is either overweight or obese. This figure rises to 75% in many westernised countries including the United Kingdom. Health costs in the UK to treat obesity and associated disease are conservatively estimated at 6% of the National Health Service (NHS) budget equating to 3.33 billion Euros. Excess adiposity, especially in visceral depots, increases the risk of type 2 diabetes, cardiovascular disease, gall stones, hypertension and cancer. Type 2 diabetes mellitus accounts for >90% of all cases of diabetes of which the majority can be attributed to increased adiposity, and approximately 70% of cardiovascular disease has been attributed to obesity in the US. Weight loss reduces risk of these complications and in some cases can eliminate the condition. However, weight loss by conventional non-medicated methods is often unsuccessful or promptly followed by weight regain. This thesis has investigated adipocytes development and adipokine signalling with a view to enhance the understanding of tissue functionality and to identify possible targets or pathways for therapeutic intervention. Adipocyte isolation from human tissue samples was undertaken for these investigative studies, and the methodology was optimised. The resulting isolates of pre-adipocytes and mature adipocytes were characterised and evaluated. Major findings from these studies indicate that mature adipocytes undergo cell division post terminal differentiation. Gene studies indicated that subcutaneous adipose tissue exuded greater concentrations and fluctuations of adipokine levels than visceral adipose tissue, indicating an important adiposensing role of subcutaneous adipose tissue. It was subsequently postulated that the subcutaneous depot may provide the major focus for control of overall energy balance and by extension weight control. One potential therapeutic target, 11ß-hydrosteroid dehydrogenase (11ß-HSD1) was investigated, and prospective inhibitors of its action were considered (BVT1, BVT2 and AZ121). Selective reduction of adiposity of the visceral depot was desired due to its correlation with the detrimental effects of obesity. However, studies indicated that although the visceral depot tissue was not unaffected, the subcutaneous depot was more susceptible to therapeutic inhibition by these compounds. This was determined to be a potentially valuable therapeutic intervention in light of previous postulations regarding long-term energy control via the subcutaneous tissue depot.

Accountability, organisational learning and risks to patient safety in England: conflict or compromise?

This article examines the current risk regulation regime, within the English National Health Service (NHS), by investigating the two, sometimes conflicting, approaches to risk embodied within the field of policies towards patient safety. The first approach focuses on promoting accountability and is built on legal principles surrounding negligence and competence. The second approach focuses on promoting learning from previous mistakes and near-misses, and is built on the development of a ‘safety culture’. Previous work has drawn attention to problems associated with risk-based regulation when faced with the dual imperatives of accountability and organisational learning. The article develops this by considering whether the NHS patient safety regime demonstrates the coexistence of two different risk regulation regimes, or merely one regime with contradictory elements. It uses the heuristic device of ‘institutional logics’ to examine the coexistence of and interrelationship between ‘organisational learning’ and ‘accountability’ logics driving risk regulation in health care.

Evaluation of disinfecting procedures for aseptic transfer in hospital pharmacy departments

Current practice in National Health Service (NHS) hospitals employs 70% Industrial Methylated Spirit spray for surface disinfection of components required in Grade A pharmaceutical environments. This study seeks to investigate other agents and procedures that may provide more effective sanitisation. Several methods are available to test the efficacy of disinfectants against vegetative organisms. However, no methods currently available test the efficacy of disinfectants against spores on the hard surfaces encountered in the pharmacy aseptic processing environment. Therefore, a method has been developed to test the efficacy of disinfectants against spores, modified from British Standard 13697 and Association of Analytical Chemists standards. The testing procedure was used to evaluate alternative biocides and disinfection methods for transferring components into hospital pharmacy cleanrooms, and to determine which combinations of biocide and application method have the greatest efficacy against spores of Bacillus subtilis subspecies subtilis 168, Bacillus subtilis American Type Culture Collection (ATCC) 6633, and Bacillus pumilis ATCC 27142. Stainless steel carrier test plates were used to represent the hard surfaces in hospital pharmacy cleanrooms. Plates were inoculated with 10(7)-10(8) colony-forming units per milliliter (CFU/mL) and treated with the various biocide formulations, using different disinfection methods. Sporicidal activity was calculated as log reduction in CFU. Of the biocides tested, 6% hydrogen peroxide and a quaternary ammonium compound/chlorine dioxide combination were most effective compared to a Quat/biguanide, amphoteric surfactant, 70% v/v ethanol in deionised water and isopropyl alcohol in water for injection. Of the different application methods tested, spraying followed by wiping was the most effective, followed closely by wiping alone. Spraying alone was least effective.

Paediatric 'care closer to home':stake-holder views and barriers to implementation

In this study we explore the views of NHS stakeholders on providing paediatric ‘care closer to home’ (CCTH), in community-based outpatient clinics delivered by consultants. Design: Semi-structured interviews and thematic framework analysis. Setting: UK specialist children's hospital and surrounding primary care trusts. Participants: 37 NHS stakeholders including healthcare professionals, managers, commissioners and executive team members. Results: Participants acknowledged that outreach clinics would involve a change in traditional ways of working and that the physical setting of the clinic would influence aspects of professional practice. Different models of CCTH were discussed, as were alternatives for improving access to specialist care. Participants supported CCTH as a good principle for paediatric outpatient services; however the challenges of setting up and maintaining community clinics meant they questioned how far it could be achieved in practice. Conclusions: The place of service delivery is both an issue of physical location and professional identity. Policy initiatives which ignore assumptions about place, power and identity are likely to meet with limited success.

Applied pharmaceutical practice

Applied Pharmaceutical Practice is an invaluable resource and will guide the student pharmacist and pharmacy technician through the main stages involved in pharmaceutical dispensing. As a core reference text, it is ideal as a companion to the compulsory dispensing courses found in all undergraduate MPharm programmes and the equivalent technical training courses. Contents include: •medicines classification and standard operating procedures •NHS supply in the community and within hospitals •non-NHS supply •controlled drugs •emergency supply •patient counselling and communication •poisons and spirits This practical textbook contains useful exercises with an answers section and numerous examples and is written by authors with extensive experience within the field. This is a comprehensive guide through the main stages of pharmaceutical dispensing.The textbook is designed to guide student pharmacists or pharmacy technicians through the main stages involved in pharmaceutical dispensing. It provides students with a core reference text to accompany the compulsory dispensing course found in all pharmacy undergraduate programmes, highlighting and explaining all key concepts behind the processes involved in pharmaceutical dispensing.

An investigation into inductive parameter learning in complex hierarchical knowledge structures representing clinical expertise

This dissertation investigates the very important and current problem of modelling human expertise. This is an apparent issue in any computer system emulating human decision making. It is prominent in Clinical Decision Support Systems (CDSS) due to the complexity of the induction process and the vast number of parameters in most cases. Other issues such as human error and missing or incomplete data present further challenges. In this thesis, the Galatean Risk Screening Tool (GRiST) is used as an example of modelling clinical expertise and parameter elicitation. The tool is a mental health clinical record management system with a top layer of decision support capabilities. It is currently being deployed by several NHS mental health trusts across the UK. The aim of the research is to investigate the problem of parameter elicitation by inducing them from real clinical data rather than from the human experts who provided the decision model. The induced parameters provide an insight into both the data relationships and how experts make decisions themselves. The outcomes help further understand human decision making and, in particular, help GRiST provide more accurate emulations of risk judgements. Although the algorithms and methods presented in this dissertation are applied to GRiST, they can be adopted for other human knowledge engineering domains.

Medicines management strategies to improve antibiotic prescribing

A systematic review was conducted to explicitly identify interventions that alone, or in combination, were effective in improving antibiotic prescribing. The citation search strategy used in the present review provided a database of 365077 studies, of which only twenty-five were included in the final review (“review studies”). Analysis of the interventions used within the review studies indicated that a combination of “guidelines” and “pharmacy” interventions have the greatest potential to improve antibiotic prescribing. Two types of qualitative research were conducted, semi-structured interviews and the collection of naturally occurring data. Semi-structured interviews were conducted in order to determine NHS managers? perceptions of current policies used to improve antibiotic prescribing within selected Primary Care Trusts and highlighted the importance of pharmacy intervention, formularies or guidelines and improved prescribing analysis (IT based intervention) on improving antibiotic prescribing. This was supported by the collection of naturally occurring data, which was used to provide further insight into interventions used to improve antibiotic prescribing. The Specialist Antibiotic Pharmacist (HD) produced and implemented an innovative electronic antibiotic prescribing analysis tool (the Antibiotic Database) to analyse and improve antibiotic prescribing in a consistent manner. The key advantage of the Antibiotic Database was the time and money saved on producing visual electronic outputs containing an inaccurate outcome measure or time period for analysis. The results concluded that an IT based intervention, such as the Antibiotic Database should be used, in addition to the use of antibiotic guidelines and pharmacy intervention, within all sectors of the NHS in order to improve antibiotic prescribing and its analysis.

Do stressful times call for team-based working? A study of psychiatric nurses in UK mental healthcase

Background: Team-based working is now an inherent part of effective health care delivery. Previous research has identified that team working is associated with positive mental health and well-being outcomes for individuals operating in an effective team environment. This is a particularly important topic in the health services context, although little empirical attention has been paid to mental-health services. Psychiatric nurses work on a day-to-day basis with a particularly stressful and demanding client group in an environment which is characterised by high demands, uncertainty, and limited resources. This paper specifically focuses on psychiatric nurses working in National Health Service (NHS) and casts some light on the ways in which effective team-based working can help to alleviate a number of occupational stressors and strains. Method: A questionnaire method (2005 NHS Staff Survey) was employed to collect data from 6655 psychiatric nurses from 64 different NHS Trusts. The hypotheses were concerned with four overall measures from the survey; effective team working, occupational stress, work pressure and social support. Hypothesis 1 stated that effective team working will have a significant negative relationship with occupational stress and work pressure. Further, Hypothesis 2 stated that social support from supervisors and co-workers will moderate this relationship. Findings: Data was treated with a series of regression analyses. For Hypothesis 1, working in a real team did have main effects on work pressure and accounted for 1.6 per cent of the variance. Using the Nagelkerke R square value, working in a real team also had main effects on occupational stress an accounted for approximately 2.8 per cent of the variance. Further, the Exp (B) value of 0.662 suggests that the odds of suffering from occupational stress are cut by 33.8 per cent when a psychiatric nurse works in a real team. Results failed to provide support for Hypothesis 2. The analysis then went on to adopt a unique approach for assessing the extent of real team-based working, distinguishing between real teams, and a number of pseudo team typologies, as well as the absence of teamwork all together. As was hypothesised, results demonstrated that psychiatric nurses working in real teams (ones with clear objectives, where-by team members work closely with one another to achieve team objectives and meet regularly to discuss team effectiveness and how it can be improved) experienced the lowest levels of stress and work pressure of the sample. However, contrary to prediction, results indicated that psychiatric nurses working in any type of pseudo team actually experienced significantly higher levels of stress and work pressure than those who did not report as working in a team at all. Discussion: These findings have serious implications for NHS Mental Health Trusts, which may not be implementing, structuring and managing their nursing teams adequately. Indeed, results suggest that poorly-structured team work may actually facilitate stress and pressure in the workplace. Conversely, well-structured real teams serve to reduce stress and work pressure, which in turn not only enhances the working lives and well-being of psychiatric nurses, but also greatly improves the service that the NHS provides to its users.

Stressful times call for team-based measures:psychiatric nursing in the UK National Health Service

Background: Team-based working is now an inherent part of effective health care delivery. Previous research has identified that team working is associated with positive mental health and well-being outcomes for individuals operating in an effective team environment. This is a particularly important topic in the health services context, although little empirical attention has been paid to mental-health services. Psychiatric nurses work on a day-to-day basis with a particularly stressful and demanding client group in an environment which is characterised by high demands, uncertainty, and limited resources. This paper specifically focuses on psychiatric nurses working in National Health Service (NHS) and casts some light on the ways in which effective team-based working can help to alleviate a number of occupational stressors and strains. Method: A questionnaire method (2005 NHS Staff Survey) was employed to collect data from 6655 psychiatric nurses from 64 different NHS Trusts. The hypotheses were concerned with four overall measures from the survey; effective team working, occupational stress, work pressure and social support. Hypothesis 1 stated that effective team working will have a significant negative relationship with occupational stress and work pressure. Further, Hypothesis 2 stated that social support from supervisors and co-workers will moderate this relationship. Findings: Data was treated with a series of regression analyses. For Hypothesis 1, working in a real team did have main effects on work pressure and accounted for 1.6 per cent of the variance. Using the Nagelkerke R square value, working in a real team also had main effects on occupational stress an accounted for approximately 2.8 per cent of the variance. Further, the Exp (B) value of 0.662 suggests that the odds of suffering from occupational stress are cut by 33.8 per cent when a psychiatric nurse works in a real team. Results failed to provide support for Hypothesis 2. The analysis then went on to adopt a unique approach for assessing the extent of real team-based working, distinguishing between real teams, and a number of pseudo team typologies, as well as the absence of teamwork all together. As was hypothesised, results demonstrated that psychiatric nurses working in real teams (ones with clear objectives, where-by team members work closely with one another to achieve team objectives and meet regularly to discuss team effectiveness and how it can be improved) experienced the lowest levels of stress and work pressure of the sample. However, contrary to prediction, results indicated that psychiatric nurses working in any type of pseudo team actually experienced significantly higher levels of stress and work pressure than those who did not report as working in a team at all. Discussion: These findings have serious implications for NHS Mental Health Trusts, which may not be implementing, structuring and managing their nursing teams adequately. Indeed, results suggest that poorly-structured team work may actually facilitate stress and pressure in the workplace. Conversely, well-structured real teams serve to reduce stress and work pressure, which in turn not only enhances the working lives and well-being of psychiatric nurses, but also greatly improves the service that the NHS provides to its users.

The association between presenteeism and engagement of National Health Service staff

Objective: Although several studies have demonstrated a relationship between staff engagement and health and wellbeing, none has analysed the association with presenteeism in the National Health Service (NHS) context. Our aim is to determine whether there is a relationship between presenteeism and staff engagement. Methods: A hierarchical logistic multilevel modelling of cross-sectional data from the NHS staff survey (2009) was conducted. We controlled for a range of demographic and socioeconomic background variables, including ethnic group, gender, age and occupational group. The sample was 156,951 respondents across all 390 English NHS trusts, each providing a random sample of employees. Engagement was measured using three facets: motivation, advocacy and involvement, which were also used in a composite score. Results: Therewas a low-to-moderate negative correlation between presenteeismand staff engagement: odds ratio 0.42 (95% confidence interval [CI] 0.42-0.43) for overall staff engagement and 0.53 (95% CI 0.52-0.54) for staff advocacy of the trust; 0.53 (95% CI 0.52-0.54) for motivation and 0.50 (95% CI 0.49-0.51) for involvement. Conclusions: Putting pressure on health-care staff to come to work when unwell is associated with poorer staff engagement with their jobs. © The Royal Society of Medicine Press Ltd 2011.

RAPD for the typing of coagulase-negative staphylococci implicated in catheter-related bloodstream infection

Objectives: A rapid random amplification of polymorphic DNA (RAPD) technique was developed to distinguish between strains of coagulase-negative staphylococci (CoNS) involved in central venous catheter (CVC)-related bloodstream infection. Its performance was compared with that of pulsed-field gel electrophoresis (PFGE). Methods: Patients at the University Hospital Birmingham NHS Foundation Trust, U.K. who underwent stem cell transplantation and were diagnosed with CVC-related bloodstream infection due to CoNS whilst on the bone marrow transplant unit were studied. Isolates of CoNS were genotyped by PFGE and RAPD, the latter employing a single primer and a simple DNA extraction method. Results: Both RAPD and PFGE were highly discriminatory (Simpson's diversity index, 0.96 and 0.99, respectively). Within the 49 isolates obtained from blood cultures of 33 patients, 20 distinct strains were identified by PFGE and 25 by RAPD. Of the 25 strains identified by RAPD, nine clusters of CoNS contained isolates from multiple patients, suggesting limited nosocomial spread. However, there was no significant association between time of inpatient stay and infection due to any particular strain. Conclusion: The RAPD technique presented allows CoNS strains to be genotyped with high discrimination within 4 h, facilitating real-time epidemiological investigations. In this study, no single strain of CoNS was associated with a significant number of CVC-related bloodstream infections. © 2005 Published by Elsevier Ltd on behalf of the British Infection Society.