Influences on general practitioner prescribing with particular reference to community pharmacy

Influences on general practitioner prescribing of drugs continue to be of interest and importance as cost containment becomes central to Government health policy. This thesis employs a plurality of research methods including quantitative and qualitative survey techniques for example, questionnaires, interviews and prescription analyses to investigate some of the factors which may influence GP prescribing such as information sources, hospital consultants and in particular the community pharmacist. When the use and influence of drug information sources by GPs was examined, the community pharmacist was given a relatively low rating as a source but a high rating, similar to that of the consultant, for helpfulness. Influences are needed to improve prescribing and reduce the incidence of iatrogenic disease for the benefit of the patient. The education and expertise of pharmacists and their familiarity with local prescribing habits places them in a unique position to meet the needs of local GPs. As 96.5% of the public always or nearly always take their prescriptions to the same pharmacy, patient medication records, now kept by 77.5% of pharmacies, provide a valuable check on the appropriateness and safety of patients' medication. The barriers to the pharmacist's greater involvement were shown to be suspicion by GPs of pharmacists' motivation, isolation of many community pharmacists, difficulties in leaving the pharmacy for domiciliary visits, residential home care and GP practice meetings. These barriers must be lowered if the pharmacist is to have a greater influence and involvement. It was concluded that changes are necessary in pharmaceutical education, staff training, organisation and remuneration. Some changes in the targeting of remuneration to the pharmaceutical care services provided and registration of patients with pharmacies would contribute greatly to these aims.

Medication -related adverse events in older people with dementia:causes and possible solutions

This submission for a PhD by previously published work is based upon six publications in peer reviewed journals, reflecting a 9-year research programme. My research has shown, in a coherent and original way, the difficulty in treating people with dementia with safe and effective medication whilst providing research-founded guidance to develop mechanisms to optimise medication choice and minimise iatrogenic events. A wide range of methods, including systematic reviews, meta-analysis, randomised controlled trials (RCTs), quantitative research and mixed methods were used to generate the data, which supported the exploration of three themes. The first theme, to understand the incidence and causes of medication errors in dementia services, identified that people with dementia may be more susceptible to medication-related iatrogenic disease partly due to inherent disease-related characteristics. One particular area of concern is the use of anti-psychotics to treat the Behavioural and Psychological Symptoms of Dementia (BPSD). The second and third themes, respectively, investigated a novel pharmacological and health services intervention to limit anti-psychotic usage. The second phase found that whilst the glutamate receptor blocker memantine showed some promise, further research was clearly required. The third phase found that anti-psychotic usage in dementia may be higher than official figures suggest and that medication review linking primary and secondary care can limit such usage. My work has been widely cited, reflecting a substantial contribution to the field, in terms of our understanding of the causes of, and possible solutions to limit, medication-related adverse events in people with dementia. More importantly, this work has already informed clinical practice, patients, carers and policy makers by its demonstrable impact on health policy. In particular my research has identified key lines of enquiry for future work and for the development of my own personal research programme to reduce the risk associated with medication in this vulnerable population.

Spatial correlations between the vacuolation, prion protein (PrPsc) deposits and the cerebral blood vessels in sporadic Creutzfeldt-Jakob disease

In the variant form of Creutzfeldt-Jakob disease (vCJD), 'florid' deposits of the protease resistant form of prion protein (PrP(sc)) were aggregated around the cerebral blood vessels suggesting the possibility that prions may spread into the brain via the cerebral microcirculation. The objective of the present study was to determine whether the pathology was spatially related to blood vessels in cases of sporadic CJD (sCJD), a disease without an iatrogenic etiology, and therefore, less likely to be caused by hematogenous spread. Hence, the spatial correlations between the vacuolation ('spongiform change'), PrP(sc) deposits, and the blood vessels were studied in immunolabelled sections of the cerebral cortex and cerebellum in eleven cases of the common M/M1 subtype of sCJD. Both the vacuolation and the PrP(sc) deposits were spatially correlated with the blood vessels; the PrP(sc) deposits being more focally distributed around the vessels than the vacuoles. The frequency of positive spatial correlations was similar in the different gyri of the cerebral cortex, in the upper and lower cortical laminae, and in the molecular layer of the cerebellum. It is hypothesized that the spatial correlation is attributable to factors associated with the blood vessels which promote the aggregation of PrP(sc) to form deposits rather than representing the hematogenous spread of the disease. The aggregated form of PrP(sc) then enhances cell death and may encourages the development of vacuolation in the vicinity of the blood vessels.