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INTRODUCTION: Drug-induced glucose dysregulation and insulin resistance have been associated with weight gain and potential induction and/or exacerbation of diabetes mellitus in the clinic suggesting they may be safety biomarkers when developing antipsychotics. Glucose and insulin have also been suggested as potential efficacy biomarkers for some oncology compounds. The objective of this study was to qualify a medium throughput rat in vivo acute Intravenous Glucose Tolerance Test (IVGTT) for predicting compounds that will induce altered blood glucose and/or insulin levels. METHODS: Acute and sub-chronic studies were performed to qualify an acute IVGTT model. Double cannulated male rats (Han-Wistar and Sprague-Dawley) were administered vehicle, olanzapine, aripiprazole or other compounds at t=-44min for acute studies and at time=-44min on the last day of dosing for sub-chronic studies, treated with dextrose (time=0min; i.v.) and blood collected using an automated Culex® system for glucose and insulin analysis (time=-45, -1, 2, 10, 15, 30, 45, 60, 75, 90, 120, 150 and 180min). RESULTS: Olanzapine significantly increased glucose and insulin area under the curve (AUC) values while aripiprazole AUC values were similar to control, in both acute and sub-chronic studies. All atypical antipsychotics evaluated were consistent with literature references of clinical weight gain. As efficacy biomarkers, insulin AUC but not glucose AUC values were increased with a compound known to have insulin growth factor-1 (IGF-1) activity, compared to control treatment. DISCUSSION: These studies qualified the medium throughput acute IVGTT model to more quickly screen compounds for 1) safety - the potential to elicit glucose dysregulation and/or insulin resistance and 2) efficacy - as a surrogate for compounds affecting the glucose and/or insulin regulatory pathways. These data demonstrate that the same in vivo rat model and assays can be used to predict both clinical safety and efficacy of compounds.

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Centrally acting dopamine agonists (e.g. bromocriptine) and dopamine transport inhibitors (e.g. GBR12909) are known to inhibit oestradiol-induced prolactin release. The capacity of peripherally restricted compounds to do likewise, however, is unknown. Here, the effects of the peripherally restricted dopamine receptor agonist carmoxirole on oestradiol-induced prolactin release were investigated. Dual-cannulated ovariectomized rats were used, so that a robust, reproducible response to exogenous oestrogen could be induced and sequential blood samples were taken with minimal stress. Carmoxirole (15 mg/kg) inhibited oestradiol-induced prolactin release, similar to bromocriptine and GBR12909. However, carmoxirole also induced a rapid, transient, oestradiol-independent release of prolactin. These data show that peripherally restricted dopamine receptor agonists are sufficient to inhibit oestradiol-induced prolactin release. Like centrally acting compounds, they may therefore be expected to affect the incidence of prolactin-dependent tumours in rat carcinogenesis studies without inducing central-mediated side effects.

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AIM: To gain some insight into the needs of community matrons from both the practitioners' and managers' perspectives. METHOD: Focus groups with community matrons in different PCTs. RESULTS: The focus groups identified that skills in physical assessment and prescribing were taken as prerequisites or essential to the role, and that the educational priorities were viewed as clinical education relating to the management of many long-term conditions linked to major causes of unplanned admissions. The preferred format for education appears to be work-based learning delivered by clinicians. CONCLUSION: PCTs need to ensure that community matrons have their learning needs assessed and to put in place systems of work-based learning that allow for appropriate development. Although community matrons themselves may not initially see the value of non-clinical education, this will be vital to the long-term success of their role.

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AIMS: This paper reports a study to elicit background data from recently qualified nurse prescribers and explore aspects of their work. BACKGROUND: Nurse prescribing has been introduced quite recently in the United Kingdom. Although a certain amount of information is available about the characteristics of nurse prescribers, relatively little is known about their professional backgrounds, their reasons for choosing to become nurse prescribers and their perceptions of their emerging role. More information is needed to inform the selection, education and support of nurse prescribers. METHOD: All nurses who undertook a nurse prescribing course in one university in the West Midlands during 2003-2004 were invited to participate in the study. A 40-item questionnaire was used to gather data on demographics, expectations of nurse prescribing, personal and professional development and perceived education needs. FINDINGS: Respondents considered that, despite initial problems, the nurse prescribing initiative would ultimately prove to be a cornerstone of improved service delivery for service users. The majority of nurses were already heavily involved in prescribing 'by proxy' and the course merely formalized what they were currently doing. Potentially, prescribing could advance the professional development of nurses, improve communication between professionals and patients, and make the experience of patients more beneficial. However, some concerns were expressed about how supportive the current climate in health care could be, given the multiple demands on time and energy required by so many other innovations. CONCLUSIONS: Respondents appeared balanced in their perceptions of this innovation and what it could realistically achieve. They were not indifferent to the many short and long-term problems that need to be resolved before it can be claimed to have become embedded in practice. The success of non-medical prescribing may depend on organizational support, coupled with a robust continuing professional development strategy for all nurse prescribers.

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