Does tamoxifen have a therapeutic role outside of breast cancer? A systematic review of the evidence.

INTRODUCTION: Tamoxifen is a widely used hormonal based therapy for breast cancer in the adjuvant and metastatic setting, prolonging overall and recurrence-free survival. There has been increasing interest in the potential for novel "off-target" effects of tamoxifen and its metabolite N-desmethyltamoxifen across a number of cancer types. We aim to review the current literature regarding the potential use of tamoxifen in other primary malignancies. METHOD: A qualitative systematic review was performed according to the PRISMA guidelines using pre-set search criteria across the PubMed, Cochrane and Scopus databases from 1985 to 2019. Additional results were generated from included papers references. RESULTS: A total of 324 papers were identified, of which 47 were included; a further 29 articles were obtained from additional referencing to give a total of 76 articles. Clinical trials have demonstrated benefits with the use of tamoxifen in isolation and combination, specifically in patients with advanced non-resectable malignancy, however results are not consistent across the literature. In vivo data consistently suggests that off target effects of tamoxifen are mediated through the ceramide pathway or through inhibition of protein kinase C (PKC). CONCLUSIONS: With increased focus upon the potential of repurposing drugs, tamoxifen may be a candidate for repurposing in the wider cancer setting. There is evidence to suggest that the ceramide or PKC pathway could act as a therapeutic target for tamoxifen or alternative chemotherapeutics and merits further investigation.

Implementation of a new tool to improve the efficacy and safety of surgical handovers.

AIMS: Compliance with European working time regulations in surgical practice has resulted in an increase in the number of clinicians caring for individual patients and subsequently an increase in the frequency of handovers. In 2007, the Royal College of Surgeons of England produced guidelines on the minimum data-set for 'safe handover'. This audit examined compliance with these guidelines before and after adopting a more detailed electronic handover 'template' with the intention of improving handover quality and patient safety. METHODS: Pre-existing surgical 'take' electronic handover sheets were reviewed daily for two weeks to assess compliance with published guidance. A new proforma was introduced, training delivered and compliance re-audited. χ2 analysis was performed to determine statistical significance. RESULTS: The handovers of 118 patients were audited before, and 114 after, the implementation of the new proforma. Name and responsible consultant were recorded in all cases. Age (52% vs. 85%, p=<0.01), location (77% vs. 95%, p=<0.01), admission date (0% vs. 39%, p=<0.01), medical history (82% vs. 94%, p=0.01), diagnosis (55% vs. 93%, p=<0.01) and management plan (81% vs. 97%, p=<0.01) showed a statistically significant improvement with the new proforma. Presenting complaint (93% vs. 98%) and investigation (90% vs. 90%) data remained good. Review frequency (5%vs.11%) and outstanding tasks (21% vs. 27%) were poorly documented. CONCLUSIONS: Significant improvement was seen in the completeness of information handed-over following the introduction of the new proforma with likely positive implications for patient safety and standard of care. Opportunity for improvement still remains however, and more specific focussed tuition for trainees is required.

Grazing and vigilance by Soay sheep on Lundy island: influence of group size, terrain and the distribution of vegetation.

Animals allocate the time spent on different behaviours according to nutritional requirements, the distribution of food and the risk of predation. When the perceived predation risk is high, animals primarily behave in ways to increase their safety such as regularly scanning their surroundings, forming large groups and feeding in habitats with cover or high visibility. This study investigated which factors Soay sheep (Ovis aries) are most sensitive to in allocating time to different behaviours when the risk of predation is negligible. Continuous focal sampling was used to record the behaviour of the free-ranging Soay sheep on Lundy Island and measures of vegetation, group size and terrain were also recorded. Stepwise multiple regression produced a model of grazing with terrain and range of grass coverage as predictors and a model of vigilance with terrain as a predictor. Sheep grazed for longer on the slopes and as the range of grass cover decreased. They were more vigilant on the slopes. The results support the view that the group size effect largely depends on anti-predatory vigilance and suggest that time-budgets are more sensitive to other factors in the absence of predation.