Effects of aromatase inhibitor therapy on adiposity and cardiometabolic health in postmenopausal women: a controlled cohort extension study.

Purpose: We previously demonstrated that 12 months of aromatase inhibitor (AI) treatment was not associated with a difference in body composition or other markers of cardiometabolic health when compared to controls. Here we report on the pre-planned extension of the study. The pre-specified primary hypothesis was that AI therapy for 24 months would lead to increased visceral adipose tissue (VAT) area when compared to controls. Methods: We completed a 12-month extension to our prospective 12-month cohort study of 52 women commencing AI treatment (median age 64.5 years) and 52 women with breast pathology not requiring endocrine therapy (63.5 years). Our primary outcome of interest was VAT area. Secondary and exploratory outcomes included other measures of body composition, hepatic steatosis, measures of atherosclerosis and vascular reactivity. Using mixed models and the addition of a fourth time point, we increased the number of study observations by 79 and were able to rigorously determine the treatment effect. Results: Among study completers (AI = 39, controls = 40), VAT area was comparable between groups over 24 months, the mean-adjusted difference was -1.54 cm2 (95% CI: -14.9; 11.9, P = 0.79). Both groups demonstrated parallel and continuous increases in VAT area over the observation period that did not diverge or change between groups. No statistically significant difference in our secondary and exploratory outcomes was observed between groups. Conclusions: While these findings provide reassurance that short-to-medium-term exposure to AI therapy is not associated with metabolically adverse changes when compared to controls, risk evolution should be less focussed on the AI-associated effect and more on the general development of cardiovascular risk over time.

Potential new approaches to modifying intestinal GLP-1 secretion in patients with type 2 diabetes mellitus: focus on bile acid sequestrants.

Type 2 diabetes mellitus is associated with a progressive decline in insulin-producing pancreatic ß-cells, an increase in hepatic glucose production, and a decrease in insulin sensitivity. The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) stimulate glucose-induced insulin secretion; however, in patients with type 2 diabetes, the incretin system is impaired by loss of the insulinotropic effects of GIP as well as a possible reduction in secretion of GLP-1. Agents that modify GLP-1 secretion may have a role in the management of type 2 diabetes. The currently available incretin-based therapies, GLP-1 receptor agonists (incretin mimetics) and dipeptidyl peptidase-4 (DPP-4) inhibitors (CD26 antigen inhibitors) [incretin enhancers], are safe and effective in the treatment of type 2 diabetes. However, they may be unable to halt the progression of type 2 diabetes, perhaps because they do not increase secretion of endogenous GLP-1. Therapies that directly target intestinal L cells to stimulate secretion of endogenous GLP-1 could possibly prove more effective than treatment with GLP-1 receptor agonists and DPP-4 inhibitors. Potential new approaches to modifying intestinal GLP-1 secretion in patients with type 2 diabetes include G-protein-coupled receptor (GPCR) agonists, α-glucosidase inhibitors, peroxisome proliferator-activated receptor (PPAR) agonists, metformin, bile acid mimetics and bile acid sequestrants. Both the GPCR agonist AR231453 and the novel bile acid mimetic INT-777 have been shown to stimulate GLP-1 release, leading to increased insulin secretion and improved glucose tolerance in mice. Similarly, a study in insulin-resistant rats demonstrated that the bile acid sequestrant colesevelam increased GLP-1 secretion and improved glucose levels and insulin resistance. In addition, the bile acid sequestrant colestimide (colestilan) has been shown to increase GLP-1 secretion and decrease glucose levels in patients with type 2 diabetes; these results suggest that the glucose-lowering effects of bile acid sequestrants may be partly due to their ability to increase endogenous GLP-1 levels. Evidence suggests that GPCR agonists, α-glucosidase inhibitors, PPAR agonists, metformin, bile acid mimetics and bile acid sequestrants may represent a new approach to management of type 2 diabetes via modification of endogenous GLP-1 secretion.

Potential New Approaches to Modifying Intestinal GLP-1 Secretion in Patients with Type 2 Diabetes Mellitus : Focus on Bile Acid Sequestrants.

Type 2 diabetes mellitus is associated with a progressive decline in insulinproducing pancreatic ß-cells, an increase in hepatic glucose production, and a decrease in insulin sensitivity. The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) stimulate glucose-induced insulin secretion; however, in patients with type 2 diabetes, the incretin system is impaired by loss of the insulinotropic effects of GIP as well as a possible reduction in secretion of GLP-1. Agents that modify GLP-1 secretion may have a role in the management of type 2 diabetes. The currently available incretin-based therapies, GLP-1 receptor agonists (incretin mimetics) and dipeptidyl peptidase-4 (DPP-4) inhibitors (CD26 antigen inhibitors) [incretin enhancers], are safe and effective in the treatment of type 2 diabetes. However, they may be unable to halt the progression of type 2 diabetes, perhaps because they do not increase secretion of endogenous GLP-1. Therapies that directly target intestinal L cells to stimulate secretion of endogenous GLP-1 could possibly prove more effective than treatment with GLP-1 receptor agonists and DPP-4 inhibitors. Potential new approaches to modifying intestinal GLP-1 secretion in patients with type 2 diabetes include G-protein-coupled receptor (GPCR) agonists, α-glucosidase inhibitors, peroxisome proliferator-activated receptor (PPAR) agonists, metformin, bile acid mimetics and bile acid sequestrants. Both the GPCR agonist AR231453 and the novel bile acid mimetic INT-777 have been shown to stimulate GLP-1 release, leading to increased insulin secretion and improved glucose tolerance in mice. Similarly, a study in insulin-resistant rats demonstrated that the bile acid sequestrant colesevelam increased GLP-1 secretion and improved glucose levels and insulin resistance. In addition, the bile acid sequestrant colestimide (colestilan) has been shown to increase GLP-1 secretion and decrease glucose levels in patients with type 2 diabetes; these results suggest that the glucose-lowering effects of bile acid sequestrants may be partly due to their ability to increase endogenous GLP-1 levels. Evidence suggests that GPCR agonists, α-glucosidase inhibitors, PPAR agonists, metformin, bile acid mimetics and bile acid sequestrants may represent a new approach to management of type 2 diabetes via modification of endogenous GLP-1 secretion.

A virtual surgery in general practice: evaluation of a novel undergraduate virtual patient learning package.

BACKGROUND: A suite of 10 online virtual patients developed using the IVIMEDS 'Riverside' authoring tool has been introduced into our undergraduate general practice clerkship. These cases provide a multimedia-rich experience to students. Their interactive nature promotes the development of clinical reasoning skills such as discriminating key clinical features, integrating information from a variety of sources and forming diagnoses and management plans. AIMS: To evaluate the usefulness and usability of a set of online virtual patients in an undergraduate general practice clerkship. METHOD: Online questionnaire completed by students after their general practice placement incorporating the System Usability Scale questionnaire. RESULTS: There was a 57% response rate. Ninety-five per cent of students agreed that the online package was a useful learning tool and ranked virtual patients third out of six learning modalities. Questions and answers and the use of images and videos were all rated highly by students as useful learning methods. The package was perceived to have a high level of usability among respondents. CONCLUSION: Feedback from students suggest that this implementation of virtual patients, set in primary care, is user friendly and rated as a valuable adjunct to their learning. The cost of production of such learning resources demands close attention to design.

Self care and end of life care in advanced cancer: literature review.

BACKGROUND: Self care is a key feature of health care policy in the UK. It has been suggested that self care by patients with cancer improves quality of life, symptom management, and patient satisfaction. However, little is known about self care and end of life care. OBJECTIVES: This review sets out to find out what is known about how people experiencing end of life care manage their illness themselves, in the advanced stages of their disease. METHODS: A systematic review was conducted; searching key databases; extracting relevant literature, using RefMan, NVIVO; grading, analysing, and appraising the literature. RESULTS: Eighteen articles were included in the review. Themes identified were; interventions for end of life care; self care behaviours used by patients; factors that prevent patients to self care. CONCLUSION: The nurses' role in supporting self care for people with advanced cancer is important. The review identifies various ways nurses can empower patients to self care related to oncology.

Perceptions of the use of a remote monitoring system in patients receiving palliative care at home.

In remote communities, where frequent face-to-face contact with health professionals may be difficult, the ongoing review and management of symptoms--a fundamental part of good palliative care--can be difficult to achieve. Telecare and other developments in information technology are increasingly being sought as a means of addressing shifting population demographics and rising demands on stretched health services, and may help in providing a system which allows patients to report their symptoms as they are happening. This may be one way of enhancing symptom management and improving quality of care at the end of life. A study testing the feasibility of using mobile phone-based technology (Advanced Symptom Management System in Palliative Care (ASyMSp)) to monitor and manage symptoms reported by patients being cared for at home in the advanced stages of their illness was carried out in two rural communities in the north of Scotland. The results of this study show that the system was usable and acceptable to patients and the health professionals who cared for them.

Pressure ulcer prevention in palliative care 1: results of a UK survey.

Pressure ulcer prevention is an important aspect of palliative care nursing. This article reports part 1 of the results of a postal questionnaire survey of all 206 palliative care inpatient units listed in the St Christopher's' information service hospice directory. The key areas surveyed were current pressure ulcer prevention policies in use in UK palliative care units and current practice in relation to pressure ulcer risk assessment. Issues arising from these results are also discussed: the key elements of a pressure ulcer policy and the role and timing of pressure ulcer risk assessment.