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ItemADRENERGIC FACTORS REGULATING CELL-DIVISION IN THE COLONIC CRYPT EPITHELIUM DURING CARCINOGENESIS AND IN COLONIC ADENOMA AND ADENOCARCINOMAKENNEDY, MFG ; TUTTON, PJM ; BARKLA, DH (CHURCHILL LIVINGSTONE, 1985-01-01)Evidence exists implicating adrenergic factors in the control of intestinal epithelial cell proliferation in both normal and diseased states. In this report, attention is focussed on changes in the amine requirements of proliferating cells during the chemical induction of tumours in the colon of mouse. Cell proliferation rates were measured stathmokinetically. Tumours were induced by s.c. injection of dimethylhydrazine (DMH). Results with a series of adrenoceptor agonists and antagonists suggest that there is an alpha 2-adrenoceptor mediated excitatory effect in normal colon but an alpha 2 adrenoceptor mediated inhibitory effect in adenoma and carcinoma. Alpha 1 adrenoceptors, on the other hand, have an inhibitory effect in normal crypts and in adenomas, and an excitatory effect in carcinomas. Beta adrenoceptors have an inhibitory effect in the normal and DMH-treated crypt, and in adenomas, but not in carcinomas. In the crypt epithelium of DMH-treated mice, two regions on cell proliferation, with differing regulatory factors, could be identified. In the upper region of the carcinogen-exposed crypt is a zone where cell proliferation is stimulated by an alpha 2 adrenergic mechanism, thus resembling the basal region of the normal crypt. By contrast, in the basal region of these crypts, cell proliferation is stimulated by an alpha 1 mechanism, thus resembling a malignant tumour.
ItemPeer-to-Peer, Interactive GP Education can Reduce Barriers to Best Practice in Diabetes ManagementDeed, G ; Kilov, G ; Phillips, P ; Sharma, A ; Leow, S ; Arthur, I ; Barlow, J ; Kennedy, M (SPRINGER HEIDELBERG, 2016-03-01)INTRODUCTION: Perceived difficulties in initiating insulin in patients with type 2 diabetes (T2D) may prevent many general practitioners (GPs) from using insulin even when recommended in guidelines. This paper describes a Royal Australian College of General Practitioners accredited education program on starting insulin in T2D, and its impact on GPs' attitudes and behavior. METHODS: A faculty comprising GPs with diabetes expertise, Credentialed Diabetes Nurse Educators, and endocrinologist developed and implemented the education program. The program content was highly procedure focussed, emphasizing simple, best-practice processes for starting insulin therapy and focussing on multidisciplinary models of care. The highly interactive format of the workshops included peer-to-peer learning, in which education was led by diabetes-experienced GP educators, as well as case study-based approaches and small group discussions. GP attendees were asked to rate their individual confidence and attitudes at the beginning and end of the meeting. In addition, participants (n = 220) from two workshops in 2013 were sent a survey 3 months after the meeting to gauge the longer-term impact on their clinical practice. RESULTS: Since 2008, more than 2500 GPs have attended the workshops, and report substantial improvements in confidence; after attending, more GPs were willing to start insulin within their practice. Evaluations at 3 months post-meeting indicate that the increased confidence was associated with behavioral changes in the subgroup evaluated at this time (n = 48). Success of this program was attributed to peer-to-peer education, multidisciplinary input, easily implemented best practice procedures and checklists for starting insulin, and constant adjustment of meeting process and content based on feedback and guideline changes. CONCLUSION: A peer-to-peer, interactive GP education program reduced GPs' perceptions of the difficulties of starting insulin in T2D and achieved changes in attendees' clinical practice. This education program offers an effective approach to overcome the therapeutic inertia that is too common in diabetes management.
ItemGP-OSMOTIC trial protocol: an individually randomised controlled trial to determine the effect of retrospective continuous glucose monitoring (r-CGM) on HbA1c in adults with type 2 diabetes in general practiceFurler, J ; O'Neal, DN ; Speight, J ; Blackberry, I ; Manski-Nankervis, J-A ; Thuraisingam, S ; de La Rue, K ; Ginnivan, L ; Browne, JL ; Holmes-Truscott, E ; Khunti, K ; Dalziel, K ; Chiang, J ; Audehm, R ; Kennedy, M ; Clark, M ; Jenkins, AJ ; Liew, D ; Clarke, P ; Best, J (BMJ PUBLISHING GROUP, 2018-09-01)INTRODUCTION: Optimal glycaemia can reduce type 2 diabetes (T2D) complications. Observing retrospective continuous glucose monitoring (r-CGM) patterns may prompt therapeutic changes but evidence for r-CGM use in T2D is limited. We describe the protocol for a randomised controlled trial (RCT) examining intermittent r-CGM use (up to 14 days every three months) in T2D in general practice (GP). METHODS AND ANALYSIS: General Practice Optimising Structured MOnitoring To achieve Improved Clinical Outcomes is a two-arm RCT asking 'does intermittent r-CGM in adults with T2D in primary care improve HbA1c?' PRIMARY OUTCOME: Absolute difference in mean HbA1c at 12 months follow-up between intervention and control arms. SECONDARY OUTCOMES: (a) r-CGM per cent time in target (4-10 mmol/L) range, at baseline and 12 months; (b) diabetes-specific distress (Problem Areas in Diabetes). ELIGIBILITY: Aged 18-80 years, T2D for ≥1 year, a (past month) HbA1c>5.5 mmol/mol (0.5%) above their individualised target while prescribed at least two non-insulin hypoglycaemic therapies and/or insulin (therapy stable for the last four months). Our general glycaemic target is 53 mmol/mol (7%) (patients with a history of severe hypoglycaemia or a recorded diagnosis of hypoglycaemia unawareness will have a target of 64 mmol/mol (8%)).Our trial compares r-CGM use and usual care. The r-CGM report summarising daily glucose patterns will be reviewed by GP and patient and inform treatment decisions. Participants in both arms are provided with 1 hour education by a specialist diabetes nurse.The sample (n=150/arm) has 80% power to detect a mean HbA1c difference of 5.5 mmol/mol (0.5%) with an SD of 14.2 (1.3%) and alpha of 0.05 (allowing for 10% clinic and 20% patient attrition). ETHICS AND DISSEMINATION: University of Melbourne Human Ethics Sub-Committee (ID 1647151.1). Dissemination will be in peer-reviewed journals, conferences and a plain-language summary for participants. TRIAL REGISTRATION NUMBER: >ACTRN12616001372471; Pre-results.