Medicine (Northwest Academic Centre) - Theses
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ItemSun exposure and type 2 diabetes mellitus: Can sun exposure lower type 2 diabetes risk?( 2015)Background: Lower serum 25-hydroxyvitamin D (25OHD) levels have been consistently associated with increased type 2 diabetes mellitus (T2DM) prevalence and incidence in systematic reviews and meta-analyses of observational studies, however this association has not consistently been replicated in vitamin D supplementation trials. This disparity may be due to a number of different factors: lack of power in the trials due to small sample size, insufficient duration of dosing, baseline vitamin D or glycaemic status differing between studies, low supplementation compliance or insufficient vitamin D dose. Alternatively, lower 25OHD levels may be a product, rather than a cause of ill-health, or they may share pathology earlier in life or in disease progression so that supplementing with vitamin D in adulthood has no effect on disease outcome. This body of work presents another explanation: given that sun exposure is the most influential contributor to serum 25OHD levels, observational studies may be reporting an effect of sun exposure, rather than vitamin D, on T2DM. Therefore vitamin D supplementation trials may be failing to capture any additional benefits of sun exposure through non-vitamin D pathways. The aim of this body of work was to investigate the possible association between sun exposure and T2DM endpoints reported in scientific literature as well as in an original analysis. A major objective of the original analysis was to determine whether or not any association found between sun exposure and T2DM incidence was through non-vitamin D pathways. Methods: Following a literature review, a systematic review of observational studies reporting on associations between sun exposure variables and T2DM-related endpoints was conducted. The potential of an association between sun exposure- measured using ambient ultraviolet radiation (UVR), and five-year cumulative incidence of T2DM was explored using a prospective, national diabetes cohort (AusDiab). A causal mediation analysis was undertaken to explore whether or not there were effects of ambient UVR on cumulative T2DM incidence, via non-vitamin D pathways. Results: The systematic review revealed that high-level evidence for an association between sun exposure and T2DM-related outcomes was lacking. There was moderate-level evidence for greater sun exposure reducing T2DM incidence. The opposite was found in the original analysis using the AusDiab cohort: ambient UVR was associated with increased T2DM incidence (OR=1.17, 95% CI: 1.01-1.36, p=0.04). This association was independent of an effect of age, sex, body mass index, physical activity, ethnicity, smoking status and serum 25OHD levels, but was likely to be confounded by area-level determinants of health due to the nature of the exposure variable. The major limitations of this work were that the sun exposure measures were suboptimal. Time-of-year measures were the most common sun exposure variables contained in the systematic review, and ambient UVR at the site of participant recruitment was the proxy for sun exposure in the original analysis. Conclusion: There is likely to be a complex relationship between sun exposure and T2DM. The direction of the association between sun exposure and T2DM incidence, as well as delineation of the mechanistic pathways through which this association may exist, are yet to be confirmed. Future studies are encouraged to use person-level sun exposure measurements, and findings from such studies may influence sun protection policy.
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ItemTo validate a preoperative risk stratification model developed at Barwon Health for mortality and major morbidity in major colorectal surgery( 2013)Colorectal surgery is associated with significant mortality, with reported rates of 1% to 2% in elective surgery and 5% to 10% in emergency surgery. The majority of the colorectal workload is attributed to colorectal cancer and according to the National Health and Medical Research Council guidelines, being the second leading cause of cancer related death in Australia. Each year at least 12,600 new cases are diagnosed with an estimated annual increase of 0.3%. Therefore in the past decade, there has been much initiative to create a prognostic model that could predict patient’s mortality and morbidity before colorectal surgery. Currently there are three known models; Association Française de Chirurgie index score, Barwon Health 2009 model and the American College of Surgeons National Surgery Quality Improvement Program colorectal risk calculator. These prognostic models were created for the purpose of informed consent, to discuss a patient’s risk for surgery and to identify high risk patients for early medical, high dependency unit or intensive care unit admission. Although all three models have reported reliable results in predicting patient mortality, these models have never been validated with another independent dataset in Australia. The purpose of validating the prognostic models was to ensure they were reliable at predicting patient’s mortality in other institutions. However only the Association Française de Chirurgie score and the Barwon Health 2009 model were validated and neither predicted mortality accurately. The American College of Surgeons National Surgery Quality Improvement Program colorectal risk calculator was not validated as it was password protected and available only to the participating hospitals. As there were no reliable models for colorectal surgery, the Colorectal preOperative Surgical Score was created. The Colorectal preOperative Surgical Score is a 4-variable pre-operative model that predicts a patient’s mortality risk following emergency or elective colorectal surgery. This model was successfully validated at two independent institutions. We hope to use this model to guide pre-operative counselling with individual patients and as a simple tool for risk stratification of outcomes as reported in colorectal surgical audit.