Medicine (St Vincent's) - Theses
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ItemInflammatory bowel disease in the East and West: clinical, serological and microbiological studies( 2013)The incidence of inflammatory bowel disease (IBD) in Australia is equal to the highest in the world, in contrast to the incidence in Asia which is low but rapidly increasing. The pathophysiology of IBD relates to the mucosal immune response to antigenicstimulation from the gut microbiota, on a background of genetic susceptibility. Immigrants from low to high incidence areas, have a high incidence of IBD, suggesting that exposure to new environmental factors is a key factor in the development of IBD. “Westernization” of lifestyle and industrialization in Asia likely also plays a role. Our gut microbiota is affected by our genes, our immune system, and environmental factors. Patients with IBD have altered gut microbiota. Little is known about the gut microbiota of IBD patients in the Asia, and in particular whether it is changing to Western patterns, especially after migration. Initially the clinical characteristics and management of IBD patients in Australia and Asia were compared. Then gut microbiota was assessed and compared, using state-of-the-art metagenomic techniques, within and between China and Australia (countries with different IBD incidence) both in the healthy, and IBD populations in subjects of Caucasian and Asian (Chinese) ethnicity. Serological antibodies to microbial antigens, and environmental factors were also assessed. Studying clinical characteristics of disease, the gut microbiota and serological antibodies to microbial antigens in populations with changing incidence offers great hope of identifying potentially important aetiological factors in IBD.
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ItemEpidemiology, natural history and impact of inflammatory bowel disease in Australia( 2010)The inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC), are chronic inflammatory disorders of the gastrointestinal tract. International studies have demonstrated a dramatic rise in the incidence of these conditions over the past several decades. There are no corresponding studies from Australia to determine the local incidence. CD has been shown to have a complicated disease course, with high requirements for surgery and progression to disability. Psychological morbidity is also common, with a negative impact on health related quality of life. International studies have also demonstrated high direct and indirect health economic costs associated with CD. Australian data in each of these areas is either limited or totally absent. The aim of this work was to address the deficiencies in each of these key areas. The first Australian population-based study of IBD incidence was conducted prospectively over a one-year period in the region of Barwon. This utilised an extensive capture-recapture methodology, with near complete case identification and rigorous verification of diagnosed cases. The IBD incidence rates observed are among the highest reported in the world literature. The natural history of CD was then assessed in a retrospective, inception cohort study over a five-year period from the time of diagnosis. There was the progressive development of a more complicated disease phenotype, with high requirements for surgery. The results from surgery were not durable, with 60 percent needing escalation of therapy within 5 years. 41 percent of the cohort met the definition of disabling disease, with the presence of perianal fistulae at diagnosis highlighted as a key risk factor. This was followed by two cross-sectional, questionnaire-based, cohort studies to assess psychological health and health related quality of life (HRQoL) in CD. The first study was conducted in patients from the Inflammatory Bowel Disease Clinic at St. Vincent’s Hospital, Melbourne. The second was in a cohort of patients from the same institution who had required the formation of an ileostomy for CD. Both studies revealed high rates of depression, anxiety and poor HRQoL. These negative factors were contributed to by increased disease activity, but the strongest predictive factor was found to be the use of a negative, maladaptive coping style. Some patients with a stoma have adapted well, but others found it to be a negative experience, with ongoing concerns regarding sexuality and body image. The health economic costs of CD were then established using prospective cost diaries. Both direct and indirect costs were high, in keeping with the complicated natural history of CD. These studies highlight that IBD is common in Australia, and that CD has a complicated natural history, with negative impacts on psychological health and HRQoL, and with high economic costs. There is a need for increased public awareness as well as ongoing research and funding to improve clinical care.