Medicine (St Vincent's) - Theses

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    The natural history of inflammatory bowel disease in an Australian community cohort: investigating the aetiology, clinical course, predictors of severe disease and health cost
    Niewiadomski, Olga ( 2015)
    Inflammatory Bowel Disease (IBD), including Crohn’s Disease (CD), Ulcerative colitis (UC) and IBD undifferentiated (IBDU), are chronic disorders of the gastrointestinal tract that exert a major impact on an individual’s quality of life and result in very high usage of health care resources. The aetiology of IBD remains unknown. Clinical course can vary from mild to severe and debilitating, and it remains unclear at diagnosis what disease progression will be. Identifying early clinical prognostic factors that predict a severe course is important, thereby enabling early medical therapy to minimize complications of disease. In recent years there has been greater emphasis on intensive therapy and disease monitoring. The greatest impact has been the introduction of biological therapy. However, it remains unclear if these advances are translating into better disease outcomes in the community and at what cost. A population based inception cohort study of patients with IBD was set up in Barwon, Victoria. The aims of the study were to validate the previously reported high incidence, to identify environmental exposures that are associated with disease aetiology, to assess the early course of disease as measured by objective markers such as surgery and hospitalization rates, to identify early clinical prognostic factors associated with severe disease and to determine the health care cost early in the course of IBD. Incident cases from 2007/2008 and 2010-2013 in a well-defined geographical area were prospectively identified through a multifaceted approach to ensure complete capture. Cases were subsequently enrolled into the IBD registry that was used as a basis to collect outcome data on the disease progression, environmental exposures and health care cost. A number of environmental exposures were found to be associated with increased risk of CD included smoking, frequent fast food intake and childhood events such as tonsillectomy and chicken pox infection. In UC, the risk factors included smoking, childhood chicken pox infection as well as frequent fast food. In UC, high caffeine intake was protective (a novel finding), while frequent fruit intake and pets as a child reduced the risk of UC. Objective clinical outcomes were measured for a median of 18 months from diagnosis (range 12-60 months) for 252 patients comprising 146 CD, 96 with Ulcerative colitis UC and 10 IBDU. Immunomodulators (IM) were prescribed in 57% of CD patients, and 19% with UC; biological therapy in 13% of CD patients. A third of all CD patients were hospitalised, the majority (77%) in the first 12 months. Risk factors for hospitalisation included penetrating, perianal and ileocolonic disease. A quarter of UC patients were hospitalized, most within the first 12 months. Resective surgery rates were 13% at 1 year in CD, and 26% at 5 years. Risk factors at diagnosis included penetrating, stricturing and ileal disease. Colectomy rates in UC were 2% and 13% at 1 and 5 years. High CRP at diagnosis was associated with colectomy. Health cost analysis in the first year of disease showed that per patient cost was higher in CD than UC; and that there has been a shift from inpatient to outpatient resources driving the majority of health cost in IBD compared to older studies. This was primarily due to the expense from medications. This first Australian population based study of an inception cohort confirms a high incidence of IBD in Barwon, Victoria that has remained stable over 6 years. A number of environmental risk factors associated with an increased risk of IBD were identified, as well as protective factors, of which high caffeine intake is a novel finding. Disease progress in this cohort was optimistic, compared to historical cohorts, with low rates of intestinal surgery. This was associated with high rates of IM and biological therapy. Early clinical predictors of severe disease were identified that can be used in clinical practice to tailor therapy. Health cost analysis in the first year shows a shift from inpatient to outpatient resources, with medications and investigations contributing the most.
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    Inflammatory bowel disease in the East and West: clinical, serological and microbiological studies
    Prideaux, Lani ( 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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    The evaluation of endoscopic technologies in the investigation and management of colonic neoplasia and obscure gastrointestinal bleeding
    EFTHYMIOU, MARIOS ( 2010)
    The aim of this work is to evaluate the use of endoscopic technology in colorectal neoplasia and obscure gastrointestinal bleeding. The focus is on the specific evaluation of cold forceps polypectomy, balloon enteroscopy, narrow band imaging and capsule endoscopy. The accuracy of cold forceps polypectomy for diminutive polyps (≤5mm) is assessed in a prospective study using a novel protocol. Patients referred for colonoscopy with one or more diminutive polyps, underwent cold forceps polypectomy followed by endoscopic mucosal resection of the polypectomy site with a 2-3mm resection margin. The two specimens were collected in separate pathology jars and assessed by a pathologist blinded to the study protocol. Comparison between the two specimens allowed for unequivocal assessment of resection efficacy. Fifty-two patients were enrolled and fifty-four polyps were resected. The complete resection rate with cold forceps polypectomy was 39%. Histology was predictive of resection efficacy, with the resection rate for adenomas at 62% compared to 24% for hyperplastic polyps, P=0.008. Polyp size and the number of bites of the forceps were not predictive of resection. A pilot study is then presented, assessing the feasibility of a protocol comparing narrow band imaging and chromoendoscopy, for dysplasia surveillance in patients with chronic colitis. The secondary aim of the study was to assess the accuracy of the Kudo classification (using narrow band imaging) in predicting the neoplastic potential of detected lesions. Twenty-two patients were enrolled in the study. The colon was divided into segments, using the flexures. Each segment was independently examined using narrow band imaging followed by examination with chromoendoscopy. Seven dysplastic lesions were detected in four patients. Both narrow band imaging and chromoendoscopy detected six of the seven dysplastic lesions. Narrow band imaging failed to diagnose one dysplastic lesion detected by chromoendoscopy. Both narrow band imaging and chromoendoscopy detected far more benign lesions than neoplastic. The sensitivity and specificity of the Kudo classification for neoplasia, (using narrow band imaging) was 60% and 79% respectively with a negative predictive value of 95%. Attention is then turned to capsule endoscopy, in a prospective assessment of the accuracy of faecal occult blood tests (FOBT) as a screening test pre-capsule endoscopy in obscure gastrointestinal bleeding. Patients referred for capsule endoscopy underwent two FOBTs within a fortnight preceding capsule endoscopy. The results of the FOBTs were correlated with clinically significant findings on capsule endoscopy. The primary aim of the study was to calculate the predictive value of FOBT in this setting. Fifty-six patients were enrolled. Fifty four percent had occult obscure gastrointestinal bleeding and the remainder overt obscure gastrointestinal bleeding. The overall yield of capsule endoscopy for clinically significant findings was 41%. The combination of immunochemical and guaiac FOBT had only modest sensitivity (63%), specificity (59%), negative predictive value (68%) and positive predictive value (54%). The last project presented in this thesis, is a randomised controlled study comparing single balloon enteroscopy (SBE) and double balloon enteroscopy (DBE) for the investigation and treatment of small bowel conditions. Patients referred for balloon enteroscopy were randomized in 1:1 allocation to single balloon enteroscopy or double balloon enteroscopy. Ninety-nine patients were enrolled and in total, 110 procedures were undertaken, 46 with SBE and 64 with DBE. The primary endpoint was diagnostic yield. Secondary endpoints were therapeutic yield, depth of insertion and procedural characteristics. The diagnostic yield of single and double balloon enteroscopy for small bowel findings was similar at 46% and 41% respectively, P=0.60. Therapeutic interventions were undertaken in 28% of those with SBE and 23% of those with DBE, P=0.57. The depth of insertion was longer for antegrade double balloon enteroscopy, however this was not statistically significant (200cm for SBE and 250cm for DBE, P=0.13). Insertion depth for retrograde procedures was 70cm median for SBE and 85cm for DBE, P=0.86. Despite shorter endoscope setup times with single balloon enteroscopy (3min vs. 11min, P<0.005), total procedure times were similar at median 90 minutes for SBE and 85 minutes for DBE, P=0.84. Cost identification analysis confirmed that the initial set up costs for SBE were considerably lower than those for DBE for hospitals with compatible Olympus equipment, however the overall procedure costs over time were similar. Each of these studies has addressed unique questions involving the use of endoscopic technology in the areas of colorectal neoplasia as well as obscure bleeding, which is a common presentation of small bowel neoplasia.
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    Epidemiology, natural history and impact of inflammatory bowel disease in Australia
    Wilson, Jarrad Leigh ( 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.