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Objectives Perturbations of the intestinal microbiota have been associated with mental health disorders, including major depressive disorder (MDD). Therefore, faecal microbiota transplantation (FMT) holds promise as a microbiota-modulating treatment for MDD. Yet, to date, there are no published controlled studies evaluating the use of FMT for MDD. This study aimed to address this gap by evaluating the feasibility, acceptability, and safety of FMT for MDD. Methods The study was an 8-week, double-blind, 2:1 parallel group, randomized controlled pilot trial ( n = 15) of enema-delivered FMT ( n = 10) compared with a placebo enema ( n = 5) in adults with moderate-to-severe MDD. Results Recruitment was completed within 2 months, with 0% attrition and 100% attendance at key study appointments. There were no major protocol deviations. The placebo and blinding strategies were considered successful; nurses and participants correctly guessing their treatment allocation at a rate similar to that anticipated by chance. No serious or severe adverse events were reported in either group, and there were no significant differences in mild-to-moderate adverse events between groups (median of 2 adverse events per participant reported in both groups). Furthermore, the 12/15 participants who completed the Week 2 participant satisfaction survey agreed or strongly agreed that the enema delivery was tolerable and that they would have the treatment again if required. Whilst the study was not designed to measure clinical outcomes, exploratory data also suggested that the active FMT treatment may lead to improvements in gastrointestinal symptoms and quality of life in this population, noting that irritable bowel syndrome is commonly comorbid with MDD. Conclusions All feasibility targets were met or exceeded. This study found that enema-delivered FMT is feasible, acceptable, well-tolerated, and safe in patients with MDD. The findings of this study support further research to evaluate clinical efficacy, and the use of this protocol is supported.

Background Mental disorders, including major depressive disorder (MDD), are a leading cause of non-fatal burden of disease globally. Current conventional treatments for depression have significant limitations, and there have been few new treatments in decades. The microbiota-gut-brain-axis is now recognised as playing a role in mental and brain health, and promising preclinical and clinical data suggest Faecal Microbiota Transplants (FMT) may be efficacious for treating a range of mental illnesses. However, there are no existing published studies in humans evaluating the efficacy of FMT for MDD. Methods and design This protocol describes an 8-week, triple-blind, 2:1 parallel group, randomised controlled pilot trial (n = 15), of enema-delivered FMT treatment (n = 10) compared with a placebo enema (n = 5) in adults with moderate-to-severe MDD. There will be a further 26-week follow-up to monitor longer-term safety. Participants will receive four FMT or placebo enemas over four consecutive days. The primary aims of the study are to evaluate feasibility and safety of FMT as an adjunctive treatment for MDD in adults. Changes in gut microbiota will be assessed as a secondary outcome. Other data will be collected, including changes in depression and anxiety symptoms, and safety parameters. Discussion Modification of the microbiota-gut-brain axis via FMT is a promising potential treatment for MDD, but there are no published rigorous clinical trials evaluating its use. If this study finds that our FMT strategy is safe and feasible, a larger fully powered RCT is planned. Further high-quality research in this field is urgently needed to address unmet need. Trial registration Australian and New Zealand Clinical Trials Registry: ACTRN12621000932864

The intestinal microbiome has been identified as a key modifier for a variety of health conditions. Fecal Microbiota Transplantation (FMT) has emerged as a fast, safe, and effective means by which to modify the intestinal microbiome and potentially treat a variety of health conditions. Despite extensive research of FMT for CDI, there is a lack of clarity informed by systematic synthesis of data regarding the safety and efficacy of FMT for other health conditions. This systematic review used PRISMA guidelines and was prospectively registered with PROSPERO (CRD42018104243). In March 2020, a search of MEDLINE, EMBASE, and PsycINFO was conducted. We identified 26 eligible studies. A meta-analysis of FMT for active Ulcerative Colitis (UC) showed that FMT significantly improved rates of clinical remission (OR = 3.634, 95% CI = 1.940 to 6.808, I2 = 0%, p

Background The Barwon area in Australia has one of the highest incidence rates of inflammatory bowel disease (IBD) and therefore is an ideal location to study the impact of environmental exposures on the disease's development. Aim To study these exposures prior to the development of IBD in a population-based cohort. Method One hundred and thirty-two incident cases (81 Crohn disease (CD) and 51 ulcerative colitis (UC)) from an IBD registry and 104 controls replied to the International Organization of Inflammatory Bowel Diseases environmental questionnaire. This included 87 questions about pre-illness exposures that included childhood illnesses, vaccinations, breastfeeding, house amenities, pets and swimming, diet and smoking. Results The factors associated with CD included smoking (odds ratio (OR): 1.42, confidence interval (CI): 1–2.02, P = 0.029); childhood events, including tonsillectomy (OR: 1.74, CI: 1.15–2.6, P = 0.003) and chicken pox infection (OR: 3.89, CI: 1.61–9.4, P = 0.005) and pre-diagnosis intake of frequent fast food (OR: 2.26, CI: 1.76–4.33, P = 0.003). In UC, the risk factors included smoking (OR: 1.39, CI: 1.1–1.92, P = 0.026) and pre-diagnosis intake of frequent fast food (OR: 2.91, CI: 1.54–5.58, P

Background and Aims: Regional variations in inflammatory bowel disease (IBD) rates have been observed. Limited epidemiological data are available from Australasia. IBD prevalence rates have never been assessed in an Australian population-based setting. In addition, there are few historical IBD incidence data to allow assessment of rate changes. The aims were to calculate Australia's first population-based IBD prevalence rates, to reassess local IBD incidence rates, and to establish a population-based inception cohort. Methods: An observational, prospective population-based epidemiological study was performed to assess IBD prevalence and incidence rates from July 2010 to June 2011 in a geographically defined Australian population (Barwon, Victoria). Results: There were 1011 prevalent IBD cases identified, representing a crude point prevalence rate of 344.6 per 100 000 on June 30, 2011. Crohn's disease was the most common prevalent subtype. Seventy-one incident cases of IBD were identified, with a crude incidence rate of 24.2 per 100 000. Crohn's disease was again more common. Local incidence rates have not changed between 2007 and the present study. All incident cases were successfully incorporated into an inception cohort. Conclusion: The burden of IBD in our local region is high. Demographic similarities allow these results to be applied to the broader Australian community. We propose that the number of existing and new cases each year in Australia has been previously underestimated. These revised figures will be important when planning the provision of health resources for these patients in the future and when assessing need for research funding priorities.

Background and Aim We have previously found high incidence of inflammatory bowel disease (IBD) in Australia. A population-based registry was established to assess disease severity, frequency of complications, and prognostic factors. Methods Incident cases were prospectively identified over 4 years. Early disease severity was assessed according to need for hospitalization and resective surgery and medication use. Results We report on the early outcomes (median 18 months, range 12–60 months) for 252 patients comprising 146 with Crohn's disease (CD), 96 with ulcerative colitis (UC), and 10 IBD undifferentiated. Eighty-seven percent of CD patients had inflammatory disease at diagnosis, and this reduced to 73% at 5 years (n = 38). Immunomodulators were prescribed in 57% of CD patients and 19% with UC. A third of all CD patients were hospitalized, the majority (77%) in the first 12 months. Risk factors for hospitalization included penetrating, perianal, and ileocolonic disease (P

Staphylococcus aureus bacteraemia (SAB) is an important cause of community and nosocomial sepsis, with a significant mortality rate. Infective endocarditis (IE) is a serious complication, occurring in up to 25 % of cases. Transoesophageal echocardiography (TOE) significantly improves the sensitivity of diagnosis. We compared the sensitivity and specificity of clinical evaluation alone in diagnosing IE. We evaluated all adult patients with SAB at our centre from 1998 to 2006 in order to determine what proportion of clinically unsuspected cases were diagnosed with IE on TOE. IE was defined according to modified Duke criteria. The median age of the patients was 68 years, 77 % were male and the majority of cases did not have a known pre-existing condition. Twenty-one percent were methicillin-resistant Staphylococcus aureus (MRSA). Intravascular device was the most common cause of bacteraemia. TOE was performed in 144 (100 %) of the cases. IE was suspected clinically in 15 % of cases, and the overall prevalence of possible or definite IE on TOE-inclusive Duke criteria was 29 % (n = 41). Following TOE, 22 (15 %) cases were reclassified as either possible or definite endocarditis. TOE detected a vegetation in 37 (90 %) of the 41 cases of IE. Nineteen (46 %) were not suspected clinically by Duke criteria. Sensitivity improved in the presence of pre-existing valve lesion or community acquisition. The overall in-hospital mortality was 10 %. There is a high incidence of endocarditis in SAB and a large percentage of cases are not evident on clinical grounds. TOE evaluation is indicated for all medically suitable adult patients with SAB in order to improve the detection of endocarditis.

Background: There are limited prospective population-based data on the health care cost of IBD in the post-biologicals era. A prospective registry that included all incident cases of inflammatory bowel disease [IBD] was established to study disease progress and health cost. Aim: To prospectively assess health care costs in the first year of diagnosis among a well-characterised cohort of newly diagnosed IBD patients. Method: Incident cases of IBD were prospectively identified in 2007–2008 and 2010–2013 from multiple health care providers, and enrolled into the population-based registry. Health care resource utilisation for each patient was collected through active surveillance of case notes and investigations including specialist visits, diagnostic tests, medications, medical hospitalisation, and surgery. Results: Off 276 incident cases of IBD, 252 [91%] were recruited to the registry, and health care cost was calculated for 242 (146 Crohn’s disease [CD] and 96 ulcerative colitis [UC] patients). The median cost in CD was higher at A$5905 per patient (interquartile range [IQR]: A$1571-$91,324) than in UC at A$4752 [IQR: A$1488-A$58,072]. In CD, outpatient resources made up 55% of all cost, with medications accounting for 32% of total cost [15% aminosalicylates, 15% biological therapy], followed by surgery [31%], and diagnostic testing [21%]. In UC, medications accounted for 39% of total cost [of which 37% was due to 5-aminosalicylates, and diagnostics 29%; outpatient cost contributed 71% to total cost. Conclusion: In the first year of diagnosis, outpatient resources account for the majority of cost in both CD and UC. Medications are the main cost driver in IBD.

Regional variations in inflammatory bowel disease (IBD) rates have been observed. Limited epidemiological data are available from Australasia. IBD prevalence rates have never been assessed in an Australian population-based setting. In addition, there are few historical IBD incidence data to allow assessment of rate changes. The aims were to calculate Australia's first population-based IBD prevalence rates, to reassess local IBD incidence rates, and to establish a population-based inception cohort.An observational, prospective population-based epidemiological study was performed to assess IBD prevalence and incidence rates from July 2010 to June 2011 in a geographically defined Australian population (Barwon, Victoria).There were 1011 prevalent IBD cases identified, representing a crude point prevalence rate of 344.6 per 100,000 on June 30, 2011. Crohn's disease was the most common prevalent subtype. Seventy-one incident cases of IBD were identified, with a crude incidence rate of 24.2 per 100,000. Crohn's disease was again more common. Local incidence rates have not changed between 2007 and the present study. All incident cases were successfully incorporated into an inception cohort.The burden of IBD in our local region is high. Demographic similarities allow these results to be applied to the broader Australian community. We propose that the number of existing and new cases each year in Australia has been previously underestimated. These revised figures will be important when planning the provision of health resources for these patients in the future and when assessing need for research funding priorities.

Background: To date, there have been no population-based epidemiological studies published from Australia concerning the incidence of inflammatory bowel disease (IBD). Our hypothesis was that the incidence of IBD in Australia is at least as high as other industrialized countries, given similar genetic and environmental risk factors. Methods: A prospective, population-based IBD incidence study was conducted between April 2007 and March 2008 in Greater Geelong, Victoria, Australia. According to 2006 Australian Census data, this comprises an at-risk population of 259,015. Cases were ascertained from multiple overlapping sources. All local general practitioners, gastroenterologists, surgeons, and pediatricians were contacted every 2 months to identify new IBD cases. The Royal Children's Hospital in Melbourne, local endoscopy and pathology centers were also searched to ensure completeness of case capture. Standard IBD case definitions were used with clinical, endoscopic, and histological criteria. Results: In all, 76 new cases of IBD were identified during the 1-year period. There were 45 cases of Crohn's disease, 29 of ulcerative colitis, and 2 of indeterminate colitis. The crude annual incidence rates for IBD overall, Crohn's disease, ulcerative colitis, and indeterminate colitis were 29.3 per 100,000 (95% confidence interval [CI] 23.5–36.7 per 100,000), 17.4 per 100,000, 11.2 per 100,000, and 0.8 per 100,000, respectively. When directly age-standardized to the World Health Organization standard population the overall IBD incidence rate was 29.6 per 100,000. Conclusions: This is the first prospective, Australian population-based IBD incidence study. The incidence rates are among the highest reported in the literature of IBD. (Inflamm Bowel Dis 2009)

The incidence of cardiac metastases is rising due to increasingly sensitive diagnostic investigations and longer patient survival as a result of improved treatment for malignancies. We report a rare case of right atrial metastasis from a large cell neuroendocrine carcinoma successfully resected with cardiopulmonary bypass. The surgical management of advanced cardiac malignancy is discussed. In appropriately selected cases surgical resection of cardiac metastases can be beneficial, allowing improvement in quality of life, and prolongation of life.

and statistically significant in the Quebec general population. Mortality rates for digestive neoplasms and colorectal cancer in particular had a small but significant decrease in both CD and UC, whereas in the Quebec general population we observed a significant increase with calendar year (data available from ISQ for 2003-2008). Conclusions All-cause mortality was significantly increased in both CD and UC patients compared to the Quebec general population. Lung cancer mortality showed a significant increase with time in both CD and UC. Mortality from digestive neoplasms and colorectal cancer had a small but significant decrease with time in both CD and UC.

Hepatitis C Virus (HCV) infection is a major cause of liver disease globally.1 More than 350,000 people die from hepatitis C-related liver diseases each year.2 Persistent HCV infection can progress to liver cirrhosis and hepatocellular carcinoma.1 Thus, HCV infection is a major cause of morbidity and mortality worldwide.3 The range of liver disease severity in individual patients with HCV infection is broad. The spectrum of liver disease in patients infected with HCV ranges from asymptomatic carriers, patients with chronic hepatitis of variable severity to end-stage liver cirrhosis.4 The rate of progression to the cirrhotic stage also varies widely amongst HCV-infected individuals. Studies by our group and others5,6 have demonstrated that the low density HCV fraction represents the “infectious, active” fraction in plasma, and consists of HCV bound to low density lipoprotein (LDL). Agnello and colleagues proposed that the LDL receptor plays a role in the cellular entry of HCV into hepatocytes.7 Further studies support the role of the LDL receptor in HCV cellular entry and infection.8 In acute HCV infection, viral RNA is linked with plasma LDL, and in chronic disease states, viral RNA is linked with the high density fraction in plasma, which is thought to be immunoglobulin-bound.5 An intermediate density fraction has also been identified more recently, which is likely to be lipoprotein-bound.9 To further investigate the idiosyncratic relationship between HCV, LDL and IgG, we attempted to determine whether high, intermediate and low density HCV RNA levels in plasma are related to the clinical status of patients with liver disease. HCV RNA titer from six HCV-infected patients with varying severities of liver disease were analyzed by Differential Flotation Ultracentrifugation and HCV RNA quantification, according to the techniques reported by Watson and colleagues5 and Pumeechockchai and colleagues.10 The subjects' clinical presentation was compared to the differential HCV density fractions. Baseline and sequential liver function tests were performed and five out of six patients proceeded to liver biopsy for clinical purposes. Hepatitis C virus serology and genotype data were performed (Table 1). Table 1 Clinical and serological data of the hepatitis C infected patients analyzed. All patients, except Patient 5, had mild disease as demonstrated on liver biopsy. Patient 5 had severe liver disease, including cirrhosis and hepatocellular carcinoma. Patients 1–4 demonstrated inter-patient differences in the amount of quantitative HCV in high density (immunoglobulin-bound) fraction, and low and intermediate density (lipoprotein-bound) fractions. However, this was not statistically significant between patients or within individual patients. Patients 5 and 6 were found to have negative quantitative HCV PCR, thus, fractions could not be determined in these patients. This may be due to difficulties in the RNA extraction process after ultracentrifugation. The results of our small pilot study do not clearly demonstrate an association between the severity of clinical liver disease and buoyant density of HCV RNA fractions. A major limitation was the small sample size. However, the technique of differential ultracentrifugation, HCV RNA extraction and viral quantification is extremely labor intensive, which would render a larger sample size difficult. This study demonstrates the complexity of the relationship between HCV infection and LDL binding in the human host. Further investigation of this idiosyncratic association is required.