Publications by authors named "Samuel P Costello"

28 Publications

  • Page 1 of 1

Food-related quality of life in adults with inflammatory bowel disease is associated with restrictive eating behaviour, disease activity and surgery: A prospective multicentre observational study.

J Hum Nutr Diet 2021 May 18. Epub 2021 May 18.

Inflammatory Bowel Disease Services, The Department of Gastroenterology and Hepatology, The Queen Elizabeth Hospital, Woodville South, SA, Australia.

Background: Measuring food-related quality of life (FRQoL) quantifies the psychosocial impact of eating and drinking. FRQoL and associated factors are not well explored in people with inflammatory bowel disease (IBD), despite IBD being a chronic disease affecting the digestive tract. The present study aimed to characterise and identify any patient or disease-related predictors of FRQoL in individuals with IBD.

Methods: Adults with a formal diagnosis of IBD were recruited to a prospective multicentre cross-sectional study between April 2018 and December 2019. Participants completed questionnaires measuring FRQoL (FRQoL-29), clinical disease activity (Harvey Bradshaw Index and Simple Clinical Colitis Activity Index), restrictive eating behaviour (Nine-Item Avoidant/Restrictive Food Intake Disorder Screen), mental health (Depression Anxiety Stress Scale-21) and other patient and disease-related variables. A multivariable regression was performed to identify factors associated with FRQoL.

Results: One hundred and eight participants completed the questionnaires (n = 39, Crohn's disease; n = 69, ulcerative colitis). The mean FRQoL was 79 (95% confidence interval = 75-84) (poor, 0; superior, 145). Poorer FRQoL was observed in those with restrictive eating behaviour associated with fear of a negative consequence from eating (p < 0.0001) and reduced appetite (p < 0.030). Greater FRQoL was observed in those with lower disease activity (p < 0.0001) and previous IBD surgery (p = 0.024). FRQoL was not associated either way by IBD phenotype, duration, or gender. The majority of participants obtained their dietary information from the internet (60%) or gastroenterologist (46%).

Conclusions: FRQoL in people with IBD is poorer in those with restrictive eating behaviours and clinically active disease. Interestingly, it was greater in those with previous IBD surgery. Further research is required to validate these associations and explore longitudinal effects of poor FRQoL on patient outcomes and potential strategies for prevention or management of impaired FRQoL in IBD.
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http://dx.doi.org/10.1111/jhn.12920DOI Listing
May 2021

Dialing Back M for Monoclonal: Successful De-escalation of Dose-Intensified Anti-tumor Necrosis Factor Therapy in Inflammatory Bowel Disease.

Dig Dis Sci 2021 Mar 25. Epub 2021 Mar 25.

IBD Service, Department of Gastroenterology, The Queen Elizabeth Hospital, 28 Woodville Rd,, Woodville South, SA, 5011, Australia.

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http://dx.doi.org/10.1007/s10620-021-06946-yDOI Listing
March 2021

The Adequacy of Habitual Dietary Fiber Intake in Individuals With Inflammatory Bowel Disease: A Systematic Review.

J Acad Nutr Diet 2021 Apr 20;121(4):688-708.e3. Epub 2021 Jan 20.

Background: Dietary fiber may influence disease course in individuals with inflammatory bowel disease (IBD), yet there is a paucity of understanding of habitual fiber intakes.

Objectives: To identify studies measuring fiber intakes of individuals with IBD, compare the adequacy of fiber intakes with that of control groups or respective national dietary guidelines, and examine factors associated with fiber consumption.

Methods: Five electronic databases-MEDLINE, CINAHL, SCOPUS, PROQUEST, and COCHRANE LIBRARY-were systematically searched, using search terms inflammatory bowel disease, Crohn's disease, ulcerative colitis, dietary intake, and fiber, until December 2019, with hand searching of reference lists. Primary studies were included if fiber intakes were measured in participants 18 years of age or older, with confirmed IBD, with or without comparison to a control.

Results: A total of 2105 publications were identified, and 26 met inclusion criteria. Total fiber intake of 4164 participants with IBD ranged broadly (9.9 ± 7.8 g/day to 21.0 ± 10.5 g/day). Most (18/26) used cross-sectional study design, with a large degree of heterogeneity in tools measuring fiber intake. Sixty-six percent of studies comparing participants with IBD with control groups found that participants with IBD consumed significantly less fiber than control subjects. Four studies reported that less than 10% to 21% of IBD participants met their national fiber recommendations. Data conflicted regarding an association between disease type, disease activity, or rate of relapse and fiber intake.

Conclusions: Individuals with IBD consume less fiber than healthy populations. Fiber intakes are inadequate compared with respective national fiber guidelines. Interpretation of factors associated with fiber intakes were limited by data quality and conflicting results. Future research is required into factors associated with fiber intake and whether increasing fiber intakes can influence disease course and behavior.
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http://dx.doi.org/10.1016/j.jand.2020.12.001DOI Listing
April 2021

Physician and patient perceptions of fecal microbiota transplant for recurrent or refractory in the first 6 years of a central stool bank.

JGH Open 2020 Oct 6;4(5):950-957. Epub 2020 Aug 6.

Department of Gastroenterology The Queen Elizabeth Hospital Adelaide South Australia Australia.

Background And Aim: Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent or refractory infection (rCDI). Despite inclusion in society guidelines, the uptake of FMT therapy has been variable. Physician and patient attitudes may be a barrier to evidence-based uptake of therapies; however, data assessing attitudes regarding FMT for rCDI are limited.

Methods: The South Australian FMT for CDI database prospectively recorded patient outcomes of FMT for CDI from August 2013 to January 2019. A total of 93 consecutive patients who underwent FMT for rCDI in South Australia were invited to participate in a 20-question survey regarding the patient experience of FMT. All gastroenterologists and infectious disease physicians practicing in South Australia were invited to participate in an online survey comprised of 22 questions that addressed referral experience, indications for referral, perceived risks, and regulation and funding.

Results: Fifty-four patients (54/93, 58%) returned the survey, of whom 52 (96%) would recommend FMT to others, and 51 (94%) were satisfied with treatment outcome. Fifty physicians returned the online survey (50/100, 50%), of whom 23 (46%) were concerned about disease transmission risk, and 15 (30%) believed that the risk of FMT would outweigh the benefit. Infectious diseases physicians and advanced trainees had significantly greater concern regarding the potential alteration of the microbiome than gastroenterology physicians and advanced trainees (8/17 (47%) 6/33 (18%); = 0.047).

Conclusion: Despite high levels of patient-reported satisfaction following FMT, physician-reported reservations exist and may present a barrier to uptake of this therapy.
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http://dx.doi.org/10.1002/jgh3.12396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578309PMC
October 2020

ABC of topical therapy in inflammatory bowel disease.

JGH Open 2020 Aug 26;4(4):556-557. Epub 2020 Apr 26.

IBD Service, Department of Gastroenterology The Queen Elizabeth Hospital Adelaide South Australia Australia.

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http://dx.doi.org/10.1002/jgh3.12323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411570PMC
August 2020

Practical management of inflammatory bowel disease patients during the COVID-19 pandemic: expert commentary from the Gastroenterological Society of Australia Inflammatory Bowel Disease faculty.

Intern Med J 2020 07;50(7):798-804

Department of Gastroenterology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.

The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has emerged as a public health emergency and challenged healthcare systems globally. In a minority of patients, SARS-CoV-2 manifests with a severe acute respiratory illness and currently there is insufficient data regarding the virulence of COVID-19 in inflammatory bowel disease patients taking immunosuppressive therapy. This review aims to summarise the current literature and provide guidance on the management of inflammatory bowel disease patients in the context of the COVID-19 pandemic in the Australasian setting.
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http://dx.doi.org/10.1111/imj.14889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405147PMC
July 2020

Histological Healing in Ulcerative Colitis: Near Enough Is Not Good Enough.

J Crohns Colitis 2020 Oct;14(10):1341-1342

IBD Service, Department of Gastroenterology, Queen Elizabeth Hospital, Adelaide, SA, Australia.

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http://dx.doi.org/10.1093/ecco-jcc/jjaa095DOI Listing
October 2020

COVID-19 and implications for thiopurine use.

Med J Aust 2020 06 13;212(10):490-490.e1. Epub 2020 May 13.

Queen Elizabeth Hospital, Adelaide, SA.

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http://dx.doi.org/10.5694/mja2.50613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272893PMC
June 2020

Faecal microbiota transplantation: indications, evidence and safety.

Aust Prescr 2020 04 1;43(2):36-38. Epub 2020 Apr 1.

Inflammatory Bowel Disease Service, Department of Gastroenterology, Queen Elizabeth Hospital, Adelaide.

The human gut contains many species of microorganisms, many of which have a role in maintaining good health. The gut microbiota can be affected by diet, diseases and drugs, especially antibiotics. Faecal microbiota transplantation involves transplanting faecal material from a healthy person to a patient, with the aim of treating disease. It is a recommended treatment option for patients with recurrent or refractory Clostridioides difficile as it has a cure rate over 90%. There is evidence that faecal microbiota transplantation can induce remission in ulcerative colitis, however maintenance of remission data are lacking. For other diseases it currently should not be used outside a clinical trial. Stool donors have to be healthy and are screened for a range of diseases. As faecal material is usually transplanted during colonoscopy, the recipient must have bowel preparation before the procedure. Adverse effects are mainly gastrointestinal and usually resolve in the week following transplantation. There are limited data on long-term safety.
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http://dx.doi.org/10.18773/austprescr.2020.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186269PMC
April 2020

Gastrointestinal ultrasound in inflammatory bowel disease care: Patient perceptions and impact on disease-related knowledge.

JGH Open 2020 Apr 9;4(2):267-272. Epub 2019 Oct 9.

IBD Service, Department of Gastroenterology The Queen Elizabeth Hospital Adelaide South Australia Australia.

Background And Aim: Objective monitoring of disease activity is integral to therapeutic decision-making in inflammatory bowel disease (IBD). Data are sparse on patients' perspectives of tools used to monitor disease activity in IBD. To evaluate patients' perspectives of gastrointestinal ultrasound (GIUS) performed during routine IBD clinical care, along with its impact on IBD-specific knowledge.

Methods: Patients with a formal diagnosis of IBD who underwent GIUS at two tertiary IBD services between March 2017 and January 2019 participated in this prospective study. Participants completed a questionnaire measuring the acceptability, tolerability, and usefulness of GIUS using a visual analogue scale (VAS) from 0 (disagree) to 10 (strongly agree). Comparative acceptability of IBD monitoring tools and the impact of GIUS on IBD-specific knowledge was measured.

Results: A total of 121 participants completed the questionnaire, with a mean age of 42 years (range 17-78), 54 (45%) males, and 79 (65%) Crohn's disease patients. In the overall population, GIUS was scored as highly acceptable for monitoring IBD (mean 9.20 ± 1.37) compared to colonoscopy (7.94 ± 2.30), stool sampling (8.17 ± 1.96), blood sampling (8.87 ± 1.62), and imaging (8.67 ± 1.60);  < 0.01 for each comparison. GIUS caused little patient discomfort (1.88 ± 1.83), and 98 (81%) participants ranked GIUS as their preferred IBD monitoring tool. GIUS also improved patients' overall IBD-specific knowledge (VAS IBD-specific knowledge 7.96 ± 1.92), including their understanding of the need for medical therapy and disease extent.

Conclusion: GIUS is a highly acceptable and well-tolerated tool for monitoring disease activity in IBD patients. GIUS is preferred by patients and enhances IBD-specific knowledge.
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http://dx.doi.org/10.1002/jgh3.12268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144798PMC
April 2020

Australian consensus statements for the regulation, production and use of faecal microbiota transplantation in clinical practice.

Gut 2020 05 11;69(5):801-810. Epub 2020 Feb 11.

The University of Sydney, Sydney, New South Wales, Australia

Objective: Faecal microbiota transplantation (FMT) has proved to be an extremely effective treatment for recurrent infection, and there is interest in its potential application in other gastrointestinal and systemic diseases. However, the recent death and episode of septicaemia following FMT highlights the need for further appraisal and guidelines on donor evaluation, production standards, treatment facilities and acceptable clinical indications.

Design: For these consensus statements, a 24-member multidisciplinary working group voted online and then convened in-person, using a modified Delphi approach to formulate and refine a series of recommendations based on best evidence and expert opinion. Invitations to participate were directed to Australian experts, with an international delegate assisting the development. The following issues regarding the use of FMT in clinical practice were addressed: donor selection and screening, clinical indications, requirements of FMT centres and future directions. Evidence was rated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system.

Results: Consensus was reached on 27 statements to provide guidance on best practice in FMT. These include: (1) minimum standards for donor screening with recommended clinical selection criteria, blood and stool testing; (2) accepted routes of administration; (3) clinical indications; (4) minimum standards for FMT production and requirements for treatment facilities acknowledging distinction between single-site centres (eg, hospital-based) and stool banks; and (5) recommendations on future research and product development.

Conclusions: These FMT consensus statements provide comprehensive recommendations around the production and use of FMT in clinical practice with relevance to clinicians, researchers and policy makers.
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http://dx.doi.org/10.1136/gutjnl-2019-320260DOI Listing
May 2020

Systematic Review: Patient Perceptions of Monitoring Tools in Inflammatory Bowel Disease.

J Can Assoc Gastroenterol 2021 Apr 24;4(2):e31-e41. Epub 2020 Jan 24.

Department of Gastroenterology, The Queen Elizabeth Hospital, Adelaide, Australia.

Background And Aims: Inflammatory bowel disease (IBD) is a lifelong disease requiring frequent assessment to guide treatment and prevent flares or progression. Multiple tools are available for clinicians to monitor disease activity; however, there are a paucity of data to inform which monitoring tools are most acceptable to patients. The review aims to describe the available evidence for patient preference, satisfaction, tolerance and/or acceptability of the available monitoring tools in adults with IBD.

Methods: Embase, Medline, Cochrane Central and Clinical Trials.gov were searched from January 1980 to April 2019 for all study types reporting on the perspectives of adults with confirmed IBD on monitoring tools, where two or more tools were compared. Outcome measures with summary and descriptive data were presented.

Results: In 10 studies evaluating 1846 participants, monitoring tools included venipuncture, stool collection, gastrointestinal ultrasound, computed tomography, magnetic resonance imaging, wireless capsule endoscopy, barium follow-through and endoscopy. Outcome domains were patient satisfaction, acceptability of monitoring tool and patient preference. Noninvasive investigations were preferable to endoscopy in nine studies. When assessed, gastrointestinal ultrasound was consistently associated with greater acceptability and satisfaction compared with endoscopy or other imaging modalities.

Conclusions: Adults with IBD preferred noninvasive investigations, in particular gastrointestinal ultrasound, as compared to endoscopy for monitoring disease activity. When assessing disease activity, patient perceptions should be considered in the selection of monitoring tools. Further research should address whether adpoting monitoring approaches considered more acceptable to patients results in greater satisfaction, adherence and ultimately more beneficial clinical outcomes.
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http://dx.doi.org/10.1093/jcag/gwaa001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023822PMC
April 2021

Editorial: faecal microbiota transplantation-the silver bullet for severe and fulminant Clostridioides difficile infection?

Aliment Pharmacol Ther 2020 01;51(1):180-181

Department of Gastroenterology, The Queen Elizabeth Hospital, Woodville, SA, Australia.

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http://dx.doi.org/10.1111/apt.15584DOI Listing
January 2020

Deficient Resident Memory T Cell and CD8 T Cell Response to Commensals in Inflammatory Bowel Disease.

J Crohns Colitis 2020 May;14(4):525-537

Antigen Presentation Research Group, Imperial College London, Northwick Park and St Mark's Campus, Harrow, London, UK.

Background And Aims: The intestinal microbiota is closely associated with resident memory lymphocytes in mucosal tissue. We sought to understand how acquired cellular and humoral immunity to the microbiota differ in health versus inflammatory bowel disease [IBD].

Methods: Resident memory T cells [Trm] in colonic biopsies and local antibody responses to intraepithelial microbes were analysed. Systemic antigen-specific immune T and B cell memory to a panel of commensal microbes was assessed.

Results: Systemically, healthy blood showed CD4 and occasional CD8 memory T cell responses to selected intestinal bacteria, but few memory B cell responses. In IBD, CD8 memory T cell responses decreased although B cell responses and circulating plasmablasts increased. Possibly secondary to loss of systemic CD8 T cell responses in IBD, dramatically reduced numbers of mucosal CD8+ Trm and γδ T cells were observed. IgA responses to intraepithelial bacteria were increased. Colonic Trm expressed CD39 and CD73 ectonucleotidases, characteristic of regulatory T cells. Cytokines/factors required for Trm differentiation were identified, and in vitro-generated Trm expressed regulatory T cell function via CD39. Cognate interaction between T cells and dendritic cells induced T-bet expression in dendritic cells, a key mechanism in regulating cell-mediated mucosal responses.

Conclusions: A previously unrecognised imbalance exists between cellular and humoral immunity to the microbiota in IBD, with loss of mucosal T cell-mediated barrier immunity and uncontrolled antibody responses. Regulatory function of Trm may explain their association with intestinal health. Promoting Trm and their interaction with dendritic cells, rather than immunosuppression, may reinforce tissue immunity, improve barrier function, and prevent B cell dysfunction in microbiota-associated disease and IBD aetiology.
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http://dx.doi.org/10.1093/ecco-jcc/jjz175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242004PMC
May 2020

A necessary discussion after transmission of multidrug-resistant organisms through faecal microbiota transplantations.

Lancet Infect Dis 2019 11;19(11):1161-1162

Department I of Internal Medicine, University of Cologne, Cologne, Germany; Center for Integrated Oncology Aachen-Bonn-Cologne-Duesseldorf, Cologne, Germany; German Centre for Infection Research, partner site Bonn-Cologne, Germany; Department of Internal Medicine and Infectious Diseases, Goethe University Frankfurt, Frankfurt am Main, Germany.

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http://dx.doi.org/10.1016/S1473-3099(19)30545-6DOI Listing
November 2019

Alternative and Complementary Approaches for the Treatment of Inflammatory Bowel Disease: Evidence From Cochrane Reviews.

Inflamm Bowel Dis 2020 05;26(6):843-851

Division of Gastroenterology, Department of Medicine, University of Western Ontario, London, Ontario, Canada.

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http://dx.doi.org/10.1093/ibd/izz223DOI Listing
May 2020

Uncovering the cause of ulcerative colitis.

JGH Open 2019 Aug 6;3(4):274-276. Epub 2019 Aug 6.

School of Medicine University of Adelaide Adelaide South Australia Australia.

The cause of ulcerative colitis still remains unclear. The most popular hypothesis is that colitis develops because of a complex interaction of genetic, microbial, environmental, and immunologic factors. This editorial summarizes the widely accepted hypothesis and comments on a variation of this hypothesis promoted by Dr Roediger.
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http://dx.doi.org/10.1002/jgh3.12216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6684508PMC
August 2019

Fecal Microbiota Transplantation for Ulcerative Colitis-Reply.

JAMA 2019 06;321(22):2240-2241

Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, Australia.

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http://dx.doi.org/10.1001/jama.2019.3950DOI Listing
June 2019

Editorial: assessing histological disease activity in Crohn's disease-a call for standardisation of mucosal biopsy location.

Aliment Pharmacol Ther 2019 07;50(1):103-104

IBD Service, Department of Gastroenterology, The Queen Elizabeth Hospital, Adelaide, Australia.

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http://dx.doi.org/10.1111/apt.15284DOI Listing
July 2019

Bacterial viability in faecal transplants: Which bacteria survive?

EBioMedicine 2019 Mar 19;41:509-516. Epub 2019 Feb 19.

The South Australian Health and Medical Research Institute (SAHMRI), Adelaide, South Australia, Australia; The SAHMRI Microbiome Research Laboratory, School of Medicine, Flinders University, Bedford Park, South Australia, Australia.

Background: The therapeutic potential of faecal microbiota transplantation (FMT) is under investigation for a range of inflammatory conditions. While mechanisms of benefit are poorly understood, most models rely on the viability of transplanted microbes. We hypothesised that protocols commonly used in the preparation of faecal transplants will substantially reduce the number, diversity and functional potential of viable microbes.

Methods: Stools from eight screened donors were processed under strict anaerobic conditions, in ambient air, and freeze-thawed. Propidium monoazide (PMA) sample treatment was combined with quantitative PCR, 16S rRNA gene amplicon sequencing and short-chain fatty acid (SCFA) analysis to define the viable microbiota composition and functional potential.

Findings: Approximately 50% of bacterial content of stool processed immediately under strict anaerobic conditions was non-viable. Homogenisation in ambient air or freeze-thaw reduced viability to 19% and 23% respectively. Processing of samples in ambient air resulted in up to 12-fold reductions in the abundance of important commensal taxa, including the highly butyrogenic species Faecalibacterium prausnitzii, Subdoligranulum variable, and Eubacterium hallii. The adverse impact of atmospheric oxygen exposure on the capacity of the transplanted microbiota to support SCFA biosynthesis was demonstrated by significantly reduced butyrate and acetate production by faecal slurries processed in ambient air. In contrast, while reducing overall levels of viable bacteria, freeze-thaw did not significantly alter viable microbiota composition.

Interpretation: The practice of preparing material for faecal transplantation in ambient air profoundly affects viable microbial content, disproportionately reducing the abundance of anaerobic commensals and the capacity for biosynthesis of important anti-inflammatory metabolites. FUND: This work was supported by the South Australian Health and Medical Research Institute. LP is supported by a scholarship from the Flinders Foundation. GR is supported by a Matthew Flinders Research Fellowship.
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http://dx.doi.org/10.1016/j.ebiom.2019.02.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6444077PMC
March 2019

Faecal microbiota transplantation in Australia: bogged down in regulatory uncertainty.

Intern Med J 2019 02;49(2):148-151

Inflammatory Bowel Disease Service, Department of Gastroenterology, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia.

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http://dx.doi.org/10.1111/imj.14212DOI Listing
February 2019

Effect of Fecal Microbiota Transplantation on 8-Week Remission in Patients With Ulcerative Colitis: A Randomized Clinical Trial.

JAMA 2019 01;321(2):156-164

Centre for Nutrition and Gastrointestinal Disease, Adelaide Medical School, University of Adelaide and South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.

Importance: High-intensity, aerobically prepared fecal microbiota transplantation (FMT) has demonstrated efficacy in treating active ulcerative colitis (UC). FMT protocols involving anaerobic stool processing methods may enhance microbial viability and allow efficacy with a lower treatment intensity.

Objective: To assess the efficacy of a short duration of FMT therapy to induce remission in UC using anaerobically prepared stool.

Design, Setting, And Participants: A total of 73 adults with mild to moderately active UC were enrolled in a multicenter, randomized, double-blind clinical trial in 3 Australian tertiary referral centers between June 2013 and June 2016, with 12-month follow-up until June 2017.

Interventions: Patients were randomized to receive either anaerobically prepared pooled donor FMT (n = 38) or autologous FMT (n = 35) via colonoscopy followed by 2 enemas over 7 days. Open-label therapy was offered to autologous FMT participants at 8 weeks and they were followed up for 12 months.

Main Outcomes And Measures: The primary outcome was steroid-free remission of UC, defined as a total Mayo score of ≤2 with an endoscopic Mayo score of 1 or less at week 8. Total Mayo score ranges from 0 to 12 (0 = no disease and 12 = most severe disease). Steroid-free remission of UC was reassessed at 12 months. Secondary clinical outcomes included adverse events.

Results: Among 73 patients who were randomized (mean age, 39 years; women, 33 [45%]), 69 (95%) completed the trial. The primary outcome was achieved in 12 of the 38 participants (32%) receiving pooled donor FMT compared with 3 of the 35 (9%) receiving autologous FMT (difference, 23% [95% CI, 4%-42%]; odds ratio, 5.0 [95% CI, 1.2-20.1]; P = .03). Five of the 12 participants (42%) who achieved the primary end point at week 8 following donor FMT maintained remission at 12 months. There were 3 serious adverse events in the donor FMT group and 2 in the autologous FMT group.

Conclusions And Relevance: In this preliminary study of adults with mild to moderate UC, 1-week treatment with anaerobically prepared donor FMT compared with autologous FMT resulted in a higher likelihood of remission at 8 weeks. Further research is needed to assess longer-term maintenance of remission and safety.

Trial Registration: anzctr.org.au Identifier: ACTRN12613000236796.
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http://dx.doi.org/10.1001/jama.2018.20046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439766PMC
January 2019

Limited uptake of ulcerative colitis "treat-to-target" recommendations in real-world practice.

J Gastroenterol Hepatol 2018 Mar;33(3):599-607

School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, South Australia, Australia.

Background And Aims: A "treat-to-target" approach has been proposed for ulcerative colitis (UC), with a target of combined clinical and endoscopic remission. The aim of the study was to evaluate the extent to which proposed targets are achieved in real-world care, along with clinician perceptions and potential challenges.

Methods: A multicentre, retrospective, cross-sectional review of patients with UC attending outpatient services in South Australia was conducted. Clinical and objective assessment of disease activity (endoscopy, histology, and/or biomarkers) was recorded. A survey evaluated gastroenterologists' perceptions of treat to target in UC. Statistical analysis included logistic regression and Fisher's exact tests.

Results: Of 246 patients with UC, 61% were in clinical remission (normal bowel habit and no rectal bleeding), 35% in clinical and endoscopic remission (Mayo endoscopic sub-score ≤ 1), and 16% in concordant clinical, endoscopic, and histological (Truelove and Richards' Index) remission. Rather than disease-related factors (extent/activity), clinician-related factors dominated outcome. Hospital location and the choice of therapy predicted combined clinical and endoscopic remission (OR 3.6, 95% CI 1.6-8.7, P < 0.001; OR 3.3, 95% CI 1.1-12.5, P = 0.04, respectively). Clinicians used C-reactive protein more often than endoscopy as a biomarker for disease activity (75% vs 47%, P < 0.001). In the survey, 45/61 gastroenterologists responded, with significant disparity between clinician estimates of targets achieved in practice and real-world data (P < 0.001 for clinical and endoscopic remission).

Conclusions: Most patients with UC do not achieve composite clinical and endoscopic remission in "real-world" practice. Clinician uptake of proposed treat-to-target guidelines is a challenge to their implementation.
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http://dx.doi.org/10.1111/jgh.13923DOI Listing
March 2018

Opioidergic effects on enteric and sensory nerves in the lower GI tract: basic mechanisms and clinical implications.

Am J Physiol Gastrointest Liver Physiol 2016 09 28;311(3):G501-13. Epub 2016 Jul 28.

School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, South Australia, Australia; Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, South Australia, Australia; and.

Opioids are one of the most prescribed drug classes for treating acute pain. However, chronic use is often associated with tolerance as well as debilitating side effects, including nausea and dependence, which are mediated by the central nervous system, as well as constipation emerging from effects on the enteric nervous system. These gastrointestinal (GI) side effects limit the usefulness of opioids in treating pain in many patients. Understanding the mechanism(s) of action of opioids on the nervous system that shows clinical benefit as well as those that have unwanted effects is critical for the improvement of opioid drugs. The opioidergic system comprises three classical receptors (μ, δ, κ) and a nonclassical receptor (nociceptin), and each of these receptors is expressed to varying extents by the enteric and intestinal extrinsic sensory afferent nerves. The purpose of this review is to discuss the role that the opioidergic system has on enteric and extrinsic afferent nerves in the lower GI tract in health and diseases of the lower GI tract, particularly inflammatory bowel disease and irritable bowel syndrome, and the implications of opioid treatment on clinical outcomes. Consideration is also given to emerging developments in our understanding of the immune system as a novel source of endogenous opioids and the mechanisms underlying opioid tolerance, including the potential influence of opioid receptor splice variants and heteromeric complexes.
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http://dx.doi.org/10.1152/ajpgi.00442.2015DOI Listing
September 2016

Establishing a Fecal Microbiota Transplant Service for the Treatment of Clostridium difficile Infection.

Clin Infect Dis 2016 Apr 30;62(7):908-14. Epub 2015 Nov 30.

Department of Gastroenterology & School of Medicine, University of Adelaide at Royal Adelaide Hospital.

Recurrent or refractory Clostridium difficile infection (CDI) has become an increasing problem in the past decade. Fecal microbiota transplant (FMT) is a highly efficacious treatment for recurrent CDI; however, a number of technical, logistical, and regulatory issues have hampered the development of an FMT capability at many hospitals. The development of a frozen stool bank of screened donor stool is an important step in the standardization of the procedure. This gives clinicians rapid access to thoroughly screened donor stool when needed, without the ethical and logistical problems associated with patient-selected donors. We describe the practicalities of establishing such a service using a stool bank of prescreened donor stool including detail regarding donor recruitment and screening, stool preparation, and delivery of the FMT.
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http://dx.doi.org/10.1093/cid/civ994DOI Listing
April 2016

Role of FDG-PET in surgical management of patients with colorectal liver metastases.

ANZ J Surg 2004 Aug;74(8):646-52

University of Adelaide Department of Surgery, The Queen Elizabeth Hospital, Woodville, SA 5011, Australia.

Background: [(18)F]-fluorodeoxyglucose positron emission tomography (FDG-PET) is reported to change the management in 20-56% of patients with recurrent or metastatic colorectal cancer. It is not clear if FDG-PET has a role in all such patients or only a subgroup. The aim of the present study was to assess the influence of FDG-PET on the surgical management of patients with known or suspected colorectal liver metastases.

Methods: Patients undergoing FDG-PET for investigation of known or suspected colorectal liver metastases were identified from a South Australian database. Case notes were reviewed retrospectively to determine the influence of FDG-PET findings on patient management. Findings from FDG-PET scanning were compared with findings from conventional diagnostic investigations and operative findings.

Results: Overall, in four of 16 patients (25%) management was influenced by FDG-PET findings. FDG-PET altered management in four of eight (50%) patients with non-diagnostic liver lesions on computed tomography (CT) or with elevated carcinoembryonic antigen levels but no liver lesion on CT. In all eight patients with CT diagnosed resectable liver metastases, the addition of FDG-PET did not influence the management.

Conclusions: The findings support the use of FDG-PET in the assessment of selected patients with suspected colorectal liver metastases and equivocal findings on conventional diagnostic investigation.
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http://dx.doi.org/10.1111/j.1445-1433.2004.02948.xDOI Listing
August 2004