Publications by authors named "Emily K Wright"

21 Publications

  • Page 1 of 1

A Single Educational Intervention Improves Pregnancy-Related Knowledge and Emotional Health Among Women With IBD Who Are Pregnant or Wish to Conceive.

Inflamm Bowel Dis 2021 Mar 11. Epub 2021 Mar 11.

Department of Gastroenterology, St. Vincent's Hospital, Melbourne, Australia.

Background: There is considerable interest in improving the education and care of women with inflammatory bowel disease (IBD) to improve pregnancy outcomes. Despite increased awareness, not all women with IBD have access to pregnancy-related education and the quality of counseling is variable. We aimed to assess the effectiveness of a simple educational intervention for improving pregnancy-related knowledge and to evaluate the effect of education on patient outcomes including anxiety, depression, and quality of life in women with IBD.

Methods: This prospective study of women with IBD who were pregnant or planning a pregnancy evaluated the effectiveness of a single gastroenterologist-led educational intervention in improving pregnancy-related knowledge, measured using the Crohn's and Colitis Pregnancy Knowledge score 1 month postintervention. Secondary outcomes included the effect on anxiety and depression, quality of life, medication adherence, and patient satisfaction.

Results: One hundred women with IBD were recruited. Fifty percent were pregnant at the time of the intervention. Baseline knowledge scores were similar independent of the patients' pregnancy status or whether they had previously received counseling from their gastroenterologist. Median Crohn's and Colitis Pregnancy Knowledge scores postintervention (n = 82) were higher than preintervention scores (14/17 vs 10/17; P < 0.001). In addition, 32% of patients had poor knowledge at baseline (score ≤7/17), compared to only 5% after the intervention (P < 0.001). There was a significant improvement in total anxiety and depression and quality of life scores postintervention. Medication adherence and patient satisfaction were excellent.

Conclusions: Uptake of this gastroenterologist-led educational intervention has the potential to improve pregnancy knowledge, promote medication adherence, and enhance quality of life for women with IBD globally.
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http://dx.doi.org/10.1093/ibd/izab021DOI Listing
March 2021

Standardisation of intestinal ultrasound scoring in clinical trials for luminal Crohn's disease.

Aliment Pharmacol Ther 2021 04 28;53(8):873-886. Epub 2021 Feb 28.

Calgary, AB, Canada.

Background: Intestinal ultrasound (IUS) is a valuable tool for assessment of Crohn's disease (CD). However, there is no widely accepted luminal disease activity index.

Aims: To identify appropriate IUS protocols, indices, items, and scoring methods for measurement of luminal CD activity and integration of IUS in CD clinical trials.

Methods: An expert international panel of adult and paediatric gastroenterologists (n = 15) and radiologists (n = 3) rated the appropriateness of 120 statements derived from literature review and expert opinion (scale of 1-9) using modified RAND/UCLA methodology. Median panel scores of 1 to ≤3.5, >3.5 to <6.5 and ≥6.5 to 9 were considered inappropriate, uncertain and appropriate ratings respectively. The statement list and survey results were discussed prior to voting.

Results: A total of 91 statements were rated appropriate with agreement after two rounds of voting. Items considered appropriate measures of disease activity were bowel wall thickness (BWT), vascularity, stratification and mesenteric inflammatory fat. There was uncertainty if any of the existing IUS disease activity indices were appropriate for use in CD clinical trials. Appropriate trial applications for IUS included patient recruitment qualification when diseased segments cannot be adequately assessed by ileocolonoscopy and screening for exclusionary complications. At outcome assessment, remission endpoints including BWT and vascularity, with or without mesenteric inflammatory fat, were considered appropriate. Components of an ideal IUS disease activity index were identified based upon panel discussions.

Conclusions: The panel identified appropriate component items and applications of IUS for CD clinical trials. Empiric evidence, and development and validation of an IUS disease activity index are needed.
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http://dx.doi.org/10.1111/apt.16288DOI Listing
April 2021

Maternal thiopurine metabolism during pregnancy in inflammatory bowel disease and clearance of thiopurine metabolites and outcomes in exposed neonates.

Aliment Pharmacol Ther 2021 04 19;53(7):810-820. Epub 2021 Feb 19.

Melbourne, Vic., Australia.

Background: Azathioprine and mercaptopurine are considered safe during pregnancy. However, the pharmacokinetic effects of pregnancy on thiopurine metabolism are undefined.

Aims: To characterise thiopurine metabolism in pregnancy and measure infant metabolite levels and outcomes.

Methods: Women with IBD who were taking a thiopurine and pregnant or trying to conceive were recruited. Maternal thiopurine metabolites were measured pre-conception, in each trimester, at delivery and post-partum. Infant metabolite levels, full blood examination and liver function testing were performed at birth, and repeated until levels undetectable and haematological and biochemical abnormalities resolved.

Results: Forty patients were included with measurements on at least two occasions, and two with only mother-baby levels at delivery. The median maternal 6-TGN level dropped in the second trimester compared with post-partum (179.0 vs 323.5 pmol/8 × 10 RBCs, P < 0.001) and the median 6-MMP level increased in the second trimester compared with post-partum (1103.0 vs 329.5 pmol/8 × 10 RBCs, P < 0.01). At delivery, the median 6-TGN level was lower in infants (n = 20) than mothers (78.5 vs 217 pmol/8 × 10 RBCs) (P < 0.001). Metabolites were not detected at 6 weeks in any infants. Anaemia was not seen, but thrombocytosis and abnormal liver biochemistry were detected in 80% of infants from 6 weeks, which gradually improved.

Conclusions: 6-TGN levels decrease and 6-MMP levels increase in the second trimester of pregnancy. Infants are exposed to thiopurine metabolites at low levels with clearance by 6 weeks and no anaemia. The cause of infant thrombocytosis and abnormal liver biochemistry in the absence of metabolites is unclear.
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http://dx.doi.org/10.1111/apt.16294DOI Listing
April 2021

Efficacy of drug and endoscopic treatment of Crohn's disease strictures: A systematic review.

J Gastroenterol Hepatol 2021 Feb 27;36(2):344-361. Epub 2020 Dec 27.

Department of Gastroenterology, St Vincent's Hospital, Fitzroy, Victoria, Australia.

Background And Aims: Strictures are the commonest complication in Crohn's disease. Surgery and endoscopic dilation are the mainstays of treatment, while drug therapy has often been considered contraindicated. The benefit of nonsurgical treatments, particularly drug and endoscopic therapy, need to be defined.

Methods: Ovid MEDLINE, Embase, Emcare, PsycINFO, CINAHL and the Cochrane Library (inception until August 30, 2019) were searched. Studies with ≥ 10 patients with Crohn's disease strictures, reporting on outcomes following medication or endoscopic treatment, were included.

Results: Of 3480 records, 85 studies met inclusion criteria and formed the basis of this analysis. Twenty-five studies assessed drug therapy; none were randomized trials. Despite study heterogeneity anti-tumor necrosis factor (TNF) therapy appeared effective, with 50% of patients avoiding surgery after 4 years of follow up. No other drug therapy was of demonstrable benefit. Sixty studies assessed endoscopic therapy including 56 on endoscopic balloon dilation, two assessed needle knife stricturotomy, and two stent insertion. Dilation was equally effective for de novo and anastomotic strictures ≤ 5 cm in length, with most studies reporting a subsequent surgical rate of 30% to 50%. Repeat dilation was required in approximately half of all patients.

Conclusions: Anti-TNF drug therapy and endoscopic balloon dilation are effective strategies for avoiding surgery in patients with stricturing Crohn's disease. Additional endoscopic therapies require further evaluation. Early data suggest that combining these therapies may provide greater benefit than individual therapies. Optimization of current drug and endoscopic therapy, and the incorporation of newer therapies, are needed for stricturing Crohn's disease.
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http://dx.doi.org/10.1111/jgh.15330DOI Listing
February 2021

Infliximab, adalimumab and vedolizumab concentrations across pregnancy and vedolizumab concentrations in infants following intrauterine exposure.

Aliment Pharmacol Ther 2020 11 27;52(10):1551-1562. Epub 2020 Sep 27.

Fitzroy, VIC, Australia.

Background: The impact of pregnancy on levels of biologic agents in patients with IBD is undefined and time to elimination in vedolizumab-exposed infants is unknown.

Aims: To determine the effect of pregnancy on infliximab, adalimumab and vedolizumab levels and to study infant vedolizumab clearance METHODS: In a prospective observational study, maternal drug levels were measured pre-conception, in each trimester, at delivery and postpartum. The association between drug levels and gestation in weeks was assessed using generalised estimating equation modelling. Infant vedolizumab levels were performed at birth (cord blood), 6 weeks and 3 months or until undetectable.

Results: We included 50 IBD patients (23 on infliximab, 15 on adalimumab and 12 on vedolizumab) with at least two intrapartum observations, plus 5 patients on vedolizumab with only mother and baby samples at delivery. Modelling showed no change in adalimumab levels, an increase in infliximab levels of 0.16 (95% CI 0.08-0.24) µg/L/week (P < 0.001) and a decrease of 0.18 (95% CI: -0.33 to -0.02) µg/L/week (P = 0.03) for vedolizumab. In 17 mother-baby pairs, median infant vedolizumab levels at birth were lower than maternal levels (P < 0.05) with an infant:maternal ratio of 0.7 (IQR 0.5-0.9). Vedolizumab was undetectable between 15 and 16 weeks of age in all 12 infants completing follow-up testing.

Conclusions: During pregnancy, adalimumab levels remain stable, while infliximab levels increase and vedolizumab levels decrease. However, the increments were small suggesting that intrapartum therapeutic drug monitoring and dose adjustment are not indicated. Unlike infliximab and adalimumab, infant vedolizumab levels are lower in cord blood than in mothers and appear to clear rapidly.
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http://dx.doi.org/10.1111/apt.16102DOI Listing
November 2020

Luminal microbiota related to Crohn's disease recurrence after surgery.

Gut Microbes 2020 11 21;11(6):1713-1728. Epub 2020 Jun 21.

Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, Australia and Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge , Cambridge, UK.

Background: Microbial factors are likely to be involved in the recurrence of Crohn's disease (CD) after bowel resection. We investigated the luminal microbiota before and longitudinally after surgery, in relation to disease recurrence, using 16S metagenomic techniques.

Methods: In the prospective Post-Operative Crohn's Endoscopic Recurrence (POCER) study, fecal samples were obtained before surgery and 6, 12, and 18 months after surgery from 130 CD patients. Endoscopy was undertaken to detect disease recurrence, defined as Rutgeerts score ≥i2, at 6 months in two-thirds of patients and all patients at 18 months after surgery. The V2 region of the 16S rRNA gene was sequenced using Illumina MiSeq. Cluster analysis was performed at family level, assessing microbiome community differences between patients with and without recurrence.

Results: Six microbial cluster groups were identified. The cluster associated with maintenance of remission was enriched for the family [adjusted OR 0.47 (0.27-0.82), = .007]. The OTU diversity of within this cluster was significantly greater than in all other clusters. The cluster enriched for was associated with an increased risk of disease recurrence [adjusted OR 6.35 (1.24-32.44), = .026]. OTU diversity of within this cluster was significantly greater than in other clusters.

Conclusions: Luminal bacterial communities are associated with protection from, and the occurrence of, Crohn's disease recurrence after surgery. Recurrence may relate to a higher abundance of facultatively anaerobic pathobionts from the family. The ecologic change of depleted , a genus of butyrate-producing bacteria, may permit expansion of through luminal environmental perturbation.
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http://dx.doi.org/10.1080/19490976.2020.1778262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524166PMC
November 2020

Monitoring Inflammatory Bowel Disease in Pregnancy Using Gastrointestinal Ultrasonography.

J Crohns Colitis 2020 Oct;14(10):1405-1412

Department of Gastroenterology, St Vincent's Hospital, Melbourne, VIC, Australia.

Background And Aims: Inflammatory bowel disease [IBD] affects women during their childbearing years. Gastrointestinal ultrasonography [GIUS] accurately identifies disease activity in non-pregnant patients with IBD. The utility of GIUS in pregnancy has not been established. We aimed to determine the feasibility and accuracy of GIUS in the assessment of IBD during pregnancy progression.

Methods: A multicentre observational study of women with IBD undergoing GIUS during pregnancy. Clinicians assessed the adequacy of bowel views and disease activity in four colonic segments and the terminal ileum. Location[s] in which views were impeded by the uterus were documented. GIUS disease activity [bowel wall thickness >3 mm] was compared with biochemical disease activity [faecal calprotectin >100 μg/g].

Results: Ninety patients and 127 GIUS examinations were included [median gestation 19 weeks, range 4-33]. Adequate colonic views were obtained in 116/127 [91%] scans. Adequate ileal views were obtained in 62/67 [93%] scans <20 weeks and 30/51 [59%] scans at 20-26 weeks. There was a positive correlation between bowel wall thickness and calprotectin [r = 0.26, p = 0.03]. GIUS delivered a specificity of 83%, sensitivity of 74%, and negative predictive value of 90% compared with calprotectin.

Conclusions: GIUS is a feasible and accurate modality for monitoring IBD in pregnancy. Adequate GIUS views of the colon and terminal ileum can be obtained in the majority of patients up to 20 weeks of gestation. Beyond 20 weeks, GIUS provides good views of the colon but the terminal ileum becomes difficult to assess.
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http://dx.doi.org/10.1093/ecco-jcc/jjaa082DOI Listing
October 2020

Magnetic resonance enterography for predicting the clinical course of Crohn's disease strictures.

J Gastroenterol Hepatol 2020 Jun 11;35(6):980-987. Epub 2019 Nov 11.

Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia.

Background And Aims: Strictures are the most common Crohn's disease complication, but their natural history is unknown. This study aimed to characterize inflammation, predict prognosis, and understand the impact of drug therapy using magnetic resonance enterography (MRE).

Methods: Patients with a stricture diagnosed on MRE over a 5-year period were reviewed for MRE disease extent and inflammation, clinical course, C-reactive protein, response to anti-TNF therapy, endoscopic dilatation, hospitalization, and surgery.

Results: 136 patients had 235 strictures (77, one and 59, ≥ 2 strictures).

Treatment: 46% of patients underwent surgery after a median 6 months; median follow-up for those not requiring surgery was 41 months. Predictors of surgery: Hospitalization because of obstruction predicted subsequent surgery (OR 2.50; 95% CI 1.06-5.90) while anti-TNF therapy commenced at stricture diagnosis was associated with a reduced risk (OR 0.23; 95% CI 0.05-0.99). MRE characteristics associated with surgery were proximal bowel dilatation ≥ 30-mm diameter (OR 2.98; 95% CI 1.36-6.55), stricture bowel wall thickness ≥ 10-mm (OR 2.42; 95% CI 1.11-5.27), and stricture length > 5-cm (OR 2.56; 95% CI 1.21-5.43). 81% of patients with these three adverse MRE features required surgery versus 17% if none were present (P < 0.001). Accuracy for these three MRE variables predicting surgery was high (AUC 0.76).

Conclusion: Magnetic resonance enterography findings in Crohn's disease strictures are highly predictive of the disease course and the need for future surgery. MRE may also identify who would benefit from treatment intensification. Anti-TNF therapy is associated with reduced risk of surgery and appears to alter the natural history of this complication.
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http://dx.doi.org/10.1111/jgh.14908DOI Listing
June 2020

Management of inflammatory bowel disease.

Med J Aust 2018 09;209(7):318-323

St Vincent's Hospital Melbourne, Melbourne, VIC.

Australia has one of the highest incidence rates of inflammatory bowel disease (IBD) in the world. Early diagnosis and treatment for IBD is critical. For Crohn disease, in particular, this may change the natural history of disease and reduce disability. Faecal calprotectin is a sensitive test that can be used by primary care physicians to assist in determining which patients with gastrointestinal symptoms may have IBD. This allows for prompt identification of patients who may benefit from endoscopy. Regular re-evaluation of disease status with strategies that can safely, readily and reliably detect the presence of inflammation with faecal biomarkers and imaging is important. To avoid the risks of cumulative radiation exposure, magnetic resonance imaging and/or intestinal ultrasound, rather than computed tomography scanning, should be performed when possible. Drug treatments for IBD now include five biological drugs listed by the Pharmaceutical Benefits Scheme: adalimumab, infliximab, golimumab, vedolizumab and ustekinumab. Such developments offer the possibility for improved disease control in selected patients.
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http://dx.doi.org/10.5694/mja17.01001DOI Listing
September 2018

Anti-TNF Therapeutic Drug Monitoring in Postoperative Crohn's Disease.

J Crohns Colitis 2018 May;12(6):653-661

Department of Gastroenterology, St Vincent's Hospital and University of Melbourne, Melbourne, Australia.

Background: Anti-TNF prevents postoperative Crohn's disease recurrence in most patients but not all. This study aimed to define the relationship between adalimumab pharmacokinetics, maintenance of remission and recurrence.

Methods: As part of a study of postoperative Crohn's disease management, some patients undergoing resection received prophylactic postoperative adalimumab. In these patients, serum and fecal adalimumab concentration and serum anti-adalimumab antibodies [AAAs] were measured at 6, 12 and 18 months postoperatively. Levels of Crohn's disease activity index [CDAI], C-reactive protein [CRP] and fecal calprotectin [FC] were assessed at 6 and 18 months postoperatively. Body mass index and smoking status were recorded. A colonoscopy was performed at 6 and/or 18 months.

Results: Fifty-two patients [32 on monotherapy and 20 on combination therapy with thiopurine] were studied. Adalimumab concentration did not differ significantly between patients in endoscopic remission vs recurrence [Rutgeerts ≥ i2] [9.98µg/mL vs 8.43 µg/mL, p = 0.387]. Patients on adalimumab monotherapy had a significantly lower adalimumab concentration [7.89 µg/mL] than patients on combination therapy [11.725 µg/mL] [p = 0.001], and were significantly more likely to have measurable AAA [31% vs 17%, p = 0.001]. Adalimumab concentrations were lower in patients with detectable AAA compared with those without [3.59 µg/mL vs 12.0 µg/mL, p < 0.001]. Adalimumab was not detected in fecal samples. Adalimumab serum concentrations were lower in obese patients compared with in non-obese patients [p = 0.046].

Conclusion: Adalimumab concentration in patients treated with adalimumab to prevent symptomatic endoscopic recurrence postoperatively is, for most patients, well within the therapeutic window, and is not significantly lower in patients who develop recurrence compared with in those who remain in remission. Mechanisms of anti-TNF failure to prevent postoperative recurrence remain to be determined in these patients.
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http://dx.doi.org/10.1093/ecco-jcc/jjy003DOI Listing
May 2018

Serologic antibodies in relation to outcome in postoperative Crohn's disease.

J Gastroenterol Hepatol 2017 Jun;32(6):1195-1203

Department of Gastroenterology, St Vincent's Hospital, Melbourne, Victoria, Australia.

Background And Aim: Disease recurs frequently after Crohn's disease resection. The role of serological antimicrobial antibodies in predicting recurrence or as a marker of recurrence has not been well defined.

Methods: A total of 169 patients (523 samples) were prospectively studied, with testing peri-operatively, and 6, 12 and 18 months postoperatively. Colonoscopy was performed at 18 months postoperatively. Serologic antibody presence (perinuclear anti-neutrophil cytoplasmic antibody [pANCA], anti-Saccharomyces cerevisiae antibodies [ASCA] IgA/IgG, anti-OmpC, anti-CBir1, anti-A4-Fla2, anti-Fla-X) and titer were tested. Quartile sum score (range 6-24), logistic regression analysis, and correlation with phenotype, smoking status, and endoscopic outcome were assessed.

Results: Patients with ≥ 2 previous resections were more likely to be anti-OmpC positive (94% vs 55%, ≥ 2 vs < 2, P = 0.001). Recurrence at 18 months was associated with anti-Fla-X positivity at baseline (49% vs 29%; positive vs negative, P = 0.033) and 12 months (52% vs 31%, P = 0.04). Patients positive (n = 28) for all four antibacterial antibodies (anti-CBir1, anti-OmpC, anti-A4-Fla2, and anti-Fla-X) at baseline were more likely to experience recurrence at 18 months than patients negative (n = 32) for all four antibodies (82% vs 18%, P = 0.034; odds ratio 6.4, 95% confidence interval 1.16-34.9). The baseline quartile sum score for all six antimicrobial antibodies was higher in patients with severe recurrence (Rutgeert's i3-i4) at 18 months, adjusted for clinical risk factors (odds ratio 1.16, 95% confidence interval 1.01-1.34, P = 0.039). Smoking affected antibody status.

Conclusions: Anti-Fla-X and presence of all anti-bacterial antibodies identifies patients at higher risk of early postoperative Crohn's disease recurrence. Serologic screening pre-operatively may help identify patients at increased risk of recurrence.
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http://dx.doi.org/10.1111/jgh.13677DOI Listing
June 2017

Microbial Factors Associated with Postoperative Crohn's Disease Recurrence.

J Crohns Colitis 2017 Feb 27;11(2):191-203. Epub 2016 Jul 27.

Enteric Virus Group, Murdoch Children's Research Institute, Parkville, VIC, Australia.

Background And Aims: The intestinal microbiota is a key antigenic driver in Crohn's disease [CD]. We aimed to identify changes in the gut microbiome associated with, and predictive of, disease recurrence and remission.

Methods: A total of 141 mucosal biopsy samples from 34 CD patients were obtained at surgical resection and at colonoscopy 6 and/or 18 months postoperatively; 28 control samples were obtained: 12 from healthy patients [healthy controls] and 16 from hemicolectomy patients [surgical controls]. Bacterial 16S ribosomal profiling was performed using the Illumina MiSeq platform.

Results: CD was associated with reduced alpha diversity when compared with healthy controls but not surgical controls [p < 0.001 and p = 0.666, respectively]. Beta diversity [composition] differed significantly between CD and both healthy [p < 0.001] and surgical [p = 0.022] controls, but did not differ significantly between those with and without endoscopic recurrence. There were significant taxonomic differences between recurrence and remission. Patients experiencing recurrence demonstrated elevated Proteus genera [p = 0.008] and reduced Faecalibacterium [p< 0.001]. Active smoking was associated with elevated levels of Proteus [p = 0.013] postoperatively. Low abundance of Faecalibacterium [< 0.1%] and detectable Proteus in the postoperative ileal mucosa was associated with a higher risk of recurrence (odds ratio [OR] 14 [1.7-110], p = 0.013 and 13 [1.1-150], p = 0.039, respectively) when corrected for smoking. A model of recurrence comprising the presence of Proteus, abundance of Faecalibacterium, and smoking status showed moderate accuracy (area under the curve [AUC] 0.740, 95% confidence interval [CI] [0.69-0.79]).

Conclusions: CD is associated with a microbial signature distinct from health. Microbial factors and smoking independently influence postoperative CD recurrence. The genus Proteus may play a role in the development of CD.
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http://dx.doi.org/10.1093/ecco-jcc/jjw136DOI Listing
February 2017

Cost-effectiveness of Crohn's disease post-operative care.

World J Gastroenterol 2016 Apr;22(14):3860-8

Emily K Wright, Michael A Kamm, Peter Dr Cruz, Amy L Hamilton, Kathryn J Ritchie, Sally J Bell, Steven J Brown, William R Connell, Paul V Desmond, Department of Gastroenterology, St Vincent's Hospital, University of Melbourne, Fitzroy VIC 3065, Melbourne, Australia.

Aim: To define the cost-effectiveness of strategies, including endoscopy and immunosuppression, to prevent endoscopic recurrence of Crohn's disease following intestinal resection.

Methods: In the "POCER" study patients undergoing intestinal resection were treated with post-operative drug therapy. Two thirds were randomized to active care (6 mo colonoscopy and drug intensification for endoscopic recurrence) and one third to drug therapy without early endoscopy. Colonoscopy at 18 mo and faecal calprotectin (FC) measurement were used to assess disease recurrence. Administrative data, chart review and patient questionnaires were collected prospectively over 18 mo.

Results: Sixty patients (active care n = 43, standard care n = 17) were included from one health service. Median total health care cost was $6440 per patient. Active care cost $4824 more than standard care over 18 mo. Medication accounted for 78% of total cost, of which 90% was for adalimumab. Median health care cost was higher for those with endoscopic recurrence compared to those in remission [$26347 (IQR 25045-27485) vs $2729 (IQR 1182-5215), P < 0.001]. FC to select patients for colonoscopy could reduce cost by $1010 per patient over 18 mo. Active care was associated with 18% decreased endoscopic recurrence, costing $861 for each recurrence prevented.

Conclusion: Post-operative management strategies are associated with high cost, primarily medication related. Calprotectin use reduces costs. The long term cost-benefit of these strategies remains to be evaluated.
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http://dx.doi.org/10.3748/wjg.v22.i14.3860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4814750PMC
April 2016

Calprotectin or Lactoferrin: Do They Help.

Authors:
Emily K Wright

Dig Dis 2016 16;34(1-2):98-104. Epub 2016 Mar 16.

Department of Gastroenterology, St. Vincent's Hospital, The University of Melbourne, Melbourne, Australia.

Background: The diagnosis and monitoring of inflammatory bowel disease (IBD) has traditionally relied on clinical assessment, serum markers of inflammation and endoscopic examination. Fecal biomarkers such as calprotectin (FC) and lactoferrin (FL) are predominantly derived from neutrophils, are easily detectable in the feces and are now established as valuable markers of intestinal inflammation. In recent years, a 'treat to target' concept has emerged for the management of IBD. Adequate control of inflammation in IBD at a biochemical level is quickly becoming an important target in IBD management.

Key Messages: Fecal biomarkers have been shown to be significantly and consistently increased in both adult and pediatric patients with IBD versus those without IBD. Fecal biomarkers are therefore useful in determining those patients with gastrointestinal symptoms who are likely to benefit from colonoscopy versus those in whom colonoscopy is likely to be normal. Fecal biomarkers correlate significantly with endoscopic disease in both Crohn's disease and ulcerative colitis. Suggested cutoffs for FC for endoscopically active disease in IBD range from 50 to 280 μg/g. Fecal biomarkers reflect the success of treatment intensification and can help predict clinical relapse. Both FC and FL are accurate in the detection of postoperative endoscopic recurrence of Crohn's disease, and FC may be clinically useful in predicting those patients with acute severe ulcerative colitis who may progress to colectomy. There are limitations to these fecal tests including a false positive rate and intra-individual variability.

Conclusions: This review focuses on the role of fecal biomarkers in the diagnosis, monitoring and management of IBD and how best to interpret results. We will discuss the emerging role of these biomarkers in the IBD management landscape including FC-guided drug dosing and the development of home-based testing and e-health applications. Fecal biomarker results must always be interpreted in a clinical context. Endoscopic assessment remains the gold standard for diagnosis and monitoring of IBD.
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http://dx.doi.org/10.1159/000442935DOI Listing
December 2016

Comparison of Fecal Inflammatory Markers in Crohn's Disease.

Inflamm Bowel Dis 2016 May;22(5):1086-94

*Department of Gastroenterology, St Vincent's Hospital and University of Melbourne, Melbourne, Australia; †Imperial College London, London, United Kingdom; ‡Department of Surgery, University of Otago, Christchurch, New Zealand; §School of Women's and Children's Health, University of NSW, Sydney, Australia; ‖Department of Paediatrics, University of Otago, Christchurch, New Zealand; ¶Melbourne EpiCentre, University of Melbourne and Melbourne Health, Melbourne, Australia; and **Department of Medicine, University of Otago, Christchurch, New Zealand.

Background: Fecal biomarkers are used increasingly to monitor Crohn's disease (CD). However, the relative accuracy of different markers in identifying inflammation has been poorly evaluated. We evaluated fecal calprotectin (FC), lactoferrin (FL), and S100A12 (FS) using endoscopic validation in a prospective study of the progression of CD after intestinal resection.

Methods: Data were collected from 135 participants in a prospective, randomized, controlled trial aimed at preventing postoperative CD recurrence. Three hundred nineteen stool samples were tested for FC, FL, and FS preoperatively and 6, 12, and 18 months after resection. Colonoscopy was performed at 6 and/or 18 months. Endoscopic recurrence was assessed blindly using the Rutgeerts score. C-reactive protein (CRP) and Crohn's Disease Activity Index (CDAI) were assessed.

Results: FC, FL, and FS concentrations were elevated preoperatively (median: 1347, 40.9, and 8.4 μg/g, respectively). At 6 months postoperatively, marker concentrations decreased (166, 3.0, 0.9 μg/g) and were higher in recurrent disease than remission (275 versus 72 μg/g, P < 0.001; 5.7 versus 1.6 μg/g, P = 0.007; 2.0 versus 0.8 μg/g, P = 0.188). FC > 135 μg/g, FL > 3.4 μg/g, and FS > 10.5 μg/g indicated endoscopic recurrence (score ≥ i2) with a sensitivity, specificity, and negative predictive value (NPV) of 0.87, 0.66, and 91%; 0.70, 0.68, and 81%; 0.91, 0.12, and 71%, respectively. FC and FL correlated significantly with the presence and severity of endoscopic recurrence, whereas FS, CRP and CDAI did not.

Conclusions: FC was the optimal fecal marker for monitoring disease activity in postoperative CD and was superior to CRP and CDAI. FL offered modest sensitivity for detecting recurrent disease, whereas S100A12 was sensitive but had low specificity and NPV.
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http://dx.doi.org/10.1097/MIB.0000000000000671DOI Listing
May 2016

Transperineal ultrasonography in perianal Crohn disease: A valuable imaging modality.

Can J Gastroenterol Hepatol 2015 Nov-Dec;29(8):445-7. Epub 2015 May 21.

Aims of treatment for Crohn disease have moved beyond the resolution of clinical symptoms to objective end points including endoscopic and radiological normality. Regular re-evaluation of disease status to safely, readily and reliably detect the presence of inflammation and complications is paramount. Improvements in sonographic technology over recent years have facilitated a growing enthusiasm among radiologists and gastroenterologists in the use of ultrasound for the assessment of inflammatory bowel disease. Transabdominal intestinal ultrasound is accurate, affordable and safe for the assessment of luminal inflammation and complications in Crohn disease, and can be performed with or without the use of intravenous contrast enhancement. Perianal fistulizing disease is a common, complex and often treatment-refractory complication of Crohn disease, which requires regular radiological monitoring. Endoanal ultrasound is invasive, uncomfortable and yields limited assessment of the perineal region. Although magnetic resonance imaging of the pelvis is established, timely access may be a problem. Transperineal ultrasound has been described in small studies, and is an accurate, painless and cost-effective method for documenting perianal fluid collections, fistulas and sinus tracts. In the present article, the authors review the literature regarding perineal ultrasound for the assessment of perianal Crohn disease and use case examples to illustrate its clinical utility.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4699595PMC
http://dx.doi.org/10.1155/2015/120123DOI Listing
September 2016

Impact of drug therapy and surgery on quality of life in Crohn's disease: a systematic review.

Inflamm Bowel Dis 2015 May;21(5):1187-94

*St Vincent's Hospital and University of Melbourne, Melbourne, Australia; and †Imperial College, London, United Kingdom.

Crohn's disease is associated with substantially impaired health-related quality of life (HRQoL). Even in the absence of active disease, patients with Crohn's disease report lower HRQoL, poorer function, and greater concerns, than those without disease. Achievement of disease remission in Crohn's disease, whether by pharmacological or surgical means, is associated with improved HRQoL, although the durability of the improvement seen after intestinal resection is uncertain because of the high rate of postoperative disease recurrence. This review focuses on the available literature on HRQoL in patients with Crohn's disease with an emphasis on the effects of intestinal resection and immunomodulatory therapy.
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http://dx.doi.org/10.1097/MIB.0000000000000271DOI Listing
May 2015

Effect of intestinal resection on quality of life in Crohn's disease.

J Crohns Colitis 2015 Jun 8;9(6):452-62. Epub 2015 Apr 8.

Department of Gastroenterology, St Vincent's Hospital and University of Melbourne, Melbourne, VIC, Australia.

Introduction: Patients with Crohn's disease have poorer health-related quality of life [HRQoL] than healthy individuals, even when in remission. Although HRQoL improves in patients who achieve drug-induced or surgically induced remission, the effects of surgery overall have not been well characterised.

Methods: In a randomised trial, patients undergoing intestinal resection of all macroscopically diseased bowel were treated with postoperative drug therapy to prevent disease recurrence. All patients were followed prospectively for 18 months. C-reactive protein [CRP], Crohn's Disease Activity Index [CDAI], and faecal calprotectin [FC] were measured preoperatively and at 6, 12, and 18 months. HRQoL was assessed with a general [SF36] and disease-specific [IBDQ] questionnaires at the same time points.

Results: A total of 174 patients were included. HRQoL was poor preoperatively but improved significantly [p < 0.001] at 6 months postoperatively. This improvement was sustained at 18 months. Females and smokers had a poorer HRQoL when compared with males and non-smokers, respectively. Persistent endoscopic remission, intensification of drug treatment at 6 months, and anti-tumour necrosis factor therapy were not associated with HRQoL outcomes different from those when these factors were not present. There was a significant inverse correlation between CDAI, [but not endoscopic recurrence, CRP, or FC] on HRQoL.

Conclusion: Intestinal resection of all macroscopic Crohn's disease in patients treated with postoperative prophylactic drug therapy is associated with significant and sustained improvement in HRQoL irrespective of type of drug treatment or endoscopic recurrence. HRQoL is lower in female patients and smokers. A higher CDAI, but not direct measures of active disease or type of drug therapy, is associated with a lower HRQoL.
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http://dx.doi.org/10.1093/ecco-jcc/jjv058DOI Listing
June 2015

Recent advances in characterizing the gastrointestinal microbiome in Crohn's disease: a systematic review.

Inflamm Bowel Dis 2015 Jun;21(6):1219-28

*Department of Gastroenterology, St Vincent's Hospital Melbourne, Australia; †Department of Pathology, University of Melbourne, Australia; ‡Imperial College, London, United Kingdom; and §Enteric Virus Group, Murdoch Children's Research Institute, Melbourne, Australia.

Background: The intestinal microbiota is involved in the pathogenesis of inflammatory bowel disease. A reduction in the diversity of the intestinal microbiota as well as specific taxonomic and functional shifts have been reported in Crohn's disease and may play a central role in the inflammatory process. The aim was to systematically review recent developments in the structural and functional changes observed in the gastrointestinal microbiome in patients with Crohn's Disease.

Results: Seventy-two abstracts were included in this review. The effects of host genetics, disease phenotype, and inflammatory bowel disease treatment on the gastrointestinal microbiome in Crohn's disease were reviewed, and taxonomic shifts in patients with early and established disease were described. The relative abundance of Bacteroidetes is increased and Firmicutes decreased in Crohn's disease compared with healthy controls. Enterobacteriaceae, specifically Eschericia coli, is enriched in Crohn's disease. Faecalibacterium prausnitzii is found at lower abundance in Crohn's disease and in those with postoperative recurrence. Observed functional changes include major shifts in oxidative stress pathways, a decrease in butanoate and propanoate metabolism gene expression, lower levels of butyrate, and other short-chain fatty acids, decreased carbohydrate metabolism, and decreased amino acid biosynthesis.

Conclusions: Changes in microbial composition and function have been described, although a causative role remains to be established. Larger, prospective, and longitudinal studies are required with deep interrogation of the microbiome if causality is to be determined, and refined microbial manipulation is to emerge as a focused therapy.
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http://dx.doi.org/10.1097/MIB.0000000000000382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4450900PMC
June 2015

Measurement of fecal calprotectin improves monitoring and detection of recurrence of Crohn's disease after surgery.

Gastroenterology 2015 May 22;148(5):938-947.e1. Epub 2015 Jan 22.

Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia; University of Melbourne, Melbourne, Australia.

Background & Aims: Crohn's disease (CD) usually recurs after intestinal resection; postoperative endoscopic monitoring and tailored treatment can reduce the chance of recurrence. We investigated whether monitoring levels of fecal calprotectin (FC) can substitute for endoscopic analysis of the mucosa.

Methods: We analyzed data collected from 135 participants in a prospective, randomized, controlled trial, performed at 17 hospitals in Australia and 1 hospital in New Zealand, that assessed the ability of endoscopic evaluations and step-up treatment to prevent CD recurrence after surgery. Levels of FC, serum levels of C-reactive protein (CRP), and Crohn's disease activity index (CDAI) scores were measured before surgery and then at 6, 12, and 18 months after resection of all macroscopic Crohn's disease. Ileocolonoscopies were performed at 6 months after surgery in 90 patients and at 18 months after surgery in all patients.

Results: Levels of FC were measured in 319 samples from 135 patients. The median FC level decreased from 1347 μg/g before surgery to 166 μg/g at 6 months after surgery, but was higher in patients with disease recurrence (based on endoscopic analysis; Rutgeerts score, ≥i2) than in patients in remission (275 vs 72 μg/g, respectively; P < .001). Combined 6- and 18-month levels of FC correlated with the presence (r = 0.42; P < .001) and severity (r = 0.44; P < .001) of CD recurrence, but the CRP level and CDAI score did not. Levels of FC greater than 100 μg/g indicated endoscopic recurrence with 89% sensitivity and 58% specificity, and a negative predictive value (NPV) of 91%; this means that colonoscopy could have been avoided in 47% of patients. Six months after surgery, FC levels less than 51 μg/g in patients in endoscopic remission predicted maintenance of remission (NPV, 79%). In patients with endoscopic recurrence at 6 months who stepped-up treatment, FC levels decreased from 324 μg/g at 6 months to 180 μg/g at 12 months and 109 μg/g at 18 months.

Conclusions: In this analysis of data from a prospective clinical trial, FC measurement has sufficient sensitivity and NPV values to monitor for CD recurrence after intestinal resection. Its predictive value might be used to identify patients most likely to relapse. After treatment for recurrence, the FC level can be used to monitor response to treatment. It predicts which patients will have disease recurrence with greater accuracy than CRP level or CDAI score.
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http://dx.doi.org/10.1053/j.gastro.2015.01.026DOI Listing
May 2015

Fecal biomarkers in the diagnosis and monitoring of Crohn's disease.

Inflamm Bowel Dis 2014 Sep;20(9):1668-77

*St. Vincent's Hospital and University of Melbourne, Melbourne, Australia; and †Christchurch Hospital and University of Otago, Christchurch, New Zealand.

The diagnosis and monitoring of Crohn's disease has traditionally relied on clinical assessment, serum markers of inflammation, and endoscopic examination. Fecal biomarkers such as calprotectin, lactoferrin, and S100A12 are predominantly derived from neutrophils, are easily detectable in the feces, and are emerging as valuable markers of intestinal inflammation. This review focuses on the role of fecal biomarkers in the diagnosis and monitoring of Crohn's disease, in particular how these biomarkers change with disease activity and remission, how they can be used to monitor the response to medical therapy, their value in predicting clinical relapse, and their role in monitoring the postoperative state.
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http://dx.doi.org/10.1097/MIB.0000000000000087DOI Listing
September 2014