Publications by authors named "William R Connell"

17 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

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

Anti-TNF Therapy in Pregnant Women With Inflammatory Bowel Disease: Effects of Therapeutic Strategies on Disease Behavior and Birth Outcomes.

Inflamm Bowel Dis 2020 01;26(1):93-102

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

Background: Active inflammatory bowel disease (IBD) adversely affects pregnancy outcomes. Little is known about the risk of relapse after stopping anti-tumor necrosis factor (anti-TNF) treatment during pregnancy. We assessed the risk of relapse before delivery in women who discontinued anti-TNF treatment before gestational week (GW) 30, predictors of reduced infant birth weight, a marker associated with long-term adverse outcomes, and rates and satisfaction with counseling.

Methods: Pregnant women with IBD receiving anti-TNF treatment were prospectively invited to participate in an electronic questionnaire carried out in 22 hospitals in Denmark, Australia, and New Zealand from 2011 to 2015. Risk estimates were calculated, and birth weight was investigated using t tests and linear regression.

Results: Of 175 women invited, 153 (87%) responded. In women in remission, the relapse rate did not differ significantly between those who discontinued anti-TNF before GW 30 (1/46, 2%) compared with those who continued treatment (8/74, 11%; relative risk, 0.20; 95% confidence interval [CI], 0.02 to 1.56; P = 0.08). Relapse (P = 0.001) and continuation of anti-TNF therapy after GW 30 (P = 0.007) were independently associated with reduced mean birth weight by 367 g (95% CI, 145 to 589 g; relapse) and 274 g (95% CI, 77 to 471 g; anti-TNF exposure after GW 30). Of 134 (88%) women who received counseling, 116 (87%) were satisfied with the information provided.

Conclusions: To minimize fetal exposure in women in remission, discontinuation of anti-TNF before GW 30 seems safe. Relapse and continuation of anti-TNF therapy after GW 30 were each independently associated with lower birth weight, although without an increased risk for birth weight <2500 g. Most women received and were satisfied with counseling.
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http://dx.doi.org/10.1093/ibd/izz110DOI Listing
January 2020

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

Predicting response after infliximab salvage in acute severe ulcerative colitis.

J Gastroenterol Hepatol 2018 Jul 27;33(7):1347-1352. Epub 2018 Feb 27.

Department of Gastroenterology, Austin Health, Melbourne, Australia.

Background And Aim: Acute severe ulcerative colitis (ASUC) is a medical emergency requiring prompt therapeutic intervention. Although infliximab has been used as salvage therapy for over 15 years, clinical predictors of treatment success are lacking. We performed a retrospective analysis to identify factors that predict colectomy and may guide dose intensification.

Methods: Fifty-four hospitalized patients received infliximab for ASUC at seven Australian centers (April 2014-May 2015). Follow-up was over 12 months. The data were primarily analyzed for predictors of colectomy. Accelerated (AI) versus standard (SI) infliximab induction strategies were also compared.

Results: Of 54 patients identified, the overall colectomy rate was 15.38% (8/52) at 3 months and 26.92% (14/52) at 12 months. Two patients were lost to follow-up. There was a numerically higher colectomy rate in those treated with AI compared with SI (P = 0.3); however, those treated with AI had more severe biochemical disease. A C-reactive protein (CRP)/albumin ratio cut-off of 0.37 post-commencement of infliximab and before discharge was a significant predictor of colectomy with an area under receiver operating curve of 0.73. Pretreatment CRP and albumin levels were not predictive of colectomy. A Mayo Endoscopic Score of 2 had a 94% PPV for avoidance of colectomy following infliximab salvage.

Conclusions: The baseline Mayo Endoscopic Score and the CRP/albumin ratio following infliximab salvage are significant predictors of treatment response for ASUC and identify patients at high risk of colectomy. Whether this risk can be mitigated using infliximab dose intensification requires prospective evaluation before the CRP/albumin ratio can be integrated into ASUC management algorithms.
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http://dx.doi.org/10.1111/jgh.14072DOI Listing
July 2018

Examining maintenance care following infliximab salvage therapy for acute severe ulcerative colitis.

J Gastroenterol Hepatol 2018 Jan;33(1):226-231

Department of Gastroenterology, Austin Health, Melbourne, Australia.

Background And Aim: Data supporting the optimal maintenance drug therapy and strategy to monitor ongoing response following successful infliximab (IFX) induction, for acute severe ulcerative colitis (ASUC), are limited. We aimed to evaluate maintenance and monitoring strategies employed in patients post-IFX induction therapy.

Methods: Patients in six Australian tertiary centers treated with IFX for steroid-refractory ASUC between April 2014 and May 2015 were identified via hospital IBD and pharmacy databases. Patients were followed up for 1 year with clinical data over 12 months recorded. Analysis was limited to patient outcomes beyond 3 months.

Results: Forty one patients were identified. Five of the 41 (12%) patients underwent colectomy within 3 months, and one patient was lost to follow-up. Six of 35 (17%) of the remaining patients progressed to colectomy by 12 months. Maintenance therapy: Patients maintained on thiopurine monotherapy (14/35) versus IFX/thiopurine therapy (15/35) were followed up. Two of 15 (13%) patients who received combination maintenance therapy underwent a colectomy at 12 months, compared with 1/14 (7%) patients receiving thiopurine monotherapy (P = 0.610). Monitoring during maintenance: Post-discharge, thiopurine metabolites were monitored in 15/27 (56%); fecal calprotectin in 11/32 (34%); and serum IFX levels in 4/20 (20%). Twenty of 32 (63%) patients had an endoscopic evaluation after IFX salvage with median time to first endoscopy of 109 days (interquartile range 113-230).

Conclusion: Following IFX induction therapy for ASUC, the uptake of maintenance therapy in this cohort and strategies to monitor ongoing response were variable. These data suggest that the optimal maintenance and monitoring strategy post-IFX salvage therapy remains to be defined.
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http://dx.doi.org/10.1111/jgh.13850DOI Listing
January 2018

Exploration of Health Status, Illness Perceptions, Coping Strategies, Psychological Morbidity, and Quality of Life in Individuals With Fecal Ostomies.

J Wound Ostomy Continence Nurs 2017 Jan/Feb;44(1):69-73

Simon R. Knowles, PhD, M(Clin), Faculty of Life and Social Sciences, Swinburne University of Technology, Melbourne, Victoria, Australia; Departments of Gastroenterology and Mental Health, St Vincent's Hospital, Melbourne, Australia; and University of Melbourne, Melbourne, Victoria, Australia. Davina Tribbick, B.Soc Sci Hons, Faculty of Life and Social Sciences, Swinburne University of Technology, Melbourne, Victoria, Australia. William R. Connell, MD, Department of Gastroenterology, St Vincent's Hospital, Melbourne, Victoria, Australia. David Castle, MD, Department of Mental Health, St Vincent's Hospital, Melbourne, Victoria, Australia; University of Melbourne, Melbourne, Victoria, Australia; and Cardiovascular Research Centre, Australian Catholic University, Melbourne, Victoria, Australia. Michael Salzberg, MBBS, Department of Mental Health, St Vincent's Hospital, Melbourne, Australia; and University of Melbourne, Melbourne, Victoria, Australia. Michael A. Kamm, MD, PhD, Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia; University of Melbourne, Melbourne, Victoria, Australia; and Imperial College, London, United Kingdom.

Purpose: In a previous paper focusing on the common sense model (CSM) for ostomies in people with inflammatory bowel disease, cancer, and diverticular disease, we reported that (1) illness perceptions were directly related to illness status, and both illness perceptions and coping strategies (maladaptive coping) directly influenced anxiety and depression; (2) self-efficacy and emotion-focused coping style ameliorated depression but not anxiety; and (3) time since surgery was associated with improved health status, a reduction in negative illness perceptions, and increased emotional-focused coping. The purpose of this article was to perform a secondary analysis with the addition of a stoma quality-of-life measure.

Subjects And Setting: One hundred fifty adults with ostomies (54 males, and 96 females; mean age = 44 years) completed an online survey.

Design: Descriptive, cross-sectional, questionnaire-based study.

Methods: Participants completed the Health Perceptions Questionnaire, Brief Illness Perceptions Questionnaire, Carver Brief Coping Questionnaire, Stoma Self-efficacy Scale, Hospital Anxiety and Depression Scale, and the Stoma Quality-of-Life Scale.

Results: Using structural equation modeling, the final model provided an excellent fit to the data (χ27 = 19.20, P = .37, χ/N = 1.08, Standardized Root Mean Square Residual (SRMR) <0.03, Steiger-Lind Root Mean Square Error of Approximation (RMSEA) <0.03, Goodness of Fit Index (GFI) >0.98). Extending upon our previous paper, self-efficacy, anxiety, and depression were found to have a significant direct influence on stoma-specific quality of life (β= .47, P < .001, β=-.25, P < .001, and β=-.35, P < .001, respectively).

Conclusions: The findings of this secondary analysis extends our previous report by identifying that, consistent with the CSM, illness status, illness perceptions, and coping influence health-related quality of life via self-efficacy, anxiety, and depression. The results suggest that to improve an individual's quality of life, psychological interventions should target the psychological processes underpinning mental illness and also help develop and maintain an individual's self-efficacy in relation to ostomy care.
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http://dx.doi.org/10.1097/WON.0000000000000295DOI Listing
August 2017

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

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

Concentrations of Adalimumab and Infliximab in Mothers and Newborns, and Effects on Infection.

Gastroenterology 2016 07 8;151(1):110-9. Epub 2016 Apr 8.

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

Background & Aims: Little is known about in utero exposure to and postnatal clearance of anti-tumor necrosis factor (anti-TNF) agents in neonates. We investigated the concentrations of adalimumab and infliximab in umbilical cord blood of newborns and rates of clearance after birth, and how these correlated with drug concentrations in mothers at birth and risk of infection during the first year of life.

Methods: We performed a prospective study of 80 pregnant women with inflammatory bowel diseases at tertiary hospitals in Denmark, Australia, and New Zealand from March 2012 through November 2014: 36 received adalimumab and 44 received infliximab; 39 received concomitant thiopurines during pregnancy. Data were collected from medical records on disease activity and treatment before, during, and after pregnancy. Concentrations of anti-TNF agents were measured in blood samples from women at delivery and in umbilical cords, and in infants for every 3 months until the drug was no longer detected.

Results: The time from last exposure to anti-TNF agent during pregnancy correlated inversely with the concentration of the drugs in the umbilical cord (adalimumab: r = -0.64, P = .0003; infliximab: r = -0.77, P < .0001) and in mothers at time of birth (adalimumab, r = -0.80; infliximab, r = -0.80; P < .0001 for both). The median ratio of infant:mother drug concentration at birth was 1.21 for adalimumab (95% confidence interval [CI], 0.94-1.49) and 1.97 for infliximab (95% CI, 1.50-2.43). The mean time to drug clearance in infants was 4.0 months for adalimumab (95% CI, 2.9-5.0) and 7.3 months for infliximab (95% CI, 6.2-8.3; P < .0001). Drugs were not detected in infants after 12 months of age. Bacterial infections developed in 4 infants (5%) and viral infections developed in 16 (20%), all with benign courses. The relative risk for infection was 2.7 in infants whose mothers received the combination of an anti-TNF agent and thiopurine, compared with anti-TNF monotherapy (95% CI, 1.09-6.78; P = .02).

Conclusions: In a prospective study of infants born to mothers who received anti-TNF agents during pregnancy, we detected the drugs until 12 months of age. There was an inverse correlation between the time from last exposure during pregnancy and drug concentration in the umbilical cord. Infliximab was cleared more slowly than adalimumab from the infants. The combination of an anti-TNF agent and thiopurine therapy during pregnancy increased the relative risk for infant infections almost 3-fold compared with anti-TNF monotherapy. Live vaccines therefore should be avoided for up to 1 year unless drug clearance is documented, and pregnant women should be educated on the risks of anti-TNF use.
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http://dx.doi.org/10.1053/j.gastro.2016.04.002DOI Listing
July 2016

Prevalence of mental health disorders in inflammatory bowel disease: an Australian outpatient cohort.

Clin Exp Gastroenterol 2015 17;8:197-204. Epub 2015 Jul 17.

Faculty of Life and Social Sciences, Swinburne University of Technology, Melbourne, VIC, Australia ; Department of Psychiatry, St Vincent's Hospital, Melbourne, VIC, Australia ; Department of Psychiatry, The University of Melbourne, Melbourne, VIC, Australia ; Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Melbourne, VIC, Australia ; Department of Medicine, University of Melbourne, Melbourne, VIC, Australia.

Background: This study aimed to characterize prevalence of anxiety and depressive conditions and uptake of mental health services in an Australian inflammatory bowel disease (IBD) outpatient setting.

Methods: Eighty-one IBD patients (39 males, mean age 35 years) attending a tertiary hospital IBD outpatient clinic participated in this study. Disease severity was evaluated according to the Manitoba Index. Diagnosis of an anxiety or depressive condition was based upon the Mini-International Neuropsychiatric Interview and the Hospital Anxiety and Depression Scale.

Results: Based on Hospital Anxiety and Depression Scale subscale scores >8 and meeting Mini-International Neuropsychiatric Interview criteria, 16 (19.8%) participants had at least one anxiety condition, while nine (11.1%) had a depressive disorder present. Active IBD status was associated with higher prevalence rates across all anxiety and depressive conditions. Generalized anxiety was the most common (12 participants, 14.8%) anxiety condition, and major depressive disorder (recurrent) was the most common depressive condition reported (five participants, 6.2%). Seventeen participants (21%) reported currently seeking help for mental health issues while 12.4% were identified has having at least one psychological condition but not seeking treatment.

Conclusion: We conclude that rates of anxiety and depression are high in this cohort, and that IBD-focused psychological services should be a key component of any holistic IBD service, especially for those identified as having active IBD.
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http://dx.doi.org/10.2147/CEG.S77567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4512611PMC
July 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

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

Crohn's disease management after intestinal resection: a randomised trial.

Lancet 2015 Apr 24;385(9976):1406-17. Epub 2014 Dec 24.

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

Background: Most patients with Crohn's disease need an intestinal resection, but a majority will subsequently experience disease recurrence and require further surgery. This study aimed to identify the optimal strategy to prevent postoperative disease recurrence.

Methods: In this randomised trial, consecutive patients from 17 centres in Australia and New Zealand undergoing intestinal resection of all macroscopic Crohn's disease, with an endoscopically accessible anastomosis, received 3 months of metronidazole therapy. Patients at high risk of recurrence also received a thiopurine, or adalimumab if they were intolerant to thiopurines. Patients were randomly assigned to parallel groups: colonoscopy at 6 months (active care) or no colonoscopy (standard care). We used computer-generated block randomisation to allocate patients in each centre to active or standard care in a 2:1 ratio. For endoscopic recurrence (Rutgeerts score ≥i2) at 6 months, patients stepped-up to thiopurine, fortnightly adalimumab with thiopurine, or weekly adalimumab. The primary endpoint was endoscopic recurrence at 18 months. Patients and treating physicians were aware of the patient's study group and treatment, but central reading of the endoscopic findings was undertaken blind to the study group and treatment. Analysis included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT00989560.

Findings: Between Oct 13, 2009, and Sept 28, 2011, 174 (83% high risk across both active and standard care groups) patients were enrolled and received at least one dose of study drug. Of 122 patients in the active care group, 47 (39%) stepped-up treatment. At 18 months, endoscopic recurrence occurred in 60 (49%) patients in the active care group and 35 (67%) patients in the standard care group (p=0.03). Complete mucosal normality was maintained in 27 (22%) of 122 patients in the active care group versus four (8%) in the standard care group (p=0.03). In the active care arm, of those with 6 months recurrence who stepped up treatment, 18 (38%) of 47 patients were in remission 12 months later; conversely, of those in remission at 6 months who did not change therapy recurrence occurred in 31 (41%) of 75 patients 12 months later. Smoking (odds ratio [OR] 2.4, 95% CI 1.2-4.8, p=0.02) and the presence of two or more clinical risk factors including smoking (OR 2.8, 95% CI 1.01-7.7, p=0.05) increased the risk of endoscopic recurrence. The incidence and type of adverse and severe adverse events did not differ significantly between patients in the active care and standard care groups (100 [82%] of 122 vs 45 [87%] of 52; p=0.51) and (33 [27%] of 122 vs 18 [35%] of 52; p=0.36), respectively.

Interpretation: Treatment according to clinical risk of recurrence, with early colonoscopy and treatment step-up for recurrence, is better than conventional drug therapy alone for prevention of postoperative Crohn's disease recurrence. Selective immune suppression, adjusted for early recurrence, rather than routine use, leads to disease control in most patients. Clinical risk factors predict recurrence, but patients at low risk also need monitoring. Early remission does not preclude the need for ongoing monitoring.

Funding: AbbVie, Gutsy Group, Gandel Philanthropy, Angior Foundation, Crohn's Colitis Australia, and the National Health and Medical Research Council.
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http://dx.doi.org/10.1016/S0140-6736(14)61908-5DOI Listing
April 2015

Exploration of health status, illness perceptions, coping strategies, and psychological morbidity in stoma patients.

J Wound Ostomy Continence Nurs 2014 Nov-Dec;41(6):573-80

Simon R. Knowles, PhD, Faculty of Life and Social Sciences, Swinburne University of Technology, Melbourne, Australia; Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia; Department of Mental Health, St Vincent's Hospital, Melbourne, Australia; and University of Melbourne, Melbourne, Australia. Davina Tribbick, B.Soc Sci Hons, Faculty of Life and Social Sciences, Swinburne University of Technology, Melbourne, Australia. William R. Connell, MD, Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia. David Castle, MD, Chair of Psychiatry, St. Vincent's Hospital Melbourne and The University of Melbourne; Adjunct Professor, Faculty of Health Sciences, Australian Catholic University. Michael Salzberg, MBBS, Department of Mental Health, St Vincent's Hospital, Melbourne, Australia; and University of Melbourne, Melbourne, Australia. Michael A. Kamm, MD, PhD, Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia; University of Melbourne, Melbourne, Australia; University of Melbourne, Melbourne, Australia; and Imperial College, London, United Kingdom.

Purpose: We employed the Common Sense Model (CSM) of illness perceptions to examine the relative contribution of illness perceptions, stoma self-efficacy, and coping strategies in explaining anxiety and depression symptoms in patients with a fecal ostomy. The CSM suggests that the consequences of illness activity, such as psychological distress, are influenced by an individual's illness perceptions as well as what coping strategies they engage in.

Design: Descriptive, cross-sectional questionnaire-based study.

Subjects And Setting: One hundred fifty adults with a stoma (54 males, and 96 females; mean age 44 years) completed an online survey.

Methods: Several instruments were used to measure study outcomes, including the Health Perceptions Questionnaire, Brief Illness Perceptions Questionnaire, Carver Brief Coping Questionnaire, Stoma Self-Efficacy Scale, and the Hospital Anxiety and Depression Scale. Participants were advised of the study through online forums containing a link to the survey. Outcome measures used in the current study are valid and reliable and have been extensively used in medically ill patients.

Results: Using structural equation modeling, the final model provided an excellent fit to the data (χ23= 16.53, P = .22, χ/N = 1.27, SRMR < 0.03, RMSEA < 0.05, GFI > 0.97, CFI > 0.99). There was a direct pathway from health status to illness perceptions months since surgery directly influenced health status, illness beliefs, and adaptive emotion-focused coping (β= .81, P < .001). Several indirect (mediating) pathways were also identified. Illness perceptions mediated the relationship between health status and stoma self-efficacy and maladaptive and adaptive emotion-focused coping. Maladaptive coping mediated the relationship between illness perceptions and depression and anxiety, and adaptive emotion-focused coping mediated the relationship between illness perception and depression. The final model provided support for the CSM, in that illness perceptions were directly related to illness status, and that both illness perceptions and coping strategies directly influenced anxiety and depression. More specifically, maladaptive coping style (eg, ignore problems) exacerbated depression and anxiety symptoms, while self-efficacy and emotion-focused coping style (eg, seek advice) ameliorate depression, but not anxiety. Months since surgery was associated with improved health status, reduced poorer illness perceptions, and increased emotional-focused coping.

Conclusions: Illness perceptions and coping were found to mediate anxiety and depression. The results confirm that how individuals perceive their illness and what coping strategies they engage in impacts their psychological well-being. Study findings support the need for designing targeting psychological interventions based on individual illness perceptions and self-efficacy rather than exclusively focusing on coping strategies in patients with a stoma.
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http://dx.doi.org/10.1097/WON.0000000000000073DOI Listing
June 2016

Comparison of clinical characteristics and management of inflammatory bowel disease in Hong Kong versus Melbourne.

J Gastroenterol Hepatol 2012 May;27(5):919-27

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

Background And Aim: Inflammatory bowel disease (IBD), common in Melbourne, was rare but is now increasing in incidence in Hong Kong (HK). To investigate whether these are the same diseases in the West and East, potential causes of changing incidence, and to plan resource needs, an appreciation of clinical characteristics in contrasting populations is essential.

Methods: Disease characteristics were collected from prospectively populated IBD databases in two specialist centers in Melbourne, Australia and HK.

Results: Of 795 patients (Crohn's disease [CD] : ulcerative colitis [UC] Melbourne 272:159 and HK 161:203), the age of diagnosis was higher, there were proportionally more male patients with CD but no UC sex difference, fewer patients were current or ex-smokers (CD 8% vs 50%; UC 17% vs 35%) and a family history of IBD was less common (2% vs 11%; P < 0.001) in HK compared to Melbourne. Stricturing and perianal CD were more common in HK (12% vs 6%; P < 0.001; and 29% vs 16%; P = 0.001, respectively). In HK for UC, more patients had extensive disease at diagnosis (42% vs 22%) but colectomy was less common (7% vs 20%; P < 0.001). In Melbourne there was greater steroid use at diagnosis and patients were more likely to receive an immunomodulator or anti-tumor necrosis factor agent.

Conclusions: IBD in HK was diagnosed at an older age, and had more complicated disease behavior than in Melbourne. Medical therapy, however, was less intense in HK. These differences may relate to real differences in disease or delayed diagnosis due to late presentation and less disease recognition in HK.
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http://dx.doi.org/10.1111/j.1440-1746.2011.06984.xDOI Listing
May 2012

Altered immune system glycosylation causes colitis in alpha1,2-fucosyltransferase transgenic mice.

Inflamm Bowel Dis 2004 Sep;10(5):546-56

Immunology Research Centre, St. Vincent's Hospital, Fitzroy, Victoria 3056, Australia.

Background And Aims: Altered glycosylation of the mucosal barrier has been proposed as a primary defect in the pathogenesis of IBD. Glycosylation defects however may also have a profound influence on immune function. Mice transgenic for human alpha1,2-fucosyl-transferase (hFUT1) have widespread disturbances in cell surface glycosylation and spontaneously develop colitis. The aims of this study were to characterize colitis in hFUT1 mice and to determine whether glycosylation-induced changes of the mucosal barrier or the immune system were critical for its pathogenesis.

Methods: The pathologic features of hFUT1 transgenic mice were characterized. The mucosal barrier was assessed by lectin binding and permeability studies. T-cells and the thymus were assessed by FACS analysis and histology. To isolate the hFUT1 mucosal barrier from the hFUT1 immune system, bone marrow chimeras were generated.

Results: Seventy percent of hFUT1 mice raised in SPF conditions developed histologic evidence of colitis. The mucosal barrier demonstrated altered glycosylation but intestinal permeability was preserved. HFUT1 mice were profoundly lymphopenic, with aberrant T-cell markers and thymic medullary hypoplasia. Reconstitution with wild type bone marrow restored thymic morphology and prevented colitis in hFUT1 mice.

Conclusion: Altered glycosylation in hFUT1 mice has a profound influence on T-cell development and this defect, rather than a mucosal barrier defect, is crucial for the development of colitis.
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http://dx.doi.org/10.1097/00054725-200409000-00008DOI Listing
September 2004