Inflammatory bowel disease in pregnancy: a population-based study of prevalence and pregnancy outcomes.

OBJECTIVE: To determine the prevalence of the inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn's disease (CD), in pregnant women and determine pregnancy and fetal/neonatal outcomes. DESIGN: Population-based cohort study. SETTING: New South Wales, Australia, 2001-11. POPULATION: A total of 630 742 women who delivered at ≥20 weeks of gestation. METHODS: Descriptive and multivariate regression analyses of perinatal data linked to hospital admission data. We compared birth outcomes of women with and without a documented diagnosis of IBD. MAIN OUTCOME MEASURES: Caesarean section, severe maternal morbidity, preterm birth <37 weeks of gestation, planned preterm birth, small-for-gestational-age (birthweight <10th centile), perinatal mortality (stillbirth/neonatal death ≤28 days). RESULTS: In all, 1960 women (0.31%) with IBD, who had 2781 births (1183 UC, 1287 CD and 311 IBD-indeterminate). Women with IBD were more likely than women without IBD to have a caesarean section [41.5 versus 28.2%, adjusted risk ratio (aRR) 1.38, 95% CI 1.31-1.45], severe maternal morbidity (2.6 versus 1.6%, aRR 1.54, 95% CI 1.17-2.03), preterm birth (9.7 versus 6.6%, aRR 1.47, 95% CI 1.30-1.66), planned preterm birth (5.3 versus 2.9%, aRR 1.74, 95% CI 1.47-2.07), and their infants to be small-for-gestational-age (9.7 versus 9.5%, aRR 1.19, 95% CI 1.04-1.36). There was no evidence of a difference in perinatal mortality. CONCLUSION: Pregnancy-associated IBD is more common than previously reported. Pregnancies complicated by IBD at or near the time of birth have significantly higher rates of adverse pregnancy outcomes than pregnancies of women without IBD. TWEETABLE ABSTRACT: Increased rates preterm birth and caesarean section in women with inflammatory bowel disease.

Efficacy of thiopurines and adalimumab in preventing Crohn's disease recurrence in high-risk patients - a POCER study analysis.

BACKGROUND: Crohn's disease recurs in the majority of patients after intestinal resection. AIM: To compare the relative efficacy of thiopurines and anti-TNF therapy in patients at high risk of disease recurrence. METHODS: As part of a larger study comparing post-operative management strategies, patients at high risk of recurrence (smoker, perforating disease, ≥2nd operation) were treated after resection of all macroscopic disease with 3 months metronidazole together with either azathioprine 2 mg/kg/day or mercaptopurine 1.5 mg/kg/day. Thiopurine-intolerant patients received adalimumab induction then 40 mg fortnightly. Patients underwent colonoscopy at 6 months with endoscopic recurrence assessed blind to treatment. RESULTS: A total of 101 patients [50% male; median (IQR) age 36 (25-46) years] were included. There were no differences in disease history between thiopurine- and adalimumab-treated patients. Fifteen patients withdrew prior to 6 months, five due to symptom recurrence (of whom four were colonoscoped). Endoscopic recurrence (Rutgeerts score i2-i4) occurred in 33 of 73 (45%) thiopurine vs. 6 of 28 (21%) adalimumab-treated patients [intention-to-treat (ITT); P = 0.028] or 24 of 62 (39%) vs. 3 of 24 (13%) respectively [per-protocol analysis (PPA); P = 0.020]. Complete mucosal endoscopic normality (Rutgeerts i0) occurred in 17/73 (23%) vs. 15/28 (54%) (ITT; P = 0.003) and in 27% vs. 63% (PPA; P = 0.002). The most advanced disease (Rutgeerts i3 and i4) occurred in 8% vs. 4% (thiopurine vs. adalimumab). CONCLUSIONS: In Crohn's disease patients at high risk of post-operative recurrence adalimumab is superior to thiopurines in preventing early disease recurrence.

Patient and clinician preferences for surgical and medical treatment options in ulcerative colitis.

AIM: When treating patients with refractory ulcerative colitis (UC), the choice between escalating medical management or surgery can be difficult. The aim of this study was to quantify the preferences of patients and clinicians for the treatment options in UC. METHOD: Ulcerative colitis outpatients were interviewed to measure their preferences for five scenarios examining the management of acute and chronic UC, using a prospective measure of preference method that generates two utility scores: willingness and amount of expected life to trade or gamble. A self-administered questionnaire was mailed to Australian and New Zealand colorectal surgeons and gastroenterologists. RESULTS: Fifty-five patients (26 medical and 29 surgical), 91 surgeons and 78 gastroenterologists were surveyed. In the acute setting, 89% of patients, 69% of gastroenterologists and 55% of surgeons were willing to trade part of their life expectancy to avoid a permanent stoma, while for chronic disease 71% of patients were prepared to trade to avoid an operation with a permanent stoma compared with 55% for an operation with a pouch (P = 0.01). Both patients and gastroenterologists were more prepared to gamble or trade to avoid any surgery than were colorectal surgeons. All groups were aligned in their decision to undergo yearly colonoscopy surveillance rather than to undergo definitive surgery that would result in a stoma. CONCLUSION: Patient preferences for the treatment of UC were more aligned to those of gastroenterologists than those of colorectal surgeons. Despite postoperative studies revealing an equal quality of life for pouch and stoma patients, this study confirmed that a pouch is the preferred surgical option.

Implementing guidelines on the prevention of opportunistic infections in inflammatory bowel disease.

INTRODUCTION: Opportunistic infections are a key safety concern in the management of patients with inflammatory bowel disease (IBD). Despite the existence of international guidelines, many gastroenterologists have not adopted routine screening and vaccination. The aim of this study was to modify clinical behaviour by use of a simple screening tool. METHODS: A screening and vaccination proforma for hepatitis B, varicella, Influenza, Pneumococcus, human papillomavirus, tuberculosis, hepatitis C and HIV was provided to each participating gastroenterologist. Gastroenterologists were surveyed for awareness of vaccine recommendations and current practice prior to and following the introduction of the proforma. Rates of immunity and the proportion of patients receiving the recommended screening and vaccinations were documented. RESULTS: 30 gastroenterologists at 8 different IBD centres took part in the assessment. A total of 919 patients were included (55% female, 65% Crohn's, 33% ulcerative colitis, 2% indeterminate IBD). Introduction of the proforma increased self-reported gastroenterologist screening from 47% to 97% pre- and post-intervention respectively, p<0.001. After the proforma was applied, vaccination against hepatitis B, varicella, Influenza, and Pneumococcus was recommended in 67%, 2.5%, 75% and 69% of the patients respectively. Of these, 42%, 39%, 66% and 49% patients followed the recommendations and were vaccinated. Cervical smears were recommended in 31%, with 62% of these obtaining the recommended cervical smear. CONCLUSIONS: Implementation of a screening and vaccination proforma significantly changed gastroenterologist self-reported behaviour. Patient compliance with these recommendations was not optimal and suggests the need for further patient education, in addition to other forms of support.

Hyoscine butylbromide administered at the cecum increases polyp detection: a randomized double-blind placebo-controlled trial.

BACKGROUND AND STUDY AIMS: Removal of colonic polyps prevents progression of colonic neoplasia. Miss rates of polyps range from 5 % to 32 %. The effect of colonic contractility on polyp detection has not been studied adequately. Hyoscine butylbromide results in colonic spasmolysis and may improve polyp detection. PATIENTS AND METHODS: Patients undergoing colonoscopy for standard indications were included and randomized to receive either 20  mg hyoscine butylbromide or placebo at cecal intubation. Operators were blind to the intervention. Data on indication, preparation, sedation, colonoscope type, times of insertion/withdrawal, polyps, and failure were recorded. The primary end point was the number of polyps detected per patient. Secondary endpoints were adenoma detection rate and polyp detection rate. RESULTS: A total of 303 patients received hyoscine butylbromide and 298 received placebo. More polyps per patient were identified in the hyoscine group than in the placebo group (0.91 vs. 0.70; P = 0.044). Adenoma detection rate and polyp detection rate were higher in the hyoscine arm but not significantly different (27.1 % vs. 21.8 % [P = 0.13] and 43.6 % vs. 36.6 % [P = 0.08], respectively). After adjusting for confounding variables, the odds of detecting any polyp were 1.56 higher in the hyoscine than the placebo group (95 % confidence interval [CI] 1.09 - 2.21, P = 0.014). The adjusted odds of detecting any adenoma were 1.62 higher in the hyoscine group compared with the placebo group (95 %CI 1.09 - 2.42, P = 0.017). There were no differences in baseline characteristics between the groups. No adverse colonoscopy-related events were recorded. One patient experienced transient tachycardia without sequelae. CONCLUSIONS: Hyoscine butylbromide administered at the cecum aids polyp detection. Further studies are required to determine the contribution of colonic spasm to polyp miss rates.

Patients' knowledge of pregnancy-related issues in inflammatory bowel disease and validation of a novel assessment tool ('CCPKnow').

BACKGROUND: Inflammatory bowel diseases (IBD) require complex therapeutic decisions and life choices concerning pregnancy, but little is known about patient's knowledge of IBD and its treatment before and during pregnancy. AIM: To develop a novel tool (Crohn's and Colitis Pregnancy Knowledge Score 'CCPKnow') to assess knowledge of pregnancy-related issues in IBD. The validated tool was then applied to determine knowledge in patients. METHOD: Discriminate ability of 'CCPKnow' was validated in four groups with different levels of IBD knowledge. Reliability and readability were tested by Cronbach-α and Flesch-Kencaid. Construct validity was subsequently assessed against general IBD knowledge (CCKnow) in 145 women with IBD. Associations between patient factors and knowledge were studied. RESULTS: Median CCPKnow scores differed significantly between the validation groups (P < 0.001). CCPKnow displayed excellent internal consistency, reliability (Cronbach-α 0.94), readability (reading age 9 years) and close correlation with CCKnow (Spearman's ρ 0.64; P < 0.001). Of 145 patients, 44.8% had poor, 27.6% adequate, 17.3% good and only 10.3% very good knowledge. Better knowledge was associated with Caucasian ethnicity, higher income, having a partner, having children, Crohn's and Colitis Association membership, longer disease duration and Crohn's disease. CONCLUSIONS: Crohn's and Colitis Pregnancy Knowledge Score, a novel knowledge assessment tool of pregnancy and IBD, demonstrated excellent test characteristics. We found that nearly half of the women with IBD had poor knowledge, identifying a pressing need for better education.

Antegrade double balloon enteroscopy for continued obscure gastrointestinal bleeding following push enteroscopy: is there a role?

BACKGROUND: The benefit of double balloon endoscopy (DBE) over push enteroscopy (PE) for the proximal small bowel in patients with obscure gastrointestinal bleeding remains unclear. AIM: To quantify the benefit of DBE if PE fails to benefit patients with obscure gastrointestinal bleeding. METHODS: This retrospective DBE database review between July 2004 and April 2008 was conducted at a tertiary university hospital in Australia. Thirty-three patients with obscure gastrointestinal bleeding who had undergone PE for proximal small bowel lesions were identified from a DBE database of 280 patients. Mean age was 68.6 (range 30-91) years, and 17 were men. In group A (n = 15) the target lesion was not reached by PE, and in group B (n = 18) an abnormality was found by PE (angioectasia in 17 and red spots in 1) but the patient had ongoing bleeding. Mean follow-up for the cohort was 19.2 (range 5-39) months. DBE interventions were performed as appropriate. RESULTS: An abnormality was found at DBE in 28/33 (85%) patients. DBE found an abnormality in 12/15 (80%) in group A and 16/18 (89%) in group B. Endoscopic intervention was performed in 23/33 patients (70%). In 27/33 (82%) patients a clinical benefit was seen following DBE. Six patients (18%) had no clinical benefit from DBE. CONCLUSIONS: In patients with obscure gastrointestinal bleeding and proximal small bowel lesions who fail to benefit from PE, DBE offers a very high benefit in finding and treating lesions with good long-term outcomes.

The current pattern of hepatitis B virus infection in Australia.

There is little recent data of the seroprevalence of hepatitis B in Australia. We have surveyed a large cohort of endoscopy patients attending a teaching hospital in central Sydney, and related the presence of hepatitis B virus (HBV) markers with putative risk factors for exposure using the SAS statistical package. Of the 2115 patients tested: 2.1% (45/2115) were HBV surface antigen positive, 0.75% (14/2115) viraemic, 9.5% (200/2115) anti-HBs and anti-HBc positive, 20.1% (430/2115) vaccinated (anti-HBs only) and the remaining 70% were susceptible. The adjusted OR of HBV infection was significantly increased in patients who had been diagnosed with human immunodeficiency virus (36.3-fold), born in Asia or Pacific islands (12.4-fold), born in North Africa, Middle East & Mediterranean countries (6-fold) or born abroad elsewhere in the world (2.7-fold), had household contact with someone diagnosed with hepatitis between 1980 and 1990 (3.9-fold), injected drugs between 1980 and 1990 (4.4-fold), resided in a military establishment for 3 months (2.3-fold) or in a hospital for 3 months (2.2-fold), never been vaccinated for hepatitis B (2.8-fold), received blood transfusion due to an accident and/or a haemorrhage (1.92-fold) and finally been a male gender (1.59-fold). The prevalence of HBV in this hospital population was higher than predicted on the basis of notifications to the passive surveillance scheme. Most HBV patients had multiple risk factors for infection, but the hierarchy of odds ratios provides a rational basis for targeted programmes to identify asymptomatic HBV carriers who might benefit from treatment.

Microscopic colitis: an underdiagnosed cause of chronic diarrhoea--the clue is in the biopsies.

Microscopic forms of colitis (collagenous colitis and lymphocytic colitis) are uncommon but important causes of chronic diarrhoea that are often overlooked. The clinical features of these disorders are similar, and they are more common in middle-aged females, although the female predominance is greater in collagenous colitis. Although their cause is unclear, both are associated with a variety of autoimmune diseases. Colonoscopy and barium enema are typically normal, so that the diagnosis depends on the demonstration of characteristic changes on histopathological examination of colorectal biopsies. These should be taken in all patients undergoing colonoscopy for the investigation of chronic diarrhoea. There are no large controlled trials of therapy available. Treatment is empirical, generally using the same agents as for inflammatory bowel -disease. Assessment of therapy is also difficult as spontaneous remissions occur often.

Assessment and relevance of enzyme-linked immunosorbent assay for antibodies to Saccharomyces cerevisiae in Australian patients with inflammatory bowel disease.

The frequency of antibodies to Saccharomyces cerevisiae (ASCA) in Crohn's disease, ulcerative colitis and non-inflammatory bowel disease controls has been compared using two commercially available assays. The Medizym test resulted in sensitivity of 50% and specificity of 93% for Crohn's disease. The corresponding figures for the QUANTA Lite assay were 79% and 74%, respectively. Using ASCA and perinuclear antineutrophil cytoplasmic antibody (pANCA) in combination, the sensitivity and specificity of ASCA+/pANCA- for Crohn's disease using the Medizym kit were 50% and 100%, respectively, compared with 79% and 93% using QUANTA Lite. ASCA-/pANCA+ was 100% specific for ulcerative colitis with either assay. ASCA can be found in Australian patients with Crohn's disease at a similar frequency to that reported overseas.

Early Australian experience with infliximab, a chimeric antibody against tumour necrosis factor-alpha, in the treatment of Crohn's disease: is its efficacy augmented by steroid-sparing immunosuppressive therapy? The Infliximab User Group.

BACKGROUND: Tumour necrosis factor-alpha (TNF-alpha) plays an important role in the pathology of Crohn's disease. Infliximab, a chimeric antibody against TNF-alpha, has been shown in controlled clinical trials to be effective in two-thirds of patients with refractory or fistulating Crohn's disease. The factors that determine a clinical response in some patients but not others are unknown. AIMS: To document the early Australian experience with infliximab treatment for Crohn's disease and to identify factors that may determine a beneficial clinical response. METHODS: Gastroenterologists known to have used infliximab for Crohn's disease according to a compassionate use protocol were asked to complete a spreadsheet that included demographic information, Crohn's disease site, severity, other medical or surgical treatments and a global clinical assessment of Crohn's disease outcome, judged by participating physicians as complete and sustained (remission for the duration of the study), complete but unsustained (remission at 4 weeks but not for the whole study) or partial clinical improvement (sustained or unsustained). RESULTS: Fifty-seven patients were able to be evaluated, with a median follow-up time of 16.4 (4-70) weeks, including 23 patients with fistulae. There were 21 adverse events, including four serious events. Fifty-one patients (89%) had a positive clinical response for a median duration (range) of 11 (2-70) weeks. Thirty patients (52%) had a remission at 4 weeks, 10 of whom had remission for longer than 12 weeks. Forty-two per cent of fistulae closed. Sustained remission (P = 0.065), remission at 4 weeks (P = 0.033) and a positive clinical response of any sort (P = 0.004) were more likely in patients on immunosuppressive therapy, despite there being more smokers in this group. CONCLUSION: This review of the first Australian experience with infliximab corroborates the reported speed and efficacy of this treatment for Crohn's disease. The excellent response appears enhanced by the concomitant use of conventional steroid-sparing immunosuppressive therapy.

Pathogenesis and therapeutic aspects of Crohn's disease.

Crohn's disease is a chronic, relapsing inflammatory condition affecting any part of the human gastrointestinal tract. It is characterised by transmural inflammation with deep ulceration, thickening of the bowel wall and fistula formation. The hallmark is the non-caseating granuloma. Clinical presentation depends upon the site of the inflammation. Pain and diarrhoea are frequent. Extraintestinal manifestations develop in up to 25% of patients and perianal disease is also frequent. The aetiology of Crohn's disease remains unknown. On the host side, genetic factors are important and the immune system is central to the development of the inflammation. Several environmental factors also play a role, in particular smoking. The presence of intestinal luminal contents appears to be essential for the development of Crohn's disease. A number of specific infectious causes have also been proposed, most recently measles virus and M. avium subsp. paratuberculosis. The latter has been considered because of the similarity between BJD and Crohn's disease, although there are also important differences. Evidence suggesting that this agent plays a role includes isolation of the organism from some patients, clustering, and identification by PCR of M.a. paratuberculosis DNA in tissue. However, many other workers have been unable to reproduce these findings.Treatment of Crohn's disease is generally with 5-aminosalicylic acid (5-ASA) compounds, corticosteroids, immunosuppressive agents and antibiotics. The majority of patients with active disease will respond to one or a combination of the therapies. Recently, broad-spectrum antibiotics have been shown to be as effective as oral corticosteroids. The challenge in Crohn's disease remains the prevention of relapse once remission has been achieved. Oral 5-ASA preparations can be beneficial, particularly after surgery. Immunosuppression, particularly with azathioprine or 6-mercaptopurine, is helpful in patients with resistant inflammation. Antibiotics may delay the time to relapse when used for active disease. The use of antimycobacterial therapy directed against M.a. paratuberculosis shows promising results but needs further evaluation.Up to 80% of patients with Crohn's disease will require surgery at some stage in the course of their illness. The challenge remains to try and prevent resection of inflamed intestine and to improve the quality of life of those affected by this disorder.

Use of 6-mercaptopurine in patients with inflammatory bowel disease previously intolerant of azathioprine.

Both azathioprine and its active metabolite, 6-mercaptopurine, are of benefit in the treatment of inflammatory bowel disease, either in resistant cases, or for their steroid-sparing effect. Azathioprine treatment is limited in some patients by hypersensitivity reactions or other side effects. We report our experience in 11 patients previously unable to tolerate azathioprine for a variety of reasons, who were switched to 6-mercaptopurine. Of seven patients with ulcerative colitis and four patients with Crohn's disease who were treated with 6-mercaptopurine following failed azathioprine therapy, six were able to successfully tolerate the substitute medication, with good response. Where patients have previously been intolerant of azathioprine yet ongoing indications for immunosuppressive therapy remain, a trial of 6-mercatopurine may be warranted. Given the similar efficacies of the two drugs in inflammatory bowel disease, these findings also favor the use of 6-mercaptopurine rather than the parent compound as initial therapy.

Persistent mucosal abnormalities in coeliac disease are not related to the ingestion of trace amounts of gluten.

BACKGROUND: It is expected that in patients with coeliac disease the small-bowel mucosal mucosa will return to normal if they adhere to a gluten-free diet (GFD). However, in many this is not the case. This study aims to determine whether this persistent villous atrophy (VA) could be due to continued ingestion of the trace amounts of gluten in 'gluten-free' foods, as defined by the WHO/FAO Codex Alimentarius. METHODS: Duodenal biopsy specimens from 89 adults with long-standing coeliac disease were examined, and the findings correlated with their form of gluten-free diet. RESULTS: In 51 subjects the duodenal specimen was normal, whereas in 38 there was villous atrophy (partial, 28; subtotal, 8; total, 2). There was no relationship between the presence or absence of VA and ingestion of either a GFD as defined by the Codex Alimentarius (Codex-GFD; 39 patients) or a GFD that contained no detectable gluten (NDG diet: 50 patients). Intraepithelial lymphocyte counts were higher, and lactase levels lower, in subjects with an abnormal biopsy specimen than in those in whom it was normal. However, within each of these biopsy groups there was no difference in these variables between patients on a Codex-GFD and those on an NDG-GFD. IgA antigliadin antibody was detected in 4 of 29 patients on a Codex-GFD and in 3 of 13 on a NDG-GFD (NS). CONCLUSION: The persistent mucosal abnormalities seen in patients with coeliac disease on a GFD are not due to the ingestion of trace amounts of gluten. The consequences of these abnormalities have yet to be determined.