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.

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.

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.

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.

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.

Heterogeneity of HLA-DR-positive histiocytes in human intestinal lamina propria: a combined histochemical and immunohistological analysis.

HLA-DR-positive histiocytes in the lamina propria of the human intestine have been characterised using combined histochemical and immunohistological techniques. In the small intestine, 80-90% of the HLA-DR+ histiocytes had irregular surfaces with stellate processes, and exhibited strong membrane adenosine triphosphatase (ATPase) activity, but weak acid phosphatase (ACP) and non-specific esterase (NSE) activities (HLA-DR+ ACP+/- NSA+/- ATP++; type 1 cell). In contrast, in the lamina propria of the colon the majority (60-70%) of HLA-DR+ cells were large, round cells with strong ACP and NSE activities but no detectable ATPase activity (HLA-DR+ ACP++ NSE++ ATP+/-; type 2 cell). The colon also contained a population of type 1 cells (30-40%). In active inflammatory bowel disease affecting the colon a third population of HLA-DR+ histiocytes was seen. These cells were irregular in outline, with many processes, and were ACP++ NSE+ ATP+/- (type 3 cell). The type 3 cells appeared to replace type 2 cells. After treatment, the appearances returned to normal. These findings suggest that the different populations of HLA-DR+ histiocytes in the human intestine may have several functions, reflecting the different forms of antigen present in the intestine. The alterations in inflammatory bowel disease may represent activation in response to an invading antigen.

Detection of persistent vegetative bacteria and amplified viral nucleic acid from in-use testing of gastrointestinal endoscopes.

Hospital-acquired infection attributed to inadequate decontamination of gastrointestinal endoscopes prompted an in use evaluation of recommended procedures. Specimens were obtained from the internal channels of 123 endoscopes before, during and after decontamination by flushing with saline and brushing with a sterile brush, and examined for vegetative bacteria by broth and plate culture. Four endoscopy units were tested; the chemical disinfectants used were: 2% glutaraldehyde in Centres 1 and 2 (automated) and Centre 3 (manual); peracetic acid in Centre 4 (automated). Samples from patients in Centre 1 with known chronic hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV-1) infection were also examined for viral nucleic acid by ultracentrifugation, nucleic acid extraction, reverse transcription (for RNA) and polymerase chain reaction (PCR). No persistent vegetative bacteria were found following standard manual cleaning and disinfection for 20 min in 2% glutaraldehyde in Centres 2 and 3 (N = 37). At Centre 1, while plate culture yielded no growth, 34% of samples (10/29) grew vegetative bacteria in broth culture after cleaning and disinfection for 20 min in 2% glutaraldehyde. Investigation revealed an error in manual cleaning; no bacteria were detected in 37 samples taken after this was corrected. At Centre 4, despite the use of peracetic acid as a sterilant, three out of 20 (15%) of post decontamination samples grew bacteria; one contained persistent bacteria. HBV and HCV PCR analysis detected viral nucleic acid in three out of four and four out of six samples from viraemic patients undergoing endoscopy in Centre 1 during the period of improper manual washing. After proper cleaning was instituted, samples from nine out of nine HCV viraemic patients were negative. HIV RNA was detected in five of 14 samples taken from endoscopes after use on HIV positive patients but all post decontamination samples were negative. Detection of bacteria in washes from endoscope channels is a useful warning of a breakdown in decontamination practice. Inadequate brushing of internal channels may result in persistent HCV and HBV viral nucleic acid, the significance of which is not clear. These results reinforce the importance of adequate manual cleaning of endoscopes before chemical disinfection.

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.

Diarrhoea--differential diagnosis.

Diarrhoea may present as an acute or chronic illness. The causes are numerous, and can usually be determined by consideration of the mechanics of the diarrhoea, the site of the disease process and its nature. A careful history and physical examination are essential, followed by appropriate investigation.

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.

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.

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.

Current management of inflammatory bowel disease.

The aetiology of ulcerative colitis and Crohn's disease remains unknown. While this remains so, treatment must be directed towards pathogenetic mechanisms. Corticosteroids, sulphasalazine and the new salicylates, the immunosuppressants azathioprine, 6-MP and, more recently, cyclosporin and metronidazole have become the accepted and standard forms of treatment. The importance of maintaining nutritional status is often overlooked but must be considered in every patient. Recognition of the occurrence of disease in all age groups, and in particular in children and adolescents, is also important, as is an appreciation of the special problems involved. The possibility of surgery at some stage of the disease should be raised with the patient. As the pathogenetic mechanisms of inflammatory bowel disease are further elucidated, new forms of treatment will be developed. This is already happening, with studies looking at such agents as immunoglobulin G, eicosapentaenoic acid and a new specific inhibitor of 5-lipoxygenase. These offer hope of more potent drugs with low side-effect profiles that may complement or replace the currently available agents used in the management of inflammatory bowel disease.

The natural history of ulcerative colitis.

The majority of patients with ulcerative colitis (UC) will run a typical chronic, relapsing course. The proportion with chronic, continuous symptoms diminishes with time. The greatest impact of the disease is in the first few years after diagnosis, especially in patients with extensive or severe colitis. After this time, the likelihood of requiring surgery declines rapidly, and survival is no different from that of the general population. The long-term course can be best predicted by the course in the preceding period. Most patients are able to lead an essentially normal lifestyle, at work and at home, with either medical or surgical treatment. Awareness of how the patient feels the disease affects his or her life is important. Educating the patient about their illness will also help in management.

Isolation studies--intestinal T lymphocytes.

Despite the variation in results of studies on isolated intestinal mucosal T cells obtained in different laboratories, it can be said that: 1) T lymphocytes and their subsets can be isolated from normal and from diseased intestinal mucosa. 2) Most of the functions of these T cells are, as far as has been studied, similar to those of peripheral blood T tions of T lymphocytes and the different distribution of these antigens between intestinal epithelium, which normally shows strong expression of HLA-A,B,C antigens but weak or no expression of HLA-DR antigens, and the lamina propria, which contains large numbers of histiocytic cells which are rich in HLA-DR antigens, may be vital to the functions of intestinal T cells. Removal of cells from the close association with these antigens may therefore alter their functions. Secondly, studies of isolated cell populations must be interpreted in combination with morphological examination of cell populations in situ. Such an approach will increase our understanding of the role of T cells in gut immunity in health and disease.

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.

T lymphocyte subsets in inflammatory bowel disease: peripheral blood.

Peripheral blood T lymphocytes and T lymphocyte subsets have been quantified in 28 patients with ulcerative colitis and 26 with Crohn's disease by an indirect immunofluorescence technique using monoclonal antibodies: OKT3, which detects all peripheral blood T lymphocytes; OKT4 (T cells of helper phenotype); and OKT8 (T cells of supressor-cytotoxic phenotype). Eighteen normal subjects and 16 patients with a variety of non-inflammatory gastrointestinal disorders were studied as controls. No significant differences were found between patient and control groups in the proportions of circulating T lymphocytes or their subsets. When compared with normal subjects, absolute numbers of T lymphocytes were reduced in patients with active ulcerative colitis or Crohn's disease (p less than 0.05). OKT4+ T cell numbers were reduced in ulcerative colitis, whether active (p less than 0.02) or inactive (p less than 0.05) and in active Crohn's disease (p less than 0.05) Numbers of OKT8+ T cells were reduced in active Crohn's disease (p less than 0.01). There were no differences in T lymphocyte numbers between the patient groups and the disease control subjects. The OKT4+:OKT8+ ratio in patients with inflammatory bowel disease did not differ from that in controls. No relation was found between any of the parameters studied and disease activity, site, or extent of disease, or treatment with sulphasalazine or corticosteroids. The presence of Ia-like, HLA-DR antigens on T cells was detected using a double marker immunofluorescence technique. In control subjects up to 7% of OKT3+ cells were HLA-DR+. In only three patients was the proportion of HLA-DR+ cells greater than in controls. These results indicate that the pathogenesis of ulcerative colitis or Crohn's disease does not depend upon an alteration in the proportion of circulating T lymphocytes nor upon an imbalance of T lymphocyte subsets as defined by monoclonal antibodies. The reduction in T lymphocyte numbers may result from mucosal infiltration. The findings also suggest that circulating T lymphocytes are not activated.