http://nova.newcastle.edu.au/vital/access/services/Feed ${session.getAttribute("locale")} 5 http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12436 Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory disorders of the gastrointestinal tract. Collectively they are termed inflammatory bowel disease (IBD) and it is estimated that 1.5 million Americans suffer from UC and CD. Their etiologies are unknown, although both are thought to arise from a disordered immune response to the gut contents in genetically predisposed individuals. The characteristics of the inflammatory response are different, with CD typically causing transmural inflammation and occasionally associated with granulomas, whereas in UC the inflammation is usually confined to the mucosa. Both UC and CD exhibit a relapsing and remitting course and there is a significant, often dramatic, reduction in quality of life during exacerbations of the disease. This has an impact on psychological health, with active IBD patients experiencing greater levels of distress and feelings of lack of sense of self-control compared with the normal population and patients with inactive IBD. Extrapolation from US administrative claims databases suggests that IBD is responsible for 2.3 million physician visits, 180,000 hospital admissions, and costs $6.3 billion annually. There have been recent guidelines on the management of both UC and CD that direct the clinician on diagnosis and treatment. Approximately 33% of the cost of IBD is due to medical therapy, and given the substantial clinical burden and economic cost of IBD it is important to establish the effectiveness of current medical therapies in both UC and CD. Although there have been several systematic reviews on the efficacy of therapy, this is a rapidly changing field and there is a need for a comprehensive review of the literature. The American College of Gastroenterology IBD Task Force developed a protocol for systematically reviewing the data on currently available therapies for UC and CD, both in inducing remission and in preventing relapse of the disease. Evidence-based statements were then developed and the strength of recommendation for each was graded according to standard criteria. 2013-01-16T00:50:03.767Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12431 Objectives: Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory disorders of the gastrointestinal tract of unknown etiology. Evidence for treatment of the condition with biological therapies exists, but no systematic review and meta-analysis has examined this issue in its entirety. Methods: MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (through to December 2010). Trials recruiting adults with active or quiescent CD or UC and comparing biological therapies (anti-tumor necrosis factor-α (TNFα) antibodies or natalizumab) with placebo were eligible. Dichotomous symptom data were pooled to obtain relative risk (RR) of failure to achieve remission in active disease and RR of relapse of activity in quiescent disease once remission had occurred, with a 95% confidence interval (CI). Results: The search strategy identified 3,061 citations, 27 of which were eligible. Anti-TNFα antibodies and natalizumab were both superior to placebo in inducing remission of luminal CD (RR of no remission=0.87; 95% CI 0.80–0.94 and RR=0.88; 95% CI 0.83–0.94, respectively). Anti-TNFα antibodies were also superior to placebo in preventing relapse of luminal CD (RR of relapse=0.71; 95% CI 0.65–0.76). Infliximab was superior to placebo in inducing remission of moderate to severely active UC (RR=0.72; 95% CI 0.57–0.91). Conclusions: Biological therapies were superior to placebo in inducing remission of active CD and UC, and in preventing relapse of quiescent CD. 2013-01-16T00:20:04.015Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12403 Objectives: There remains controversy regarding the efficacy of thiopurine analogs (azathioprine (AZA) and 6-mercaptopurine (6-MP)), methotrexate (MTX), and cyclosporine for the treatment of inflammatory bowel disease (IBD). We performed an updated systematic review of the literature to clarify the efficacy of immunosuppressive therapy at inducing remission and preventing relapse in ulcerative colitis (UC) and Crohn's disease (CD). Methods: Only parallel group randomized controlled trials (RCTs) were considered eligible. Studies with adult IBD patients receiving immunosuppressive therapy compared with placebo for at least 14 days and up to 17 weeks for active disease, or at least 6 months in quiescent disease were analyzed. Two reviewers independently assessed eligibility and extracted data. The primary outcome was remission or relapse using an intention-to-treat analysis. The data were summarized using relative risk (RR) and pooled using a random effects model. Results: Data on MTX and cyclosporine in IBD were limited although there were some data to support the use of intramuscular MTX in CD but not UC. There were five trials of AZA/6-MP in 380 active CD patients and there was no significant effect of therapy inducing remission (RR=0.87; 95% confidence interval (CI)=0.71–1.06). In quiescent CD, there were two trials involving 198 patients with no significant benefit of active therapy preventing relapse compared with placebo (RR=0.64; 95% CI=0.34–1.23). There were, however, three additional AZA withdrawal trials in 163 patients that indicated continuing medication did prevent relapse (RR=0.39; 95% CI=0.21–0.74). There were two AZA RCTs in 130 active UC patients that suggested a trend for benefit of therapy, but this did not reach statistical significance (RR=0.85; 95% CI=0.71–1.01). In quiescent UC, there were three trials involving 127 patients and there was a statistically significant benefit of AZA preventing relapse (RR=0.60; 95% CI=0.37–0.95). Conclusions: Most evidence relates to AZA/6-MP where there is no statistically significant benefit at inducing remission in active CD and UC. Thiopurine analogs may prevent relapse in quiescent UC and CD. However, there is a paucity of data for immunosuppressive therapy in IBD and more research is needed. 2013-01-11T05:30:04.618Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12402 Objectives: The use of glucocorticosteroids to treat both Crohn's disease (CD) and ulcerative colitis (UC) is widespread, but no systematic review and meta-analysis has examined the issue of efficacy of these agents in its entirety. Methods: MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (through December 2010). Randomized controlled trials (RCTs) recruiting adults with active or quiescent CD comparing standard glucocorticosteroids or budesonide with placebo or each other, or comparing standard glucocorticosteroids with placebo in active UC, were eligible. Dichotomous data were extracted to obtain relative risk (RR) of failure to achieve remission in active disease, and RR of relapse of activity in quiescent disease, with a 95% confidence interval (CI). Adverse events data were extracted where reported. Results: The search identified 3,061 citations, and 20 trials were eligible. Only one trial was at low risk of bias. Standard glucocorticosteroids were superior to placebo for UC remission (RR of no remission=0.65; 95% CI 0.45–0.93). Both trials of standard glucocorticosteroids in CD remission reported a statistically significant effect, but because of heterogeneity between studies, the overall effect was not significant (RR=0.46; 95% CI 0.17–1.28). Budesonide was superior to placebo for CD remission (RR=0.73; 95% CI 0.63–0.84), but not in preventing CD relapse (RR=0.93; 95% CI 0.83–1.04). Standard glucocorticosteroids were superior to budesonide for CD remission (RR=0.82; 95% CI 0.68–0.98), but glucocorticosteroid-related adverse events were commoner (RR=1.64; 95% CI 1.34–2.00). Conclusions: Standard glucocorticosteroids are probably effective in inducing remission in UC, and may be of benefit in CD. Budesonide induces remission in active CD, but is less effective than standard glucocorticosteroids, and is of no benefit in preventing CD relapse. 2013-01-11T01:10:04.886Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12400 The etiology of inflammatory bowel disease (IBD) is unknown but may relate to an unidentified bacterial pathogen or an immunological reaction to gut microbiota. Antibiotics have therefore been proposed as a therapy for Crohn's disease (CD) and ulcerative colitis (UC) to induce remission in active disease to prevent relapse. Current data are conflicting and we therefore conducted a systematic review of randomized controlled trials (RCTs) evaluating antibiotics in IBD. Only parallel group RCTs were considered eligible. Studies with adult patients receiving any dose of therapy for at least 7 days and up to 16 weeks for active disease, or at least 6 months of follow-up for preventing relapse in quiescent disease were analyzed. We included any antibiotics alone or in combination using predefined definitions of remission and relapse. Two reviewers independently assessed eligibility and extracted data. The primary outcome was remission or relapse using an intention-to-treat methodology. The data were summarized using relative risk (RR) and pooled using a random effects model. For active CD, there were 10 RCTs involving 1,160 patients. There was a statistically significant effect of antibiotics being superior to placebo (RR of active CD not in remission=0.85; 95% confidence interval (CI)=0.73–0.99, P=0.03). There was moderate heterogeneity between results (I²=48%) and a diverse number of antibiotics were tested (anti-tuberculosis therapy, macrolides, fluroquinolones, 5-nitroimidazoles, and rifaximin) either alone or in combination. Rifamycin derivatives either alone or in combination with other antibiotics appeared to have a significant effect at inducing remission in active CD. In perianal CD fistula there were three trials evaluating 123 patients using either ciprofloxacin or metronidazole. There was a statistically significant effect in reducing fistula drainage (RR=0.8; 95% CI=0.66–0.98) with no heterogeneity (I²=0%) and an number needed to treat 5 (95% CI=3–20). For quiescent CD, there were 3 RCTs involving 186 patients treated with different antibiotics combinations (all including antimycobacterials) vs. placebo. There was a statistically significant effect in favor of antibiotics vs. placebo (RR of relapse=0.62; 95% CI=0.46–0.84), with no heterogeneity (I²=0%). In active UC, there were 9 RCTs with 662 patients and there was a statistically significant benefit for antibiotics inducing remission (RR of UC not in remission=0.64; 95% CI=0.43–0.96). There was moderate heterogeneity (I²=69%) and antibiotics used were all different single or combination drugs. Antibiotic therapy may induce remission in active CD and UC, although the diverse number of antibiotics tested means the data are difficult to interpret. This systematic review is a mandate for further trials of antibiotic therapy in IBD. 2013-01-11T00:00:05.523Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12396 Diverticular disease and its complications overlap with both irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Diverticular disease and IBS are common gastrointestinal disorders and share common pathophysiologic factors including visceral hypersensitivity, gastrointestinal motor disturbance, a fiber-depleted diet, and subtle mucosal inflammation. New onset IBS-like symptoms in older patients warrant further investigation including colonoscopy to exclude organic diseases. It can be difficult to differentiate symptomatic diverticular disease from IBS, and fecal calprotectin may help in such cases. Rifaximin treatment improves symptoms of both IBS and diverticular disease. The pathogenesis of diverticulitis and diverticular colitis (or known as segmental colitis associated with diverticular disease) may overlap with that of IBD. Pathologic features of IBD can be observed in both diverticulitis and diverticular colitis. Diverticulitis mimics Crohn’s disease in presentation and radiologic findings. A follow-up colonoscopy helps to differentiate diverticulitis from Crohn’s disease. Diverticular colitis is an infrequent complication of diverticular disease and is limited to the segment of colon with diverticula. Patients with diverticular colitis usually respond to mesalamine and have a better prognosis than IBD. Further understanding of the overlap of IBS, IBD, and diverticular disease may shed light into new therapeutic interventions. 2013-01-10T22:30:03.743Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12376 Objectives: The efficacy of 5-aminosalicylic acids (5-ASAs) in ulcerative colitis (UC) has been studied previously in meta-analyses. However, several randomized controlled trials (RCTs) have been published recently, and no previous meta-analysis has studied the effect of 5-ASA dosage used. Methods: MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (through December 2010). Eligible trials recruited adults with active or quiescent UC, comparing different doses of 5-ASAs with themselves or placebo. Dichotomous data were pooled to obtain relative risk (RR) of failure to achieve remission in active UC, and RR of relapse of disease activity in quiescent UC, with a 95% confidence interval (CI). The number needed to treat (NNT) was calculated from the reciprocal of the risk difference. Results: The search identified 3,061 citations, and 37 RCTs were eligible. Of these, 11 compared 5-ASA with placebo in active UC remission, with the RR of no remission with 5-ASAs of 0.79 (95% CI 0.73–0.85; NNT=6). Doses of ≥2.0 g/day were more effective than <2.0 g/day for remission (RR=0.91; 95% CI 0.85–0.98). There were 11 RCTs comparing 5-ASAs with placebo in preventing relapse of quiescent UC, with the RR of relapse of 0.65 (95% CI 0.55–0.76; NNT=4). Doses of ≥2.0 g/day appeared more effective than <2.0 g/day for preventing relapse (RR=0.79; 95% CI 0.64–0.97). Conclusions: 5-ASAs are highly effective for inducing remission and preventing relapse in UC. Evidence suggests that doses of ≥2.0 g/day have greater efficacy, although doses >2.5 g/day do not appear to lead to higher remission rates. 2013-01-09T04:40:05.706Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:5116 Background and Aims: The pathogenesis of Crohn's disease (CD) remains unclear. A major controversy has been whether infection with Mycobacterium avium subspecies paratuberculosis (MAP) plays a significant role. Current support for a role of MAP is largely based on epidemiological data. The aim of this study was to determine whether MAP detection in gut biopsies is associated with a different cytokine secretion profile as observed in whole blood culture. Methods: A whole blood culture system was employed to measure cytokine secretion, using an ELISA assay, in subjects with CD (n = 46), ulcerative colitis (n = 30), irritable bowel syndrome (n = 22) and normal controls (n = 18). MAP status was defined by nested PCR using an IS900 sequence unique to MAP. Results: Significantly higher levels of interleukin (IL)-4 (P < 0.05) and IL-2 (P < 0.05) were found in MAP+ CD compared to MAP− CD. This was selective, as MAP+ subjects in both normal and disease controls had similar levels of IL-4 and IL-2 to those with no detectable MAP. IL-4 secretion was correlated with IL-2 production in blood cultures in CD (P < 0.01), consistent with a skewed Th2 immune response. Conclusions: This data set provides the first evidence of altered T cell function linked to MAP infection in CD, and provides a link between detection of MAP and disease. The pattern of cytokine shift in CD is consistent with the concept that the increasing incidence of CD is in part related to the hygiene theory. 2010-04-27T04:41:45.757Z ]]>