Urgent Versus Standard Colonoscopy for Management of Acute Lower Gastrointestinal Bleeding: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Acute lower gastrointestinal bleeding (LGIB) is a common indication for hospitalization. However, the optimum timing of colonoscopy following patient presentation remains unclear. This systematic review and meta-analysis aims to evaluate the effect of urgent versus standard colonoscopy timing on management of acute LGIB. MATERIALS AND METHODS: Medline, EMBASE, CENTRAL, and PubMed were searched up to January 2020. Randomized controlled trials were eligible for inclusion if they compared patients with hematochezia receiving urgent (<24 h) versus standard (>24 h) colonoscopy. Nonrandomized observational studies were also included based on the same criteria for additional analysis. Pooled estimates were calculated using random effects meta-analyses and heterogeneity was quantified using the inconsistency statistic. Certainty of evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluation (GRADE). RESULTS: Of 3782 potentially relevant studies, 4 randomized controlled trials involving 463 patients met inclusion criteria. Urgent colonoscopy did not differ significantly to standard timing with respect to length of stay (LOS), units of blood transfused, rate of additional intervention required, or mortality. Colonoscopy-related outcomes such as patient complications, rebleeding rates, and diagnosis of bleeding source did not differ between groups. However, meta-analysis including nonrandomized studies (9 studies, n=111,950) revealed a significantly higher rate of mortality and complications requiring surgery in the standard group and shorter LOS in the urgent group. Overall GRADE certainty of evidence was low in the majority of outcomes. CONCLUSIONS: Timing of colonoscopy in acute LGIB may not significantly affect patient outcomes. Timing should therefore be decided on a case-by-case basis.

Resident Survey on Gastroenterology Training in Canada.

BACKGROUND: Gastroenterology training in Canada is guided by the Royal College of Physicians and Surgeons of Canada. Resident perspectives on training and the degree of heterogeneity across training programs have not been previously surveyed. AIM: This study aims to evaluate the current Canadian adult gastroenterology training experience from a resident perspective and provide insight into the heterogeneity among training programs. METHOD: A survey designed by three current gastroenterology residents was distributed to trainees attending the Gastroenterology Residents-in-Training course at Canadian Digestive Diseases Week 2018. Categorical data from the survey was analyzed in table format. Other continuous data was converted to dichotomous data and analyzed in groups of small and large programs, the large program defined as greater than six trainees. RESULTS: The overall response rate was 45 of 56 (80%), representing 13 of 14 accredited training sites. Mandatory rotations and core procedures varied widely across respondents, with only inpatient training consistent across all sites. Small programs had a higher call burden (P=0.039), but staff were more likely to be available to cover call if the resident coverage was unavailable (P=0.002). There were nonsignificant trends in small programs in the inability to take a post-call day (P=0.07) and a resident perception of being well trained (P=0.07). CONCLUSIONS: There is heterogeneity across programs in mandatory rotations and core procedures. With the upcoming shift to competency-based medical education, it is an opportune time to re-evaluate and perhaps standardize how gastroenterology training is delivered in Canada.

The Benefit of Fentanyl in Effective Sedation and Quality of Upper Endoscopy: A Double-Blinded Randomized Trial of Fentanyl Added to Midazolam Versus Midazolam Alone for Sedation.

AIMS: Our goals were to compare the effect of adding fentanyl to midazolam in a double-blinded, randomized, placebo-controlled trial and determine if fentanyl enhances sedation, increases adverse events or effects time of the procedure or discharge. METHODS: Patients 18 to 65 years scheduled for outpatient upper endoscopy were eligible for the study. Patients were randomized to receive either 100 mcg/2 mL of Fentanyl or 2 mL of placebo IV with a double-blinded protocol. All patients received 2 mg of intravenous midazolam initially. Additional midazolam could be given to achieve adequate sedation. RESULTS: There were 68 patients randomized to the Fentanyl group and 69 patients to the placebo group. The mean dose of midazolam was 4.0 mg for the Fentanyl group and 5.2 mg for placebo group (P=0.003). Both endoscopist and nurse independently rated sedation to be better in the fentanyl group (P=0001). The patient did not perceive any difference in sedation (P=0.4). Procedure time was significantly shorter in the Fentanyl group (8.5 versus 11.1 minutes, P=0.001), with no difference in the discharge time. There was significantly less retching observed in patients in the fentanyl group (P<0.001). There were no major complications. CONCLUSIONS: Endoscopists and nurses found adding fentanyl significantly improved sedation, led to a shorter procedure time, and allowed for less midazolam to be used per case. It did not affect the patient experience of sedation and was safe. Fentanyl use for routine outpatient upper endoscopy should be considered as a safe option to improve procedural sedation.NCT:01514695 (www.clinicaltrials.gov)Accepted as an abstract for the Canadian Digestive Diseases Week meeting in February 2014.

Epidemiology and risk factors for bloodstream infections in a home parenteral nutrition program.

BACKGROUND: An increasing number of patients with intestinal failure are receiving home parenteral nutrition (HPN). Associated complications include bloodstream infections (BSIs), but data on rates and risk factors for HPN-related BSIs are scarce. METHODS: A retrospective review was conducted of patients enrolled in the regional HPN program between 2001 and 2008. Demographic information and data on indication for HPN, duration of PN therapy, type and date of insertion of central venous access device, and blood culture results were recorded. RESULTS: In total, 155 patients (165 courses of HPN) were included for a total of 45,876 catheter days. The mean patient age was 49 years, and 105 (64%) patients were female. A total of 105 organisms were cultured from 93 distinct episodes of BSIs. The rate of BSI was found to be 2.0 per 1000 catheter days, but excluding BSIs with a single positive culture of coagulase-negative staphylococcus and diphtheroid bacilli, the rate of infection was 1.4 per 1000 catheter days. Male sex and underlying malignancy were significant predictors of BSI, with hazard ratios of 1.69 (95% confidence interval [CI], 1.14-2.60; P = .009) and 2.38 (95% CI, 1.53-3.50; P < .001). CONCLUSION: In a large heterogeneous group of HPN patients, the BSI rate ranged between 1.4 and 2.0 infections per 1000 catheter days. Isolated organisms were similar to those found in hospitalized patients. Male sex and underlying malignancy were significant risk factors for BSI. These high-risk patients are likely to benefit from interventions aimed at reducing BSIs.

Prophylactic PPI help reduce marginal ulcers after gastric bypass surgery: a systematic review and meta-analysis of cohort studies.

BACKGROUND: Marginal ulceration after gastric bypass surgery is a recognized complication and has been reported in 1-16% of patients. There is evidence that acidity may play a role in the disease pathophysiology and it is a common practice for bariatric surgeons to begin a prophylactic course of proton pump inhibitors (PPI), postoperatively. METHODS: MEDLINE, EMBASE, CINAHL, and the Cochrane Controlled Trials Register were searched using the most comprehensive timeline for each database up to January 2012. Studies that included patients undergoing gastric bypass who received a prophylactic course of PPI postoperatively were eligible. Two reviewers independently selected trials and extracted data. The primary outcome was the incidence of marginal ulcers diagnosed on the basis of endoscopic findings. Inverse variance random effects models were used to estimate odds ratio (OR) and weighted proportion of ulcers. Odds ratio and weighted pooled proportion with corresponding 95% confidence intervals (CI) are reported. RESULTS: The strategic search identified 167 citations. A total of seven studies involving 2,917 participants were eligible for inclusion and 2,114 were used for analysis. The weighted pooled proportion of ulcer formation in PPI groups including all seven studies (four single group cohort studies and PPI arm of three cohort studies) was 5.0% [95% CI 2-10%] (N = 1,407). The OR of marginal ulcer formation comparing PPI to no PPI for three comparative cohort studies was 0.50 [95% CI 0.28-0.90, p = 0.02] (N = 1,022) with low heterogeneity (I(2) = 12%) showing that the PPI group significantly experienced twice less ulceration with PPI treatment compared to no PPI treatment. CONCLUSION: This finding suggests a significant incremental benefit of prophylactic PPI in reducing marginal ulcer after gastric bypass surgery. Prospective randomized trials are needed to further define the role of PPI following gastric bypass surgery.

Optimum duration of regimens for Helicobacter pylori eradication.

BACKGROUND: The optimal duration for Helicobacter pylori (H. pylori) eradication therapy is controversial, with recommendations ranging from 7 to 14 days. Several systematic reviews have attempted to address this issue but have given conflicting results and limited their analysis to proton pump inhibitor (PPI), two antibiotics (PPI triple) therapy. We performed a systematic review and meta-analysis to investigate the optimal duration of multiple H. pylori eradication regimens. OBJECTIVES: The primary objective was to assess the relative effectiveness of different durations (7, 10 or 14 days) of a variety of regimens for eradicating H. pylori. The primary outcome was H. pylori persistence. The secondary outcome was adverse events. SEARCH METHODS: The Cochrane Library, MEDLINE, EMBASE, and CINAHL were searched up to December 2011 to identify eligible randomised controlled trials (RCTs). We also searched the proceedings of six conferences from 1995 to 2011, dissertations and theses, and grey literature. There were no language restrictions applied to any search. SELECTION CRITERIA: Only parallel group RCTs assessing the efficacy of one to two weeks duration of first line H. pylori eradication regimens in adults were eligible. Within each regimen, the same combinations of drugs at the same dose were compared over different durations. Studies with at least two arms comparing 7, 10, or 14 days were eligible. Enrolled participants needed to be diagnosed with at least one positive test for H. pylori on the basis of a rapid urease test (RUT), histology, culture, urea breath test (UBT), or a stool antigen test (HpSA) before treatment. Eligible trials needed to confirm eradication of H. pylori as their primary outcome at least 28 days after completion of eradication treatment. Trials using only serology or a polymerase chain reaction (PCR) to determine H. pylori infection or eradication were excluded. DATA COLLECTION AND ANALYSIS: Study eligibility and data extraction were performed by two independent review authors. Data analyses were performed within each type of intervention, for both primary and secondary outcomes. The relative risk (RR) and number needed to treat (NNT)/number needed to harm (NNTH) according to duration of therapy were calculated using the outcomes of H. pylori persistence and adverse events. A random-effects model was used. Subgroup analyses and sensitivity analyses were planned a priori. MAIN RESULTS: In total, 75 studies met the inclusion criteria. Eight types of regimens were reported with at least two comparative eligible durations. They included: PPI + two antibiotics triple therapy (n = 59), PPI bismuth-based quadruple therapy (n = 6), PPI + three antibiotics quadruple therapy (n = 1), PPI dual therapy (n = 2), histamine H2-receptor antagonist (H2RA) bismuth quadruple therapy (n = 3), H2RA bismuth-based triple therapy (n = 2), H2RA + two antibiotics triple therapy (n = 3), and bismuth + two antibiotics triple therapy (n = 2). Some studies provided data for more than one regimen or more than two durations.For the PPI triple therapy, 59 studies with five regimens were reported: PPI + clarithromycin + amoxicillin (PCA); PPI + clarithromycin + a nitroimidazole (PCN); PPI + amoxicillin + nitroimidazole (PAN); PPI + amoxicillin + a quinolone (PAQ); and PPI + amoxicillin + a nitrofuran (PANi). Regardless of type and dose of antibiotics, increased duration of PPI triple therapy from 7 to 14 days significantly increased the H. pylori eradication rate (45 studies, 72.9% versus 81.9%), the RR for H. pylori persistence was 0.66 (95% CI 0.60 to 0.74), NNT was 11 (95% CI 9 to 14). Significant effects were seen in the subgroup of PCA (34 studies, RR 0.65, 95% CI 0.57 to 0.75; NNT 12, 95% CI 9 to 16); PAN (10 studies, RR 0.67, 95% CI 0.52 to 0.86; NNT = 11, 95% CI 8 to 25); and in PAQ (2 studies, RR 0.37, 95% CI 0.16 to 0.83; NNT 3, 95% CI 2 to 10); but not in PCN triple therapy (4 studies, RR 0.87, 95% CI 0.71 to 1.07). Significantly increased eradication rates were also seen for PPI triple therapy with 10 versus 7 days (24 studies, 79.9% versus 75.7%; RR 0.80, 95% CI 0.72 to 0.89; NNT 21, 95% CI 15 to 38) and 14 versus 10 days (12 studies, 84.4% versus 78.5%; RR 0.72, 95% CI 0.58 to 0.90; NNT 17, 95% CI 11 to 46); especially in the subgroup of PAC for 10 versus 7 days (17 studies, RR 0.80, 95% CI 0.70 to 0.91) and for 14 versus 10 days (10 studies, RR 0.69, 95% CI 0.52 to 0.91). A trend towards increased H. pylori eradication rates was seen with increased duration of PCN for 10 versus 7 days, and of PAN for 10 versus 7 days and 14 versus 10 days, though this was not statistical significant. The proportion of patients with adverse events, defined by authors, was marginally significantly increased only between 7 days and 14 days (15.5% versus 19.4%; RR 1.21, 95% CI 1.06 to 1.37; NNTH 31, 95% CI 18 to 104) but not for other duration comparisons. The proportion of patients discontinuing treatment due to adverse events was not significantly different between treatment durations.Only limited data were reported for different durations of regimens other than PPI triple therapy. No significant difference of the eradication rate was seen for all regimens according to different durations except for H2RA bismuth quadruple therapy, where a significantly higher eradication rate was seen for 14 days versus 7 days, however only one study reported outcome data. AUTHORS' CONCLUSIONS: Increasing the duration of PPI-based triple therapy increases H. pylori eradication rates. For PCA, prolonging treatment duration from 7 to 10 or from 10 to 14 days is associated with a significantly higher eradication rate. The optimal duration of therapy for PCA and PAN is at least 14 days. More data are needed to confirm if there is any benefit of increasing the duration of therapy for PCN therapy. Information is limited for regimens other than PPI triple therapy; more studies are needed to draw meaningful conclusions for optimal duration of other H. pylori eradication regimens.

Safety of esophagogastroduodenoscopy within 30 days of myocardial infarction: a retrospective cohort study from a Canadian tertiary centre.

BACKGROUND: Patients who experience myocardial infarction (MI) are at risk of gastrointestinal (GI) bleeding complications. Endoscopic evaluation may lead to cardiopulmonary complications. Guidelines and studies regarding the safety of endoscopy in this population are limited. OBJECTIVE: To evaluate the safety of endoscopy in a retrospective cohort of post-MI patients at a Canadian tertiary centre. METHODS: Using hospital diagnostic/procedure codes, the charts of patients meeting the inclusion criteria of having ST elevation MI or non-ST elevation MI, and GI bleeding detected at endoscopy were reviewed. The information retrieved included demographics, medical history, medications, endoscopy details and cardiopulmonary/GI events. RESULTS: A total of 121 patients experienced an MI and underwent endoscopy within 30 days. However, only 44 met the inclusion criteria and were reviewed. The mean age of the patients was 75 years, and 55% were female. The mean hemoglobin level was 86 g/L, and 38 of 44 patients required a transfusion. Comorbidities included hypertension (82%), diabetes (46%), heart failure (55%), stroke (21%), lung disease (27%), previous MI (46%), cardiac bypass surgery (30%), history of GI bleed (25%), history of ulcer (18%) and ejection fraction <50% (48%). The median number of days to endoscopy after MI was three. Complications included seven patients with acute coronary syndrome, one with arrhythmia, one with respiratory failure, one with aspiration pneumonia and two with perforation. Age, hemoglobin level or timing of endoscopy did not significantly predict a complication. CONCLUSIONS: Patients with GI bleeding after MI often have comorbidities and are on antiplatelet agents. Endoscopy is a valuable tool in the diagnosis and management of bleeding complications, but must be weighed against the potential risk of other complications, which in the present study occurred in more than 25% of procedures.

Efficacy of topical 5-aminosalicylates in preventing relapse of quiescent ulcerative colitis: a meta-analysis.

BACKGROUND & AIMS: Topical 5-aminosalicylates (5-ASAs) such as mesalamine are effective in inducing remission in patients with mild to moderately active ulcerative colitis (UC). However, there has been no meta-analysis of their efficacy in preventing relapse of quiescent UC. METHODS: We searched MEDLINE, EMBASE, and the Cochrane central register of controlled trials through July 2011 for randomized controlled trials comparing the effects of topical 5-ASAs with placebo in adults with quiescent UC. Dichotomous data were pooled to obtain relative risk (RR) of relapse of disease activity. The number needed to treat (NNT) was calculated from the reciprocal of the risk difference. Adverse events data were summarized. RESULTS: The search identified 3061 citations; we analyzed data from seven (555 patients). All trials used mesalamine, but only one included patients with extensive disease. The duration of therapy ranged from 6-24 months. The RR of relapse of disease activity in patients with quiescent UC who were given topical mesalamine, compared with placebo, was 0.60 (95% confidence interval, 0.49-0.73; NNT = 3); there was no significant heterogeneity between studies (I(2) = 21%, P = .27). No significant differences in rates of adverse events rates were detected (RR = 1.01; 95% confidence interval, 0.59-1.72). CONCLUSIONS: On the basis of a meta-analysis of 7 randomized controlled trials, topical mesalamine is effective in preventing relapse of quiescent UC, with no greater number of adverse events than placebo. However, because most studies included only patients with left-sided disease or proctitis, the efficacy of topical mesalamine in preventing relapse in patients with more extensive quiescent UC is not known.

Efficacy of oral vs. topical, or combined oral and topical 5-aminosalicylates, in Ulcerative Colitis: systematic review and meta-analysis.

OBJECTIVES: Efficacy of 5-aminosalicylic acids (5-ASAs) in ulcerative colitis (UC) has been studied previously in meta-analyses. However, no recent meta-analysis has studied the relative efficacies of differing routes of administration. METHODS: MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (through May 2011). Eligible trials recruited adults with mildly to moderately active UC, or quiescent UC, and compared oral 5-ASAs with either topical 5-ASAs or a combination of oral and topical 5-ASAs. 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 12 randomized controlled trials (RCTs) were eligible. Four compared topical with oral 5-ASAs in active UC remission, with an RR of no remission with topical 5-ASAs of 0.82 (95% CI=0.52-1.28). Four trials compared combined with oral 5-ASAs in active UC (RR of no remission=0.65; 95% CI=0.47-0.91; NNT=5). Three RCTs compared intermittent topical with oral 5-ASAs in preventing relapse of quiescent UC (RR=0.64; 95% CI=0.43-0.95; NNT=4), and two compared combined with oral 5-ASAs (RR of relapse=0.48; 95% CI=0.17-1.38). CONCLUSIONS: Combined 5-ASA therapy appeared superior to oral 5-ASAs for induction of remission of mildly to moderately active UC. Intermittent topical 5-ASAs appeared superior to oral 5-ASAs for preventing relapse of quiescent UC.

Once-daily dosing vs. conventional dosing schedule of mesalamine and relapse of quiescent ulcerative colitis: systematic review and meta-analysis.

OBJECTIVES: Maintenance therapy with 5-aminosalicylates (5-ASAs) is recommended in patients with quiescent ulcerative colitis (UC), but compliance rates are low. Once-daily dosing may improve adherence, but impact on the relapse of disease activity is unclear as no previous meta-analysis has studied this issue. METHODS: MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (through April 2011). Eligible randomized controlled trials (RCTs) recruited adults with quiescent UC, and compared once-daily dosing of 5-ASAs with a more frequent dosing schedule of an identical total daily dose of the same 5-ASA drug. Minimum treatment duration was 6 months. Trials reported a dichotomous assessment of relapse of disease activity at last point of follow-up. Data concerning non-compliance and adverse events were extracted, where reported. Effect of once-daily vs. more frequent dosing schedule was reported as relative risk (RR) of relapse with a 95% confidence interval (CI). RESULTS: The search identified 3,061 citations, and seven RCTs containing 2,745 patients were eligible. All RCTs used mesalamine. Relapse rates were not significantly different between once-daily and conventional dosing schedules for mesalamine (RR of relapse=0.94; 95% CI: 0.82-1.08). Non-compliance (RR=0.87; 95% CI: 0.46-1.66) and adverse events were no more likely with once-daily dosing (RR=1.08; 95% CI: 0.97-1.20). CONCLUSIONS: Once-daily dosing with mesalamine is as effective as conventional dosing schedules for the prevention of relapse of quiescent UC, although there is no definitive evidence that compliance with once-daily dosing is better. Adverse events occur at a similar frequency.

Glucocorticosteroid therapy in inflammatory bowel disease: systematic review and meta-analysis.

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.

Efficacy of biological therapies in inflammatory bowel disease: systematic review and meta-analysis.

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.

Efficacy of immunosuppressive therapy for inflammatory bowel disease: a systematic review and meta-analysis.

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.

Antibiotic therapy in inflammatory bowel disease: a systematic review and meta-analysis.

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 (I(2)=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 (I(2)=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 (I(2)=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 (I(2)=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.

Efficacy of 5-aminosalicylates in ulcerative colitis: systematic review and meta-analysis.

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.

Efficacy of 5-aminosalicylates in Crohn's disease: systematic review and meta-analysis.

OBJECTIVES: Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract. Evidence for treatment with 5-aminosalicylic acid (5-ASA) drugs is conflicting. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to examine this issue. METHODS: MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (through December 2010). Authors of studies were contacted to provide additional information on trials where required, and experts in the field were contacted to identify unpublished studies. Eligible trials recruited adults with active or quiescent CD and compared 5-ASAs with placebo, or no treatment. Dichotomous data were pooled to obtain relative risk (RR) of failure to achieve remission in active CD, and RR of relapse of disease activity in quiescent CD, 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. Twenty-two RCTs were eligible. Six RCTs compared 5-ASA with placebo in active CD remission. There was a trend towards a benefit with sulfasalazine over placebo (two RCTs, RR of failure to achieve remission=0.83; 95% CI=0.69-1.00), but no definite benefit of mesalamine over placebo (four RCTs, RR=0.91; 95% CI=0.77-1.06). Neither sulfasalazine nor mesalamine were effective in preventing quiescent CD relapse, but in a per protocol analysis mesalamine appeared to reduce risk of relapse (RR=0.79; 95% CI=0.66-0.95, NNT=13). CONCLUSIONS: The role of 5-ASAs in inducing remission of active CD and preventing relapse of quiescent CD remains uncertain, and more RCTs are required.

5-aminosalicylates prevent relapse of Crohn's disease after surgically induced remission: systematic review and meta-analysis.

OBJECTIVES: Evidence from randomized controlled trials (RCTs) for the use of 5-aminosalicylic acid (5-ASA) drugs in Crohn's disease (CD) in remission after a surgical resection is conflicting. We conducted a systematic review and meta-analysis of RCTs to examine this issue. METHODS: MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (through April 2010). Eligible trials recruited adults with luminal CD in remission after a surgical resection and compared 5-ASAs with placebo, or no treatment. Dichotomous data were pooled to obtain relative risk (RR) of relapse of disease activity, with a 95% confidence interval (CI). The number needed to treat (NNT) was calculated from the reciprocal of the risk difference. RESULTS: The search strategy identified 3,061 citations. Eleven RCTs were eligible for inclusion containing 1,282 patients. The RR of relapse of CD in remission after surgery with 5-ASA vs. placebo or no therapy was 0.86 (95% CI=0.74-0.99) (NNT=13). Sulfasalazine was of no benefit in preventing relapse in 448 patients (RR=0.97; 95% CI=0.72-1.31), but mesalamine was more effective than placebo or no therapy (RR=0.80; 95% CI=0.70-0.92) in 834 patients, with an NNT of 10. CONCLUSIONS: Mesalamine is of modest benefit in preventing relapse of CD in remission after surgery. Its use should be considered in those in whom immunosuppressive therapy is either not warranted or contraindicated.