Repeat Rifaximin for Irritable Bowel Syndrome: No Clinically Significant Changes in Stool Microbial Antibiotic Sensitivity.

BACKGROUND: Rifaximin has demonstrated efficacy and safety for diarrhea-predominant irritable bowel syndrome (IBS-D). AIM: To determine the rifaximin repeat treatment effect on fecal bacterial antibiotic susceptibility. METHODS: Patients with IBS in Trial 3 (TARGET 3) study who responded to open-label rifaximin 550 mg three times daily for 2 weeks, with symptom recurrence within 18 weeks, were randomized to double-blind treatment: two 2-week repeat courses of rifaximin or placebo, separated by 10 weeks. Prospective stool sample collection occurred before and after open-label rifaximin, before and after the first repeat course, and at the end of the study. Susceptibility testing was performed with 11 antibiotics, including rifaximin and rifampin, using broth microdilution or agar dilution methods. RESULTS: Of 103 patients receiving open-label rifaximin, 73 received double-blind rifaximin (n = 37) or placebo (n = 36). A total of 1429 bacterial and yeast isolates were identified, of which Bacteroidaceae (36.7%) and Enterobacteriaceae (33.9%) were the most common. In the double-blind phase, Clostridium difficile was highly susceptible to rifaximin [minimum inhibitory concentration (MIC) range 0.008-1 µg/mL] and rifampin (MIC range 0.004-0.25 µg/mL). Following double-blind rifaximin treatment, Staphylococcus isolates remained susceptible to rifaximin at all visits (MIC50 range ≤0.06-32 µg/mL). Rifaximin exposure was not associated with long-term cross-resistance of Bacteroidaceae, Enterobacteriaceae, and Enterococcaceae to rifampin or nonrifamycin antibiotics tested. CONCLUSIONS: In this study, short-term repeat treatment with rifaximin has no apparent long-term effect on stool microbial susceptibility to rifaximin, rifampin, and nonrifamycin antibiotics. CLINICALTRIALS. GOV IDENTIFIER: NCT01543178.

Status of Competency-Based Medical Education in Endoscopy Training: A Nationwide Survey of US ACGME-Accredited Gastroenterology Training Programs.

OBJECTIVES: The Accreditation Council for Graduate Medical Education (ACGME) emphasizes the importance of medical trainees meeting specific performance benchmarks and demonstrating readiness for unsupervised practice. The aim of this study was to examine the readiness of Gastroenterology (GI) fellowship programs for competency-based evaluation in endoscopic procedural training. METHODS: ACGME-accredited GI program directors (PDs) and GI trainees nationwide completed an online survey of domains relevant to endoscopy training and competency assessment. Participants were queried about current methods and perceived quality of endoscopy training and assessment of competence. Participants were also queried about factors deemed important in endoscopy competence assessment. Five-point Likert items were analyzed as continuous variables by an independent t-test and χ(2)-test was used for comparison of proportions. RESULTS: Survey response rate was 64% (94/148) for PDs and 47% (546/1,167) for trainees. Twenty-three percent of surveyed PDs reported that they do not have a formal endoscopy curriculum. PDs placed less importance (1­very important to 5­very unimportant) on endoscopy volume (1.57 vs. 1.18, P<0.001), adenoma detection rate (2.00 vs. 1.53, P<0.001), and withdrawal times (1.96 vs. 1.68, P=0.009) in determining endoscopy competence compared with trainees. A majority of PDs report that competence is assessed by procedure volume (85%) and teaching attending evaluations (96%). Only a minority of programs use skills assessment tools (30%) or specific quality metrics (28%). Specific competencies are mostly assessed by individual teaching attending feedback as opposed to official documentation or feedback from a PD. PDs rate the overall quality of their endoscopy training and assessment of competence as better than overall ratings by trainees. CONCLUSIONS: Although the majority of PDs and trainees nationwide believe that measuring specific metrics is important in determining endoscopy competence, most programs still rely on procedure volume and subjective attending evaluations to determine overall competence. As medical training transitions from an apprenticeship model to competency-based education, there is a need for improved endoscopy curricula which are better suited to demonstrate readiness for unsupervised practice.

Safety and tolerability of rifaximin for the treatment of irritable bowel syndrome without constipation: a pooled analysis of randomised, double-blind, placebo-controlled trials.

BACKGROUND: The efficacy of rifaximin, a nonsystemic, gut-targeted antibiotic for reducing non-constipation-predominant irritable bowel syndrome (non-C IBS) symptoms, has been demonstrated in one phase 2b and two phase 3 randomised, double-blind, placebo-controlled trials, but detailed data about rifaximin safety and tolerability during treatment and subsequent follow-up periods are lacking. AIM: To assess and determine the frequency of rifaximin and placebo adverse events (AEs) in phase 2b and phase 3 non-C IBS trials. METHODS: A post hoc pooled safety analysis of the phase 2b (rifaximin 275, 550, and 1100 mg twice daily for 2 weeks; 550 mg twice daily for 4 weeks) and phase 3 (rifaximin 550 mg three times daily for 2 weeks) studies was performed. Data on treatment and post-treatment AEs were collected. Patients were followed up for 12 weeks and 10 weeks post-treatment in the phase 2b and phase 3 trials, respectively. RESULTS: Patients receiving rifaximin (n = 1103) and placebo (n = 829) had a similar incidence of drug-related AEs (12.1% vs. 10.7%), serious AEs (1.5% vs. 2.2%), drug-related AEs resulting in study discontinuation (0.8% vs. 0.8%), gastrointestinal-associated AEs (12.2% vs. 12.2%) and infection-associated AEs (8.5% vs. 9.5%). There were no cases of Clostridium difficile colitis or deaths. CONCLUSIONS: The safety and tolerability profile of rifaximin during treatment and post-treatment was comparable to placebo. Future research should define the safety and tolerability profile, including risk of C. difficile colitis and microbial antibiotic resistance, with repeated courses of rifaximin in patients with non-constipation-predominant irritable bowel syndrome (ClinicalTrials.gov: NCT00269412, NCT00731679, and NCT00724126).

Dysregulation of iron protein expression in the G93A model of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by selective loss of motor neurons which leads to progressive paralysis and death by respiratory failure. Although the cause of sporadic ALS is still unknown, oxidative stress is suggested to play a major role in the pathogenesis of this disease and of the rare familial form, which often exhibits mutations of the superoxide dismutase 1 (SOD1) gene. Since enhanced iron levels are discussed to participate in oxidative stress and neuronal death, we analyzed the expression levels of Fe-related mRNAs in a cell culture ALS model with the G93A mutation of SOD1. We observed an increased total iron content in G93A-SOD1 SH-SY5Y neuroblastoma cells compared to wild-type (WT)-SOD1 cells. mRNA expression for transferrin receptor 1 (TfR1) and divalent metal transporter 1 was increased in G93A-SOD1 cells, which was in accordance with higher iron uptake. Experiments with the iron chelator deferoxamine revealed a normal reaction of WT and mutant cells to cytoplasmic iron depletion, i.e. TfR1 upregulation, suggesting a basically conserved function of the iron-responsive element/iron regulatory protein (IRE/IRP) pathway, designed to adapt gene expression to iron levels. Expression levels of mitoferrin 1 and 2, frataxin, and iron-sulfur cluster scaffold protein were also significantly increased in G93A-SOD1 cells, suggesting higher mitochondrial iron import and utilization in biosynthetic pathways within the mitochondria. Moreover, expression of these transcripts was further enhanced, if G93A-SOD1 cells were differentiated by retinoic acid (RA). Since RA treatment increased cytoplasmic reactive oxygen species (ROS) levels in these cells, an IRE/IRP independent, ROS-mediated mechanism may account for dysregulation of iron-related genes.

Prophylactic 5-Fr pancreatic duct stents are superior to 3-Fr stents: a randomized controlled trial.

BACKGROUND: Temporary prophylactic pancreatic duct stenting effectively reduces post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in high-risk patients, but the optimal stent remains unclear. We compared rate of spontaneous passage, and technical difficulty of placement for 3-Fr and 5-Fr stents. METHODS: A randomized controlled trial at a single academic medical center. Patients deemed high risk for PEP randomly received 5-Fr or 3-Fr pancreatic duct stents. Primary outcome was spontaneous stent passage by 2 weeks. Secondary outcomes were ease and time for stent placement, and number of guide wires required for the entire procedure. RESULTS: Patients (69 female [89 %]; mean age 44.9 years, standard deviation [SD] 16.8) were randomly assigned to receive 5-Fr (n = 38) and 3-Fr (n = 40) stents. Indications for stenting were similar. Seven patients in the 3-Fr group actually received a 5-Fr stent, and two in the 5-Fr group had a 3-Fr stent. Spontaneous passage or non-passage was confirmed in 64 (83 %). No statistically significant difference in spontaneous passage rates was seen (5-Fr group, 68.4 %; 3-Fr group 75.0 %; P = 0.617). Non-passage rates were 10.5 % (5-Fr group) and 10.0 % (3-Fr group) ( P = 1.00). The study was stopped after a futility analysis for the primary end point. Placement of 5-Fr stents was rated easier, at a mean score of 1.8 (5-Fr) vs. 3.4 (3-Fr), P < 0.001, with a trend towards being faster, 9.2 vs. 11.1 minutes ( P = 0.355). Fewer guide wires were required for 5-Fr stent placement, 1.5 vs. 1.9 ( P = 0.002). PEP rates did not differ ( P = 0.519). CONCLUSION: Placement of 5-Fr compared to 3-Fr pancreatic duct stents for PEP prophylaxis is easier, faster, and requires fewer wires. No statistically significant difference in spontaneous passage was found between the two sizes.

Meta-analysis: re-treatment of genotype I hepatitis C nonresponders and relapsers after failing interferon and ribavirin combination therapy.

BACKGROUND: The efficacy of re-treating genotype I hepatitis C virus (HCV) patients who failed combination therapy with interferon/pegylated interferon (PEG-IFN) and ribavirin remains unclear. AIMS: To quantify sustained virological response (SVR) rates with different re-treatment regimens through meta-analysis of randomized controlled trials (RCTs). METHODS: Randomized controlled trials of genotype I HCV treatment failure patients that compared currently available re-treatment regimens were selected. Two investigators independently extracted data on patient population, methods and results. The pooled relative risk of SVR for treatment regimens was computed using a random effects model. RESULTS: Eighteen RCTs were included. In nonresponders to standard interferon/ribavirin, re-treatment with high-dose PEG-IFN combination therapy improved SVR compared with standard PEG-IFN combination therapy (RR=1.49; 95% CI: 1.09-2.04), but SVR rates did not exceed 18% in most studies. In relapsers to standard interferon/ribavirin, re-treatment with high-dose PEG-IFN or prolonged CIFN improved SVR (RR=1.57; 95% CI: 1.16-2.14) and achieved SVR rates of 43-69%. CONCLUSIONS: In genotype I HCV treatment failure patients who received combination therapy, re-treatment with high-dose PEG-IFN combination therapy is superior to re-treatment with standard combination therapy, although SVR rates are variable for nonresponders (≤18%) and relapsers (43-69%). Re-treatment may be appropriate for select patients, especially relapsers and individuals with bridging fibrosis or compensated cirrhosis.

Systematic review: efficacy and safety of pancreatic enzyme supplements for exocrine pancreatic insufficiency.

BACKGROUND: Pancreatic enzyme supplements are standard therapy for fat malabsorption in patients with exocrine pancreatic insufficiency. The FDA determined that published data are insufficient to support the efficacy and safety of these agents. AIM: To determine if pancreatic enzyme supplements are: (i) superior to placebo for treating fat malabsorption and (ii) superior to other supplements based on randomized cross-over trials. METHODS: A computer-assisted search of MEDLINE and EMBASE was performed to identify relevant studies. Data extraction on study design, improvement in coefficient of fat absorption, diarrhoea and adverse events using prespecified forms. RESULTS: A total of 12 manuscripts met inclusion criteria. Most studies (10/12) compared pancreatic enzyme supplements that used different delivery systems, while using similar quantities of enzymes. These studies found no consistent difference in fat malabsorption or gastrointestinal symptoms between different active treatments. Two small placebo-controlled trials (n = 65 patients) demonstrate that pancreatic enzyme supplements are superior to placebo for fat absorption. Data are inadequate to determine if pancreatic enzyme supplements lead to weight gain or improvement in diarrhoea. CONCLUSIONS: Based on data from randomized cross-over trials, pancreatic enzyme supplements appear to improve fat malabsorption. No specific branded product or specific delivery system is superior for treatment of fat malabsorption in patients with exocrine pancreatic insufficiency.

Systematic review: pancreatic enzyme treatment of malabsorption associated with chronic pancreatitis.

BACKGROUND: Pancreatic enzyme supplementation is standard treatment for malabsorption caused by chronic pancreatitis. The FDA recently required all manufacturers to submit New Drug Applications to continue to market these agents because published data demonstrated variation in formulation, bioavailability and shelf-life while providing limited data about efficacy and safety. AIM: To review systematically the design and results of randomized, parallel-design trials of pancreatic enzyme supplements in chronic pancreatitis patients with steatorrhea. METHODS: A computer-assisted search of MEDLINE and EMBASE was performed to identify relevant studies. Two authors performed duplicate data extraction on study design, improvement in coefficient of fat absorption (CFA), diarrhoea and adverse events using pre-specified forms. Agreement between investigators for data extraction was greater than 95%. RESULTS: Of 619 articles found through literature searching, 20 potentially relevant articles were identified and four manuscripts met inclusion criteria. No studies performed head-to-head comparisons of different supplements. Enzyme supplementation is more likely to improve CFA compared with placebo, but fat malabsorption remained abnormal. Important differences in patient population, study endpoint, study design, pancreatic enzyme dosage and measurement of CFA were present across trials, which precluded comparison of different agents. CONCLUSIONS: Enzyme supplementation improves CFA compared to placebo, but may not abolish steatorrhoea.

Efficacy of antidepressants and psychological therapies in irritable bowel syndrome: systematic review and meta-analysis.

OBJECTIVE: Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder. Evidence for treatment of the condition with antidepressants and psychological therapies is conflicting. DESIGN: Systematic review and meta-analysis of randomised controlled trials (RCTs). MEDLINE, EMBASE and the Cochrane Controlled Trials Register were searched (up to May 2008). SETTING: RCTs based in primary, secondary and tertiary care. PATIENTS: Adults with IBS. INTERVENTIONS: Antidepressants versus placebo, and psychological therapies versus control therapy or "usual management". MAIN OUTCOME MEASURES: Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, 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 571 citations. Thirty-two RCTs were eligible for inclusion: 19 compared psychological therapies with control therapy or "usual management", 12 compared antidepressants with placebo, and one compared both psychological therapy and antidepressants with placebo. Study quality was generally good for antidepressant but poor for psychological therapy trials. The RR of IBS symptoms persisting with antidepressants versus placebo was 0.66 (95% CI, 0.57 to 0.78), with similar treatment effects for both tricyclic antidepressants and selective serotonin reuptake inhibitors. The RR of symptoms persisting with psychological therapies was 0.67 (95% CI, 0.57 to 0.79). The NNT was 4 for both interventions. CONCLUSIONS: Antidepressants are effective in the treatment of IBS. There is less high-quality evidence for routine use of psychological therapies in IBS, but available data suggest these may be of comparable efficacy.

[Rules of good clinical practice for atrial fibrillation in family practice]. / Règles de bonne pratique clinique pour la fibrillation auriculaire en médecine générale.

The epidemiologic observations show that atrial fibrillation is a major challenge of public health. This article underlines the central role of the general practitioner to detect and treat the arrhythmia precociously, and to follow attentively the treatment (in particular, but not only, anticoagulant and antiarrhythmic therapies). The choice between various therapeutic strategies is reviewed. The family practitioner is also placed best to educate the patient to manage his pathology and his treatment in an optimal way. Pharmacological prospects exceeding the antiarrhythmic ones are evoked, as well as the contribution of nonpharmacological strategies, either already accepted in current practice, or under development.

Systematic review: the prevalence of suicidal behaviour in patients with chronic abdominal pain and irritable bowel syndrome.

BACKGROUND: Chronic abdominal pain syndromes may increase the risk of suicidal behaviour - a feature well described in non-visceral pain syndromes. AIM: To perform a systematic review to summarize and interpret published data linking chronic abdominal pain syndromes and suicidal behaviour. METHODS: We performed a structured search to identify studies pertaining to the following questions: (i) What is the prevalence of suicidal behaviour in patients with chronic abdominal pain syndromes, including bowel syndrome (IBS)? (ii) Is the prevalence of suicidal behaviour in chronic abdominal pain syndromes higher than in matched controls? And (iii) is suicidal behaviour in abdominal pain syndromes simply due to psychiatric co-morbidities? RESULTS: Thirty-two relevant titles were identified, of which six manuscripts, describing eight studies, met inclusion criteria. Patients with non-IBS syndromes were 3-11 times more likely to demonstrate suicidal behaviour vs. controls, while patients with IBS were two to four times more likely to have suicidal behaviour. Chronic abdominal pain was an independent predictor of suicidal behaviour after adjusting for co-morbid psychiatric conditions. CONCLUSIONS: Chronic abdominal pain syndromes increase the risk for suicidal behaviours. This relationship may exist independently of co-morbid depression, although additional research is needed to better understand this link. These data indicate that clinicians should survey for suicidal behaviour in chronic abdominal pain patients.

Review article: the safety profile of tegaserod.

Gastrointestinal symptoms are the most common side-effects of tegaserod therapy. In data pooled from Phase III randomized controlled trials in patients with irritable bowel syndrome with constipation, diarrhoea was reported by 8.8% of patients treated with tegaserod 6 mg b.d. vs. 3.8% of patients treated with placebo. Similar rates were observed in international post-US marketing randomized controlled trials. In most patients, tegaserod-induced diarrhoea was mild and transient. In randomized controlled trials, it did not elicit fluid or electrolyte disturbances, and fewer than 3% of irritable bowel syndrome patients discontinued tegaserod due to diarrhoea. The incidence of other gastrointestinal symptoms (e.g. abdominal pain, nausea and flatulence) was similar in tegaserod-treated and placebo-treated patients. Pooled analysis of Phase III and post-US marketing randomized controlled trials did not demonstrate significant differences between tegaserod-treated and placebo-treated patients in the incidence of abdominal/pelvic surgery. No episodes of ischaemic colitis were reported in tegaserod-using patients in any Phase III or post-marketing randomized controlled trials, and post-marketing surveillance indicated that the rate of ischaemic colitis in tegaserod-using patients was lower than that in non-tegaserod-using patients. Pooled analysis of Phase III randomized controlled trials demonstrated an increase in the incidence of headaches in tegaserod-treated (6 mg b.d.) vs. placebo-treated patients (15% vs. 12.3%, respectively; P < 0.05), although post-US marketing randomized controlled trials did not demonstrate this increase. Other extra-gastrointestinal adverse events occurred with similar frequency in tegaserod-treated and placebo-treated patients. Tegaserod-treated patients in randomized controlled trials did not demonstrate significant prolongation of the QTc interval or cardiac arrhythmias compared with placebo-treated patients. In summary, tegaserod exhibits a favourable safety and tolerability profile in irritable bowel syndrome patients based on data from clinical trials.

Systemic review: Natural history of irritable bowel syndrome.

BACKGROUND: The natural history of irritable bowel syndrome is unclear, including the likelihood that these patients will be diagnosed with an alternative organic or functional gastrointestinal disorder. Understanding the stability of an irritable bowel syndrome diagnosis may limit repeated diagnostic evaluation among these patients. METHODS: The inclusion criteria included observational longitudinal studies of clinic-based samples of adult patients with irritable bowel syndrome. Only studies published in the English language in full manuscript form were included. Literature searches, selection and review of eligible articles, and data abstraction were performed in a duplicate, independent manner. RESULTS: Fourteen studies met study selection criteria. In six studies with relevant information, 2-5% of irritable bowel syndrome patients were diagnosed with an alternative organic GI disorder after 6 months to 6 years of follow-up. Long-term follow-up indicated that 2-18% of patients developed worse irritable bowel syndrome symptoms, approximately 30-50% of patients had unchanged symptoms, and the rest either improved or had symptoms disappear. Prior surgery (one study), higher somatic scores (one study), higher baseline anxiety (two studies), depression scores (one study) were predictive of worsening of symptoms during long-term follow-up. CONCLUSIONS: Irritable bowel syndrome, a chronic disorder, is a stable diagnosis. Once initial investigations are negative, fewer than 5% are diagnosed with an alternative organic GI disorder. Repeated diagnostic evaluations of patients with recurrent or persistent symptoms similar to their baseline symptoms are not warranted.

Systematic review: incidence of abdominal/pelvic surgery amongst patients using tegaserod in randomized controlled trials.

BACKGROUND: In the USA, tegaserod is contraindicated in patients with a history of bowel obstruction, abdominal adhesions or symptomatic gall-bladder disease due to a non-significant difference in abdominal surgery between tegaserod-using and placebo-using patients in Phase III trials. AIM: To calculate the incidence of abdominal and pelvic surgery in tegaserod-using and placebo-using patients in randomized controlled trials and to assess the possible association between medication and surgery, using pre-specified criteria in a blind adjudication procedure. METHODS: Primary study selection criteria included: (i) randomized controlled trial; (ii) comparison of tegaserod vs. placebo; and (iii) results reporting the incidence of abdominal and pelvic surgery. A panel of experts in epidemiology and functional bowel disorders reviewed the history of each patient who underwent surgery. Experts were blind with regard to whether patients used tegaserod or placebo. Using pre-specified criteria, experts rated the likelihood of an association between medication use and surgery. RESULTS: Thirteen randomized controlled trials (n =9857 patients) met the primary study selection criteria. No significant difference in the incidence of abdominal/pelvic surgery was identified between tegaserod-using and placebo-using patients: pelvic surgery, 0.16% vs. 0.19% (P = 0.80); abdominal surgery (non-cholecystectomy), 0.15% vs. 0.19% (P = 0.61); cholecystectomy, 0.13% vs. 0.03% (P = 0.17); total abdominal/pelvic surgery, 0.44% vs. 0.41% (P = 1.00). Post-adjudication, there was no significant difference in the incidence of abdominal/pelvic surgery between tegaserod-using and placebo-using patients. CONCLUSION: Data from randomized controlled trials demonstrate a similar incidence of abdominal/pelvic surgery in tegaserod-using and placebo-using patients.

Systematic review: Abdominal and pelvic surgery in patients with irritable bowel syndrome.

AIM: To systematically review research on the prevalence of abdominal and pelvic surgery in patients with irritable bowel syndrome. METHODS: Computer searches of MEDLINE, EMBASE and Current Contents were performed independently by both investigators to identify appropriate studies. Primary study selection criteria included: (i) population-based samples of adult irritable bowel syndrome patients; (ii) the use of appropriate symptom-based criteria to identify irritable bowel syndrome patients; and (iii) comparison of the prevalence of abdominal and pelvic surgery in irritable bowel syndrome patients vs. control populations. Secondary analysis was performed on published studies of referral populations and case series. RESULTS: Two population-based studies met the primary study selection criteria and revealed an increased prevalence of surgery in irritable bowel syndrome patients vs. controls for cholecystectomy (4.6% vs. 2.4%, respectively; odds ratio, 1.9; 95% confidence interval, 1.2-3.2) and hysterectomy (18% vs. 12%, respectively; odds ratio, 1.6; 95% confidence interval, 1.1-2.2). Secondary analysis revealed an increased prevalence of appendectomy and other abdominal and pelvic surgery in irritable bowel syndrome patients. CONCLUSIONS: Irritable bowel syndrome is associated with a disproportionately high prevalence of abdominal and pelvic surgery, but most studies exhibit sub-optimal study design and do not define the factors causing the increased prevalence of surgery in these patients.

The effectiveness of budesonide therapy for Crohn's disease.

AIM: To assess the effectiveness and safety of budesonide in comparison to corticosteroids, 5-aminosalicylic acid (5-ASA), or placebo for inducing remission of active Crohn's disease and for maintaining remission. STUDY SELECTION CRITERIA: Randomized controlled trials comparing budesonide to corticosteroids, 5-ASA products or placebo were included. Trials had to report on the effectiveness of treatment (defined as decreasing or maintaining Crohn's Disease Activity Index, CDAI, scores < or = 150) or adverse events. DATA ANALYSIS: After assessing the validity of study design and independent, duplicate data extraction from selected trials, summary relative risks (RR) were calculated for each outcome. A test of heterogeneity was also calculated for each outcome using a random effects model. RESULTS: Budesonide was more likely to induce remission than placebo (RR=1.82, 95% CI: 1.15-2.88) or 5-ASA (RR=1.73, 95% CI: 1.26-2.39), although only one trial compared budesonide to 5-ASA products. Although budesonide induced remission less frequently than conventional corticosteroids (RR=0.87, 95% CI: 0.76-0.995), there was no significant difference between conventional corticosteroids and budesonide for inducing remission among patients with a low disease activity (initial CDAI=200-300). Budesonide was significantly less likely to cause corticosteroid-associated adverse events than conventional corticosteroids (RR=0.65, 95% CI: 0.53-0.80). No significant difference in total adverse events or corticosteroid-associated adverse events was demonstrated between budesonide and 5-ASA or placebo. CONCLUSION: Budesonide is significantly more effective than placebo or 5-ASA for inducing remission of active Crohn's disease. Although budesonide is 13% less effective for the induction of remission in active Crohn's disease than conventional corticosteroids, it is less likely to cause corticosteroid-related adverse effects. Budesonide is ineffective in maintaining remission.

The epidemiology and natural history of Crohn's disease in population-based patient cohorts from North America: a systematic review.

AIM: To quantify, through systematic review, the epidemiology and natural history of Crohn's disease in North America. METHODS: The selected articles contained: (i) population-based samples of patients followed from the time of diagnosis; and (ii) objective diagnostic criteria for disease. Studies on the natural history of Crohn's disease also contained sufficient follow-up. DATA COLLECTION AND ANALYSIS: For prevalence studies, data on the incidence, prevalence, gender and age at diagnosis were extracted. For natural history studies, data on the disease activity, use of medications and surgery were extracted. MAIN RESULTS: The prevalence of Crohn's disease in North America ranges from 26.0 to 198.5 cases per 100,000 persons. The incidence rates range from 3.1 to 14.6 cases per 100,000 person-years. Most patients have a chronic intermittent disease course, while 13% have an unremitting disease course and 10% have a prolonged remission. Less than half require corticosteroids at any point. During any given year, approximately 10% are treated with corticosteroids and 30% are treated with 5-aminosalicylates. Up to 57% of patients require at least one surgical resection. CONCLUSIONS: Between 400,000 and 600,000 patients in North America have Crohn's disease, and the natural history is marked by frequent exacerbations requiring treatment with corticosteroids, 5-aminosalicylate products and surgery.