A leading hypothesis for the role of bacteria in inflammatory bowel diseases is that an imbalance in normal gut flora is a prerequisite for inflammation. Testing this hypothesis requires comparisons ...between the microbiota compositions of ulcerative colitis and Crohn's disease patients and those of healthy individuals. In this study, we obtained biopsy samples from patients with Crohn's disease and ulcerative colitis and from healthy controls. Bacterial DNA was extracted from the tissue samples, amplified using universal bacterial 16S rRNA gene primers, and cloned into a plasmid vector. Insert-containing colonies were picked for high-throughput sequencing, and sequence data were analyzed, yielding species-level phylogenetic data. The clone libraries yielded 3,305 sequenced clones, representing 151 operational taxonomical units. There was no significant difference between floras from inflamed and healthy tissues from within the same individual. Proteobacteria were significantly (P = 0.0007) increased in Crohn's disease patients, as were Bacteroidetes (P < 0.0001), while Clostridia were decreased in that group (P < 0.0001) in comparison with the healthy and ulcerative colitis groups, which displayed no significant differences. Thus, the bacterial flora composition of Crohn's patients appears to be significantly altered from that of healthy controls, unlike that of ulcerative colitis patients. Imbalance in flora in Crohn's disease is probably not sufficient to cause inflammation, since microbiotas from inflamed and noninflamed tissues were of similar compositions within the same individual.
A globally acceptable definition and classification of gastroesophageal reflux disease (GERD) is desirable for research and clinical practice. The aim of this initiative was to develop a consensus ...definition and classification that would be useful for patients, physicians, and regulatory agencies.
A modified Delphi process was employed to reach consensus using repeated iterative voting. A series of statements was developed by a working group of five experts after a systematic review of the literature in three databases (Embase, Cochrane trials register, Medline). Over a period of 2 yr, the statements were developed, modified, and approved through four rounds of voting. The voting group consisted of 44 experts from 18 countries. The final vote was conducted on a 6-point scale and consensus was defined a priori as agreement by two-thirds of the participants.
The level of agreement strengthened throughout the process with two-thirds of the participants agreeing with 86%, 88%, 94%, and 100% of statements at each vote, respectively. At the final vote, 94% of the final 51 statements were approved by 90% of the Consensus Group, and 90% of statements were accepted with strong agreement or minor reservation. GERD was defined as a condition that develops when the reflux of stomach contents causes troublesome symptoms and/or complications. The disease was subclassified into esophageal and extraesophageal syndromes. Novel aspects of the new definition include a patient-centered approach that is independent of endoscopic findings, subclassification of the disease into discrete syndromes, and the recognition of laryngitis, cough, asthma, and dental erosions as possible GERD syndromes. It also proposes a new definition for suspected and proven Barrett's esophagus.
Evidence-based global consensus definitions are possible despite differences in terminology and language, prevalence, and manifestations of the disease in different countries. A global consensus definition for GERD may simplify disease management, allow collaborative research, and make studies more generalizable, assisting patients, physicians, and regulatory agencies.
CONTEXT Many individuals experience lower gastrointestinal tract symptoms, most commonly attributable to functional conditions. These individuals are frequently diagnosed with irritable bowel ...syndrome (IBS) based on their symptoms; however, some may require additional testing or referral to specialists before this diagnosis is made. OBJECTIVE To systematically review the literature of the accuracy of individual symptoms and combinations of findings in diagnosing IBS. DATA SOURCES Search of MEDLINE and EMBASE (up to June 2008) for prospective studies reporting on unselected cohorts of adult patients with lower gastrointestinal tract symptoms recorded before investigation. STUDY SELECTION Studies prospectively evaluating accuracy of individual symptoms or combinations of findings compared with results from investigations of the lower gastrointestinal tract. DATA EXTRACTION Two authors independently assessed studies and extracted data to estimate likelihood ratios (LRs) of individual symptoms and combinations of findings in diagnosing IBS. RESULTS Ten studies evaluating 2355 patients were identified, with a summary prevalence of IBS following investigation of 57%. Individual symptom items yielded positive LRs from 1.2 (95% confidence interval CI, 0.93-1.6) for passage of mucus per rectum to 2.1 (95% CI, 1.4-3.0) for looser stools at onset of abdominal pain and negative LRs from 0.29 (95% CI, 0.12-0.72) for no lower abdominal pain to 0.88 (95% CI, 0.72-1.1) for no passage of mucus per rectum in diagnosing IBS. The Manning criteria had a summary positive LR of 2.9 (95% CI, 1.3-6.4) and a summary negative LR of 0.29 (95% CI, 0.12-0.71). The Rome I criteria had a positive LR of 4.8 (95% CI, 3.6-6.5) and a negative LR of 0.34 (95% CI, 0.29-0.41). The Kruis scoring system provided a summary positive LR of 8.6 (95% CI, 2.9-26.0) and a summary negative LR of 0.26 (95% CI, 0.17-0.41). The Rome II and III criteria have not been studied. CONCLUSIONS Individual symptoms have limited accuracy for diagnosing IBS in patients referred with lower gastrointestinal tract symptoms. The accuracy of the Manning criteria and Kruis scoring system were only modest. Despite strong advocacy for use of the Rome criteria, only the Rome I classification has been validated. Future research should concentrate on validating existing diagnostic criteria or developing more accurate ways of predicting a diagnosis of IBS without the need for investigation of the lower gastrointestinal tract.
To conduct a systematic review and meta-analysis that defines the worldwide incidence of celiac disease (CD) and examines temporal trends.
MEDLINE and EMBASE were searched for population-based ...studies reporting the incidence of CD in the overall population, children, or adults. No limits were placed on year or language of publication. Studies solely examining at-risk populations (e.g., patients with type 1 diabetes) were excluded. Random-effects models were performed to meta-analyze sex- and age-specific incidence in the 21st century. Temporal trend analyses assessed the average annual percent change in CD incidence over time.
Of 11,189 citations, 86 eligible studies were identified for inclusion, of which 50 were deemed suitable for analyses. In the 21st century, the pooled female incidence of CD was 17.4 (95% confidence interval CI: 13.7, 21.1) (I = 99.5%) per 100,000 person-years, compared with 7.8 (95% CI: 6.3, 9.2) (I = 98.6%) in males. Child-specific incidence was 21.3 per 100,000 person-years (95% CI: 15.9, 26.7) (I = 99.7%) compared with 12.9 (95% CI: 7.6, 18.2) (I = 99.9%) in adults. Pooling average annual percent changes showed the incidence of CD to be increasing by 7.5% (95% CI: 5.8, 9.3) (I = 79.6%) per year over the past several decades.
Incidence of CD is highest in females and children. Overall, the incidence has been significantly rising in the latter half of the 20th century and into the 21st century throughout the Western world. Population-based studies in Africa, Asia, and Latin America are needed to provide a comprehensive picture of the global incidence of CD.
The main problem for all database studies evaluating the risks of PPI is that none was specifically created to assess PPI-related events. ...many confounders, such as socioeconomic status or ...comorbidities, are not recorded in sufficient detail to allow for adequate adjusting in a multivariate model. Furthermore, sicker patients are more likely to develop additional illnesses, and this is the explanation that PPIs have been associated with an ever-increasing number of diseases.2 A careful evaluation of the data would suggest that most, if not all, of these presumed PPI associations are attributable to residual confounding.3 It is noteworthy that the authors’ adjustment for confounders produced modest attenuation of the HR. More dramatic risk reductions have been reported by other authors after adjusting for confounders in similar studies.3 Cheung et al conducted a propensity-matched analysis as this can partially adjust for unknown and known confounders, but this approach is only as good as the underlying dataset and it can have many inherent biases.4 In this case, the approach is likely to be flawed as the HR actually increases with the trimmed results and is similar to the univariate analysis.
The Internet is a widely used information resource for patients with inflammatory bowel disease, but there is variation in the quality of Web sites that have patient information regarding Crohn's ...disease and ulcerative colitis. The purpose of the current study is to systematically evaluate the quality of these Web sites.
The top 50 Web sites appearing in Google using the terms "Crohn's disease" or "ulcerative colitis" were included in the study. Web sites were evaluated using a (a) Quality Evaluation Instrument (QEI) that awarded Web sites points (0-107) for specific information on various aspects of inflammatory bowel disease, (b) a five-point Global Quality Score (GQS), (c) two reading grade level scores, and (d) a six-point integrity score.
Thirty-four Web sites met the inclusion criteria, 16 Web sites were excluded because they were portals or non-IBD oriented. The median QEI score was 57 with five Web sites scoring higher than 75 points. The median Global Quality Score was 2.0 with five Web sites achieving scores of 4 or 5. The average reading grade level score was 11.2. The median integrity score was 3.0.
There is marked variation in the quality of the Web sites containing information on Crohn's disease and ulcerative colitis. Many Web sites suffered from poor quality but there were five high-scoring Web sites.
The efficacy of colorectal cancer (CRC) screening is dependent on participation and subsequent adherence to surveillance. The internet increasingly is used for health information and is important to ...support decision making. We evaluated the accuracy, quality, and readability of online information on CRC screening and surveillance.
A Website Accuracy Score and Polyp Score were developed, which awarded points for various aspects of CRC screening and surveillance. Websites also were evaluated using validated internet quality instruments (Global Quality Score, LIDA, and DISCERN), and reading scores. Two raters independently assessed the top 30 websites appearing on Google.com. Portals, duplicates, and news articles were excluded.
Twenty websites were included. The mean website accuracy score was 26 of 44 (range, 9-41). Websites with the highest scores were www.cancer.org, www.bowelcanceraustralia.org, and www.uptodate.com. The median polyp score was 3 of 10. The median global quality score was 3 of 5 (range, 2-5). The median overall LIDA score was 74% and the median DISCERN score was 45, both indicating moderate quality. The mean Flesch-Kincaid grade level was 11th grade, rating the websites as difficult to read, 30% had a reading level acceptable for the general public (Flesch Reading Ease > 60). There was no correlation between the Google rank and the website accuracy score (r
= -0.31; P = .18).
There is marked variation in quality and readability of websites on CRC screening. Most websites do not address polyp surveillance. The poor correlation between quality and Google ranking suggests that screenees will miss out on high-quality websites using standard search strategies.
This document addresses the design of trials to assess the efficacy of new treatments for functional gastrointestinal disorders (FGID), emphasizing trials in irritable bowel syndrome and dyspepsia, ...because most research has been undertaken in these conditions. The double-blind, randomized, placebo-controlled, parallel group trial remains the preferred design. Randomized withdrawal designs, although encouraged by the European Agency for the Evaluation of Medicinal Products, have the same potential disadvantages as a crossover design, including carryover effects, unmasking (unblinding), and overestimation of the potential benefit for clinical practice. Innovative trial designs that evaluate intermittent (on demand) treatment are likely to become more common in the future. Investigators should include as broad a spectrum of patients as possible and should report recruitment strategies, inclusion/exclusion criteria, and attrition data. The primary analysis should be based on the proportion of patients in each treatment arm who satisfy an a priori treatment responder definition, or a prespecified clinically meaningful change in a patient-reported symptom improvement measure. Such measures of improvement are psychometrically validated subjective global assessments or a change from baseline in a validated symptom severity questionnaire. It is unethical to change the responder definition after a trial begins. Data analysis should address all patients enrolled, using an intention-to-treat principle. Reporting of results should follow the Consolidated Standards for Reporting Trials guidelines and include an analysis of harms data and secondary outcome measures to support or explain the primary outcome. Trials should be registered in a public location, prior to initiation, and should be published even if the results are negative or inconclusive.
A relationship between ulcerative colitis (UC) and diet has been shown in epidemiological and experimental studies. In a 6-month, open-label, randomized, placebo-controlled trial, adult UC patients ...in clinical remission were randomized to either an “Anti-inflammatory Diet (AID)” or “Canada’s Food Guide (CFG)”. Menu plans in the AID were designed to increase the dietary intake of dietary fiber, probiotics, antioxidants, and omega-3 fatty acids and to decrease the intake of red meat, processed meat, and added sugar. Stool was collected for fecal calprotectin (FCP) and microbial analysis. Metabolomic analysis was performed on urine, serum, and stool samples at the baseline and study endpoint. In this study, 53 patients were randomized. Five (19.2%) patients in the AID and 8 (29.6%) patients in the CFG experienced a clinical relapse. The subclinical response to the intervention (defined as FCP < 150 µg/g at the endpoint) was significantly higher in the AID group (69.2 vs. 37.0%, p = 0.02). The patients in the AID group had an increased intake of zinc, phosphorus, selenium, yogurt, and seafood versus the control group. Adherence to the AID was associated with significant changes in the metabolome, with decreased fecal acetone and xanthine levels along with increased fecal taurine and urinary carnosine and p-hydroxybenzoic acid levels. The AID subjects also had increases in fecal Bifidobacteriaceae, Lachnospiraceae, and Ruminococcaceae. In this study, we found thatdietary modifications involving the increased intake of anti-inflammatory foods combined with a decreased intake of pro-inflammatory foods were associated with metabolic and microbial changes in UC patients in clinical remission and were effective in preventing subclinical inflammation.
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