Functional gastrointestinal disorders in inflammatory bowel disease: Time for a paradigm shift?

Recent advances in biological therapies have revolutionalised and redefined treatment targets in inflammatory bowel disease (IBD). There is now a stronger emphasis on achieving the more stringent therapeutic goals of mucosal and histological healing, rather than clinical remission alone. Consequently, the treatment of refractory “functional” gastrointestinal symptoms, often attributed as the aftermath of previous inflammation, has recently become more prominent in quiescent disease. With further expected advances in anti-inflammatory treatments on the horizon, the burden of such symptoms in quiescent disease, which have been relatively neglected, is set to become an even bigger problem. In this article, we highlight the current state of research and understanding in this field, including recent developments and clinical practice guidelines on the diagnosis and management of functional gastrointestinal symptoms, such as irritable bowel syndrome and functional anorectal and pelvic floor disorders, in patients with quiescent IBD. These disorders are not only highly prevalent in these patients, they are often misdiagnosed, and are difficult to treat, with very few evidence-based therapies. Moreover, they are associated with substantial impairment in quality-of-life, considerable morbidity, and psychological distress. There is therefore an urgent need for a change in emphasis towards earlier recognition, positive diagnosis, and targeted treatment for patients with ongoing functional gastrointestinal symptoms in the absence of active IBD. This article also highlights the need for further research to develop much needed evidence-based therapies

Small Vessel Disease in the Heart and Brain: Current Knowledge, Unmet Therapeutic Need and Future Directions

No abstract available

Effectiveness of management strategies for uninvestigated dyspepsia: systematic review and network meta-analysis

Objective To determine the effectiveness of management strategies for uninvestigated dyspepsia. Design Systematic review and network meta-analysis. Data sources Medline, Embase, Embase Classic, the Cochrane Central Register of Controlled Trials, and clinicaltrials.gov from inception to September 2019, with no language restrictions. Conference proceedings between 2001 and 2019. Eligibility criteria for selecting studies Randomised controlled trials that assessed the effectiveness of management strategies for uninvestigated dyspepsia in adult participants (age ≥18 years). Strategies of interest were prompt endoscopy; test for Helicobacter pylori and perform endoscopy in participants who test positive; test for H pylori and eradication treatment in those who test positive (“test and treat”); empirical acid suppression; or symptom based management. Trials reported dichotomous assessment of symptom status at final follow-up (≥12 months). Results The review identified 15 eligible randomised controlled trials that comprised 6162 adult participants. Data were pooled using a random effects model. Strategies were ranked according to P score, which is the mean extent of certainty that one management strategy is better than another, averaged over all competing strategies. “Test and treat” ranked first (relative risk of remaining symptomatic 0.89, 95% confidence interval 0.78 to 1.02, P score 0.79) and prompt endoscopy ranked second, but performed similarly (0.90, 0.80 to 1.02, P score 0.71). However, no strategy was significantly less effective than “test and treat.” Participants assigned to “test and treat” were significantly less likely to receive endoscopy (relative risk v prompt endoscopy 0.23, 95% confidence interval 0.17 to 0.31, P score 0.98) than all other strategies, except symptom based management (relative risk v symptom based management 0.60, 0.30 to 1.18). Dissatisfaction with management was significantly lower with prompt endoscopy (P score 0.95) than with “test and treat” (relative risk v “test and treat” 0.67, 0.46 to 0.98), and empirical acid suppression (relative risk v empirical acid suppression 0.58, 0.37 to 0.91). Upper gastrointestinal cancer rates were low in all trials. Results remained stable in sensitivity analyses, with minimal inconsistencies between direct and indirect results. Risk of bias of individual trials was high; blinding was not possible because of the pragmatic trial design. Conclusions “Test and treat” was ranked first, although it performed similarly to prompt endoscopy and was not superior to any of the other strategies. “Test and treat” led to fewer endoscopies than all other approaches, except symptom based management. However, participants showed a preference for prompt endoscopy as a management strategy for their symptoms. Systematic review registration PROSPERO registration number CRD42019132528

Helicobacter pylori eradication therapy to prevent gastric cancer in healthy asymptomatic infected individuals: systematic review and meta-analysis of randomised controlled trials

OBJECTIVES: To determine whether searching for Helicobacter pylori and treating with eradication therapy leads to a reduction in incidence of gastric cancer among healthy asymptomatic infected individuals. DESIGN: Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES: Medline, Embase, and the Cochrane central register of controlled trials were searched through to December 2013. Conference proceedings between 2001 and 2013 were hand searched. A recursive search was performed with bibliographies of relevant studies. There were no language restrictions. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials examining the effect of at least seven days of eradication therapy on subsequent occurrence of gastric cancer in adults who tested positive for Helicobacter pylori but otherwise healthy and asymptomatic were eligible. The control arm had to receive placebo or no treatment. Subjects had to be followed for ≥ 2 years. MAIN OUTCOME MEASURES: Primary outcome, defined a priori, was the effect of eradication therapy on the subsequent occurrence of gastric cancer expressed as a relative risk of gastric cancer with 95% confidence intervals. RESULTS: The search strategy identified 1560 citations, of which six individual randomised controlled trials were eligible. Fifty one (1.6%) gastric cancers occurred among 3294 individuals who received eradication therapy versus 76 (2.4%) in 3203 control subjects (relative risk 0.66, 95% confidence interval 0.46 to 0.95), with no heterogeneity between studies (I(2)=0%, P=0.60). If the benefit of eradication therapy was assumed to persist lifelong the number needed to treat was as low as 15 for Chinese men and as high as 245 for US women. CONCLUSIONS: These data provide limited, moderate quality evidence that searching for and eradicating H pylori reduces the incidence of gastric cancer in healthy asymptomatic infected Asian individuals, but these data cannot necessarily be extrapolated to other populations

Eradication therapy for peptic ulcer disease in Helicobacter pylori-positive people

BACKGROUND: Peptic ulcer disease is the cause of dyspepsia in about 10% of people. Ninety-five percent of duodenal and 70% of gastric ulcers are associated with Helicobacter pylori. Eradication of H. pylori reduces the relapse rate of ulcers but the magnitude of this effect is uncertain. This is an update of Ford AC, Delaney B, Forman D, Moayyedi P. Eradication therapy for peptic ulcer disease in Helicobacter pylori-positive patients. Cochrane Database of Systematic Reviews 2006, Issue 2. Art. No.: CD003840. DOI: 10.1002/14651858.CD003840.pub4. OBJECTIVES: To assess the proportion of peptic ulcers healed and the proportion of participants who remained free from relapse with eradication therapy against placebo or other pharmacological therapies in H. pylori-positive people.To assess the proportion of participants that achieved complete relief of symptoms and improvement in quality of life scores.To compare the incidence of adverse effects/drop-outs (total number for each drug) associated with the different treatments.To assess the proportion of participants in whom successful eradication was achieved. SEARCH METHODS: In this update, we identified trials by searching the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE (1950 to March 2016) and Ovid EMBASE (1980 to March 2016). To identify further relevant trials, we handsearched reference lists from trials selected by electronic searching, and published abstracts from conference proceedings from the United European Gastroenterology Week (published in Gut) and Digestive Disease Week (published in Gastroenterology). The search was last updated in March 2016. We contacted members of Cochrane Upper GI and Pancreatic Diseases, and experts in the field and asked them to provide details of outstanding clinical trials and any relevant unpublished materials. SELECTION CRITERIA: We analysed randomised controlled trials of short- and long-term treatment of peptic ulcer disease in H. pylori-positive adults. Participants received at least one week of H. pylori eradication compared with ulcer healing drug, placebo or no treatment. Trials were included if they reported assessment from two weeks onwards. DATA COLLECTION AND ANALYSIS: We collected data on ulcer healing, recurrence, relief of symptoms and adverse effects. We calculated the risk ratio (RR) with 95% confidence intervals (CI) using both fixed-effect and random-effects models with Review Manager software (RevMan 5.3) based on intention-to-treat analysis as far as possible. MAIN RESULTS: A total of 55 trials were included for one or more outcomes for this review.In duodenal ulcer healing, eradication therapy was superior to ulcer healing drug (UHD) (34 trials, 3910 participants, RR of ulcer persisting = 0.66, 95% confidence interval (CI) 0.58 to 0.76; 381/2286 (adjusted proportion: 12.4%) in eradication therapy plus UHD versus 304/1624 (18.7%) in UHD; low quality evidence) and no treatment (two trials, 207 participants, RR 0.37, 95% CI 0.26 to 0.53; 30/125 (adjusted proportion: 21.7%) in eradication therapy versus 48/82 (58.5%) in no treatment; low quality evidence).In gastric ulcer healing, the differences were imprecise between eradication therapy and UHD (15 trials, 1974 participants, RR 1.23, 95% CI 0.90 to 1.68; 220/1192 (adjusted proportion: 16.0%) in eradication therapy plus UHD versus 102/782 (13.0%) in UHD; very low quality evidence). In preventing duodenal ulcer recurrence the differences were imprecise between maintenance therapy with H.pylori eradication therapy and maintenance therapy with UHD (four trials, 319 participants, RR of ulcer recurring 0.73; 95% CI 0.42 to 1.25; 19/159 (adjusted proportion: 11.9%) in eradication therapy versus 26/160 (16.3%) in UHD; very low quality evidence), but eradication therapy was superior to no treatment (27 trials 2509 participants, RR 0.20, 95% CI 0.15 to 0.26; 215/1501 (adjusted proportion: 12.9%) in eradication therapy versus 649/1008 (64.4%) in no treatment; very low quality evidence).In preventing gastric ulcer recurrence, eradication therapy was superior to no treatment (12 trials, 1476 participants, RR 0.31, 95% CI 0.22 to 0.45; 116/697 (adjusted proportion: 16.3%) in eradication therapy versus 356/679 (52.4%) in no treatment; very low quality evidence). None of the trials reported proportion of people with gastric ulcer not healed after initial therapy between H.pylori eradication therapy and no active treatment or the proportion of people with recurrent gastric ulcer or peptic ulcers during maintenance therapy between H.pylori eradication therapy and ulcer healing drug therapy. AUTHORS' CONCLUSIONS: Adding a one to two-week course of H. pylori eradication therapy is an effective treatment for people with H. pylori-positive duodenal ulcer when compared to ulcer healing drugs alone and no treatment. H. pylori eradication therapy is also effective in preventing recurrence of duodenal and gastric ulcer compared to no treatment. There is currently no evidence that H. pylori eradication therapy is an effective treatment in people with gastric ulcer or that it is effective in preventing recurrence of duodenal ulcer compared to ulcer healing drug. However, confidence intervals were wide and significant benefits or harms of H. pylori eradication therapy in acute ulcer healing of gastric ulcers compared to no treatment, and in preventing recurrence of duodenal ulcers compared to ulcer healing drugs cannot be ruled out

Latent class analysis does not support the existence of Rome IV functional bowel disorders as discrete entities

Background Previously, we used latent class analysis (LCA) to identify novel subgroups in people with irritable bowel syndrome (IBS). There are four other functional bowel disorders that, although characterized as discrete disorders, overlap considerably with, and fluctuate to, IBS. These might instead be conceptualized as a milder form of IBS. We explored this hypothesis using LCA in a cohort of people with non-IBS functional bowel disorders. Methods We collected demographic, symptom, and psychological health data from 1375 adults in the community who self-identified as having IBS and identified individuals meeting Rome IV criteria for any non-IBS functional bowel disorder. We performed LCA to identify specific subgroups (clusters). We followed participants up at 12 months to reassess gastrointestinal and psychological heath and also gather data about healthcare utilization and impact of symptoms. Key results 811 people met Rome IV criteria for IBS and 558 Rome IV criteria for another functional bowel disorder (76 (5.5%) functional constipation; 198 (14.5%) functional diarrhea; 129 (9.5%) functional abdominal bloating or distension; and 155 (11.4%) unspecified functional bowel disorder). LCA in these 558 people identified five clusters defined by a combination of gastrointestinal symptoms and the extent of psychological co-morbidity. However, correlation between these clusters and the Rome IV functional bowel disorder diagnoses was poor and 75% of people were classified as having mild IBS using our previous IBS-derived model. By 12 months, one-third of people had fluctuated and met criteria for IBS. Clusters with high psychological burden had a poorer prognosis, with higher rates of medical consultation, medication use, and greater impact of symptoms on daily life. Conclusions and inferences The functional bowel disorders may be better characterized as a spectrum of IBS rather than separate disorders. Adopting this pragmatic stance may help to simply diagnosis, treatment, and recruitment of patients to research trials