David J. Gracie

Prevalence of, and predictors of, bile acid malabsorption in outpatients with chronic diarrhea.

Background  Many physicians do not consider the diagnosis of bile acid malabsorption in patients with chronic diarrhea, or do not have access to testing. We examined yield of 23‐seleno‐25‐homo‐tauro‐cholic acid (SeHCAT) scanning in chronic diarrhea patients, and attempted to identify predictors of a positive test.

Systematic review with meta-analysis: the accuracy of diagnosing irritable bowel syndrome with symptoms, biomarkers and/or psychological markers

Irritable bowel syndrome (IBS) is a complex, heterogeneous disease which can be challenging to diagnose. No study has identified and assessed the accuracy of all available methods of diagnosing IBS.

Systematic review with meta-analysis: the adverse effects of tobacco smoking on the natural history of Crohn's disease.

Tobacco smoking is a well‐established risk factor for the development of Crohns disease, and this may lead to a more complicated disease course. However, recent evidence suggests that many patients with Crohns disease are unaware of this fact.

Poor Correlation Between Clinical Disease Activity and Mucosal Inflammation, and the Role of Psychological Comorbidity, in Inflammatory Bowel Disease

OBJECTIVES:There is a move toward patient-reported outcome measures as end points in clinical trials of novel therapies for inflammatory bowel disease (IBD). However, the association between patient-reported symptoms and mucosal inflammation, and the influence of psychological factors, remains unclear. We examined this in a secondary care population.METHODS:Validated patient-reported disease activity indices were used to define clinically active disease in a cohort of 356 patients with ulcerative colitis (UC) or Crohn’s disease (CD). A fecal calprotectin ≥250 μg/g was used to define active mucosal inflammation. The hospital anxiety and depression scale (HADS) and patient health questionnaire (PHQ)-15 were used to assess for anxiety, depression, or somatization, respectively. Logistic regression analysis was performed to determine the association between symptoms, mucosal inflammation, and psychological comorbidity.RESULTS:Clinical disease activity was associated with mucosal inflammation in UC (odds ratio (OR) 3.36; 95% confidence interval (CI) 1.34–8.47) but not in CD (OR 1.69; 95% CI 0.74–3.83). Depression in UC (OR 1.21 per 1-point increase in HADS; 95% CI 1.02–1.44) and somatization in UC (OR 1.17 per 1-point increase in PHQ-15; 95% CI 1.03–1.33) and CD (OR 1.31 per 1-point increase in PHQ-15; 95% CI 1.13–1.52) were associated with clinical disease activity. Overall, patient-reported symptoms yielded poor positive predictive values for mucosal inflammation in both CD and UC.CONCLUSIONS:Patient-reported symptoms and the Harvey–Bradshaw index were poor predictors of mucosal inflammation in CD. Psychological comorbidity was associated with gastrointestinal symptom-reporting. A shift in the focus of IBD management toward one addressing both psychological and physical well-being is required.

Systematic review with meta‐analysis: the efficacy of probiotics in inflammatory bowel disease

Ulcerative colitis (UC) and Crohns disease (CD) are inflammatory bowel diseases (IBD). Evidence implicates disturbances of the gastrointestinal microbiota in their pathogenesis.

Negative Effects on Psychological Health and Quality of Life of Genuine Irritable Bowel Syndrome–type Symptoms in Patients With Inflammatory Bowel Disease

BACKGROUND & AIMS Symptoms compatible with irritable bowel syndrome (IBS) are common in patients with inflammatory bowel disease (IBD), but it is unclear whether this relates to occult IBD activity. We attempted to resolve this issue in a secondary care population by using a cross‐sectional study design. METHODS We analyzed Rome III IBS symptoms, disease activity indices, and psychological, somatization, and quality of life data from 378 consecutive, unselected adult patients with IBD seen in clinics at St Jamess University Hospital in Leeds, United Kingdom from November 2012 through June 2015. Participants provided a stool sample for fecal calprotectin (FC) analysis; levels ≥250 &mgr;g/g were used to define mucosal inflammation. By using symptom data and FC levels we identified 4 distinct groups of patients: those with true IBS‐type symptoms (IBS‐type symptoms with FC levels <250 &mgr;g/g, regardless of disease activity indices), quiescent IBD (no IBS‐type symptoms with FC levels <250 &mgr;g/g, regardless of disease activity indices), occult inflammation (normal disease activity indices and FC levels ≥250 &mgr;g/g, regardless of IBS symptom status), or active IBD (abnormal disease activity indices with FC levels ≥250 &mgr;g/g, regardless of IBS symptom status). We compared characteristics between these groups. RESULTS Fifty‐seven of 206 patients with Crohns disease (27.7%) and 34 of 172 patients with ulcerative colitis (19.8%) had true IBS‐type symptoms. Levels of psychological comorbidity and somatization were significantly higher among patients with true IBS‐type symptoms than patients with quiescent IBD or occult inflammation. Quality of life levels were also significantly reduced compared with patients with quiescent disease or occult inflammation and were similar to those of patients with active IBD. By using FC levels ≥100 &mgr;g/g to define mucosal inflammation, we found a similar effect of IBS‐type symptoms on psychological health and quality of life. CONCLUSIONS In a cross‐sectional study, we identified a distinct group of patients with IBD and genuine IBS‐type symptoms in the absence of mucosal inflammation. These symptoms had negative effects on psychological well‐being and quality of life to the same degree as active IBD. New management strategies are required for this patient group.

Effect of psychological therapy on disease activity, psychological comorbidity, and quality of life in inflammatory bowel disease: a systematic review and meta-analysis

BACKGROUND Inflammatory bowel disease is associated with psychological comorbidity and impaired quality of life. Psychological comorbidity could affect the natural history of inflammatory bowel disease. Psychological therapies might therefore have beneficial effects on disease activity, mood, and quality of life in patients with inflammatory bowel disease. We did a systematic review and meta-analysis examining these issues. METHODS In this systematic review and meta-analysis, we searched MEDLINE, Embase, Embase Classic, PsychINFO, and the Cochrane Central Register of Controlled Trials for articles published between 1947 and Sept 22, 2016. Randomised controlled trials (RCTs) recruiting patients with inflammatory bowel disease aged at least 16 years that compared psychological therapy with a control intervention or usual treatment were eligible. We pooled dichotomous data to obtain relative risks of induction of remission in active disease or prevention of relapse of quiescent disease, with 95% CIs. We pooled continuous data to estimate standardised mean differences in disease activity indices, anxiety, depression, perceived stress, and quality-of-life scores in patients dichotomised into those with clinically active or quiescent disease, with 95% CIs. We extracted data from published reports and contacted the original investigators of studies for which the required data were not available. We pooled all data using a random-effects model. FINDINGS The search identified 1824 studies, with 14 RCTs of 1196 patients eligible for inclusion. The relative risk of relapse of quiescent inflammatory bowel disease with psychological therapy versus control was 0·98 (95% CI 0·77-1·24; p=0·87; I2=50%; six trials; 518 patients). We observed a significant difference in depression scores (standardised mean difference -0·17 [-0·33 to -0·01]; p=0·04; I2=0%; seven trials; 605 patients) and quality of life (0·30 [0·07-0·52]; p=0·01; I2=42%; nine trials; 578 patients) with psychological therapy versus control at the end of therapy for patients with quiescent disease. However, these beneficial effects were lost at final point of follow-up (depression scores -0·11 [-0·27 to 0·05], p=0·17, I2=0%, eight trials, 593 patients; quality of life 0·15 [-0·05 to 0·34], p=0·14, I2=22%, ten trials, 577 patients). When we assessed the effect of individual physiological therapies on quality of life, only cognitive behavioural therapy had any significant beneficial effect (0·37 [0·02-0·72]). We noted no effect on disease activity indices or other psychological wellbeing scores when compared with control in patients with quiescent disease. Dichotomous data for induction of remission and continuous data for change in clinical disease activity indices, depression, anxiety, and perceived stress scores were only reported in one RCT of patients with active disease. Quality of life was assessed in two RCTs of patients with active disease, but was not significantly different between intervention and control groups (0·27 [-0·05 to 0·59]). INTERPRETATION Psychological therapies, and cognitive behavioural therapy in particular, might have small short-term beneficial effects on depression scores and quality of life in patients with inflammatory bowel disease. Further RCTs of these interventions in patients with coexistent psychological distress are required. FUNDING None.

Systematic review with meta-analysis: the effect of tobacco smoking on the natural history of ulcerative colitis

Tobacco smoking is associated with a reduced risk of developing ulcerative colitis (UC). A high proportion of UC patients perceive a benefit in disease outcomes secondary to smoking. However, the effects of smoking on the natural history of UC are uncertain.

Enhancing Diagnostic Performance of Symptom-Based Criteria for Irritable Bowel Syndrome by Additional History and Limited Diagnostic Evaluation

OBJECTIVES:Symptom-based criteria to diagnose irritable bowel syndrome (IBS) positively perform only modestly. Our aim was to assess whether including other items from the clinical history and limited diagnostic evaluation improves their performance.METHODS:We collected complete symptom, colonoscopy, and histology data from 318 consecutive, unselected adult patients with lower gastrointestinal (GI) symptoms in secondary care. All participants underwent colonoscopy, with relevant organic findings recorded. The reference standard used to define the presence of true IBS was patient-reported lower abdominal pain or discomfort associated with a change in bowel habit, in the absence of organic GI disease. Sensitivity, specificity, and positive and negative likelihood ratios (LRs), with 95% confidence intervals, were calculated for Rome III criteria, as well as for modifications, incorporating nocturnal stools, results of simple blood tests (hemoglobin and C-reactive protein (CRP)), measures of somatization, and/or affective disorders (hospital anxiety or depression scale (HADS) score).RESULTS:The sensitivity and specificity of the Rome III criteria for identifying IBS was 69.6%, and 82.0%, respectively, with positive and negative LRs of 3.87 and 0.37, respectively. Clinically useful enhancements in positive LRs were provided by combining Rome III criteria with: (a) high level of somatization (7.27); (b) normal hemoglobin and CRP with HADS score of ≥8 (5.04); (c) normal hemoglobin and CRP with a high level of somatization (7.56); or (d) no nocturnal passage of stool with a high level of somatization (17.3). Specificity was ≥95% with each of these modifications.CONCLUSIONS:Incorporating nocturnal stools, somatization, and affective disorders from the clinical history, and hemoglobin and CRP measurements, enhances the positive LR and specificity of symptom-based Rome III criteria for IBS.

iBS-like symptoms in patients with ulcerative colitis

Ulcerative colitis (UC) and irritable bowel syndrome (IBS) are chronic gastrointestinal disorders that, until recently, have been considered dichotomous conditions falling on either side of a functional-organic divide. However, persistent gastrointestinal symptoms, akin to those of IBS, are observed in up to one in three patients with quiescent UC. Whether these lower gastrointestinal symptoms are secondary to coexistent IBS or occult UC disease activity is uncertain, but when objective evidence of disease activity is lacking, escalation of conventional pharmacotherapy in such patients is often ineffective. The etiologies of both UC and IBS remain unclear, but dysregulation of the enteric nervous system, an altered microbiome, low-grade mucosal inflammation, and activation of the brain–gut axis is common to both; this suggests that some overlap between the two conditions is plausible. How best to investigate and manage IBS-type symptoms in UC patients remains unclear. Studies that have assessed patients with UC who meet criteria for IBS for subclinical inflammation have been conflicting in their results. Although evidence-based treatments for IBS exist, their efficacy in UC patients reporting these types of symptoms remains unclear. Given the disturbances in gut microbiota in UC, and the possible role of the brain–gut axis in the generation of such symptoms, treatments such as probiotics, fecal transfer, antidepressants, or psychological therapies would seem logical approaches to use in this group of patients. However, there are only limited data for all of these therapies; this suggests that randomized controlled trials to investigate their efficacy in this setting may be warranted.