Young people's priorities for the self-management of distress after stoma surgery due to inflammatory bowel disease: A consensus study using online nominal group technique.

INTRODUCTION: The aim of this study was to gain consensus among young people with a stoma due to inflammatory bowel disease (IBD) on the priorities for the content of an intervention for the self-management of stoma-related distress. The current identification and management of distress in young people with a stoma is often suboptimal in clinical settings and there is a need for improved support resources. METHODS: Two consensus group meetings were carried out via online video conferencing, using nominal group technique. Participants generated, rated on a Likert scale and discussed, topics for inclusion in a future self-management intervention. RESULTS: Nineteen young people, aged 19-33, with a stoma due to IBD took part in one of two group meetings. Participants were located across England, Scotland, and Northern Ireland. Twenty-nine topics were generated by participants, seven of which reached consensus of ≥80%, that is, a mean of ≥5.6 on a 7-point Likert scale. These were: receiving advice from young people with lived experience of stoma surgery; advice on/addressing concerns about romantic relationships, sex and intimacy; information about fertility and pregnancy related to stoma surgery; stoma 'hacks', for example, useful everyday tips regarding clothing, making bag changes easier and so forth; reflecting on and recognising own emotional response to surgery; tips on managing the stoma during the night; and processing trauma related to the illness and surgery journey. CONCLUSIONS: Findings extend previous research on young people's experiences of stoma surgery, by generating consensus on young people's priorities for managing distress related to surgery and living with a stoma. These priorities include topics not previously reported in the literature, including the need for information about fertility and pregnancy. Findings will inform the development of a self-management resource for young people with an IBD stoma and have relevance for the clinical management of stoma-related distress in this population. PATIENT OR PUBLIC CONTRIBUTION: Three patient contributors are co-authors on this paper, having contributed to the study design, interpretation of results and writing of the manuscript. The study's Patient and Public Involvement and Engagement advisory group also had an integral role in the study. They met with the research team for four 2-h virtual meetings, giving input on the aims and purpose of the study, recruitment methods, and interpretation of findings. The group also advised on the age range for participants. The views of young people with a stoma are the central component of the study reported in this paper, which aims to gain consensus among young people with an IBD stoma on their priorities for the content of a resource to self-manage distress related to stoma surgery.

Healthcare professionals' priorities for training to identify and manage distress experienced by young people with a stoma due to inflammatory bowel disease: a consensus study using online nominal group technique.

OBJECTIVES: Young people with a stoma due to inflammatory bowel disease (IBD) commonly experience distress; however, this is not always well managed in clinical settings. More effective support may/is likely to reduce the possibility of individuals experiencing sustained distress, which may engender depression or anxiety. This study aimed to gain consensus among a multidisciplinary group of healthcare professionals (HCPs) on priorities for training in the identification and management of distress in this population. One of the authors is a young person with a stoma. DESIGN: Participants were recruited through Twitter (X) and the researchers' clinical/research contacts. Two consensus group meetings were conducted using Nominal Group Technique, involving participants generating, discussing and rating on a Likert scale, topics for inclusion in an HCP training package. SETTING: Online video conferencing. Participants were located across England, with one based in the USA. PARTICIPANTS: Nineteen HCPs participated: three general practitioners, three stoma nurses, two IBD nurses, nine clinical psychologists and two gastroenterologists. RESULTS: Twenty-five topics were generated by participants; 19 reached consensus of ≥80%, that is, a mean of ≥5.6 on a 7-point Likert scale. These included: recognising and validating different levels of, and variation in, distress; tackling stigma and normalising having a stoma; everyday practicalities of stoma management, including food and sleep; opening and holding conversations about stoma-related distress; considering the impact of different cultural beliefs on adaptation after stoma surgery; training in simple techniques for gauging the patient's distress during clinical encounters; having conversations about body image; and myth-busting common fears, such as odour. CONCLUSIONS: This study is the first to identify HCP training priorities for managing stoma-related distress in young people. Consensus was reached for 19 topics, reflecting the varied needs of young people with a stoma. Findings will inform development of a training package for HCPs treating young people with IBD and a stoma.

Recommendations for the management of opioid-induced constipation - how to improve usability in clinical practice.

INTRODUCTION: Opioid-induced constipation remains undertreated despite effective and safe treatment options exists. Previous guidelines have only been partially effective in improving management, possibly due to their complexity, and studies suggest that a simple setup of concise and behaviorally-orientated steps improves usability. AREAS COVERED: This article introduces the concept of opioid-induced constipation and provides an overview of existing guidelines in this field. We also propose simplified recommendations for managing opioid-induced constipation, derived from a synthesis of current guidelines and the principles of optimal guideline design theory. EXPERT OPINION: Despite standard treatment with laxatives and fluid intake in patients with opioid-induced constipation, escalation of treatment is often needed where µ-opioid receptor antagonists or newer medications such as lubiprostone, linaclotide, or prucalopride are used. Previous guidelines have not been used sufficiently and thus management of the condition is often insufficient. We therefore propose simplified recommendations to management, which we believe can come into broader use. It was validated in primary care for credibility, clarity, relevance, usability, and overall benefit. We believe that this initiative can lead to better management of the substantial proportion of patients suffering from side effects of opioids.

A mathematical model of cell movement and clustering due to chemotaxis.

This paper presents a numerical method for modelling cell migration and aggregation due to chemotaxis where the cell is attracted towards the direction in which the concentration of a chemical signal is increasing. In the model presented here, each cell is represented by a system of springs connected together at node points on the cell's membrane and on the boundary of the cell's nucleus. The nodes located on a cell's membrane are subject to a force which is proportional to the gradient of the concentration of the chemical signal which mimics the behaviour of the chemical receptors in the cell's membrane. In particular, the model developed here will consider what happens when two (or more) cells collide and how their membranes connect to each other to form clusters of cells. The methods described in this paper will be illustrated with a number of typical examples simulating cells moving in response to a chemical signal and how they combine to form clusters.

Self-directed self-management interventions to prevent or address distress in young people with long-term physical conditions: A rapid review.

BACKGROUND: Comorbid distress in adolescents and young adults with physical long-term conditions (LTCs) is common but can be difficult to identify and manage. Self-directed self-management interventions to reduce distress and improve wellbeing may be beneficial. It is unknown, however, which intervention characteristics are successful in supporting young people. This rapid review aimed to identify characteristics of self-directed self-management interventions that aimed, in whole or part, to address distress, wellbeing or self-efficacy in this population. METHODS: A systematic search was conducted for relevant controlled studies in six databases. Data on study settings, population, intervention characteristics, outcome measures, process measures and summary effects were extracted. The risk of bias was assessed using the Cochrane Risk of Bias tool v1, and the strength of evidence was rated (informed by Grading of Recommendations, Assessment, Development and Evaluations). Patient and public involvement members supported the review process, including interpretation of results. The rapid review was registered with PROSPERO (ID: CRD42021285867). RESULTS: Fourteen studies were included, all of which were randomised trials. Heterogeneity was identified in the health conditions targeted; type of intervention; outcome measures; duration of intervention and follow-up. Three had distress, wellbeing or self-efficacy as their primary outcome. Four modes of delivery were identified across interventions-websites, smartphone applications, text messages and workbooks; and within these, 38 individual components. Six interventions had a significant benefit in mental health, wellbeing or self-efficacy; however, intervention characteristics were similar for beneficial and non-beneficial interventions. CONCLUSIONS: There is a paucity of interventions directly targeting distress and wellbeing in young people with physical LTCs. In those identified, the heterogeneity of interventions and study design makes it difficult to identify which characteristics result in positive outcomes. We propose the need for high-quality, evidence-based self-management interventions for this population; including (1) more detailed reporting of intervention design, content and delivery; (2) robust process evaluation; (3) a core outcome set for measuring mental health and wellbeing for self-management interventions and (4) consistency in follow up periods. PUBLIC CONTRIBUTION: Seven young people with an LTC were involved throughout the rapid review, from the development of the review protocol where they informed the focus and aims, with a central role in the interpretation of findings.

Patients' views and experiences of delayed diagnosis of inflammatory bowel disease: a qualitative study.

BACKGROUND: Diagnosing inflammatory bowel disease (IBD) can be challenging. Patients have been found to experience significant diagnostic delay, which can lead to poorer clinical outcomes. The reasons for this delay are not fully understood, and exploring patients' perspectives can offer important insights. AIM: To explore the views and experiences of patients who self-report a delay in IBD diagnosis. DESIGN & SETTING: Qualitative methodology using semi-structured interviews. Participants were recruited via social media and a national IBD charity. METHOD: Interviews were conducted by telephone between December 2018 and February 2019. Data were analysed using thematic analysis and drawing on the constant comparison method. RESULTS: Sixteen interviews were carried out. Ten participants were female and six were male; participants were aged 20-65 years. Four main themes were identified: patient factors contributing to delay; primary care factors contributing to delay; systemic factors contributing to delay; and perceived consequences of delayed diagnosis. Participants reported initially not seeking help due to embarrassment or normalising their symptoms. Having consulted, participants reported further delay in receiving a diagnosis due to their perception that GPs had either mislabelled symptoms, expressed uncertainty, or not taken symptoms seriously. Systemic factors, including lack of access to test results and communication issues across primary and secondary care, were also cited as contributing to delayed diagnosis. Several participants felt that their delayed diagnosis led to poorer clinical outcomes. CONCLUSION: These findings can support patients and GPs in their conversations about symptoms that may indicate IBD, and potentially contribute to reducing diagnostic delay, as well as informing future primary care interventions.

The analysis of gut microbiota in patients with bile acid diarrhoea treated with colesevelam.

Introduction: Bile acid diarrhoea (BAD) is a common disorder that results from an increased loss of primary bile acids and can result in a change in microbiome. The aims of this study were to characterise the microbiome in different cohorts of patients with BAD and to determine if treatment with a bile acid sequestrant, colesevelam, can alter the microbiome and improve microbial diversity. Materials and methods: Patients with symptoms of diarrhoea underwent 75-selenium homocholic acid (75SeHCAT) testing and were categorised into four cohorts: idiopathic BAD, post-cholecystectomy BAD, post-operative Crohn's disease BAD and 75SeHCAT negative control group. Patients with a positive 75SeHCAT (<15%) were given a trial of treatment with colesevelam. Stool samples were collected pre-treatment, 4-weeks, 8-weeks and 6-12 months post-treatment. Faecal 16S ribosomal RNA gene analysis was undertaken. Results: A total of 257 samples were analysed from 134 patients. α-diversity was significantly reduced in patients with BAD and more specifically, in the idiopathic BAD cohort and in patients with severe disease (SeHCAT <5%); p < 0.05. Colesevelam did not alter bacterial α/ß-diversity but patients who clinically responded to treatment had a significantly greater abundance of Fusobacteria and Ruminococcus, both of which aid in the conversion of primary to secondary bile acids. Conclusion: This is the first study to examine treatment effects on the microbiome in BAD, which demonstrated a possible association with colesevelam on the microbiome through bile acid modulation in clinical responders. Larger studies are now needed to establish a causal relationship with colesevelam and the inter-crosstalk between bile acids and the microbiome.

Randomised, placebo-controlled trial and meta-analysis show benefit of ondansetron for irritable bowel syndrome with diarrhoea: The TRITON trial.

BACKGROUND: Ondansetron may be beneficial in irritable bowel syndrome with diarrhoea (IBS-D). AIM: To conduct a 12-week parallel group, randomised, double-blind, placebo-controlled trial of ondansetron 4 mg o.d. (titrated up to 8 mg t.d.s.) in 400 IBS-D patients. PRIMARY ENDPOINT: % responders using the Food and Drug Administration (FDA) composite endpoint. Secondary and mechanistic endpoints included stool consistency (Bristol Stool Form Scale) and whole gut transit time (WGTT). After literature review, results were pooled with other placebo-controlled trials in a meta-analysis to estimate relative risks (RR), 95% confidence intervals (CIs) and number needed to treat (NNT). RESULTS: Eighty patients were randomised. On intention-to-treat analysis, 15/37 (40.5%; 95% CI 24.7%-56.4%) met the primary endpoint on ondansetron versus 12/43 (27.9%; 95% CI 14.5%-41.3%) on placebo (p = 0.19). Ondansetron improved stool consistency compared with placebo (adjusted mean difference - 0.7; 95% CI -1.0 to-0.3, p < 0.001). Ondansetron increased WGTT between baseline and week 12 (mean (SD) difference 3.8 (9.1) hours, versus placebo -2.2 (10.3) hours, p = 0.01). Meta-analysis of 327 patients from this, and two similar trials, demonstrated ondansetron was superior to placebo for the FDA composite endpoint (RR of symptoms not responding = 0.86; 95% CI 0.75-0.98, NNT = 9) and stool response (RR = 0.65; 95% CI 0.52-0.82, NNT = 5), but not abdominal pain response (RR = 0.95; 95% CI 0.74-1.20). CONCLUSIONS: Although small numbers meant the primary endpoint was not met in this trial, when pooled with other similar trials meta-analysis suggests ondansetron improves stool consistency and reduces days with loose stool and urgency. Trial registration - http://www.isrctn.com/ISRCTN17508514.

Diagnostic delay in adult inflammatory bowel disease: A systematic review.

BACKGROUND: The extent of diagnostic delay in inflammatory bowel disease (IBD) is incompletely understood. We aimed to understand the extent of diagnostic delay of IBD in adults and identify associations between patient or healthcare characteristics and length of delay. METHODS: Articles were sourced from EMBASE, Medline and CINAHL from inception to April 2021. Inclusion criteria were adult cohorts (18 ≥ years old) reporting median time periods between onset of symptoms for Crohn's disease (CD), ulcerative colitis (UC) or IBD (i.e. CD and UC together) and a final diagnosis (diagnostic delay). Narrative synthesis was used to examine the extent of diagnostic delay and characteristics associated with delay. Sensitivity analysis was applied by the removal of outliers. RESULTS: Thirty-one articles reporting median diagnostic delay for IBD, CD or UC were included. After sensitivity analysis, the majority of IBD studies (7 of 8) reported a median delay of between 2 and 5.3 months. From the studies examining median delay in UC, three-quarters (12 of 16) reported a delay between 2 and 6 months. In contrast, three-quarters of the CD studies (17 of 23) reported a delay of between 2 and 12 months. No characteristic had been examined enough to understand their role in diagnostic delay in these populations. CONCLUSIONS: This systematic review provides robust insight into the extent of diagnostic delay in IBD and suggests further intervention is needed to reduce delay in CD particularly. Furthermore, our findings provide a benchmark value range for diagnostic delay, which such future work can be measured against.

Factors influencing rectal hypersensitivity in irritable bowel syndrome: A systematic review and meta-analysis.

BACKGROUND: A frequent, although not universal, feature of irritable bowel syndrome (IBS) is heightened sensitivity to mechanical stimulation of the rectum, termed rectal hypersensitivity (RH). Differences in RH-based on sex, IBS subtype, IBS diagnostic criteria and age of population studied are incompletely understood. We aimed to determine whether IBS population had lower pain thresholds than healthy controls. METHODS: We searched MEDLINE and EMBASE databases (1970-2021). Prospective studies that compared pain/discomfort thresholds to mechanical rectal stimuli in IBS and healthy controls were included. Data were pooled for meta-analyses and effect sizes were calculated with 95% confidence interval (CIs). RESULTS: Our search strategy identified 809 studies of which 32 studies met the inclusion criteria. Reduced rectal pain thresholds was more common in IBS patients compared to healthy controls with an effect size of 1.00 95% CIs (0.77-1.24) (p < 0.0001) (I2  = 78.6%). The pediatric IBS population had lower pain thresholds than adult IBS populations (p = 0.05) but no difference based on IBS diagnostic criteria, subtype or sex. CONCLUSION & INFERENCES: The results suggest that reduced rectal pain threshold to experimental stimulation is far more common in IBS patients than healthy controls. Further research is required to understand the pathophysiological and therapeutic implications of rectal sensitivity such as its role in measuring response to treatment and prognosis in IBS.

Intra-sphincteric botulinum toxin in the management of functional biliary pain.

Background and study aims The management of functional biliary-type pain remains a clinical challenge. Intra sphincteric botulinum toxin putatively exerts an anti-spasmodic and anti-nociceptive effect. The objective of this study was to examine the clinical response to intra sphincteric botulinum toxin in patients with functional biliary-type pain. Patients and methods This was a cross-sectional (hypothesis-generating) study of prospectively collected data from patients referred to a tertiary center from 2014 to 2019. The efficacy of ampullary botulinum toxin injection for relief of pain was recorded at post-procedure outpatient review. Opioid analgesia, neuromodulatory medication, and frequency of hospital admissions were recorded. Results A total of 119 consecutive patients (109 women, 10 men, mean age 45 years; range 17-77) underwent 411 intra-sphincteric botulinum toxin injection procedures (mean 2 procedures; range 1-15). A total of 103 patients (87 %) had a significant improvement in pain on post-procedure review and 77 % and 76 % of patients were opioid and admission free, respectively. Of the patients, 59 % were prescribed tricyclic antidepressants (amitriptyline), 18 % duloxetine, 13 % pregabalin, and 3 % mirtazapine. Loss of response with the initial dose of botulinum toxin occurred in 56 % of patients. Pain control was reestablished in 80 % of patients in this cohort following botulinum toxin injection at a higher dose. Conclusions These data suggest that botulinum toxin may improve outcomes in patients with functional biliary pain. Further controlled studies are needed to clarify the role of Botox and neuromodulatory agents.

Performance and Interpretation of Hydrogen and Methane Breath Testing Impact of North American Consensus Guidelines.

BACKGROUND: Hydrogen and methane breath tests (HMBT) are widely used clinical investigations but lack standardization. To address this, the North American Consensus (NAC) group published evidence-based recommendations for HMBT. AIMS: To evaluate results obtained using NAC recommendations for HMBT, compared to retrospective data that utilized guidelines previously recommended. METHODS: HMBT data from 725 patients referred for small intestinal bacterial overgrowth (SIBO) and/or carbohydrate malabsorption (CM) testing were analyzed. Data were compared regarding dose of substrate for SIBO testing (16 vs. 10 g lactulose, and 50 vs. 75 g glucose) and the effect of post-ingestion sampling period for malabsorption testing. The effect of different recommended cut-off values for SIBO were examined. RESULTS: Substrate dose did not affect methane production. 10 g lactulose significantly reduced positive SIBO results compared to 16 g lactulose (42 vs. 53%, p = 0.04). 75 g glucose significantly increased positive results compared to 50 g glucose (36 vs. 22%, p = 0.04). Provoked symptoms were significantly more prevalent in patients testing positive by both North American Consensus and Ledochowski cut-off values. 34.5% of patients tested positive for CM at 180-min compared to 28% at 120-min (not significant, p = 0.19). CONCLUSIONS AND INFERENCES: 10 g lactulose substrate produces fewer positive SIBO results than 16 g lactulose, while 75 g glucose dose produces more positive SIBO results than 50 g. Performing CM breath tests for 180 min increases number of positive results when compared to 120 min. SIBO cut-off timings require further investigation, but our findings broadly support the NAC recommendations for SIBO and CM testing.

Diagnostic Delay in Pediatric Inflammatory Bowel Disease: A Systematic Review.

INTRODUCTION: Delays in diagnosing pediatric inflammatory bowel disease (IBD) are common, but the extent of this delay remains unclear due to variations in reported time-periods between studies. The objectives of this systematic review were to examine the extent of diagnostic delay in pediatric IBD and examine any association between specific characteristics and length of diagnostic delay. METHODS: We identified studies from several medical bibliographical databases (EMBASE, Medline and CINAHL) from their inception to April 2021. Studies examining pediatric cohorts (< 18 years old) defined as having a diagnosis of Crohn's Disease (CD), ulcerative colitis (UC), or by the more general definition of IBD, and reporting a median time-period between the onset of symptoms and a final diagnosis (diagnostic delay) were included. Two reviewers selected each study, extracted data, and assessed their quality using the Newcastle-Ottawa scale. Narrative synthesis was then used to examine the extent of overall diagnostic delay and delay associated with specific sample characteristics. RESULTS: Of the 10,119 studies initially identified, 24 were included in the review. The overall median diagnostic delay range was 2-10.4 months for IBD, 2.0-18.0 months for UC and 4.0-24.0 months for CD. However, for approximately two thirds of UC (68.8%) and CD (66.7%) studies, delay ranged from 2.0-3.0 and 4.0-6.3 months, respectively. A longer delay was significantly associated with several sample characteristics; however, these were too infrequently examined to draw robust conclusion on their role. CONCLUSION: Children continue to wait several months for a final diagnosis of IBD, and those with CD experience longer delay than those with UC. The role of specific characteristics on delay needs further exploration.

United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on functional dyspepsia.

BACKGROUND: Functional dyspepsia (FD) is one of the most common conditions in clinical practice. In spite of its prevalence, FD is associated with major uncertainties in terms of its definition, underlying pathophysiology, diagnosis, treatment, and prognosis. METHODS: A Delphi consensus was initiated with 41 experts from 22 European countries who conducted a literature summary and voting process on 87 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 36 statements. RESULTS: The panel agreed with the definition in terms of its cardinal symptoms (early satiation, postprandial fullness, epigastric pain, and epigastric burning), its subdivision into epigastric pain syndrome and postprandial distress syndrome, and the presence of accessory symptoms (upper abdominal bloating, nausea, belching), and overlapping conditions. Also, well accepted are the female predominance of FD, its impact on quality of life and health costs, and acute gastrointestinal infections, and anxiety as risk factors. In terms of pathophysiological mechanisms, the consensus supports a role for impaired gastric accommodation, delayed gastric emptying, hypersensitivity to gastric distention, Helicobacter pylori infection, and altered central processing of signals from the gastroduodenal region. There is consensus that endoscopy is mandatory for establishing a firm diagnosis of FD, but that in primary care, patients without alarm symptoms or risk factors can be managed without endoscopy. There is consensus that H. pylori status should be determined in every patient with dyspeptic symptoms and H. pylori positive patients should receive eradication therapy. Also, proton pump inhibitor therapy is considered an effective therapy for FD, but no other treatment approach reached a consensus. The long-term prognosis and life expectancy are favorable. CONCLUSIONS AND INFERENCES: A multinational group of European experts summarized the current state of consensus on the definition, diagnosis and management of FD.

The autonomic brain: Multi-dimensional generative hierarchical modelling of the autonomic connectome.

The autonomic nervous system governs the body's multifaceted internal adaptation to diverse changes in the external environment, a role more complex than is accessible to the methods-and data scales-hitherto used to illuminate its operation. Here we apply generative graphical modelling to large-scale multimodal neuroimaging data encompassing normal and abnormal states to derive a comprehensive hierarchical representation of the autonomic brain. We demonstrate that whereas conventional structural and functional maps identify regions jointly modulated by parasympathetic and sympathetic systems, only graphical analysis discriminates between them, revealing the cardinal roles of the autonomic system to be mediated by high-level distributed interactions. We provide a novel representation of the autonomic system-a multidimensional, generative network-that renders its richness tractable within future models of its function in health and disease.

United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on functional dyspepsia.

BACKGROUND: Functional dyspepsia (FD) is one of the most common conditions in clinical practice. In spite of its prevalence, FD is associated with major uncertainties in terms of its definition, underlying pathophysiology, diagnosis, treatment, and prognosis. METHODS: A Delphi consensus was initiated with 41 experts from 22 European countries who conducted a literature summary and voting process on 87 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 36 statements. RESULTS: The panel agreed with the definition in terms of its cardinal symptoms (early satiation, postprandial fullness, epigastric pain, and epigastric burning), its subdivision into epigastric pain syndrome and postprandial distress syndrome, and the presence of accessory symptoms (upper abdominal bloating, nausea, belching), and overlapping conditions. Also, well accepted are the female predominance of FD, its impact on quality of life and health costs, and acute gastrointestinal infections, and anxiety as risk factors. In terms of pathophysiological mechanisms, the consensus supports a role for impaired gastric accommodation, delayed gastric emptying, hypersensitivity to gastric distention, Helicobacter pylori infection, and altered central processing of signals from the gastroduodenal region. There is consensus that endoscopy is mandatory for establishing a firm diagnosis of FD, but that in primary care, patients without alarm symptoms or risk factors can be managed without endoscopy. There is consensus that H. pylori status should be determined in every patient with dyspeptic symptoms and H. pylori positive patients should receive eradication therapy. Also, proton pump inhibitor therapy is considered an effective therapy for FD, but no other treatment approach reached a consensus. The long-term prognosis and life expectancy are favorable. CONCLUSIONS AND INFERENCES: A multinational group of European experts summarized the current state of consensus on the definition, diagnosis and management of FD.

British Society of Gastroenterology guidelines on the management of irritable bowel syndrome.

Irritable bowel syndrome (IBS) remains one of the most common gastrointestinal disorders seen by clinicians in both primary and secondary care. Since publication of the last British Society of Gastroenterology (BSG) guideline in 2007, substantial advances have been made in understanding its complex pathophysiology, resulting in its re-classification as a disorder of gut-brain interaction, rather than a functional gastrointestinal disorder. Moreover, there has been a considerable amount of new evidence published concerning the diagnosis, investigation and management of IBS. The primary aim of this guideline, commissioned by the BSG, is to review and summarise the current evidence to inform and guide clinical practice, by providing a practical framework for evidence-based management of patients. One of the strengths of this guideline is that the recommendations for treatment are based on evidence derived from a comprehensive search of the medical literature, which was used to inform an update of a series of trial-based and network meta-analyses assessing the efficacy of dietary, pharmacological and psychological therapies in treating IBS. Specific recommendations have been made according to the Grading of Recommendations Assessment, Development and Evaluation system, summarising both the strength of the recommendations and the overall quality of evidence. Finally, this guideline identifies novel treatments that are in development, as well as highlighting areas of unmet need for future research.

Constipation Predominant Irritable Bowel Syndrome and Functional Constipation Are Not Discrete Disorders: A Machine Learning Approach.

INTRODUCTION: Chronic constipation is classified into 2 main syndromes, irritable bowel syndrome with constipation (IBS-C) and functional constipation (FC), on the assumption that they differ along multiple clinical characteristics and are plausibly of distinct pathophysiology. Our aim was to test this assumption by applying machine learning to a large prospective cohort of comprehensively phenotyped patients with constipation. METHODS: Demographics, validated symptom and quality of life questionnaires, clinical examination findings, stool transit, and diagnosis were collected in 768 patients with chronic constipation from a tertiary center. We used machine learning to compare the accuracy of diagnostic models for IBS-C and FC based on single differentiating features such as abdominal pain (a "unisymptomatic" model) vs multiple features encompassing a range of symptoms, examination findings and investigations (a "syndromic" model) to assess the grounds for the syndromic segregation of IBS-C and FC in a statistically formalized way. RESULTS: Unisymptomatic models of abdominal pain distinguished between IBS-C and FC cohorts near perfectly (area under the curve 0.97). Syndromic models did not significantly increase diagnostic accuracy (P > 0.15). Furthermore, syndromic models from which abdominal pain was omitted performed at chance-level (area under the curve 0.56). Statistical clustering of clinical characteristics showed no structure relatable to diagnosis, but a syndromic segregation of 18 features differentiating patients by impact of constipation on daily life. DISCUSSION: IBS-C and FC differ only about the presence of abdominal pain, arguably a self-fulfilling difference given that abdominal pain inherently distinguishes the 2 in current diagnostic criteria. This suggests that they are not distinct syndromes but a single syndrome varying along one clinical dimension. An alternative syndromic segregation is identified, which needs evaluation in community-based cohorts. These results have implications for patient recruitment into clinical trials, future disease classifications, and management guidelines.