An implementation trial of ACT-based bibliotherapy for Irritable Bowel Syndrome

Background: Irritable Bowel Syndrome is a gastrointestinal disorder that is associated with pain, discomfort, constipation and diarrhoea. It affects around 20% of adults in Western countries. Reports of distress and self-consciousness, as well as experiential and situational avoidance are common. Previous studies have shown that ACT may be effective for people with IBS. Methods: An uncontrolled trial of ACT based bibliotherapy was undertaken in a specialist motility clinic. Outcomes were measured with standardised self-report questionnaires pre-treatment, and at two and six months. Missing data was handled using maximum likelihood imputation. Data was analysed using repeated measures ANOVA. Results: 45 participants enrolled in the study, with 36 providing data at two months, and 24 at six months. Participants were predominantly female, with an average tenyear history of IBS, and 71% of the sample had moderate or severe symptoms. At six months,participants had improved on symptom severity (hp 2 = .09, 90% CI = .01 - .18), GI specific anxiety (hp 2 = .07, 90% CI = .01 - .16) and IBS willingness (hp 2 = .14, 90% CI = .04 - .24), but had not shown behavioural changes towards greater activity, (hp 2 = .01, 90% CI = .0 - .05) or to reduce IBS avoidance behaviours (hp 2 = .05, 90% CI = .0 = .13). Contrary to hypothesis, intervention did not reduce the impact of IBS on quality of life(hp 2 = .04, 90% CI = .0 - .09). Discussion: Bibliotherapy interventions may be useful for people with refractory IBS, though greater contact and structured exposure may be necessary to change behaviour. The study was limited by problems with attrition, though these data suggest future research in this area would be worthwhile

British Society of Gastroenterology guidelines on the management of functional dyspepsia

Functional dyspepsia (FD) is a common disorder of gut-brain interaction, affecting approximately 7% of individuals in the community, with most patients managed in primary care. The last British Society of Gastroenterology (BSG) guideline for the management of dyspepsia was published in 1996. In the interim, substantial advances have been made in understanding the complex pathophysiology of FD, and there has been a considerable amount of new evidence published concerning its diagnosis and classification, with the advent of the Rome IV criteria, and management. 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 diagnosis and treatment of patients. The approach to investigating the patient presenting with dyspepsia is discussed, and efficacy of drugs in FD summarised based on evidence derived from a comprehensive search of the medical literature, which was used to inform an update of a series of pairwise and network meta-Analyses. Specific recommendations have been made according to the Grading of Recommendations Assessment, Development and Evaluation system. These provide both the strength of the recommendations and the overall quality of evidence. Finally, in this guideline, we consider novel treatments that are in development, as well as highlighting areas of unmet need and priorities for future research

The national prevalence of disorders of gut brain interaction in the United Kingdom in comparison to their worldwide prevalence: Results from the Rome foundation global epidemiology study

Background: There are minimal epidemiological data comparing the burden of disorders of gut brain interaction (DGBI) in the UK with other countries. We compared the prevalence of DGBI in the UK with other countries that participated in the Rome Foundation Global Epidemiology Study (RFGES) online. Methods: Participants from 26 countries completed the RFGES survey online including the Rome IV diagnostic questionnaire and an in-depth supplemental questionnaire with questions about dietary habits. UK sociodemographic and prevalence data were compared with the other 25 countries pooled together. Key Results: The proportion of participants with at least one DGBI was lower in UK participants compared with in the other 25 countries (37.6% 95% CI 35.5%–39.7% vs. 41.2%; 95% CI 40.8%–41.6%, p = 0.001). The UK prevalence of 14 of 22 Rome IV DGBI, including irritable bowel syndrome (4.3%) and functional dyspepsia (6.8%), was similar to the other countries. Fecal incontinence, opioid-induced constipation, chronic nausea and vomiting, and cannabinoid hyperemesis (p < 0.05) were more prevalent in the UK. Cyclic vomiting, functional constipation, unspecified functional bowel disorder, and proctalgia fugax (p < 0.05) were more prevalent in the other 25 countries. Diet in the UK population consisted of higher consumption of meat and milk (p < 0.001), and lower consumption of rice, fruit, eggs, tofu, pasta, vegetables/legumes, and fish (p < 0.001). Conclusions and Inferences: The prevalence and burden of DGBI is consistently high in the UK and in the rest of the world. Opioid prescribing, cultural, dietary, and lifestyle factors may contribute to differences in the prevalence of some DGBI between the UK and other countries

Ondansetron for irritable bowel syndrome with diarrhoea: randomised controlled trial

Background: Irritable bowel syndrome with diarrhoea is characterised by frequent, loose or watery stools with associated urgency, resulting in marked reduction of quality of life. Ondansetron, a 5-hydroxytryptamine-3 receptor antagonist, has been shown to benefit patients with irritable bowel syndrome with diarrhoea.Objective: To evaluate the effect of ondansetron in irritable bowel syndrome with diarrhoea.Design: Phase III, parallel-group, randomised, double-blind, multicentre, placebo-controlled trial in 400 patients, with embedded mechanistic studies.Setting: Hospital, primary care and community.Participants: Eighty participants meeting Rome IV criteria for irritable bowel syndrome with diarrhoea.Intervention: Ondansetron 4 mg (dose titrated up to two tablets three times a day) or matched placebo for 12 weeks.Main outcome measures: Clinical – Primary patient-reported end point was % ‘Food and Drug Administration-defined responders’ over 12 weeks. Secondary end points were worst abdominal pain intensity, worst urgency, stool consistency, stool frequency, anxiety, depression and dyspepsia at 12 and 16 weeks.Main outcome measures: Mechanistic – Whole gut transit time, faecal water, protease (FP), bile acids and assessment of rectal sensitivity using a barostat.Results: Clinical – The study closed early due to slow recruitment. Between 1 January 2018 and 11 May 2020, 80 patients were recruited and randomised (20% of target), 37 to ondansetron, 43 to placebo. Discontinuations (4 ondansetron; 2 placebo) meant 75 completed the 12-week trial treatment. There were four protocol violations. In the intention-to-treat analysis, 15 (40.5%) on ondansetron were primary end-point responders (95% CI 24.7% to 56.4%), and 12 (27.9%) on placebo (95% CI 14.5% to 41.3%), p = 0.19, adjusted OR 1.93 (0.73, 5.11). Pain intensity reduction occurred in 17 (46.0%) on ondansetron (95% CI 29.9% to 62.0%) and 16 (37.2%) on placebo (95% CI 22.8% to 51.7%), p = 0.32. Improvement in stool consistency occurred in 25 (67.6%) on ondansetron (95% CI 52.5% to 82.7%) and 22 (51.2%) on placebo (95% CI 36.2% to 66.1%), p = 0.07. Use of rescue medication, loperamide, was lower on ondansetron [7 (18.9%) vs. 17 (39.5%)]. Average stool consistency in the final month of treatment reduced significantly more on ondansetron, adjusted mean difference –0.5 [standard error (SE) 0.25, 95% CI (–1.0 to –0.02), p = 0.042]. Ondansetron improved dyspepsia score (SFLDQ), adjusted mean difference –3.2 points [SE 1.43, 95% CI (–6.1 to –0.4), p = 0.028]. There were no serious adverse events.Mechanistic – mean (SD). Ondansetron increased whole gut transit time between baseline and week 12 by 3.8 (9.1) hours on ondansetron, significantly more than on placebo –2.2 (10.3), p = 0.01. Mean volume to reach urgency threshold using the barostat increased on ondansetron by 84 (61) ml and 38 (48) ml on placebo, n = 8, p = 0.26. Ondansetron did not significantly alter protease, faecal water or bile acids. Changes in referral pathways substantially reduced referrals, impairing recruitment, which meant the study was underpowered.Conclusion: Our results are consistent with previous studies and confirmed ondansetron improves stool consistency and urgency but showed minor effect on pain. We plan to undertake a simplified version of this trial overcoming the changed referral pathways by recruiting in primary care, using software linked to primary care records to identify and randomise patients with irritable bowel syndrome with diarrhoea to ondansetron or placebo and remotely follow their progress; thus minimising barriers to recruitment.Trial registration: This trial is registered as ISRCTN17508514.Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation programme and will be published in full in Efficacy and Mechanism Evaluation; Vol. 10, No. 9. See the NIHR Journals Library website for further project information

Treatment of irritable bowel syndrome with diarrhoea using titrated ondansetron (TRITON): study protocol for a randomised controlled trial

Background: Irritable bowel syndrome with diarrhoea (IBS-D) affects up to 4% of the general population. Symptoms include frequent, loose, or watery stools with associated urgency, resulting in marked reduction of quality of life and loss of work productivity. Ondansetron, a 5HT3 receptor antagonist, has had an excellent safety record for over 20 years as an antiemetic, yet is not widely used in the treatment of IBS-D. It has, however, been shown to slow colonic transit and in a small randomised, placebo-controlled, cross-over pilot study, benefited patients with IBS-D. Methods: This trial is a phase III, parallel group, randomised, double-blind, multi-centre, placebo-controlled trial, with embedded mechanistic studies. Participants (n = 400) meeting Rome IV criteria for IBS-D will be recruited from outpatient and primary care clinics and by social media to receive either ondansetron (dose titrated up to 24 mg daily) or placebo for 12 weeks. Throughout the trial, participants will record their worst abdominal pain, worst urgency, stool frequency, and stool consistency on a daily basis. The primary endpoint is the proportion of “responders” in each group, using Food and Drug Administration (FDA) recommendations. Secondary endpoints include pain intensity, stool consistency, frequency, and urgency. Mood and quality of life will also be assessed. Mechanistic assessments will include whole gut transit, faecal tryptase and faecal bile acid concentrations at baseline and between weeks 8 and 11. A subgroup of participants will also undergo assessment of sensitivity (n = 80) using the barostat, and/or high-resolution colonic manometry (n = 40) to assess motor patterns in the left colon and the impact of ondansetron. Discussion: The TRITON trial aims to assess the effect of ondansetron across multiple centres. By defining ondansetron’s mechanisms of action we hope to better identify patients with IBS-D who are likely to respond

Investigating the role of psychological flexibility and the use of an acceptance and commitment therapy based intervention in irritable bowel syndrome

Irritable Bowel Syndrome (IBS) is a common chronic illness thought to be originated and maintained by a combination of physiological, psychological and social factors. IBS is known to be associated with a high psychosocial impact on patients’ lives. Acceptance and Commitment Therapy (ACT) is an emerging model of conceptualization and treatment that states that most suffering in chronic illness can be explained by a lack of psychological flexibility or acceptance to experience aversive bodily sensations, thoughts or emotions. ACT treatments target the increase of psychological flexibility as a key change for improvement in outcomes. Recent studies suggest that ACT could not only be an effective alternative treatment for IBS, as it might provide a valuable model of understanding of the relations between the different factors related to this condition and its outcomes. The first aim of the present research was to investigate the role of psychological flexibility in IBS, in particular, how acceptance relates to psychological, emotional and physical factors in this condition. The second aim was to investigate the effectiveness of an ACT based intervention in increasing psychological flexibility in IBS and thereby improving IBS Outcomes. These aims were addressed by conducting two related studies. In Study 1, a sample of 121 IBS patients attending a specialized gastroenterology clinic completed a series of self-report measures of psychological flexibility (acceptance), psychological factors known to be associated with IBS and IBS outcomes. Results indicated that higher levels of acceptance were generally associated with and predicted better levels of IBS biopsychosocial factors. Results also showed that acceptance mediated most of the relationships between IBS predictors and Outcomes. Also, psychometric analyses of a novel measure of IBS Acceptance (i.e. IBS Acceptance and Action Questionnaire) created for this study demonstrated that it had good reliability and validity. In Study 2, fifty six IBS patients enrolled in an intervention involving a one day ACT workshop and an ACT based self-help workbook. Thirty six participants provided follow-up data up to 6 months after the workshop. Results indicated that there were significant increases in acceptance and significant improvement in IBS outcomes between pre-treatment and follow-up. Further to that, analyses indicated that changes in IBS Outcomes occurred through changes in acceptance as hypothesized by the ACT model. These studies suggest that psychological flexibility processes are important in the understanding of IBS and that improvement in this condition may result from a more psychologically flexible stance to it. Although preliminary, these studies provide a basis for the further development and application of the ACT model of conceptualization and treatment in IBS.EThOS - Electronic Theses Online ServiceGBUnited Kingdo