Scan-Negative Cauda Equina Syndrome A Prospective Cohort Study

Objective: To describe clinical features relevant to diagnosis, mechanism, and etiology in patients with “scan-negative” cauda equina syndrome (CES). Methods: We carried out a prospective study of consecutive patients presenting with the clinical features of CES to a regional neurosurgery center comprising semi-structured interview and questionnaires investigating presenting symptoms, neurologic examination, psychiatric and functional disorder comorbidity, bladder/bowel/sexual function, distress, and disability. Results: A total of 198 patients presented consecutively over 28 months. A total of 47 were diagnosed with scan-positive CES (mean age 48 years, 43% female). A total of 76 mixed category patients had nerve root compression/displacement without CES compression (mean age 46 years, 71% female) and 61 patients had scan-negative CES (mean age 40 years, 77% female). An alternative neurologic cause of CES emerged in 14/198 patients during admission and 4/151 patients with mean duration 25 months follow-up. Patients with scan-negative CES had more positive clinical signs of a functional neurologic disorder (11% scan-positive CES vs 34% mixed and 68% scan-negative, p < 0.0001), were more likely to describe their current back pain as worst ever (41% vs 46% and 70%, p = 0.005), and were more likely to have symptoms of a panic attack at onset (37% vs 57% and 70%, p = 0.001). Patients with scan-positive CES were more likely to have reduced/absent bilateral ankle jerks (78% vs 30% and 12%, p < 0.0001). There was no significant difference between groups in the frequency of reduced anal tone and urinary retention. Conclusion: The first well-phenotyped, prospective study of scan-negative CES supports a model in which acute pain, medication, and mechanisms overlapping with functional neurologic disorders may be relevant

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

UK clinical experience up to 52 weeks with linaclotide for irritable bowel syndrome with constipation

Background: Linaclotide, a guanylate cyclase C agonist, has been shown in clinical trials to improve symptoms of irritable bowel syndrome with constipation (IBS-C). Here we report data from a real-world study of linaclotide in the UK. Methods: This 1-year, multicentre, prospective, observational study in the UK enrolled patients aged 18 years and over initiating linaclotide for IBS-C. The primary assessment was change from baseline in IBS Symptom Severity Scale (IBS-SSS) score at 12 weeks, assessed in patients with paired baseline and 12-week data. Change from baseline in IBS-SSS score at 52 weeks was a secondary assessment. Adverse events were recorded. Results: In total, 202 patients were enrolled: 185 (91.6%) were female, median age was 44.9 years (range 18.1–77.2) and 84 (41.6%) reported baseline laxative use. Mean (standard deviation) baseline IBS-SSS score was 339 (92), with most patients (n = 129; 66.8%) classified as having severe disease (score ⩾300). In patients with paired data, there was a significant mean (95% confidence interval) decrease in IBS-SSS score from baseline to 12 weeks [−77.0 (−96.3, −57.7); p < 0.001; n = 124] and baseline to 52 weeks [−70.7 (−95.0, −46.5); p < 0.001; n = 76]. Overall, 174 adverse events were reported in 77 (38.1%) patients, most commonly diarrhoea (n = 54; 26.7%), abdominal pain (n = 21; 10.4%) and abdominal distension (n = 13; 6.4%). Conclusion: Linaclotide significantly improved IBS-SSS score at 12 and 52 weeks. These results provide insights into outcomes with linaclotide treatment over 1 year in patients with IBS-C in real-world clinical practice

Uk Clinical Experience Up to 52 Weeks With Linaclotide for Irritable Bowel Syndrome With Constipation

BACKGROUND: Linaclotide, a guanylate cyclase C agonist, has been shown in clinical trials to improve symptoms of irritable bowel syndrome with constipation (IBS-C). Here we report data from a real-world study of linaclotide in the UK. METHODS: This 1-year, multicentre, prospective, observational study in the UK enrolled patients aged 18 years and over initiating linaclotide for IBS-C. The primary assessment was change from baseline in IBS Symptom Severity Scale (IBS-SSS) score at 12 weeks, assessed in patients with paired baseline and 12-week data. Change from baseline in IBS-SSS score at 52 weeks was a secondary assessment. Adverse events were recorded. RESULTS: In total, 202 patients were enrolled: 185 (91.6%) were female, median age was 44.9 years (range 18.1-77.2) and 84 (41.6%) reported baseline laxative use. Mean (standard deviation) baseline IBS-SSS score was 339 (92), with most patients (n = 129; 66.8%) classified as having severe disease (score ⩾300). In patients with paired data, there was a significant mean (95% confidence interval) decrease in IBS-SSS score from baseline to 12 weeks [-77.0 (-96.3, -57.7); p < 0.001; n = 124] and baseline to 52 weeks [-70.7 (-95.0, -46.5); p < 0.001; n = 76]. Overall, 174 adverse events were reported in 77 (38.1%) patients, most commonly diarrhoea (n = 54; 26.7%), abdominal pain (n = 21; 10.4%) and abdominal distension (n = 13; 6.4%). CONCLUSION: Linaclotide significantly improved IBS-SSS score at 12 and 52 weeks. These results provide insights into outcomes with linaclotide treatment over 1 year in patients with IBS-C in real-world clinical practice

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

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

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