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ObjectiveIrritable bowel syndrome with diarrhoea (IBS-D) is a common and challenging condition that significantly reduces quality of life. Enterosgel (polymethylsiloxane polyhydrate) is an intestinal adsorbent which sequesters harmful molecules and is safe and effective in acute infective diarrhoea. This randomised controlled multicentre trial aimed to investigate its safety and efficacy in patients with IBS-D.DesignAfter a 2-week screening phase, participants were randomised into an 8-week double-blind phase, followed by an 8-week open-label and follow-up phase. Participants recorded stool consistency, pain and global symptoms in e-diaries and questionnaires. The primary outcome was the percentage of responders on a composite abdominal pain (≥30% decrease in the weekly score) and stool consistency (50% reduction in days per week with at least one stool of BSFS type 6 or 7) score during at least 4 weeks of the treatment period.Results440 patients with IBS-D were randomised to the double-blind phase with 393 continuing to the open-label phase. The Primary outcome responder rate by intention-to-treat for enterosgel versus placebo was 37.4% vs 24.3% (OR 1.95, NNT 8, p=0.002). Enterosgel also improved stool consistency (48.5% vs 32.5%, pConclusionEnterosgel is safe and effective in IBS-D, providing an alternative to the limited current treatment options.Trial registration numberISRCTN17149988.

INTRODUCTION: Irritable bowel syndrome (IBS) is a chronic functional bowel disorder, which follows a relapsing and remitting course. Little is known about how evolving definitions of IBS or treatment for the condition affect symptom stability. We conducted a 12-month longitudinal follow-up study of individuals who self-identified as having IBS to examine these issues. METHODS: We collected demographic, gastrointestinal symptom, mood, and psychological health data at baseline, and gastrointestinal symptom data at 12 months, from adults who self-identified as having IBS, registered with 3 organizations providing services to people with IBS. We applied the Rome III and Rome IV criteria simultaneously at baseline and 12 months and subtyped participants according to predominant stool form or frequency. We examined stability of a diagnosis of IBS, and stability of IBS subtype, for the Rome IV and III criteria separately and examined the effect of commencing new therapy on fluctuation of symptoms. RESULTS: Of 1,375 individuals recruited at baseline, 784 (57.0%) provided data at 12 months. Of these, 452 met the Rome IV criteria for IBS at baseline, of whom 133 (29.4%) fluctuated to another functional bowel disorder at 12 months. In the remaining 319 (70.6%) who still met the Rome IV criteria for IBS, IBS subtype changed in 101 (31.7%) subjects, with IBS with mixed bowel habit (IBS-M) the least stable. Commencing a new treatment for IBS did not affect symptom stability. Among 631 who met the Rome III criteria at baseline responding at 12 months, 104 (16.5%) fluctuated to another functional bowel disorder. In the 527 (83.5%) who still met the Rome III criteria for IBS, IBS subtype fluctuated in 129 (24.5%), with IBS-M the most stable subtype. Again, commencing a new treatment for IBS did not affect symptom stability. DISCUSSION: Fluctuation between functional bowel disorders and predominant stool subtype is common in people with IBS and does not appear to be influenced solely by treatment. Rome IV IBS appears less stable than Rome III IBS.

Objectives\ud Sacral nerve stimulation (SNS) may provide long-term symptom relief to patients suffering from chronic constipation. Patients are currently selected for SNS using a 2-week peripheral nerve evaluation (PNE) comprising stimulation by temporary leads. However, only 40% of test responders receive long-term benefit from treatment meaning that healthcare costs per successfully treated patient are too high. The primary objective was to assess tined-lead testing to predict benefit from SNS for chronic constipation.\ud Patients and methods\ud A randomized double-blind sham-controlled cross-over design evaluated enhanced PNE (ePNE) using tined quadripolar electrode leads over 6 weeks. The design differentiated between patients with discriminate and indiscriminate responses to testing. A score improvement of 25% or more was considered to be a positive response within a stimulation period. The primary outcome was the proportion of patients showing a reduction of at least 0.5 in constipation symptom score at 6 months.\ud Results\ud A total of 45 patients were randomized, of whom 29 (64.4%) were test-phase responders. Of these, 27 were implanted providing permanent SNS. During ePNE, seven (18%) were discriminate responders, 22 (56%) were indiscriminate responders and 10 (26%) were nonresponders. Six patients were withdrawn during the test phase because of infection or noncompliance. At 6 months, there was no significant difference in primary outcome between discriminate and indiscriminate responders (60 vs. 57%, P=0.76). The study was terminated prematurely because of a persistent infection rate of 10 (22%) during ePNE of which nine (20%) were severe.\ud Conclusion\ud ePNE is a poor predictor of treatment response at 6 months. This suggests a strong and persistent placebo response during both SNS PNE and treatment. An extended 6-week PNE poses a high risk of infection.

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.

Irritable bowel syndrome (IBS) is a chronic functional bowel disorder diagnosed using the Rome criteria, which have evolved since their original description 30 years ago. Little is known about the effects on the natural history of IBS of moving to the latest iteration, Rome IV, from the previous Rome III criteria. We conducted a 12-month longitudinal follow-up study to examine this.We collected complete demographic, symptom, mood, and psychological health data at baseline from 1097 adults who self-identified as having IBS and met either Rome IV or Rome III criteria. At 12 months, we collected data regarding IBS symptom severity and impact, consultation behavior, treatments commenced, and psychological health. We examined whether subsequent disease behavior in Rome IV- or Rome III-defined IBS differed.At 12 months, 638 (58.2%) of the 1097 participants were followed up successfully. Of these, 452 met Rome IV criteria and 186 met Rome III criteria at baseline. During the 12-month study period, individuals with Rome IV IBS were significantly more likely to have seen a primary care physician (44.7% vs 28.5%; P.001) or a gastroenterologist (26.3% vs 12.4%; P.001) for their IBS symptoms, were significantly more likely to have commenced a new treatment (73.0% vs 60.2%; P = .001), and cycled through significantly more treatments (P = .007), for their IBS compared with those with Rome III IBS. At follow-up evaluation, individuals with Rome IV IBS had more severe symptoms, which had a significantly greater impact on activities of daily living, were more likely to report continuous abdominal pain, and a higher proportion showed poor psychological health, compared with those with Rome III IBS (P.001 for all analyses).The natural history of IBS defined according to Rome IV criteria is more severe than that of Rome III-defined IBS. This has important implications for future treatment trials in IBS.

Disorders of gut-brain interaction, such as irritable bowel syndrome (IBS) and functional dyspepsia (FD), frequently overlap, but the impact of this on the natural history is unknown. We examined this issue in a longitudinal follow-up study conducted in a large cohort of individuals.We collected complete demographic, symptom, mood, and psychological health data from 1374 adults who self-identified as having IBS. We applied the Rome IV criteria to examine what proportion met criteria for IBS and FD, as well as the degree of overlap between them. At 12 months, we collected data regarding IBS symptom severity and impact, consultation behavior, treatments commenced, and psychological health according to degree of overlap between IBS and FD.Overall, 807 individuals met the Rome IV criteria for IBS at baseline and provided complete data. At study entry, overlap of FD occurred in 446 (55.3%) people who met Rome IV criteria for IBS. At 12 months, 451 (55.9%) individuals were successfully followed up. The proportion of individuals consulting their primary care physician (P = .001) or a gastroenterologist (P.001) because of their IBS was significantly higher in those with overlap of IBS and FD, and the number of new IBS treatments commenced was significantly higher (P = .007). Those with overlap of IBS and FD reported significantly more severe IBS symptoms (P.001), continuous abdominal pain, and that their IBS symptoms limited normal daily activities ≥50% of the time. Finally, those with overlap were more likely to report abnormal anxiety and depression scores at 12 months compared with those with IBS alone, and to have higher levels of somatization (P.001 for all analyses).The natural history of people with IBS with overlap FD defined according to Rome IV criteria is more severe than those with IBS alone. This has important implications for future treatment trials in IBS.

Introduction Gastrointestinal symptom-specific anxiety and somatisation have both been associated with higher symptom severity in patients with irritable bowel syndrome (IBS). However, the relationship between these two factors and IBS symptom severity has not been explored fully. In addition, the performance of the instrument that measures gastrointestinal symptom-specific anxiety, the visceral sensitivity index (VSI), has not been examined in a UK population. We conducted a cross-sectional survey to examine these issues. Methods We measured levels of gastrointestinal symptom-specific anxiety, using the VSI, somatisation via the patient health questionnaire-12 (PHQ-12), as well as symptom severity in adult subjects from the UK community with Rome IV-defined IBS. We carried out exploratory factor analysis on the VSI, prior to subsequent analyses, to establish its factor structure. We carried out multiple regression analysis to determine the relationship between demographic features, different factors of the VSI, somatisation, and IBS symptom severity. Results 811 individuals with IBS provided complete data. The mean age was 47.4 years, and 85.9% were female. Factor analysis of the VSI revealed a three-factor structure, accounting for 47% of the variance. Three VSI items that loaded onto factor one were concerned with awareness of abdominal discomfort and two with worry about abdominal symptoms. Items that loaded onto factor two were concerned with fear that symptoms were caused by a serious underlying illness. Items loading onto factor three were concerned with the fear of symptoms in the context of new experiences, for example trying new foods or having access to toilets in places that someone hasn’t visited before. Both factor one of the VSI and the PHQ-12 were strongly and independently associated with IBS symptom severity, for the group as a whole (p Conclusions The factor structure of the VSI requires further investigation. Our findings cast doubt on the central role of gastrointestinal symptom-specific anxiety as a driver for symptom severity in IBS. Awareness of both gastrointestinal and extra-intestinal symptoms, however, is strongly associated with symptom severity.

Introduction Chronic constipation is classified into two 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. We tested 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 centre. 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), in order 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 (AUC 0.97) (figure 1). Syndromic models did not significantly increase diagnostic accuracy (p > 0.15). Furthermore, syndromic models from which abdominal pain was omitted performed at chance level (AUC 0.56). Statistical clustering of clinical characteristics showed no structure relatable to diagnosis, but a syndromic segregation of 16 features differentiating patients by impact of constipation on daily life. Conclusions IBS-C and FC differ only with respect to the presence of abdominal pain, arguably a self-fulfilling difference given that abdominal pain inherently distinguishes the two in current diagnostic criteria. This suggests they are not distinct syndromes, rather a single syndrome varying along one clinical dimension. An alternative syndromic segregation is identified which needs evaluation in community-based cohorts. Our results have implications for patient recruitment into clinical trials, future disease classifications and management guidelines.

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.

INTRODUCTION: Conventionally, patients with irritable bowel syndrome (IBS) are subgrouped based on their predominant bowel habit. Given the relevance of psychological comorbidity to IBS symptoms, our aim was to explore an alternative approach to subgrouping by incorporating factors beyond stool form and frequency. METHODS: We collected demographic, symptom, and psychological health data from 1,375 adult subjects in the community who self-identified as having IBS, identifying 2 cohorts meeting either Rome III or Rome IV criteria. In each cohort, we performed latent class analysis, a method of model-based clustering, to identify specific subgroups (clusters). For each cluster, we drew a radar plot and compared these by visual inspection, describing cluster characteristics. RESULTS: In total, 1,080 individuals met the Rome III criteria for IBS, and 811 met the Rome IV criteria. In both cohorts, a 7-cluster model was the optimum solution, and the characteristics of the clusters were almost identical between Rome III and IV. Four clusters were defined by the pattern of gastrointestinal symptoms (loose stools and urgency or hard stools and bloating), further differentiated by the presence of abdominal pain not relieved by defecation, and by the extent of psychological comorbidity. Two clusters had below-average gastrointestinal symptoms, differentiated by the extent of psychological comorbidity. The final cluster had well-above-average gastrointestinal symptoms and high levels of psychological comorbidity. The proportion of subjects with severe IBS symptom scores, high levels of perceived stress, and high levels of gastrointestinal symptom–specific anxiety was significantly higher in clusters with high psychological comorbidity (P < 0.001). DISCUSSION: Latent class analysis identified 7 distinct IBS subgroups characterized by varying degrees of gastrointestinal symptoms, extraintestinal symptoms, and psychological comorbidity. Further research is needed to assess whether they might be used to direct treatment.

Transanal irrigation (TAI) is a treatment for bowel dysfunction, with UK approval in patients with constipation and faecal incontinence. This article is intended for health-care professionals involved in the management of patients with bowel dysfunction and describes what TAI is and the proposed method of action. It also considers the latest evidence related to the safety and efficacy of TAI. There is now a potentially overwhelming range of equipment available on prescription to deliver this treatment. The factors to consider in the appropriate selection of equipment for individual patients will be considered, alongside an algorithm for the selection of equipment to aid health professionals with this choice.

Background: The Patient Assessment of Constipation-Symptoms (PAC-SYM) questionnaire is frequently used in clinical trials of constipation. However, the threshold for reduction in total PAC-SYM score used to define a clinical response on this 0-4 point scale has not undergone formal appraisal, and its relationship with clinical benefit as perceived by patients has not been defined. Aim: To determine the minimal important difference in PAC-SYM score, and the optimum cut-off value for defining responders. Methods: The minimal important difference was estimated using data from six international phase 3/4, double-blind, randomised controlled trials of prucalopride in patients with chronic constipation (NCT01147926, NCT01424228, NCT01116206, NCT00485940, NCT00483886, NCT00488137), with anchor- and distribution-based approaches. Five appropriate patient-reported outcomes were selected as anchors. In addition, receiver operating characteristics (ROC) curve analyses were used to investigate responder discrimination for each anchor. Results: Data from 2884 patients were included. Minimal important difference estimates ranged from –0.52 to –0.63 across the five anchors. Estimates were not affected by study location but were consistently lower for rectal symptoms than for abdominal and stool symptoms. Distribution-based estimates were considerably lower than anchor-based estimates. ROC curve analyses showed optimum cut-off scores for discriminating responders to be similar to anchor-based minimal important difference estimates. Conclusions: Anchor-based methods gave consistent results for the minimal important difference, at approximately –0.6, and this value was close to the ROC-determined optimal cut-off scores for responder discrimination. This value could be considered in clinical practice. A slightly more conservative threshold (eg –0.75) could be used in clinical trials to reduce the placebo response rate., SCOPUS: ar.j, info:eu-repo/semantics/published

Background Gastrointestinal symptom‐specific anxiety and somatization have both been associated with higher symptom severity in patients with irritable bowel syndrome (IBS); however, this relationship has not been explored fully. Moreover, the performance of the visceral sensitivity index (VSI) for measuring gastrointestinal symptom‐specific anxiety has not been examined in a UK population. We conducted a cross‐sectional survey to examine these issues. Methods Gastrointestinal symptom‐specific anxiety was measured using the VSI, and somatization was measured via the patient health questionnaire‐12 (PHQ‐12) in adults from the UK community with Rome IV‐defined IBS. Exploratory factor analysis was performed on the VSI, prior to subsequent analyses, to establish its factor structure. Multiple regression analysis was used to determine the relationship between demographic features, different factors of the VSI, somatization, and IBS symptom severity. Key Results A total of 811 individuals with IBS provided complete data. Factor analysis of the VSI revealed a three‐factor structure, accounting for 47% of the variance. The first of these VSI factors and the PHQ‐12 were both strongly and independently associated with IBS symptom severity, for the group as a whole and for all four IBS subtypes. Most VSI items concerned with overt gastrointestinal symptom‐specific anxiety loaded onto the other two VSI factors that were not associated with symptom severity. Conclusions and Inferences The factor structure of the VSI requires further investigation. Our findings cast doubt on the central role of gastrointestinal symptom‐specific anxiety as a driver for symptom severity in IBS. Awareness of both gastrointestinal and extra‐intestinal symptoms, however, is strongly associated with symptom severity.

Background Irritable bowel syndrome (IBS) with diarrhoea (IBS-D) is a common and chronic condition that can significantly impair quality of life. The emergence of new drugs for IBS-D has been slow and there is a need for new treatments, including drug-free treatments, which are easy to use and suitable for different patient groups. Currently available drug-free treatments include Enterosgel®, an intestinal adsorbent approved for use in IBS-D and acute diarrhoea and available over-the-counter in the UK and 30 countries worldwide. The aim of this randomised, double-blind, placebo-controlled, multi-centre study is to test the efficacy and safety of Enterosgel® compared to placebo in symptomatic treatment in IBS-D. Methods/design We will recruit 430 participants with IBS-D from approximately 30 primary and secondary care sites in England. Participants meeting the required abdominal pain and stool consistency criteria over a 2-week screening period will be randomly allocated to receive blinded treatment (Enterosgel® or placebo) for 8 weeks. This will be followed by an 8-week open-label treatment phase with Enterosgel®. Participants will be allowed to adjust their daily dosage during both phases based on their symptoms. Participants will then return to standard care and those who responded to treatment will receive a follow-up call 8 weeks later. Co-medication with loperamide will be permitted and use recorded. The primary outcome measure is the percentage of participants defined as responders for abdominal pain and stool consistency during at least 4 weeks in the 8-week blinded phase. Secondary outcome measures include stool frequency, stool consistency, abdominal pain, bloating, urgency, adequate relief, questionnaire scores and rescue medication use. Exploratory outcomes will be assessed in subsets of participants including qualitative and quantitative data on faecal microorganisms and biomarkers and gut-related measurements from magnetic resonance imaging data. Discussion This is the first large scale randomised controlled trial investigating Enterosgel® in IBS-D. A study design with blinded phase followed by an open-label phase was chosen to encourage participation and study completion. Demonstrating that Enterosgel® is effective and safe in IBS-D could encourage adoption by patients and healthcare professionals and foster future clinical trials assessing its use in related conditions. Trial registration ISRCTN17149988. Prospectively registered on 14 November 2017.

Introduction There is a lack of literature regarding symptomatology following diagnosis and treatment of small intestinal bacterial overgrowth (SIBO)1. This service evaluation aimed to assess local outcomes. Methods Retrospective assessment of patients referred for hydrogen (H2)/methane (CH4) breath tests (BT) for SIBO was performed. From 201–017, 132 patients (F=94, M=48) were tested at the University Hospital of North Durham. 50 g glucose in 250 ml water was the substrate used for the tests. A positive BT was defined as an increase in hydrogen or methane of ≥10 ppm with a starting baseline Results 159 BTs were conducted, with 28 reported as positive for SIBO. 79% of these patients were treated with relevant antibiotics (abx) (– week course). No major adverse effects of treatment were described. Following a positive BT, patients were reviewed after 4.5 months (range 0.–2 months). Subsequent follow up was 10 months (range –5 months) from initial test. It is possible (though implausible) that all those returning for follow-up experienced symptom resolution. With this bold assumption, 23% of patients (Outcome Category (OC) 1,2) may have experienced lasting improvement (figure 1). We can be confident that some improvement was seen in 41% of the patients treated (OC 2,3,4). Disappointingly no patients were documented to have symptom improvement at second follow-up (OC 5). In 41% of patients no improvement related to abx treatment was reported (OC 6,7). Conclusions Abx can provide short term symptom relief in some patients with abdominal symptoms; however, this is generally not a long-term solution. There are important limitations of this work including the retrospective nature, variable follow-up duration and lack of validated symptom assessment. Findings do, however, support the need for improvements in understanding of maintaining a healthy microbiome. This maintenance is likely dependent on the aetiology of the underlying cause of the SIBO2. References Shah SC, Day LW, Somsouk M & Sewell JL. Meta-analysis: antibiotic therapy for small intestinal bacterial overgrowth. Aliment Pharmacol Ther. 2013; 38:92–34. Rezaie A, Pimentel M& Rao S. How to test and treat small bowel bacterial overgrowth: an evidence-based approach. Curr Gastroenterol Rep. 2016; 18:8.

Introduction There are few studies examining implications of applying the Rome IV criteria for irritable bowel syndrome (IBS), in preference to the previous gold standard, the Rome III criteria. We conducted a cross-sectional survey of over 1000 individuals who self-identified as having IBS in order to examine this issue. Methods We collected complete demographic, symptom, mood, and psychological health data from 1375 adult subjects in the UK community with IBS. We applied both the Rome III and the Rome IV criteria simultaneously to examine what proportion met each of these diagnostic criteria for IBS. We measured the level of agreement between the Rome III and Rome IV criteria, and assessed for presence of an alternative functional bowel disorder in individuals who no longer met diagnostic criteria for IBS with the more restrictive Rome IV criteria. Finally, we compared characteristics of individuals who met only Rome III criteria with those who met Rome IV criteria. Results In total, 1080 (78.9%) of 1368 individuals with IBS met the Rome III criteria. In contrast, only 811 (59.1%) of 1373 individuals with IBS met the Rome IV criteria. Agreement between the criteria was only moderate (Kappa = 0.50). The reasons for not meeting the Rome IV criteria for IBS among those meeting the Rome III criteria are shown in Table 1. Of those people no longer meeting Rome IV criteria for IBS, 33 (11.5%) met Rome IV criteria for functional constipation, 118 (41.3%) functional diarrhoea, 68 (23.8%) functional abdominal bloating or distension, and 67 (23.4%) an unspecified functional bowel disorder. This meant that, of those individuals with Rome III IBS who did not meet the Rome IV criteria for IBS, only 11.5% were reclassified into another functional bowel disorder where licensed and evidence-based therapies are available. Individuals with Rome IV-defined IBS had more severe symptoms, and higher levels of mood disorder and poor psychological health, compared with those who only met the Rome III criteria for IBS (P Conclusions Moving from the Rome III criteria to Rome IV IBS has substantial implications, both for individuals who believe they suffer from IBS, and for the spectrum of disease severity seen. Understanding the impact of these changes on clinical trials of novel therapies will be important.

Background Prucalopride, a selective, high-affinity 5-hydroxytryptamine 4 receptor agonist, stimulates gastrointestinal and colonic motility and alleviates common symptoms of chronic constipation (CC) in adults. The relative efficacy by gender has not been evaluated. Aim To evaluate the global efficacy and safety of prucalopride 2 mg daily in men and women with CC using data from six large, randomized, controlled clinical trials. Methods Data were combined from six phase 3 and 4, double-blind, randomized, placebo-controlled, parallel-group trials. The primary efficacy endpoint was the percentage of patients with a mean of ≥3 spontaneous complete bowel movements (SCBMs) per week over 12 weeks of treatment. Safety was assessed throughout all the trials. Results Overall, 2484 patients (597 men; 1887 women; prucalopride, 1237; placebo, 1247) were included in the integrated efficacy analysis and 2552 patients were included in the integrated safety analysis. Significantly more patients achieved a mean of ≥3 SCBMs/week over the 12 weeks of treatment in the prucalopride group (27.8 %) than in the placebo group [13.2 %, OR 2.68 (95 % CI 2.16, 3.33), p

Introduction Within the UK, there is anecdotal evidence of disparity in the training, practice, supervision and perception of efficacy among practitioners of biofeedback therapy for chronic constipation. Aims To establish the current knowledge, practice and opinions of UK practitioners. Methods Between October 2012 and October 2013, a prospective service evaluation was distributed to biofeedback practitioners in the UK through academic conferences or by invitation to complete an on-line assessment form. Results 76 practitioners responded, consisting of nurses (47%), physiotherapists (35%), physiologists (12%) and others (7%). Only 45% described ‘biofeedback’ consistent with an accepted definition. 86% use equipment to provide sensory feedback. Methods of biofeedback varied: balloon catheter (54%), brace pump technique (78%), urge resistance (83%), irrigation (16%) and relaxation (12%). Only 65% of practitioners had attended formal training courses, and 52% considered themselves to be self-taught. 36% receive formal supervision and only 38% of those by a senior. Regular audit of outcomes is undertaken by 67%. UK-wide perception of treatment response for chronic constipation is markedly variable (mean response=57% (IQR 50–75%, SD 23%)); there were no differences in perception of treatment response between nurses or physiotherapists. Practitioners’ free responses demonstrated strong positive themes of a holistic approach and an overall perception of effectiveness. Negative themes included service restrictions. Conclusions There is marked variation in practice, training and supervision of biofeedback therapists throughout the UK. Perceptions of efficacy vary greatly. Development of training and supervision standards is a priority as well as a consensus to standardise therapy.

Introduction Chronic constipation (CC) is a very common symptom, and is more commonly seen in women. This difference is much more pronounced in secondary care. It is possible that the excess prevalence to secondary care is due to greater severity or to differences in healthcare seeking. This study aims to evaluate the differences in the characteristics of constipation seen in male and female patients attending a tertiary referral clinic. Methods The study was designed as a prospective cohort study running at a single tertiary referral clinic. Data were collected prospectively from eligible patients following informed consent using a standardised proforma, and entered into a study database. Patients were categorised according to the Rome III criteria as having Functional Constipation (FC) or Irritable Bowel Syndrome- Constipation type (IBS-C), and were asked to complete PAC-SYM and PAC-QOL questionnaires Results Data were collected from 827 patients between January 2007 and October 2014; of these, 766 patients were included. Of these, 103 (13%) were male. The mean age at presentation was 42 years; for males this was 49.6 years, compared to 41.1 years for females; a mean difference of 8.4 years (p Conclusions This study reports a similar male:female ratio to other studies, with far more women than men. It also suggests that women experience symptom onset at a younger age, and that they are also younger when they present. Female patients report significantly more severe symptoms and significantly worse quality of life, with significantly higher mean PAC-SYM and PAC-QOL scores. Although QOL:SYM ratio was higher in women, suggesting greater impact of milder symptoms on QOL, this was not significant. The reasons for these differences are not clear, and further work is needed in this area

OBJECTIVES: Prucalopride is effective at alleviating symptoms of chronic constipation in women. The aim of this study was to assess the efficacy of 12 weeks of prucalopride treatment compared with placebo in men with chronic constipation. METHODS: This was a multicenter, stratified, randomized, parallel-group, double-blind, placebo-controlled, phase 3 study (ClinicalTrials.gov identifier: NCT01147926). The primary end point was the proportion of patients with a mean of three or more spontaneous complete bowel movements (SCBMs) per week across the treatment period. Efficacy end points were assessed using daily electronic diaries, global assessment of the severity of constipation and efficacy of treatment, and Patient Assessment of Constipation—Symptoms (PAC-SYM) and Patient Assessment of Constipation—Quality of Life (PAC-QOL) questionnaires. RESULTS: In total, 374 patients were enrolled in the study. Significantly more patients achieved a mean of three or more SCBMs per week in the prucalopride group (37.9%) than in the placebo group (17.7%, P

Aims The aim of this study was to explore the experiences of Clinical Research Nurses, with an emphasis on factors that may have an impact on successful study delivery. Background The Clinical Research Nurse workforce is pivotal to improving health outcomes through supporting research-active health economies. Investment in research infrastructure has led to nurses and midwives increasingly undertaking extended roles to deliver clinical research. Despite such opportunities, the recruitment of sufficient participants into research studies remains problematic. A growing body of literature is exploring barriers to successful study delivery, indicating the emergence of a caring-recruiting dichotomy in clinical research staff. Design This qualitative study investigates the experiences of Clinical Research Nurses delivering research in the United Kingdom National Health Service. Methods Four Focus groups (total 19 participants) were conducted in a large North East National Health Service Foundation Trust from November 2015 - February 2016. Findings Thematic analysis identified perceptions of the role in the wider context of professional identity. Role transition, altered relationships and workload complexity, affected participants’ practice, leading to inconsistency between core clinical values and perceived identities as research delivery staff. A duty of care as patient advocates contrasted elements of the work reflecting that of salespeople. The emotional labour of approaching patients and unease regarding peer perceptions of the Clinical Research Nurse role, affected the positive aspects of research delivery. Conclusion Professional-identity and self-concept appear to have an impact on practice in a research delivery role. Further research should explore these issues further, to enlighten the basis on which such feelings are positioned and to work towards practical solutions.

Objectives Few studies have examined the effects of applying the Rome IV criteria for irritable bowel syndrome (IBS) vs the previous standard, the Rome III criteria. We conducted a cross-sectional survey of individuals who self-identify as having IBS to examine this issue. Methods We collected complete demographic, symptom, mood, and psychological health data from 1375 adults who self-identified as having IBS, but were not recruited from a referral population. We applied the Rome III and the Rome IV criteria simultaneously to examine what proportion met each of these diagnostic criteria for IBS. We measured the level of agreement between the Rome III and Rome IV criteria, and assessed for presence of an alternative functional bowel disorder in individuals who no longer met diagnostic criteria for IBS with the more restrictive Rome IV criteria. Finally, we compared characteristics of individuals who met only Rome III criteria with those who met Rome IV criteria. Results In total, 1080 of 1368 individuals (78.9%) with IBS met the Rome III criteria. In contrast, 811 of 1373 individuals (59.1%) with IBS met the Rome IV criteria. Agreement between the criteria was only moderate (Kappa = 0.50). Among those who no longer had IBS according to the Rome IV criteria, 33 (11.5%) met Rome IV criteria for functional constipation, 118 (41.3%) for functional diarrhea, 68 (23.8%) for functional abdominal bloating or distension, and 67 (23.4%) for an unspecified functional bowel disorder. Individuals with Rome IV-defined IBS had more severe symptoms, and a higher proportion had a mood disorder and evidence of poor psychological health, compared with individuals who only met the Rome III criteria for IBS (P Conclusions The characteristics of people who believe they have IBS differ between those who meet criteria as defined by Rome IV vs Rome III, including the spectrum of disease severity. Studies are needed to determine how these changes will affect outcomes of clinical trials.

Background The term ‘difficult’ is pervasively used in relation to medically unexplained symptoms (MUS) and patients with MUS. This article scrutinises the use of the term by analysing interview data from a study of secondary care specialists' experiences with and attitudes towards patients suffering from MUS. Design Qualitative design employing semi-structured open-ended interviews systematically analysed in three stages: first, data were analysed according to the principles of content analysis. The analysis subsequently focused on the use of the term ‘difficult’. Iterations of the term were extracted by summative analysis and thematic coding revealed its different meanings. Finally, alternative expressions were explored. Setting Three NHS trust secondary care hospitals in North-East England. Participants 17 senior clinicians from seven medical and two surgical specialities. Results Unsolicited use of the term ‘difficult’ was common. ‘Difficult’ was rarely used as a patient characteristic or to describe the therapeutic relationship. Participants used ‘difficult’ to describe their experience of diagnosing, explaining, communicating and managing these conditions and their own emotional reactions. Health care system deficits and the conceptual basis for MUS were other facets of ‘difficult’. Participants also reported experiences that were rewarding and positive. Conclusions This study shows that blanket statements such as ‘difficult patients’ mask the complexity of doctors' experiences in the context of MUS. Our nuanced analysis of the use of ‘difficult’ challenges preconceived attitudes. This can help counter the unreflexive perpetuation of negative evaluations that stigmatize patients with MUS, encourage greater acknowledgement of doctors' emotions, and lead to more appropriate conceptualizations and management of MUS.

The m.3243AG MTTL1 mutation is the most common cause of mitochondrial disease; yet there is limited awareness of intestinal pseudo-obstruction (IPO) in this disorder. We aimed to determine the prevalence, severity, and clinical outcome of patients with m.3243AG-related mitochondrial disease manifesting with IPO.In this large, observational cohort study, we assessed the clinical, molecular, and radiological characteristics of patients with genetically determined m.3243AG-related mitochondrial disease, who presented with severe symptoms suggestive of bowel obstruction in the absence of an occluding lesion.Between January 2009 and June 2015, 226 patients harbouring the m.3243AG mutation were recruited to the Medical Research Council Centre Mitochondrial Disease Patient Cohort, Newcastle. Thirty patients (13%) presented acutely with IPO. Thirteen of these patients had a preceding history of stroke-like episodes, whereas 1 presented 27 years previously with their first stroke-like episode. Eight patients developed IPO concomitantly during an acute stroke-like episode. Regression analysis suggested stroke was the strongest predictor for development of IPO, in addition to cardiomyopathy, low body mass index and high urinary mutation load. Poor clinical outcome was observed in 6 patients who underwent surgical procedures.Our findings suggest, in this common mitochondrial disease, that IPO is an under-recognized, often misdiagnosed clinical entity. Poor clinical outcome associated with stroke and acute surgical intervention highlights the importance of the neurologist having a high index of suspicion, particularly in the acute setting, to instigate timely coordination of appropriate care and management with other specialists. Ann Neurol 2016;80:686-692.

While the pharmacological armamentarium for chronic constipation has expanded over the past few years, a substantial proportion of constipated patients do not respond to these medications. This review summarizes the pharmacological and behavioral options for managing constipation and details the management of refractory constipation. Refractory constipation is defined as an inadequate improvement in constipation symptoms evaluated with an objective scale despite adequate therapy (ie, pharmacological and/or behavioral) that is based on the underlying pathophysiology of constipation. Minimally invasive (ie, rectal irrigation and percutaneous endoscopic colostomy) and surgical therapies are used to manage refractory constipation. This review appraises these options, and in particular, percutaneous endoscopic colostomy, which as detailed by an article in this issue, is a less invasive option for managing refractory constipation than surgery. While these options benefit some patients, the evidence of the risk: benefit profile for these therapies is limited.

Patients with functional constipation can be classified according to symptoms and physiological parameters as either having a disorder of defecation or having normal defecation. It is hypothesized that the disordered defecation, where it exists, is a causative factor of the constipation. However, the utility of this classification has yet to be proven in terms of predicting response to therapy. The definitions are non-specific and based on tests that are done in an artificial setting and with derived normal ranges. It is therefore possible that the symptoms and physiological parameters of a defecatory disorder may occur as a continuous spectrum in these patients, rather than defining a discrete entity or subtype. The aim of this study was to use cluster analysis and factor analysis of defecatory symptoms and physiological parameters to look for evidence of subgroups in patients with functional constipation.Consecutive patients presenting to a specialist constipation clinic and satisfying the inclusion criteria were assessed to determine the severity of defecatory symptoms, and underwent isotope defecating proctography and the Sitzmark transit study. Assessments were made contemporaneously and results of any test not performed within 6 weeks of the initial assessment were excluded. Principle components analysis and cluster analysis were performed to look for evidence of subgroups. Relationships between evacuatory symptoms, index parameters, and test results were explored. The detailed and unselected nature of the analyses produced hundreds of test results, and statistically significant results were critically evaluated in this context.A total of 116 patients were studied (age range 18-73 years, mean 40.5 years). Based on the results of the transit study and proctography, 38% of patients showed evidence of slow transit constipation, 20% FDD (functional defecation disorder), 29% both, and 12% neither. Principle components analysis did not demonstrate an obvious dimension reduction for the variables tested. Cluster analysis (over 150 solutions tested) failed to show evidence of clustering. There were no useful predictive relationships between evacuatory symptoms, index parameters and test results.We used multiple statistical analyses to look for clustering and predictive relationships between clinical and physiological parameters in consecutive patients with functional constipation and found no evidence of the existence of a subgroup of patients with a defecatory disorder. This may be due to weaknesses in the study design, poor validity of the assessments performed, or that defecatory features do not identify a distinct pathophysiological entity, but rather are manifested variably as a continuous spectrum.

Background Trans-anal irrigation (TAI) is used widely to treat bowel dysfunction, although evidence for its use in adult chronic functional constipation remains unclear. Long-term outcome data are lacking, and the effectiveness of therapy in this patient group is not definitively known. Methods Evidence for effectiveness and safety was reviewed and the quality of studies was assessed. Primary research articles of patients with chronic functional constipation, treated with TAI as outpatients and published in English in indexed journals were eligible. Searching included major bibliographical databases and search terms: bowel dysfunction, defecation, constipation and irrigation. Fixed- and random-effect meta-analyses were performed. Results Seven eligible uncontrolled studies, including 254 patients, of retrospective or prospective design were identified. The definition of treatment response varied and was investigator-determined. The fixed-effect pooled response rate (the proportion of patients with a positive outcome based on investigator-reported response for each study) was 50.4 % (95 % CI: 44.3–56.5 %) but featured substantial heterogeneity (I2 = 67.1 %). A random-effects estimate was similar: 50.9 % (95 % CI: 39.4–62.3 %). Adverse events were inconsistently reported but were commonplace and minor. Conclusions The reported success rate of irrigation for functional constipation is about 50 %, comparable to or better than the response seen in trials of pharmacological therapies. TAI is a safe treatment benefitting some patients with functional constipation, which is a chronic refractory condition. However findings for TAI vary, possibly due to varying methodology and context. Well-designed prospective trials are required to improve the current weak evidence base.

Despite the fact that functional bowel disorders (FBDs) are the most common gastrointestinal conditions, neurogastroenterology has for years been the Cinderella subspecialty in gastroenterology, and one of the least popular specialities among trainees in gastrointestinal (GI) surgery. Is this all about to change? Approximately 25% of the adult population suffers from FBDs, and yet the specialty is poorly developed, and research funding is relatively limited compared with subspecialties such as inflammatory bowel disease or hepatology. The cause of this indifference relates, largely, to the lack of effective treatments, this in turn being ultimately due to the lack of understanding of pathophysiology. While advances in molecular biology, imaging and endoscopy have revolutionised the characterisation and treatment of many GI disorders, it can be argued that there has been little progress in understanding the dysmotile gut. The causes of this are understandable. Full thickness biopsy of the gut to allow study of the myenteric neuromusculature is rarely possible. Functional studies of the gut have been inadequate due to the tortuous and extensive nature of the organ and the need to study it over prolonged periods of time (since visualisation of gut function over minutes or even hours is inadequate to understand abnormal physiology). The inability to understand the molecular, biochemical and neuromuscular dysfunction in these conditions has led to treatments that are ineffective. There is, of course, little job satisfaction trying to manage conditions where there are inadequate treatments. Invasive diagnostic procedures are less than ideal in the assessment of gut dysmotility, as they usually alter normal function and cannot be used for prolonged measurement. Technological refinements will provide an increased ability to study motility non-invasively. Improvements in dynamic MRI scanning will allow detailed analysis of gastric, small bowel and colonic activity in an unprepared state (though only for short periods of …

Introduction: Sacral nerve stimulation testing (TSNS) for chronic constipation is not accurately predictive of a long-term response1. The decision to implant a permanent device relies on these results. Aims/Background: We recognised that the testing stimulator was an analogue device with potentially inaccurate dial settings. We sought verification of the output waveform. Method: 19 test stimulators were connected to a cross-calibrated oscilloscope. The output Frequency (f), and Pulse Width (pw) of the waveforms generated were measured according to: run 1) the physician's best attempt to set the dials correctly (pw=210 µ Sec, f=14 Hz), and run 2) the closest dial increment to these settings (pw=200 µ Sec, f=10 Hz). Output Voltage (V) was measured in run 3 at dial increments of 0V, 1V, 2V, 5V, and 10V. Results: We assumed an acceptable margin of error of 20% in runs 1 and 2, and 0.5V in run 3. There was a marked range of frequency values; run 1) 10.6 to 29.0 Hz (26% failed), and run 2) 7.9 to 13.0 Hz (11% failed). Findings for pulse width were similarly variable; run 1) 242 to 326 µ Sec (89% failed), and run 2)215 to 274 µ Sec (63% failed). All devices had a residual positive voltage at zero(range:0.29 to 1.00V), and the failure rates at 0,1,2,5 and 10V were 53%, 100%, 100%, 68% and 47% respectively. Conclusion: All fields of clinical practice and research have their instrumentation which requires calibration to provide verifiable readings. Failure to calibrate during TSNS results in patients receiving variable stimulation, potentially reducing the clarity of research findings, and may be a factor in the poor predictive power of testing in chronic constipation.