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.

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.

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.

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.

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.

Rectal Hypersensitivity in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

Abdominal pain is a key symptom of inflammatory bowel disease (IBD), particularly in active IBD, but also occurs in patients with quiescent disease suggesting that mechanisms other than active inflammation may be responsible. Putative hypothesis to explain chronic abdominal pain in patients with quiescent IBD includes crossover with irritable bowel syndrome where rectal hypersensitivity is common and has pathophysiological implications. In contrast, in IBD, the role of rectal hypersensitivity has not been established. We aimed to determine if rectal hypersensitivity was more common in IBD compared to a healthy control population. We searched MEDLINE and EMBASE databases (1970-2018). Prospective studies that measured pain/discomfort thresholds to mechanical rectal stimuli in IBD and healthy controls were included. Data were pooled for meta-analysis and effect sizes were calculated with 95% confidence intervals (CIs). Our search strategy identified 222 citations of which 8 met the inclusion criteria, covering 133 individuals with IBD (67 men), aged between 10 and 77 compared to 99 healthy controls (55 men), aged between 10 and 67. The prevalence of rectal hypersensitivity in IBD compared to healthy controls was similar with an effect size of 0.59 (95% CIs: -0.27 to 1.44, P = .16, I 2 = 87.3%). Subgroup analysis did show a significant effect size for patients compared to healthy controls with active disease (1.32) but not for quiescent disease (-0.02). These results suggest that reduced rectal pain thresholds to experimental stimulation are not seen in IBD populations except during active flares of the disease. Further research is required to understand the pathophysiology of chronic abdominal pain in quiescent IBD populations with and without chronic abdominal pain to identify appropriate management strategies.

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.

Gastrointestinal symptoms and cardiac vagal tone in type 1 diabetes correlates with gut transit times and motility index.

BACKGROUND: Although gastrointestinal (GI) symptoms are common in diabetes, they frequently do not correlate with measurable sensorimotor abnormalities. The wireless motility capsule (WMC) measures pressure, temperature, and pH as it traverses the GI tract wherefrom transit times and motility indices are derived. The aim was to investigate whether GI symptoms correlate with changes in (a) segmental transit times, (b) segmental motility index, (c) cardiac vagal tone, or (d) presence/absence of peripheral neuropathy in type 1 diabetes. METHODS: Gastrointestinal symptoms in 104 participants with type 1 diabetes were measured using Gastroparesis Cardinal Symptoms Index and Gastrointestinal Symptom Rating Scale. All underwent standardized WMC investigation measuring segmental transit time and motility. Cardiac vagal tone and presence of peripheral neuropathy were measured using electrocardiographic and nerve conduction velocity testing. KEY RESULTS: Colonic transit time was correlated with postprandial fullness (P = .01) and constipation (P = .03), while decreased colonic motility index was correlated with diarrhea (P = .01) and decreased bloating (P < .05). Symptoms were not correlated with gastric or small bowel transit time or motility index. In participants with low cardiac vagal tone, gastric motility index (P < .01) and colonic transit time (P < .05) were increased, but not in those with peripheral neuropathy. Abdominal pain was decreased with both peripheral neuropathy (P = .04) and decreased cardiac vagal tone (P = .02). CONCLUSIONS AND INFERENCES: This study supports the rationale for whole gut investigation, using not only transit times but incorporating contractility indices as well. Furthermore, a decreased parasympathetic modulation and an increased hyposensate state appear to be present in type 1 diabetes.

Chronic constipation in adults: Contemporary perspectives and clinical challenges. 1: Epidemiology, diagnosis, clinical associations, pathophysiology and investigation.

BACKGROUND: Chronic constipation is a prevalent disorder that affects patients' quality of life and consumes resources in healthcare systems worldwide. In clinical practice, it is still considered a challenge as clinicians frequently are unsure as to which treatments to use and when. Over a decade ago, a Neurogastroenterology & Motility journal supplement devoted to the investigation and management of constipation was published (2009; 21 (Suppl.2)). This included seven articles, disseminating all themes covered during a preceding 2-day meeting held in London, entitled "Current perspectives in chronic constipation: a scientific and clinical symposium." In October 2018, the 3rd London Masterclass, entitled "Contemporary management of constipation" was held, again over 2 days. All faculty members were invited to author two new review articles, which represent a collective synthesis of talks presented and discussions held during this meeting. PURPOSE: This article represents the first of these reviews, addressing epidemiology, diagnosis, clinical associations, pathophysiology, and investigation. Clearly, not all aspects of the condition can be covered in adequate detail; hence, there is a focus on particular "hot topics" and themes that are of contemporary interest. The second review addresses management of chronic constipation, covering behavioral, conservative, medical, and surgical therapies.

Access to Psychological Support for Young People Following Stoma Surgery: Exploring Patients' and Clinicians' Perspectives.

Psychological problems are common among people with inflammatory bowel disease (IBD) following stoma surgery. However, the ways in which stoma-related psychological needs are identified and addressed in health care settings remain unexplored. In this study, we investigated the perspectives of young people with a stoma and health care professionals about access to psychological support. Semi-structured interviews were conducted with young people with an IBD stoma (18-29 years, n = 13) and health care professionals (n = 15), including colorectal surgeons, gastroenterologists, specialist nurses in IBD and stoma care, and general practitioners in England. Data collection and analysis were informed by constructivist grounded theory. Three analytic categories were developed: "initiating support-seeking," "affirming psychological needs," and "mobilizing psychological support," which capture young peoples' trajectory to access psychological support. Based on the findings, we highlight the need for both patients and health care professionals to assign greater priority to the identification of psychological symptoms post-stoma surgery. More effective care pathways, which include responsive psychological services, would enhance access to psychological support for young people with a stoma.

Transcutaneous vagus nerve stimulation prevents the development of, and reverses, established oesophageal pain hypersensitivity.

BACKGROUND: The vagus nerve exerts an anti-nociceptive effect on the viscera. AIM: To investigate whether transcutaneous vagal nerve stimulation (t-VNS) prevents the development of and/or reverses established visceral hypersensitivity in a validated model of acid-induced oesophageal pain. METHODS: Before and after a 30-minute infusion of 0.15M hydrochloric acid into the distal oesophagus, pain thresholds to electrical stimulation were determined in the proximal non-acid exposed oesophagus. Validated sympathetic (cardiac sympathetic index) and parasympathetic (cardiac vagal tone [CVT]) nervous system measures were recorded. In study 1, 15 healthy participants were randomised in a blinded crossover design to receive either t-VNS or sham for 30 minutes during acid infusion. In study 2, 18 different healthy participants were randomised in a blinded crossover design to receive either t-VNS or sham, for 30 minutes after acid infusion. RESULTS: Study 1: t-VNS increased CVT (31.6% ± 58.7 vs -9.6 ± 20.6, P = 0.02) in comparison to sham with no effect on cardiac sympathetic index. The development of acid-induced oesophageal hypersensitivity was prevented with t-VNS in comparison to sham (15.5 mA per unit time (95% CI 4.9 - 26.2), P = 0.004). Study 2: t-VNS increased CVT (26.3% ± 32.7 vs 3 ± 27.1, P = 0.03) in comparison to sham with no effect on cardiac sympathetic index. t-VNS reversed established acid-induced oesophageal hypersensitivity in comparison to sham (17.3mA/unit time (95% CI 9.8-24.7), P = 0.0001). CONCLUSIONS: t-VNS prevents the development of, and reverses established, acid-induced oesophageal hypersensitivity. These results have therapeutic implications for the management of visceral pain hypersensitivity.

Outcomes of Percutaneous Coronary Intervention in Patients With Crohn's Disease and Ulcerative Colitis (from a Nationwide Cohort).

Patients with inflammatory bowel disease (IBD) are at an increased risk of ischemic heart disease. However, there is limited evidence on how their outcomes after percutaneous coronary intervention (PCI) compare with those without IBD. All PCI-related hospitalizations from the National Inpatient Sample from 2004 to 2015 were included, stratified into 3 groups: no-IBD, Crohn's disease (CD), and ulcerative colitis (UC). We assessed the association between IBD subtypes and in-hospital outcomes. A total of 6,689,292 PCI procedures were analyzed, of which 0.3% (n = 18,910) had an IBD diagnosis. The prevalence of IBD increased from 0.2% (2004) to 0.4% (2015). Patients with IBD were less likely to have conventional cardiovascular risk factors and more likely to undergo PCI for an acute indication, and to receive bare metal stents. In comparison to patients without IBD, those with IBD had reduced or similar adjusted odds ratios (OR) of major adverse cardiovascular and cerebrovascular events (CD OR 0.69, 95% confidence interval (CI) 0.62 to 0.78; UC OR 0.75, 95% CI 0.66 to 0.85), mortality (CD: OR 0.94, 95% CI 0.79 to 1.11; UC OR 0.35, 95% CI 0.27 to 0.45) or acute cerebrovascular accident (CD: OR 0.73, 95% CI 0.60 to 0.89; UC: OR 0.94, 95% CI 0.77 to 1.15). However, IBD patients had an increased odds for major bleeding (CD: OR 1.42 95% CI 1.23 to 1.63, and UC: OR 1.35 95% CI 1.16 to 1.58). In summary, IBD is associated with a decreased risk of in-hospital post-PCI complications other than major bleeding that was significantly higher in this group. Long term follow-up is required to evaluate the safety of PCI in IBD patients from both bleeding and ischemic perspectives.

Liraglutide accelerates colonic transit in people with type 1 diabetes and polyneuropathy: A randomised, double-blind, placebo-controlled trial.

BACKGROUND: Glucagon-like peptide-1 receptor agonists, such as liraglutide, reduce hyperglycaemia and induce weight loss and are used as a treatment in diabetes. However, common adverse effects include nausea, loss of appetite and prolonged gastric emptying. It is not known whether these changes are centrally generated or if liraglutide alters the enteric motility. OBJECTIVE: To investigate the effects of liraglutide on gastrointestinal function and symptoms. METHODS: A total of 48 adults with type 1 diabetes and confirmed distal symmetric polyneuropathy were randomised to receive liraglutide 1.8 mg/day or placebo for 26 weeks. Regional transit times and motility indexes were assessed with a wireless motility capsule, whereas symptoms were evaluated using the validated gastroparesis cardinal symptom index. RESULTS: Liraglutide treatment reduced large bowel transit time (31.7%, p = 0.04) and decreased motility index (6.1%, p = 0.04) compared to placebo, whereas the groups did not differ in gastric emptying or small-bowel transit times. Liraglutide increased postprandial fullness with 29% (p = 0.01). Increased small bowel transit time was associated with decreased bloating (p = 0.008). CONCLUSION: Liraglutide accelerates large bowel transit and decreases motility index, which may indicate better coordination of propulsive motility. This potentially improves the function of the enteric nervous system, leading to normalised colonic function and positive effects in type 1 diabetes.