Publications by authors named "Adam Farmer"

95 Publications

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

Neurogastroenterol Motil 2021 09;33(9):e14238

Gastroenterology Unit, Departmento of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.

Background: Functional dyspepsia (FD) is one of the most common conditions in clinical practice. In spite of its prevalence, FD is associated with major uncertainties in terms of its definition, underlying pathophysiology, diagnosis, treatment, and prognosis.

Methods: A Delphi consensus was initiated with 41 experts from 22 European countries who conducted a literature summary and voting process on 87 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 36 statements.

Results: The panel agreed with the definition in terms of its cardinal symptoms (early satiation, postprandial fullness, epigastric pain, and epigastric burning), its subdivision into epigastric pain syndrome and postprandial distress syndrome, and the presence of accessory symptoms (upper abdominal bloating, nausea, belching), and overlapping conditions. Also, well accepted are the female predominance of FD, its impact on quality of life and health costs, and acute gastrointestinal infections, and anxiety as risk factors. In terms of pathophysiological mechanisms, the consensus supports a role for impaired gastric accommodation, delayed gastric emptying, hypersensitivity to gastric distention, Helicobacter pylori infection, and altered central processing of signals from the gastroduodenal region. There is consensus that endoscopy is mandatory for establishing a firm diagnosis of FD, but that in primary care, patients without alarm symptoms or risk factors can be managed without endoscopy. There is consensus that H. pylori status should be determined in every patient with dyspeptic symptoms and H. pylori positive patients should receive eradication therapy. Also, proton pump inhibitor therapy is considered an effective therapy for FD, but no other treatment approach reached a consensus. The long-term prognosis and life expectancy are favorable.

Conclusions And Inferences: A multinational group of European experts summarized the current state of consensus on the definition, diagnosis and management of FD.
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http://dx.doi.org/10.1111/nmo.14238DOI Listing
September 2021

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

Cortex 2021 10 23;143:164-179. Epub 2021 Jul 23.

Queen Square Institute of Neurology, University College London, UK.

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.
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http://dx.doi.org/10.1016/j.cortex.2021.06.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500219PMC
October 2021

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

United European Gastroenterol J 2021 04;9(3):307-331

Gastroenterology Unit, Departmento of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.

Background: Functional dyspepsia (FD) is one of the most common conditions in clinical practice. In spite of its prevalence, FD is associated with major uncertainties in terms of its definition, underlying pathophysiology, diagnosis, treatment, and prognosis.

Methods: A Delphi consensus was initiated with 41 experts from 22 European countries who conducted a literature summary and voting process on 87 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 36 statements.

Results: The panel agreed with the definition in terms of its cardinal symptoms (early satiation, postprandial fullness, epigastric pain, and epigastric burning), its subdivision into epigastric pain syndrome and postprandial distress syndrome, and the presence of accessory symptoms (upper abdominal bloating, nausea, belching), and overlapping conditions. Also, well accepted are the female predominance of FD, its impact on quality of life and health costs, and acute gastrointestinal infections, and anxiety as risk factors. In terms of pathophysiological mechanisms, the consensus supports a role for impaired gastric accommodation, delayed gastric emptying, hypersensitivity to gastric distention, Helicobacter pylori infection, and altered central processing of signals from the gastroduodenal region. There is consensus that endoscopy is mandatory for establishing a firm diagnosis of FD, but that in primary care, patients without alarm symptoms or risk factors can be managed without endoscopy. There is consensus that H. pylori status should be determined in every patient with dyspeptic symptoms and H. pylori positive patients should receive eradication therapy. Also, proton pump inhibitor therapy is considered an effective therapy for FD, but no other treatment approach reached a consensus. The long-term prognosis and life expectancy are favorable.

Conclusions And Inferences: A multinational group of European experts summarized the current state of consensus on the definition, diagnosis and management of FD.
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http://dx.doi.org/10.1002/ueg2.12061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259261PMC
April 2021

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

Gut 2021 07 26;70(7):1214-1240. Epub 2021 Apr 26.

Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, UK

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.
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http://dx.doi.org/10.1136/gutjnl-2021-324598DOI Listing
July 2021

International Consensus Based Review and Recommendations for Minimum Reporting Standards in Research on Transcutaneous Vagus Nerve Stimulation (Version 2020).

Front Hum Neurosci 2020 23;14:568051. Epub 2021 Mar 23.

Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.

Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation (tVNS) across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation(VNS) and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice.
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http://dx.doi.org/10.3389/fnhum.2020.568051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040977PMC
March 2021

Blood test monitoring of immunomodulatory therapy in inflammatory disease.

BMJ 2021 02 8;372:n159. Epub 2021 Feb 8.

Department of Clinical Biochemistry, University Hospitals of North Midlands NHS Trust, Stoke-on-Trent, UK

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http://dx.doi.org/10.1136/bmj.n159DOI Listing
February 2021

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

Neurogastroenterol Motil 2021 06 2;33(6):e14050. Epub 2020 Dec 2.

NIHR Nottingham Biomedical Research Centre (BRC), Hospitals NHS Trust and the University of Nottingham, Nottingham University, Nottingham, UK.

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.
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http://dx.doi.org/10.1111/nmo.14050DOI Listing
June 2021

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

Qual Health Res 2021 02 23;31(3):535-549. Epub 2020 Nov 23.

School of Medicine, Keele University, Keele, United Kingdom.

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, = 13) and health care professionals ( = 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.
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http://dx.doi.org/10.1177/1049732320972338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802047PMC
February 2021

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

Am J Gastroenterol 2021 01;116(1):142-151

Durham Bowel Dysfunction Service, University Hospital North Durham, County Durham and Darlington NHS Trust, Durham, United Kingdom.

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.
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http://dx.doi.org/10.14309/ajg.0000000000000816DOI Listing
January 2021

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

Aliment Pharmacol Ther 2020 09 7;52(6):988-996. Epub 2020 Aug 7.

Centre for Neuroscience, Surgery and Trauma, Blizard Institute, Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine & Dentistry, Mary University of London, London, UK.

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.
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http://dx.doi.org/10.1111/apt.15869DOI Listing
September 2020

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

Am J Cardiol 2020 09 17;130:30-36. Epub 2020 Jun 17.

Keele Cardiovascular Research Group, Centre for Prognosis Research, Institutes of Applied Clinical Science and Primary Care and Health Sciences, Keele University, United Kingdom; Department of Cardiology, Royal Stoke University Hospital, Stoke-on-Trent, United Kingdom; Department of Cardiology, Jefferson University, Philadelphia, Pennsylvania. Electronic address:

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.
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http://dx.doi.org/10.1016/j.amjcard.2020.06.013DOI Listing
September 2020

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

Neurogastroenterol Motil 2021 01 22;33(1):e13885. Epub 2020 Jun 22.

Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.

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.
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http://dx.doi.org/10.1111/nmo.13885DOI Listing
January 2021

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

United European Gastroenterol J 2020 07 9;8(6):695-704. Epub 2020 May 9.

Mech-Sense, Department of Gastroenterology and Hepatology Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.

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%,  = 0.04) and decreased motility index (6.1%,  = 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% ( = 0.01). Increased small bowel transit time was associated with decreased bloating ( = 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.
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http://dx.doi.org/10.1177/2050640620925968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7437086PMC
July 2020

An approach to the care of patients with irritable bowel syndrome.

CMAJ 2020 03;192(11):E275-E282

Department of Gastroenterology (Farmer, Wood), University Hospitals of North Midlands, Stoke-on-Trent, UK; Institute of Applied Clinical Science (Farmer), University of Keele, Keele, Staffordshire, UK; Centre for Neuroscience, Surgery and Trauma (Farmer, Ruffle), Blizard Institute, Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

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http://dx.doi.org/10.1503/cmaj.190716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083544PMC
March 2020

Association between opioid usage and rectal dysfunction in constipation: A cross-sectional study of 2754 patients.

Neurogastroenterol Motil 2020 07 13;32(7):e13839. Epub 2020 Mar 13.

National Bowel Research Centre and GI Physiology Unit, Blizard Institute, Centre for Neuroscience, Surgery & Trauma, Queen Mary University of London, London, UK.

Background: Opioid use has reached epidemic proportions. In contrast to the known effect of opioids on gut transit, the effect on rectal sensorimotor function has not been comprehensively investigated.

Methods: Cross-sectional (hypothesis-generating) study of anorectal physiology studies in 2754 adult patients referred to a tertiary unit (2004-2016) for investigation of functional constipation (defined by "derived" Rome IV core criteria). Statistical associations between opioid usage, symptoms, and anorectal physiological variables were investigated. Opioids were sub-classified as prescriptions for mild-moderate or moderate-severe pain.

Key Results: A total of 2354 patients (85.5%) were classified as non-opioid users, 162 (5.9%) as opioid users for mild-moderate pain, and 238 (8.6%) for moderate-severe pain. Opioids for moderate-severe pain were associated with increased symptomatic severity (Cleveland Clinic constipation score 18.5 vs 15.1; mean difference 2.9 [95%-CI 2.3-3.6]; P < .001), rectal hyposensitivity (odds ratio 1.74 [95%-CI 1.23-2.46]; P = .002), functional evacuation disorders (odds ratio 1.73 [95%-CI 1.28-2.34]; P < .001), and delayed whole-gut transit (odds ratio 1.68 [95%-CI 1.19-2.37]; P = .003). Differences in anorectal variables between opioid users for mild-moderate pain and non-opioid users were not statistically significant. Hierarchical opioid use (non vs mild-moderate vs moderate-severe) was associated with decreasing proportions of patients with no physiological abnormality on testing (40.2% vs 38.1% vs 29.2%) and increasing proportions with both delayed whole-gut transit and rectal sensorimotor dysfunction (16.6% vs 17.5% vs 28.5%).

Conclusions And Inferences: Opioid use is over-represented in patients referred for investigation of constipation. Opioids for moderate-severe pain are associated with rectal sensorimotor abnormalities. Further studies are required to determine whether this association indicates causation.
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http://dx.doi.org/10.1111/nmo.13839DOI Listing
July 2020

Gastrointestinal pain.

Nat Rev Dis Primers 2020 01 6;6(1). Epub 2020 Jan 6.

Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.

Gastrointestinal (GI) pain - a form of visceral pain - is common in some disorders, such as irritable bowel syndrome, Crohn's disease and pancreatitis. However, identifying the cause of GI pain frequently represents a diagnostic challenge as the clinical presentation is often blurred by concomitant autonomic and somatic symptoms. In addition, GI pain can be nociceptive, neuropathic and associated with cancer, but in many cases multiple aetiologies coexist in an individual patient. Mechanisms of GI pain are complex and include both peripheral and central sensitization and the involvement of the autonomic nervous system, which has a role in generating the symptoms that frequently accompany pain. Treatment of GI pain depends on the precise type of pain and the primary disorder in the patient but can include, for example, pharmacological therapy, cognitive behavioural therapies, invasive surgical procedures, endoscopic procedures and lifestyle alterations. Owing to the major differences between organ involvement, disease mechanisms and individual factors, treatment always needs to be personalized and some data suggest that phenotyping and subsequent individual management of GI pain might be options in the future.
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http://dx.doi.org/10.1038/s41572-019-0135-7DOI Listing
January 2020

Critical evaluation of animal models of visceral pain for therapeutics development: A focus on irritable bowel syndrome.

Neurogastroenterol Motil 2020 04 13;32(4):e13776. Epub 2019 Dec 13.

Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.

The classification of chronic visceral pain is complex, resulting from persistent inflammation, vascular (ischemic) mechanisms, cancer, obstruction or distension, traction or compression, and combined mechanisms, as well as unexplained functional mechanisms. Despite the prevalence, treatment options for chronic visceral pain are limited. Given this unmet clinical need, the development of novel analgesic agents, with defined targets derived from preclinical studies, is urgently needed. While various animal models have played an important role in our understanding of visceral pain, our knowledge is far from complete. Due to the complexity of visceral pain, this document will focus on chronic abdominal pain, which is the major complaint in patients with disorders of the gut-brain interaction, also referred to as functional gastrointestinal disorders, such as irritable bowel syndrome (IBS). Models for IBS are faced with challenges including a complex clinical phenotype, which is comorbid with other conditions including anxiety, depression, painful bladder syndrome, and chronic pelvic pain. Based upon the multifactorial nature of IBS with complicated interactions between biological, psychological, and sociological variables, no single experimental model recapitulates all the symptoms of IBS. This position paper will contextualize chronic visceral pain using the example of IBS and focus on its pathophysiology while providing a critical review of current animal models that are most relevant, robust, and reliable in which to screen promising therapeutics to alleviate visceral pain and delineate the gaps and challenges with these models. We will also highlight, prioritize, and come to a consensus on the models with the highest face/construct validity.
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http://dx.doi.org/10.1111/nmo.13776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890461PMC
April 2020

The anatomical basis for transcutaneous auricular vagus nerve stimulation.

J Anat 2020 04 19;236(4):588-611. Epub 2019 Nov 19.

The Wingate Institute of Neurogastroenterology, The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Whitechapel, London, UK.

The array of end organ innervations of the vagus nerve, coupled with increased basic science evidence, has led to vagus nerve stimulation (VNS) being explored as a management option in a number of clinical disorders, such as heart failure, migraine and inflammatory bowel disease. Both invasive (surgically implanted) and non-invasive (transcutaneous) techniques of VNS exist. Transcutaneous VNS (tVNS) delivery systems rely on the cutaneous distribution of vagal afferents, either at the external ear (auricular branch of the vagus nerve) or at the neck (cervical branch of the vagus nerve), thus obviating the need for surgical implantation of a VNS delivery device and facilitating further investigations across a wide range of uses. The concept of electrically stimulating the auricular branch of the vagus nerve (ABVN), which provides somatosensory innervation to several aspects of the external ear, is relatively more recent compared with cervical VNS; thus, there is a relative paucity of literature surrounding its operation and functionality. Despite the increasing body of research exploring the therapeutic uses of auricular transcutaneous VNS (tVNS), a comprehensive review of the cutaneous, intracranial and central distribution of ABVN fibres has not been conducted to date. A review of the literature exploring the neuroanatomical basis of this neuromodulatory therapy is therefore timely. Our review article explores the neuroanatomy of the ABVN with reference to (1) clinical surveys examining Arnold's reflex, (2) cadaveric studies, (3) fMRI studies, (4) electrophysiological studies, (5) acupuncture studies, (6) retrograde tracing studies and (7) studies measuring changes in autonomic (cardiovascular) parameters in response to auricular tVNS. We also provide an overview of the fibre composition of the ABVN and the effects of auricular tVNS on the central nervous system. Cadaveric studies, of which a limited number exist in the literature, would be the 'gold-standard' approach to studying the cutaneous map of the ABVN; thus, there is a need for more such studies to be conducted. Functional magnetic resonance imaging (fMRI) represents a useful surrogate modality for discerning the auricular sites most likely innervated by the ABVN and the most promising locations for auricular tVNS. However, given the heterogeneity in the results of such investigations and the various limitations of using fMRI, the current literature lacks a clear consensus on the auricular sites that are most densely innervated by the ABVN and whether the brain regions secondarily activated by electrical auricular tVNS depend on specific parameters. At present, it is reasonable to surmise that the concha and inner tragus are suitable locations for vagal modulation. Given the therapeutic potential of auricular tVNS, there remains a need for the cutaneous map of the ABVN to be further refined and the effects of various stimulation parameters and stimulation sites to be determined.
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http://dx.doi.org/10.1111/joa.13122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083568PMC
April 2020

Embracing a 'new normal': the construction of biographical renewal in young adults' narratives of living with a stoma.

Sociol Health Illn 2020 02 27;42(2):342-358. Epub 2019 Sep 27.

School of Primary, Community and Social Care, Keele University, Keele, UK.

Stoma surgery can be a life-changing procedure due to bodily changes and related psychological responses. Despite previous literature identifying unique challenges for young adults living with a long-term condition, no studies have explored the biographical implications of stoma formation. Drawing on interviews with 13 young adults, aged 18-29 years, with a stoma resulting from inflammatory bowel disease, this article aims to generate new theoretical insights in understanding the process of biographical (re)construction and the wider implications of stoma formation among this group. Data analysis combined constructivist grounded theory and narrative analysis. Whilst two narratives display 'biographical suspension' characterised by a distancing of self from their stoma, the majority of narratives highlight positive transformations in the young adults' conceptions of self; which we explain through the concept of 'biographical renewal'. The liberating effects of stoma surgery allowed young adults to reclaim aspects of their pre-illness selves, yet also reconfigure a new, altered sense of self, culminating in a 'new normal'. However, psychological distress also co-existed alongside these positive representations, revealing a tension that young adults attempt to reconcile through narrativising their experiences. Our findings have implications for the identification and management of the psychological needs of young people with a stoma.
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http://dx.doi.org/10.1111/1467-9566.13005DOI Listing
February 2020

Severe and Fatal Multilobar Nonclassic Radiation Pneumonitis following Stereotactic Body Radiation Therapy (SBRT) for Treatment of Inoperable Non-Small-Cell Lung Cancer: A Report of Two Cases and Possible Enhancement by Concurrent Amiodarone.

Case Rep Pulmonol 2019 4;2019:8754951. Epub 2019 Aug 4.

Carl Kirkland Cancer Center, 620 W. Forest Ave., Jackson, TN 38301, USA.

Stereotactic body radiation therapy (SBRT) is considered the standard of care for treatment of inoperable early stage non-small cell carcinoma of the lung. SBRT delivers a very high dose of ionizing radiation to a relatively small region encompassing the tumor and spares a significant portion of the remaining lung from high doses. However, the conformal high dose comes at the expense of treating a larger volume of normal lung to lower doses. In general, this has been deemed to be acceptable with an overall lower risk of radiation pneumonitis. However, in the face of predisposing factors, the higher doses delivered by this technique may lead to an increase in radiation pneumonitis. We report on two patients being treated with SBRT in which severe radiation pneumonitis developed in spite of our radiation dosimetry being significantly below the acceptable limit for lung toxicity. Both patients developed a "fulminant" form of radiation pneumonitis with radiographic abnormalities well beyond the treated volume. In one patient, the disease proved fatal. Both patients were on amiodarone at the time SBRT was administered. Given the rarity of fulminant radiation pneumonitis, especially with the relatively small fields treated by SBRT, we suspect that amiodarone enhanced the pulmonary toxicity.
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http://dx.doi.org/10.1155/2019/8754951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6699306PMC
August 2019

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

Trials 2019 Aug 20;20(1):517. Epub 2019 Aug 20.

NIHR Nottingham Digestive Diseases Biomedical Research Centre, University of Nottingham, Nottingham, UK.

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 5HT 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.

Trial Registration: ISRCTN, ISRCTN17508514 , Registered on 2 October 2017.
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http://dx.doi.org/10.1186/s13063-019-3562-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700805PMC
August 2019

Diabetic Gastroparesis: Perspectives From a Patient and Health Care Providers.

J Patient Cent Res Rev 2019 29;6(2):148-157. Epub 2019 Apr 29.

Department of Surgery, Broomfield Hospital NHS Trust, Chelmsford, United Kingdom.

Gastroparesis is defined as a delay in gastric emptying in the absence of mechanical obstruction in the stomach. Gastroparesis has a number of causes, including postsurgical, secondary to medications, postinfectious, idiopathic, and as a complication of diabetes mellitus, where it is underrecognized. The cardinal symptoms of diabetic gastroparesis are nausea, early satiety, bloating, and vomiting. Diabetic gastroparesis is more common in females and has a cumulative incidence of 5% in type 1 diabetes and 1% in type 2 diabetes. It is associated with a reduction in quality of life and exerts a significant burden on health care resources. The pathophysiology of this disorder is incompletely understood. Diagnosis is made based on typical symptoms associated with the demonstration of delayed gastric emptying in the absence of gastric outlet obstruction. Gastric emptying scintigraphy is the gold standard for demonstrating delayed gastric emptying, but other methods exist including breath testing and the wireless motility capsule. Diabetic gastroparesis should be managed within a specialist multidisciplinary team, and general aspects involve dietary manipulations/nutritional support, pharmacological therapy, and surgical/endoscopic interventions. Specific pharmacological therapies include prokinetics and antiemetics, with several new medications in the drug development pipeline. Surgical/endoscopic interventions include botulinum toxin injection into the pylorus, gastric peroral endoscopic myotomy and gastric electrical stimulation. This article provides a detailed review and summary of the epidemiology, pathophysiology, investigation, and management of diabetic gastroparesis, and also gives an individual patient's perspective of living with this disabling disorder.
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http://dx.doi.org/10.17294/2330-0698.1689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6676757PMC
April 2019

Liraglutide treatment reduced interleukin-6 in adults with type 1 diabetes but did not improve established autonomic or polyneuropathy.

Br J Clin Pharmacol 2019 11 30;85(11):2512-2523. Epub 2019 Aug 30.

Steno Diabetes Center Copenhagen, Region Hovedstaden, Gentofte, Denmark.

Aims: Type 1 diabetes can be complicated with neuropathy that involves immune-mediated and inflammatory pathways. Glucagon-like peptide-1 receptor agonists such as liraglutide, have shown anti-inflammatory properties, and thus we hypothesized that long-term treatment with liraglutide induced diminished inflammation and thus improved neuronal function.

Methods: The study was a randomized, double-blinded, placebo-controlled trial of adults with type 1 diabetes and confirmed symmetrical polyneuropathy. They were randomly assigned (1:1) to receive either liraglutide or placebo. Titration was 6 weeks to 1.2-1.8 mg/d, continuing for 26 weeks. The primary endpoint was change in latency of early brain evoked potentials. Secondary endpoints were changes in proinflammatory cytokines, cortical evoked potential, autonomic function and peripheral neurophysiological testing.

Results: Thirty-nine patients completed the study, of whom 19 received liraglutide. In comparison to placebo, liraglutide reduced interleukin-6 (-22.6%; 95% confidence interval [CI]: -38.1, -3.2; P = .025) with concomitant numerical reductions in other proinflammatory cytokines. However neuronal function was unaltered at the central, autonomic or peripheral level. Treatment was associated with -3.38 kg (95% CI: -5.29, -1.48; P < .001] weight loss and a decrease in urine albumin/creatinine ratio (-40.2%; 95% CI: -60.6, -9.5; P = .02).

Conclusion: Hitherto, diabetic neuropathy has no cure. Speculations can be raised whether mechanism targeted treatment, e.g. lowering the systemic level of proinflammatory cytokines may lead to prevention or treatment of the neuroinflammatory component in early stages of diabetic neuropathy. If ever successful, this would serve as an example of how fundamental mechanistic principles are translated into clinical practice similar to those applied in the cardiovascular and nephrological clinic.
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http://dx.doi.org/10.1111/bcp.14063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6848951PMC
November 2019

Pathophysiology and management of diabetic gastroenteropathy.

Therap Adv Gastroenterol 2019 17;12:1756284819852047. Epub 2019 Jun 17.

Mech-Sense, Department of Gastroenterology and Hepatology and Department of Clinical Medicine, Aalborg University Hospital, Denmark.

Polyneuropathy is a common complication to diabetes. Neuropathies within the enteric nervous system are associated with gastroenteropathy and marked symptoms that severely reduce quality of life. Symptoms are pleomorphic but include nausea, vomiting, dysphagia, dyspepsia, pain, bloating, diarrhoea, constipation and faecal incontinence. The aims of this review are fourfold. First, to provide a summary of the pathophysiology underlying diabetic gastroenteropathy. Secondly to give an overview of the diagnostic methods. Thirdly, to provide clinicians with a focussed overview of current and future methods for pharmacological and nonpharmacological treatment modalities. Pharmacological management is categorised according to symptoms arising from the upper or lower gut as well as sensory dysfunctions. Dietary management is central to improvement of symptoms and is discussed in detail, and neuromodulatory treatment modalities and other emerging management strategies for diabetic gastroenteropathy are discussed. Finally, we propose a diagnostic/investigation algorithm that can be used to support multidisciplinary management.
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http://dx.doi.org/10.1177/1756284819852047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6580709PMC
June 2019

Inhaled corticosteroids prescriptions increased in the ED for recurrent asthma exacerbations by automated electronic reminders in the ED.

J Asthma 2020 10 8;57(10):1140-1144. Epub 2019 Jul 8.

Pediatric Pulmonology, Phoenix Children's Hospital, Phoenix, AZ, USA.

The objective of this study was to evaluate the impact of an electronic alert on the prescription rate of inhaled corticosteroids (ICS) by ED providers for poorly controlled persistent asthmatic children. Study subjects included asthmatic patients age 4-18 presenting to the ED at Phenix Children's Hospital between February 9, 2018 and December 4, 2018, with a history of at least two previous ED visits for acute exacerbation of asthma within 365 days, no active ICS prescription within 90 days, and free from developmental delay, bronchopulmonary dysplasia due to prematurity, cystic fibrosis, sickle cell disease, and/or interstitial ling disease. Patients meeting these criteria triggered an electronic alert prompting the medical provider to prescribe ICS or indicate reason for not prescribing. Instruction on the alert was provided to ED attending physicians and residents by email and through several educational sessions held prior to the implementation. Among 62 patients without prior ICS who were discharged home from the ED, ICS was prescribed for 48 (77%). No statistically significant differences were detected in baseline characteristics between patients discharged home from the ED with and without ICS prescription. While ICS was prescribed by a larger proportion of physicians (56%) compared to residents (42%), statistical significance was not reached. For the 14 (33%) patients who were discharged home without ICS, no reason was provided to indicate why ICS were not prescribed.: An electronic alert incorporated into the ED workflow to populate a discharge order set is effective to initiate asthma controller medication for poorly controlled pediatric patients. Additional data describing reasons for not prescribing ICS can further refine recommendations for ICS prescriptions, and provide a comprehensive strategy to support clinical decision for pediatric asthma control in acute care settings.
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http://dx.doi.org/10.1080/02770903.2019.1635152DOI Listing
October 2020

Exciting news from the editors of Neurogastroenterology and Motility.

Neurogastroenterol Motil 2019 11 7;31(11):e13622. Epub 2019 May 7.

Neurogastroenterology Group, Wingate Institute of Neurogastroenterology, Barts and The London School of Medicine and Dentistry, London, UK.

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http://dx.doi.org/10.1111/nmo.13622DOI Listing
November 2019

In-hospital gastrointestinal bleeding following percutaneous coronary intervention.

Catheter Cardiovasc Interv 2020 01 8;95(1):109-117. Epub 2019 Apr 8.

Keele Cardiovascular Research Group, Keele University, Stoke-on-Trent, UK.

Objectives: This study aims to examine in-hospital gastrointestinal (GI) bleeding, its predictors and clinical outcomes, including long-term outcomes, in a national cohort of patients undergoing percutaneous coronary intervention (PCI) in England and Wales.

Background: GI bleeding remains associated with significant morbidity, mortality, and socioeconomic burden.

Methods: We examined the temporal changes in in-hospital GI bleeding in a national cohort of patients undergoing PCI between 2007 and 2014 in England and Wales, its predictors and prognostic consequences. Multivariate analysis was performed to identify independent risk factors between GI bleeding and 30-day mortality. Survival analysis was performed comparing patients with, and without, GI bleeding.

Results: There were 480 in-hospital GI bleeds in 549,298 patients (0.09%). Overall, rates of GI bleeding remained stable over time but a significant decline was observed for patients with ST segment elevation myocardial infarction (STEMI). The strongest predictors of bleeding events were STEMI-odds ratio (OR) 7.28 (95% confidence interval [95% CI] 4.82-11.00), glycoprotein IIb/IIIa inhibitor use OR 3.42 (95% CI 2.76-4.24) and use of circulatory support OR 2.65 (95% CI 1.90-3.71). Antiplatelets/coagulants (clopidogrel, prasugrel, and warfarin) were not independently associated with GI bleeding. GI bleeding was independently associated with a significant increase in all-cause 30-day mortality (OR 2.08 [1.52-2.83]). Patients with in-hospital GI bleed who survived to 30-days had increased all-cause mortality risk at 1 year compared to non-bleeders (HR 1.49 [1.07-2.09]).

Conclusions: In-hospital GI bleeding following PCI is rare but is a clinically important event associated with increased 30-day and long-term mortality.
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http://dx.doi.org/10.1002/ccd.28222DOI Listing
January 2020

Pathophysiology and management of opioid-induced constipation: European expert consensus statement.

United European Gastroenterol J 2019 02 14;7(1):7-20. Epub 2018 Dec 14.

Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.

Background: Opioid-induced bowel dysfunction is a complication of opioid therapy, in which constipation is the most common and problematic symptom. However, it is frequently under-recognised and thus effective management is often not instituted despite a number of treatment options.

Objective: The central objective of this study is to provide a summary of the pathophysiology and clinical evaluation of opioid-induced constipation and to provide a pragmatic management algorithm for day-to-day clinical practice.

Methods: This summary and the treatment algorithm is based on the opinion of a European expert panel evaluating current evidence in the literature.

Results: The pathophysiology of opioid-induced constipation is multi-faceted. The key aspect of managing opioid-induced constipation is early recognition. Specific management includes increasing fluid intake, exercise and standard laxatives as well as addressing exacerbating factors. The Bowel Function Index is a useful way of objectively evaluating severity of opioid-induced constipation and monitoring response. Second-line treatments can be considered in those with recalcitrant symptoms, which include gut-restricted or peripherally acting mu-opioid receptor antagonists. However, a combination of interventions may be needed.

Conclusion: Opioid-induced constipation is a common, yet under-recognised and undertreated, complication of opioid therapy. We provide a pragmatic step-wise approach to opioid-induced constipation, which should simplify management for clinicians.
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http://dx.doi.org/10.1177/2050640618818305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374852PMC
February 2019

Attitudes to out-of-programme experiences, research and academic training of gastroenterology trainees between 2007 and 2016.

Frontline Gastroenterol 2019 Jan 19;10(1):57-66. Epub 2018 Jun 19.

Department of Gastroenterology, Royal Wolverhampton NHS Trust, Wolverhampton, UK.

Objective: Academic medical training was overhauled in 2005 after the Walport report and Modernising Medical Careers to create a more attractive and transparent training pathway. In 2007 and 2016, national web-based surveys of gastroenterology trainees were undertaken to determine experiences, perceptions of and perceived barriers to out-of-programme research experience (OOP-R).

Design Setting And Patients: Prospective, national web-based surveys of UK gastroenterology trainees in 2007 and 2016.

Main Outcome Measure: Attitudes to OOP-R of two cohorts of gastroenterology trainees.

Results: Response rates were lower in 2016 (25.8% vs 56.7%) (p<0.0001), although female trainees' response rates increased (from 28.8% to 37.6%) (p=0.17), along with higher numbers of academic trainees. Over 80% of trainees planned to undertake OOP-R in both surveys, with >50% having already undertaken it. Doctor of Philosophy/medical doctorate remained the most popular OOP-R in both cohorts. Successful fellowship applications increased in 2016, and evidence of gender inequality in 2007 was no longer evident in 2016. In the 2016 cohort, 91.1% (n=144) felt the development of trainee-led research networks was important, with 74.7% (n=118) keen to get involved.

Conclusions: The majority of gastroenterology trainees who responded expressed a desire to undertake OOP-R, and participation rates in OOP-R remain high. Despite smaller absolute numbers responding than in 2007, 2016 trainees achieved higher successful fellowship application rates. Reassuringly more trainees in 2016 felt that OOP-R would be important in the future. Efforts are needed to tackle potential barriers to OOP-R and support trainees to pursue research-active careers.
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http://dx.doi.org/10.1136/flgastro-2018-100993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319145PMC
January 2019

Functional brain networks and neuroanatomy underpinning nausea severity can predict nausea susceptibility using machine learning.

J Physiol 2019 03 27;597(6):1517-1529. Epub 2019 Feb 27.

Centre for Neuroscience and Trauma, Blizard Institute, Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, 26 Ashfield Street, London, E1 2AJ, UK.

Key Points: Nausea is an adverse experience characterised by alterations in autonomic and cerebral function. Susceptibility to nausea is difficult to predict, but machine learning has yet to be applied to this field of study. The severity of nausea that individuals experience is related to the underlying morphology (shape) of the subcortex, namely of the amygdala, caudate and putamen; a functional brain network related to nausea severity was identified, which included the thalamus, cingulate cortices (anterior, mid- and posterior), caudate nucleus and nucleus accumbens. Sympathetic nervous system function and sympathovagal balance, by heart rate variability, was closely related to both this nausea-associated anatomical variation and the functional connectivity network, and machine learning accurately predicted susceptibility or resistance to nausea. These novel anatomical and functional brain biomarkers for nausea severity may permit objective identification of individuals susceptible to nausea, using artificial intelligence/machine learning; brain data may be useful to identify individuals more susceptible to nausea.

Abstract: Nausea is a highly individual and variable experience. The central processing of nausea remains poorly understood, although numerous influential factors have been proposed, including brain structure and function, as well as autonomic nervous system (ANS) activity. We investigated the role of these factors in nausea severity and if susceptibility to nausea could be predicted using machine learning. Twenty-eight healthy participants (15 males; mean age 24 years) underwent quantification of resting sympathetic and parasympathetic nervous system activity by heart rate variability. All were exposed to a 10-min motion-sickness video during fMRI. Neuroanatomical shape differences of the subcortex and functional brain networks associated with the severity of nausea were investigated. A machine learning neural network was trained to predict nausea susceptibility, or resistance, using resting ANS data and detected brain features. Increasing nausea scores positively correlated with shape variation of the left amygdala, right caudate and bilateral putamen (corrected P = 0.05). A functional brain network linked to increasing nausea severity was identified implicating the thalamus, anterior, middle and posterior cingulate cortices, caudate nucleus and nucleus accumbens (corrected P = 0.043). Both neuroanatomical differences and the functional nausea-brain network were closely related to sympathetic nervous system activity. Using these data, a machine learning model predicted susceptibility to nausea with an overall accuracy of 82.1%. Nausea severity relates to underlying subcortical morphology and a functional brain network; both measures are potential biomarkers in trials of anti-nausea therapies. The use of machine learning should be further investigated as an objective means to develop models predicting nausea susceptibility.
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http://dx.doi.org/10.1113/JP277474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418775PMC
March 2019
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