Publications by authors named "Alexander C Ford"

310 Publications

Natural History and Disease Impact of Rome IV versus Rome III Irritable Bowel Syndrome: A Longitudinal Follow-up Study.

Clin Gastroenterol Hepatol 2021 May 3. Epub 2021 May 3.

Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK; Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK. Electronic address:

Objectives: Irritable bowel syndrome (IBS) is a chronic functional bowel disorder diagnosed using the Rome criteria, which have evolved since their original description 30 years ago. Little is known about the effects on the natural history of IBS of moving to the latest iteration, Rome IV, from the previous Rome III criteria. We conducted a 12-month longitudinal follow-up study examining this.

Methods: We collected complete demographic, symptom, mood, and psychological health data at baseline from 1097 adults who self-identified as having IBS and met either Rome IV or III criteria. At 12 months, we collected data regarding IBS symptom severity and impact, consultation behavior, treatments commenced, and psychological health. We examined whether subsequent disease behavior in Rome IV or Rome III-defined IBS differed.

Results: At 12 months, 638 (58.2%) of the 1097 participants were successfully followed up. Of these, 452 met Rome IV criteria and 186 met Rome III criteria at baseline. During the 12-month study period, individuals with Rome IV IBS were significantly more likely to have seen a primary care physician (44.7% vs 28.5%, p<0.001) or a gastroenterologist (26.3% vs 12.4%, p<0.001) for their IBS symptoms, were significantly more likely to have commenced a new treatment (73.0% vs 60.2%, p=0.001), and cycled through significantly more treatments (p=0.007), for their IBS compared with those with Rome III IBS. At follow-up, individuals with Rome IV IBS had more severe symptoms, which had a significantly greater impact on activities of daily living, were more likely to report continuous abdominal pain, and a higher proportion demonstrated poor psychological health, compared with those with Rome III IBS (p<0.001 for all analyses).

Conclusions: The natural history of IBS defined according to Rome IV criteria is more severe than that of Rome III-defined IBS. This has important implications for future treatment trials in IBS.
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http://dx.doi.org/10.1016/j.cgh.2021.04.043DOI Listing
May 2021

Psychometric evaluation of an experience sampling method-based patient-reported outcome measure in functional dyspepsia.

Neurogastroenterol Motil 2021 May 2:e14136. Epub 2021 May 2.

Division of Gastroenterology-Hepatology, Department of Internal Medicine, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Centre+, Maastricht, The Netherlands.

Background: Due to important biases, conventional end-of-day and end-of-week assessment methods of gastrointestinal symptoms in functional dyspepsia (FD) are considered suboptimal. Real-time symptom assessment based on the experience sampling method (ESM) could be a more accurate measurement method. This study aimed to evaluate validity and reliability of an ESM-based patient-reported outcome measure (PROM) for symptom assessment in FD.

Methods: Thirty-five patients with FD (25 female, mean age 44.7 years) completed the ESM-based PROM (a maximum of 10 random moments per day) and an end-of-day symptom diary for 7 consecutive days. On day 7, end-of-week questionnaires were completed including the Nepean Dyspepsia Index (NDI) and Patient Assessment of Gastrointestinal Symptom Severity Index (PAGI-SYM).

Key Results: Experience sampling method and corresponding end-of-day scores for gastrointestinal symptoms were significantly associated (ICCs range 0.770-0.917). However, end-of-day scores were significantly higher (Δ0.329-1.031) than mean ESM scores (p < 0.05). Comparing ESM with NDI and PAGI-SYM scores, correlations were weaker (Pearson's r range 0.467-0.846). Cronbach's α coefficient was good for upper gastrointestinal symptoms (α = 0.842). First half-week and second half-week scores showed very good consistency (ICCs range 0.913-0.975).

Conclusion And Inferences: Good validity and reliability of a novel ESM-based PROM for assessing gastrointestinal symptoms in FD patients was demonstrated. Moreover, this novel PROM allows to evaluate individual symptom patterns and can evaluate interactions between symptoms and environmental/contextual factors. ESM has the potential to increase patients' disease insight, provide tools for self-management, and improve shared decision making. Hence, this novel tool may aid in the transition toward personalized health care for FD patients.
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http://dx.doi.org/10.1111/nmo.14136DOI Listing
May 2021

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

Gut 2021 Apr 26. Epub 2021 Apr 26.

Leeds Gastroenterology Institute, St James's University Hospital, 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
April 2021

Irritable bowel syndrome: a spotlight on future research needs.

Lancet Gastroenterol Hepatol 2021 Apr 16. Epub 2021 Apr 16.

Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK; Leeds Gastroenterology Institute, St James's University Hospital, Leeds, UK. Electronic address:

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http://dx.doi.org/10.1016/S2468-1253(21)00131-XDOI Listing
April 2021

Editorial: co-morbid gastrointestinal conditions are an important consideration in IBS management-authors' reply.

Aliment Pharmacol Ther 2021 May;53(10):1153-1154

Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK.

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http://dx.doi.org/10.1111/apt.16351DOI Listing
May 2021

Impact of Psychological Comorbidity on the Prognosis of Irritable Bowel Syndrome.

Am J Gastroenterol 2021 Apr 6. Epub 2021 Apr 6.

Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, United Kingdom; Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, United Kingdom; School of Psychology, Deakin University Geelong, Melbourne, Australia; County Durham and Darlington NHS Foundation Trust, Durham, United Kingdom.

Introduction: Psychological comorbidities are associated with irritable bowel syndrome (IBS), but little is known about their cumulative effect on its prognosis. We examined this issue in a longitudinal 12-month follow-up study.

Methods: We collected complete demographic, symptom, and psychological comorbidity data (anxiety, depression, somatic symptom disorder, perceived stress, and gastrointestinal symptom-specific anxiety) at baseline from 807 adults who met Rome IV criteria for IBS. At 12 months, we collected data regarding IBS symptom severity and impact, consultation behavior, and treatments commenced from 452 individuals successfully followed up. We examined the cumulative effects of psychological comorbidities at baseline on subsequent IBS disease behavior.

Results: At baseline, among the 807 participants, 177 (21.9%) had 1, 139 (17.2%) 2, 103 (12.8%) 3, 89 (11.0%) 4, and 54 (6.7%) 5 psychological comorbidities. IBS symptom severity at baseline increased significantly with the number of psychological comorbidities (72.2% of those with 5 psychological comorbidities reported severe symptoms, vs 29.1% of those with none, P < 0.001). Among 452 (56.0%) participants followed up at 12 months, those with a higher number of psychological comorbidities at baseline were significantly more likely to have seen a gastroenterologist (33.3% of those with 5 psychological comorbidities, vs 21.4% of those with none, P = 0.001), cycle through more treatments (P < 0.0001), to report more severe IBS symptoms (66.7% with 5, vs 24.4% with none, P < 0.001) and continuous abdominal pain (22.1% with none, vs 61.9% with 5, P < 0.001), and to report that symptoms impacted on daily activities ≥50% of the time (90.5% with 5, vs 41.2% with none, P < 0.001).

Discussion: The prognosis of individuals with Rome IV-defined IBS worsens according to incremental increases in psychological comorbidity. This has important clinical and research implications.
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http://dx.doi.org/10.14309/ajg.0000000000001247DOI Listing
April 2021

Overlap of Rome IV Irritable Bowel Syndrome and Functional Dyspepsia and Effect on Natural History: A Longitudinal Follow-Up Study.

Clin Gastroenterol Hepatol 2021 Apr 9. Epub 2021 Apr 9.

Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, United Kingdom; Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, United Kingdom. Electronic address:

Objectives: Disorders of gut-brain interaction, such as irritable bowel syndrome (IBS) and functional dyspepsia (FD), frequently overlap, but the impact of this on the natural history is unknown. We examined this issue in a longitudinal follow-up study conducted in a large cohort of individuals.

Methods: We collected complete demographic, symptom, mood, and psychological health data from 1374 adults who self-identified as having IBS. We applied the Rome IV criteria to examine what proportion met criteria for IBS and FD, as well as the degree of overlap between them. At 12 months, we collected data regarding IBS symptom severity and impact, consultation behavior, treatments commenced, and psychological health according to degree of overlap between IBS and FD.

Results: Overall, 807 individuals met the Rome IV criteria for IBS at baseline and provided complete data. At study entry, overlap of FD occurred in 446 (55.3%) people who met Rome IV criteria for IBS. At 12 months, 451 (55.9%) individuals were successfully followed up. The proportion of individuals consulting their primary care physician (P = .001) or a gastroenterologist (P < .001) because of their IBS was significantly higher in those with overlap of IBS and FD, and the number of new IBS treatments commenced was significantly higher (P = .007). Those with overlap of IBS and FD reported significantly more severe IBS symptoms (P < .001), continuous abdominal pain, and that their IBS symptoms limited normal daily activities ≥50% of the time. Finally, those with overlap were more likely to report abnormal anxiety and depression scores at 12 months compared with those with IBS alone, and to have higher levels of somatization (P < .001 for all analyses).

Conclusions: The natural history of people with IBS with overlap FD defined according to Rome IV criteria is more severe than those with IBS alone. This has important implications for future treatment trials in IBS.
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http://dx.doi.org/10.1016/j.cgh.2021.04.011DOI Listing
April 2021

Satiation or satiety? More than mere semantics - Authors' reply.

Lancet 2021 Mar;397(10279):1061

Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK; Leeds Gastroenterology Institute, St James's University Hospital, Leeds LS9 7TF, UK. Electronic address:

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http://dx.doi.org/10.1016/S0140-6736(21)00239-7DOI Listing
March 2021

Prevalence of symptoms of anxiety and depression in patients with inflammatory bowel disease: a systematic review and meta-analysis.

Lancet Gastroenterol Hepatol 2021 05 12;6(5):359-370. Epub 2021 Mar 12.

Leeds Gastroenterology Institute, St James' University Hospital, Leeds, UK; Leeds Institute of Medical Research at St James', University of Leeds, Leeds, UK. Electronic address:

Background: Inflammatory bowel disease (IBD) is a lifelong condition with no cure. Patients with IBD might experience symptoms of common mental disorders such as anxiety and depression because of bidirectional communication via the gut-brain axis and chronicity of symptoms, and because of impaired quality of life and reduced social functioning. However, uncertainties remain about the magnitude of this problem. We aimed to assess prevalence of symptoms of anxiety or depression in adult patients with IBD.

Methods: In this systematic review and meta-analysis, we searched MEDLINE, Embase, Embase Classic, and PsycINFO for papers published from inception to Sept 30, 2020, reporting observational studies that recruited at least 100 adult patients with IBD and that reported prevalence of symptoms of anxiety or depression according to validated screening instruments. We excluded studies that only used a structured interview to assess for these symptoms and studies that did not provide extractable data. We extracted data from published study reports and calculated pooled prevalences of symptoms of anxiety and depression, odds ratios (OR), and 95% CIs.

Findings: Of 5544 studies identified, 77 fulfilled the eligibility criteria, including 30 118 patients in total. Overall, pooled prevalence of anxiety symptoms was 32·1% (95% CI 28·3-36·0) in 58 studies (I=96·9%) and pooled prevalence of depression symptoms was 25·2% (22·0-28·5) in 75 studies (I=97·6%). In studies that reported prevalence of anxiety or depression in patients with Crohn's disease and ulcerative colitis within the same study population, patients with Crohn's disease had higher odds of anxiety symptoms (OR 1·2, 95% CI 1·1-1·4) and depression symptoms (1·2, 1·1-1·4) than patients with ulcerative colitis. Overall, women with IBD were more likely to have symptoms of anxiety than were men with IBD (pooled prevalence 33·8% [95% CI 26·5-41·5] for women vs 22·8% [18·7-27·2] for men; OR 1·7 [95% CI 1·2-2·3]). They were also more likely to have symptoms of depression than men were (pooled prevalence 21·2% [95% CI 15·4-27·6] for women vs 16·2% [12·6-20·3] for men; OR 1·3 [95% CI 1·0-1·8]). The prevalence of symptoms of anxiety (57·6% [95% CI 38·6-75·4]) or depression (38·9% [26·2-52·3]) was higher in patients with active IBD than in patients with inactive disease (38·1% [30·9-45·7] for anxiety symptoms and 24·2% [14·7-35·3] for depression symptoms; ORs 2·5 [95% CI 1·5-4·1] for anxiety and 3·1 [1·9-4·9] for depression).

Interpretation: There is a high prevalence of symptoms of anxiety and depression in patients with IBD, with up to a third of patients affected by anxiety symptoms and a quarter affected by depression symptoms. Prevalence was also increased in patients with active disease: half of these patients met criteria for anxiety symptoms and a third met criteria for depression symptoms. Encouraging gastroenterologists to screen for and treat these disorders might improve outcomes for patients with IBD.

Funding: None.
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http://dx.doi.org/10.1016/S2468-1253(21)00014-5DOI Listing
May 2021

Longitudinal follow-up of a novel classification system for irritable bowel syndrome: natural history and prognostic value.

Aliment Pharmacol Ther 2021 May 11;53(10):1126-1137. Epub 2021 Mar 11.

Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK.

Background: Conventionally, irritable bowel syndrome (IBS) is subgrouped using predominant stool form, yet it is a complex disorder, with multiple biopsychosocial contributors. We previously derived and validated a latent class model subgrouping people with IBS into seven clusters based on gastrointestinal and extraintestinal symptoms and psychological profile.

Aims: To conduct longitudinal follow-up examining the natural history and prognostic value of these clusters.

Methods: Participants completed a 12-month follow-up questionnaire. We applied our model to these data, comparing cluster membership between the two time points in those still meeting Rome IV criteria at follow-up, including stratifying the analysis by predominant stool pattern, and level of psychological burden, at baseline. We examined whether baseline cluster predicted the course of IBS, and whether starting new treatment was associated with changing cluster.

Results: Eight hundred and eleven participants met Rome IV criteria for IBS at baseline, of whom 452 (55.7%) responded, and 319 (70.6%) still met Rome IV criteria for IBS at follow-up. Of these, 172 (53.9%) remained in the same IBS cluster as at baseline and 147 changed cluster. Cluster membership stratified according to psychological comorbidity was more stable; 84% of those in a cluster with high psychological burden at baseline remained in such a cluster at follow-up. People in clusters with high psychological burden at baseline had more severe symptoms (P < 0.001), received a higher mean number of subsequent treatments (P < 0.001), and were more likely to consult a doctor than people in clusters with low psychological burden (P < 0.001). There was no significant association between starting a new treatment and changing cluster at follow-up.

Conclusions: Longitudinal follow-up demonstrated little transition between clusters with respect to psychological burden, and these appeared to predict disease course. Directing treatment according to cluster, including earlier use of psychological therapies, and exploring how this approach influences outcomes in IBS, should be examined.
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http://dx.doi.org/10.1111/apt.16322DOI Listing
May 2021

Systematic review with meta-analysis: risk factors for Barrett's oesophagus in individuals with gastro-oesophageal reflux symptoms.

Aliment Pharmacol Ther 2021 05 11;53(9):968-976. Epub 2021 Mar 11.

Leeds Institute of Medical Research, St. James's University of Leeds, Leeds, UK.

Background: Gastro-oesophageal reflux is considered the main risk factor for Barrett's oesophagus. The role of other potential risk factors for the development of Barrett's oesophagus in patients with gastro-oesophageal reflux symptoms is controversial.

Aims: To perform a systematic review and meta-analysis examining risk factors in development of Barrett's oesophagus.

Methods: Medline, Embase and Embase Classic were searched (until December 2020) to identify cross-sectional studies reporting prevalence of Barrett's oesophagus based on presence of one or more proposed risk factors in individuals with gastro-oesophageal reflux symptoms. Prevalence of Barrett's oesophagus was compared according to presence or absence of each risk factor in individuals with gastro-oesophageal reflux symptoms.

Results: Of 7164 citations evaluated, 13 studies reported prevalence of Barrett's oesophagus in 11 856 subjects. Pooled prevalence of histologically confirmed Barrett's oesophagus in individuals with gastro-oesophageal reflux symptoms in all studies was 7.0% (95% CI 4.8% to 9.6%). Prevalence was higher in subjects with hiatal hernia (OR 2.74; 95% CI 1.58 to 4.75) and in those who drank alcohol (OR 1.51; 95% CI 1.17 to 1.95). Other features including non-steroidal anti-inflammatory drugs and/or aspirin use (OR 1.19; 95% CI 1.00 to 1.42), smoking (OR 1.14; 95% CI 0.96 to 1.35) or obesity (OR 1.10; 95% CI 0.92 to 1.33) were not significantly associated with Barrett's oesophagus.

Conclusions: The prevalence of Barrett's oesophagus in individuals with gastro-oesophageal reflux symptoms was higher in those who drank alcohol, although this association was modest. The strongest association found was between hiatal hernia and Barrett's oesophagus. Other potential risk factors assessed in this study did not appear to be associated with presence of Barrett's oesophagus among individuals with gastro-oesophageal symptoms.
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http://dx.doi.org/10.1111/apt.16321DOI Listing
May 2021

Common mental disorders in irritable bowel syndrome: pathophysiology, management, and considerations for future randomised controlled trials.

Lancet Gastroenterol Hepatol 2021 05 13;6(5):401-410. Epub 2021 Feb 13.

Leeds Gastroenterology Institute, St James's University Hospital, Leeds, UK; Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK.

The frequent co-occurrence of irritable bowel syndrome and the common mental disorders of anxiety and depression is well established. A range of biological and psychosocial disease mechanisms are common to both disorders, many of which contribute to a dysregulated gut-brain axis. Clinical and subthreshold psychological comorbidity adds to the functional impairment and disease burden in individuals with irritable bowel syndrome. Progress is being made with regard to understanding irritable bowel syndrome in the clinical setting from a biopsychosocial perspective. However, until now, most trials of irritable bowel syndrome treatment still consider the disease as a gut disorder in isolation, which leaves major gaps in knowledge about disease-disease interactions and treatment outcomes in irritable bowel syndrome. In this Viewpoint, we review the epidemiology, pathophysiology, and management of anxiety and depression in individuals with irritable bowel syndrome. We also provide methodological recommendations for future randomised controlled trials and outline guidance for research that better incorporates psychiatric comorbidity into its design, with a view to improve treatment outcomes for individuals with irritable bowel syndrome.
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http://dx.doi.org/10.1016/S2468-1253(20)30363-0DOI Listing
May 2021

Editorial: will clusters for anxiety, depression, sleep disturbance and fatigue symptoms predict treatment outcomes in functional dyspepsia? Authors' reply.

Aliment Pharmacol Ther 2021 03;53(5):652-653

Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.

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http://dx.doi.org/10.1111/apt.16247DOI Listing
March 2021

Healthy Mind, Healthy Body: Chronic Depression May Predate the Development of Inflammatory Bowel Disease by up to 9 Years.

Gastroenterology 2021 Feb 5. Epub 2021 Feb 5.

Leeds Gastroenterology Institute and, Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK.

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http://dx.doi.org/10.1053/j.gastro.2021.02.004DOI Listing
February 2021

Chronic constipation in adults: Contemporary perspectives and clinical challenges. 2: Conservative, behavioural, medical and surgical treatment.

Neurogastroenterol Motil 2021 Feb 1:e14070. Epub 2021 Feb 1.

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

Background: Chronic constipation is a prevalent disorder that affects quality of life of patients 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 and Motility journal supplement devoted to the investigation and management of constipation was published (Neurogastroenterol Motil 2009;21(Suppl 2):1). In October 2018, the 3rd London Masterclass, entitled "Contemporary management of constipation" was held. The faculty members of this symposium were invited to write two reviews to present a collective synthesis of talks presented and discussions held during this meeting. The first review addresses epidemiology, diagnosis, clinical associations, pathophysiology, and investigation.

Purpose: The present is the second of these reviews, providing contemporary perspectives and clinical challenges regarding behavioral, conservative, medical, and surgical treatments for patients presenting with constipation. It includes a management algorithm to guide clinical practice.
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http://dx.doi.org/10.1111/nmo.14070DOI Listing
February 2021

Efficacy of Oral, Topical, or Combined Oral and Topical 5-Aminosalicylates, in Ulcerative Colitis: Systematic Review and Network Meta-Analysis.

J Crohns Colitis 2021 Jan 12. Epub 2021 Jan 12.

Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.

Background: 5-aminosalicylates (5-ASAs) are the mainstay of treatment for ulcerative colitis (UC). The optimum preparation, dose, and route of administration for UC remains unclear. We conducted a network meta-analysis to examine this issue.

Methods: We searched MEDLINE, EMBASE, EMBASE Classic, and the Cochrane central register of controlled trials from inception to December 2020. We included randomised controlled trials (RCTs) comparing oral, topical, or combined oral and topical 5-ASAs, with each other, or placebo for induction of remission or prevention of relapse of UC. Results were reported as pooled relative risks (RRs) with 95% confidence intervals (CIs) to summarize effect of each comparison tested, with treatments ranked according to P-score.

Results: We identified 40 RCTs for induction of remission and 23 for prevention of relapse. Topical mesalazine (P-score 0.99), or oral and topical mesalazine combined (P-score 0.87) ranked first and second for clinical and endoscopic remission combined. Combined therapy ranked first in trials where ≥50% of patients had left-sided/extensive disease, and topical mesalazine first in trials where ≥50% of patients had proctitis/proctosigmoiditis. High-dose (≥3.3g/day) oral mesalazine ranked third in most analyses, with the most trials and most patients. For relapse of disease activity, combined therapy and high-dose oral mesalazine ranked first and second, with topical mesalazine third. 5-ASAs were safe and well-tolerated, regardless of regimen.

Conclusions: Our results support previous evidence, however, higher doses of oral mesalazine had more evidence for induction of remission than combined therapy and were significantly more efficacious than lower doses. Future RCTs should better establish the role of combined therapy for induction of remission, as well as optimal doses of oral 5-ASAs to prevent relapse.
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http://dx.doi.org/10.1093/ecco-jcc/jjab010DOI Listing
January 2021

Derivation and validation of a novel method to subgroup patients with functional dyspepsia: beyond upper gastrointestinal symptoms.

Aliment Pharmacol Ther 2021 01 5;53(2):253-264. Epub 2020 Dec 5.

Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.

Background: Conventionally, patients with functional dyspepsia are subgrouped based on upper gastrointestinal symptoms, according to the Rome criteria. However, psychological co-morbidity and extraintestinal symptoms are also relevant to functional gastrointestinal disorders.

Aim: To investigate whether it is possible to subgroup people with functional dyspepsia using factors beyond upper gastrointestinal symptoms.

Methods: We collected demographic, symptom and psychological health data from adult subjects meeting the Rome III criteria for functional dyspepsia in two secondary care cross-sectional surveys in Canada and the UK. We performed latent class analysis, a method of model-based clustering, to identify specific subgroups (clusters). For each cluster, we drew a radar plot, and compared these by visual inspection, describing cluster characteristics.

Results: In total, 400 individuals met Rome III criteria for functional dyspepsia in the Canadian cohort, and 262 the UK cohort. A four-cluster model was the optimum solution and the characteristics of the clusters were almost identical between the two cohorts. The clusters were defined by a pattern of gastrointestinal symptoms and were further differentiated by the extent of extraintestinal and psychological co-morbidity. Cluster 1 (mean age 46.7 years, 66.7% female) consisted of epigastric pain and nausea with high psychological burden, cluster 2 (mean age 41.5 years, 77.7% female) high overall gastrointestinal symptom severity with high psychological burden, cluster 3 (45.8 years, 67.2% female) oesophageal symptoms and early satiety with low psychological burden, and cluster 4 (mean age 40.4 years, 71.5% female) postprandial fullness with low psychological burden. We validated the model derived using the Canadian study population externally by applying it to the UK dataset. We demonstrated reproducibility; it would perform similarly when applied to a different dataset.

Conclusions: Latent class analysis identified four distinct functional dyspepsia subgroups characterised by varying degrees of gastrointestinal symptoms, extraintestinal symptoms and psychological co-morbidity. Further research is needed to assess whether they might be used to direct treatment.
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http://dx.doi.org/10.1111/apt.16184DOI Listing
January 2021

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

Neurogastroenterol Motil 2020 Dec 2: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
December 2020

Bugs and the Brain in Inflammatory Bowel Disease: A Novel Treatment Target?

Clin Gastroenterol Hepatol 2020 Nov 25. Epub 2020 Nov 25.

Leeds Gastroenterology Institute, St. James's University Hospital, Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, United Kingdom.

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http://dx.doi.org/10.1016/j.cgh.2020.10.021DOI Listing
November 2020

In the Face of Adversity: Is Resilience a New Target for Inflammatory Bowel Disease Therapy?

Gastroenterology 2021 Jan 19;160(1):466-467. Epub 2020 Nov 19.

Leeds Gastroenterology Institute; Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK.

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http://dx.doi.org/10.1053/j.gastro.2020.11.023DOI Listing
January 2021

Efficacy of Ondansetron for Irritable Bowel Syndrome With Diarrhea.

Am J Gastroenterol 2021 02;116(2):428-429

Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.

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http://dx.doi.org/10.14309/ajg.0000000000000932DOI Listing
February 2021

Ciclosporin or Infliximab as Rescue Therapy in Acute Glucorticosteroid-Refractory Ulcerative Colitis: Systematic Review and Network Meta-Analysis.

J Crohns Colitis 2021 May;15(5):733-741

Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.

Background: Despite randomized controlled trials [RCTs] and trial-based meta-analyses, the optimal rescue therapy for patients with acute glucorticosteroid-refractory ulcerative colitis [UC], to avoid colectomy and improve long-term outcomes, remains unclear. We conducted a network meta-analysis examining this issue.

Methods: We searched MEDLINE, EMBASE, EMBASE Classic and the Cochrane central register up to June 2020. We included RCTs comparing ciclosporin and infliximab, either with each other or with placebo, in patients with glucorticosteroid-refractory UC.

Results: We identified seven RCTs containing 534 patients [415 in head-to-head trials of ciclosporin vs infliximab]. Risk of colectomy at ≤ 1 month was reduced significantly with both treatments, compared with placebo (relative risk [RR] of colectomy with infliximab vs placebo = 0.37; 95% confidence interval [CI] 0.21-0.65, RR with ciclosporin vs placebo = 0.40; 95% CI 0.21-0.77). In terms of colectomy between > 1 month and < 1 year, both drugs ranked equally [P-score 0.75]. Neither treatment was more effective than placebo in reducing the risk of colectomy at ≥ 1 year. Both ciclosporin and infliximab were significantly more efficacious than placebo in achieving a response. Neither treatment was more effective than placebo in inducing remission, nor more likely to cause serious adverse events than placebo.

Conclusions: Both ciclosporin and infliximab were superior to placebo in terms of response to therapy and avoiding colectomy up to 1 year, with no significant differences in efficacy or safety between the two. Ciclosporin remains a valid option to treat refractory UC patients, especially those who do not respond to previous treatment with infliximab, or as a bridge to other biological therapies.
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http://dx.doi.org/10.1093/ecco-jcc/jjaa226DOI Listing
May 2021

Efficacy of Senna and Magnesium Oxide for the Treatment of Chronic Idiopathic Constipation.

Am J Gastroenterol 2020 Oct 28. Epub 2020 Oct 28.

Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.

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http://dx.doi.org/10.14309/ajg.0000000000001041DOI Listing
October 2020

A Novel Method to Classify and Subgroup Patients With IBS Based on Gastrointestinal Symptoms and Psychological Profiles.

Am J Gastroenterol 2021 02;116(2):372-381

Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.

Introduction: Conventionally, patients with irritable bowel syndrome (IBS) are subgrouped based on their predominant bowel habit. Given the relevance of psychological comorbidity to IBS symptoms, our aim was to explore an alternative approach to subgrouping by incorporating factors beyond stool form and frequency.

Methods: We collected demographic, symptom, and psychological health data from 1,375 adult subjects in the community who self-identified as having IBS, identifying 2 cohorts meeting either Rome III or Rome IV criteria. In each cohort, we performed latent class analysis, a method of model-based clustering, to identify specific subgroups (clusters). For each cluster, we drew a radar plot and compared these by visual inspection, describing cluster characteristics.

Results: In total, 1,080 individuals met the Rome III criteria for IBS, and 811 met the Rome IV criteria. In both cohorts, a 7-cluster model was the optimum solution, and the characteristics of the clusters were almost identical between Rome III and IV. Four clusters were defined by the pattern of gastrointestinal symptoms (loose stools and urgency or hard stools and bloating), further differentiated by the presence of abdominal pain not relieved by defecation, and by the extent of psychological comorbidity. Two clusters had below-average gastrointestinal symptoms, differentiated by the extent of psychological comorbidity. The final cluster had well-above-average gastrointestinal symptoms and high levels of psychological comorbidity. The proportion of subjects with severe IBS symptom scores, high levels of perceived stress, and high levels of gastrointestinal symptom-specific anxiety was significantly higher in clusters with high psychological comorbidity (P < 0.001).

Discussion: Latent class analysis identified 7 distinct IBS subgroups characterized by varying degrees of gastrointestinal symptoms, extraintestinal symptoms, and psychological comorbidity. Further research is needed to assess whether they might be used to direct treatment.
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http://dx.doi.org/10.14309/ajg.0000000000000975DOI Listing
February 2021

Faecal incontinence is not rare in irritable bowel syndrome.

Frontline Gastroenterol 2020 Oct 15;11(6):494-496. Epub 2020 May 15.

Leeds Gastroenterology Institute, St James's University Hospital, Leeds, West Yorkshire, UK.

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http://dx.doi.org/10.1136/flgastro-2020-101518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569511PMC
October 2020

Irritable bowel syndrome.

Lancet 2020 11 10;396(10263):1675-1688. Epub 2020 Oct 10.

Clinical Enteric Neuroscience Translational and Epidemiological Research, Mayo Clinic, Rochester, MN, USA.

Irritable bowel syndrome is a functional gastrointestinal disorder with symptoms including abdominal pain associated with a change in stool form or frequency. The condition affects between 5% and 10% of otherwise healthy individuals at any one point in time and, in most people, runs a relapsing and remitting course. The best described risk factor is acute enteric infection, but irritable bowel syndrome is also more common in people with psychological comorbidity and in young adult women than in the rest of the general population. The pathophysiology of irritable bowel syndrome is incompletely understood, but it is well established that there is disordered communication between the gut and the brain, leading to motility disturbances, visceral hypersensitivity, and altered CNS processing. Other less reproducible mechanisms might include genetic associations, alterations in gastrointestinal microbiota, and disturbances in mucosal and immune function. In most people, diagnosis can be made on the basis of clinical history with limited and judicious use of investigations, unless alarm symptoms such as weight loss or rectal bleeding are present, or there is a family history of inflammatory bowel disease or coeliac disease. Once the diagnosis is made, an empathetic approach is key and can improve quality of life and symptoms, and reduce health-care expenditure. The mainstays of treatment include patient education about the condition, dietary changes, soluble fibre, and antispasmodic drugs. Other treatments tend to be reserved for people with severe symptoms and include central neuromodulators, intestinal secretagogues, drugs acting on opioid or 5-HT receptors, or minimally absorbed antibiotics (all of which are selected according to predominant bowel habit), as well as psychological therapies. Increased understanding of the pathophysiology of irritable bowel syndrome in the past 10 years has led to a healthy pipeline of novel drugs in development.
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http://dx.doi.org/10.1016/S0140-6736(20)31548-8DOI Listing
November 2020

Functional dyspepsia.

Lancet 2020 11 10;396(10263):1689-1702. Epub 2020 Oct 10.

Australian Gastrointestinal Research Alliance, University of Newcastle, Newcastle, NSW, Australia.

Dyspepsia is a complex of symptoms referable to the gastroduodenal region of the gastrointestinal tract and includes epigastric pain or burning, postprandial fullness, or early satiety. Approximately 80% of individuals with dyspepsia have no structural explanation for their symptoms and have functional dyspepsia. Functional dyspepsia affects up to 16% of otherwise healthy individuals in the general population. Risk factors include psychological comorbidity, acute gastroenteritis, female sex, smoking, use of non-steroidal anti-inflammatory drugs, and Helicobacter pylori infection. The pathophysiology remains incompletely understood, but it is probably related to disordered communication between the gut and the brain, leading to motility disturbances, visceral hypersensitivity, and alterations in gastrointestinal microbiota, mucosal and immune function, and CNS processing. Although technically a normal endoscopy is required to diagnose functional dyspepsia, the utility of endoscopy in all patients with typical symptoms is minimal; its use should be restricted to people aged 55 years and older, or to those with concerning features, such as weight loss or vomiting. As a result of our incomplete understanding of its pathophysiology, functional dyspepsia is difficult to treat and, in most patients, the condition is chronic and the natural history is one of fluctuating symptoms. Eradication therapy should be offered to patients with functional dyspepsia who test positive for Helicobacter pylori. Other therapies with evidence of effectiveness include proton pump inhibitors, histamine-2 receptor antagonists, prokinetics, and central neuromodulators. The role of psychological therapies is uncertain. As our understanding of the pathophysiology of functional dyspepsia increases, it is probable that the next decade will see the emergence of truly disease-modifying therapies for the first time.
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http://dx.doi.org/10.1016/S0140-6736(20)30469-4DOI Listing
November 2020

Functional gastrointestinal disorders: advances in understanding and management.

Lancet 2020 11 10;396(10263):1664-1674. Epub 2020 Oct 10.

Leeds Gastroenterology Institute, St James's University Hospital, Leeds, UK; Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK. Electronic address:

Gastrointestinal symptoms are highly prevalent, but many people who have them will have no organic explanation for their symptoms. Most of these people will be labelled as having a functional gastrointestinal disorder, such as irritable bowel syndrome, functional dyspepsia, or functional constipation. These conditions affect up to 40% of people at any one point in time, and two-thirds of these people will have chronic, fluctuating symptoms. The pathophysiology of functional gastrointestinal disorders is complex, but involves bidirectional dysregulation of gut-brain interaction (via the gut-brain axis), as well as microbial dysbiosis within the gut, altered mucosal immune function, visceral hypersensitivity, and abnormal gastrointestinal motility. Hence, nomenclature refers to the conditions as disorders of gut-brain interaction. Psychological comorbidity is common; however, whether or not this predates, or is driven by, symptoms is not clear. Patients with functional gastrointestinal disorders can feel stigmatised, and often this diagnosis is not communicated effectively by physicians, nor is education provided. Prompt identification and treatment of these conditions is crucial as they have a considerable impact on health-care systems and society as a whole because of repeated consultations, unnecessary investigations and surgeries, prescriptions and over-the-counter medicine use, and impaired health-related quality of life and ability to work. Symptom-based criteria are used to make a diagnosis, with judicious use of limited investigations in some patients. The general principles of treatment are based on a biopsychosocial understanding and involve management of physical symptoms and, if present, psychological comorbidity. In the future, treatment approaches to functional gastrointestinal disorders are likely to become more personalised, based not only on symptoms but also underlying pathophysiology and psychology.
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http://dx.doi.org/10.1016/S0140-6736(20)32115-2DOI Listing
November 2020

Biochemical Tests for Bile Acid Diarrhea: Real-World Studies Required.

Am J Gastroenterol 2020 Oct 8. Epub 2020 Oct 8.

Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.

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http://dx.doi.org/10.14309/ajg.0000000000000976DOI Listing
October 2020

Efficacy of surgical or endoscopic treatment of idiopathic achalasia: a systematic review and network meta-analysis.

Lancet Gastroenterol Hepatol 2021 01 6;6(1):30-38. Epub 2020 Oct 6.

Leeds Gastroenterology Institute, St James's University Hospital, Leeds, UK; Leeds Institute of Medical Research, St James's University Hospital, Leeds, UK. Electronic address:

Background: Treatment of achalasia has changed substantially over the past 20 years. Therapeutic options offered to patients vary, depending on access to both resources and expertise, and include pneumatic dilation (PD), laparoscopic Heller's myotomy (LHM), or per-oral endoscopic myotomy (POEM). Although there are head-to-head trials of these interventions, many of these are small and underpowered, so relative efficacy is unknown. We did a systematic review and network meta-analysis to try to resolve this uncertainty.

Methods: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and Embase Classic from database inception up to June 11, 2020, for randomised controlled trials (RCTs) assessing the efficacy of POEM, LHM, or PD, compared with each other in adults with idiopathic achalasia. We extracted all data as dichotomous outcomes (treatment success or failure) after completion of therapy. We also extracted country of origin, number of centres, duration of follow-up, and primary outcome measure used to define treatment success or failure. Data were extracted for intention-to-treat analyses, with all dropouts assumed to be treatment failures (ie, symptomatic at final point of follow-up), wherever trial reporting allowed this. We pooled data using a random effects model, and assessed heterogeneity between studies using the I statistic. Risk of bias was examined for all studies. The primary outcome was efficacy, in terms of a dichotomous measure of treatment success or failure, after a minimum of 1 year of follow-up. Secondary outcomes were occurrence of perforation, adverse events, serious adverse events (including death), need for reintervention, need for surgery as a result of complications, development of gastro-oesophageal reflux, or erosive oesophagitis. Efficacy was reported as a pooled relative risk (RR) of treatment failure, with a 95% CI, for each comparison tested, and ranked by therapy according to P-score.

Findings: Of 1044 studies initially assessed, nine were eligible RCTs, which comprised 911 participants in total. None of the nine studies were at low risk of bias. Of the 911 participants 372 (41%) participants were randomly assigned to LHM, 317 (35%) participants to PD, and 222 (24%) participants to POEM. Of the three strategies, POEM was ranked first (RR of failure of treatment 0·33, 95% CI 0·15-0·71; P-score 0·89), then LHM (RR 0·45, 0·26-0·78, P-score 0·61). There was moderate heterogeneity between studies (I=61·5%). Both POEM and LHM were superior to PD on direct and indirect comparison, but neither was significantly more effective than the other. There were no significant differences in perforation rates, need for re-intervention or surgery, gastro-oesophageal reflux, erosive oesophagitis, or serious adverse events, but PD was less likely to lead to adverse events than POEM.

Interpretation: POEM and LHM should be the preferred treatments for idiopathic achalasia. PD performed worst in terms of treatment success, and therefore its role in the management of patients with achalasia is less certain.

Funding: None.
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http://dx.doi.org/10.1016/S2468-1253(20)30296-XDOI Listing
January 2021