Results from a psychometric validation study: irritable bowel syndrome patients report higher symptom burden using end-of-day versus real-time assessment.

OBJECTIVE: Real-time assessment of gastrointestinal (GI) symptoms in irritable bowel syndrome (IBS) using the experience sampling method (ESM) is suggested as a more appropriate approach than currently used end-of-day or end-of-week reports. This psychometric evaluation study assesses the validity and reliability of a previously developed ESM-based patient-reported outcome measure (PROM) for real-time GI symptom assessment in IBS. METHODS: This multicenter validation study included 230 Rome IV IBS patients (80% female; mean age 41.2 years) in three European countries. Patients completed the electronic ESM-PROM (up to ten random moments daily, with a weekly minimum completion rate of 33%) and an end-of-day symptom diary for seven consecutive days. End-of-week questionnaires (GSRS-IBS, IBS-SSS, PHQ-9, and GAD-7) were completed at the end of the 7-day period. RESULTS: The ESM assessment had a mean completion rate of 71%. Strong and significant correlations (0.651-0.956) with moderately-to-good consistency (ICCs 0.580-0.779) were observed between ESM and end-of-day scores. However, end-of-day scores were significantly higher (Δ0.790-1.758, p<0.001) than mean daily ESM scores. Differences with end-of-week scores were more pronounced, with weaker correlations (Pearson's r 0.393-0.802). ESM-PROM exhibited moderate-to-good internal consistency (Cronbach's α 0.585-0.887) across five symptom domains. First and second half-week scores demonstrated good-to-excellent consistency (ICCs 0.871-0.958). CONCLUSIONS: Psychometric evaluation demonstrated strong validity and reliability of the ESM-PROM for real-time GI symptom assessment in IBS. In addition, the ESM-PROM provides a precise and reliable ascertainment of individual symptom pattern and trigger interactions, without the bias of peak reporting when compared to retrospective methods. This highlights its potential as a valuable tool for personalized healthcare in monitoring disease course and treatment response in IBS patients.

Relationship Between Abuse History and Gastrointestinal and Extraintestinal Symptom Severity in Irritable Bowel Syndrome.

OBJECTIVE: This study aimed to investigate the associations between the different abuse types, and gastrointestinal (GI) and extraintestinal symptom severity in irritable bowel syndrome (IBS), and possible mediators of these relationships. METHODS: We assessed sexual and physical abuse in childhood and adulthood with the Drossman and Leserman abuse questionnaire, whereas GI and extraintestinal symptoms were assessed with the Gastrointestinal Symptom Rating Scale and the Symptom Check List-90 Revised. General linear models with bootstrapping tested the mediating role of depressive symptoms, anxiety symptoms, and GI-specific anxiety and rectal pain threshold. A path model analysis testing all relationships simultaneously was also performed. RESULTS: Among our 186 patients with IBS, an overall history of abuse (i.e., at least one type) was found in 37%. The effects of child and adult sexual abuse on GI symptom severity were fully mediated by GI-specific anxiety and rectal pain threshold (F = 21.540, R2 = 0.43, and F = 22.330, R2 = 0.44, respectively; p < .001 for both). The effect of adult sexual abuse and child physical abuse on extraintestinal symptom severity was fully mediated by GI-specific anxiety, depressive symptoms, and rectal pain threshold, whereas the effect of child sexual abuse was partially mediated (F = 14.992, R2 = 0.28; F = 15.065, R2 = 0.30; and F = 18.037, R2 = 0.32, respectively; p < .001 for all). When analyzed in a single path model, child sexual abuse and adult physical abuse only had a direct effect on extraintestinal symptom severity, whereas child physical abuse had an indirect effect through depressive symptoms. CONCLUSIONS: Abuse is associated with increased GI and extraintestinal symptom severity in IBS. These associations are mediated by levels of GI-specific anxiety, depressive symptoms, and rectal sensitivity.

Cumulative Effect of Psychological Alterations on Gastrointestinal Symptom Severity in Irritable Bowel Syndrome.

INTRODUCTION: Psychological alterations are common and considered important for symptom generation in irritable bowel syndrome (IBS). However, the possible cumulative effect of having multiple psychological alterations on gastrointestinal (GI) symptom severity in IBS is largely unknown. METHODS: Patients with IBS (Rome IV) completed validated questionnaires assessing GI symptoms (Gastrointestinal Symptom Rating Scale, IBS version and IBS Severity Scoring System), personality traits (Big Five), posttraumatic stress and psychological alterations, anxiety (Generalized Anxiety Disorder 7-item scale and State-Trait Anxiety Inventory), depression (Patient Health Questionnaire, 9-item version), fatigue (Multidimensional Fatigue Inventory), pain catastrophizing, somatization (Patient Health Questionnaire, 12-item version), stress (Perceived Stress Scale), and GI-specific anxiety (Visceral Sensitivity Index). Of the 18 possible psychological factors, those with significant associations with GI symptom severity, corrected for multiple comparisons, were identified. The associations between increasing number of psychological alterations (validated cutoff values or uppermost tertile) and the severity of GI symptoms were analyzed with linear trend analyses. RESULTS: In total, 106 patients with IBS (Rome IV criteria) were included (72 [68%] women, median age of 35 [interquartile range: 26-45] years). Psychological alterations were common and overlap among these factors were frequently seen. Five psychological factors (physical fatigue, GI-specific anxiety, perceived stress, pain catastrophizing, and trait anxiety) demonstrated significant, noncollinear associations with GI symptom severity. With increasing number of these psychological alterations, a gradual increase was seen in the overall severity of GI symptoms (Gastrointestinal Symptom Rating Scale, IBS version: partial η = 0.268, P < 0.001; IBS Severity Scoring System: partial η = 0.219, P < 0.001, both large effect sizes). DISCUSSION: Distinct associations were seen between the severity of GI symptoms and individual, as well as an increasing number of psychological alterations. This highlights the importance of understanding different psychological alterations for the disease burden in IBS (visual abstract, Supplementary Digital Content 1, http://links.lww.com/AJG/B756).

Associations between postprandial symptoms, hydrogen and methane production, and transit time in irritable bowel syndrome.

BACKGROUND: Abnormal oroanal transit time (OATT) and visceral hypersensitivity are key pathophysiological factors in irritable bowel syndrome (IBS). The lactulose nutrient challenge test (LNCT) has been developed to assess the postprandial symptoms and gut microbial fermentation. We aimed to investigate associations between OATT, rectal sensitivity, and LNCT in IBS patients. METHODS: We included 263 IBS patients from two study cohorts, where the link between pathophysiology and symptoms was investigated. During the LNCT, severity of postprandial symptoms was graded, and breath hydrogen/methane concentrations were measured after ingestion of a combined lactulose nutrient drink every 15 min for 4 h. The patients underwent rectal sensitivity (rectal barostat) and OATT (radiopaque markers) investigations. Comorbid conditions (functional dyspepsia, anxiety, depression, and somatization) were assessed with questionnaires. KEY RESULTS: After controlling for comorbid conditions, rectal sensitivity was associated with abdominal pain (p < 0.05), and more rapid OATT was associated with higher severity of abdominal discomfort, rumbling, nausea, and urgency (p < 0.05 for all) both pre- and post-prandially. Postprandial nausea, urgency, and abdominal pain changed differently over time depending on OATT (p < 0.05 for all). OATT, but not rectal sensitivity, was associated with hydrogen and methane concentrations (p = 0.002 for both). Trajectories over time of postprandial symptoms and exhaled hydrogen/methane concentrations were correlated with different correlations depending on OATT. CONCLUSION AND INFERENCES: This study highlights the importance of oroanal transit and hydrogen and methane production in the pathophysiology of IBS and increases our understanding of pathophysiological factors involved in postprandial symptom generation. Treatments targeting oroanal transit and hydrogen and methane production may improve specific postprandial symptoms.

Central sensitization and severity of gastrointestinal symptoms in irritable bowel syndrome, chronic pain syndromes, and inflammatory bowel disease.

BACKGROUND: Central sensitization has been suggested as an explanation of the wide range of gastrointestinal and extraintestinal symptoms commonly seen in irritable bowel syndrome (IBS). In this study, the presence and level of central sensitization, and its association to gastrointestinal (GI) symptoms were explored in IBS in comparison with control groups. METHODS: We investigated patients with IBS (n = 215), chronic pain disorders (n = 36), and inflammatory bowel disease (IBD) (n = 40) and volunteers without chronic diseases (n = 112). The Central Sensitization Inventory (CSI) was translated and validated in Swedish and used together with the Highly Sensitive Person (HSP) scale to measure the presence and level of central sensitization. Furthermore, severity of GI symptoms (GSRS-IBS and IBS-SSS), and anxiety and depression (HAD) were determined. KEY RESULTS: The Swedish translation of CSI demonstrated excellent validity. Central sensitization, defined by validated cut-off levels for CSI and HSP, was common in the whole cohort (40% and 28%) and in IBS (57% and 35%). Study participants with central sensitization had more severe GI symptoms, anxiety and depression, than participants without central sensitization. Strong associations were seen between CSI and GI symptom severity in the whole cohort (GSRS-IBS: partial η2  = 0.455, p < 0.001; IBS-SSS: partial η2  = 0.408, p < 0.001), with decreasing strength in patients with chronic pain, IBD, IBS, and volunteers. CONCLUSION AND INFERENCES: Central sensitization was common in IBS and associated with GI symptom severity, but with stronger associations in chronic pain disorders and IBD. This implies that other mechanisms may be of equal or greater importance for GI symptom severity in IBS.

Associations among neurophysiology measures in irritable bowel syndrome (IBS) and their relevance for IBS symptoms.

Abnormal gut-brain interactions are common in irritable bowel syndrome (IBS), but the associations between neurophysiological measures and their relation to gastrointestinal (GI) symptoms are poorly understood. Our aim was to explore these relationships and define the most relevant neurophysiology measures for GI symptom severity in IBS. IBS patients underwent small intestinal motility (manometry; fasted and fed contraction frequency, phase III time) and secretion (transmural potential difference), rectal sensorimotor (barostat; sensory thresholds, tone response, compliance), autonomic nervous system (baroreceptor sensitivity and effectiveness), and colonic motor function (transit time) examinations. GI symptom severity (GSRS-IBS), and anxiety and depression (HAD) as a proxy measure of central nervous system (CNS) dysfunction, were assessed. In total 281 IBS patients (Rome II criteria) were included (74% females, median age 36 [interquartile range 28-50] years). Significant correlations between neurophysiology measures were stronger within, rather than between, different neurophysiological examinations. The strongest neurophysiology-symptom correlations occurred between a combination of CNS and visceral sensitivity parameters, and GSRS-IBS total score and pain domain (ρ = 0.40, p < 0.001, and ρ = 0.38, p < 0.001). Associations between GI symptoms in IBS and individual and combinations of neurophysiological factors occurred, primarily in CNS and visceral sensitivity measures, providing new insights into the clinical presentation of IBS.

Anxiety and depression in irritable bowel syndrome: Exploring the interaction with other symptoms and pathophysiology using multivariate analyses.

BACKGROUND: Anxiety or depression, in other words, psychological distress, are common comorbidities in patients with irritable bowel syndrome (IBS), but their interaction with pathophysiological factors and other symptoms are unclear. METHODS: Patients with IBS (Rome III criteria), thoroughly characterized regarding pathophysiology (colonic transit time, visceral sensitivity, and autonomic nervous system [ANS] function), symptom profile (IBS severity, somatic symptoms, gastrointestinal [GI]-specific anxiety and fatigue), and quality of life, were explored for differences regarding pathophysiology and symptoms between patients with and without reported psychological distress in univariate and multivariate analyses (Principal Component Analysis [PCA] with Hotelling's T2 and Orthogonal Partial Least Squares-Discriminant Analysis [OPLS-DA]). KEY RESULTS: When using Hospital Anxiety and Depression Scale score ≥8 as cut-off score, including both borderline and clinically significant cases, 345 (44.9%) out of 769 IBS patients reported anxiety, and 198 (25.7%) depression. In univariate analyses, patients reporting psychological distress demonstrated more severe GI and non-GI symptoms, fatigue, GI-specific anxiety and lower quality of life, and differences for some pathophysiological measures. IBS patients with and without reported psychological distress showed significant differences between the multivariate means in symptom reporting (PCA; both P < 0.001), and in pathophysiological measures in patients with and without anxiety (P = 0.018). Visceral hypersensitivity, altered ANS function, more severe GI-specific anxiety, fatigue, and higher somatic non-GI symptoms were the factors that most strongly separated patients with and without psychological distress (OPLS-DA). CONCLUSIONS AND INFERENCES: Reported anxiety and depression are common in IBS patients, and our study demonstrates that they are interwoven in the complex pathophysiological and clinical picture of IBS.