Prevalence and determinants of postprandial diarrhea in a tertiary care center.

BACKGROUND AND AIMS: Postprandial diarrhea (PPD) is commonly seen in patients with disorders of gut-brain interaction (DGBI), but the factors associated with it have not been well studied. In this study, we aim to study the burden, impact, and predictors of PPD using a clinical cohort of DGBI patients. METHODS: This study included patients with chronic diarrhea fulfilling ROME IV criteria for irritable bowel syndrome (IBS) or functional diarrhea (FDiarr). PPD was defined as patients reporting mushy/watery stools following meals ≥30% of the time in the last 3 months using a ROME IV question on PPD. Age, sex, and BMI, the severity of diarrhea, abdominal pain, depression, anxiety, somatization, and quality of life were assessed using validated measures. Person's chi-square test and Student's t-test were used to compare variables. A multiple linear regression model with backward elimination was done to determine predictors of PPD severity. KEY RESULTS: Of 213 eligible patients, more than three-fourth of patients (75.6%) had PPD. Women (79.0%, p = 0.037), patients with ROME IV diagnosis of IBS-D (90.5%, p = 0.002), and functional dyspepsia (83.2%, p = 0.014), and those with a history of cholecystectomy (CCY) (95.5%, p = 0.022) were more likely to report PPD. PPD patients experienced more severe abdominal pain, diarrhea, and decreased quality of life (QoL) but showed no significant difference in BMI, anxiety, depression, sleep, or somatization. In our regression model, female sex and history of CCY were independent predictors of PPD. CONCLUSIONS AND INFERENCES: PPD is frequently reported among chronic diarrhea patients and is associated with more severe GI symptoms and decreased QoL. Female sex and CCY predict PPD, while psychological factors do not.

Burden and Treatment of Chronic Upper GI Symptoms and Diagnoses: A Nationwide Study.

BACKGROUND & AIMS: Chronic gastrointestinal (GI) symptoms are a common reason for seeking medical care. We aim to determine the rates of ambulatory care use and to characterize demographics, work-up, and treatment (pharmacologic and nonpharmacologic) for patients with chronic upper GI symptoms and conditions in the United States. METHODS: Estimates of annual visits for the most common upper GI symptoms and diagnoses including gastroesophageal reflux disease, dyspepsia, nausea and vomiting, and gastroparesis were recorded from the 2007-2015 National Ambulatory Medical Care Surveys. Only chronic conditions, defined as >3 months, were included. We calculated the weighted proportion of ambulatory visits associated with pharmacologic, nonpharmacologic treatment (eg, diet, complementary and alternative medicine), or both. RESULTS: A total of 116,184,475 weighted ambulatory visits were identified between the years of 2007 and 2015 for adults (average of 12,909,386 annual visits) with chronic upper GI symptoms and diagnoses. Gastroesophageal reflux disease was the most common reason for an ambulatory visit (n = 11,200,193), followed by dyspepsia (n = 1,232,598), nausea and vomiting (n = 714,834), and gastroparesis (n = 140,312). Pharmacologic treatment was more common than nonpharmacologic treatment (44.7% vs 28.5%). A total of 37.6% of patients were not receiving treatment at the time of the visit. These treatment patterns did not significantly change over the time of our study. Upper endoscopies were the most ordered test, representing 7.5% of all investigated upper GI symptoms. CONCLUSIONS: Chronic upper GI symptoms and diagnoses account for a high number of annual health care visits, both in primary care and specialty care. Although there are several treatments, many of these patients are not on any treatments.

Optimizing the Management Algorithm for Adults With Functional Constipation Failing a Fiber/Laxative Trial in General Gastroenterology: Cost-Effectiveness and Cost-Minimization Analysis.

INTRODUCTION: Anorectal function testing is traditionally relegated to subspecialty centers. Yet, it is an office-based procedure that appears capable of triaging care for the many patients with Rome IV functional constipation that fail empiric over-the-counter therapy in general gastroenterology, as an alternative to empirical prescription drugs. We aimed to evaluate cost-effectiveness of routine anorectal function testing in this specific population. METHODS: We performed a cost-effectiveness analysis from the patient perspective and a cost-minimization analysis from the insurer perspective to compare 3 strategies: (i) empiric prescription drugs followed by pelvic floor physical therapy (PFPT) for drug failure, (ii) empiric PFPT followed by prescription drugs for PFPT failure, or (iii) care directed by up-front anorectal function testing. Model inputs were derived from systematic reviews of prospective clinical trials, national cost data sets, and observational cohort studies of the impact of chronic constipation on health outcomes, healthcare costs, and work productivity. RESULTS: The most cost-effective strategy was upfront anorectal function testing to triage patients to appropriate therapy, in which the subset of patients without anal hypocontractility on anorectal manometry and with a balloon expulsion time of at least 6.5 seconds would be referred to PFPT. In sensitivity analysis, empiric PFPT was more cost effective than empiric prescription drugs except for situations in which the primary goal of treatment was to increase bowel movement frequency. If adopted, gastroenterologists would refer ∼17 patients per year to PFPT, supporting feasibility. DISCUSSION: Anorectal function testing seems to be an emergent technology to optimize cost-effective outcomes, overcoming testing costs by phenotyping care.

How Would You Manage This Patient With Recurrent Diverticulitis? : Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

Acute diverticulitis, which refers to inflammation or infection, or both, of a colonic diverticulum, is a common medical condition that may occur repeatedly in some persons. It most often manifests with left-sided abdominal pain, which may be associated with low-grade fever and other gastrointestinal symptoms. Complications may include abscess, fistula formation, perforation, and bowel obstruction. The American College of Physicians recently published practice guidelines on the diagnosis and management of acute diverticulitis, the role of colonoscopy after resolution, and interventions to prevent recurrence of this condition. Among the recommendations were the use of abdominal computed tomography (CT) scanning in cases where there was diagnostic uncertainty, initial management of uncomplicated cases in the outpatient setting without antibiotics, referral for colonoscopy after an initial episode if not performed recently, and discussion of elective surgery to prevent recurrent disease in patients with complicated diverticulitis or frequent episodes of uncomplicated disease. Here, 2 gastroenterologists with expertise in acute diverticulitis debate CT scanning for diagnosis, antibiotics for treatment, colonoscopy to screen for underlying malignancy, and elective surgery to prevent recurrent disease.

Prevalence and Associated Factors of Bloating: Results From the Rome Foundation Global Epidemiology Study.

BACKGROUND & AIMS: Bloating is a common symptom in the general population and among disorders of gut-brain interaction, although its prevalence has not been well characterized. The aim of this study was to report the prevalence of bloating as a symptom in the worldwide population and to identify factors associated with this symptom in the general population. METHODS: Rome Foundation Global Epidemiology Study internet survey data were analyzed. After excluding respondents with potential organic causes of bowel symptoms, the current analysis included 51,425 individuals in 26 countries. Data included diet, medical history, quality of life, and Rome IV diagnostic questions. Presence of bloating was defined as experiencing bloating at least once per week for the last 3 months. Descriptive statistics estimated prevalence by country, region, and disorder of gut-brain interaction diagnosis. Logistic regression evaluated predictors of bloating. RESULTS: Nearly 18% of the global study population reported bloating (ranging from 11% in East Asia to 20% in Latin America). Prevalence decreased with age and women were approximately twice as likely as men to report bloating. More than one-half of respondents who reported weekly epigastric pain (71.39%), nausea (59.7%), or abdominal pain (61.69%) also reported bloating at least once per week. In logistic regression, the strongest associations were with abdominal pain (odds ratio, 2.90) and epigastric pain (odds ratio, 2.07). CONCLUSIONS: Bloating is common throughout the world. Nearly 18% of the general population experience bloating at least once per week. Reported bloating prevalence is lower in older age groups, most common in women, and strongly associated with abdominal pain.

What Is Unspecified Functional Bowel Disorder? A Commonly Seen, Rarely Recognized, and Poorly Understood Diagnosis.

INTRODUCTION: Unspecified functional bowel disorder (FBD-U) is a Rome IV diagnosis of exclusion and occurs when patients report bowel symptoms but do not meet the criteria for other functional bowel disorders (FBD; irritable bowel syndrome [IBS], functional constipation [FC], functional diarrhea [FDr], or functional bloating). Previous research suggests that FBD-U is as/more common than IBS. METHODS: One thousand five hundred one patients at a single-center tertiary care center completed an electronic survey. Study questionnaires included Rome IV Diagnostic Questionnaires, anxiety, depression, sleep, health care utilization, and bowel symptom severity measures. RESULTS: Eight hundred thirteen patients met Rome IV criteria for a FBD and 194 patients (13.1%) met criteria for FBD-U, representing the second most common FBD after IBS. Severity of abdominal pain, constipation, and diarrhea were lower in FBD-U compared with other FBD, whereas health care utilization was similar among the groups. Scores on measures of anxiety, depression, and sleep disturbances were similar in FBD-U compared with FC and FDr but were less severe than IBS. Between 25% and 50% of patients with FBD-U did not meet Rome IV criteria for other FBD due to timing of onset of the target symptom (e.g., constipation for FC, diarrhea for FDr, and abdominal pain for IBS). DISCUSSION: FBD-U, by Rome IV criteria, is highly prevalent in clinical settings. These patients are not represented in mechanistic studies or clinical trials for not having met Rome IV criteria for other FBD. Making future Rome criteria less stringent would minimize the number fulfilling criteria for FBD-U and maximize the true representation of FBD in clinical trials.

Emergency department burden of hyperemesis gravidarum in the United States from 2006 to 2014.

BACKGROUND: Hyperemesis gravidarum is the most severe form of nausea and vomiting of pregnancy, potentially affecting both maternal and pregnancy health. Hyperemesis gravidarum often results in emergency department visits, although the exact frequency and costs associated with these visits have not been well studied. OBJECTIVE: This study aimed to analyze the trends in hyperemesis gravidarum emergency department visits, inpatient admissions, and the associated costs between 2006 and 2014. STUDY DESIGN: Patients were identified from the 2006 and 2014 Nationwide Emergency Department Sample database files using International Classification of Diseases, Ninth Revision diagnosis codes. Patients with a primary diagnosis of hyperemesis gravidarum, nausea and vomiting of pregnancy, and all nondelivery pregnancy-related diagnoses (all antepartum visits) were identified. All groups were analyzed; trends in demographics, number of emergency department visits, and visit costs were compared. Costs were inflation-adjusted to 2021 US dollars. RESULTS: Emergency department visits for hyperemesis gravidarum increased by 28% from 2006 to 2014; however, the proportion of those who were subsequently admitted to the hospital decreased. The average cost of an emergency department visit for hyperemesis gravidarum increased by 65% ($2156 to $3549), as opposed to an increase of 60% for all antepartum visits ($2218 to $3543). The aggregate cost for all hyperemesis gravidarum visits increased by 110% ($383,681,346 to $806,696,513) from 2006 to 2014, which was similar to the increase observed for all antepartum emergency department visits. CONCLUSION: From 2006 to 2014, emergency department visits for hyperemesis gravidarum increased by 28%, with associated costs increasing by 110%, whereas the number of admissions from the emergency department for hyperemesis gravidarum decreased by 42%.

Up-Front Endoscopy Maximizes Cost-Effectiveness and Cost-Satisfaction in Uninvestigated Dyspepsia.

BACKGROUND & AIMS: Practice guidelines promote a routine noninvasive, non-endoscopic initial approach to investigating dyspepsia without alarm features in young patients, yet many patients undergo prompt upper endoscopy. We aimed to assess tradeoffs among costs, patient satisfaction, and clinical outcomes to inform discrepancy between guidelines and practice. METHODS: We constructed a decision-analytic model and performed cost-effectiveness/cost-satisfaction analysis over a 1-year time horizon on patients with uninvestigated dyspepsia without alarm features referred to gastroenterology. A RAND/UCLA expert panel informed model design. Four competing diagnostic/management strategies were evaluated: prompt endoscopy, testing for Helicobacter pylori and eradicating if present (test-and-treat), testing for H pylori and performing endoscopy if present (test-and-scope), and empiric acid suppression. Outcomes were derived from systematic reviews of clinical trials. Costs were informed by prospective observational cohort studies and national commercial/federal cost databases. Health gains were represented using quality-adjusted life years. RESULTS: From the patient perspective, costs and outcomes were similar for all strategies (maximum out-of-pocket difference of $30 and <0.01 quality-adjusted life years gained/year regardless of strategy). Prompt endoscopy maximized cost-satisfaction and health system reimbursement. Test-and-scope maximized cost-effectiveness from insurer and patient perspectives. Results remained robust on multiple one-way sensitivity analyses on model inputs and across most willingness-to-pay thresholds. CONCLUSIONS: Noninvasive management strategies appear to result in inferior cost-effectiveness and patient satisfaction outcomes compared with strategies promoting up-front endoscopy. Therefore, additional studies are needed to evaluate the drivers of patient satisfaction to facilitate inclusion in value-based healthcare transformation efforts.

Gastroenterologist Primer: Endometriosis for Gastroenterologists.

BACKGROUND AND AIM: A comprehensive understanding of endometriosis and its common gastrointestinal presentations are critical for gastroenterologists to ensure appropriate and timely screening and diagnosis. Endometriosis is a common inflammatory disease that frequently presents with gastrointestinal symptoms overlapping with irritable bowel syndrome (IBS) and other gastrointestinal disorders. Many endometriosis patients first present to a gastroenterologist or generalist, which may prolong the time to diagnosis and appropriate care. METHOD AND RESULTS: This review describes the current literature on endometriosis presentation, overlap with gastrointestinal conditions, and standard diagnostic and treatment options for gastroenterologists to consider. For appropriate and swift treatment, gastroenterologists must consider an endometriosis diagnosis in females of menstruating age presenting with pain, bloating, altered stools, and non-gastrointestinal symptoms and refer patients for further evaluation.

Speedometer for withdrawal time monitoring during colonoscopy: a clinical implementation trial.

OBJECTIVES: Meticulous inspection of the mucosa during colonoscopy, represents a lengthier withdrawal time, but has been shown to increase adenoma detection rate (ADR). We investigated if artificial intelligence-aided speed monitoring can improve suboptimal withdrawal time. METHODS: We evaluated the implementation of a computer-aided speed monitoring device during colonoscopy at a large academic endoscopy center. After informed consent, patients ≥18 years undergoing colonoscopy between 5 March and 29 April 2021 were examined without the use of the speedometer, and with the speedometer between 29 April and 30 June 2021. All colonoscopies were recorded, and withdrawal time was assessed based on the recordings in a blinded fashion. We compared mean withdrawal time, percentage of withdrawal time ≥6 min, and ADR with and without the speedometer. RESULTS: One hundred sixty-six patients in each group were eligible for analyses. Mean withdrawal time was 9 min and 6.6 s (95% CI: 8 min and 34.8 s to 9 min and 39 s) without the use of the speedometer, and 9 min and 9 s (95% CI: 8 min and 45 s to 9 min and 33.6 s) with the speedometer; difference 2.3 s (95% CI: -42.3-37.7, p = 0.91). The ADRs were 45.2% (95% CI: 37.6-52.8) without the speedometer as compared to 45.8% (95% CI: 38.2-53.4) with the speedometer (p = 0.91). The proportion of colonoscopies with withdrawal time ≥6 min without the speedometer was 85.5% (95% CI: 80.2-90.9) versus 86.7% (95% CI: 81.6-91.9) with the speedometer (p = 0.75). CONCLUSIONS: Use of speed monitoring during withdrawal did not increase withdrawal time or ADR in colonoscopy. CLINICALTRIALS.GOV IDENTIFIER: NCT04710251.

Examining the Nocebo Effect in Trials of Neuromodulators for Use in Disorders of Gut-Brain Interaction.

INTRODUCTION: Nocebo effects are believed to influence the rate of reported adverse events (AE) and subject withdrawal in both the treatment and placebo groups of randomized clinical trials (RCT). Neuromodulators are commonly prescribed to treat disorders of gut-brain interaction (DGBI), but adherence to these medications is often limited by side effects such as headache, dry mouth, fatigue, and altered bowel habits. We performed a systematic review and meta-analysis to assess the proportion and risk difference of patients who experienced side effects leading to withdrawal in the placebo arm vs the treatment arm of RCT of neuromodulators for DGBI. We also sought to estimate the risk of developing any AE in the placebo arm of these studies and the rate of specific individual AEs. METHODS: We searched MEDLINE, Embase, Web of Science Core Collection, and the Cochrane Central Register of Controlled Trials Searches to identify RCT that included terms for DGBI and for commonly prescribed neuromodulators. We calculated pooled proportions of patients experiencing an AE leading to withdrawal in the active treatment group vs the placebo group with 95% confidence intervals (CI), the pooled proportions of patients experiencing any AE, the pooled proportions of patients experiencing specific AE such as dizziness and headache, the pooled proportions of patients experiencing severe AE, and corresponding pooled risk differences with 95% CI. RESULTS: There were 30 RCT included representing 2,284 patients with DGBI. Twenty-seven RCT reported data on AE leading to withdrawal. The pooled proportion of total patients with AE leading to withdrawal in the placebo group was 4% (95% CI 0.02-0.04). The pooled proportion of patients with AE leading to withdrawal who received neuromodulators was 9% (95% CI 0.06-0.13). In the 12 studies reporting data on patients experiencing at least 1 AE, the pooled proportion of patients experiencing any AE in the placebo group was 18% (95% CI 0.08-0.30), compared with 43% (95% CI 0.24-0.63) in the neuromodulator group. Thus, approximately 44% of the rate of withdrawal (0.04/0.09) and 42% of the rate reporting any side effects (0.18/0.43) in the neuromodulator group may be attributed to nocebo effects in the right context. Subgroup analysis by sex, medication class, risk of bias, and specific DGBI revealed differing withdrawal rates. There was no statistically significant difference in patients experiencing individual AE of dizziness, headache, or diarrhea. Rates of dry mouth, fatigue, and constipation were higher in treatment groups compared with those in placebo groups. DISCUSSION: Patients with DGBI in RCT randomized to placebo groups frequently experience AE and AE that lead to withdrawal consistent with a strong nocebo effect. Nonspecific AE such as dizziness, headaches, and diarrhea occurred similarly in patients receiving placebo compared with those receiving neuromodulators.

Clinical Characteristics of Patients Presenting With Bloating as a Predominant Symptom.

BACKGROUND: The estimated prevalence of bloating is 15 to 30% in the adult US population and is even higher in patients with disorders of gut-brain interaction (DGBIs). Despite this frequency, there is little research into patients who endorse bloating as a predominant symptom. The aim of this study was to better characterize these patients. MATERIALS AND METHODS: New patients with DGBIs were asked to identify their 3 most predominant symptoms over the preceding 3 months; those who reported bloating were classified as "bloating predominant." Rome IV and symptom-specific questionnaires were administered to assess for the frequency of DGBIs and other predominant symptoms in this patient population. Using univariable and multivariable modeling, we analyzed the associations between bloating predominance, DGBI subtype, and clinical characteristics. RESULTS: Of the 586 patients surveyed, 242 (41%) reported predominant bloating. Bloating-predominant patients were more likely to be female, younger, and meet the criteria for IBS-mixed (IBS-M), functional constipation, and functional dyspepsia compared with nonbloating-predominant patients. Bloating-predominant patients were also more likely to endorse concurrently predominant constipation, incomplete evacuation, abdominal pain, belching, and/or nausea. On multivariable logistic regression, constipation and abdominal pain severity were positively associated, although depression was negatively associated with predominant bloating. CONCLUSIONS: Patients with predominant bloating are more likely to have constipation-related symptoms than diarrhea-related symptoms. They are also more likely to have more severe abdominal pain than patients without predominant bloating. These findings help characterize patients with bloating as a predominant symptom and suggest that diagnosing and treating constipation should be considered as first-line treatment.

Dysphagia Worsens With Increasing Ineffective Swallows Among Patients With Ineffective Esophageal Motility.

INTRODUCTION: Ineffective esophageal motility (IEM) is the most common motility disorder identified on esophageal high-resolution manometry (HRM), but patients with this finding may be asymptomatic. Therefore, we aimed to identify specific HRM findings predictive of symptoms in IEM. METHODS: Adult patients (≥18 y) who underwent HRM between March 2016 and July 2019 were retrospectively evaluated and reclassified according to Chicago Classification 4.0 (CC4.0). Demographic information, HRM parameters, and gastroesophageal reflux disease Health-Related Quality of Life Questionnaire responses were captured among those with normal manometry or IEM. We evaluated the association between heartburn, regurgitation, and dysphagia, with respect to HRM findings including ineffective swallows. RESULTS: Of 379 patients, 243 (64.1%) had a normal manometry, 136 (35.9%) were on IEM spectrum, and 73 (19.3%) had conclusive IEM by CC4.0. Mean dysphagia scores were significantly higher in those with conclusive IEM compared with those with normal HRM (2.00 vs. 1.36, P =0.002), as was the percentage of individuals reporting dysphagia affecting daily activities (21.9% vs. 11.4%, P =0.02). Heartburn and regurgitation symptoms did not differ between groups. In a multivariable model of IEM patients, the percentage of ineffective swallows independently predicted a higher dysphagia burden (ß regression coefficient: 0.032, P =0.04). CONCLUSIONS: Applying the CC4.0 definition for conclusive IEM identifies a group of patients with worse dysphagia symptoms. Within this group, the percentage of ineffective swallows was an independent predictor of dysphagia severity. These findings may help practitioners and patients contextualize the heterogeneous diagnosis of IEM.

Systematic review and meta-analysis: efficacy of peppermint oil in irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is one of the most common disorders of gut-brain interaction, with a complex pathophysiology. Antispasmodics are prescribed as first-line therapy because of their action on gut dysmotility. In this regard, peppermint oil also has antispasmodic properties. AIM: To update our previous meta-analysis to assess efficacy and safety of peppermint oil, particularly as recent studies have cast doubt on its role in the treatment of IBS METHODS: We searched the medical literature up to 2nd April 2022 to identify randomised controlled trials (RCTs) of peppermint oil in IBS. Efficacy and safety were judged using dichotomous assessments of effect on global IBS symptoms or abdominal pain, and occurrence of any adverse event or of gastro-oesophageal reflux. Data were pooled using a random effects model, with efficacy and safety reported as pooled relative risks (RRs) with 95% confidence intervals (CIs). RESULTS: We identified 10 eligible RCTs (1030 patients). Peppermint oil was more efficacious than placebo for global IBS symptoms (RR of not improving = 0.65; 95% CI 0.43-0.98, number needed to treat [NNT] = 4; 95% CI 2.5-71), and abdominal pain (RR of abdominal pain not improving = 0.76; 95% CI 0.62-0.93, NNT = 7; 95% CI 4-24). Adverse event rates were significantly higher with peppermint oil (RR of any adverse event = 1.57; 95% CI 1.04-2.37). CONCLUSIONS: Peppermint oil was superior to placebo for the treatment of IBS, but adverse events were more frequent, and quality of evidence was very low. Adequately powered RCTs of peppermint oil as first-line treatment for IBS are needed.

Genotypes of Pain and Analgesia in a Randomized Trial of Irritable Bowel Syndrome.

Background: Irritable bowel syndrome (IBS) is a highly prevalent chronic pain disorder with multiple underlying mechanisms and few treatments that have been demonstrated to be effective in placebo controlled trials. One potential reason may be the use of composite outcomes, such as the IBS Symptom Severity Scale (IBS-SSS) which includes descriptive items related to pain frequency and pain intensity as well as bowel dysfunction and bloating. We investigated if different features of IBS pain have distinct genetic associations and if these may be moderated by sex hormones. Participants and Setting: Adult outpatients with moderately severe IBS (>175 on IBS-SSS) enrolled in a clinical trial reported IBS-SSS at baseline and after 6 weeks of therapy. Methods: Fixed effects modeling was used to test the effect of COMT rs4680 genotype to change in pain severity (rated 0-100) and pain frequency (defined as number of days with pain in the past 10 days) from baseline to week 6 with IBS treatment. Parallel exploratory genome-wide association studies (GWAS) were also performed to identify single nucleotide polymorphisms (SNPs) associated with change in pain severity or pain frequency across all participants. Results: A total of 212 participants (74% female) were included. The COMT rs4680 met allele was associated with decreased pain severity over the course of the trial in gene dosage models [beta(SE) -5.9 (2.6), P = 0.028]. Exploratory GWAS for change in pain frequency identified 5 SNPs in close proximity on chromosome 18 near L3MBTL4 which reached genome-wide significance (all P < 5.0E-8). This effect was not mediated by changing estradiol levels. There was also a region of chromosome 7 with 24 SNPs of genome-wide suggestive significance for change in pain severity (all P < 1.0E-5). Conclusions: Previously reported association between COMT rs4680 genotype and treatment response as measured by IBS-SSS is related to pain severity, but not pain frequency. We also identified new candidate genes associated with changes in IBS pain severity (SNX13) and pain frequency (L3MBTL4) in response to treatment. Further studies are needed to understand these associations and genetic determinants of different components of IBS-SSS. ClinicalTrials.gov, Identifier: NCT0280224.

Psychological Predictors of Response to Open-Label Versus Double-Blind Placebo in a Randomized Controlled Trial in Irritable Bowel Syndrome.

OBJECTIVE: There is growing evidence that open-label placebo (OLP) may be an efficacious treatment of chronic and functional conditions. However, patient-level predictors of response to OLP have not been clearly identified. The aim of this study is to evaluate the psychological predictors of response to OLP and to compare this to double-blind placebo (DBP) and no-pill control (NPC). METHODS: This study is a secondary analysis of data collected in a 6-week randomized controlled trial evaluating placebo effects in irritable bowel syndrome (IBS). The primary outcome was change in IBS severity. Hierarchical linear regression identified predictors of placebo response in general and compared them between those randomized to OLP, DBP, and NPC. Predictor variables included personality traits, generalized anxiety, depression, visceral sensitivity (a measure of symptom-specific anxiety), and pain catastrophizing. RESULTS: A total of 210 participants (mean age = 42.3 years, 73.3% female) were included. Regression models revealed that visceral sensitivity was a predictor of response to OLP and NPC but not DBP. Interestingly, the effects were opposite, with high visceral sensitivity predicting less improvement in NPC and more improvement in OLP. Pain catastrophizing was a negative predictor of response to OLP (i.e., high pain catastrophizing was associated with less improvement in OLP). Neither visceral sensitivity nor pain catastrophizing played a significant role for response to DBP. CONCLUSIONS: IBS participants who score low on the Pain Catastrophizing Scale but high on the Visceral Sensitivity Index seem to benefit particularly from OLP. Our study suggests that different psychological mechanisms may be involved in DBP and OLP interventions.

Are They Side Effects? Extraintestinal Symptoms Reported During Clinical Trials of Irritable Bowel Syndrome May Be More Severe at Baseline.

BACKGROUND & AIMS: Many of the reported adverse events in clinical trials of irritable bowel syndrome are extraintestinal symptoms, which typically are assessed by open-ended questions during the trial and not at baseline. This may lead to misattribution of some pre-existing symptoms as side effects to the treatment. METHODS: The current study analyzed data from a 6-week clinical trial of irritable bowel syndrome. Participants were randomized to receive double-blind peppermint oil, double-blind placebo, or treatment as usual. Extraintestinal symptoms were assessed at baseline and at the end of the study. RESULTS: This analysis included 173 participants (30 received double-blind peppermint oil, 72 received treatment as usual, and 71 received double-blind placebo). At baseline, each group reported approximately 5 extraintestinal symptoms per participant. The number of symptoms per participant decreased to an average of 3 by the end-of-study visit, and this change was statistically significant in all groups (P < .001 for each group). When evaluating individual extraintestinal symptoms, the majority of participants did not report new/worse symptoms. In fact, between the baseline assessment and the final assessment, the average symptom severity decreased significantly in all 3 groups (P < .001). CONCLUSIONS: Our study suggests that participants with irritable bowel syndrome often experience extraintestinal symptoms at baseline and that these symptoms generally improve in severity over the course of a clinical trial, regardless of the treatment arm. Systematic assessment of extraintestinal symptoms at the beginning of a clinical trial is necessary to determine more definitively whether these symptoms may be considered an adverse event attributable to a study medication.