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.

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%.

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.

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.

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.

Patients' experiences treated with open-label placebo versus double-blind placebo: a mixed methods qualitative study.

BACKGROUND: There is increasing evidence suggesting that open-label placebo (OLP) is an effective treatment for several medical conditions defined by self-report. However, little is known about patients' experiences with OLP, and no studies have directly compared patients' experiences in double-blind placebo (DBP) conditions. METHODS: This study was nested in a large randomized-controlled trial comparing the effects of OLP and DBP treatments in individuals with irritable bowel syndrome (IBS). We randomly selected 33 participants for interviews concerning their experiences in the parent trial. The data were qualitatively analyzed using an iterative immersion/crystallization approach. We then compared the qualitative interview data to the quantitative IBS severity data assessed during the parent trial, using a mixed methods approach. RESULTS: Two prominent interview themes were identified: (1) the participants' feelings about their treatment allocation and (2) their reflections about the treatment. Both OLP and DBP participants mentioned hope and curiosity as major feelings driving them to engage with their treatment. However, while DBP participants tended to be more enthusiastic about their allocation, OLP participants were more ambivalent. Furthermore, OLP participants reflected more on their treatment, often involving noticeable cognitive and emotional processes of self-reflection. They offered a variety of explanations for their symptom improvement and were significantly less likely to attribute it to the treatment itself than DBP participants (Χ2 [3] = 8.28; p = .041). Similarly, the participants' retrospective narratives of symptom improvement were significantly correlated with their corresponding quantitative IBS severity scores only in DBP (p's ≤ .006) but not in OLP (p's ≥ .637). CONCLUSION: OLP and DBP participants share feelings of hope, uncertainty and curiosity but differ in the extent of conscious reflection. The counter-intuitive OLP prompts more self-examination, ambivalent feelings and active engagement compared to DBP. At the same time, OLP participants are more reluctant to attribute symptom improvement to their treatment. Our findings substantially add to the emerging picture of factors that distinguish OLP and DBP and their potential mechanisms.

Effect of antibiotic pretreatment on bacterial engraftment after Fecal Microbiota Transplant (FMT) in IBS-D.

Fecal microbiota transplantation (FMT) is an attractive strategy to correct microbial dysbiosis in diarrhea-predominant irritable bowel syndrome (IBS-D). Although the mechanism of FMT is thought to be bacterial engraftment, the best approach to achieve engraftment after FMT in IBS-D (and other diseases) is not clear. We evaluated the effect of FMT (with or without pretreatment with antibiotics) on gut microbiome and symptoms in patients with IBS-D. In this randomized, placebo-controlled, single-center study, 44 patients with IBS-D with a least moderate severity (IBS severity scoring system, i.e., IBS-SSS, ≥175) were randomly assigned to one of four groups: single-dose oral FMT alone, single-dose oral FMT following a 7-day pretreatment course of Ciprofloxacin and Metronidazole (CM-FMT) or Rifaximin (R-FMT), or Placebo FMT. Primary endpoint was engraftment post-FMT and secondary endpoints were changes in IBS-SSS, and IBS-quality of life (IBS-QOL) at week 10. Median engraftment was significantly different among the three FMT groups (P = .013). Engraftment post-FMT was significantly higher in the FMT alone arm (15.5%) compared to that in R-FMT group (5%, P = .04) and CM-FMT group (2.4%, P = .002). The mean change in IBS-SSS and IBS-QOL from baseline were not significantly different among the four groups or between the three FMT groups combined vs. placebo at week 10. In summary, antibiotic pretreatment significantly reduced bacterial engraftment after FMT in patients with IBS-D.

Improvement in constipation and diarrhea is associated with improved abdominal pain in patients with functional bowel disorders.

BACKGROUND: Abdominal pain is a bothersome and lifestyle limiting symptom in patients with functional bowel disorders. It is associated with decreased quality of life in affected individuals, as well as significant annual healthcare expenditure. Knowledge of specific factors that predict improvement in abdominal pain in those with functional bowel disorders is thus far limited. METHODS: Consecutive patients presenting for outpatient care at a major academic medical center between October 2017 and March 2020 completed an electronic symptom survey prior to initial clinic visit, and again after 3 months. The Rome IV questionnaires for functional dyspepsia, irritable bowel syndrome, functional constipation, and functional diarrhea were all included. Additionally, all subjects completed the Patient Reported Outcomes Measurement Information System Anxiety, Depression, and sleep disturbance questionnaires. Patients with a diagnosis of a Rome IV functional gastrointestinal disorder without any organic cause for symptoms were identified based on both chart review as well as survey response data. Univariable and multivariable analysis was used to assess predictors of improved abdominal pain after 3 months. KEY RESULTS: 180 patients with a mean age of 45.3 years were included in the final analysis. 78.3% of patients were female, and 77.2% met Rome IV criteria for irritable bowel syndrome. On multivariable analysis, improvement in constipation and diarrhea were both independent predictors of improved abdominal pain after 3 months. CONCLUSIONS AND INFERENCES: Improvement in constipation and diarrhea both predicted improvement in abdominal pain, suggesting that addressing these factors is central to the management of abdominal pain in functional gastrointestinal disorders.

Belching: Pathogenesis, Clinical Characteristics, and Treatment Strategies.

PURPOSE: Belching is a common condition that frequently overlaps with other functional gastrointestinal disorders. While not associated with any increase in mortality, it is associated with impaired health-related quality of life. Management is challenging, as there are no pharmacologic therapies specifically targeted towards this disorder. This review covers pathogenesis, prevalence, and treatments for this condition, with specific emphasis on the evolving role of behavioral treatments in management. KEY FINDINGS: The diagnosis of gastric and supragastric belching can usually be made clinically, without the need for invasive testing. If necessary, multichannel intraluminal impedance and pH testing can provide a more definitive diagnosis and can also be used to estimate the frequency of gastric and supragastric belching episodes, which each have a distinct appearance on impedance tracing. Belching disorders are commonly associated with gastroesophageal reflux disease and functional disorders of the gastrointestinal tract. Supragastric belching is also associated with behavioral disorders like anxiety and obsessive-compulsive disorder. Speech therapy, cognitive-behavioral therapy, and diaphragmatic breathing are all interventions that have recently shown promise in the management of this challenging disorder.

Symptom severity and clinical characteristics of patients with bloating.

BACKGROUND: Abdominal bloating is common in functional gastrointestinal disorders (FGID). To better characterize this patient population, we evaluated clinical and psychological characteristics of bloating and analyzed their differences by bloating severity. METHODS: Patients with FGIDs evaluated at a single academic outpatient referral gastroenterology clinic were surveyed. Bloating severity was classified as minimal, moderate or severe. Symptom-specific questionnaires were used to evaluate bowel habits, abdominal bloating, depression, anxiety, somatization and sleep disturbance. Associations between bloating severity, clinical characteristics and FGID subtypes were analyzed in univariate and multivariate modeling. KEY RESULTS: Of 612 FGID patients included (78% female, mean age of 44 ± 16.5 years), bloating was reported as minimal in 231(37.8%), moderate in 217(35.4%), or severe in 164(26.8%). Patients with severe bloating were more likely to be female, younger, and have co-existing functional dyspepsia than those with minimal bloating (p < 0.05). Bloating severity and severity of abdominal distension were significantly correlated (p < 0.05). On multivariable regression, patients who met criteria for functional constipation and functional dyspepsia had 80% and 125% higher odds, respectively, of severe bloating compared to minimal to moderate bloating. Younger age, abdominal pain and constipation severity, and somatization scores were also independently associated with severity of bloating. CONCLUSIONS & INFERENCES: Severe bloating is associated with younger age, and with more severe abdominal pain, constipation, and somatization. Patients who met criteria for functional constipation and functional dyspepsia are more likely to experience severe bloating.

Clinical and Psychological Factors Predict Outcome in Patients With Functional Dyspepsia: A Prospective Study.

BACKGROUND & AIMS: Symptoms of functional dyspepsia (FD) fluctuate over time but there are limited data on the impact of factors on change in dyspepsia symptom severity over time. We aimed to evaluate the demographic, clinical, and psychological factors associated with change in dyspepsia symptom severity. METHODS: Consecutive patients with FD presenting to a tertiary care center completed questionnaires assessing clinical and psychological symptoms at the time of the initial visit (baseline) and 3- to 6-month follow-up evaluations. FD and irritable bowel syndrome (IBS) were diagnosed using Rome IV criteria. FD severity was measured using patient assessment of gastrointestinal symptom severity. Patient-reported outcome measures information scales were used to assess the severity of anxiety, depression, and sleep disturbance. RESULTS: Of 128 FD patients, 64 (50%) also met Rome IV criteria for IBS. In the final multivariable model, lower baseline sleep disturbance, improvement in anxiety scores, absence of IBS, and a lower number of medications taken for gastrointestinal symptoms were associated with improvement in dyspepsia scores (P < .05 for all). Conversely, higher baseline dyspepsia severity was associated with greater improvement in dyspepsia severity at follow-up evaluation (P < .001). CONCLUSIONS: Improvement in FD symptom severity over 3 to 6 months was associated with improvement of anxiety, lower sleep disturbance at baseline, absence of IBS, and higher baseline dyspepsia severity.

Improving Medication Tolerance: A Pilot Study in Disorders of Gut-brain Interaction Treated With Tricyclic Antidepressants.

OBJECTIVES: Tricyclic antidepressants (TCAs) are commonly used to treat disorders of gut-brain interaction (DGBI). However, these medications are often associated with side effects that lead to early treatment discontinuation. Research in other chronic medical conditions suggests that many TCA side effects may be caused by nocebo (negative placebo) effects. The current study tests a brief, verbal intervention aimed at improving tolerance of TCAs in DGBI by providing education about nocebo effects. MATERIALS AND METHODS: This pilot randomized controlled trial was performed in a tertiary care gastroenterology clinic. Participants with DGBI were randomized "standard information," describing the benefits and risks of TCAs, or "augmented information," which included an additional <30-second education about nocebo effects. Two weeks after their visit, participants were emailed a survey evaluating the number and bothersomeness of side effects, adequate relief, global improvement, and treatment satisfaction. RESULTS: Thirty-one patients were randomized and 22 responded to the survey. The average age was 40% and 59% were women. Although not statistically significant, the augmented group attributed nominally fewer symptoms to TCAs than the standard group, with a medium effect size (1.5 vs. 4.2, effect size d=0.56, P=0.212) and reported being significantly less bothered by those symptoms (13.4 vs. 38.1, P=0.037). A nominally larger percentage of the augmented group reported adequate relief of symptoms after 2 weeks of treatment compared with the standard group (55% vs. 27%, respectively). CONCLUSIONS: This pilot study demonstrates that a brief (≈30 s) clinical intervention addressing nocebo effects may improve tolerance of TCAs. These findings provide support for future, fully powered studies to evaluate the impact of framing on clinical outcomes, especially in chronic conditions.

Peppermint Oil Treatment for Irritable Bowel Syndrome: A Randomized Placebo-Controlled Trial.

INTRODUCTION: Peppermint oil is often used to treat irritable bowel syndrome (IBS); however, the overall quality of previous studies is low, and findings have been heterogeneous. This study aimed to compare the effects of peppermint oil vs placebo in relieving IBS symptoms. METHODS: In a 6-week, randomized, double-blind, placebo-controlled trial at a single academic center in the United States, individuals diagnosed with IBS (Rome IV criteria), with moderate to severe symptoms based on the IBS Severity Scoring System (IBS-SSS score ≥175), were randomized to enteric-coated peppermint oil 180 mg 3 times daily vs placebo in a 1:2 ratio. The primary outcome was mean change in IBS-SSS scores from baseline to 6-week endpoint. RESULTS: A modified intent-to-treat analysis revealed that there were substantial mean improvements from baseline to 6-week endpoint in the main outcome measure (IBS-SSS) for both peppermint oil (90.8, SD = 75.3) and placebo (100.3, SD = 99.6). Although the peppermint oil group reported numerically lower improvement than the placebo group, the effect size was small (d = -0.11), and the difference between the groups was not statistically significant (P = 0.97). Similarly, both groups reported substantial improvements on the secondary endpoints; but again, there were no statistically significant differences between the groups on any of the secondary measures. Sensitivity analyses using multiple imputation to replace missing data produced similar results and revealed no significant differences between peppermint oil and placebo on any outcome measure. DISCUSSION: Peppermint oil and placebo both showed clinically meaningful improvement in IBS symptoms. However, there were no significant differences between the groups. Further large, rigorous trials are needed to evaluate the role of peppermint oil for the treatment of IBS.

Abdominal Pain and Depression, Not Bowel Habits, Predict Health Care Utilization in Patients With Functional Bowel Disorders.

INTRODUCTION: Patients with disorders of gut-brain interaction (DGBIs) are high users of health care. Past studies exploring predictors of utilization have lacked patient-level clinical data. The aim of the current study is to identify demographic, clinical, and psychological predictors of health care utilization in patients with irritable bowel syndrome (IBS), functional constipation (FC), and functional diarrhea (FDr). METHODS: Consecutive new patients diagnosed with IBS, FC, and FDr (using Rome IV criteria) completed questionnaires assessing health care utilization as well as clinical and psychological symptoms. Health care utilization was assessed using a 13-item measure inquiring about the previous 6 months. Patient-Reported Outcome Measures Information System (PROMIS) was used to assess severity of abdominal pain, constipation, diarrhea, anxiety, depression, and sleep disturbance. RESULTS: Of the 507 patients diagnosed with IBS, FC, or FDr, 434 completed the health care utilization questionnaire (mean age of 44 years, 79.5% female, and 73.5% IBS). In the final multivariable models, more severe abdominal pain and higher depression scores were significantly associated with increased utilization of (i) total outpatient visits, (ii) outpatient visits for gastrointestinal (GI) symptoms, and (iii) number of medications for GI symptoms. More severe abdominal pain was also significantly predictive of GI-related emergency department visits. Altered bowel habits were not consistent predictors of health care utilization. DISCUSSION: Severity of abdominal pain and depressive symptoms, but not bowel habits, is a primary driver of increased care-seeking behavior in patients with IBS, FC, and FDr.

Anorectal manometry to diagnose dyssynergic defecation: Systematic review and meta-analysis of diagnostic test accuracy.

BACKGROUND: Chronic constipation is a common condition, and dyssynergic defecation underlies up to 40% of cases. Anorectal manometry is recommended to assess for dyssynergic defecation among chronically constipated patients but remains poorly standardized. We aimed to evaluate the diagnostic accuracy of anorectal manometry and determine optimal testing parameters. METHODS: We performed a systematic review with meta-analysis of diagnostic test accuracy including cohort studies of chronically constipated patients and case-control studies of patients with dyssynergic defecation or healthy controls. Meta-analysis was performed to determine summary sensitivity, specificity, and area under the curve (AUC) with 95% confidence intervals (CI). KEY RESULTS: A total of 15 studies comprising 2140 patients were included. Including all studies (estimating optimal diagnostic accuracy), the AUC was 0.78 [95% CI 0.72-0.82], summary sensitivity was 79% [61%-90%], and summary specificity was 64% [44%-79%] to diagnose dyssynergic defecation. In cohort studies only (estimating real-world diagnostic accuracy), the AUC was 0.72 [0.66-0.77], summary sensitivity was 86% [64%-95%], and summary specificity was 49% [30%-68%]. Employing three consecutive simulated defecation attempts improved sensitivity to 94%. A fourth simulated defecation maneuver with air insufflation may improve accuracy. Measuring anorectal pressures to identify complex dyssynergic patterns did not improve real-world diagnostic accuracy estimates over anal pressure measurement alone. Choice of manometry system did not impact diagnostic accuracy. CONCLUSIONS & INFERENCES: Following the current iteration of the London consensus protocol (three simulated defecation attempts measuring anal relaxation), the role of anorectal manometry in evaluating dyssynergic defecation appears limited. Future iterations of this protocol may improve diagnostic accuracy.