Lacy, Brian E.

ABSTRACT Background Gastric emptying scintigraphy (GES) is considered the standard for differentiating gastroparesis from functional dyspepsia and other foregut disorders characterized by nausea and vomiting but provides only a brief physiologic snapshot that may not accurately reflect daily function. We utilized a non‐invasive wireless patch system (WPS) to characterize multiday gastric myoelectrical activity, evaluate its relationship with GES, and assess changes following a therapeutic intervention. Methods Adults referred for GES for symptoms thought to represent gastroparesis were enrolled in a prospective study. Patients wore a WPS for up to 6 days, starting on the day of scintigraphy. Gastric myoelectrical activity was analyzed and categorized into relatively weak, relatively moderate, and relatively strong activity phenotypes. A subset of patients underwent repeat monitoring following individualized therapeutic interventions (e.g., anti‐emetics, proton pump inhibitors, lifestyle changes). Results Forty‐eight patients (mean age 44; 79% female) completed the study. GES identified delayed gastric emptying in 18%, rapid in 22%, and normal in 60% of subjects. During the 4‐h concurrent GES window, gastric activity in patients with delayed emptying was lower, but this difference did not reach statistical significance ( p = 0.08). When compared to the full multiday recording period, GES results showed no correlation with the myoelectric readings. Significant day‐to‐day variability was observed, both random and systemic. In the latter category, a “Test‐Day” dip was observed with gastric activity lowest on Day 1 (GES test day) and increasing significantly on subsequent days, stabilizing by Day 4 ( p < 0.001). Healthy control subjects recorded during normal daily routines showed no such day‐to‐day variation. In the retesting cohort, anti‐emetics produced robust increases in gastric amplitude, whereas PPIs showed minimal impact. Conclusions The WPS effectively captures distinct gastric phenotypes and quantifies physiologic responses to therapy in both gastric and intestinal regions, demonstrating its clinical utility as a robust tool for evaluating and managing foregut symptoms in real‐world settings. Importantly, the multiday WPS highlights significant day‐to‐day physiologic variability in gastric activity that extends beyond the single‐day GES ‘snapshot’.

ABSTRACT Background Data on the global prevalence of alarm features in the general population and among individuals with disorders of gut–brain interaction (DGBI) are limited. Methods We analysed data from the Rome Foundation Global Epidemiology Study to estimate the prevalence of fourteen self‐reported alarm features in the global population and among individuals with Rome IV defined DGBI, including 54,127 participants from 26 countries. Differences between participants with and without DGBI were evaluated in a sample excluding those with self‐reported organic gastrointestinal disease, using univariable logistic regression. Analyses were stratified by age (< 50 vs. ≥ 50 years). Results Alarm features were reported by 63.1% of participants aged < 50 years and 51.8% of those aged ≥ 50 years. Individual self‐reported alarm features ranged from 0.9% to 18.3% in younger participants to 0.3%–13.3% in older participants. Haematemesis was the least frequently reported feature, while a major change in bowel movements was the most frequent in both age groups. Self‐reported alarm features were more frequent among participants with than without DGBI (< 50 years: 75.3% vs. 50.7%; OR 3.0 [2.8–3.1]; ≥ 50 years: 67.5% vs. 38.8%; OR 3.3 [3.1–3.5]). Participants with DGBI were also more likely to report multiple alarm features. Discussion Self‐reported alarm features are common in the general population and more prevalent among individuals with DGBI. These findings underscore the importance of interpreting alarm features within a broader clinical context rather than in isolation. Further studies are needed to clarify the diagnostic utility of alarm features in unselected populations, particularly among individuals with DGBI.

The accurate diagnosis of disorders of gut-brain interaction (DGBI), such as functional dyspepsia and irritable bowel syndrome, is crucial for improving patient symptoms, outcomes and ultimately, quality of life. However, busy clinicians often face challenges in diagnosing and managing these conditions, particularly when patients present with non-specific gastrointestinal symptoms together with psychosocial distress and/or social issues. DGBI are among the most common reasons for gastroenterology referral, with a global prevalence of approximately 40% in adults based on large-scale epidemiologic studies. While diagnostic algorithms aid in positively identifying DGBI, they often overlook key factors influencing treatment decisions. The Rome V Multidimensional Clinical Profile (MDCP) offers a comprehensive, patient-centered framework that extends beyond diagnosis alone. It integrates five core domains: (1) the primary diagnosis, (2) clinical modifiers, (3) impact on daily activities and quality of life, (4) psychosocial modifiers, and (5) physiological features and biomarkers. By considering comorbidities, illness severity, psychosocial contributors, and potential biomarkers, the MDCP enables clinicians to develop a holistic understanding of the patient's condition. This multidimensional approach facilitates tailored, evidence-based treatment plans that address the biopsychosocial aspects of DGBI, ultimately enhancing symptom management and patient well-being. Furthermore, it highlights gaps in knowledge and stimulates targeted research into these highly prevalent disorders. This case-oriented educational review will evaluate three DGBIs – functional dyspepsia, irritable bowel syndrome, and chronic abdominal pain – using the MDCP approach.

Myths and misconceptions about the evaluation and treatment of constipation persist. Many widely prevalent misconceptions about laxatives, specifically stimulant laxatives, interfere with the effective management of constipation. Although some of these myths and misconceptions have been dispelled in recent years, there is additional room for improving the awareness and understanding of the pathophysiology of constipation, the mechanisms of action and the efficacy and safety of available therapies. An evolution in our understanding of pathophysiology and the availability of new treatments requires that primary care practitioners be better positioned to treat this common disorder that reduces patients’ quality of life and negatively impacts the healthcare system. This review defines constipation and elucidates various factors that contribute to its aetiology, including lifestyle, dietary habits, medications and underlying medical conditions. This review addresses and refutes common myths and misconceptions about constipation, such as the belief that regular bowel movements must occur daily or the use of laxatives leads to dependence. This review also highlights the importance of distinguishing between normal and abnormal bowel habits and emphasises the need for individualised management approaches to address constipation effectively. Finally, the review discusses different classes of laxatives, dispelling misconceptions about their safety, efficacy and potential for misuse, with a specific focus on stimulant laxatives. In summary, this review enhances awareness and knowledge of this prevalent disorder, provides evidence-based insights into common myths and misconceptions surrounding constipation and promotes more informed decision-making regarding constipation and the use of laxatives.

Patients with ineffective esophageal motility continue to experience significant symptoms years after diagnosis. In this survey of 47 patients diagnosed ≥5 years earlier, 45% reported GERD symptoms and 75% reported dysphagia. Greater numbers of failed swallows correlated with worse GERD and dysphagia scores, highlighting the long-term clinical impact of IEM and its association with esophageal symptom burden.

Background: In patients with irritable bowel syndrome with constipation (IBS-C), rapid, sustained relief from constipation and abdominal symptoms, such as pain, discomfort, and bloating, can improve quality of life. Objective: This post hoc analysis evaluates the time to constipation and abdominal symptom relief achieved with tenapanor. Design: Post hoc analysis of data pooled from three randomized placebo-controlled studies (phase IIb, T3MPO-1, and T3MPO-2) of tenapanor 50 mg twice daily in patients with IBS-C. Methods: The time to first response for complete spontaneous bowel movement (CSBM) frequency, abdominal pain, discomfort, bloating, and 3-item abdominal score (AS3) were assessed. The AS3 was derived as the average of the weekly scores for abdominal pain, discomfort, and bloating. Cumulative incidences of response over time were estimated using the Kaplan–Meier method. A Cox proportional hazards model was used to assess the effect of baseline and demographic characteristics on the time to first response. Results: Among 1372 patients with IBS-C (684 tenapanor; 688 placebo), median time to first CSBM response was 2 weeks, and median time to abdominal pain, discomfort, bloating, or AS3 response was 4–5 weeks in those treated with tenapanor, with 67.8%–76.7% achieving first response in CSBM frequency and abdominal symptoms by week 12. These time frames were shorter than those observed with the placebo (4 weeks for CSBM and 6–8 weeks for pain, discomfort, bloating, and AS3), of whom 59.1%–69.4% achieved the first response in CSBM and abdominal symptoms by week 12. Higher weekly response rates were observed with tenapanor than with placebo for all endpoints in each week of the 12-week treatment period. Conclusion: This novel post hoc analysis demonstrates that, compared with placebo, tenapanor reduces the time to first response in CSBM frequency and abdominal symptoms and consistently increases the weekly response rate during 12 weeks of treatment. Trial registration: NCT01923428; NCT02621892; NCT02686138.

ABSTRACTIntroductionInvestigation of an evacuation disorder is often pursued in patients with symptoms of obstructive defecation. High‐resolution anorectal manometry (HR‐ARM) is a simple, safe, and widely available test to diagnose pelvic floor dysfunction. A more costly and less accessible test is magnetic resonance defecography (MRD). This study aims to quantify the added value of MRD in diagnosing pelvic floor disorders.MethodsHR‐ARM and MRD performed in patients with a diagnosis of constipation between January 1, 2020 and May 15, 2022 at Mayo Clinic were identified using Epic Slicer Dicer. Univariate and multivariate analyses were used to compare findings on MRD in patients with and without abnormal HR‐ARM. Categorical variables were compared using the Pearson's chi‐square test, and continuous variables were compared using the two‐sample t‐test.ResultsSeventy‐six consecutive patients (81.8% female, 94.8% White, ages 19–82) who underwent both HR‐ARM and MRD were included. The majority had evidence of dyssynergia on HR‐ARM (n = 49, 64.5%). Patients with dyssynergia on HR‐ARM were significantly more likely to have prolonged balloon expulsion at both > 60 and > 30 s (p < 0.001) and incomplete gel expulsion on MRD (p < 0.001). However, they were not more likely to have a clinically significant rectocele measuring > 2 cm (p = 0.17) or evidence of rectal prolapse (p = 0.07).DiscussionAnatomic findings on MRD were similar between patients with and without evidence of dyssynergia identified by HR‐ARM. In this retrospective review, simultaneously undergoing MRD in addition to HR‐ARM does not appear to provide significant additional diagnostic information to guide therapeutic recommendations. Large prospective studies to evaluate the added value of MRD are needed.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are commonly used to treat obesity and diabetes but are linked to a variety of gastrointestinal (GI) adverse events (AEs). Real-world data on GLP-1 RA-related GI AEs and outcomes are limited. This study assessed GI AEs and adverse outcomes using the US FDA Adverse Event Reporting System (FAERS). Methods: This retrospective pharmacovigilance study used the US FDA FAERS database (2007–2023). We searched GLP-1 RA medications, AEs, and adverse outcomes. Demographic, treatment indication, and AE data were collected. Descriptive analysis involved frequencies and percentages, while reporting odds ratio (ROR), proportional reporting ratio, Bayesian confidence propagation neural network, and multivariate logistic regression were used to analyze GLP-1 RA-related GI AEs and outcomes. Results: From 2007 to 2023, a total of 187,757 AEs were reported with GLP-1 RAs, and 16,568 were GLP-1 RA-associated GI AEs in the US. Semaglutide was linked to higher odds of nausea (IC025: 0.151, βCoeff: 0.314), vomiting (IC025: 0.334, βCoeff: 0.495), and delayed gastric emptying (IC025: 0.342, βCoeff: 0.453). Exenatide was associated with pancreatitis (IC025: 0.601, βCoeff: 0.851) and death (ROR: 4.50, IC025: 1.101). Overall, semaglutide had a broader range of notable adverse effects; by comparison, dulaglutide and liraglutide use was associated with fewer significant GI AEs. Conclusions: Analysis of the FAERS data reveals that GLP-1 RAs, particularly semaglutide and exenatide, are significantly associated with specific GI AEs, such as nausea, vomiting, delayed gastric emptying, and pancreatitis. Clinicians should be aware of these potential risks to ensure optimal monitoring and patient safety. This study demonstrated the utility of pharmacovigilance data in identifying safety signals, which can inform future pharmacoepidemiological investigations to confirm causal relationships. Clinicians should be aware of these potential risks to ensure optimal monitoring and patient safety.