Lacy, Brian E.

Irritable bowel syndrome (IBS) is a common gastrointestinal (GI) condition involving numerous potential causative factors (e.g. alterations in gut microbiota, motility, brain–gut axis). Several interventions are available for the management of patients with IBS, but no universal management algorithm currently exists. The aim of this article is to review interventions that may be considered in the management of patients with IBS with diarrhea (IBS-D). Nonpharmacological interventions include dietary and lifestyle modification, which are generally used as first-line therapy. Probiotics have demonstrated efficacy and safety in patients with IBS, but studies are inconsistent in strains examined, dosing, and treatment duration. Psychological therapies (e.g. cognitive behavioral therapy, hypnotherapy) also may improve IBS symptoms. Pharmacological interventions for the management of IBS-D include the US Food and Drug Administration–approved agents eluxadoline, rifaximin, and alosetron, as well as loperamide, smooth muscle antispasmodics, bile acid sequestrants, and antidepressants (i.e. tricyclic antidepressants, selective serotonin reuptake inhibitors). Eluxadoline and rifaximin have been shown to improve abdominal pain and stool consistency in patients with IBS-D. In addition, data indicate that alosetron improves IBS symptoms; however, it is approved only for women with severe IBS-D. Of the three approved agents, rifaximin has the most favorable safety profile. The risk–benefit ratio is an important consideration with every medication, but is especially important in the treatment of functional GI disorders such as IBS-D. Thus, the most troublesome symptoms, quality of life, symptom intensity, and individual patient preferences should be considered when formulating a management plan for patients with IBS-D.

OBJECTIVE: Data regarding opioid effects on esophageal function are limited. We previously demonstrated an association between chronic opioid use and esophageal motor dysfunction characterized by esophagogastric junction outflow obstruction, distal esophageal spasm, achalasia type III, and possibly Jackhammer esophagus. Our aim was to characterize the influence of different opioids and doses on esophageal dysfunction. METHODS: Retrospective review of 225 patients prescribed oxycodone, hydrocodone, or tramadol for >3 months, who completed high-resolution manometry from 2012 to 2017. Demographic and manometric data were extracted from a prospectively maintained motility database. Frequency of opioid-induced esophageal dysfunction (OIED, defined as distal esophageal spasm, esophagogastric junction outflow obstruction, achalasia type III, or Jackhammer esophagus on high-resolution manometry, was compared among different opioids. The total 24-hour opioid doses for oxycodone, hydrocodone, and tramadol were converted to a morphine equivalent for dose effect analysis. RESULTS: OIED was present in 24% (55 of 225) of opioid users. OIED was significantly more prevalent with oxycodone or hydrocodone use compared with tramadol (31% vs 28% vs 12%, P = 0.0162), and for oxycodone alone vs oxycodone with acetaminophen (43% vs 21%, P = 0.0482). There was no difference in OIED for patients taking hydrocodone alone vs hydrocodone with acetaminophen. Patients with OIED were taking a higher median 24-hour opioid dose than those without OIED (45 vs 30 mg, P = 0.058). DISCUSSION: OIED is more prevalent in patients taking oxycodone or hydrocodone compared with tramadol. There is greater likelihood of OIED developing with higher doses. Reducing the opioid dose or changing to tramadol may reduce OIED in opioid users.

Rheumatological diseases (RDs) represent a diverse group of diseases that are inherited or related to environmental factors. RDs frequently affect the gastrointestinal (GI) tract, and gastroenterologists are often asked to evaluate patients with symptoms thought to represent an underlying or coexisting RD. GI manifestations of RDs vary based on the organ involved as well as the extent and duration of involvement. Although most manifestations of RD are nonspecific and not life-threatening, the chronicity and severity of symptoms can be debilitating and may lead to serious injury. This narrative review discusses the most common RD encountered by gastroenterologists: systemic lupus erythematosus, systemic sclerosis (scleroderma), dermatomyositis/polymyositis, rheumatoid arthritis, Sjögren syndrome, overlap syndromes, mixed connective tissue disease, Ehlers-Danlos syndromes, and other vasculitides. Each section begins with a brief overview of the condition, followed by a discussion of the etiopathophysiology, physical examination findings, GI manifestations, diagnostic tools (i.e., serologic, imaging, endoscopic, and functional), and treatment options.

Background: Irritable bowel syndrome with diarrhea (IBS-D) is a prevalent gastrointestinal (GI) disorder with a varied presentation, often overlapping with other GI and non-GI disorders. Eluxadoline is a locally active mixed µ- and κ-opioid receptor agonist and δ-opioid receptor antagonist approved for the treatment of IBS-D in adults. As IBS-D is a heterogeneous disease, factors such as patient demographics, symptom severity, and symptom pattern history can potentially inform treatment selection. Methods: Here, we report additional prospectively planned analyses of two large double-blind, placebo-controlled studies (IBS-3001 and IBS-3002) enrolling patients meeting Rome III criteria for IBS-D. Patients were randomized 1:1:1 to receive placebo or eluxadoline 75 mg or 100 mg twice daily. Efficacy (abdominal pain, stool consistency, and composite, simultaneous improvement in both) and safety were assessed for prospectively defined patient subgroups stratified by age, sex, race, presence of comorbidities, and baseline disease characteristics. Results: Across all age, sex, race, comorbidity, and disease characteristic subgroups, a greater proportion of patients were composite responders with both eluxadoline doses as compared with placebo, including patients with a history of depression or a history of gastroesophageal reflux disease. Among patients aged ⩾65 years, a greater proportion of patients receiving eluxadoline 75 mg were composite, abdominal pain, and stool consistency responders compared with those receiving 100 mg. The proportion of patients with at least one adverse event was slightly higher in patients aged ⩾65 years and also in female patients. Conclusions: This analysis suggests that eluxadoline is effective in treating IBS-D across a range of commonly encountered patient types. In contrast to the overall population, patients aged ⩾65 years demonstrated a greater proportion of responders at the lower approved 75 mg eluxadoline dose.

OBJECTIVES: We conducted a randomized, placebo-controlled trial, which evaluated a novel formulation of caraway oil and L-menthol using microsphere-based site-specific targeting (COLM-SST) vs placebo in patients with functional dyspepsia (FD). METHODS: Adult men and women with FD defined by Rome III criteria were recruited. Patients were randomized to COLM-SST (25 mg of caraway oil and 20.75 mg of L-menthol per capsule, at 2 capsules per dose, twice per day) or placebo. Efficacy was measured at 24 hours, 2 weeks, and 4 weeks. Patients were allowed to take concomitant medications for their FD throughout the trial, and rescue medicines were allowed, 48 hours after start of dosing. RESULTS: Ninety-five patients were enrolled (mean age = 43.4 years; 75.8% women). At 24 hours, the active arm reported a statistically significant reduction in postprandial distress syndrome symptoms ( P = 0.039), and a nonsignificant trend toward benefit of epigastric pain syndrome symptoms ( P = 0.074). In patients with more severe symptoms, approximately 3 quarters of patients showed substantial global improvement (i.e., clinical global impressions), after 4 weeks of treatment, vs half in the control arm. These differences were statistically significant for patients with epigastric pain syndrome ( P = 0.046), and trending toward significance for patients with postprandial distress syndrome ( P = 0.091). There was no statistically significant difference between groups for Global Overall Symptom scores for the overall population at 2 and 4 weeks. Treatment emergent adverse events were mild to moderate, and no serious adverse events were reported. DISCUSSION: In patients taking their usual medications for FD, COLM-SST provided rapid relief (within 24 hours) and relief of severe FD symptoms. It was safe and well tolerated.

Linked ContentThis article is linked to Ford et al and Sun et al papers. To view these articles, visit https://doi.org/10.1111/apt.15001 and https://doi.org/10.1111/apt.15230.

SummaryBackgroundGastroparesis has a significant negative impact on patients’ quality of life. Only one medication is approved for gastroparesis and it is associated with a significant risk of side effects.AimTo assess the willingness of patients to take risks associated with medications to treat gastroparesis symptoms.MethodsWe developed a questionnaire to assess medication risk‐taking behaviour in patients identified as having documented gastroparesis (consistent symptoms, normal upper endoscopy, delayed gastric emptying). The survey assessed demographics, symptoms, medication use, anxiety, depression and impulsivity. A standard reference gamble evaluated respondents’ willingness to take medication risks.ResultsTwo hundred seven questionnaires were mailed to patients, 103 questionnaires were completed. Seventy‐six percent were female; the mean age was 48 years; average duration of gastroparesis symptoms was 10 years. Self‐reported symptom severity was severe in 52% and moderate in 32%. Gastroparesis patients reported that they would accept a median 13.4% risk of sudden death to cure their symptoms using a hypothetical medication. Self‐reported gastroparesis symptom severity and Gastroparesis Cardinal Symptom Index scores correlated significantly with increased willingness to take risks associated with medications to treat gastroparesis, while anxiety was negatively associated.ConclusionsGastroparesis patients are willing to accept markedly high risks with a hypothetical medication to cure their symptoms. Patients with severe gastroparesis symptoms and higher Gastroparesis Cardinal Symptom Index scores were more willing to take these risks. This study, the first to quantify gastroparesis patients’ willingness to accept medication associated risks, should help clinicians through the complex maze of gastroparesis therapies and their associated risks and benefits.

Background: Irritable bowel syndrome (IBS) reduces quality of life and burdens healthcare systems. This study identified factors associated with frequent use of IBS diagnostic tests and procedures. Methods: Using a United States claims database (2001–2012), tests and procedures in IBS patients occurring in the 2-year study period (12 months before/following the first IBS diagnosis) were analyzed: endoscopy, GI transit testing, anorectal procedures, and radiologic imaging. Patients were classified based on test/procedure frequency (3+, 1–2, or 0). Multivariate logistic regression identified factors associated with more frequent tests/procedures. Results: Among 201,322 IBS patients, 41.7% had 3+ tests/procedures, 35.1% had 1–2, and 23.3% had 0. Patients with more tests/procedures were older [mean age 50.6 (3+ group), more likely to be female and had more comorbidities, including anxiety, depressive disorders, and somatization. Dyspepsia [odds ratio (95% confidence interval): 1.80 (1.72–1.87)], interstitial cystitis [1.60 (1.45–1.77)], gastroesophageal reflux disease [1.59 (1.55–1.63)], constipation [1.50 (1.45–1.54)], and dyspareunia [1.38 (1.25–1.52)] were significantly associated with more tests/procedures (3+ versus 1–2), while anxiety, depressive disorders, and somatization were not. Patients with more frequent specialist visits [emergency department (ED; 1.10 (1.09–1.11)) and gastroenterologists (1.26 (1.26–1.27))] or at least one GI-related ED visit or inpatient admission [1.95 (1.86–2.04) and 3.67 (3.48–3.87), respectively] were more likely to have more tests/procedures (all p < 0.05). Conclusions: Test frequency in patients with IBS is strongly associated with demographic and clinical characteristics, especially comorbid conditions related to IBS. Presence of common overlapping comorbid conditions should increase clinicians’ confidence in making the diagnosis of IBS, thus curtailing redundant testing and reducing healthcare costs.