Plecanatide Improves Abdominal Bloating and Bowel Symptoms of Irritable Bowel Syndrome with Constipation.

BACKGROUND: Bloating is a bothersome symptom in irritable bowel syndrome with constipation (IBS-C). AIM: To evaluate plecanatide efficacy in patients with IBS-C stratified by bloating intensity. METHODS: Pooled phase 3 data (2 randomized, controlled IBS-C trials) from adults treated with plecanatide 3 mg or placebo for 12 weeks were analyzed. Patients were stratified post-hoc by baseline bloating severity (11-point scale: mild [≤ 5] and moderate-to-severe [> 5]). Assessments included change from baseline in bloating, abdominal pain, and complete spontaneous bowel movement (CSBM) frequency. Abdominal pain and bloating composite responders were defined as patients with ≥ 30% improvement from baseline in both bloating and abdominal pain at Week 12. RESULTS: At baseline, 1104/1436 patients with IBS-C (76.9%) reported moderate-to-severe bloating. In the moderate-to-severe bloating subgroup, plecanatide significantly reduced bloating severity versus placebo (least-squares mean change [LSMC]: - 1.7 vs - 1.3; P = 0.002), reduced abdominal pain (- 1.7 vs - 1.3; P = 0.006), and increased CSBM frequency (1.4 vs 0.8; P < 0.0001). In the mild bloating subgroup, significant improvements were observed with plecanatide versus placebo for abdominal pain (LSMC: - 1.3 vs - 1.0; P = 0.046) and CSBM frequency (2.0 vs 1.2; P = 0.003) but not bloating (- 0.9 vs - 0.8; P = 0.28). A significantly greater percentage of patients were abdominal pain and bloating composite responders with plecanatide versus placebo (moderate-to-severe bloating: 33.6% vs 26.8% [P = 0.02]; mild bloating: 38.4% vs 27.2% [P = 0.03]). CONCLUSION: Plecanatide treatment improved IBS-C abdominal and bowel symptoms, including in those who present with moderate-to-severe bloating.

Optimizing the Utility of Anorectal Manometry for Diagnosis and Therapy: A Roundtable Review and Recommendations.

BACKGROUND & AIMS: Anorectal manometry (ARM) is a comprehensive diagnostic tool for evaluating patients with constipation, fecal incontinence, or anorectal pain; however, it is not widely utilized for reasons that remain unclear. The aim of this roundtable discussion was to critically examine the current clinical practices of ARM and biofeedback therapy by physicians and surgeons in both academic and community settings. METHODS: Leaders in medical and surgical gastroenterology and physical therapy with interest in anorectal disorders were surveyed regarding practice patterns and utilization of these technologies. Subsequently, a roundtable was held to discuss survey results, explore current diagnostic and therapeutic challenges with these technologies, review the literature, and generate consensus-based recommendations. RESULTS: ARM identifies key pathophysiological abnormalities such as dyssynergic defecation, anal sphincter weakness, or rectal sensory dysfunction, and is a critical component of biofeedback therapy, an evidence-based treatment for patients with dyssynergic defecation and fecal incontinence. Additionally, ARM has the potential to enhance health-related quality of life and reduce healthcare costs. However, it has significant barriers that include a lack of education and training of healthcare providers regarding the utility and availability of ARM and biofeedback procedures, as well as challenges with condition-specific testing protocols and interpretation. Additional barriers include understanding when to perform, where to refer, and how to use these technologies, and confusion over billing practices. CONCLUSIONS: Overcoming these challenges with appropriate education, training, collaborative research, and evidence-based guidelines for ARM testing and biofeedback therapy could significantly enhance patient care of anorectal disorders.

Tegaserod: What's Old Is New Again.

Irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) are common gastrointestinal disorders imposing considerable impact on the quality of life and well-being of affected individuals. A paucity of evidence-based treatment options exist for CIC and IBS-C sufferers. Tegaserod, a 5-HT4 agonist, has a substantial body of preclinical and clinical study evidence to support its beneficial role in modulating sensorimotor function of the luminal gastrointestinal tract. Tegaserod was first approved for use by the U.S. Food and Drug Administration for the management of IBS-C and CIC in 2002 and 2004, respectively. Tegaserod enjoyed a successful uptake in the management of these disorders during its first several years of availability in the United States, but was later withdrawn from the market in 2007 over concerns related to adverse cardiovascular events. Since then, additional safety data has been generated, and following a resubmission and review by the Food and Drug Administration, in April 2019, tegaserod was once again approved for use in IBS-C under a more restricted labeling, confining use to women under 65 years of age without heart disease or additional cardiovascular risk factors. This review summarizes the regulatory journey of tegaserod and details the existing pharmacokinetic, physiologic, clinical, and safety data of tegaserod generated over the last 2 decades. The discussion also examines the future of tegaserod in the treatment of these constipation disorders, as well as its potential role in other related disorders of brain-gut interaction.

Mechanisms of Action of Current Pharmacologic Options for the Treatment of Chronic Idiopathic Constipation and Irritable Bowel Syndrome With Constipation.

Multiple therapeutic agents are currently available for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation. A better understanding of the mechanism of action of each treatment provides important insights into expected responses and is key to optimizing treatment outcomes. Some constipation treatments, such as stimulant laxatives, may increase bowel movement frequency but are ineffective at relieving, and may even exacerbate, abdominal symptoms. On the contrary, prescription treatments, such as the guanylyl cyclase-C agonists, for example, may improve bowel symptoms and reduce visceral hypersensitivity. This review summarizes the mechanisms of action of commonly used over-the-counter and prescription therapies for chronic idiopathic constipation and irritable bowel syndrome with constipation, outlining how these mechanisms contribute to the efficacy and safety of each treatment option.

Real-World Treatment Strategies to Improve Outcomes in Patients With Chronic Idiopathic Constipation and Irritable Bowel Syndrome With Constipation.

Chronic idiopathic constipation and irritable bowel syndrome with constipation are complex, overlapping conditions. Although multiple guidelines have informed healthcare providers on appropriate treatment options for patients with chronic idiopathic constipation and irritable bowel syndrome with constipation, little direction is offered on treatment selection. First-line treatment options usually include fiber and over-the-counter osmotic laxatives; however, these are insufficient for many individuals. When these options fail, prescription secretagogues (plecanatide, linaclotide, lubiprostone, and tenapanor [pending commercial availability]), or serotonergic agents (prucalopride and tegaserod) are generally preferred. Individuals experiencing concurrent abdominal pain and/or bloating may experience greater overall improvements from prescription therapies because these agents have been proven to reduce concurrent abdominal and bowel symptoms. Should initial prescription treatments fail, retrying past treatment options (if not adequately trialed initially), combining agents from alternative classes, or use of adjunctive therapies may be considered. Given the broad spectrum of available agents, therapy should be tailored by mutual decision-making between the patient and practitioner. Overall, patients need to be actively monitored and managed to maximize clinical outcomes.

Emerging therapies in the management of Irritable Bowel Syndrome (IBS).

INTRODUCTION: Irritable bowel syndrome (IBS) is a symptom-based disorder of chronic abdominal pain and altered bowel habits. The pathogenesis of IBS is multifactorial, leading to the potential for the development of diverse treatment strategies. This mechanistic heterogeneity suggests that available therapies will only prove effective in a subset of IBS sufferers. Current US Food and Drug Administration (FDA) approved therapies for IBS with diarrhea (IBS-D) and IBS with constipation (IBS-C) are reviewed. Limited symptom responses and side effect experiences lead to considerable patient dissatisfaction with currently available IBS treatments. Only a small percentage of IBS patients are on prescription therapies underscoring the potential market and need for additional therapeutic options. AREAS COVERED: Expanding on currently available therapies, the serotonergic and endogenous opioid receptor systems continue to be a focus of future IBS treatment development. Additional novel emerging therapies include the endogenous cannabinoid system, bile acid secretion and sequestration, and exploit our enhanced understanding of visceral sensory signaling and intestinal secretomotor function. EXPERT OPINION: While challenges remain for the future development of IBS therapies, the diverse etiologies underlying the disorder present an opportunity for novel therapies. Hence, great potential is anticipated for future IBS treatment options.

Increased Risk of Advanced Colonic Adenomas and Timing of Surveillance Colonoscopy Following Solid Organ Transplantation.

BACKGROUND: Detection and removal of colonic adenomatous polyps (CAP) decreases colorectal cancer (CRC) development, particularly with more or larger polyps or polyps with advanced villous/dysplastic histology. Immunosuppression following solid organ transplantation (SOT) may accelerate CAP development and progression compared to average-risk population but the benefit of earlier colonoscopic surveillance is unclear. AIMS: Study the impact of maintenance immunosuppression post-SOT on developmental timing, multiplicity and pathological features of CAP, by measuring incidence of advanced CAP (villous histology, size ≥ 10 mm, ≥ 3 polyps, presence of dysplasia) post-SOT and the incidence of newly diagnosed CRC compared to average-risk age-matched population. METHODS: Single-center retrospective cohort study of SOT recipients. RESULTS: 295 SOT recipients were included and were compared with 291 age-matched average-risk controls. The mean interval between screening and surveillance colonoscopies between SOT and control groups was 6.3 years vs 5.9 years (p = 0.13). Post-SOT maintenance immunosuppression mean duration averaged 59.9 months at surveillance colonoscopy. On surveillance examinations, SOT recipients exhibited more advanced (≥ 10 mm) adenomas compared to matched controls (9.2% vs. 3.8%, p = 0.034; adjusted OR 2.38; 95% CI 1.07-5.30). CONCLUSION: SOT recipients appear at higher risk for developing advanced CAP, suggesting that earlier surveillance should be considered.

Gallbladder Dyskinesia.

Gallbladder dyskinesia is a functional disorder of the gastrointestinal tract, which can result in debilitating episodes of abdominal pain and associated symptoms. Key diagnostic criteria include a diminished gallbladder ejection fraction on scintigraphy and absence of other causes for the symptoms. Pathologic findings and follow-up suggest a distinct mechanistic basis for this condition. Unfortunately, the complexities of diagnosis and treatment combined with patient and provider preferences will likely continue to preclude randomized controlled studies to provide a clearer evidence-based management for this disorder. Patients meeting the clinical and diagnostic criteria for gallbladder dyskinesia should be referred for cholecystectomy, and most of these patients will have relief of their symptoms. A comprehensive preoperative discussion on expected outcomes needs to take place.

Randomized Trial of 2 Delayed-Release Formulations of Linaclotide in Patients With Irritable Bowel Syndrome With Constipation.

INTRODUCTION: Immediate-release (IR) formulation of linaclotide 290 µg improves abdominal pain and constipation (APC) in patients with irritable bowel syndrome (IBS) with constipation. Delayed-release (DR) formulations were developed on the premise that targeting the ileum (delayed-release formulation 1 [DR1]) or ileocecal junction and cecum (MD-7246, formerly DR2) would modulate linaclotide's secretory effects while preserving pain relief effects. METHODS: This phase 2b study randomized patients with IBS with constipation to placebo or 1 of 7 once-daily linaclotide doses (DR1 30, 100, or 300 µg; MD-7246 30, 100, or 300 µg; or IR 290 µg) for 12 weeks. Key efficacy endpoints were change from baseline in abdominal pain and complete spontaneous bowel movement frequency, and 6/12-week combined APC+1 responder rate. RESULTS: Overall, 532 patients were randomized; mean age was 45.1 years, and most were women (83.3%) and White (64.7%). All linaclotide DR1 and MD-7246 groups experienced greater improvements in abdominal pain from baseline and vs placebo throughout treatment. Linaclotide DR1 and IR led to numerically greater improvements from baseline in complete spontaneous bowel movement frequency and higher APC+1 responder rates compared with placebo; MD-7246 results were similar to placebo. Diarrhea was the most common adverse event with DR1 and IR; rates were similar between MD-7246 and placebo. DISCUSSION: Altering the site of drug delivery in the intestine might uncouple linaclotide's pain relief from secretory effects. Persistent, modest abdominal pain improvement with limited impact on bowel symptom parameters, as seen across MD-7246 doses, warrants further study of MD-7246 as a novel treatment for abdominal pain, regardless of IBS subtype.

Patient Engagement with Interactive Text Message System Improves Successful Colonoscopy Rates in an Outpatient Endoscopy Center.

INTRODUCTION: Text message-based interventions reduce colonoscopy no-show rates and improve bowel preparation scores. In this non-randomized study, we assessed whether an interactive text messaging system could improve colonoscopy outcomes. METHODS: Colonoscopy pre-procedural instructions were programmed into a dedicated software platform created for this study. In the intervention arm, text messages were sent to veterans during a 4-week study period. Validated pre-procedural satisfaction questionnaires were completed by patients during standard protocol and intervention periods. Demographics and colonoscopy outcomes data were compared between the standard protocol and intervention arms, including procedure completion rate on scheduled date, Boston bowel preparation score (BPPS), adenoma detection rate, and satisfaction. RESULTS: Of 241 patients, 128 were in the standard protocol arm and 113 in the intervention arm. Higher proportions of patients receiving text messages underwent colonoscopy on their scheduled date (69.9%) compared to the ones in the standard protocol (50.8%, p = 0.015). Patients with ≥3 interactions with the system had 80.6% likelihood of completing colonoscopy on the scheduled date compared to 56.9% with <3 interactions and 50.8% with standard protocol (p < 0.001). Frequency of interaction with the system was similar between older (>65 years) and younger patients (p = 1.0). Among older patients, colonoscopy was completed successfully in 84.2% when alert-based human interactions occurred compared to 65.6% in those without and 47.9% with standard protocol (p = 0.018). More than 90% indicated they would recommend the system to patients undergoing future colonoscopy. CONCLUSION: An interactive text messaging system improves successful colonoscopy rates in a VA setting, with greatest impact in older patients.

Higher Esophageal Symptom Burden in Obese Subjects Results From Increased Esophageal Acid Exposure and Not From Dysmotility.

BACKGROUND & AIMS: Esophageal motor disorders (EMD) and pathologic reflux are often identified in obese individuals, but it is not clear how obesity contributes to these symptoms. We examined the relationships among symptom burden, EMD, acid exposure time (AET), symptom association probability, and body mass index (BMI). METHODS: We performed a retrospective study of 1089 consecutive patients who underwent high-resolution manometry, of which 426 patients also underwent reflux monitoring off acid suppression, over a 2-year period at a tertiary referral center. Symptom burden was assessed by questionnaires to determine dominant symptom intensity (DSI; product of symptom severity, and frequency, on 5-point Likert scales) and global symptom severity (GSS; global esophageal symptoms on 10-cm visual analog scales) at the time of esophageal testing; BMIs were recorded. We compared proportions of patients with EMD and abnormal reflux burden among BMI categories and correlated them with symptom burden. RESULTS: Four-hundred thirty-three patients (39.8%) met the criteria for EMD. Esophageal outflow obstruction was observed in higher proportions of patients with low BMIs (underweight, 25.9%; normal, 14.1%; overweight, 13.9%; and obese, 9.8%; P = .037), but EMDs were less frequent in obese patients (P = .047), despite higher symptom burden compared with non-obese patients (DSI, 10.5 ± 0.3 vs 9.7 ± 0.2; P = .03 and GSS, 6.5 ± 1 vs 5.9 ± 1; P = .01). Among the 426 patients who underwent reflux monitoring, the proportions with total AET (P = .02), and upright AET (P < .001) increased among BMI categories, supine AET trended strongly (P = .06), in combination with increasing DSI and GSS (P ≤ .001 for each comparison). BMI correlated with symptom burden, higher AET, and positive symptom association probability (P < .01 for each analysis). CONCLUSIONS: Increased symptom burden in obese individuals correlates with esophageal acid burden but not with motor disorders.

Quality metrics of screening colonoscopies performed by PAs.

BACKGROUND: Many communities face a shortage of qualified endoscopists. Training physician assistants (PAs) to perform colonoscopies can expand the availability of colorectal cancer screening. This study examined screening colonoscopy metrics and quality indicators among gastroenterologists, supervised PAs, and gastroenterology fellows. METHODS: Consecutive patients undergoing average-risk screening colonoscopy were stratified into one of three groups by endoscopist type. Procedure and pathology reports were reviewed for the technical performance and quality metrics of the providers. RESULTS: PAs performed comparably to gastroenterologists in technical performance and quality metrics, and demonstrated higher cecal intubation rates than their gastroenterologist colleagues. Comparisons of attending physicians and PAs grouped by years of experience also did not show notable differences in performance. CONCLUSIONS: In a supervised practice, PAs performed on par with their gastroenterology colleagues on established colonoscopy quality indicators. Following proper training, PAs can be employed in the provision of screening colonoscopy.

Efficacy and Safety of Eluxadoline in Patients With Irritable Bowel Syndrome With Diarrhea Who Report Inadequate Symptom Control With Loperamide: RELIEF Phase 4 Study.

OBJECTIVES: Irritable bowel syndrome with diarrhea (IBS-D) is a functional gastrointestinal disorder with limited effective treatment options. We evaluated the efficacy and safety of eluxadoline in patients with IBS-D who reported inadequate symptom control with prior loperamide. METHODS: Three hundred forty-six adults with IBS-D (Rome III criteria) were randomly assigned to placebo or eluxadoline 100 mg twice daily for 12 weeks. Patients recorded daily IBS-D symptoms, including worst abdominal pain (WAP) and stool consistency (through Bristol Stool Scale). The primary endpoint was proportion of composite responders, defined as patients who met daily composite response criteria (≥40% WAP improvement and <5 Bristol Stool Scale score) for at least 50% of treatment days, and recorded ≥60 days of diary entries over the 12-week period. RESULTS: Over 12 weeks, a significantly greater proportion of eluxadoline patients achieved the primary composite responder endpoint compared to placebo (22.7% vs 10.3%, P = 0.002), and component endpoints of improvements in stool consistency (27.9% vs 16.7%, P = 0.01) and WAP (43.6% vs 31.0%, P = 0.02). Additionally, a greater proportion of eluxadoline patients met the composite responder endpoint assessed at monthly intervals compared to placebo (weeks 1-4: 14.0% vs 6.9%, P = 0.03; weeks 5-8: 26.7% vs 14.9%, P = 0.006; weeks 9-12: 30.8% vs 16.7%, P = 0.002). Rates of adverse events were comparable in both groups (37.4% vs 35.3%); no treatment-related serious adverse event, cases of sphincter of Oddi spasm, or pancreatitis were reported. DISCUSSION: Eluxadoline appears safe and effective for treating IBS-D symptoms in patients with an intact gallbladder reporting inadequate relief with prior loperamide use.

Health-related quality of life and long-term outcomes after endoscopic therapy for walled-off pancreatic necrosis.

BACKGROUND AND AIM: Walled-off pancreatic necrosis (WON) frequently develops after necrotizing pancreatitis. Endoscopic drainage has become the preferred modality for symptomatic or infected WON. The aim of the present study was to assess health-related quality of life (HR-QOL) and long-term outcomes in patients undergoing endoscopic drainage for WON. METHODS: Patients undergoing endoscopic drainage of WON from January 2006 to May 2016 were identified. Data recorded included demographic information, and the incidence of long-term sequelae including pancreatic endocrine and exocrine insufficiency. Attempts were made to contact all patients. HR-QOL was assessed using the SF-36 questionnaire. RESULTS: Eighty patients were analyzed, 41 (51.3%) of whom completed the SF-36. One-year all-cause mortality was 6.2%, and disease-related mortality was 3.7%. A notable proportion of patients developed exocrine insufficiency (32.5%), endocrine insufficiency (27.7%), and long-term opiate use (42.5%). Development of exocrine insufficiency was predictive of lower total SF-36 scores (P = 0.016). Patients with WON had better HR-QOL compared with cohorts of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). In patients developing exocrine insufficiency versus healthy controls, poorer scores in the physical role (P < 0.001), general health (P < 0.001), vitality (P = 0.001), and emotional role (P = 0.029) domains were observed. Exocrine insufficiency patients had better HR-QOL than the IBS and IBD cohorts, although these differences were less pronounced. CONCLUSION: After undergoing endoscopic drainage for WON, patients have relatively preserved HR-QOL. The subset of patients that develop exocrine insufficiency have significantly poorer HR-QOL compared to healthy controls, although not to the degree of chronic gastrointestinal disorders such as IBS and IBD.

Editorial: Functional Dyspepsia Treatment: Trials and Tribulations of Targeted Strategies.

While functional dyspepsia (FD) is an exceedingly common disorder, the number of treatment options remains limited, and strategies for the individualized implementation of these therapies largely are lacking. In the current issue of American Journal of Gastroenterology, Saito and colleagues report on a secondary analysis of data from the Functional Dyspepsia Treatment Trial, specifically examining the role of two candidate genetic markers in predicting FD response to antidepressant treatments. Though the current study yielded a negative result, it nevertheless emphasizes the importance of our continued pursuit of therapeutic biomarkers in order to move beyond "one-size-fits-all" approaches to the treatment of FD and related disorders.

Comparison of Symptoms, Healthcare Utilization, and Treatment in Diagnosed and Undiagnosed Individuals With Diarrhea-Predominant Irritable Bowel Syndrome.

OBJECTIVES: Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by symptoms including abdominal pain and altered bowel function. Up to 75% of individuals with IBS may be undiagnosed. The aim of this study was to characterize symptoms, healthcare utilization, and treatments in populations with both diagnosed and undiagnosed IBS. METHODS: An online survey was conducted to compare gastrointestinal (GI) symptoms, healthcare visits, well-being, symptom management, and treatment satisfaction in individuals with and without medically diagnosed IBS (Rome III criteria). Symptom severity, disruptiveness, and treatment satisfaction were rated using a 7-point scale. Adjustments to daily life were determined by predefined survey responses. RESULTS: A total of 1,924 individuals with a history of GI symptoms were eligible and completed the survey. Of these, 1,094 individuals (56.9%) met the criteria for IBS; 830 individuals (43.1%) had no medical diagnosis of IBS despite meeting diagnostic criteria. Most participants received a diagnosis from either gastroenterologists (45%) or primary care physicians (42%). A greater percentage of diagnosed patients had severe GI symptoms (score ≥6) vs. undiagnosed individuals (16% vs. 8%, respectively; P<0.05); diagnosed patients were more likely to report that GI symptoms adversely affected their quality of life. Approximately 40% of participants received IBS-related treatment from primary care physicians; 26% and 43% of diagnosed and undiagnosed individuals, respectively, were not receiving treatment for GI symptoms. CONCLUSIONS: Many individuals with IBS-related symptoms have not been medically diagnosed with IBS. IBS-related symptoms impact quality of life, yet more than one-third of individuals are not receiving treatment for IBS.

Do Consultants Follow Up on Tests They Recommend? Insights from an Academic Inpatient Gastrointestinal Consult Service.

BACKGROUND: Inpatient care is a fundamental part of gastroenterology training and involves the recommendation, performance, and interpretation of diagnostic tests. However, test results are not always communicated to patients or treating providers. We determined the process of communication of test results and recommendations in our inpatient gastroenterology (GI) consult service. METHODS: Test recommendations on 304 consecutive new GI consults (age 60.2 ± 1.0 year) over a 2-month period were recorded. Demographic factors (age, race, gender, zip code, insurance status) were extracted from the electronic medical record (EMR). Charts were independently reviewed 6 months later to determine results of recommended tests, follow-up of actionable test results, 30-day readmission rates, and predictors of suboptimal communication. RESULTS: Of 490 recommended tests, 437 (89.2%) were performed, and 199 (45.5%) had actionable findings. Of these, 48 (24.1%) did not have documented follow-up. Failure of follow-up was higher for upper endoscopy (31.9%) compared to colonoscopy (18.0%, p = 0.07). Women (p = 0.07), patients on Medicare (p = 0.05), and procedures supervised by advanced GI fellows (p = 0.06) were less likely to receive follow-up. Median income and identification of a primary provider did not influence follow-up rates; 30-day readmission rates were not impacted. Female gender, insurance (Medicare) status, and attending type remained independent predictors of failure of follow-up on multivariate regression (p ≤ 0.03). CONCLUSIONS: Failure to follow up test results on inpatient services at a large academic center was unacceptably high. Maximizing personnel participation together with diligence and technology (EMR) will be required to improve communication.

Parameters on esophageal pH-impedance monitoring that predict outcomes of patients with gastroesophageal reflux disease.

BACKGROUND & AIMS: pH-impedance monitoring detects acid and nonacid reflux events, but little is known about which parameters predict outcomes of different management strategies. We evaluated a cohort of medically and surgically managed patients after pH-impedance monitoring to identify factors that predict symptom improvement after therapy. METHODS: In a prospective study, we followed up 187 subjects undergoing pH-impedance testing from January 2005 through August 2010 at Washington University in St. Louis, Missouri (mean age, 53.8 ± 0.9 y; 70.6% female). Symptom questionnaires assessed dominant symptom intensity (DSI) and global symptom severity (GSS) at baseline and at follow-up evaluation. Data collected from pH impedance studies included acid exposure time (AET), reflux exposure time (RET) (duration of impedance decrease 5 cm above lower esophageal sphincter, reported as the percentage of time similar to AET), symptom reflux correlation (symptom index and symptom association probability [SAP]), and the total number of reflux events. Univariate and multivariate analyses were performed to determine factors associated with changes in DSI and GSS after therapy. RESULTS: Of the study subjects, 49.7% were tested on proton pump inhibitor (PPI) therapy and 68.4% were managed medically. After 39.9 ± 1.3 months of follow-up, DSI and GSS scores decreased significantly (P < .05). On univariate analysis, an abnormal AET predicted decreased DSI and GSS scores (P ≤ .049 for each comparison); RET and SAP from impedance-detected reflux events (P ≤ .03) also were predictive. On multivariate analysis, abnormal AET consistently predicted symptomatic outcome; other predictors included impedance-detected SAP, older age, and testing performed off PPI therapy. Abnormal RET, acid symptom index, or SAP, and numbers of reflux events did not independently predict a decrease in DSI or GSS scores. CONCLUSIONS: Performing pH-impedance monitoring off PPI therapy best predicts response to antireflux therapy. Key parameters with predictive value include increased AET, and correlation between symptoms and reflux events detected by impedance.

Beliefs about GI medications and adherence to pharmacotherapy in functional GI disorder outpatients.

OBJECTIVES: Pharmacotherapy is a mainstay in functional gastrointestinal (GI) disorder (FGID) management, but little is known about patient attitudes toward medication regimens. Understanding patient concerns and adherence to pharmacotherapy is particularly important for off-label medication use (e.g., antidepressants) in FGID. METHODS: Consecutive tertiary GI outpatients completed the Beliefs About Medications questionnaire (BMQ). Subjects were categorized as FGID and structural GI disease (SGID) using clinician diagnoses and Rome criteria; GI-specific medications and doses were recorded, and adherence to medication regimens was determined by patient self-report. BMQ domains (overuse, harm, necessity, and concern) were compared between FGID and SGID, with an interest in how these beliefs affected medication adherence. Psychiatric measures (depression, anxiety, and somatization) were assessed to gauge their influence on medication beliefs. RESULTS: A total of 536 subjects (mean age 54.7±0.7 years, range 22-100 years; n=406, 75.7% female) were enrolled over a 5.5-year interval: 341 (63.6%) with FGID (IBS, 64.8%; functional dyspepsia, 51.0%, ≥2 FGIDs, 38.7%) and 142 (26.5%) with SGID (IBD, 28.9%; GERD, 23.2%). PPIs (n=231, 47.8%), tricyclic antidepressants (TCAs) (n=167, 34.6%), and anxiolytics (n=122, 25.3%) were common medications prescribed. FGID and SGID were similar across all BMQ domains (P>0.05 for overuse, harm, necessity, and concern). SGID subjects had higher necessity-concern framework (NCF) scores compared with FGID subjects (P=0.043). FGID medication adherence correlated negatively with concerns about medication harm (r=-0.24, P<0.001) and overuse (r=-0.15, P=0.001), whereas higher NCF differences predicted medication compliance (P=0.006). Medication concern and overuse scores correlated with psychiatric comorbidity among FGID subjects (P<0.03 for each). FGID patients prescribed TCAs (n=142, 41.6%) expressed a greater medication necessity (17.4±0.4 vs. 16.2±0.4, P=0.024) and found their GI regimen to be more helpful (P=0.054). FGID subjects not on TCAs expressed a greater apprehension about medication overuse (10.7±0.3 vs. 9.7±0.2, P=0.002) on the BMQ. CONCLUSIONS: FGID subjects report medication necessity and concern scores comparable to patients with SGID but have negative perceptions about medications, particularly in the presence of psychiatric comorbidity; these factors may affect treatment adherence and willingness to initiate neuromodulator regimens.