Treatment-Free Interval: A Novel Approach to Assessing Real-World Treatment Effectiveness and Economic Impact Among Patients with Irritable Bowel Syndrome with Diarrhea.

INTRODUCTION: Objective assessment of treatment effectiveness using real-world claims data is challenging. This study assessed treatment-free intervals (TFI) as a proxy for treatment effectiveness, and all-cause healthcare costs among adult patients with irritable bowel syndrome with diarrhea (IBS-D) treated with rifaximin or eluxadoline in the USA. METHODS: Adult patients (18-64 years) with IBS-D and ≥ 1 rifaximin or eluxadoline prescription were identified in the IQVIA PharMetrics® Plus database (10/01/2015-12/31/2021) and classified into two mutually exclusive cohorts (i.e., rifaximin and eluxadoline). Index date was the date of rifaximin or eluxadoline initiation. Entropy-balanced baseline characteristics, TFI (periods of ≥ 30 consecutive days without IBS-D treatment), and healthcare costs were reported. Healthcare costs were compared between cohorts using mean cost differences. RESULTS: There were 7094 and 2161 patients in the rifaximin and eluxadoline cohorts, respectively. After balancing, baseline characteristics (mean age 44.1 years; female 72.4%) were similar between cohorts. A higher proportion of patients treated with rifaximin achieved a TFI of ≥ 30 days (76.2% vs. 66.7%), ≥ 60 days (67.0% vs. 47.0%), ≥ 90 days (61.0% vs. 38.7%), ≥ 180 days (51.7% vs. 31.0%), and ≥ 240 days (47.7% vs. 27.9%) compared to eluxadoline. Among patients with a TFI ≥ 30 days, mean TFI durations were 8.3 and 6.0 months for the rifaximin and eluxadoline cohorts. Mean all-cause healthcare costs were lower for rifaximin vs. eluxadoline ($18,316 vs. $23,437; p = 0.008), primarily driven by pharmacy costs ($7348 vs. $10,250; p < 0.001). In a simulated health plan of one million commercially insured lives, initiating 50% of patients on rifaximin instead of eluxadoline resulted in total cost savings of $2.1 million per year or $0.18 per-member-per-month. CONCLUSIONS: This real-world study suggests that TFI is a meaningful surrogate measure of treatment effectiveness in IBS-D. Patients treated with rifaximin had longer treatment-free periods and lower healthcare costs than patients treated with eluxadoline.

Gastric Emptying Scans: Poor Adherence to National Guidelines.

BACKGROUND: Accurately diagnosing gastroparesis relies upon gastric emptying scintigraphy (GES) being performed correctly. Jointly published protocol guidelines have long been available; however, the extent to which practitioners adhere to these guidelines is unknown. AIMS: This study aimed to assess national compliance with established GES protocol guidelines. METHODS: We developed a questionnaire addressing the key protocol measures outlined in the Consensus Recommendations for Gastric Emptying Scintigraphy. Survey questions addressed patient information collection (15), patient preparation and procedure protocol (16), meal content and preparation (7), imaging (3), interpretation (4), reporting (7), and institutional demographic data (7). The anonymous questionnaire was distributed electronically to members of the Society of Nuclear Medicine and Medical Imaging (SNMMI) and non-member recipients of the SNMMI daily email newsletter. One response per medical institution was permitted. RESULTS: A total of 121 out of 872 potential medical institutions (MI) responded (13.9%); 49 (40.4%) were academic/teaching medical centers. The annual number (mean) of GES procedures was 199.9 (range 5-2000 GES/year). On average, MI performed 33.5/52 (64%) of protocol measures according to guidelines while academic medical centers performed 31.5/52 (61%) of protocol measures according to guidelines. Only 4 out of 88 MI (4.5%) performed GES while adhering to three critical measures: validated study duration; controlled blood glucose levels; and proper restriction of medications. CONCLUSIONS: Low compliance with GES protocol guidelines, even among academic medical centers, raises the likely possibility of misdiagnosis and improper management of upper gastrointestinal symptoms. These results highlight a need for increased awareness of protocol guidelines for gastric scintigraphy.

Chronic nausea and vomiting: evaluation and treatment.

Nausea is an uneasy feeling in the stomach while vomiting refers to the forceful expulsion of gastric contents. Chronic nausea and vomiting represent a diverse array of disorders defined by 4 weeks or more of symptoms. Chronic nausea and vomiting result from a variety of pathophysiological processes, involving gastrointestinal and non-gastrointestinal causes. The prevalence of chronic nausea and vomiting is unclear, although the epidemiology of specific conditions, such as gastroparesis and cyclic vomiting syndrome, is better understood. The economic impact of chronic nausea and vomiting and effects on quality of life are substantial. The initial diagnostic evaluation involves distinguishing gastrointestinal causes of chronic nausea and vomiting (e.g., gastroparesis, cyclic vomiting syndrome) from non-gastrointestinal causes (e.g., medications, vestibular, and neurologic disorders). After excluding anatomic, mechanical and biochemical causes of chronic nausea and vomiting, gastrointestinal causes can be grouped into two broad categories based on the finding of delayed, or normal, gastric emptying. Non-gastrointestinal disorders can also cause chronic nausea and vomiting. As a validated treatment algorithm for chronic nausea and vomiting does not exist, treatment should be based on a thoughtful discussion of benefits, side effects, and costs. The objective of this monograph is to review the evaluation and treatment of patients with chronic nausea and vomiting, emphasizing common gastrointestinal causes.

Variation in Care for Patients with Irritable Bowel Syndrome in the United States.

OBJECTIVES: Irritable bowel syndrome (IBS) affects nearly one in seven Americans. Significant national variations in care may exist, due to a current lack of standardized diagnosis and treatment algorithms; this can translate into a substantial additional economic burden. The study examines healthcare resource utilization in patients with IBS and in the subset of IBS patients with constipation (IBS-C) and analyzes the variation of IBS care for these patients across the United States (US). METHODS: Healthcare resource use (HRU), including gastrointestinal (GI) procedures and tests, all-cause and intestinal-related medical visits, GI specialist visits, and constipation or diarrhea pharmacy prescriptions for IBS patients enrolled in a large US administrative claims database (2001-2012) were analyzed for the 24-month period surrounding first diagnosis. Multivariate regression models, adjusting for age, gender, year of first diagnosis, insurance type, and Charlson comorbidity index, compared HRU across states (each state vs. the average of all other states). RESULTS: Of 201,322 IBS patients included, 77.2% were female. Mean age was 49.4 years. One in three patients had ≥3 distinct GI medical procedures or diagnostic tests; 50.1% visited a GI specialist. Significant HRU differences were observed in individual states compared to the national average. IBS-C patients had more medical visits, procedures, and pharmacy prescriptions for constipation/diarrhea than IBS patients without constipation. CONCLUSIONS: This study is the first to identify considerable regional variations in IBS healthcare across the US and to note a markedly higher HRU by IBS-C patients than by IBS patients without constipation. Identifying the reasons for these variations may improve quality of care and reduce the economic burden of IBS.

Multi-Dimensional Gastrointestinal Symptom Severity Index: Validation of a Brief GI Symptom Assessment Tool.

UNLABELLED: Few instruments have been developed and validated for the evaluation of multi-dimensional GI symptoms. The Gastrointestinal Symptoms Severity Index (GISSI), a multi-dimensional, self-report instrument, was designed as a brief measure of the frequency, severity, and bothersomeness of individual GI and pelvic floor/urogynecologic symptoms. AIM: To report the psychometric properties of the GISSI subscales, including factorial structure, validity, and internal consistency. METHODS: The GISSI included 32 items that assessed upper and lower GI symptoms and seven items related to pelvic floor/urogynecologic symptoms. A total of 934 patients presenting for upper and lower GI complaints completed the questionnaire between January 2013 and December 2013. The sample was randomly split into derivation (n = 466) and validation datasets (n = 468). A non-patient sample of 200 was collected separately. RESULTS: Exploratory factor analysis supported a six-factor model for the derivation sample that accounted for 69.3 % of the total variance. The six GI symptom clusters were labeled as constipation/difficult defecation (five items), abdominal pain/discomfort (four items), dyspepsia (four items), diarrhea/anal incontinence (four items), GERD/chest symptoms (four items), and nausea/vomiting (two items). Inclusion of additional items related to female pelvic floor/urogynecologic symptoms resulted in a separate factor. Confirmatory factor analysis of the validation dataset supported the a priori hypothesized six-factor measurement model (Χ (2)(428) = 1462.98; P < 0.001; GFI = .88; RMSEA = .051). CONCLUSION: The GISSI demonstrated good to excellent psychometric properties and provided multi-dimensional scaling of prominent GI symptom clusters. Further validation may provide an efficient, valid, and reliable measure of patient-reported clinical outcomes.

IBS patients' willingness to take risks with medications.

OBJECTIVES: We explored irritable bowel syndrome (IBS) patients' impulsivity and risk-taking behavior and their willingness to take medication risks. METHODS: A validated questionnaire assessed the illness experience of IBS patients. A standard gamble evaluated respondents' willingness to take medication risks. RESULTS: IBS patients with severe symptoms were more willing to take significant medication risks than those with mild or moderate symptoms. Impulsivity scores were not associated with an increased likelihood of taking medication risks. Age, gender, and years of IBS symptoms were not associated with medication risk-taking behavior. IBS patients reported they would accept a median 1% risk of sudden death for a 99% chance of cure for their symptoms using a hypothetical medication. CONCLUSIONS: IBS patients are willing to take significant medication risks to cure their symptoms. To counsel patients effectively, physicians must determine and understand IBS patients' risk aversion.

Functional Dyspepsia Treatment Trial (FDTT): a double-blind, randomized, placebo-controlled trial of antidepressants in functional dyspepsia, evaluating symptoms, psychopathology, pathophysiology and pharmacogenetics.

BACKGROUND: Functional dyspepsia (FD) is a common problem affecting up to 10-25% of individuals. FD accounts for significant health care costs and affects quality of life but has no definitive treatment. OBJECTIVES: The Functional Dyspepsia Treatment Trial (FDTT) aims to test whether treatment with an antidepressant (amitriptyline or escitalopram) leads to improvement of symptoms in patients with moderate to severe FD. DESIGN: The FDTT is an international multicenter, parallel group, randomized, double-blind, placebo-controlled trial to evaluate whether 12 weeks of treatment with escitalopram or amitriptyline improves FD symptoms compared to treatment with placebo. Secondly, it is hypothesized that acceleration of solid gastric emptying, reduction of postprandial satiation, and enhanced gastric volume change with a meal will be significant positive predictors of short- and long-term outcomes for those on antidepressants vs. placebo. The third aim is to examine whether polymorphisms of GNß3 and serotonin reuptake transporter influence treatment outcomes in FD patients receiving a tricyclic antidepressant, selective serotonin reuptake inhibitor therapy, or placebo. METHODS: The FDTT enrollment began in 2006 and is scheduled to randomize 400 patients by the end of 2012 to receive an antidepressant or placebo for 12 weeks, with a 6-month post-treatment follow-up. The study incorporates multiple validated questionnaires, physiological testing, and specific genetic evaluations. The protocol was approved by participating centers' Institutional Review Boards and an independent Data Safety Monitoring Board was established for monitoring to ensure patient safety and a single interim review of the data in December 2010 (ClinicalTrials.gov number NCT00248651).

A 32-year-old woman with chronic abdominal pain.

Functional dyspepsia is a highly prevalent disorder that accounts for 5% of visits to primary care clinicians. It frequently coexists with other gastrointestinal tract disorders, including irritable bowel syndrome and gastroesophageal reflux disease. Symptoms of functional dyspepsia, including epigastric pain, early satiety, and postprandial nausea, are nonspecific, making its diagnosis difficult. Functional dyspepsia is a heterogeneous disorder involving a number of different pathophysiologic processes, culminating in both gastrointestinal sensory and motor dysfunction. Although functional dyspepsia does not impart any increased risks to long-term health, it significantly affects both individuals and society. The economic burden of evaluating and treating functional dyspepsia is estimated to be at least $1 billion per year, and patients with functional dyspepsia experience a markedly reduced quality of life. Using the case of Ms C, we apply an evidence-based approach to highlight current knowledge in the diagnosis, evaluation, and treatment of functional dyspepsia.

Age, specialty, and practice setting predict gastroesophageal reflux disease prescribing behavior.

BACKGROUND: Gastroesophageal reflux disease (GERD) affects more than 40% of adults in the United States each month. Although the economic costs of treating this disorder are enormous, the attitudes and prescribing preferences of physicians who treat patients with GERD are not well known. This study was undertaken to determine physician prescribing practices in the treatment of GERD. METHODS: A questionnaire was mailed to 687 randomly selected, practicing gastroenterologists, internists, and family physicians in the State of Maryland. Each questionnaire was identical and contained 7 questions designed to elicit demographic data (age, sex, degree, specialty, practice setting, years in practice, community served), and 16 questions related to the evaluation and treatment of GERD. RESULTS: A total of 214 completed questionnaires were returned (31.1%), nearly equally distributed among the three different specialty groups. A total of 82% of the respondents were male; 60% of the respondents had practiced more than 15 years, and 6% had practiced 4 years or less. Older physicians prescribed proton pump inhibitors more often than younger physicians for mild or intermittent GERD symptoms. Physicians in an academic setting were more likely to use step-down therapy in patients with well-controlled GERD symptoms than were HMO-employed physicians. Family physicians requested a barium swallow in the evaluation of uncomplicated GERD more frequently than did gastroenterologists or internists. Gastroenterologists were more likely than family physicians and internists to recommend upper endoscopy for GERD patients with warning symptoms and for patients with long-standing reflux disease. CONCLUSIONS: Age, specialty, number of years in practice, and practice setting significantly influence how physicians evaluate and treat patients with GERD. Educational efforts to improve the evaluation and treatment of patients with GERD may require different strategies for different types of healthcare providers.