Prescribing of Proton Pump Inhibitors for Prevention of Upper Gastrointestinal Bleeding in US Outpatient Visits.

Antisecretory medications, primarily proton pump inhibitors (PPIs), have proven effective in reducing upper gastrointestinal toxicities, including upper gastrointestinal bleeding (UGIB), associated with nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin, which are among the most commonly used medications in the United States.1 Accordingly, professional guidance recommends PPIs for patients at high risk for UGIB.2-4 However, little is known about trends in use of antisecretory medications for gastrointestinal prophylaxis ("gastroprotection"). Herein, we examined contemporary use and prescribing of antisecretory medications in visits by patients at high risk for UGIB, relative to visits by patients diagnosed with acid-related disorders.

Yield of Repeat Endoscopy for Barrett's Esophagus After Normal Index Endoscopy.

INTRODUCTION: Guidelines suggest 1-time screening with esophagogastroduodenoscopy (EGD) for Barrett's esophagus (BE) in individuals at an increased risk of esophageal adenocarcinoma (EAC). We aimed to estimate the yield of repeat EGD performed at prolonged intervals after a normal index EGD. METHODS: We conducted a national retrospective analysis within the U S Veterans Health Administration, identifying patients with a normal index EGD between 2003 and 2009 who subsequently had a repeat EGD. We tabulated the proportion with a new diagnosis of BE, EAC, or esophagogastric junction adenocarcinoma (EGJAC) and conducted manual chart review of a sample. We fitted logistic regression models for the odds of a new diagnosis of BE/EAC/EGJAC. RESULTS: We identified 71,216 individuals who had a repeat EGD between 1 and 16 years after an index EGD without billing or cancer registry codes for BE/EAC/EGJAC. Of them, 4,088 had a new billing or cancer registry code for BE/EAC/EGJAC after the repeat EGD. On manual review of a stratified sample, most did not truly have new BE/EAC/EGJAC. A longer duration between EGD was associated with greater odds of a new diagnosis (adjusted odds ratio [aOR] for each 5 years 1.31; 95% confidence interval [CI] 1.19-1.44), particularly among those who were younger during the index EGD (ages 19-29 years: aOR 3.92; 95% CI 1.24-12.4; ages 60-69 years: aOR 1.19; 95% CI 1.01-1.40). DISCUSSION: The yield of repeat EGD for BE/EAC/EGJAC seems to increase with time after a normal index EGD, particularly for younger individuals. Prospective studies are warranted to confirm these findings.

Barriers to Guideline-Based Use of Proton Pump Inhibitors to Prevent Upper Gastrointestinal Bleeding.

PURPOSE: Gastrointestinal (GI) bleeding is one of the most common serious adverse drug events. Guidelines recommend proton pump inhibitor (PPI) gastroprotection to prevent upper GI bleeding in high-risk patients, but this practice is underused. METHODS: To explore prescribing practices and barriers to the use of PPI gastroprotection, including dynamics within and across specialties, we conducted semistructured interviews with physicians in 4 specialties at a single institution. We performed thematic analysis of barriers, organized around the theoretical domains framework. RESULTS: The sample included 5 primary care physicians (PCPs), 4 cardiologists, 3 gastroenterologists, and 3 vascular surgeons. Most PCPs, gastroenterologists, and vascular surgeons seldom prescribed PPI gastroprotection. Cardiologists varied most in their use of PPI gastroprotection, with some prescribing it consistently and others never. Major barriers related to the following 3 themes: (1) knowledge, (2) decision processes, and (3) professional role. Knowledge of guidelines was greatest among cardiologists and gastroenterologists and low among PCPs and vascular surgeons, and PCPs tended to focus on adverse effects associated with PPIs, which made them reluctant to prescribe them. For cardiologists, prevention of bleeding was usually a priority, but they sometimes deferred prescribing to others. For the other 3 specialties, PPI gastroprotection was a low priority. There was unclear delineation of responsibility for prescribing gastroprotection between specialties. CONCLUSIONS: Major barriers to PPI gastroprotection relate to knowledge, decision processes, and professional role, which operate differentially across specialties. Multicomponent interventions will likely be necessary to improve guideline-based use of PPIs to prevent upper GI bleeding.VISUAL ABSTRACT.

Regression and Random Forest Machine Learning Have Limited Performance in Predicting Bowel Preparation in Veteran Population.

BACKGROUND: Inadequate bowel preparation undermines the quality of colonoscopy, but patients likely to be affected are difficult to identify beforehand. AIMS: This study aimed to develop, validate, and compare prediction models for bowel preparation inadequacy using conventional logistic regression (LR) and random forest machine learning (RFML). METHODS: We created a retrospective cohort of patients who underwent outpatient colonoscopy at a single VA medical center between January 2012 and October 2015. Candidate predictor variables were chosen after a literature review. We extracted all available predictor variables from the electronic medical record, and bowel preparation from the endoscopy database. The data were split into 70% training and 30% validation sets. Multivariable LR and RFML were used to predict preparation inadequacy as a dichotomous outcome. RESULTS: The cohort included 6,885 Veterans, of whom 964 (14%) had inadequate preparation. Using LR, the area under the receiver operating characteristic curve (AUC) for the validation cohort was 0.66 (95% CI 0.62, 0.69) and the Brier score, in which a lower score indicates better performance, was 0.11. Using RFML, the AUC for the validation cohort was 0.61 (95% CI 0.58, 0.65) and the Brier score was 0.12. CONCLUSIONS: LR and RFML had similar performance in predicting bowel preparation, which was modest and likely insufficient for use in practice. Future research is needed to identify additional predictor variables and to test other machine learning algorithms. At present, endoscopy units should focus on universal strategies to enhance preparation adequacy.

A survey of internists' recommendations for aspirin in older adults and barriers to evidence-based use.

Recent trials suggest that aspirin for primary prevention may do more harm than good for some, including adults over 70 years of age. We sought to assess how primary care providers (PCPs) use aspirin for the primary prevention in older patients and to identify barriers to use according to recent guidelines, which recommend against routine use in patients over age 70. We surveyed PCPs about whether they would recommend aspirin in clinical vignettes of a 75-year-old patient with a 10-year atherosclerotic cardiovascular disease risk of 25%. We also queried perceived difficulty following guideline recommendations, as well as perceived barriers and facilitators. We obtained responses from 372 PCPs (47.9% response). In the patient vignette, 45.4% of clinicians recommended aspirin use, which did not vary by whether the patient was using aspirin initially (p = 0.21); 41.7% believed aspirin was beneficial. Perceived barriers to guideline-based aspirin use included concern about patients being upset (41.6%), possible malpractice claims (25.0%), and not having a strategy for discussing aspirin use (24.5%). The estimated adjusted probability of rating the guideline as "hard to follow" was higher in clinicians who believed aspirin was beneficial (29.4% vs. 8.0%; p < 0.001) and who worried the patient would be upset if told to stop aspirin (26.7% vs. 12.5%; p = 0.001). Internists vary considerably in their recommendations for aspirin use for primary prevention in older patients. A high proportion of PCPs continue to believe aspirin is beneficial in this setting. These results can inform de-implementation efforts to optimize evidence-based aspirin use.

Incomplete Response of Gastroesophageal Reflux Symptoms Poorly Predicts Erosive Esophagitis or Barrett's Esophagus.

BACKGROUND & AIMS: Many patients with symptoms of gastroesophageal reflux disease (GERD) not responding to a proton pump inhibitor (PPI) undergo an upper endoscopy. We hypothesized that an incomplete response to a PPI is not associated with findings of esophageal pathology on endoscopy, and that psychological distress is associated inversely with pathology. METHODS: We enrolled consecutive individuals aged 40 to 79 years with prior heartburn or regurgitation. Logistic regression was used to estimate the effects of incomplete response of GERD symptoms and psychological distress on the odds of finding erosive esophagitis or Barrett's esophagus. RESULTS: A total of 625 patients completed the study. A total of 254 (66.8% of those taking PPI) had GERD symptoms incompletely responsive to a PPI and 352 (56.3%) had severe somatization. An incomplete response to a PPI was associated with psychological distress (P < .001). Erosive esophagitis was found in 148 subjects (23.7%) and Barrett's esophagus in 58 (9.3%). Overall, an incomplete response to a PPI was not found to be associated with these pathologies (odds ratio, 1.17; 95% CI, 0.720-1.91). In contrast, greater psychological distress was associated inversely with erosive esophagitis or Barrett's esophagus (in particular, highest vs lowest tertile somatization: odds ratio, 0.590; 95% CI, 0.365-0.952). CONCLUSIONS: Patients undergoing upper endoscopy frequently have GERD symptoms incompletely responding to a PPI and a high burden of somatization. However, an incomplete response of GERD symptoms is a poor predictor for endoscopic pathology, and should not be relied upon for selecting patients for screening for Barrett's esophagus. Patients with high psychological distress are less likely to have esophageal pathology.

Trials of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention Lack Strategies to Ensure Appropriate Gastroprotection.

INTRODUCTION: Gastrointestinal bleeding is a morbid complication of dual antiplatelet therapy (DAPT). We evaluated the extent to which contemporary trials of DAPT included steps to ensure appropriate use of proton pump inhibitor (PPI) gastroprotection and reported rates of PPI use. METHODS: A methodological review of randomized trials comparing varying durations of DAPT after percutaneous coronary intervention. RESULTS: Among 21 trials, none incorporated protocol procedures or guidance for prescribing PPIs. Five reported rates of PPI use (range 25.6-69.1%). DISCUSSION: PPI gastroprotection is overlooked in major trials of DAPT. Appropriate use of PPI gastroprotection represents an important opportunity to improve patient safety.

Using Health Systems Engineering Approaches to Prepare for Tailoring of Implementation Interventions.

BACKGROUND: Implementation of evidence-based practices often requires tailoring implementation strategies to local contextual factors, including available resources, expertise, and cultural norms. Using an exemplar case, we describe how health systems engineering methods can be used to understand system-level variation that must be accounted for prior to broad implementation. METHODS: Within the context of a single-center quality improvement activity, a multi-disciplinary stakeholder team used health systems engineering methods to describe how pre-endoscopy antithrombotic management was executed, and implemented a redesigned process to improve clinical care. The research team then conducted multiple stakeholder focus groups at four different health-care systems to describe and compare current processes for pre-endoscopy antithrombotic medication management. Detailed work flow maps for each health-care system were developed, analyzed, and integrated to develop an overarching current work flow map, identify key process steps, and describe areas of process variation. RESULTS: Five key process steps were identified across the four health systems: (1) place an endoscopy order, (2) screen for antithrombotic use, (3) coordinate medication management, (4) instruct the patient, and (5) confirm appropriate medication management before procedure. Across health systems, we found a high degree of variation in each step (e.g., who performed, use of technology, systematic vs. ad hoc process). This variation was influenced by two key system-level contextual factors: (1) degree of health system integration and (2) role and training level of available staff. These key steps, areas of variation, and contextual factors were integrated into an assessment tool designed to facilitate tailoring of a future implementation and dissemination strategy. CONCLUSIONS: Tools from health systems engineering can be used to identify key work flow process steps, variations in how those steps are executed, and influential contextual factors. This process and the associated assessment tool may facilitate broader implementation tailoring.

Physicians' Perceptions of Proton Pump Inhibitor Risks and Recommendations to Discontinue: A National Survey.

OBJECTIVE: To provide contemporary estimates of internists' perceptions of adverse effects associated with proton pump inhibitors (PPIs) and self-reported clinical use. METHODS: We invited 799 internists, including specialists and postgraduate trainees, to complete an online survey. Topics included perceptions of PPI adverse effects (AEs) and effectiveness for upper gastrointestinal bleeding (UGIB) prevention, changes in prescribing, and management recommendations for patients using PPIs for gastroesophageal reflux disease or UGIB prevention. We used logistic regression to identify factors associated with appropriate PPI continuation in the scenario of a patient at high risk for UGIB. RESULTS: Among 437 respondents (55% response rate), 10% were trainees and 72% specialized in general medicine, 70% were somewhat/very concerned about PPI AEs, and 76% had somewhat/very much changed their prescribing. A majority believed PPIs increase the risk for 6 of 12 AEs queried. Fifty-two percent perceived PPIs to be somewhat/very effective for UGIB prevention. In a gastroesophageal reflux disease scenario in which PPI can be safely discontinued, 86% appropriately recommended PPI discontinuation. However, in a high-risk UGIB prevention scenario in which long-term PPI use is recommended, 79% inappropriately recommended discontinuation. In this latter scenario, perceived effectiveness for bleeding prevention was strongly associated with continuing PPI (odds ratio 7.68, P < 0.001 for moderately; odds ratio 17.3, P < 0.001 for very effective). Other covariates, including concern about PPI AEs, had no significant association. DISCUSSION: Most internists believe PPIs cause multiple AEs and recommend discontinuation even in patients at high risk for UGIB. Future interventions should focus on ensuring that PPIs are prescribed appropriately according to individual risks and benefits.

Identification of undocumented over-the-counter medications in an academic nephrology clinic.

OBJECTIVES: To explore how accurately over-the-counter (OTC) medications were documented in an academic nephrology clinic and the benefits of using a novel short questionnaire as part of medication reconciliation (MR). METHODS: We developed a 3-item tailored questionnaire with questions about use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and proton pump inhibitors (PPIs), which clinical leadership identified as medications of interest. Over the course of 20 days, medical assistants administered the questionnaire to clinic patients immediately after the standard MR. We summarized the rate of inaccurate medication documentation by individual drug and drug class, comparing the standard MR process with the questionnaire. We also calculated diagnostic performance characteristics of the questionnaire. We evaluated the severity of drug-drug interactions between OTC medications discovered using the OTC medication questionnaire and patients' other prescription medications. RESULTS: Nearly 30% (n = 133 of 450) of the participants had at least 1 inaccurately documented OTC medication after the standard MR. The sensitivity and specificity of the standard MR were 79.2% and 93.5%, respectively, for aspirin; 14.5% and 99.5% for NSAIDs; and 80.4% and 97.3% for PPIs. Medication omissions were resolved in the electronic health record approximately two-thirds of the time using the questionnaire. At least 1 drug-drug interaction (DDI) involving active use of an OTC medication was identified in 9.6% of the patients. Of the DDIs, the most common portended effects were increased nephrotoxicity (52.9%), increased bleeding risk (22.9%), and enhanced antiplatelet activity (7.1%). CONCLUSION: Despite the standard MR process, inaccurate documentation of commonly used OTC medications occurred in nearly one-third of outpatients in a nephrology clinic. A brief OTC medication questionnaire may be a scalable and effective strategy to address this problem.

Rethinking the Re-Prep: Attitudes Toward Noninvasive Colorectal Cancer Screening Tests After Inadequate Bowel Preparation.

OBJECTIVES: To assess patient preferences for colorectal cancer screening with stool-based tests after initial colonoscopy with suboptimal bowel preparation. METHODS: An online scenario-based survey of adults aged 45 to 75 years at average risk for colorectal cancer was performed. RESULTS: When presented with a hypothetical scenario of screening colonoscopy with suboptimal bowel preparation, 59% of respondents chose stool-based testing as a next step, 29% preferred a repeat colonoscopy within a year, and 12% preferred a repeat colonoscopy in 10 years (N = 1,080). CONCLUSIONS: Clinicians should consider offering stool-based screening tests as an alternative to repeat colonoscopy after suboptimal bowel preparation.

Patients' Perceptions of Proton Pump Inhibitor Risks and Attempts at Discontinuation: A National Survey.

OBJECTIVES: Little is known about how reports on the adverse effects of proton pump inhibitors (PPIs) impact patients' perceptions of these drugs and medication use. We sought to determine patients' level of concern about PPI adverse effects and its association with attempts to discontinue these drugs. METHODS: This study is an online survey of US adults who use PPIs for gastroesophageal reflux disease. Topics included awareness of and concern about PPI adverse effects, prior discussion with providers, and attempts to stop PPI because of concern about adverse effects. For the primary analysis, we used logistic regression to identify associations between having attempted to stop PPI and concern about PPI-related adverse effects, a provider's recommendation to stop, risk of upper gastrointestinal bleeding (UGIB), age, and gender. RESULTS: Among 755 patient participants, mean age was 49 years (s.d. 16), 71% were women, and 24% were at high risk of UGIB. Twenty percent of patients were able to write in ≥1 reported adverse effect, and 46% endorsed awareness of ≥1 adverse effect when presented with a list, most commonly chronic kidney disease (17%). Thirty-three percent of patients were slightly concerned, 32% somewhat concerned, and 14% extremely concerned about adverse effects. Twenty-four percent of patients had discussed PPI risks and benefits with a provider, and 9% had been recommended to stop. Thirty-nine percent had attempted to stop their PPI, most (83%) without a provider recommendation. Factors associated with an attempt at stopping PPI included: (i) provider recommendation to stop (odds ratio [OR] 3.26 [1.82-5.83]); (ii) concern about adverse effects (OR 5.13 [2.77-9.51] for slightly, 12.0 [6.51-22.2] for somewhat, and 19.4 [9.75-38.7] for extremely concerned); and (iii) female gender (OR 1.64 [1.12-2.39]). Patients at high risk of UGIB were as likely to have attempted to stop as others (OR 0.98 [0.66-1.44]). CONCLUSIONS: Concern about PPIs is common and strongly associated with attempts at discontinuation, even without a provider's recommendation. Notably, individuals at high risk of UGIB, who benefit from PPIs, were equally likely to have tried stopping PPIs as others. Providers should proactively discuss the risks and benefits of PPIs with their patients, who may otherwise make unwise decisions about PPI management on their own.

The Clinical and Economic Effects of Targeted Bowel Preparation: Results of a Decision Analysis.

BACKGROUND: Colonoscopy bowel preparation failure is common, costly, and clinically harmful. Prediction models can identify patients at high risk for preparation failure, but they are rarely used. GOALS: To investigate the clinical and economic effects of using a more intensive preparation upfront (a "targeted" strategy) for patients identified as high risk for preparation failure. STUDY: We developed a Markov decision analytic model to compare usual care with a targeted strategy. Usual care consisted of a 4 L preparation, followed by a 2-day preparation in the event of preparation failure. The targeted strategy consisted of a 4 L preparation for low-risk patients, and upfront 2 days preparation for high-risk patients. Base-case values were gathered from literature review. Under each strategy, we calculated days spent preparing for, or undergoing, colonoscopy (patient burden), and cost per patient (payer perspective). Sensitivity analyses were performed. RESULTS: In the base case, the targeted strategy resulted in a similar patient burden compared with usual care (2.56 vs. 2.51 d, respectively). However, it substantially reduced cost per patient ($1254 vs. $1343) by reducing the number of colonoscopies. In sensitivity analyses, the targeted strategy reduced cost across the entire plausible range of risk of preparation failure and prediction model sensitivity and specificity. The targeted strategy resulted in less patient burden than usual care when (1) preparation failure risk exceeded 20%; (2) prediction sensitivity exceeded 73%; or (3) prediction specificity exceeded 76%. CONCLUSIONS: Targeted bowel preparation is likely to reduce costs associated with repeat colonoscopy with minimal effect on patient burden.

Mind the gap: results of a multispecialty survey on coordination of care for peri-procedural anticoagulation.

To understand how physicians from various specialties perceive coordination of care when managing peri-procedural anticoagulation. Cross-sectional survey of cardiologists, gastroenterologists, and primary care physicians (PCPs) in an integrated health system (N = 251). The survey began with a vignette of a patient with atrial fibrillation co-managed by his PCP, cardiologist, and an anticoagulation clinic who must hold warfarin for a colonoscopy. Respondents' experiences and opinions around responsibilities and institutional support for managing peri-procedural anticoagulation were elicited using multiple choice questions. We examined differences in responses across specialties using Chi square analysis. The response rate was 51% (n = 127). 52% were PCPs, 28% cardiologists, and 21% gastroenterologists. Nearly half (47.2%) of respondents believed that the cardiologist should be primarily responsible for managing peri-procedural anticoagulation, while fewer identified the PCP (25.2%), anticoagulation clinic (21.3%), or gastroenterologist (6.3%; p = 0.09). Respondents across specialties had significantly different approaches to deciding how to manage the clinical case presented (p < 0.001). Most cardiologists (60.0%) would decide whether to offer bridging without consulting with other providers or clinical resources, while most PCPs would decide after consulting clinical resources (57.6%). Gastroenterologists would most often (46.2%) defer the decision to another provider. A majority of all three specialties agreed that their institution could do more to help manage peri-procedural anticoagulation, and there was broad support (88.1%) for anticoagulation clinics' managing all aspects of peri-procedural anticoagulation. Providers across specialties agree that their institution could do more to help manage peri-procedural anticoagulation, and overwhelmingly support anticoagulation clinics' taking responsibility.

Valproic Acid in Women and Girls of Childbearing Age.

PURPOSE OF REVIEW: The aim of this paper is to evaluate recent literature on valproic acid (VPA) in women and girls of childbearing age and to emphasize new findings. RECENT FINDINGS: Recent research confirms VPAs teratogenicity and risk of hormone disruption. VPA exposure in utero increases the risk for a variety of major congenital malformations (MCMs), reduced IQ and behavioral problems. In girls and women, VPA increases the risk of hormone abnormalities, obesity, and polycystic ovarian syndrome (PCOS). Despite guidelines recommending caution, VPA use continues to be prescribed to reproductive-aged women and girls. Despite significant and well-documented risk, adherence to guidelines in VPA use in reproductive-aged girls and women remains low.

A meta-analysis of the utility of C-reactive protein, erythrocyte sedimentation rate, fecal calprotectin, and fecal lactoferrin to exclude inflammatory bowel disease in adults with IBS.

OBJECTIVES: Irritable bowel syndrome (IBS) is viewed as a diagnosis of exclusion by most providers. The aim of our study was to perform a systematic review and meta-analysis to evaluate the utility of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fecal calprotectin, and fecal lactoferrin to distinguish between patients with IBS and inflammatory bowel disease (IBD) and healthy controls (HCs). METHODS: A systematic online database search was performed. Included studies were prospective, adult, diagnostic cohort studies with any of the four tests. The means and s.d. values of biomarker logarithms were estimated based on studies that gave medians and either confidence intervals for the median, interquartile ranges, or ranges. We used a Naive Bayes approach to estimate the probability of being a HC, having IBS, or having IBD based on the biomarker values. RESULTS: Systematic review identified 1,252 citations. After cross-referencing medical subject headings, detailed evaluation identified 140 potentially relevant journal articles/abstracts for CRP, ESR, calprotectin, and lactoferrin of which 4, 4, 8, and 2 fulfilled our inclusion criteria, respectively. None of the biomarkers reliably distinguished between IBS and healthy controls. At a CRP level of ≤0.5 or calprotectin level of ≤40 µg/g, there was a ≤1% probability of having IBD. Individual analysis of ESR and lactoferrin had little clinical utility. CONCLUSION: CRP and calprotectin of ≤0.5 or 40, respectively, essentially excludes IBD in patients with IBS symptoms. The addition of CRP and calprotectin to symptom-based criteria may improve the confident diagnosis of IBS.

Irritable bowel syndrome: a clinical review.

IMPORTANCE: Irritable bowel syndrome (IBS) affects 7% to 21% of the general population. It is a chronic condition that can substantially reduce quality of life and work productivity. OBJECTIVES: To summarize the existing evidence on epidemiology, pathophysiology, and diagnosis of IBS and to provide practical treatment recommendations for generalists and specialists according to the best available evidence. EVIDENCE REVIEW: A search of Ovid (MEDLINE) and Cochrane Database of Systematic Reviews was performed for literature from 2000 to December 2014 for the terms pathophysiology, etiology, pathogenesis, diagnosis, irritable bowel syndrome, and IBS. The range was expanded from 1946 to December 2014 for IBS, irritable bowel syndrome, diet, treatment, and therapy. FINDINGS: The database search yielded 1303 articles, of which 139 were selected for inclusion. IBS is not a single disease but rather a symptom cluster resulting from diverse pathologies. Factors important to the development of IBS include alterations in the gut microbiome, intestinal permeability, gut immune function, motility, visceral sensation, brain-gut interactions, and psychosocial status. The diagnosis of IBS relies on symptom-based criteria, exclusion of concerning features (symptom onset after age 50 years, unexplained weight loss, family history of selected organic gastrointestinal diseases, evidence of gastrointestinal blood loss, and unexplained iron-deficiency anemia), and the performance of selected tests (complete blood cell count, C-reactive protein or fecal calprotectin, serologic testing for celiac disease, and age-appropriate colorectal cancer screening) to exclude organic diseases that can mimic IBS. Determining the predominant symptom (IBS with diarrhea, IBS with constipation, or mixed IBS) plays an important role in selection of diagnostic tests and treatments. Various dietary, lifestyle, medical, and behavioral interventions have proven effective in randomized clinical trials. CONCLUSIONS AND RELEVANCE: The diagnosis of IBS relies on the identification of characteristic symptoms and the exclusion of other organic diseases. Management of patients with IBS is optimized by an individualized, holistic approach that embraces dietary, lifestyle, medical, and behavioral interventions.