David J. Levinthal

Irritable bowel syndrome (IBS) is a common, chronic disorder of gut-brain interaction that is characterized by core clinical features of abdominal pain and altered bowel movements. Because IBS remains defined by symptom patterns, most clinical care for patients with IBS relies on treatments directed by IBS subtype. Although the biopsychosocial model has advanced disorder of gut-brain interaction research and clinical care, and the current Rome IV criteria have greatly helped the diagnostic paradigm for IBS, the model does not identify specific pathophysiological mechanisms that operate in any one patient. Consequently, most interventions for IBS benefit only subsets of patients, and patients often progress through a series of trial and error approaches to manage their IBS symptoms. There is a major clinical need to develop a practical basis for a personalized medicine approach in IBS care. In this article, we discuss how clinicians may incorporate additional clinical features and actionable biomarkers to better inform the initial choice of therapy for patients with IBS. Ideally, such a mechanistic approach should be more efficient, and ultimately more effective, leading to improved patient satisfaction and clinical outcomes.

Background: Data are limited on the natural history and symptom patterns of cyclic vomiting syndrome (CVS), a disorder of gut–brain interaction characterized by recurrent stereotypical vomiting, retching, and nausea episodes.Methods: A 6‐month, observational, remote study prospectively assessed symptom patterns in adults with CVS using an electronic daily diary. Patients recorded their disease experience, including CVS symptoms and associated severity, in the daily diary. The study defined a CVS episode start as the first day of 5 or more vomiting and/or retching (V + R) events. Episode end was defined as the first day of ≥ 7 (prespecified main analysis) or ≥ 4 (sensitivity analysis) days without any diary V + R events.Key Results: Eighty‐eight of 93 (94.6%) enrolled patients (62 female; mean age, 37.7 years) had daily diary data recorded during the study; 61 (69.3%) patients had at least one episode. In the prespecified main analysis, 191 episodes (median, 0.6 per 30 diary days) were reported (median duration, 3.0 days); 17.8% of the episodes lasted > 10 days. In the sensitivity analysis, 248 episodes (median, 0.7 per 30 diary days) were reported (median duration, 2.0 days). Thirteen of 88 (14.8%) patients with diary data had interepisodic V + R (reported V + R events without meeting the threshold for study‐defined episode). Other CVS‐related (non‐V + R) symptoms (most frequently nausea, abdominal pain, and sweating) were reported more frequently during the episode versus the interepisodic period.Conclusions and Inferences: This prospective longitudinal study shows marked heterogeneity of CVS episodes and highlights the need to better define and characterize episodes in these patients.

Background: Cyclic vomiting syndrome (CVS) is defined by its episodic patterning. Furthermore, CVS is associated with other episodic disorders such as migraine and epilepsy. Indeed, many of the medications that are known to be useful for prophylaxis and abortive therapy in CVS are also effective in preventing and aborting migraines and seizures. These observations strongly suggest that CVS has a neural basis, but the precise pathophysiological mechanisms that operate in CVS remain unclear.Purpose: This brief review describes recent neurophysiological insights and opportunities to further advance the understanding of pathophysiological neural mechanisms that are present in patients with CVS. These insights are poised to translate into the next generation of neurotherapeutic strategies for CVS using central neuromodulation. Additionally, the development of neurophysiological tests of neural excitability could be positioned to shape management decisions in future CVS care.

Background: Cyclic vomiting syndrome (CVS) and cannabinoid hyperemesis syndrome (CHS) are both characterized by episodic, acute transitions from asymptomatic states to highly symptomatic states of nausea, repetitive vomiting, and often severe abdominal pain. Patients with CVS and CHS face significant challenges to abort or mitigate episodes at home and often require emergency department (ED)‐based care.Purpose: This paper reviews the current treatment approach to abort acute CVS and CHS episodes at home and in ED settings. Multiple pharmacologic and nonpharmacologic interventions have been demonstrated to potentially abort CVS or CHS episodes. Systemic pharmacologic agents often used as abortive therapy include triptans, antiemetics, anxiolytics, NK‐1 receptor antagonists, antipsychotics, sedatives in general, and various analgesic / anti‐inflammatory medications. Nonsystemic, nonpharmacologic approaches include reducing external stimuli (quiet room, dim lights, etc.), and hot water bathing or the application of topical capsaicin cream. More research is needed to develop evidence‐based, individualized abortive treatment plans, as well as to determine whether the abortive treatment for CVS requires a fundamentally different approach than for CHS. When home‐based approaches fail, all patients with CVS or CHS should receive nonjudgmental, informed, and compassionate care in the ED to abort their episode. Patients with more severe forms of CVS/CHS who require more frequent ED utilization should develop care plans with their ED to assure predictable and effective treatment.

Background: An increasing number of studies have explored the clinical features, epidemiology, pathophysiology, and management of cyclic vomiting syndrome (CVS). CVS is common in adults and children and negatively impacts patients, families, and the healthcare system. A related condition, cannabinoid hyperemesis syndrome (CHS), has been a focus of interest in the lay press and published literature.Purpose: Clinical presentations of CVS have been defined by small series and expert opinion, but recent prospective studies are refining our understanding of the spectrum of emetic episodes and the breadth of comorbid conditions. Large cross‐sectional population analyses are clarifying CVS prevalence and factors related to age, ethnicity, and geographic region. CVS pathophysiology is multifactorial with contributions from migraines, dysautonomia, endogenous cannabinoids, mitochondrial dysfunction, genetic abnormalities, and rapid gastric emptying. CVS treatment relies on antiemetics and antimigraine therapies to abort acute episodes coupled with prophylactic regimens employing neuromodulators and antiepileptics. CHS represents a challenge partly because of difficulties in achieving sustained cannabis abstinence. Benefits of other therapies in CHS remain poorly defined. Several areas warrant further scrutiny including better identification of CVS triggers and characterization of different CVS subsets including those with frequent severe episodes, refined description of epidemiology to allow targeting of populations predisposed to CVS development, rigorous definition of pathogenic factors to provide a foundation for exploratory studies of novel therapies, and conduct of controlled trials by multicenter collaborations to confirm benefits of existing and new therapies in development. Progress in these areas will be facilitated by generous governmental and industry support.

INTRODUCTION: Administrative health data could contribute to generalizable microscopic colitis insights, but International Classification of Diseases (ICD) codes for microscopic colitis have not been validated. METHODS: We identified individuals who received care for diarrhea in the Veterans Health Administration and classified them by receipt of microscopic colitis ICD codes. We reviewed random samples of charts to calculate the positive predictive value (PPV) and negative predictive value (NPV). We then calculated the sensitivity and specificity in clinically relevant cohorts. RESULTS: The PPV was 0.790, and the NPV was 0.995. In a cohort of individuals with diarrhea who underwent colonoscopy, the sensitivity and specificity were 0.734 and 0.996, respectively. DISCUSSION: Alternative ascertainment methods for microscopic colitis are needed because ICD codes have suboptimal performance.

INTRODUCTION: Cyclic vomiting syndrome (CVS) imposes a substantial burden, but epidemiological data are scarce. This study aimed to estimate the incidence and prevalence of CVS, comorbid conditions, and treatment patterns, using administrative databases in the United States. METHODS: This cross-sectional study used claims data from Merative MarketScan Commercial/Medicare Supplemental and Medicaid databases in all health care settings. Incidence and prevalence rates for 2019 were calculated and stratified by age, sex, region, and race/ethnicity. Patient characteristics were reported among newly diagnosed patients with CVS (i.e., no documented claims for CVS before 2019). CVS was defined as having 1+ inpatient and/or 2+ outpatient CVS claims that were 7+ days apart. RESULTS: The estimated prevalence of CVS was 16.7 (Commercial/Medicare) and 42.9 (Medicaid) per 100,000 individuals. The incidence of CVS was estimated to be 10.6 (Commercial/Medicare) and 26.6 (Medicaid) per 100,000 individuals. Both prevalence and incidence rates were higher among female individuals (for both Commercial/Medicare and Medicaid). Comorbid conditions were common and included abdominal pain (56%–64%), anxiety (32%–39%), depression (26%–34%), cardiac conditions (39%–42%), and gastroesophageal reflux disease (30%–40%). Despite a diagnosis of CVS, only 32%–35% had prescriptions for prophylactic treatment and 47%–55% for acute treatment within the first 30-day period following diagnosis. DISCUSSION: This study provides the first population-level estimates of CVS incidence and prevalence in the United States. Comorbid conditions are common, and most patients with CVS do not receive adequate treatment. These findings underscore the need for improving disease awareness and developing better screening strategies and effective treatments.

There is increasing appreciation that small intestinal bacterial overgrowth (SIBO) drives many common gastrointestinal symptoms, including diarrhea, bloating, and abdominal pain. Breath testing via measurement of exhaled hydrogen and methane gases following ingestion of a readily metabolized carbohydrate has become an important noninvasive testing paradigm to help diagnose SIBO. However, because of a number of physiological and technical considerations, how and when to use breath testing in the diagnosis of SIBO remains a nuanced clinical decision. This narrative review provides a comprehensive overview of breath testing paradigms including the indications for testing, how to administer the test, and how patient factors influence breath testing results. We also explore the performance characteristics of breath testing (sensitivity, specificity, positive and negative predictive values, likelihood ratios, and diagnostic odds ratio). Additionally, we describe complementary and alternative tests for diagnosing SIBO. We discuss applications of breath testing for research. Current estimates of SIBO prevalence among commonly encountered high-risk populations are reviewed to provide pretest probability estimates under a variety of clinical situations. Finally, we discuss how to integrate breath test performance characteristics into clinical care decisions using clinical predictors and the Fagan nomogram.