ACUTE AND LONG-TERM EFFECTS OF APP-DELIVERED HEARTFULNESS MEDITATION ON PSYCHOLOGICAL OUTCOMES AND THE ENDOCANNABINOID SIGNALING SYSTEM IN CYCLIC VOMITING SYNDROME.

BACKGROUND: Cyclic vomiting syndrome (CVS) is a disorder of gut brain interaction (DGBI) often triggered by stress. Interventions like meditation may improve psychological outcomes and Health-Related Quality of Life (HRQoL), but their efficacy and the underlying mechanism are unknown. METHODS: We conducted a 6-week single-arm pilot study to assess the effects of Heartfulness meditation (HFM) in CVS using a custom-designed meditation app. Primary outcomes included state and trait anxiety and mood state changes pre- vs. post-meditation, and secondary outcomes were psychological distress, coping, sleep quality and HRQoL at baseline and weeks 3 and 6. Serum concentrations of endocannabinoids N-arachidonylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG) and related lipids were measured pre-and-post HFM at baseline and week 6. RESULTS: In 30 treatment completers, there was a significant improvement in state anxiety (p<0.001), total mood disturbance (p<0.001), and other mood states (all p values <0.05) across the three time points. Trait anxiety was also improved at week 6. There was a significant improvement in psychological distress (global severity index), sleep quality (daytime dysfunction), coping (using religion/spirituality) and HRQoL (mental and physical) across the three time points (all p <0.05). Significant increases in AEA and related lipids N-oleoylethanolamine and palmitoylethanolamide post-vs.-pre HFM were observed at week 6 (p<0.001, 0.002, 0.003, respectively). No adverse effects were noted. DISCUSSION: App-delivered HFM is feasible, safe and effective and improves psychological outcomes and augments endocannabinoids. This provides insight into the mechanism underlying HFM and has potential for widespread use as a digital therapeutic in CVS and other DGBI.Study Highlights.

Epidemiology, Comorbidities, and Treatment of Cyclic Vomiting Syndrome in the United States.

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.

Pharmacogenomic testing for CYP2C19 and CYP2D6 in cyclic vomiting syndrome.

BACKGROUND: Amitriptyline (AT) is recommended as first-line prophylactic therapy in patients with cyclic vomiting syndrome (CVS). However, significant side effects limit its use and dosing is based on trial and error. Though the Clinical Pharmacogenetic Implementation Consortium (CPIC) Guidelines recommend dosing for AT based on CY2D6 and CYP2C19 genotype profile, this is not followed in clinical practice. METHODS: This pilot study determined CYP2C19 and CYP2D6 genotypes and ascertained its association with adverse drug reactions (ADRs), clinical response, and serum concentration of AT and nortriptyline in a well-characterized cohort of adults with CVS. KEY RESULTS: Of 46 subjects with CVS, age 33 ± 12 years, 61% female, 85% Caucasian, a third (33%) had normal CYP2C19 metabolizer status, while 4% were poor, and 43% were ultrarapid metabolizers. Most (61%) had normal CYP2D6 genotype while 9% were poor and 2% were ultra-rapid metabolizers. There was no statistically significant association between genotype and ADRs, clinical response or serum drug concentration. There was a trend towards significance between genotype and clinical response, with 64% of responders having normal CYP2D6 metabolism versus 36% of nonresponders (p = 0.06). ADRs were encountered in 46% of patients with 28% discontinuing the medication as a result. CONCLUSIONS AND INFERENCES: A subset of patients with CVS have dysfunctional alleles of CYP2C19 and CYP2D6. Larger prospective studies to evaluate the clinical impact of pharmacogenomic testing in CVS are needed. This has the potential to optimize clinical management, predict ADRs and allow for personalized therapy.

Cannabis use in the United States and its impact on gastrointestinal health.

In recent years, the legalization and social acceptability of cannabis use have increased in the United States. Concurrently, the prevalence of cannabis use has continued to rise, and cannabis products have diversified. There are growing concerns regarding the health effects of regular and high-potency cannabis use, and new research has shed light on its potentially negative effects. Here, we review evidence of the gastrointestinal (GI) effects of cannabis and cannabinoids. Dysregulation of the endocannabinoid system might contribute to various GI disorders, including irritable bowel syndrome and cyclic vomiting syndrome, and endocannabinoids have been found to regulate visceral sensation, nausea, vomiting, and the gut microbiome. Cannabis has been shown to have antiemetic properties, and the US Food and Drug Administration has approved cannabis-based medications for treating chemotherapy-induced nausea and vomiting. Yet, chronic heavy cannabis use has been linked to recurrent episodes of severe nausea and intractable vomiting (cannabinoid hyperemesis syndrome). Given the considerable heterogeneity in the scientific literature, it is unclear if cannabinoid hyperemesis syndrome is truly a distinct entity or a subtype of cyclic vomiting that is unmasked by heavy cannabis use and the associated dysregulation of the endocannabinoid system. The changes in cannabis legalization, availability, and public risk perceptions have outpaced research in this area and there is a need for robust, prospective, large-scale studies to understand the effects of cannabis use on GI health.

Percutaneous Electrical Nerve Field Stimulation for Drug-Refractory Pediatric Cyclic Vomiting Syndrome.

BACKGROUND: Cyclic vomiting syndrome (CVS) is a disabling condition frequently refractory to pharmacologic therapy. The aim of this study was to evaluate the effects of noninvasive, auricular percutaneous electrical nerve field stimulation (PENFS) as prophylactic therapy for pediatric CVS. METHODS: Children 8-18 years with drug-refractory CVS were prospectively enrolled from a tertiary care CVS clinic. Subjects received 6 consecutive weeks of PENFS. CVS severity was quantified by episode frequency and duration score (range 0-25) at baseline and at extended follow-up (4-6 months after end of therapy). Response was classified as ≥50% improvement in either frequency or duration of attacks at extended follow-up. Subjects also completed validated surveys of nausea, disability, and global response. RESULTS: Thirty subjects completed the study. Median (interquartile range, IQR) age was 10.5 (8.5-15.5) years; 60% were female. At follow-up, 80% met criteria for treatment response with a median (IQR) response duration of 113 (61-182) days. The frequency-duration score improved from baseline median (IQR) 12.0 (9.0-16.0) to 3.0 (1.0-6.0) at follow-up, P < 0.0001. Median (IQR) nausea and disability scores decreased from baseline to week 6: 2.1 (1.3-2.7) to 0.9 (0-1.6), P = 0.003 and 47.5 (41.0-53.0) to 38.0 (16.0-51.0), P = 0.001, respectively. At end of therapy, 66% and 55% patients reported global response of at least "moderately better" and "a good deal better," respectively. There were no serious side effects. CONCLUSIONS: This study suggests long-term benefits of PENFS for children with CVS. PENFS improves several disabling aspects of CVS, including episode frequency, duration, and functional disability.

Percutaneous electrical nerve field stimulation improves comorbidities in children with cyclic vomiting syndrome.

Introduction: Children with cyclic vomiting syndrome (CVS) frequently suffer from disabling abdominal pain and comorbidities that impair quality of life. A noninvasive, auricular percutaneous electrical nerve field stimulation (PENFS) device is shown to be effective for abdominal pain in children with disorders of gut-brain interaction. We aimed to determine the effects of PENFS on pain, common comorbidities, and quality of life in pediatric CVS. Methods: Children aged 8-18 years with drug-refractory CVS were enrolled in a prospective, open-label study receiving 6 consecutive weeks of PENFS. Subjects completed the following surveys at baseline, during/after therapy (week 6), and at extended follow-up approximately 4-6 months later: Abdominal Pain Index (API), State-Trait Anxiety Inventory for Children (STAI-C), Pittsburgh Sleep Quality Index (PSQI), and Patient Reported Outcome Measurement Information System (PROMIS) Pediatric Profile-37. Results: Thirty subjects were included. Median (interquartile range, IQR) age was 10.5 (8.5-15.5) years; 60% were female. Median API scores decreased from baseline to week 6 (p = 0.003) and to extended follow-up (p < 0.0001). State anxiety scores decreased from baseline to week 6 (p < 0.0001) and to extended follow-up (p < 0.0001). There were short-term improvements in sleep at 6 weeks (p = 0.031) but not at extended follow-up (p = 0.22). Quality of life measures of physical function, anxiety, fatigue, and pain interference improved short-term, while there were long-term benefits for anxiety. No serious side effects were reported. Conclusions: This is the first study to demonstrate the efficacy of auricular neurostimulation using PENFS for pain and several disabling comorbidities in pediatric CVS. PENFS improves anxiety, sleep, and several aspects of quality of life with long-term benefits for anxiety.Clinical trial registration: ClinicalTrials.gov, identifier NCT03434652.

Clinical characteristics and long-term outcomes in patients with cyclic vomiting syndrome: A 15-year experience at a tertiary referral center.

BACKGROUND: Cyclic vomiting syndrome (CVS) is a disorder of gut-brain interaction (DGBI) characterized by recurrent episodes of nausea and vomiting. Most children outgrow their CVS symptoms and develop migraine headaches, but there are limited data in adults. We thus sought to determine the natural history of CVS in adults. METHODS: We conducted a retrospective analysis of patients at a specialized tertiary care clinic. Frequency of CVS episodes, emergency department (ED) visits, and hospitalizations were recorded at the index visit and at follow-up. KEY RESULTS: Of 455 CVS patients with complete data, mean age was 33 ± 13 years, 294 (65%) were female, and 392 (86%) were Caucasian. Mean duration of follow-up was 47.4 ± 37.2 months. There was a significant reduction in frequency of CVS episodes/year (18 to 6.8), ED visits (6.1 to 2), and hospitalizations (2.3 to 0.7) (all p-values < 0.001) but only 88 (19%) of patients had complete resolution of episodes at follow-up. On multivariable regression analysis, non-white race [0.33 (0.11-0.98) p = 0.01], comorbidity count [0.77 (0.62-0.95) p = 0.01], cannabis use [0.36 (0.2-0.65) p = 0.0007], and aprepitant use [0.2 (0.08-0.005) p < 0.001] were associated with a reduced odds of complete resolution of CVS episodes. Of note, 19 patients (4%) died. CONCLUSIONS AND INFERENCES: While most adults with CVS improved with specialized care, in contrast to children, only a small subset (~1 in 5) had complete resolution of symptoms. Reasons for the effects of race, cannabis use, and comorbidity burden on outcomes in CVS are unclear and warrant further investigation.

Efficacy of aprepitant as a prophylactic medication in adults with cyclic vomiting syndrome.

BACKGROUND: Aprepitant is a neurokinin-1 receptor antagonist, and recent guidelines by the American Neurogastoenterology and Motility Society recommend its use as prophylaxis in moderate-to severe cyclic vomiting syndrome (CVS). Data are limited to small studies in children. We aimed to determine its efficacy in adults with CVS. METHODS: A retrospective review of CVS patients diagnosed using Rome criteria at a tertiary referral center was conducted. Drug response was defined as >50% reduction in symptoms and/or healthcare utilization. An intent-to-treat (ITT) analysis was conducted. KEY RESULTS: Of 96 patients prescribed aprepitant, 26 (27%) were unable to start due to cost/lack of insurance coverage. Of 70 receiving therapy, mean age was 33 ± 11 years; 51 (73%) were female and 56 (80%) Caucasian. The majority (93%) were refractory to other prophylactic medications. Aprepitant was taken thrice weekly in 51 (73%), daily in 16 (23%) and a few times a month in 3 (4%) due to cost. Fifty (71.4%) had a global symptom response to aprepitant. There was significant reduction in the number of CVS episodes (14.5 ± 11.7 to 6.2 ± 8.0, p < 0.0001), emergency department visits (4.2 ± 7.7 to 1.8 ± 3.4, p = 0.006), and hospital admissions (1.6 ± 3.9 to 0.8 ± 2.1, p = 0.02) in patients treated with aprepitant. Seven (10%) discontinued the drug due to minor side effects. CONCLUSIONS AND INFERENCES: Aprepitant is a safe and effective prophylactic medication in adults with refractory CVS. Adequate insurance coverage is a major barrier preventing its use.

Diagnosis and Management of Cyclic Vomiting Syndrome: A Critical Review.

Cyclic vomiting syndrome (CVS) is a chronic disorder of gut-brain interaction characterized by recurrent disabling episodes of nausea, vomiting, and abdominal pain. CVS affects both children and adults with a prevalence of approximately 2% in the United States. CVS is more common in female individuals and affects all races. The pathophysiology of CVS is unknown and a combination of genetic, environmental, autonomic, and neurohormonal factors is believed to play a role. CVS is also closely associated with migraine headaches and likely have a shared pathophysiology. The diagnosis of CVS is based on the Rome criteria, and minimal recommended testing includes an upper endoscopy and imaging studies of the abdomen. CVS is frequently associated with anxiety, depression, and autonomic dysfunction. Patients with CVS commonly use cannabis therapeutically for symptom relief. By contrast, cannabinoid hyperemesis syndrome is believed to be a subset of CVS with chronic heavy cannabis use leading to hyperemesis. Due to the recalcitrant nature of the illness, patients often visit the emergency department and are hospitalized for acute CVS flares. Guidelines on the management of CVS recommend a biopsychosocial approach. Prophylactic therapy consists of tricyclic antidepressants (amitriptyline), antiepileptics (topiramate), and aprepitant in refractory patients. Abortive therapy consists of triptans, antiemetics (ondansetron), and sedation. Treatment of comorbid conditions is extremely important to improve overall patient outcomes. CVS has a significant negative impact on patients, families, and the healthcare system, and future research to understand its pathophysiology and develop targeted therapies is needed.

Prevalence of Undiagnosed Acute Hepatic Porphyria in Cyclic Vomiting Syndrome and Overlap in Clinical Symptoms.

BACKGROUND AND AIMS: Acute hepatic porphyria (AHP) presents with nausea and vomiting and can mimic cyclic vomiting syndrome (CVS). The prevalence of AHP in CVS and overlap in clinical symptomatology is not known. We thus sought to determine the prevalence of pathogenic variants for AHP and characterize symptom overlap between CVS and AHP. METHODS: We conducted a cross-sectional study of 234 CVS patients using Rome criteria. Patients were eligible for AHP genetic testing if they had recurrent episodes of severe, diffuse abdominal pain with ≥ 2 of the following-peripheral nervous system (muscle weakness/aching, numbness, tingling), central nervous system (confusion, anxiety, seizures, hallucinations), autonomic nervous system (hyponatremia, tachycardia, hypertension, constipation) symptoms, red/brownish urine, or blistering skin lesions on sun-exposed areas. A family history of AHP or elevated urinary porphobilinogen (PBG)/aminolaevulinic acid (ALA) were also criteria for genetic testing and was performed using a 4-gene panel. RESULTS: Mean age was 38.7 ± 14.5 years, 180 (76.9%) were female and 200 (85.5%) were Caucasian. During a CVS attack, 173 (92%) reported abdominal pain, 166 (87.2%) had peripheral nervous system, 164 (86.8%) had central nervous system and 173 (92) % had autonomic symptoms. Ninety-one eligible patients completed genetic testing. None were positive for AHP but two had variants of uncertain significance (VUS) in the HMBS gene. CONCLUSIONS: There is a high prevalence of non-gastrointestinal symptoms in CVS, like AHP, which is important for clinicians to recognize. AHP was not detected in this study and larger studies are warranted to ascertain its prevalence.

Genetic and population diversity of Toxocara cati (Schrank, 1788) Brumpt, 1927, on the basis of the internal transcribed spacer (ITS) region.

The present investigation was aimed to study the sequence, phylogenetic and haplotype analyses of Toxocara cati based on the ITS region, along with the genetic diversity, demographic history and population-genetic structure. The maximum likelihood tree based on Kimura 2-parameter model was constructed using the complete ITS region of all the nucleotide sequences (n = 57) of Toxocara spp. and other related ascarid worms available in the GenBank™. It placed all the sequences of T. cati into four major clades designated as T. cati genotypes 1-4 (TcG1-G4). A total of 66 signature nucleotides were identified in the ITS region between genotypes. The median-joining haplotype network displayed a total of 24 haplotypes, with China exhibiting the highest number of haplotypes (h = 20) followed by India (h = 4), and Japan and Russia (h = 1). It indicated a clear distinction between all the four genotypes. The pairwise FST values between all the genotypes indicated huge genetic differentiation (> 0.25) between different T. cati genotypes. Moreover, the gene flow (Nm) between T. cati genotypes was very low. Results of AMOVA revealed higher genetic variation between genotypes (92.82%) as compared to the variation within genotypes (7.18%). The neutrality indices and mismatch distributions for the G1-G4 genotypes, Indian isolates and the overall dataset of T. cati indicated either a constant population size or a slight population increase. The geographical distribution of all the genotypes of T. cati is also reported. This is the first report of genotyping of T. cati on the basis of the ITS region.

Current understanding of the etiology of cyclic vomiting syndrome and therapeutic strategies in its management.

INTRODUCTION: Cyclic vomiting syndrome (CVS) is a chronic-debilitating disorder of the gut-brain interaction and is characterized by recurrent episodes of nausea and vomiting.Recent studies indicate that it is common and affects 2% of the US population. Unfortunately, there is significant heterogeneity in the management of these patients in the medical community. This review article aims to bridge this gap and reviews the epidemiology and etiology with a focus on the management of CVS. AREAS COVERED: This article reviews the epidemiology and pathophysiology of CVS and its impact on patients. It also discusses management based on recent guidelines intended for the busy clinician. A literature search was done using PubMed, and keywords 'cyclic vomiting,' 'management,' 'etiology,' and pathophysiology were used to identify articles of importance. EXPERT OPINION: CVS is a complex, poorly understood disorder of gut-brain interaction and has a significant negative impact on patients, families, and the healthcare system. Recent guidelines recommend a multidisciplinary approach to management using prophylactic therapy for moderate-severe CVS and abortive medication for acute flares. However, more research is needed to better understand the pathophysiology and develop targeted therapies for CVS.

Low patient engagement is associated with reduced health-related quality of life in adults with cyclic vomiting syndrome.

INTRODUCTION: Patient engagement, adaptation and self-management play a critical role in improving Health Related Quality of Life (HRQOL) and reducing health care utilization in chronic disorders. There is no data on the level of patient engagement in patients with cyclic vomiting syndrome (CVS); we thus sought to determine their level of engagement and its association with clinical covariates. METHODS: The Patient Activation Measure (PAM-13), a validated tool that measures the degree of patient engagement in their health was administered prospectively to patients with CVS. Data on demographics, health care utilization, and HRQOL (using the NIH PROMIS 10) were obtained. Patients were stratified into low engagement (PAM 1 & 2) and high engagement (PAM 3 & 4). The Fisher's exact test and Wilcoxon rank-sum tests were used to identifying significant differences between the groups. RESULTS: Of 96 patients, 45% of patients had low levels of patient engagement. On multivariate analysis, low patient engagement was significantly associated with an increased number of CVS hospitalizations in the past year (aOR 1.26 [1.07, 1.54] p = .010), lower mental HRQOL scores (aOR 0.88 [0.78, 0.97] p = .022), current tobacco use (aOR 4.85 [1.24, 22.74] p = .031), and patients who were newly established in a specialized CVS clinic (aOR 44.40 [5.38, 70.02] p = .002). CONCLUSION: Almost half of CVS patients demonstrate poor patient engagement, which is associated with poor outcomes. Identifying these patients and treatment in a specialized CVS center can potentially improve HRQOL, reduce health care utilization and improve overall healthcare outcomes.

Cyclic Vomiting Syndrome-Related Hospitalizations Trends, Comorbidities & Health Care Costs in Children: A Population Based Study.

AIM: To analyze the clinical characteristics, trends in hospitalization and health care resource utilization of pediatric patients with cyclical vomiting syndrome (CVS). METHODS: We analyzed the latest 5 Healthcare Cost and Utilization Project-Kids Inpatient Database (HCUP-KID) datasets including years 2003, 2006, 2009, 2012 and 2016 for patients aged 1-20 years with a primary diagnosis of CVS and were compared with Age/gender-matched controls for comorbidities, clinical outcomes, and healthcare resource utilization. RESULTS: A total of 12,396 CVS-related hospitalizations were analyzed. The mean age of CVS patients was 10.4 ± 6.7 years. CVS was associated with dysautonomia (OR: 12.1; CI: 7.0 to 20.8), dyspepsia (OR: 11.9; CI: 8.8 to 16.03), gastroesophageal reflux disease (OR: 6.9; Confidence Interval (CI): 6.4 to 7.5), migraine headaches (OR: 6.8; CI: 5.9 to 7.7) and irritable bowel syndrome (OR: 2.08; CI: 1.2 to 4.3) (all p < 0.001). CVS was also associated with increased cannabis use (OR: 5.26, 4.6 to 5.9; p < 0.001), anxiety disorder (OR: 3.9; CI: 3.5 to 4.4) and stress reaction (OR: 3.6; CI: 2.06 to 6.3), p < 0.001. Mean CVS-related hospitalization costs (inflation adjusted) more than doubled from $3199 in 2003 to $6721 in 2016, incurring $84 million/year in total costs. CONCLUSION: Hospitalized CVS patients have increased prevalence of DGBIs, dysautonomia, psychiatric conditions and cannabis use compared to non-CVS controls. CVS-related hospitalizations in U.S. is associated with increasing health care costs. Better management of CVS and comorbid conditions is warranted to reduce health care costs and improve outcomes.

Retrospective review of patients treated for cyclic vomiting syndrome with topiramate.

BACKGROUND: Practice guidelines recommend topiramate as second-line treatment for the prevention of moderate-severe cyclic vomiting syndrome (CVS) in adults. However, data are limited to small studies in children. AIM: To characterise the response to topiramate as prophylactic therapy in adults with CVS. METHODS: We conducted a retrospective review of patients with CVS. Clinical characteristics, number of CVS episodes, emergency department (ED) visits, and hospitalisations the year before and after initiating topiramate were recorded. Response was defined as a global improvement in symptoms or >50% reduction in the number of CVS episodes, ED visits or hospitalisations. RESULTS: Sixty-five percent (88/136) of patients responded to topiramate in an intent-to-treat analysis. There was a significant decrease in the annual number of CVS episodes (18.1 vs 6.2, P < 0.0001), CVS-related ED visits (4.3 vs 1.6, P = 0.0029), and CVS-related hospitalisations (2.0 vs 1.0, P = 0.035). Logistic regression revealed that higher doses of topiramate, longer use of topiramate (≥12 months) and topiramate as monotherapy were associated with a response to treatment. Anxiety was associated with non-response to topiramate. Fifty-five percent of patients experienced side effects, and 32% discontinued the medication as a result. The most common side effects were cognitive impairment (13%), fatigue (11%) and paresthesia (10%). This represented a refractory group with topiramate being initiated in patients (92%) who had failed treatment with tricyclic antidepressants (TCAs). CONCLUSIONS: Topiramate may be an effective second-line prophylaxis for patients with moderate-severe CVS, but its use is limited by side effects. Efforts to develop better-tolerated therapies for CVS are warranted.

Greater intolerance to uncertainty predicts poorer quality of life in adults with cyclic vomiting syndrome.

BACKGROUND: Cyclic vomiting syndrome (CVS) is an idiopathic disorder of gut-brain interaction characterized by recurrent bouts of nausea and vomiting. Although CVS negatively impacts quality of life (QOL), the determinants of impaired QOL among adult CVS sufferers are not fully understood. The unpredictability of CVS attacks may generate anticipatory anxiety and worsen quality of life in a substantial proportion of patients with CVS. Intolerance to uncertainty (IU) is a cognitive trait in which individuals experience distress when faced with unpredictable situations, particularly those with potentially negative consequences. Higher trait IU is a well-established vulnerability factor linked to the development of multiple psychiatric conditions, including anxiety. However, the extent to which higher IU is associated with impaired QOL in adults with CVS is not known. METHODS: To explore this issue, we surveyed 118 adult CVS patients and obtained demographic information, clinical features, reported healthcare utilization, and standardized assessments of IU, anxiety and panic, and QOL. KEY RESULTS: Adult CVS patients with higher IU did not report a greater frequency of CVS attacks or overall CVS-related healthcare utilization than those with lower IU. Yet, this group demonstrated substantially poorer physical and mental health-related QOL and higher rates of anxiety-spectrum disorders. CONCLUSIONS & INFERENCES: Higher degrees of IU are associated with increased anxiety and reduced QOL in patients with CVS. IU is a malleable cognitive trait that can be targeted by cognitive behavioral therapy (CBT). Our results suggest that some CVS patients may benefit from non-pharmacologic therapies such as CBT.

An integrative healthcare model with heartfulness meditation and care coordination improves outcomes in cyclic vomiting syndrome.

BACKGROUND: Cyclic vomiting syndrome (CVS) is associated with psychosocial comorbidity and often triggered by stress. Since the current disease-centered care model does not address psychosocial factors, we hypothesized that holistic, patient-centered care integrating meditation and addressing psychosocial needs through a care coordinator will improve healthcare outcomes in CVS. METHODS: We conducted a prospective randomized controlled trial: 49 patients with CVS (mean age: 34 ± 14 years; 81% female) were randomized to conventional health care (controls) or Integrative Health care (IHC) (27: controls, 22: IHC). The IHC group was assigned a care coordinator and received meditation with a certified instructor. Outcomes including psychological distress, coping strategies to manage chronic stress, cognitive symptom management, and Health-Related Quality of Life (HRQoL) were measured. KEY RESULTS: In intention-to-treat analyses, patients receiving IHC showed significant improvement in multiple domains of coping including positive reframing, planning, and reduction in self-blame (p values ≤0.05), and physical HRQoL (p = 0.03) at 6 months. They also leaned toward spirituality/religion as a coping measure (p ≤ 0.02 at 3 and 6 months). Subgroup analysis of compliant patients showed additional benefit with significant reduction in psychological distress (p = 0.04), improvement in sleep quality (p = 0.03), reduction in stress levels (0.02), improvement in physical HRQoL (0.04), and further improvement in other domains of coping (p < 0.05). CONCLUSIONS AND INFERENCES: An IHC model incorporating meditation and care coordination improves patient outcomes in CVS and is a useful adjunct to standard treatment. Studies to determine the independent effects of meditation and care coordination are warranted.

Hot-Water Bathing Improves Symptoms in Patients with Cyclic Vomiting Syndrome and Is Modulated by Chronic Cannabis Use.

BACKGROUND: Cyclic vomiting syndrome (CVS) is a chronic functional GI disorder; a characteristic compulsive "hot-water bathing" pattern is reported to alleviate symptoms during an acute episode. There is limited data on this bathing pattern: proposed mechanisms include core temperature increase via effects on cannabinoid type 1 receptors in the brain, skin transient receptor potential vanilloid 1 receptor stimulation, and blood flow shift from viscera to skin. AIMS: We thus sought to characterize the hot-water bathing pattern in patients with CVS and identify differences between heavy cannabis users in comparison to occasional and non-users. METHODS: We conducted a cross-sectional study of 111 patients with CVS at a single tertiary referral center. Questionnaires regarding clinical characteristics, hot-water bathing, and cannabis use were administered. Patients were classified based on cannabis usage into regular cannabis users (≥ 4 times/week), and occasional + non-users (< 4 times/week and no current use). RESULTS: A total of 81 (73%) respondents reported the hot-water bathing behavior during an episode. The majority (> 80%) noted a marked improvement in nausea, vomiting, abdominal pain and symptoms associated with panic. Regular cannabis users were more likely to use "very-hot" water (50% vs. 16%, p = 0.01) and time to relief of symptoms was longer (> 10 min) in this group, compared to the rest of the cohort. CONCLUSIONS: Hot-water bathing relieves both GI and symptoms related to panic in most patients which appear to be modulated by chronic cannabis use. These findings can help inform future physiologic studies in CVS pathogenesis.