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.

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.

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.

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.

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.

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.

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.

Patterns of Cannabis Use in Patients With Cyclic Vomiting Syndrome.

BACKGROUND & AIMS: Some patients with cyclic vomiting syndrome (CVS) use cannabis to relieve stress and for its antiemetic properties. However, chronic cannabis use has been associated paradoxically with cannabinoid hyperemesis syndrome (CHS) and some patients with CVS are thought to have CHS. We sought to characterize patterns of cannabis use by patients with CVS and identify those who could be reclassified as having CHS. METHODS: We performed a cross-sectional study of 140 patients with CVS (72% female; mean age, 37 ± 13 y) seen at a specialized clinic. Patients were screened for cannabis use with the cannabis use disorder identification test. Patients were classified as regular (use ≥4 times/wk) or occasional users (<4 times/wk). RESULTS: Forty-one percent of patients were current cannabis users, with 21% reporting regular use. Regular users were more likely to be male and to report an anxiety diagnosis, and smoked cannabis with higher tetrahydrocannabinol content and for a longer duration. Most users reported that cannabis helped control CVS symptoms. Among all cannabis users, 50 of 57 (88%) reported that they had abstained for longer than 1 month, but only 1 user reported resolution of CVS episodes during the abstinence period. This patient subsequently resumed using cannabis but remains free of symptoms. CONCLUSIONS: Cannabis is used commonly among patients with CVS-patients report relief of symptoms with use. We found 21% of patients with CVS to be regular users, but only 1 met the Rome IV criteria for CHS. Longitudinal studies are needed to determine the relationships among cannabis use, hyperemesis, and mood symptoms.

Recent trends in cyclic vomiting syndrome-associated hospitalisations with liberalisation of cannabis use in the state of Colorado.

BACKGROUND: Currently, 33 states in the United States along with the District of Columbia have legalised cannabis in some forms. There is a paucity of data on the impact of legalisation of cannabis use on hospitalisations due to cyclic vomiting syndrome (CVS). AIM: To study the trends in CVS-related hospitalisations and cannabis use in CVS in relation to legalisation of recreational cannabis use in Colorado. METHODS: All hospital admissions in Colorado between 2010 and 2014 with the diagnosis of CVS were identified using the Colorado State Inpatient Database. Five-year trends in CVS-related hospitalisations along with the cannabis use were analysed. Multivariate logistic regression analysis was performed to determine predictors of cannabis use in CVS. RESULTS: There was a significant increase in CVS-related hospitalisations by 46% from 806 in 2010 to 1180 in 2014 when CVS was included as all-listed diagnoses (P < 0.001). The overall prevalence of cannabis use in CVS (13% with CVS as primary diagnosis and 17% with CVS as all-listed diagnoses) was much higher than non-CVS-related hospitalisations (1.7%) (P < 0.001 for both comparisons). Cannabis use increased dramatically in both CVS and non-CVS-related hospitalisations following legalisation of cannabis for recreational use in 2012. CONCLUSION: Our study shows a significant increase in CVS-related hospitalisations concomitant with an increase in cannabis use with its liberalisation in Colorado. Future studies on the relationship between cannabis use and hyperemesis are warranted, especially with its ongoing legalisation in the United States.

Cyclic Vomiting Syndrome in Children and Adults: What Is New in 2018?

PURPOSE OF REVIEW: Cyclic vomiting syndrome (CVS) is a disabling functional gastrointestinal disorder characterized by severe vomiting episodes that alternate with symptom-free periods. The purpose of this review is to summarize current knowledge and highlight most recent data on prevalence, diagnosis, management, and impact of CVS in children and adults. RECENT FINDINGS: Originally thought to be a pediatric disorder, the past decade has witnessed a considerable increase in CVS diagnosed in adults. Despite improved recognition of CVS, without a delineated pathophysiology and specific biomarker, it remains classified as a functional gastrointestinal disorder. Migraines and CVS share a common pathway based on several studies and response to migraine therapy. Recent work has begun to expand the list of comorbidities and identify plausible mechanisms and new therapeutic avenues. This review seeks to highlight best practices and novel therapies for CVS based on expert consensus and review of available literature.

Cyclic vomiting syndrome: epidemiology, diagnosis, and treatment.

Cyclic-vomiting syndrome (CVS) is a chronic functional gastrointestinal disorder characterized by recurrent episodes of nausea and vomiting. Although once thought to be a pediatric disorder, there has been a considerable increase in recognition of CVS in adults. The exact pathogenesis is unknown and several theories have been proposed. Migraine and CVS share a similar pathophysiology as suggested by several studies. Since there are no specific biomarkers available for this disorder, physicians should rely on Rome criteria for the diagnosis. Due to the lack of randomized control trials, the treatment of CVS is primarily empirical.

Risk, Outcomes, and Predictors of Clostridium difficile Infection in Lymphoma: A Nationwide Study.

OBJECTIVE: The risk of Clostridium difficile infection (CDI) has not been well studied in patients with lymphoma. We thus sought to determine the risk of CDI in hospitalizations with lymphoma along with its trend, outcomes, and predictors using a large database. METHODS: Hospital discharge data from the Nationwide Inpatient Sample (NIS) from 2007 to 2011 were used for the study. Using the International Classification of Diseases, Ninth Revision, Clinical Modification codes, all adult patients aged 18 years or older having a primary diagnosis of lymphoma were queried for the presence of CDI as any of the secondary diagnoses. The risk of CDI in lymphoma and its yearly trend were assessed. We performed multivariate logistic regression to determine the independent risk factors of CDI in lymphoma. Furthermore, we studied mortality and other adverse outcomes of CDI in patients with lymphoma. RESULTS: There were 236,312 discharges (weighted) with the primary diagnosis of lymphoma. CDI was present in 2.13% of patients with lymphoma versus 0.8% in the nonlymphoma group (P < 0.001). On multivariate analysis, the significant predictors of CDI in lymphoma were presence of infection (odds ratio [OR] 3.1, 95% confidence interval [CI] 2.7-3.6), stem cell transplant (OR 2.7, 95% CI 2.3-3.4), graft-versus-host disease (OR 1.9, 95% CI 1.4-2.8), race (Asian vs white, OR 1.6, 95% CI 1.1-2.4), chemotherapy (OR 1.6, 95% CI 1.4-1.8), gastrointestinal surgery (OR 1.4, 95% CI 1.2-1.7), and Charlson Comorbidity Index (CCI) (CCI of 2 vs 0-1: OR 1.2, 95% CI 1.1-1.4; CCI of 3 vs 0-1: OR 1.3, 95% CI 1.03-1.6). CDI in lymphoma was associated with worse hospital outcomes such as increased mortality (17% vs 8%), increased length of stay (23.6 vs 9.9 days), mean total hospital charges ($197,015 vs $79,392), rate of intubation (13% vs 4% vs 13%), and rate of total parenteral nutrition (11% vs 3%). CONCLUSIONS: Hospitalization with lymphoma was associated with an increased risk of CDI. The significant predictors for CDI in lymphoma were infection, stem cell transplant, graft-versus-host disease, race, chemotherapy, gastrointestinal surgery, and Charlson Comorbidity Index. CDI in lymphoma was associated with increased mortality and other adverse outcomes warranting a need of more vigilance for CDI in patients with lymphoma.

Cannabinoid Receptor Type 1 and mu-Opioid Receptor Polymorphisms Are Associated With Cyclic Vomiting Syndrome.

OBJECTIVES: Cyclic vomiting syndrome (CVS) is a disorder defined by recurrent, unexplained episodes of severe nausea and vomiting. Our aim was to investigate whether CVS and pathophysiological mechanisms underlying this condition are associated with selected variations in genes encoding the components of the endogenous cannabinoid and opioid systems. METHODS: This case-control study included 65 patients with CVS-16 male and 49 female, and 1,092 healthy controls-525 male and 567 female from the 1000 Genomes Project. CVS subjects filled out study-specific questionnaires. Single-nucleotide polymorphisms (SNPs) in genes encoding cannabinoid receptors (CNR1 and CNR2), fatty acid amide hydrolase (FAAH) and mu-opioid receptor (OPRM1) were analyzed using the TaqMan SNP genotyping assay. Correlations between SNP's and clinical characteristics of CVS were ascertained. RESULTS: Our study disclosed an increased risk of CVS among individuals with AG and GG genotypes of CNR1 rs806380 (P<0.01), whereas the CC genotype of CNR1 rs806368 and AG and GG genotypes of OPRM1 rs1799971 were associated with a decreased risk of CVS (P<0.05). In addition, AG and GG genotypes of OPRM1 rs1799971 were correlated with migraine episodes, AG and GG of OPRM1 rs1799971, and CT and CC of CNR1 rs806368 with a family history of migraines (second degree relatives), and CT and CC of CNR1 rs2023239 with a positive response to therapy. CONCLUSIONS: Our results show for the first time that the variations in CNR1 and OPRM1 genes are associated with CVS and that different genotypes may contribute to the risk of CVS.

Clinical Characteristics, Comorbidities and Hospital Outcomes in Hospitalizations with Cyclic Vomiting Syndrome: A Nationwide Analysis.

BACKGROUND: Data on cyclic vomiting syndrome (CVS) are limited to studies from tertiary care centers. There is a paucity of information about CVS on a national scale. AIM: To study the clinical characteristics, comorbidities, and hospital outcomes in patients hospitalized with CVS using a nationwide database. METHODS: We identified all hospitalizations associated with a primary diagnosis of CVS in 2010 and 2011 using the Nationwide Inpatient Sample with an age category of 18-55 years. A 1:2 random sample of non-CVS hospitalizations with the same age category was obtained, and comparisons between groups were made. Multivariate logistic regression analysis was used to determine comorbidities independently associated with CVS. RESULTS: Our study included 20,952 CVS and 44,262 non-CVS patients. CVS patients tended to be younger, male, and white compared to non-CVS patients. On multivariate analysis, CVS was significantly associated with comorbidities including dysautonomia, migraine, anxiety, marijuana use, irritable bowel syndrome, gastroparesis, gastroesophageal reflux disease, asthma, cigarette smoking, and hypertension. CVS patients underwent esophagogastroduodenoscopy, colonoscopy, and gastric emptying tests more frequently. They had more favorable hospital outcomes like more routine discharges (discharge to home/self-care), lower mortality, and shorter length of stay but tended to leave against medical advice more frequently. CVS patients incurred total hospital charges of about $400 million over the 2 years. CONCLUSIONS: Our study showed that CVS is associated with several comorbidities and incurred substantial health care costs despite benign outcomes. Efforts to optimize therapy of CVS, manage comorbid conditions and reduce healthcare utilization are warranted.

An Internet survey of marijuana and hot shower use in adults with cyclic vomiting syndrome (CVS).

Cyclic vomiting syndrome (CVS) is a chronic disorder characterized by episodic nausea and vomiting. A large proportion of patients use marijuana to control their symptoms. Several case reports implicate marijuana as a cause of intractable vomiting with compulsive hot water bathing considered pathognomonic of "cannabinoid hyperemesis." We sought to examine the relationship between marijuana use and CVS. Patients >18 years of age diagnosed by a health care provider were invited to participate in an anonymous internet-based survey. A total of 514 patients participated and 437 completed questions about marijuana use. Mean age was 34 ± 12 years with patients being predominantly female (63%), Caucasian (92%) and from the USA (82%). Nineteen percent never used marijuana and 81% did. Fifty-four percent used marijuana for health issues and 43% for recreational purposes. Users stated that it improved nausea, appetite, general well-being, stress levels and vomiting. Users were more likely to be male and have an associated anxiety disorder. Sixty-seven percent of patients reported taking hot showers/baths for symptom relief, and this was associated with marijuana use. (OR 2.54, CI 1.50-4.31, P = 0.0006). Eighty-one percent of patients with CVS who completed an internet survey reported frequent use of marijuana. With marijuana use, patients noted the greatest improvement with stress levels, appetite and nausea. Marijuana users were more likely to be male and have associated anxiety. Hot showers were not pathognomonic of marijuana use though they were more likely to be associated with its use.

Quantitative pedigree analysis and mitochondrial DNA sequence variants in adults with cyclic vomiting syndrome.

BACKGROUND: Children with cyclic vomiting syndrome (CVS) have a high degree of maternal inheritance of functional gastrointestinal and neurological disorders. CVS in children is also associated with an increased prevalence of mitochondrial DNA single-nucleotide polymorphisms (mtDNA SNPs) 16519 T and 3010A. Preliminary data suggests that age of onset of symptoms (pediatric vs. adult) may be a determinant of the presence of such mtDNA SNP's. We sought to examine the degree of maternal inheritance pattern of functional disorders and the prevalence of mtDNA SNP's16519T and 3010A in adults with CVS and correlate this with age of onset of disease. METHODS: A Quantitative Pedigree Analysis (QPA) was performed in 195 of a total of 216 patients and all were genotyped using Restriction Fragment Length Polymorphism (RFLP) or sequencing. RESULTS: Adults with CVS had a higher degree of probable maternal inheritance (PMI) of functional disorders than controls (12% vs. 1%, p < 0.001). However, the prevalence of mitochondrial SNP's 16519 T, 3010A and the AT genotype were similar in Haplogroup H CVS patients compared to historical controls. There was no correlation between age of onset of disease and prevalence of these mtDNA SNP's. CONCLUSIONS: A subset of adults with CVS has a significantly higher degree of maternal inheritance pattern of functional disorders than controls. There was no association with mtDNA SNP's 16519 T and 3010A as seen in children and future studies sequencing the entire mitochondrial and nuclear genome to identify potential causes for this maternal inheritance pattern in adults are warranted.

Irritable bowel syndrome may be associated with maternal inheritance and mitochondrial DNA control region sequence variants.

BACKGROUND AND AIM: Mitochondrial dysfunction has been implicated in various functional disorders that are co-morbid to irritable bowel syndrome (IBS) such as migraine, depression and chronic fatigue syndrome. The aim of the current case-control pilot study was to determine if functional symptoms in IBS show a maternal inheritance bias, and if the degree of this maternal inheritance is related to mitochondrial DNA (mtDNA) polymorphisms. METHODS: Pedigrees were obtained from 308 adult IBS patients, 102 healthy controls, and 36 controls with inflammatory bowel disease (IBD), all from Caucasian heritage, to determine probable maternal inheritance. Two mtDNA polymorphisms (16519T and 3010A), which have previously been implicated in other functional disorders, were assayed in mtDNA haplogroup H IBS subjects and compared to genetic data from 344 published haplogroup H controls. RESULTS: Probable maternal inheritance was found in 17.5 % IBS, 2 % healthy controls and 0 % IBD controls (p < .0001). No difference was found between IBS and control for 3010A, and a trend was found for 16519T (p = 0.05). IBS with maternal inheritance were significantly more likely to have the 16519T than controls (OR 5.8; 95 % CI 1.5-23.1) or IBS without maternal inheritance (OR 5.2; 95 % CI 1.2-22.6). CONCLUSIONS: This small pilot study shows that a significant minority (1/6) of IBS patients have pedigrees suggestive of maternal inheritance. The mtDNA polymorphism 16519T, which has been previously implicated in other functional disorders, is also associated with IBS patients who display maternal inheritance. These findings suggest that mtDNA-related mitochondrial dysfunction may constitute a sub-group within IBS. Future replication studies in larger samples are needed.

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.

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.