Cyclic vomiting syndrome: Pathophysiology, comorbidities, and future research directions.

Cyclic vomiting syndrome (CVS) is characterized by severe episodic emesis in adults and children. Cannabinoid hyperemesis syndrome is an increasingly recognized CVS-like illness that has been associated with chronic cannabis use. There are significant gaps in our understanding of the pathophysiology, clinical features, comorbidities, and effective management options of CVS. Recommendations for treating CVS are based on limited clinical data, as no placebo-controlled, randomized trials have yet been conducted. Diseases associated with CVS, including migraine, mitochondrial disorders, autonomic dysfunction, and psychiatric comorbidities, provide clues about pathophysiologic mechanisms and suggest potential therapies. We review our current understanding of CVS and propose future research directions with the aim of developing effective therapy. Establishing a multicenter, standardized registry of CVS patients could drive research on multiple fronts including developing CVS-specific outcome measures to broaden our understanding of clinical profiles, to serve as treatment end points in clinical trials, and to provide a platform for patient recruitment for randomized clinical trials. Such a robust database would also facilitate conduct of research that aims to determine the underlying pathophysiological mechanisms and genetic basis for CVS, as well as identifying potential biomarkers for the disorder. Soliciting government and industry support is crucial to establishing the necessary infrastructure and achieving these goals. Patient advocacy groups such as the Cyclic Vomiting Syndrome Association (CVSA), which partner with clinicians and researchers to disseminate new information, to promote ongoing interactions between patients, their families, clinicians, investigators, to support ongoing CVS research and education, must be an integral part of this endeavor.

Management of cyclic vomiting syndrome in adults: Evidence review.

BACKGROUND: This evidence review was conducted to inform the accompanying clinical practice guideline on the management of cyclic vomiting syndrome (CVS) in adults. METHODS: We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework and focused on interventions aimed at prophylactic management and abortive treatment of adults with CVS. Specifically, this evidence review addresses the following clinical questions: (a) Should the following pharmacologic agents be used for prophylaxis of CVS: amitriptyline, topiramate, aprepitant, zonisamide/levetiracetam, or mitochondrial supplements? (b) Should the following pharmacologic agents be used for abortive treatment: triptans or aprepitant? RESULTS: We found very low-quality evidence to support the use of the following agents for prophylactic and abortive treatment of CVS: amitriptyline, topiramate, aprepitant, zonisamide/levetiracetam, and mitochondrial supplements. We have moderate certainty of evidence for the use of triptans as abortive therapy. We found limited evidence to support the use of ondansetron and the treatment of co-morbid conditions and complementary therapies. CONCLUSIONS: This evidence review helps inform the accompanying guideline for the management of adults with CVS which is aimed at helping clinicians, patients, and policymakers, and should improve patient outcomes.

Role of chronic cannabis use: Cyclic vomiting syndrome vs cannabinoid hyperemesis syndrome.

Cannabis is commonly used in cyclic vomiting syndrome (CVS) due to its antiemetic and anxiolytic properties. Paradoxically, chronic cannabis use in the context of cyclic vomiting has led to the recognition of a putative new disorder called cannabinoid hyperemesis syndrome (CHS). Since its first description in 2004, numerous case series and case reports have emerged describing this phenomenon. Although not pathognomonic, a patient behavior called "compulsive hot water bathing" has been associated with CHS. There is considerable controversy about how CHS is defined. Most of the data remain heterogenous with limited follow-up, making it difficult to ascertain whether chronic cannabis use is causal, merely a clinical association with CVS, or unmasks or triggers symptoms in patients inherently predisposed to develop CVS. This article will discuss the role of cannabis in the regulation of nausea and vomiting, specifically focusing on both CVS and CHS, in order to address controversies in this context. To this objective, we have collated and analyzed published case series and case reports on CHS in order to determine the number of reported cases that meet current Rome IV criteria for CHS. We have also identified limitations in the existing diagnostic framework and propose revised criteria to diagnose CHS. Future research in this area should improve our understanding of the role of cannabis use in cyclic vomiting and help us better understand and manage this disorder.

Guidelines on management of cyclic vomiting syndrome in adults by the American Neurogastroenterology and Motility Society and the Cyclic Vomiting Syndrome Association.

The increasing recognition of cyclic vomiting syndrome (CVS) in adults prompted the development of these evidence-based guidelines on the management of CVS in adults, which was sponsored by the American Neurogastroenterology and Motility Society (ANMS) and the Cyclic Vomiting Syndrome Association (CVSA). GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) framework was used and a professional librarian performed the literature search. The expert committee included the President of the CVSA who brought a patient perspective into the deliberations. The committee makes recommendations for the prophylaxis of CVS, treatment of acute attacks, diagnosis, and overall management of CVS. The committee strongly  recommends that adults with moderate-to-severe CVS receive a tricyclic antidepressant (TCA), such as amitriptyline, as a first-line prophylactic medication and receive topiramate or aprepitant as alternate prophylactic medications. Zonisamide or levetiracetam and mitochondrial supplements (Coenzyme Q10, L-carnitine, and riboflavin) are conditionally recommended as alternate prophylactic medications, either alone or concurrently with other prophylactic medications. For acute attacks, the committee conditionally recommends using serotonin antagonists, such as ondansetron, and/or triptans, such as sumatriptan or aprepitant to abort symptoms. Emergency department treatment is best achieved with the use of an individualized treatment protocol and shared with the care team (example provided). The committee recommended screening and treatment for comorbid conditions such as anxiety, depression, migraine headache, autonomic dysfunction, sleep disorders, and substance use with referral to appropriate allied health services as indicated. Techniques like meditation, relaxation, and biofeedback may be offered as complementary therapy to improve overall well-being and patient care outcomes.

Consent2Share: an integrated broad consenting process for re-contacting potential study subjects.

Background and Aim: Obtaining sufficient subjects into research studies is an ongoing barrier to conducting clinical research. Privacy rules add to the complexity of identifying qualified study subjects. The process described facilitates consent of patients coming to their clinically scheduled appointments who are asked to consent to having researchers review their electronic medical records (EHR), and if they meet study criteria for future research, being contacted by those researchers and asked if they wish to be involved in a research project. Methods: An interdisciplinary group representing the Institutional Review Board (IRB), Information Technology (IT), Hospital, University and Research developed an initial paper then electronic method to consent all patients attending a medical subspecialty clinic. All consent data are integrated to the EHR to facilitate linking to clinical information. Results: Although the paper consenting method resulted in over an 80% "yes" rate of consent, it was complicated by significant procedural challenges which prevented scalability. Revising the process has resulted in nearly 28,000 patients consenting in a 3 year period and in 20 IRB approved protocols using subjects who agreed to Consent2Share. Conclusions: A multi-disciplinary effort is essential to develop a successful electronic based, integrated process to assist investigators and patients to facilitate study subject accrual. Relevance for patients: Consent2Share more efficiently assists researchers in identifying and contacting potential study subjects that meet entrance criteria. The process provides a model to comply with the proposed Notice of Public Rule Making (NPRM) where institutions will be strongly encouraged to develop broad research consent procedures.

Falling forever: the price of chronic shock.

Manifestations of chronic shock and annihilation anxiety-including autistic defenses, chaotic relationships, disorganized attachment, split-off affective states, and vulnerability to disintegration--exist side by side with apparent ego strength and high functioning, even in nonabused patients. Chronic shock stemming from uncontained distress and failed dependency during childhood can persist throughout the lifespan, creating ripples of dysfunction that mask as character distortion and contribute to therapeutic impasse. Patients rely on omnipotent defenses to provide a sense of "having skin" in the face of the fear of breakdown, striving to avoid vulnerability, and trying to insulate themselves from shock experience. Although the relinquishment of autistic defenses and subsequent integration of disowned affect states are overwhelming and painful, patients can emerge from this process with significant shifts in intrapsychic, interpersonal, and existential/spiritual functioning. Clinical material from one psychodynamic psychotherapy group tracks the group process and growth trajectories of seven group members struggling with chronic shock. The ability to recognize subtle dissociative states is a valuable tool in the repertoire of the group psychotherapist.