Creating a data dictionary for pediatric autonomic disorders.

PURPOSE: Whether evaluating patients clinically, documenting care in the electronic health record, performing research, or communicating with administrative agencies, the use of a common set of terms and definitions is vital to ensure appropriate use of language. At a 2017 meeting of the Pediatric Section of the American Autonomic Society, it was determined that an autonomic data dictionary comprising aspects of evaluation and management of pediatric patients with autonomic disorders would be an important resource for multiple stakeholders. METHODS: Our group created the list of terms for the dictionary. Definitions were prioritized to be obtained from established sources with which to harmonize. Some definitions needed mild modification from original sources. The next tier of sources included published consensus statements, followed by Internet sources. In the absence of appropriate sources, we created a definition. RESULTS: A total of 589 terms were listed and defined in the dictionary. Terms were organized by Signs/Symptoms, Triggers, Co-morbid Disorders, Family History, Medications, Medical Devices, Physical Examination Findings, Testing, and Diagnoses. CONCLUSION: Creation of this data dictionary becomes the foundation of future clinical care and investigative research in pediatric autonomic disorders, and can be used as a building block for a subsequent adult autonomic data dictionary.

Assessment of comorbid symptoms in pediatric autonomic dysfunction.

PURPOSE: Pediatric patients with autonomic dysfunction and orthostatic intolerance (OI) often present with co-existing symptoms and signs that might or might not directly relate to the autonomic nervous system. Our objective was to identify validated screening instruments to characterize these comorbidities and their impact on youth functioning. METHODS: The Pediatric Assembly of the American Autonomic Society reviewed the current state of practice for identifying symptom comorbidities in youth with OI. The assembly includes physicians, physician-scientists, scientists, advanced practice providers, psychologists, and a statistician with expertise in pediatric disorders of OI. A total of 26 representatives from the various specialties engaged in iterative meetings to: (1) identify and then develop consensus on the symptoms to be assessed, (2) establish committees to review the literature for screening measures by member expertise, and (3) delineate the specific criteria for systematically evaluating the measures and for making measure recommendations by symptom domains. RESULTS: We review the measures evaluated and recommend one measure per system/concern so that assessment results from unrelated clinical centers are comparable. We have created a repository to apprise investigators of validated, vetted assessment tools to enhance comparisons across cohorts of youth with autonomic dysfunction and OI. CONCLUSION: This effort can facilitate collaboration among clinical settings to advance the science and clinical treatment of these youth. This effort is essential to improving management of these vulnerable patients as well as to comparing research findings from different centers.

Use of Cluster Analysis to Identify Subtypes of Pediatric Functional Nausea.

OBJECTIVE: The aim of the study was to evaluate whether there are clinical subtypes in children with functional nausea based on comorbidities and responses to the Nausea Profile questionnaire. METHODS: Patients from the Neurointestinal and Motility Program clinical registry at Lurie Children's Hospital were included if they met Rome IV criteria for functional nausea. Patients completed the Nausea Profile, a multidimensional measure of nausea with gastrointestinal, emotional, and somatic subscales. Comorbidities were assessed by chart review and self-report measures. Latent class analysis was used to identify patient groups based on comorbidities. To assess if model-identified groups were predictive of differences in nausea quality, Nausea Profile subscale means were compared between groups and used to predict group membership. Conversely, k-means analysis was used to divide the sample into groups based upon Nausea Profile subscale scores, to determine if identified groups had different comorbidities. RESULTS: Seventy-two patients (n = 53 girls) with a mean age (±SD) 14.5 ±â€Š2.9 were included. Two clinical subtypes were identified based on comorbidities, with responses on the emotional subscale of the Nausea Profile predicting group membership (P < 0.04). When patients were grouped by nausea quality, the resulting clusters differed on psychiatric comorbidities (P < 0.001). CONCLUSIONS: Our findings support the existence of nausea subtypes within the broad diagnosis of functional nausea. One such subtype is an emotional predominant nausea supporting the notion that anxiety and depression constitute a subset of patients with nausea. Thus, patients may benefit from a treatment approach that integrates both GI assessment and psychiatric support in their care.

Family ties: the impact of celiac disease on children and caregivers.

PURPOSE: To evaluate the impact of celiac disease (CD) and the gluten-free diet (GFD) on the health-related quality of life (HRQoL) in children with CD in the United States using validated measures. We hypothesize that CD negatively impacts the child and caregivers' HRQoL. METHODS: Participants included children with a confirmed diagnosis of CD and their caregivers (n = 246) seen in a CD multidisciplinary clinic. Caregivers completed the Pediatric Quality of Life (PedsQL) parent-proxy scale to report on their child's HRQoL and the Family Impact Module (FIM), which assesses the impact of caring for a child with a chronic illness. Their children completed the age-appropriate PedsQL. PedsQL and FIM results were compared to published data for children with gastroenterological conditions and a healthy cohort using non-parametric tests. RESULTS: Children with CD reported significantly lower HRQoL than reports from healthy controls across all PedsQL domains (P < 0.001, Cohen d = 0.8), and lower compared to children with other organic gastrointestinal conditions in Social Functioning (P < 0.001, Cohen d = 0.5) and overall Psychosocial Functioning (P < 0.001, Cohen d = 0.3) domains. Results from the caregiver's report on their own HRQoL were significantly worse than that reported by historical controls in the domains of Communication (P < 0.001, Cohen d = 0.3) and Worry (P < 0.001, Cohen d = 0.8), yet similar on all other domains. CONCLUSIONS: In our population, CD is associated with low HRQoL scores for both children and their caregivers. Screening children and families for HRQoL can identify patients and families in need of additional support in this higher-risk population.

Children with Functional Nausea-Comorbidities outside the Gastrointestinal Tract.

OBJECTIVE: To detail common comorbidities and procedures performed to evaluate functional nausea in children. STUDY DESIGN: In total, 63 children age 7-18 years seen in a tertiary care pediatric clinic who met Rome IV criteria for functional nausea prospectively completed an Intake Questionnaire, the Pediatric and Parent-Proxy PROMIS-25 Profile v 2.0, the Pediatric and Parent-Proxy Pediatric Sleep Disturbance-Short Form 4a, and the COMPASS 31 orthostatic intolerance scale to assess comorbidities. Medical records were reviewed for diagnostic tests performed to evaluate nausea and for additional comorbidities. Summary statistics were used to determine the most common comorbidities and diagnostic yield of the procedures. Intraclass correlation coefficients assessed agreement between parent and child reports on the PROMIS scales. RESULTS: Patients with functional nausea experienced multisystem comorbidities. A majority reported abdominal pain, headache, orthostatic intolerance, fatigue, disturbed sleep, anxiety, constipation, allergies, and vomiting. Agreement between parent-proxy and child report of symptoms on PROMIS scales was good to excellent (intraclass correlation coefficients = .78-.83; all P < .001). Patients underwent extensive diagnostic testing: 96 endoscopic procedures, 199 radiologic tests, and 4 cholecystectomies. Most of the procedures were not diagnostically informative. CONCLUSIONS: Children with functional nausea have comorbidities outside the gastrointestinal tract that warrant evaluation. Gastrointestinal diagnostic tests were of low-yield in identifying a cause. Understanding the relationship with comorbidities may provide insight into etiologies for the nausea and define clinical phenotypes to better tailor care.

Family Health-related Quality of Life in Pediatric Cyclic Vomiting Syndrome.

OBJECTIVE: The aim of the study was to evaluate the relationship of disease characteristics and child anxiety symptoms to family health-related quality of life (FHRQoL) in youth with cyclic vomiting syndrome (CVS). METHODS: Forty-two parents of youth ages 8 to 18 years diagnosed with CVS completed the Family Impact Module of the PedsQL, a measure of the impact of the child's illness on the family. We evaluated the relationship of disease characteristics and child and parent proxy reports of anxiety symptoms on the Screen for Childhood Anxiety and Related Emotional Disorders to FHRQoL. RESULTS: Parent report of child anxiety symptoms and missed school days (mean = 11.93, standard deviation = 14.62) were the strongest predictors of FHRQoL (r = 0.33, df = 1.39, F = 8.51, P = 0.006). Other disease characteristics, including frequency, duration, chronicity of CVS episodes, and delay in initial CVS diagnosis were not significantly associated with the FHRQoL total score. Child anxiety symptoms by either parent and/or child report were associated with subscales of the FHRQoL, including family physical functioning, family communication, and family daily activities. CONCLUSIONS: HRQoL for the families assessed in this study was associated with anxiety symptoms to a greater extent than disease characteristics, indexing the importance of a biopsychosocial approach to CVS management. Screening for anxiety symptoms and support for school absences due to illness are indicated to help lessen the impact of CVS on the family as a whole.

Cannabis and Pediatric Inflammatory Bowel Disease: Change Blossoms a Mile High.

The trend toward decriminalization of cannabis (marijuana) continues sweeping across the United States. Colorado has been a leader of legalization of medical and recreational cannabis use. The growing public interest in the medicinal properties of cannabis and its use by patients with a variety of illnesses including inflammatory bowel disease (IBD) makes it important for pediatric gastroenterologists to understand this movement and its potential effect on patients. This article describes the path to legalization and "medicalization" of cannabis in Colorado and the public perception of safety despite the known adverse health effects of use. We delineate the mammalian endocannabinoid system and our experience of caring for children and adolescents with IBD in an environment of increasing awareness and acceptance of its use. We then summarize the rationale for considering that cannabis may have beneficial and harmful effects for patients with IBD. Finally, we highlight the challenges federal laws impose on conducting research on cannabis in IBD. The intent of this article is to inform health care providers about the issues around cannabis use and research in adolescents and young adults with IBD.

Anxiety Measures Predict Health-Related Quality of Life in Children and Adolescents with Cyclic Vomiting Syndrome.

OBJECTIVE: To evaluate the relationship between anxiety and health-related quality of life (HRQoL) in children and adolescents with cyclic vomiting syndrome (CVS). STUDY DESIGN: Forty children aged 8-18 years diagnosed with CVS and 40 parents completed the Screen for Child Anxiety Related Emotional Disorders (SCARED) and the child and parent forms of the Pediatric Quality of Life Generic Core Scale, a measure of HRQoL. RESULTS: Eleven of the 40 children (27%) by self-report and 6 of 40 (15%) by parent-proxy report met the clinical cutoff for an anxiety disorder on the SCARED. Parent and child SCARED ratings were moderately correlated (intraclass correlation coefficient 0.68; P < .001). Child-rated HRQoL (mean ± SD, 74.3 ± 15.2) and parent-rated HRQoL (mean, 72.1 ± 14.6) were lower than healthy norms (P < .001). Disease severity (mean duration of CVS episodes, 3 ± 2.4 days), annual frequency of CVS episodes (mean, 8.2 ± 15.3), chronicity of CVS (mean, 5.8 ± 3.4 years), and delay in diagnosis (mean, 2.4 ± 1.9 years) were not associated with child-reported HRQoL; however, child SCARED scores accounted for approximately 50% of the variance in child-reported HRQoL (adjusted R(2) = 0.49; df = 1, 38; P < .001). CONCLUSION: Children and adolescents with CVS appear to be at increased risk for anxiety. Anxiety symptoms are a stronger predictor of HRQoL than disease characteristics in children and adolescents with CVS. Assessment and treatment of anxiety in children and adolescents with CVS may have a positive impact on HRQoL.

Relationship among nausea, anxiety, and orthostatic symptoms in pediatric patients with chronic unexplained nausea.

This study evaluated the relationship among nausea, anxiety, and orthostatic symptoms in pediatric patients with chronic unexplained nausea. We enrolled 48 patients (36 females) aged 15 ± 2 years. Patients completed the Nausea Profile, State-Trait Anxiety Inventory for Children and underwent 70° head upright tilt testing (HUT) to assess for orthostatic intolerance (OI) and measure heart rate variability (HRV). We found nausea to be significantly associated with trait anxiety, including total nausea score (r = 0.71, p < 0.01) and 3 subscales: somatic (r = 0.64, p < 0.01), gastrointestinal (r = 0.48, p = 0.01), and emotional (r = 0.74, p < 0.01). Nausea was positively associated with state anxiety, total nausea (r = 0.55, p < 0.01), somatic (r = 0.48, p < .01), gastrointestinal (r = .30, p < .05), and emotional (r = .64, p < .01) subscales. Within 10 min of HUT, 27 patients tested normal and 21 demonstrated OI. After 45 min of HUT, only 13 patients (27%) remained normal. Nausea reported on the Nausea Profile before HUT was associated with OI measured at 10 min of tilt (nausea total r = 0.35, p < 0.05; nausea emotional subscale r = 0.40, p < 0.01) and lower HRV at 10 min of HUT (F = 6.39, p = 0.01). We conclude that nausea is associated with both anxiety symptoms and OI. The finding of decreased HRV suggests an underlying problem in autonomic nervous system function in children and adolescents with chronic unexplained nausea.

Health-related quality of life in children and adolescents with cyclic vomiting syndrome: a comparison with published data on youth with irritable bowel syndrome and organic gastrointestinal disorders.

OBJECTIVE: To evaluate health-related quality of life (HRQoL) in children with cyclic vomiting syndrome (CVS) and to compare child self-reports with those of their parents and with published reports of children with irritable bowel syndrome (IBS), children with organic gastrointestinal disorders, and a healthy control group. STUDY DESIGN: Sixty-eight children aged 5-18 years with CVS confirmed in a gastroenterology clinic completed the Pediatric Quality of Life Inventory (PedsQL). Eighty-two parents completed the parent-proxy PedsQL for children aged 2-18 years. These results were compared with published data for children with IBS, organic gastrointestinal disorders, and a healthy control group using ANOVA. Intraclass correlation was used to evaluate concordance between child and parent reports of HRQoL. RESULTS: HRQoL reported on the PedsQL by children with CVS was lower than that reported by children with IBS (P < .01) and healthy controls (P < .001), but did not differ from that reported by children with organic gastrointestinal disorders. Children with CVS also had lower HRQoL compared with healthy controls by parent-proxy report on the PedsQL (P < .001). Correlations between HRQoL reports by parents and children were moderate to good (intraclass correlation coefficients, 0.504-0.805; P < .01). Duration of CVS episodes, delay in CVS diagnosis, and number of school days missed due to CVS were associated with lower parent-rated HRQoL (P = .01). CONCLUSION: Children with CVS reported lower HRQoL compared with those with IBS, and both parents and children reported lower HRQoL compared with healthy controls. Parent and child ratings of HRQoL converged. Improved recognition of CVS and school support might help mitigate the impact of CVS on HRQoL.

A survey of emergency department use in patients with cyclic vomiting syndrome.

BACKGROUND: Cyclic vomiting syndrome (CVS), a chronic disorder characterized by recurrent episodes of vomiting, is frequently unrecognized and is associated with high utilization of emergency department (ED) services. METHODS: A web-based survey was posted on the Cyclic Vomiting Syndrome Association (CVSA) website to assess utilization of ED services in patients with CVS. RESULTS: Of 251 respondents, 104 (41.4%) were adult CVS patients and 147 (58.6%) were caregivers of pediatric and adult patients. In the adult group, the median number of ED visits for CVS symptoms was 15(range 1 - 200), with a median of 7 ED visits prior to a diagnosis of CVS (range 0 - 150). In the caregiver group, the median number of ED visits was 10 (range 1 - 175) and the median number of ED visits prior to a diagnosis of CVS was 5 (range 0 - 65). CVS was not diagnosed in the ED in 89/104 (93%) adults and 119/147 (93%) patients in the caregiver group. CVS was not recognized in the ED in 84/95 (88%) of adults and 97/122 (80%) of patients in the caregiver group, despite an established diagnosis of CVS. CONCLUSION: There is a sub-group of adult and pediatric CVS patients who are high utilizers of ED services and CVS is not recognized in the ED in the majority of patients. Improved efforts to educate ED physicians are indicated to optimize treatment of patients with CVS and to decrease potential overuse of ED services.

Editorial: Anxiety in Pediatric Chronic Illness: The Elephant in the Exam Room.

Anxiety disorders are the most prevalent psychiatric conditions in childhood, with a rate that increases approximately twofold in youths with a chronic illness.1 Anxiety in youths with a chronic illness is associated with greater functional impairment than would be expected by either the anxiety disorder or the medical illness alone.2 Left untreated, the significant functional impairment associated with anxiety in childhood can persist into adulthood and may compromise medical outcomes across the life span.3 Cobham et al.4 conducted a systematic review to evaluate the prevalence of anxiety and the association of anxiety with medical outcomes in studies of children with select chronic medical conditions. The authors reviewed 53 studies meeting inclusion criteria. Clear evidence was found for an increased prevalence of anxiety in children and youths with asthma, type 1 diabetes, epilepsy, inflammatory bowel disease, juvenile idiopathic arthritis, congenital heart disease, and sickle cell disease, with estimates ranging from 20% to 50%. Evidence for the impact of anxiety on disease outcomes was more limited. This detailed review reveals the following limitations of the current evidence.

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.

Chronic nausea and orthostatic intolerance: Diagnostic utility of orthostatic challenge duration, Nausea Profile Questionnaire, and neurohumoral measures.

BACKGROUND: Chronic nausea in pediatrics is a debilitating condition with unclear etiology. We aimed to define hemodynamic and neurohumoral characteristics of chronic nausea associated with orthostatic intolerance in order to improve identification and elucidate mechanism. METHODS: Children (10-18 years) meeting Rome III criteria for functional dyspepsia with nausea and symptoms of orthostatic intolerance (OI) completed a Nausea Profile Questionnaire followed by prolonged (45 minutes rather than the traditional 10 minutes) head-upright tilt (HUT) (70° tilt up) test. Circulating catecholamines, vasopressin, aldosterone, renin, and angiotensins were measured supine and after 15 minutes into HUT. Beat-to-beat heart rate and blood pressure were continuously recorded to calculate their variability and baroreflex sensitivity. KEY RESULTS: Within 10 and 45 minutes of HUT, 46% and 85% of subjects, respectively, had an abnormal tilt test (orthostatic hypotension, postural orthostatic tachycardia, or syncope). At 15 and 45 minutes of HUT, nausea was elicited in 42% and 65% of subjects respectively. Higher Nausea Profile Questionnaire scores correlated with positive HUT testing at 10 minutes (P = 0.004) and baroreflex sensitivity at 15 minutes (P ≤ 0.01). Plasma vasopressin rose 33-fold in subjects with HUT-induced nausea compared to twofold in those who did not experience HUT-induced nausea (P < 0.01). CONCLUSIONS AND INFERENCES: In children with chronic nausea and OI, longer duration HUT elicited higher frequency of abnormal tilt testing and orthostatic-induced nausea. The Nausea Profile Questionnaire predicted the orthostatic response to tilt testing. Exaggerated vasopressin release differentiated patients with HUT-induced nausea (vs those without nausea), suggesting a possible mechanism for chronic nausea in childhood.

Pediatric Disorders of Orthostatic Intolerance.

Orthostatic intolerance (OI), having difficulty tolerating an upright posture because of symptoms or signs that abate when returned to supine, is common in pediatrics. For example, ∼40% of people faint during their lives, half of whom faint during adolescence, and the peak age for first faint is 15 years. Because of this, we describe the most common forms of OI in pediatrics and distinguish between chronic and acute OI. These common forms of OI include initial orthostatic hypotension (which is a frequently seen benign condition in youngsters), true orthostatic hypotension (both neurogenic and nonneurogenic), vasovagal syncope, and postural tachycardia syndrome. We also describe the influences of chronic bed rest and rapid weight loss as aggravating factors and causes of OI. Presenting signs and symptoms are discussed as well as patient evaluation and testing modalities. Putative causes of OI, such as gravitational and exercise deconditioning, immune-mediated disease, mast cell activation, and central hypovolemia, are described as well as frequent comorbidities, such as joint hypermobility, anxiety, and gastrointestinal issues. The medical management of OI is considered, which includes both nonpharmacologic and pharmacologic approaches. Finally, we discuss the prognosis and long-term implications of OI and indicate future directions for research and patient management.

Anxiety and physiological responses to the Trier Social Stress Test for Children in adolescents with cyclic vomiting syndrome.

This study compared anxiety and physiological responses during the Trier Social Stress Test for Children (TSST-C) in adolescents. 38 subjects (26 females) were enrolled: 11 cyclic vomiting syndrome (CVS), 11 anxiety, and 16 controls. Salivary cortisol, α-amylase and heart rate variability (HRV) were assessed during the TSST-C. Anxiety was measured by the Screen for Childhood Anxiety Related Emotional Disorders (SCARED), Anxiety Disorders Interview Schedule, and State-Trait Anxiety Inventory for Children (STAI-C). 11 anxiety and 7 CVS subjects had ≥1 anxiety disorder. 82% in the anxiety and CVS groups met criteria for an anxiety disorder on the SCARED. Combining groups, cortisol increased from baseline to recovery during the TSST-C (p=0.0004) and the stressor to recovery (p=0.005). α-amylase did not differ during the TSST-C for the total sample, but increased for anxiety compared to controls from baseline to recovery (p=0.01). HRV decreased during the stressor (p=0.0001) and increased at recovery (p=0.004). No associations were found between biomarkers and trait anxiety. Associations were found between baseline HRV and pre-test state anxiety (r=-0.406, p=0.012) and between recovery HRV and post-test state anxiety (r=-0.501, p=0.002) for the total sample. Anxiety is prevalent in CVS warranting screening. HRV may serve as a biomarker for evaluating stress as a potential trigger for CVS episodes. State but not trait anxiety was associated with changes in HRV, suggesting acute anxiety may be more relevant in linking stress and CVS episodes.