A multicenter registry study on percutaneous electrical nerve field stimulation for pediatric disorders of gut-brain interaction.

OBJECTIVES: Percutaneous electrical nerve field stimulation (PENFS) has demonstrated promise in single-center trials for pediatric abdominal pain-related disorders of gut-brain interaction (DGBI). Our aim was to explore efficacy of PENFS as standard therapy for DGBI in a registry involving multiple pediatric gastroenterology referral centers. METHODS: This was a multicenter, prospective open-label registry of children (8-18 years) undergoing PENFS for DGBI at seven tertiary care gastroenterology clinics. DGBI subtypes were classified by Rome IV criteria. Parents and patients completed Abdominal Pain Index (API), Nausea Severity Scale (NSS), and Functional Disability Inventory (FDI) questionnaires before, during therapy and at follow-up visits up to 1 year later. RESULTS: A total of 292 subjects were included. Majority (74%) were female with median (interquartile range [IQR]) age 16.3 (14.0, 17.7) years. Most (68%) met criteria for functional dyspepsia and 61% had failed ≥4 pharmacologic therapies. API, NSS, and FDI scores showed significant declines within 3 weeks of therapy, persisting long-term in a subset. Baseline (n = 288) median (IQR) child-reported API scores decreased from 2.68 (1.84, 3.58) to 1.99 (1.13, 3.27) at 3 weeks (p < 0.001) and 1.81 (0.85, 3.20) at 3 months (n = 75; p < 0.001). NSS scores similarly improved from baseline, persisting at three (n = 74; p < 0.001) and 6 months later (n = 55; p < 0.001). FDI scores displayed similar reductions at 3 months (n = 76; p = 0.01) but not beyond. Parent-reported scores were consistent with child reports. CONCLUSIONS: This large, comprehensive, multicenter registry highlights efficacy of PENFS for gastrointestinal symptoms and functionality for pediatric DGBI.

Children with functional gastrointestinal disorders with and without co-existing nausea: A comparison of clinical and psychological characteristics.

BACKGROUND: Nausea co-existing with functional gastrointestinal disorders (FGIDs) has been suggested to negatively impact physical and psychological factors in children. This study aims to compare clinical and psychological characteristics of a large cohort of pediatric patients with an FGID with and without nausea. METHODS: Patients of two previous randomized controlled trials were included, the first assessing the effect of hypnotherapy (HT) in 260 children fulfilling Rome criteria of irritable bowel syndrome (IBS) or functional abdominal pain (FAP), the second examining the effect of HT in 100 children with nausea in children with either functional nausea (FN) or functional dyspepsia (FD). At inclusion, demographics, clinical features, including the presence of nausea, depression and anxiety, somatization, and health-related quality of life (QoL) were assessed in patients. KEY RESULTS: In total, 355 patients with IBS (n = 131), FAP (n = 127), FN (n = 62), and FD (n = 35) were included, of which 255 (72%) patients experienced nausea versus 100 (28%) without nausea. Age at onset of symptoms was higher in children experiencing nausea (12.0y vs. 9.0y, p = 0.000). Significantly higher somatization, anxiety and depression scores, and lower health-related QoL were reported for children with nausea. There were no significant differences between children with only nausea and children with nausea and abdominal pain. CONCLUSIONS AND INFERENCES: Children with nausea, either with or without abdominal pain, report higher somatization scores, increased anxiety and depression, and lower overall QoL, compared to children with pain-related FGIDs without accompanying nausea. Addressing the presence of nausea in children with FGIDs seems essential to customize their treatment and improve overall quality of life.

Skills or Pills: Randomized Trial Comparing Hypnotherapy to Medical Treatment in Children With Functional Nausea.

BACKGROUND & AIMS: The potential effectiveness of gut-directed hypnotherapy (HT) is unknown for pediatric chronic nausea. This randomized controlled trial compared HT with standard medical treatment (SMT). METHODS: One hundred children (ages, 8-18 y) with chronic nausea and fulfilling functional nausea (FN) or functional dyspepsia (FD) criteria were allocated randomly (1:1) to HT or SMT, with a 3-month intervention period. Outcomes were assessed at baseline, at the halfway point, after treatment, and at the 6- and 12-month follow-up evaluation. Children scored nausea symptoms in a 7-day diary. The primary outcome was treatment success, defined as a reduction in nausea of 50% or more, at the 12-month follow-up evaluation. Secondary outcomes included adequate relief of nausea. RESULTS: After treatment and at the 6-month follow-up evaluation, there was a trend toward higher treatment success in the HT group compared with the SMT group (45% vs 26%, P = .052; and 57% vs 40%, P = .099, respectively). At 12 months, treatment success was similar in both groups (60% in the HT group and 55% in the SMT group; P = .667). In the FN group, significantly higher success rates were found for HT, but no differences were found in patients with FD. Adequate relief was significantly higher in the HT group than in the SMT group at the 6-month follow-up evaluation (children: 81% vs 55%, P = .014; parents: 79% vs 53%; P = .016), but not at the 12-month follow-up evaluation. CONCLUSIONS: HT and SMT were effective in reducing nausea symptoms in children with FN and FD. In children with FN, HT was more effective than SMT during and after the first 6 months of treatment. Therefore, HT and SMT, applied separately or in combination, should be offered to children with FN as a treatment option (Clinical trials registration number: NTR5814).

Gut-directed hypnotherapy versus standard medical treatment for nausea in children with functional nausea or functional dyspepsia: protocol of a multicentre randomised trial.

INTRODUCTION: The treatment of chronic functional nausea or nausea due to functional dyspepsia in children is generally symptomatic. Moreover, these disorders pose a risk for worse psychosocial and health outcomes in children. Hypnotherapy (HT), by its ability to positively influence gastrointestinal and psychosocial functioning, may be an effective treatment for chronic nausea. METHODS AND ANALYSIS: To test efficacy, this multicentre, parallel, randomised controlled, open label trial evaluates whether gut-directed HT is superior to standard medical treatment (SMT) for reducing nausea. The study will be conducted at eleven academic and non-academic hospitals across the Netherlands. A total of 100 children (8-18 years), fulfilling the Rome IV criteria for chronic idiopathic nausea or functional dyspepsia with prominent nausea, will be randomly allocated (1:1) to receive HT or SMT. Children allocated to the HT group will receive six sessions of HT during 3 months, while children allocated to the SMT group will receive six sessions of SMT+supportive therapy during the same period. The primary outcome will be the difference in the proportion of children with at least 50% reduction of nausea, compared with baseline at 12 months' follow-up. Secondary outcomes include the changes in abdominal pain, dyspeptic symptoms, quality of life, anxiety, depression, school absences, parental absence of work, healthcare costs and adequate relief of symptoms, measured directly after treatment, 6 and 12 months' follow-up. If HT proves effective for reducing nausea, it may become a new treatment strategy to treat children with chronic functional nausea or functional dyspepsia with prominent nausea. ETHICS AND DISSEMINATION: Results of the study will be publicly disclosed to the public, without any restrictions, in peer-reviewed journal and international conferences. The study is approved by the Medical Research Ethics Committees United (MEC-U) in the Netherlands. TRIAL REGISTRATION NUMBER: NTR5814.

Pharmacological treatments for functional nausea and functional dyspepsia in children: a systematic review.

INTRODUCTION: Chronic idiopathic nausea (CIN) and functional dyspepsia (FD) cause considerable strain on many children's lives and their families. Areas covered: This study aims to systematically assess the evidence on efficacy and safety of pharmacological treatments for CIN or FD in children. CENTRAL, EMBASE, and Medline were searched for Randomized Controlled Trials (RCTs) investigating pharmacological treatments of CIN and FD in children (4-18 years). Cochrane risk of bias tool was used to assess methodological quality of the included articles. Expert commentary: Three RCTs (256 children with FD, 2-16 years) were included. No studies were found for CIN. All studies showed considerable risk of bias, therefore results should be interpreted with caution. Compared with baseline, successful relief of dyspeptic symptoms was found for omeprazole (53.8%), famotidine (44.4%), ranitidine (43.2%) and cimetidine (21.6%) (p = 0.024). Compared with placebo, famotidine showed benefit in global symptom improvement (OR 11.0; 95% CI 1.6-75.5; p = 0.02). Compared with baseline, mosapride versus pantoprazole reduced global symptoms (p = 0.011; p = 0.009). One study reported no occurrence of adverse events. This systematic review found no evidence to support the use of pharmacological drugs to treat CIN or FD in children. More high-quality clinical trials are needed. ABBREVIATIONS: AP-FGID: Abdominal Pain Related Functional Gastrointestinal Disorders; BART: Biofeedback-Assisted Relaxation Training; CIN: Chronic Idiopathic Nausea; COS: Core Outcomes Sets; EPS: Epigastric Pain Syndrome; ESPGHAN: European Society for Pediatric Gastroenterology Hepatology and Nutrition; FAP: Functional Abdominal Pain; FD: Functional Dyspepsia; GERD: Gastroesophageal Reflux Disease; GES: Gastric Electrical Stimulation; H2RAs: H2 Receptor Antagonists; IBS: irritable bowel syndrome; NASPGHAN: North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition; PDS: Postprandial Distress Syndrome; PPIs: Proton Pump Inhibitor; PROMs: Patient Reported Outcome Measures; RCTs: Randomized Controlled Trials; SSRIs: selective serotonin reuptake inhibitors; TCAs: tricyclic antidepressants.

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.

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.

Functional Nausea in Children: A Review of the Literature and Need for Diagnostic Criteria.

Nausea is common amongst children with functional gastrointestinal disorders and is associated with a high burden of somatic and psychosocial comorbidities in both the short and long-term. Current treatments including medications, phytotherapy, stress-reduction techniques, and gastric electrical stimulation for recalcitrant cases, are reviewed. Functional nausea merits its own diagnostic criteria as a pediatric functional gastrointestinal disorder.