"An urgent need for transition of care programs for adolescents and young adults with neurogastroenterology and motility disorders".

Transition of Care for Adolescents and Young Adults (AYA) with Neurogastroenterology & Motility (NGM) Disorders.

High prevalence of gastrointestinal disorders in a large cohort of patients with joint hypermobility.

The gastrointestinal (GI) manifestations in children with hypermobile Ehlers-Danlos syndrome/joint hypermobility syndrome (hEDS/JHS) are not well described. We investigated the prevalence of GI disorders in children and young adults with hEDS/JHS through a single-center retrospective review. Demographic data, clinical history, symptoms, and diagnostic studies were reviewed. Of 435 patients with hEDS/JHS, 66% were females (age 5-28 years). We noted a high prevalence of constipation (61%), dysphagia (32%), dyspepsia and/or gastroparesis (25%), eosinophilic esophagitis (EoE) (21%), and celiac disease (4%) in our cohort. Upper endoscopy and gastric emptying scans had the highest yield to detect abnormalities. Motility studies were abnormal in 31% of the 80 patients who underwent them. Dysphagia symptoms are significantly associated with EoE. Thirty-three percent of dysphagia patients had EoE, versus 16% of non-dysphagia patients (p < 0.001). Screening hEDS/JHS patients for GI issues should be routine, with further investigations and referrals guided by identified symptoms.

Percutaneous Electrical Nerve Field Stimulation in Children and Adolescents With Functional Dyspepsia-Integrating a Behavioral Intervention.

OBJECTIVES: Functional dyspepsia (FD) includes postprandial distress and epigastric pain syndrome. Percutaneous electrical nerve field stimulation (PENFS) in addition to behavioral interventions (BI) has shown benefits in children with functional abdominal pain but not specifically in FD. We aimed to assess the efficacy of PENFS for treating FD and compare the outcomes with those who received the combination of PENFS + BI. MATERIALS AND METHODS: Charts of patients with FD who completed four weeks of PENFS were evaluated. A subset of patients received concurrent BI. Demographic data, medical history, and symptoms were documented. Outcomes at different time points included subjective symptom responses and validated questionnaires collected clinically (Abdominal Pain Index [API], Nausea Severity Scale [NSS], Functional Disability Inventory [FDI], Pittsburgh Sleep Quality Index [PSQI], Children's Somatic Symptoms Inventory [CSSI], Patient-Reported Outcomes Measurement Information Systems [PROMIS] Pediatric Anxiety and Depression scales). RESULT: Of 84 patients, 61% received PENFS + BI, and 39% received PENFS alone. In the entire cohort, API (p < 0.0001), NSS (p = 0.001), FDI (p = 0.001), CSSI (p < 0.0001), PSQI (p = 0.01), PROMIS anxiety (p = 0.02), and depression (p = 0.01) scores improved from baseline to three weeks and at three months. Subjective responses showed nausea improvement (p = 0.01) and a trend for improvement in abdominal pain (p = 0.07) at week three. Abdominal pain subjectively improved at week three and three months (p = 0.003 and 0.02, respectively), nausea at week three and three months (p = 0.01 and 0.04, respectively), and a trend for improvement in sleep disturbances at week three and three months (p = 0.08 and p = 0.07, respectively) in the PENFS + BI group vs PENFS alone. CONCLUSION: Abdominal pain, nausea, functioning, somatization, sleep disturbances, anxiety, and depression improved at three weeks and three months after PENFS in pediatric FD. Subjective pain and nausea improvement were greater in the PENFS + BI group than in the group with PENFS alone, suggesting an additive effect of psychologic therapy.

Clinical Hypnosis for Pediatric Gastrointestinal Disorders: A Practical Guide for Clinicians.

Functional abdominal pain disorders (FAPDs) are common in the pediatric population and are associated with a significant reduction in quality of life. Bidirectional communication of the brain-gut axis plays an important role in pain generation and perception in FAPDs. There is a paucity of data on the best approach to treat this group of disorders, with no Food and Drug Administration (FDA)-approved drugs and scarce research to substantiate the use of most medications. Use of hypnosis in pediatric FAPDs is supported by evidence and has long-term benefits of up to at least 5 years beyond completion of treatment, highlighting the importance of incorporating this therapy into the care of these patients. The mechanisms by which clinical hypnosis is beneficial in the treatment of FAPDs is not completely understood, but there is growing evidence that it impacts functioning of the brain-gut axis, potentially through influence on central pain processing, visceral sensitivity, and motility. The lack of side effects or potential for significant harm and low cost makes it an attractive option compared to pharmacologic therapies. This review addresses current barriers to clinical hypnosis including misconceptions among patients and families, lack of trained clinicians, and questions around insurance reimbursement. The recent use of telemedicine and delivery of hypnosis via audio-visual modalities allow more patients to benefit from this treatment. As the evidence base for hypnosis grows, acceptance and training will likely increase as well. Further research is needed to understand how hypnosis works and to develop tools that predict who is most likely to respond to hypnosis. Studies on cost-effectiveness in comparing hypnosis to other therapies for FAPDs will increase evidence for appropriate healthcare utilization. Because hypnosis has applications beyond pain and is child-friendly with minimal to no risk, hypnosis could be an important therapeutic tool in the wider pediatric gastrointestinal population.

Self-Efficacy in Children with Functional Constipation Is Associated with Treatment Success.

OBJECTIVES: To assess the relationship between self-efficacy, the belief that an individual can succeed at a goal, and short-term treatment outcome in children with functional constipation. STUDY DESIGN: Patients with functional constipation age 8-16 years completed the Self-Efficacy for Functional Constipation Questionnaire (SEFCQ), consisting of 14 statements about performing tasks needed for defecation. Patients completed SEFCQ before, immediately after, and 3 weeks after their clinic visit. Treatment success was defined as ≥3 bowel movements into the toilet and no fecal incontinence in the third week. RESULTS: 75% of patients had a successful outcome. Scores were higher in the group that was successful than in those that failed before, immediately after the visit, and 3 weeks later (P < .001). Self-efficacy improved at all time points in the group that was successful (P < .001). In the group that failed, scores improved immediately after clinic visit (P < .01) but were unchanged at follow-up (P > .05). CONCLUSIONS: Improved self-efficacy is associated with successful outcomes in children with functional constipation, thus, it may be beneficial to enhance self-efficacy for defecation during treatment.

Biliary Dyskinesia in Children: A Systematic Review.

Cholecystectomy rates for biliary dyskinesia in children are rising in the United States, but not in other countries. Biliary dyskinesia is a validated functional gallbladder disorder in adults, requiring biliary colic in the diagnosis. In contrast, most studies in children require upper abdominal pain, absent gallstones on ultrasound, and an abnormal gallbladder ejection fraction (GBEF) on cholecystokinin-stimulated cholescintigraphy for diagnosis. We aimed to systematically review existing literature in biliary dyskinesia in children, determine the validity and reliability of diagnostic criteria, GBEF, and to assess outcomes following cholecystectomy. We performed a systematic review following the PRISMA checklist and searched 7 databases including PubMed, Scopus, Embase, Ovid, MEDLINE, ProQuest, Web of Science, and the Cochrane library. Bibliographies of articles were screened for additional studies. Our search terms yielded 916 articles of which 28 were included. Three articles were manually added from searched references. We reviewed 31 peer-reviewed publications, all retrospective chart reviews. There was heterogeneity in diagnostic criteria and GBEF values. Outcomes after laparoscopic cholecystectomy varied from 34% to 100% success, and there was no consensus concerning factors influencing outcomes. The observational, retrospective study designs that comprised our review limited interpretation of safety and efficacy of the investigations and treatment in biliary dyskinesia in children. Symptoms of biliary dyskinesia overlapped with functional dyspepsia. There is a need for consensus on symptoms defining biliary dyskinesia, validation of testing required for diagnosis of biliary dyskinesia, and randomized controlled trials comparing medical versus surgical management in children with upper abdominal pain.

Vitamin and zinc status pretreatment and posttreatment in patients with inflammatory bowel disease.

Vitamin deficiencies are common in inflammatory bowel disease. Here we present 5-year follow-up data of 61 patients. No folate or vitamin B12 deficiency was identified throughout the study. A daily multivitamin supplement was sufficient to replete 100% of vitamin A-deficient and vitamin E-deficient patients. A total of 52% of vitamin D-deficient patients corrected, but 15% who had normal vitamin D levels at diagnosis developed deficiency. A total of 63% of zinc-deficient patients normalized their zinc status, but 15% developed zinc deficiency at follow-up despite supplementation.

Physiology of lower gastrointestinal tract.

BACKGROUND: The lower gastrointestinal (GI) tract, formed from the midgut and hindgut, encompasses the colon, rectum and anal canal. AIM: The aim of this review is to provide an overview of the anatomy and physiology of the lower GI tract. METHODS: Literature review on anatomy and physiology of the lower GI tract, including normal motility and phases of defecation. It derives its blood supply from the superior and inferior mesenteric arteries while it is innervated by the extrinsic autonomic (the thoracolumbar and sacral nerves) and the intrinsic enteric nervous system. The colon has four layers: mucosa, submucosa, muscularis externa and serosa. The anal canal ends in the internal and external anal sphincters (EASs) involved in continence and defecation. The lower GI tract is predominantly involved in digestion, absorption, defecation and protection. Defecation is a complex process that requires inter-neural (enteric and autonomic nervous systems), neurohormonal and neuromuscular coordination. It has four phases which include basal, pre-expulsive, expulsive and end phase. High-propagating contractions in the colon propel stool to the rectum leading to rectal distention and the recruitment of the recto-anal inhibitory reflex. Once able, the EAS, under full conscious control, is then relaxed allowing stool to be evacuated. Other defecation reflexes include the gastrocolic, gastroileal and coloanal reflexes. CONCLUSIONS: Recent advances provide novel techniques to investigate motility patterns including high-resolution manometry protocols with automated assessments, magnetic resonance imaging techniques for defecography, wireless motility capsules and fecobionics.

Liquid and solid gastric emptying and correlation with clinical characteristics in pediatric patients with dyspepsia.

BACKGROUND: There is limited data on gastric emptying in dyspeptic children. We aimed to determine solid and liquid emptying rates in dyspeptic children and correlate with clinical characteristics. METHODS: Charts of dyspeptic children undergoing 4-hour dual-phase gastric scintigraphy were reviewed for demographics, symptoms, and comorbidities. KEY RESULTS: In 1078 dyspeptic patients (65% females, median age 13 years) vomiting (55%), nausea (53%), and abdominal pain (52%) were the most common symptoms. The most common comorbidities were mental health (32%), neurologic (27%), and hypermobility spectrum disorders (20%). Solid and liquid emptying rates were aligned in 61.23%. Delayed solid with normal liquid emptying were noted in 2.5%, compared to delayed liquid with normal solid emptying in 26.16%. Abdominal pain had a trend for association with delayed or normal solid emptying (p = 0.06). Nausea was mostly reported with normal solid emptying (p < 0.0001) and underreported in patients <12 years with vomiting (29%). Abnormal solid emptying (rapid and delayed) was noted more frequently in children with mental health disorders (p = 0.027). Rapid liquid emptying was more common in children with genetic disorders (p = 0.032). CONCLUSION AND INFERENCES: Over half of children with dyspepsia had delayed liquid gastric emptying, and one quarter had delayed liquid with normal solid emptying. Dual-phase gastric emptying studies may help target therapy in dyspeptic children. Nausea is not a reliable symptom for dyspepsia in younger children. Given the significant association of abnormal gastric emptying in children with mental health disorders, we recommend screening and treating children with dyspepsia.

Psychological distress and coping efficacy in children with disorders of gut-brain interaction.

BACKGROUND: Multiple psychological factors influence disorders of gut-brain interaction (DGBIs). We aimed to evaluate psychological distress in Colombian schoolchildren with and without DGBIs. METHODS: We included children ages 8-18 years without organic medical conditions from largest regional public schools in Colombia. Children completed Spanish versions of Rome III diagnostic questionnaire for DGBIs, State Trait Anxiety Inventory for Children (STAIC), Children's Somatization Inventory (CSI), and a measure of coping efficacy. These data, demographic and socioeconomic characteristics, were compared between children with DGBIs and healthy peers. Exploratory analyses investigated differences between youth with symptoms of functional abdominal pain disorders (FAPDs) compared with healthy peers. KEY RESULTS: Of 1496 children, 281 (mean age 12.9 ± 2.2 years, 49.8% females) self-reported criteria for DGBIs and 125 reported (44.5%) FAPDs. Children with DGBIs had higher trait anxiety, emotional sensitivity, somatization including GI, non-GI, pain-related, and non-pain-related subscales (p < 0.001 each) and lower coping efficacy (p = 0.02) compared to healthy peers. Females had higher trait anxiety and somatization (p = 0.04 and p = 0.005, respectively). State and trait anxiety and coping efficacy differed based on location in children with DGBIs (p = 0.02, p = 0.03, and p < 0.001, respectively). Children with FAPDs had higher trait anxiety (p = 0.02) and somatization (p < 0.001) compared to healthy youth. CONCLUSIONS & INFERENCES: Children with DGBIs had higher anxiety, emotional sensitivity, and somatization, and lower coping efficacy compared with healthy youth. This highlights the importance of appraising psychological distress characteristics as well as incorporating conflict resolution, assertiveness training, and resilience building during the treatment of DGBIs.

Exploring Diagnostic Priorities: The Role of Colonic Manometry in Evaluating Pediatric Patients with Intractable Idiopathic Constipation Prior to Sacral Nerve Stimulation.

BACKGROUND: Despite the limited understanding of its precise mechanism of action, sacral nerve stimulation (SNS) has proven to be helpful for pediatric patients with constipation, particularly those with fecal incontinence. It is unclear whether the outcome of SNS is impacted by normal or abnormal colonic motility. Our study aimed to determine whether colonic manometry results had an impact on the outcome of SNS as a treatment in pediatric patients with refractory idiopathic constipation. METHODS: Electronic medical records of patients with idiopathic constipation who underwent colonic manometry and SNS placement at our center over 6 years were reviewed. A comparison of post-SNS outcomes was performed between patients with normal and abnormal colonic manometry studies. RESULTS: Twenty patients [12 (60%) females, median age of 10.2 years] met inclusion criteria, with fecal incontinence in 12 (60%) and abnormal colonic manometry in 6 (30%). Significantly more patients had an improvement in fecal incontinence following SNS placement (p = 0.045). There were no significant differences in post-SNS constipation outcome measures between patients with normal versus abnormal colonic manometry. CONCLUSIONS: Colonic manometry did not help with patient selection for those being considered for SNS therapy. Our findings do not support performing colonic manometry as a screening prior to SNS placement.

Safety and Effectiveness of Prucalopride in Children with Functional Constipation with and without Upper Symptoms.

INTRODUCTION: Pediatric prucalopride studies for treatment of gastrointestinal (GI) disorders have reported mixed results. We aimed to assess the safety and effectiveness of prucalopride in functional constipation (FC) with and without upper GI symptoms. METHODS: Retrospective data on patients with FC receiving combined prucalopride and conventional therapy was compared with those receiving conventional therapy alone within 12 months. Thirty patients on combined therapy and those on conventional therapy were each matched on the basis of age, gender, race, and presence of fecal soiling. Response (complete, partial, or no resolution) was compared. Similarly, response to concurrent functional upper GI symptoms (postprandial pain, bloating, weight loss, vomiting, early satiety, or nausea) and dysphagia, as well as adverse effects, were evaluated in the combined group. RESULTS: Mean age of 57 cases was 14.7 ± 4.9 years and 68% were female. Comorbidities included functional upper GI (UGI) symptoms (84%), dysphagia (12%), mood disorders (49%), and hypermobility spectrum disorder (37%). Unmatched cases reported 63% improvement to FC; response did not differ between the matched cohorts (70% versus 76.6%, p = 0.84). Cases showed a 56% improvement in functional UGI symptoms and 100% in dysphagia. Adverse effects were reported in 30%, abdominal cramps being most common. Four (7%) patients with a known mood disorder reported worsened mood, of which two endorsed suicidal ideation. CONCLUSION: Prucalopride efficaciously treated concurrent UGI symptoms and dysphagia in constipated pediatric patients and was overall well tolerated. Preexisting mood disorders seemed to worsen in a small subset of cases.

The microbiome in adolescents with irritable bowel syndrome and changes with percutaneous electrical nerve field stimulation.

BACKGROUND: Irritable bowel syndrome (IBS), a disorder of the gut-brain axis, is affected by the microbiome. Microbial studies in pediatric IBS, especially for centrally mediated treatments, are lacking. We compared the microbiome between pediatric IBS patients and healthy controls (HC), in relation to symptom severity, and with percutaneous electrical nerve field stimulation (PENFS), a non-invasive treatment targeting central pain pathways. METHODS: We collected a stool sample, questionnaires and a 1-2 week stool and pain diary from 11 to 18 years patients with IBS. A patient subset completed 4 weeks of PENFS and repeated data collection immediately after and/or 3 months after treatment. Stool samples were collected from HC. Samples underwent metagenomic sequencing to evaluate diversity, composition, and abundance of species and MetaCyc pathways. KEY RESULTS: We included 27 cases (15.4 ± 2.5 year) and 34 HC (14.2 ± 2.9 year). Twelve species including Firmicutes spp., and carbohydrate degradation/long-chain fatty acid (LCFA) synthesis pathways, were increased in IBS but not statistically significantly associated with symptom severity. Seventeen participants (female) who completed PENFS showed improvements in pain (p = 0.012), disability (p = 0.007), and catastrophizing (p = 0.003). Carbohydrate degradation and LCFA synthesis pathways decreased post-treatment and at follow-up (FDR p-value <0.1). CONCLUSIONS AND INFERENCES: Firmicutes, including Clostridiaceae spp., and LCFA synthesis pathways were increased in IBS patients suggesting pain-potentiating effects. PENFS led to marked improvements in abdominal pain, functioning, and catastrophizing, while Clostridial species and LCFA microbial pathways decreased with treatment, suggesting these as potential targets for IBS centrally mediated treatments.

Percutaneous electrical nerve field stimulation compared to standard medical therapy in adolescents with functional abdominal pain disorders.

Introduction: Standard medical therapy (SMT) in children with functional abdominal pain disorders (FAPD) includes cyproheptadine and amitriptyline. While percutaneous electrical nerve field stimulation (PENFS) has shown benefit, no study has compared outcomes of PENFS to SMT. We aimed to examine changes in abdominal pain, nausea and disability before and after treatment and compare outcomes between treatments. Methods: The records of FAPD patients ages 11-21 years, treated with 4 weeks of PENFS, cyproheptadine or amitriptyline were reviewed. Outcomes were evaluated using validated questionnaires [Abdominal Pain Index (API), Nausea Severity Scale (NSS), and the Functional Disability Inventory (FDI)] at baseline and follow-up within 3 months (FU). Result: Of 101 patients, 48% received PENFS, 31% cyproheptadine and 21% received amitriptyline. Median ages were 17 (15-19), 16 (15-18) and 15 (11-16) years respectively and the majority were females (75%, 90% and 52% respectively). In the PENFS group, API (p = 0.001), NSS (p = 0.059) and FDI (p = 0.048) were significantly lower at FU. API (p = 0.034) but not NSS and FDI (p > 0.05) decreased significantly at FU in the amitriptyline group. API, NSS and FDI did not change significantly with cyproheptadine at FU (p > 0.05). FU API scores were lower in PENFS vs. cyproheptadine (p = 0.04) but not vs. amitriptyline (p = 0.64). The FDI scores were significantly lower in the amitriptyline vs. cyproheptadine group (p = 0.03). Conclusion: Therapy with PENFS showed improvements in abdominal pain, nausea and disability while amitriptyline showed improvements in abdominal pain within 3 months of treatment. PENFS was more effective than cyproheptadine in improving abdominal pain. Amitriptyline improved disability scores more than cyproheptadine and showed promise for treatment. PENFS may be a good non-pharmacologic alternative for FAPD.

High amplitude propagated contractions with Glycerin versus Bisacodyl: A within-subject comparison in children undergoing colonic manometry.

BACKGROUND: The presence of high amplitude propagated contractions (HAPCs) measured by colonic manometry (CM) reflect an intact neuromuscular function of the colon. Bisacodyl and Glycerin are colonic stimulants that induce HAPCs and are used for the treatment of constipation. HAPCs characteristics with each drug have not been compared before. We aimed to compare the HAPC characteristics with Bisacodyl and Glycerin in children undergoing CM for constipation. METHODS: This is a prospective single-center cross-over study of children aged 2-18 years undergoing CM. All patients received both Glycerin and Bisacodyl during CM. They were randomized to group A with Bisacodyl first (n = 22) and group B with Glycerin first (n = 23), with 1.5 hours in between each dose. Differences in patient and HAPC characteristics between groups were summarized using descriptive statistics and compared using Chi-square test or Wilcoxon rank sum test as appropriate. KEY RESULTS: A total of 45 patients were included. HAPCs post Bisacodyl had a longer duration of action (median of 40 vs 21.5 min, p < 0.0001), longer propagation (median of 70 vs 60 cm, p = 0.02), and more HAPCs (median of 10 vs 5, p < 0.0001) compared Glycerin. No differences were found in the HAPC amplitude and onset of action between both medications.

Pediatric gastrointestinal neuromodulation: A review.

Neuromodulation, also known as bioelectric neuromodulation or neurostimulation, is the therapeutic use of electrical stimulation of nerves or brain centers. Neuromodulation has been trialed in an increasing range of human diseases as well as gastrointestinal disorders. The application of neuromodulation to treat pediatric motility and functional disorders is an exciting recent development. This review aims to briefly discuss the use of neuromodulation for the treatment of pediatric gastroparesis, constipation, and visceral hyperalgesia.

Herbal Approaches to Pediatric Functional Abdominal Pain.

Chronic abdominal pain is one of the most common problems seen by both pediatricians and pediatric gastroenterologists. Abdominal-pain-related functional gastrointestinal disorders (AP-FGIDs) are diagnosed in children with chronic and recurrent abdominal pain meeting clinical criteria set forth in the Rome IV criteria. AP-FGIDs affect approximately 20% of children worldwide and include functional dyspepsia (FD), irritable bowel syndrome (IBS), functional abdominal pain (FAP), and abdominal migraine. IBS accounts for 45% of pediatric AP-FGIDs. The pathophysiology of functional abdominal pain involves an interplay of factors including early life events, genetics, psychosocial influences, and physiologic factors of visceral sensitivity, motility disturbance, altered mucosal immune function, and altered central nervous system processing. Treatment approaches are varied and can include dietary, pharmacologic, and complementary medicine interventions, as well as psychosocial support, depending on the many aspects of the disorder and the needs of the individual patient. There is a strong interest in complementary and integrative medicine approaches to pediatric pain from both patients, providers, and families. In this article, we discuss popular herbal treatments typically used in the field of complementary medicine to treat pediatric AP-FGIDs: peppermint oil, Iberogast®, cannabis, fennel, and licorice. While high-quality data are rather limited, studies generally show that these remedies are at least as effective as placebo, and are well tolerated with minimal side effects. We will need more placebo-controlled, double-blind, and unbiased prospective studies to document and quantify efficacy.