Meal related symptoms in youth with chronic abdominal pain: Relationship to anxiety, depression, and sleep dysfunction.

OBJECTIVE: The objective of the current study was to describe meal-related symptoms in youth with chronic abdominal pain fulfilling criteria for a disorder of gut-brain interaction (DGBI) and their associations with anxiety, depression, and sleep disturbances. METHODS: This was a retrospective evaluation of 226 consecutive patients diagnosed with an abdominal pain-associated DGBI. As part of routine care, all had completed a standardized symptom history, the Sleep Disturbances Scale for Children (utilized to assess for disorders of initiation and maintenance of sleep and excessive daytime somnolence) and the Behavior Assessment System for Children-Third Edition (utilized to assess for anxiety and depression). Four meal related symptoms were assessed: early satiety, postprandial bloating, postprandial abdominal pain, and postprandial nausea. RESULTS: Overall, 87.6% of patients reported at least one meal related symptom and the majority reported at least three symptoms. All meal related symptoms were significantly related to each other. Postprandial pain and nausea were more often reported by females. Early satiety, postprandial bloating, and postprandial nausea, but not postprandial pain demonstrated significant though variable associations with anxiety, depression, disorders of initiation and maintenance of sleep, and disorders of excessive somnolence, but only in adolescents. CONCLUSIONS: Meal related symptoms are very common in youth with abdominal pain-associated DGBIs. Early satiety, bloating, and postprandial nausea demonstrate variable associations with anxiety, depression, and disordered sleep while increased postprandial pain was not associated with psychologic or sleep dysfunction, suggesting a different pathway for symptom generation.

High Rate of Emergency Department Care in Youth With Abdominal Pain-Associated Functional Gastrointestinal Disorders.

OBJECTIVES: The primary objective was to describe patterns of care delivery locations in youth with abdominal pain-associated functional gastrointestinal disorders (AP-FGID) and assess for differences in patterns of care delivery by sex and race. A secondary objective was to describe cost variability within the emergency department (ED). METHODS: Data were obtained using a large, single-vendor database that extracts and deidentifies data from the electronic health record across the outpatient, ED, and inpatient continuum of care. We evaluated patients 8 to 17 years of age seen over an 8-year period for a priority 1 diagnosis of an AP-FGID. Data collected included age, sex, race, encounter location, and total cost of ED encounters. We specifically assessed how often patients seen in the ED were also seen in outpatient or inpatient settings. RESULTS: A total of 53,750 patients (64% female; mean age, 13.3 ± 2.8 years) were identified and assessed. The most common location of care was the ED (48.8%) followed by the outpatient setting (46.2%). Of patients seen for a priority 1 AP-FGID diagnosis in the ED, only 3.7% were seen for a priority 1 diagnosis in the outpatient setting, and only 1% were seen in an inpatient setting. Overall, females received 42.5% of their care and males received 44.8% of their care in the ED. The overall rate of ED care was 66.9% for Hispanic, 61.5% for African American, 55.1% for Asian, 46.6% for Native American, and 36.9% for Caucasian patients. CONCLUSIONS: The ED is the most common location for care for youth with AP-FGIDs and, for the majority, seems to be the only location. This seems to be particularly true for Hispanic and African American patients. Given the often complex psychosocial needs of this patient group, processes need to be developed to transition these patients into the outpatient setting, ideally to programs specializing in chronic pain.

Pediatric Gastroenterology, Hepatology, and Nutrition Entrustable Professional Activities: Development of an Assessment Tool and Curricular Resources.

BACKGROUND: Entrustable professional activities (EPAs) are critical activities performed by medical professionals, which can be observed and assessed. Adding on to common EPAs for all pediatric subspecialty trainees, specialty-specific EPAs for pediatric gastroenterology, hepatology, and nutritional fellowship were developed by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) EPA Task Force. METHODS: Having developed specialty-specific EPAs, building EPA assessments is the next logical step, as EPAs are included under a larger umbrella of competency-based assessment. Thus, the NASPGHAN EPA Task Force and Training Committee collaborated on an assessment tool and associated curricular resources to aid in tracking trainees' progression to entrustment within individual EPAs and readiness for independent practice. RESULTS: This manuscript reports the development of an EPA assessment tool, including guiding principles and the theory behind the assessment tool, with a focus on simple, meaningful assessments that can provide crucial performance feedback to trainees. In addition, curricular resources were developed, based on the assessment tool, to support training. Ultimately, it is the hope of the NASPGHAN EPA Task Force and Training Committee that this tool can aid training programs in providing formative feedback for trainees, and can be used by training programs and clinical competency committees for summative evaluation.

A Pilot Study of Ketotifen in Patients Aged 8-17 Years with Functional Dyspepsia Associated with Mucosal Eosinophilia.

BACKGROUND AND OBJECTIVE: Mast cells have been implicated in abdominal pain-associated disorders of gut-brain interaction, such as functional dyspepsia. As such, ketotifen, a second-generation antihistamine and mast cell stabilizer, could represent a viable treatment option in these conditions. The primary aim of the current pilot study was to assess clinical response to ketotifen and assess pharmacokinetics in youth with functional dyspepsia. METHODS: We conducted a pilot randomized, double-blind, placebo-controlled, cross-over trial of ketotifen in 11 youth with functional dyspepsia and duodenal mucosal eosinophilia with 4 weeks of active treatment at a dose of 1 mg twice daily. Global clinical response was graded on a 5-point Likert Scale. A single plasma sample was obtained at steady state for pharmacokinetic analysis. RESULTS: Ketotifen was not superior to placebo with regard to global clinical response. Only 18% of patients demonstrated a complete or near-complete clinical response. The estimated half-life was 3.3 h. CONCLUSIONS: While ketotifen was not superior to placebo, this study highlights several important challenges for developing drug trials for youth with chronic abdominal pain. Recommendations are made for designing a larger treatment trial for ketotifen in this patient group. CLINICAL TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov: NCT02484248.

Overactive bladder syndrome symptoms in youth with abdominal pain-associated disorders of gut-brain interaction.

The purpose of the current study was to assess the frequency of overactive bladder syndrome (OBS) symptoms and their relationship to gastrointestinal symptoms in youth with abdominal pain-associated disorders of gut-brain interaction (AP-DGBI). This is a retrospective study of 226 youth diagnosed with an AP-DGBI. As part of standard care, all patients completed a symptom questionnaire regarding gastrointestinal and non-gastrointestinal symptoms including increased urinary frequency, nighttime urination, and urinary urgency. Overall, 54% of patients reported at least one OBS symptom. Increased frequency of urination was reported by 19%, urinary urgency by 34%, and nighttime urination by 36%. Increased frequency of urination and urinary urgency were associated with a change in stool form, a change in stool frequency, and in those fulfilling criteria for IBS. Increased frequency of urination was reported more frequently in those reporting predominantly loose stools (33% vs. 12%). Urinary symptoms are common in youth with AP-DGBI. Increased urinary frequency and urinary urgency are specifically associated with IBS, with increased urinary frequency being primarily associated with diarrhea predominant IBS. Further studies are needed to determine the impact of OBS on AP-DGBI severity and quality of life, and whether they impact DGBI treatment.

A Cross-Sectional Study of Sleep Disturbances in Children and Adolescents With Abdominal Pain-Associated Disorders of Gut-Brain Interaction.

The aims of the current study were to determine the frequencies of specific sleep disturbances in youth with abdominal pain-associated disorders of gut-brain interaction (AP-DGBIs) and to assess relationships with psychological dysfunction. This was a retrospective evaluation of 226 consecutive patients diagnosed with an AP-DGBI. All had undergone a systematic evaluation of gastrointestinal symptoms, the Sleep Disturbance Scale for Children, and the Behavior Assessment System for Children. Disorders of initiation and maintenance of sleep (DIMS; 40%) and disorders of excessive daytime somnolence (DOES; 14%) were each present in more than 10% of the patients. Both DIMS and DOES scores were more likely to be elevated in patients with anxiety and/or depression scores in the at-risk or elevated-risk ranges. Sleep disorders are common in youth with AP-DGBIs and are associated with anxiety and depression, even in those patients with anxiety and depression in the at-risk range.

An unusual presentation of inflammatory bowel disease.

Erythema nodosum (EN) is an infrequent but well-described extraintestinal manifestation of inflammatory bowel disease (IBD). We report a case of a previously healthy 8-year-old girl who presented to her primary care manager with a chief complaint of EN and was later found to have Crohn's disease. This article reviews the causes of EN, the significance of EN in IBD, and the recommended diagnostic approach to IBD in children.

Pediatric Rome IV diagnosis agreement is greater than agreement on diagnostic testing.

BACKGROUND: Pediatric Rome IV criteria are used to diagnose childhood functional gastrointestinal disorders (FGIDs). This study of pediatric gastroenterology physicians measured their agreement in (1) Making a pediatric Rome IV FGID diagnosis; and (2) Diagnostic testing for patients with FGIDs. METHODS: Pediatric gastroenterologists and pediatric gastroenterology fellows at two medical centers completed a survey containing clinical FGID vignettes. For each vignette, raters identified the most likely Rome IV diagnosis(es) and selected which diagnostic test(s) (if any) they typically would obtain. The survey was re-administered within 3 months. Inter-rater and intra-rater weighted percent agreement was determined. Linear mixed modeling identified sources of variability in diagnostic testing. KEY RESULTS: Thirty-four raters completed the initial survey of whom thirty-one (91%) completed the repeat survey. Overall inter-rater agreement on Rome IV diagnoses was 68% for initial and repeat surveys whereas intra-rater agreement was 76%. In contrast, overall inter-rater agreement on diagnostic testing was <30% for both initial and repeat surveys and intra-rater agreement was only 57%. Between-physician differences accounted for 43% of the variability in the number of tests selected. Rater identified use of Rome criteria in clinical practice was associated with 1.1 fewer diagnostic tests on average (95% CI 0.2-2.0, p = 0.015). Higher intra-rater agreement was noted for diagnostic testing in faculty when compared to fellows (p = 0.009). CONCLUSIONS & INFERENCES: In a multicenter evaluation among pediatric gastroenterology physicians, pediatric Rome IV diagnostic agreement was higher than that reported for previous Rome versions, and higher than agreement on diagnostic testing.

Update on the Role of Allergy in Pediatric Functional Abdominal Pain Disorders: A Clinical Perspective.

Both functional abdominal pain disorders (FAPDs) and food allergies are relatively common in children and adolescents, and most studies report an association between FAPDs and allergic conditions. FAPDs share pathophysiologic processes with allergies, including both immune and psychological processes interacting with the microbiome. No conclusive data are implicating IgE-mediated reactions to foods in FAPDs; however, there may be patients who have IgE reactions localized to the gastrointestinal mucosa without systemic symptoms that are not identified by common tests. In FAPDs, the data appears stronger for aeroallergens than for foods. It also remains possible that food antigens initiate an IgG reaction that promotes mast cell activation. If a food allergen is identified, the management involves eliminating the specific food from the diet. In the absence of systemic allergic symptoms or oral allergy syndrome, it appears unlikely that allergic triggers for FAPDs can be reliably identified by standard testing. Medications used to blunt allergic reactions or symptomatically treat allergic reactions may be useful in FAPDs. The purpose of the current manuscript is to review the current literature regarding the role of allergy in FAPDs from a clinical perspective, including how allergy may fit in the current model of FAPDs.

An Update on the Assessment and Management of Pediatric Abdominal Pain.

Chronic abdominal pain is very common in children and adolescent and results in high personal and social costs. Most youth with chronic abdominal pain fulfill criteria for a functional abdominal pain disorder (FAPD) as defined by Rome criteria. These are complex conditions with a wide array of biological, psychological, and social factors contributing to the experience of pain. The purpose of the current review is to provide an overview of the pathophysiology of FAPDs and an up-to-date summary of the literature related to FAPDs in children and adolescents, with additional focus on several areas (eg, diet and probiotics) where patients and families frequently have questions or implement self-directed care. We also provide an approach to the assessment and treatment of pediatric FAPDs focusing on the robust literature regarding psychological interventions and much sparser literature regarding medication treatment.

Heartburn in children and adolescents in the presence of functional dyspepsia and/or irritable bowel syndrome correlates with the presence of sleep disturbances, anxiety, and depression.

ABSTRACT: The aim of this study was to assess the relationship of heartburn in pediatric patients with functional dyspepsia (FD) and irritable bowel syndrome (IBS) with gastrointestinal symptoms, sleep disturbances, and psychologic distress.The overlap in symptoms of FD, IBS, and gastroesophageal reflux disease (GERD) predicts greater symptom severity and decreased quality of life and presents opportunities for improved diagnostic classification and personalized therapeutics.A cross-sectional observational study of 260 pediatric patients with abdominal pain was conducted. Patients completed standardized questionnaires assessing clinical symptoms, sleep quality, and psychologic symptoms during routine clinical care. Questionnaire data were compared for patients reporting heartburn and not reporting heartburn using χ2 and t tests where appropriate.Gastrointestinal symptoms were significantly more prevalent among patients with a positive report of heartburn (vs a negative report of heartburn): pain with eating (83% vs 67%, P = .007), bloating (63% vs 44%, P = .005), acid regurgitation (47% vs 24%, P ≤ .001), and chest pain (45% vs 20%, P ≤ .001). Likewise, initiating and maintaining sleep (P = .007), arousal/nightmares (P = .046), sleep-wake transition (P = .001), hyperhidrosis during sleep (P = .016), and anxiety (P = .001) and depression (P = .0018) were also significantly increased in patients who reported heartburn versus patients who did not report heartburn.Patients with a positive report of heartburn, whether classified as having FD and/or IBS, had increased gastrointestinal symptoms, sleep disturbances, anxiety, and depression than patients with a negative report of heartburn. A better understanding of these associations may allow for personalized treatment for youth with abdominal pain and heartburn as a primary symptom.

Relationships between disaccharidase deficiencies, duodenal inflammation and symptom profile in children with abdominal pain.

Abdominal pain has been associated with disaccharidase deficiencies. While relationships with individual symptoms have been assessed, relationships between disaccharidase deficiencies and symptom complexes or inflammation have not been evaluated in this group. The primary aims of the current study were to assess relationships between disaccharidase deficiency and symptoms or symptom complexes and duodenal inflammation, respectively. Patients with abdominal pain who underwent endoscopy with evaluation of disaccharidase activity levels were identified. After excluding all patients with inflammatory bowel disease, celiac disease, H. pylori, or gross endoscopic lesions, patients were evaluated for disaccharidase deficiency frequency. Disaccharidase were compared between patients with and without histologic duodenitis. Lastly, relationships between individual gastrointestinal symptoms or symptom complexes were evaluated. Lactase deficiency was found in 34.3% of patients and disaccharidase pan-deficiency in 7.6%. No individual symptoms or symptom complexes predicted disaccharidase deficiency. While duodenitis was not associated with disaccharidase deficiency, it was only present in 5.9% of patients. Disaccharidase deficiency, particularly lactase deficiency, is common in youth with abdominal pain and multiple deficiencies are not uncommon. Disaccharidase deficiency cannot be predicted by symptoms in this population. Further studies are needed to assess the clinical significance of disaccharidase deficiency.

Healthcare System-to-System Cost Variability in the Care of Pediatric Abdominal Pain-Associated Functional Gastrointestinal Disorders.

The purpose of this study was to assess cost variability in the care of abdominal pain-associated functional gastrointestinal disorders (AP-FGIDS) in youth across health systems, races, and specific AP-FGID diagnoses. Patients, aged 8-17 years, with a priority 1 diagnosis corresponding to a Rome IV defined AP-FGID were identified within the Health Facts® database. Total costs were obtained across the continuum of care including outpatient clinics, emergency department, and inpatient or observation units. Cost variability was described comparing different health systems, races, and diagnoses. Thirteen thousand two hundred and fourteen patients were identified accounting for 17,287 encounters. Total costs were available for 38.7% of the encounters. There was considerable variability in costs within and, especially, across health systems. Costs also varied across race, urban vs. rural site of care, and AP-FGID diagnoses. In conclusion, there was considerable variability in the costs for care of AP-FGIDs which is sufficient to support multi-site studies to understand the value of specific tests and treatments. Significant differences in costs by race merit further investigation to understand key drivers.

Medicine and Media: The Ranitidine Debate.

Ranitidine has been the topic of recent media reports. Current findings, confirmed by the US Food and Drug Administration, indicate that some ranitidine products contain a substance that may be carcinogenic. Providers and patients require additional information on the risks of continuing therapy vs. the benefits of the medication. This article comments on what is currently known about the evolving situation of elevated N-nitrosodimethylamine levels in ranitidine and the limits of the existing information to assess best practices.

Sucrase Breath Testing in Children Presenting With Chronic Abdominal Pain.

Sucrase deficiency has been implicated in chronic abdominal pain. Testing for sucrase deficiency generally involves invasive procedures or lengthy clinical visits, but now noninvasive kits that allow home testing are available to test for sucrase deficiency. In order to assess feasibility and utility of at-home testing, we reviewed our experience in 75 consecutive patients. All patients seen in the abdominal pain clinic had histories obtained in a standardized fashion and all had sucrase breath tests completed at home utilizing a commercially available kit. Testing was completed by 46 patients (61.3%). Tests were abnormal indicating sucrase deficiency in 34.8% of those completing testing. No symptoms were predictive of a positive test although there were trends of an association of an abnormal test with diarrhea and bloating. Our findings suggest that sucrase deficiency occurs frequently enough that more widespread testing and/or an empiric trial of sucrose and starch restriction should be considered.

Biliary Dyskinesia in Children and Adolescents: A Mini Review.

Introduction: While functional gallbladder disorder is a well-recognized and defined condition in adults, its pediatric analog, biliary dyskinesia, lacks uniformity in diagnosis. Yet, biliary dyskinesia is among the most common conditions resulting in cholecystectomy in youth and its frequency continues to rise. The primary aims of the current review were assess the efficacy of cholecystectomy in children diagnosed with biliary dyskinesia and the utility of cholescintigraphy in predicting outcomes. Results: All previous studies assessing outcomes in youth with biliary dyskinesia have been retrospective and therefore of low quality. There is a lack of uniformity in patient selection. Short term follow-up reveals partial response in 63.4-100% with complete resolution in 44.2-100%. Only 4 studies have reported long-term outcomes with complete symptom resolution in 44-60.7%. The published research generally indicates that the gallbladder ejection fraction (GBEF) as determined by cholescintigraphy lacks utility in predicting cholecystectomy outcome utilizing the commonly used cut-off values. There are data suggesting that more extreme cut-off values may improve the predictive value of GBEF. Conclusion: There is a lack of consensus on the symptom profile defining biliary dyskinesia in youth and current literature does not support the use of cholescintigraphy to select patients for cholecystectomy. There is a substantial portion of pediatric patients diagnosed with biliary dyskinesia who do not experience long-term benefit from cholecystectomy. Well-designed prospective studies of surgical outcomes are lacking. Increasing the uniformity in patient selection, including both symptom profiles and cholescintigraphy results, will be key in understanding the utility of cholecystectomy for this condition.

The relationship between mucosal inflammatory cells, specific symptoms, and psychological functioning in youth with irritable bowel syndrome.

Both mucosal inflammation and psychologic dysfunction have been implicated in irritable bowel syndrome (IBS). While some relationships between inflammation (mast cells and eosinophils) and depression have been reported in adults with IBS, relationships between inflammation and psychologic function have not been studied in children and adolescents. The aims of the current study were to: (1) assess densities of colonic mast cells, eosinophils, and TH17 cells in youth with IBS; and, (2) explore relationships between these cells and specific IBS symptoms and psychologic functioning. Utilizing previously obtained biopsies from the descending and rectosigmoid colons, densities were determined for mast cells, eosinophils, and TH17 cells, respectively, in 37 youth with IBS and 10 controls. In IBS patients, densities were assessed in relation to specific IBS symptoms and in relation to self-report anxiety and depression scores. In both the descending and rectosigmoid colons, densities of mast cells, eosinophils, and TH17 cells were higher in IBS patients as compared to controls. In IBS patients, rectosigmoid mast cell density was higher in those reporting pain relief with defecation. Also, in IBS patients, rectosigmoid eosinophilia was associated with higher anxiety scores and eosinophil density correlated with depression scores. In the descending colon, eosinophil and mast cell densities both correlated with depression scores. In conclusion, mucosal inflammation (mast cells and eosinophils) is associated with pain relief with defecation and with anxiety and depression in youth with IBS.

Comparison of the use of wireless capsule endoscopy with magnetic resonance enterography in children with inflammatory bowel disease.

BACKGROUND: Magnetic resonance enterography (MRE) and wireless capsule endoscopy (WCE) are equally accepted modalities for noninvasive screening of small bowel involvement (SBI) in children with Crohn's disease (CD) and indeterminate colitis (IC) albeit there is a paucity of data comparing the two and thereby guiding the clinician in selecting the ideal diagnostic approach. Therefore, the goal of this study is to provide additional evidence for capsule endoscopy role in the evaluation of established Crohn's disease exacerbation compared to MRE in relation to Pediatric Crohn's Disease Activity Index (PCDAI), and histological indices. AIM: To prospectively compare the findings of MRE and WCE and their agreement with PCDAI or histology in children with CD or IC. METHODS: Consecutive patients diagnosed with CD and IC were screened for inclusion. After informed consent, patient's demographic and clinical data was abstracted. The current pediatric disease activity index (PCDAI) and endoscopic findings were included. Patients underwent MRE and WCE including preprocedural patency capsule within a maximum of 7 d of each other. Pathological presence of active small bowel disease in ileal and duodenal biopsies were collected if the endoscopy was performed within 2 mo of the WCE study. Patients who failed to pass the PC were excluded from the study. WCE was read by two different experienced gastroenterologists (Attard TM and Colombo JM) blinded to each other's findings and to the findings on MRE (Mardis NJ). Agreement between WCE reviewers, WCE and MRE findings and concordance between positive PCDAI and SBI based on MRE compared with WCE was computed. RESULTS: Forty-five patients were included in the study, 18 withdrew and 27 (20 males and 20 CD), mean age (standard deviation) 13.46 (2.4) years, completed the study protocol. There were no instances of capsule retention. Concordance between gastroenterologist reviewers was excellent for the diagnosis of small intestinal CD with good correlation between the two Lewis scores (r = 0.875, P < 0.001). Concordance between WCE and MRE was poor (69%). In CD patients, when both MRE and WCE were compared using PCDAI > 10 as the standard reference reflecting active small intestinal CD, the sensitivity of MRE and WCE were 100% and 83% respectively and the specificity of MRE and WCE were 57.14% and 78.6%, respectively. If the histology in ileum or/and duodenum was used as the reference for active small bowel involvement, WCE had a higher specificity as compared to MRE (83.3% vs 50%). In patients with Crohn's disease, those with a positive PCDAI (> 10) were more likely to have a positive WCE as compared to those with a negative PCDAI (83% vs 21%; P = 0.018). CONCLUSION: We suggest that MRE and WCE have a complementary role in the assessment of SBI in CD. WCE detected SBI with a much higher specificity while MRE had a higher sensitivity.