Metabolomic comparison of postprandial distress syndrome patients with and without duodenal eosinophilia.

OBJECTIVE: In functional dyspepsia patients, duodenal mucosal eosinophilia has been associated with early satiety but is not present in all patients suggesting varied pathways to symptom generation. The objective of the current study was to explore metabolic differences comparing those with duodenal mucosal eosinophilia to those without eosinophilia. METHODS: This study was conducted utilizing an existing biorepository. Patients had plasma samples obtained at the time of endoscopy. All had undergone endoscopy for dyspepsia and reported early satiety. Two groups were identified including those with peak duodenal mucosal eosinophil densities above 30/high power field (N = 28) and those below 30 (N = 16). The fasting plasma samples were analyzed by liquid chromatography/high-resolution mass spectrometry. Significant differences between groups were determined. RESULTS: The eosinophilia group demonstrated significant elevations in several gamma-glutamyl amino acids. The eosinophilia group had elevations of metabolites associated with oxidative stress including glutathione metabolites (cysteinlyglycine and cys-gly oxidized), and metabolites related to nitric oxide synthesis (arginine, citrulline, ornithine, and dimethylarginine). Eosinophilia was also associated with alterations in lipid metabolism including several long-chain acylcarnitine conjugated fatty acids. Carnitine levels were lower in the eosinophilia group. Lastly, vanillymandelate, a derivative of norepinephrine and epinephrine was elevated in the eosinophilia group. CONCLUSIONS: In patients with dyspepsia and early satiety, duodenal mucosal eosinophilia is associated with metabolites levels which are consistent with increased oxidative stress and alterations in lipid metabolism. Eosinophilia was also associated with lower carnitine levels. These alterations may contribute to pathophysiology and represent therapeutic targets.

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.

The Association Between Affect and Sleep in Adolescents With and Without FGIDs.

OBJECTIVE: Adolescents with chronic pain associated with functional gastrointestinal disorders (FGIDs) experience negative impacts on their health behaviors (i.e., sleep) and are at risk for a range of problems related to negative affect, which may serve to exacerbate one another in a reciprocal fashion. This study aimed to determine if the strength of the relationship between affect and sleep differs across community adolescents and adolescents with FGIDs. It was hypothesized that shorter sleep durations would be associated with more negative affect and longer sleep durations would be associated with more positive affect, and that group membership would moderate these relationships. METHODS: Twenty-five adolescents with FGIDs were compared with 25 matched peers to examine the differential association between affect and total sleep time (TST). Models were estimated using SAS PROC MIXED for inter- and intraindividual differences. RESULTS: Models predicting TST revealed a significant three-way interaction among weekday, group status, and negative affect. Simple slopes indicated that when negative affect is one standard deviation below the child's own average on weekends, participants with FGIDs obtained significantly more sleep than those in the comparison group (ß = 47.67, p < .05). CONCLUSIONS: The findings of the present study show that when adolescents with FGIDs have lower negative affect on the weekend, when demands are likely reduced, they are able to obtain more TST. These findings confirm that unique relationships exist between negative affect and sleep duration for youth with FGIDs, and their interaction may hold value in understanding and addressing these targets.

Mucosal Th17 Cells Are Increased in Pediatric Functional Dyspepsia Associated with Chronic Gastritis.

BACKGROUND: Chronic gastritis is a common histologic finding in children with functional dyspepsia (FD). While Th17 cells have been implicated in other forms of gastritis, they have not been evaluated in chronic gastritis. AIMS: The aim of the current study was to assess Th17 cells in children with FD with and without chronic gastritis. METHODS: Densities were determined for Th17 cells, eosinophils, and mast cells, respectively, in both the gastric antrum and the duodenum. Densities were compared between five groups: FD with chronic gastritis (N = 20), FD without chronic gastritis (N = 20), Helicobacter pylori-associated gastritis (N = 10), Crohn's gastritis (N = 10), and normal controls (N = 10). Th17 densities were also compared between patients with and without early satiety. RESULTS: FD with chronic gastritis was associated with higher Th17 cell density as compared to normal controls and comparable to both H. pylori-associated gastritis and Crohn's gastritis. Eosinophil and mast cell densities were higher in FD patients with chronic gastritis as compared to either FD without gastritis or normal controls. Th17 density was higher in patients reporting early satiety but not in those with epigastric pain. CONCLUSIONS: FD with chronic gastritis is associated with higher Th17 cell, eosinophil, and mast cell density as compared to FD without chronic gastritis or normal controls. Chronic gastritis demonstrated Th17 cell density similar to that seen in other conditions where Th17 cells are believed to play a pathogenic role. Th17 cells may represent another therapeutic target in these patients.

Heart Rate Variability and Gastric Electrical Response to a Cold Pressor Task in Youth with Functional Dyspepsia.

BACKGROUND/AIMS: While stress has been implicated in functional dyspepsia (FD), the mechanisms by which stress results in symptoms are not well defined. The aim of the current study was to assess gastric myoelectric and autonomic changes in response to a physical stressor in youth with FD. METHODS: In a group of healthy controls and pediatric FD subjects, we recorded ECG and EGG signals 30 min before and 60 min after, a cold pressor task (CPT). Gastric EGG and heart rate variability (HRV) parameters were calculated in pre- and post-CPT stages and in short intervals. RESULTS: The pre-CPT percent tachygastria was higher in FD subjects as compared to controls. However, CPT did not induce any EGG changes in either controls or FD subjects and the two groups did not differ from each other post-CPT. The CPT resulted in an increase in HRV and standard deviation of NN intervals in controls; there was no change in any HRV parameter in FD subjects. CONCLUSIONS: Acute physical stress does not appear to induce gastric electrical abnormalities in youth with FD. Youth with FD appear to lack the normal flexible autonomic response to a physical stressor.

Novel Protective Role of Nicotinamide Phosphoribosyltransferase in Acetaminophen-Induced Acute Liver Injury in Mice.

Acetaminophen overdose is the most common cause of acute liver injury (ALI) or acute liver failure in the United States. Its pathogenetic mechanisms are incompletely understood. Additional studies are warranted to identify new genetic risk factors for more mechanistic insights and new therapeutic target discoveries. The objective of this study was to explore the role and mechanisms of nicotinamide phosphoribosyltransferase (NAMPT) in acetaminophen-induced ALI. C57BL/6 Nampt gene wild-type (Nampt+/+), heterozygous knockout (Nampt+/-), and overexpression (NamptOE) mice were treated with overdose of acetaminophen, followed by histologic, biochemical, and transcriptomic evaluation of liver injury. The mechanism of Nampt in acetaminophen-induced hepatocytic toxicity was also explored in cultured primary hepatocytes. Three lines of evidence have convergently demonstrated that acetaminophen overdose triggers the most severe oxidative stress and necrosis, and the highest expression of key necrosis driving genes in Nampt+/- mice, whereas the effects in NamptOE mice were least severe relative to Nampt+/+ mice. Treatment of P7C3-A20, a small chemical molecule up-regulator of Nampt, ameliorated acetaminophen-induced mouse ALI over the reagent control. These findings support the fact that NAMPT protects against acetaminophen-induced ALI.

A comparison of the diagnosis of gastroparesis in 4 h pediatric gastric emptying studies versus 2 h studies.

BACKGROUND: In adults, there is a consensus for standards to diagnose gastroparesis utilizing a gastric emptying study as the key diagnostic modality but there is no consensus for a standard in pediatrics. Additionally, some cost savings might be achieved if symptoms could be utilized to predict patients with gastroparesis. The aims of the current study were to confirm the sensitivity of a 4 h study in the pediatric population and to assess whether the severity of symptoms were predictive of delayed gastric emptying. STUDY: This was a single site, two part study. In the first part, results were reviewed for all patients who had completed a 4-h, solid gastric emptying study over the course of a 3 year period. In the second portion of the study, participants scheduled for a gastric emptying study, completed a modified GCSI questionnaire. RESULTS: Out of a total of 109 participants, at 2 h, 14 participants (12.8%) had abnormal studies as compared to 26 (23.85%) participants who had abnormal studies at 4 h (p = .0027). Of the 95 participants with normal studies at 2 h, 15% (14/95) were abnormal at 4 h. There were no differences in symptom severity scores between those with slow and those with normal emptying at either 2 h or 4 h. CONCLUSIONS: Our study adds independent confirmation that extending studies from 2 to 4 h increases the diagnostic yield and should be the standard in children and adolescents as it is in adults.

Is histologic esophagitis associated with dental erosion: a cross-sectional observational study?

BACKGROUND: Gastroesophageal reflux disease (GERD) affects 15-25% of children and adolescents in the United States. The diagnosis of GERD in children is complex as reported symptoms or symptom profiles have been found to be unreliable. Frequently, the diagnosis must be confirmed by objective tests such as pH monitoring or histological evidence of esophagitis on an esophageal biopsy. Dental erosion has been shown to be associated with GERD as an atypical complication and has the potential to be a marker of GERD. The purposes of this study were to compare the frequency and patterns of dental erosion in children and adolescents with and without histologic esophagitis. METHODS: Twenty-five subjects were recruited from patients scheduled for an upper gastrointestinal endoscopy. Information regarding potential GERD symptoms, food habits, and dental hygiene habits were obtained. Intra-oral photographs were taken, and a dental exam for erosion was performed. The results of a standard biopsy taken from the lower third of the esophagus during an endoscopy were used to divide subjects into either the control group or the GERD group (i.e. those with histologic esophagitis). RESULTS: Twenty-two subjects yielded 586 evaluable teeth. No significant difference was found between frequency or erosion patterns of those with and without histologic esophagitis. Dental erosions were more frequent in primary teeth. CONCLUSIONS: Dental erosions do not appear to be associated with histologic esophagitis indicative of GERD.

Prevalence of overlap syndromes and symptoms in pediatric functional dyspepsia.

BACKGROUND: The purpose was to evaluate the overlap frequency of irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD), and overactive bladder syndrome (OBS), as well as other gastrointestinal and systemic symptoms, in functional dyspepsia (FD). Additionally, we sought to determine whether adult Rome III FD subtypes were uniquely related to overlap syndromes or symptoms. METHODS: The study was a retrospective review of 100 consecutive pediatric patients, age 8-17 years, diagnosed with FD. All had completed a standardized medical history including gastrointestinal and systemic symptoms as well as specific symptoms related to GERD and OBS. The frequency of overlap with IBS, GERD, and OBS were determined for the whole group and for those fulfilling adult FD subtype criteria. Individual symptoms were also compared by FD subtype. RESULTS: Overlap IBS was present in 33 % of the FD patients. At least one GERD symptom was present in 74 % of patients with 41 % reporting heartburn. At least one OBS symptom was present in 44 % of patients with 29 % reporting urinary urgency. Other than pain, the most common reported gastrointestinal symptom was nausea (86 %). Systemic symptoms were common. Overlap syndromes/symptoms did not vary by FD subtype. Postprandial distress syndrome was associated with pain with eating, weight loss, and waking at night to have a stool. CONCLUSIONS: FD is a heterogeneous condition in children and adolescents with significant variability in the presence of gastrointestinal and non-gastrointestinal symptoms and overlap syndromes. Varying symptom profiles need to be accounted for and analyzed in studies involving subjects with FD.

Investigation of potential early Histologic markers of pediatric inflammatory bowel disease.

BACKGROUND: Early manifestations of pediatric inflammatory bowel disease (IBD) can be relatively nonspecific. Initial mucosal biopsies may not be conclusive, delaying the diagnosis until subsequent biopsies demonstrate typical histologic features of IBD. We hypothesized that certain inflammatory cell types may be utilized as early histologic indicators of IBD in children. METHODS: A retrospective analysis compared histologic findings from initially inconclusive or negative endoscopic studies in 22 patients who were subsequently diagnosed with IBD (after diagnostic endoscopy) to those of 20 comparison patients with functional abdominal pain matched for age, gender, and study type. A pediatric pathologist, blinded to study group, reviewed biopsies for histologic abnormalities. Eosinophil densities were obtained from the stomach, duodenum, and rectosigmoid areas. Immunohistochemistry (IHC) staining for tumor necrosis factor-α (TNF-α) and matrix metalloproteinase-9 (MMP-9) was performed on the stomach and rectosigmoid areas. RESULTS: Gastritis and colonic crypt distortion were present in the IBD group at a greater rate (61 % vs. 22 %, p = 0.020; 34 % vs. 4 %, p = 0.008, respectively). Peak and mean eosinophil densities in the rectosigmoid area were greater in the IBD group (17.0/hpf vs. 5.0/hpf, p = 0.0063; 12.3/hpf vs. 4.2/hpf, p = 0.0106, respectively). TNF-α and MMP-9 staining did not reveal any significant differences. CONCLUSIONS: Our data suggests that significantly greater inflammation in the stomach, crypt distortion in the colon, and eosinophilia in the rectosigmoid distinguished the IBD group from the comparison group at the time of the initial endoscopic 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.

Genomic insights into pediatric intestinal inflammatory and eosinophilic disorders using single-cell RNA-sequencing.

Introduction: Chronic inflammation of the gastrointestinal tissues underlies gastrointestinal inflammatory disorders, leading to tissue damage and a constellation of painful and debilitating symptoms. These disorders include inflammatory bowel diseases (Crohn's disease and ulcerative colitis), and eosinophilic disorders (eosinophilic esophagitis and eosinophilic duodenitis). Gastrointestinal inflammatory disorders can often present with overlapping symptoms necessitating the use of invasive procedures to give an accurate diagnosis. Methods: This study used peripheral blood mononuclear cells from individuals with Crohn's disease, ulcerative colitis, eosinophilic esophagitis, and eosinophilic duodenitis to better understand the alterations to the transcriptome of individuals with these diseases and identify potential markers of active inflammation within the peripheral blood of patients that may be useful in diagnosis. Single-cell RNA-sequencing was performed on peripheral blood mononuclear cells isolated from the blood samples of pediatric patients diagnosed with gastrointestinal disorders, including Crohn's disease, ulcerative colitis, eosinophilic esophagitis, eosinophilic duodenitis, and controls with histologically healthy gastrointestinal tracts. Results: We identified 730 (FDR < 0.05) differentially expressed genes between individuals with gastrointestinal disorders and controls across eight immune cell types. Discussion: There were common patterns among GI disorders, such as the widespread upregulation of MTRNR2L8 across cell types, and many differentially expressed genes showed distinct patterns of dysregulation among the different gastrointestinal diseases compared to controls, including upregulation of XIST across cell types among individuals with ulcerative colitis and upregulation of Th2-associated genes in eosinophilic disorders. These findings indicate both overlapping and distinct alterations to the transcriptome of individuals with gastrointestinal disorders compared to controls, which provide insight as to which genes may be useful as markers for disease in the peripheral blood of patients.

Parental illness encouragement behavior among children with functional gastrointestinal disorders: a factor analysis with implications for research and clinical practice.

The objective of the current study was to assess the factor structure of the Illness Behavior Encouragement Scale (IBES) by Walker and Zeman (1992) among children with functional gastrointestinal disorders (FGIDs). Two hundred seventy nine children (63 % female), and 135 primary caregivers (90.8 % mothers), recruited from a large Midwestern children's hospital completed the IBES, a 12-item measure of parental behavior in response to abdominal pain episodes. Findings suggested the IBES possesses two conceptually distinct scales that are invariant across parent self- and child-report, and are consistent with previous factor analysis in a Dutch sample of children with headaches. Different types of parental behaviors exist that naturally cluster and diverge in reliable ways. Future research is warranted to determine if these different types of parental behavior may differentially influence illness outcomes among children with FGIDs.

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.

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.

Sleep problems and functional disability in children with functional gastrointestinal disorders: an examination of the potential mediating effects of physical and emotional symptoms.

BACKGROUND: Sleep disturbances are increasingly recognized as a common problem for children and adolescents with chronic pain conditions, but little is known about the prevalence, type, and impact of sleep problems in pediatric functional gastrointestinal disorders (FGIDs). The objectives of the current study were two-fold: 1) to describe the pattern of sleep disturbances reported in a large sample of children and adolescents with FGIDs; and, 2) to explore the impact of sleep by examining the inter-relationships between sleep disturbance, physical symptoms, emotional problems, and functional disability in this population. METHODS: Over a 3-year period, 283 children aged 8-17 years who were diagnosed with an FGID and a primary caretaker independently completed questionnaires regarding sleep, emotional functioning, physical symptoms, and functional disability during an initial evaluation for chronic abdominal pain at a pediatric tertiary care center. A verbal review of systems also was collected at that time. Descriptive statistics were used to characterize the pattern of sleep disturbances reported, while structural equation modeling (SEM) was employed to test theorized meditational relationships between sleep and functional disability through physical and emotional symptoms. RESULTS: Clinically significant elevations in sleep problems were found in 45% of the sample, with difficulties related to sleep onset and maintenance being most common. No difference was seen by specific FGID or by sex, although adolescents were more likely to have sleep onset issues than younger children. Sleep problems were positively associated with functional disability and physical symptoms fully mediated this relationship. Emotional symptoms, while associated with sleep problems, evidenced no direct link to functional disability. CONCLUSIONS: Sleep problems are common in pediatric FGIDs and are associated with functional disability through their impact on physical symptoms. Treatments targeting sleep are likely to be beneficial in improving physical symptoms and, ultimately, daily function in pediatric FGIDs.

A randomized trial of enema versus polyethylene glycol 3350 for fecal disimpaction in children presenting to an emergency department.

OBJECTIVE: This study aimed to compare efficacy of enema versus polyethylene glycol (PEG) 3350 for pediatric fecal impaction treatment. METHODS: We conducted a prospective, randomized comparison of treatments of fecal impaction in children in a pediatric emergency department (ED). Treatment arms were a single milk and molasses enema in the ED or PEG 3350 for 3 days outpatient. Telephone follow-up was done on days 1, 3, and 5. The primary outcome was main symptom improvement. Additional outcomes were stool frequency, consistency, and ease of stool passage. Treatment failures (home enema, ED return, or hospital admission) were tracked. RESULTS: Seventy-nine subjects participated (39 PEG; 40 enema). At day 1, PEG subjects were less likely to have improved main symptom (odds ratio [OR], 0.3; 95% confidence interval [CI], 0.1-0.8) but no difference in other outcomes. Half (54%) in enema arm were reported as upset by ED therapy, whereas no children in PEG arm were upset (P < 0.05). At day 3, more patients in enema arm reported ideal stool consistency (74% vs 38%; P < 0.05). At day 5, no difference between groups was noted. Most treatment failures were in PEG arm (83%; P = 0.08). CONCLUSIONS: This pilot study suggests that disimpaction by enema may be superior to PEG for immediate relief of symptoms. Larger trials are needed to assess any advantage.

The effect of neuropsychiatric medication on pediatric nonalcoholic fatty liver disease.

Obese and overweight children are at risk of developing nonalcoholic fatty liver disease (NAFLD), which can lead to steatohepatitis, cirrhosis, and liver transplantation. Neuropsychiatric conditions affect an increasing proportion of children and often require neuropsychiatric medications (NPMs) that are associated with weight gain and/or drug-induced liver injury. We sought to evaluate the role that the extended use of NPMs play in pediatric NAFLD. Medical chart review was conducted for 260 patients with NAFLD (NPM = 77, non-NPM = 183) seen in the Liver Care Center at Children's Mercy Hospital between 2000 and 2016. Outcome measures included body mass index (BMI) percentile, BMI z-score, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, and gamma glutamyltransferase, and were collected at diagnosis, 6-18 month follow-up, and 18-36 months. Controlling for race and metformin, there was a significant increase over time in BMI z-score (p < 0.01) and total bilirubin (p = 0.03), with only initial decreases in ALT (p < 0.01) and AST (p < 0.01). Except for higher total bilirubin in the non-NPM group, no main effect of group or interaction effect was found. Similar patterns remained when subjects were analyzed by NPM drug class. Further study is needed to confirm these findings and to evaluate the effects of NPM dose and duration of exposure, by drug class, on pediatric NAFLD outcomes.

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.

Leveraging Institutional Support to Build an Integrated Multidisciplinary Care Model in Pediatric Inflammatory Bowel Disease.

While the biopsychosocial nature of inflammatory bowel disease (IBD) is now well accepted by clinicians, the need for integrated multidisciplinary care is not always clear to institutional administrators who serve as decision makers regarding resources provided to clinical programs. In this commentary, we draw on our own experience in building successful integrated care models within a division of pediatric gastroenterology (GI) to highlight key considerations in garnering initial approval, as well as methods to maintain institutional support over time. Specifically, we discuss the importance of making a strong case for the inclusion of a psychologist in pediatric IBD care, justifying an integrated model for delivering care, and addressing finances at the program level. Further, we review the benefit of collecting and reporting program data to support the existing literature and/or theoretical projections, demonstrate outcomes, and build alternative value streams recognized by the institution (e.g., academic, reputation) alongside the value to patients. Ultimately, success in garnering and maintaining institutional support necessitates moving from the theoretical to the practical, while continually framing discussion for a nonclinical/administrative audience. While the process can be time-consuming, ultimately it is worth the effort, enhancing the care experience for both patients and clinicians.