Variability in Swallowed Topical Corticosteroid Practice Patterns for Treatment of Pediatric Eosinophilic Esophagitis.

Given the variety of preparations and lack of standardization of swallowed topical corticosteroids (STC) for treatment of eosinophilic esophagitis (EoE), we sought to better understand STC prescribing practices of pediatric gastroenterologists. A 12-question survey was distributed to members of North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Eosinophilic Gastrointestinal Disease Special Interest Group and responses were analyzed. Forty-two of 68 physicians responded. Oral viscous budesonide (OVB) was overall first choice STC in 31 (74%) survey respondents, with OVB most frequently utilized in patients under 5 years old and fluticasone propionate in patients 13-18 years old. Nineteen types of mixing vehicles were used for OVB preparation, the 3 most frequent being sucralose, honey, and artificial maple syrup. Insurance coverage, cost, and patient compliance were most frequently cited barriers to STC use. Highly variable STC prescribing practices reported by this group highlights the need for standardization of STC treatment in EoE.

North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Position Statement for Telehealth.

Telehealth (TH) broadly encompasses remote activities of clinical care (telemedicine), provider and patient education, and general health services. The use of synchronous video for TH first occurred in 1964 and then catapulted to the forefront in 2020 during the coronavirus disease 2019 public health emergency. Due to the sudden need for increased TH utilization by nearly all health care providers at that time, TH became essential to clinical practice. However, its sustainable future is unclear in part given that best practices for TH in pediatric gastroenterology (GI), hepatology, and nutrition remain undefined and non-standardized. Key areas for review include historical perspective, general and subspeciality usage, health care disparities, quality of care and the provider-patient interaction, logistics and operations, licensure and liability, reimbursement and insurance coverage, research and quality improvement (QI) priorities, and future use of TH in pediatric GI with a call for advocacy. This position paper from the Telehealth Special Interest Group of North American Society of Gastroenterology, Hepatology and Nutrition provides recommendations for pediatric GI-focused TH best practices, reviews areas for research and QI growth, and presents advocacy opportunities.

Equity and Inclusion in Pediatric Gastroenterology Telehealth: A Study of Demographic, Socioeconomic, and Digital Disparities.

OBJECTIVES: The purpose of our study is to compare in-person and telehealth pediatric care ambulatory visits for gastroenterology (GI) at the Nemours Children's Health System in the Delaware Valley (NCH-DV) based on geospatial, demographic, socioeconomic, and digital disparities. METHODS: Characteristics of 26,565 patient encounters from January 2019 to December 2020 were analyzed. U.S. Census Bureau geographic identifiers were assigned to each participant and aligned with the American Community Survey (2015-2019) socioeconomic and digital outcomes. Reported odds ratios (OR) are telehealth encounter/in-person encounter. RESULTS: GI telehealth usage increased 145-fold in 2020 compared to 2019 for NCH-DV. Comparing telehealth to in-person usage in 2020 revealed that GI patients who required a language translator were 2.2-fold less likely to choose telehealth [individual level adjusted OR (I-OR a ) [95% confidence interval, CI], 0.45 [0.30-0.66], P < 0.001]. Individuals of Hispanic ethnicity or non-Hispanic Black or African American race are 1.3-1.4-fold less likely to utilize telehealth than non-Hispanic Whites (I-OR a [95% CI], 0.73 [0.59-0.89], P = 0.002 and 0.76 [0.60-0.95], P = 0.02, respectively). Households in census block groups (BG) that are more likely to utilize telehealth: have broadband access (BG-OR = 2.51 [1.22-5.31], P = 0.014); are above the poverty level (BG-OR = 4.44 [2.00-10.24], P < 0.001); own their own home (BG-OR = 1.79 [1.25-2.60], P = 0.002); and have a bachelor's degree or higher (BG-OR = 6.55 [3.25-13.80], P < 0.001). CONCLUSIONS: Our study is the largest reported pediatric GI telehealth experience in North America that describes racial, ethnic, socioeconomic, and digital inequities. Advocacy and research for pediatric GI focused on telehealth equity and inclusion is urgently needed.

Medical treatment of eosinophilic esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic antigen-mediated eosinophilic inflammatory disease isolated to the esophagus. As a clinicopathologic disorder, a diagnosis of EoE requires a constellation of clinical symptoms of esophageal dysfunction and histologic findings (at least 15 eosinophils/high-powered microscope field (eos/hpf)). Current guidelines no longer require the failure of response to proton pump inhibitor medications to establish a diagnosis of EoE, but continue to suggest the exclusion of other etiologies of esophageal eosinophilia. The treatment goals for EoE are improvement in clinical symptoms, resolution of esophageal eosinophilia and other histologic abnormalities, endoscopic improvement, improved quality of life, improved esophageal function, minimized adverse effects of treatment, and prevention of disease progression and subsequent complications. Currently, there is no cure for EoE, making long-term treatment necessary. Standard treatment modalities include dietary modifications, esophageal dilation, and pharmacologic therapy. Effective pharmacologic therapies include corticosteroids, rapidly emerging biological therapies, and proton pump inhibitor medications. OBJECTIVES: To evaluate the efficacy and safety of medical interventions for people with eosinophilic esophagitis. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and WHO ICTRP to 3 March 2023. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing any medical intervention or food elimination diet for the treatment of eosinophilic esophagitis, either alone or in combination, to any other intervention (including placebo). DATA COLLECTION AND ANALYSIS: Pairs of review authors independently selected studies and conducted data extraction and risk of bias assessment. We expressed outcomes as a risk ratio (RR) and as the mean or standardized mean difference (MD/SMD) with 95% confidence interval (CI). We assessed the certainty of the evidence using GRADE. Our primary outcomes were: clinical, histological, and endoscopic improvement, and withdrawals due to adverse events. Secondary outcomes were: serious and total adverse events, and quality of life. MAIN RESULTS: We included 41 RCTs with 3253 participants. Eleven studies included pediatric patients while the rest recruited both children and adults. Four studies were in patients with inactive disease while the rest were in patients with active disease. We identified 19 intervention comparisons. In this abstract we present the results of the primary outcomes for the two main comparisons: corticosteroids versus placebo and biologics versus placebo, based on the prespecified outcomes defined of the primary studies. Fourteen studies compared corticosteroids to placebo for induction of remission and the risk of bias for these studies was mostly low. Corticosteroids may lead to slightly better clinical improvement (20% higher), measured dichotomously (risk ratio (RR) 1.74, 95% CI 1.08 to 2.80; 6 studies, 583 participants; number needed to treat for an additional beneficial outcome (NNTB) = 4; low certainty), and may lead to slightly better clinical improvement, measured continuously (standard mean difference (SMD) 0.51, 95% CI 0.17 to 0.85; 5 studies, 475 participants; low certainty). Corticosteroids lead to a large histological improvement (63% higher), measured dichotomously (RR 11.94, 95% CI 6.56 to 21.75; 12 studies, 978 participants; NNTB = 3; high certainty), and may lead to histological improvement, measured continuously (SMD 1.42, 95% CI 1.02 to 1.82; 5 studies, 449 participants; low certainty). Corticosteroids may lead to little to no endoscopic improvement, measured dichotomously (RR 2.60, 95% CI 0.82 to 8.19; 5 studies, 596 participants; low certainty), and may lead to endoscopic improvement, measured continuously (SMD 1.33, 95% CI 0.59 to 2.08; 5 studies, 596 participants; low certainty). Corticosteroids may lead to slightly fewer withdrawals due to adverse events (RR 0.64, 95% CI 0.43 to 0.96; 14 studies, 1032 participants; low certainty). Nine studies compared biologics to placebo for induction of remission. Biologics may result in little to no difference in clinical improvement, measured dichotomously (RR 1.14, 95% CI 0.85 to 1.52; 5 studies, 410 participants; low certainty), and may result in better clinical improvement, measured continuously (SMD 0.50, 95% CI 0.22 to 0.78; 7 studies, 387 participants; moderate certainty). Biologics result in better histological improvement (55% higher), measured dichotomously (RR 6.73, 95% CI 2.58 to 17.52; 8 studies, 925 participants; NNTB = 2; moderate certainty). We could not draw conclusions for this outcome when measured continuously (SMD 1.01, 95% CI 0.36 to 1.66; 6 studies, 370 participants; very low certainty). Biologics may result in little to no difference in endoscopic improvement, measured dichotomously (effect not estimable, low certainty). We cannot draw conclusions for this outcome when measured continuously (SMD 2.79, 95% CI 0.36 to 5.22; 1 study, 11 participants; very low certainty). There may be no difference in withdrawals due to adverse events (RR 1.55, 95% CI 0.88 to 2.74; 8 studies, 792 participants; low certainty). AUTHORS' CONCLUSIONS: Corticosteroids (as compared to placebo) may lead to clinical symptom improvement when reported both as dichotomous and continuous outcomes, from the primary study definitions. Corticosteroids lead to a large increase in histological improvement (dichotomous outcome) and may increase histological improvement (continuous outcome) when compared to placebo. Corticosteroids may or may not increase endoscopic improvement (depending on whether the outcome is measured dichotomously or continuously). Withdrawals due to adverse events (dichotomous outcome) may occur less frequently when corticosteroids are compared to placebo. Biologics (as compared to placebo) may not lead to clinical symptom improvement when reported as a dichotomous outcome and may lead to an increase in clinical symptom improvement (as a continuous outcome), from the primary study definitions. Biologics lead to a large increase in histological improvement when reported as a dichotomous outcome, but this is uncertain when reported as a continuous outcome, as compared to placebo. Biologics may not increase endoscopic improvement (dichotomous outcome), but this is uncertain when measured as a continuous outcome. Withdrawals due to adverse events as a dichotomous outcome may occur as frequently when biologics are compared to placebo.

Comparative Effectiveness of Intravenous Azithromycin Versus Erythromycin Stimulating Antroduodenal Motility in Children.

BACKGROUND: Azithromycin has been shown to improve gastrointestinal motility in adults and may have fewer drug interactions and reduced arrhythmogenic effects than erythromycin. We hypothesized that azithromycin is comparable to erythromycin in eliciting pharmacodynamic outcomes for antral and small bowel motility. OBJECTIVE: To compare the pharmacodynamic effectiveness of azithromycin and erythromycin for eliciting antral and duodenal motility in pediatric patients who underwent antroduodenal manometry for different indications. METHODS: We conducted a retrospective comparison of clinic data and manometric pharmacodynamics outcomes in patients who underwent antroduodenal manometry between 2013 and 2017. RESULTS: Fifty-one patients mean age (± standard deviation) 9.7 (5.4) years, received either azithromycin 3 mg/kg (n = 20) or erythromycin 2 mg/kg (n = 31) during antroduodenal manometry. For patients receiving erythromycin, mean area under the curve (AUC) across all eight pressure ports increased from median [95% confidence interval] 2256 [1585, 2602] to 8742 [5876, 11761] mmHg × s (P < 0.001) and mean motility index increased from 8.63 [7.87, 9.42] to 11.98 [11.20, 12.21] (P < 0.001). For patients receiving azithromycin, mean AUC increased from 2255 [1585, 2602] to 8254 [5649, 10470] mmHg × s (P < 0.001) and motility index increased from 8.63 [7.87,9.42] to 11.79 [11.03, 12.21] (P < 0.001). Neither mean stimulated AUC nor mean motility index was significantly different between azithromycin and erythromycin treatments. There was no significant difference in side effects between groups. CONCLUSIONS: Azithromycin and erythromycin have similar pharmacodynamic effects on antral and small bowel contractility in children. Azithromycin should be considered an acceptable alternative to erythromycin as an upper gastrointestinal tract prokinetic for children and has historically had fewer side effects than erythromycin.

STAT6 Variants Associate With Relapse of Eosinophilic Esophagitis in Patients Receiving Long-term Proton Pump Inhibitor Therapy.

BACKGROUND & AIMS: Based on histologic features, variants in STAT6 are associated with a poor initial response to proton pump inhibitor (PPI) therapy in pediatric patients with eosinophilic esophagitis (EoE). We investigated whether these genetic variants are associated with a poor long-term response in children with EoE who initially responded to PPI therapy. METHODS: We performed a prospective longitudinal cohort study of children ages 2 to 16 years who met the diagnostic criteria for EoE (≥15 eosinophils/high-power field [eos/hpf]), responded to 8 weeks of treatment with 2 mg/kg/d PPI (<15 eos/hpf), and whose dose then was reduced to 1 mg/kg/d PPI (maintenance therapy) for 1 year, at which point biopsy specimens were collected by endoscopy. Genomic DNA was isolated from formalin-fixed paraffin-embedded biopsy tissue and was genotyped for variants of STAT6. Remission of inflammation was assessed at eos/hpf thresholds of <15 and ≤5. RESULTS: Among 73 patients who received 1 mg/kg/d PPI maintenance therapy for 1 year, 13 patients (18%) had 6 to 14 eos/hpf, 36 patients (49%) had 5 or fewer eos/hpf, and 24 patients (33%) relapsed to EoE (≥15 eos/hpf). Carriage of any of 3 STAT6 variants in linkage disequilibrium (r2 ≥0.8; rs324011, rs167769, or rs12368672) was associated with a 2.3- to 2.8-fold increase in the odds of EoE relapse, and with a 2.8- to 4.1-fold increase in the odds of having 6 to 14 eos/hpf. For rs324011, the odds ratio [95% CI] for relapse was 2.77 [1.11, 6.92]; P = .029, and the odds ratio [95% CI] for having 6 to 14 eos/hpf was 3.06 [1.27, 7.36]; P = .012. CONCLUSIONS: Pediatric EoE patients who initially respond to PPI therapy and carry STAT6 variants rs324011, rs167769, or rs12368672 are at increased risk of relapse after 1 year of PPI maintenance therapy.

A Provider-Focused Intervention to Promote Optimal Care of Pediatric Patients With Suspected Elbow Fracture.

OBJECTIVE: Emergency department (ED) and urgent care (UC) physicians' accurate assessment of the neurovascular and musculoskeletal (NV/MSK) examination in pediatric patients with suspected elbow fracture is crucial to the early recognition of neurovascular compromise. Our objective was to determine the impact of computer-based simulation (CBS) and computerized clinical decision support systems (CCDSS) on ED and UC physicians' assessment of the NV/MSK examination of pediatric patients with elbow fracture as noted in their documentation. METHODS: All ED UC physician participants received CBS training about management of pediatric patients with suspected elbow fracture. Participants were then randomized to receive CCDSS (intervention arm) when an eligible patient was seen or no further intervention (comparison arm.) Participants received feedback on the proportion of patients with discharge diagnosis of elbow fracturewith proper examination elements documented. RESULTS: Twenty-eight ED and UC physicians were enrolled - 14 in each arm. Over the span of 16 weeks, 50 patients with a discharge diagnosis of elbow fracture were seen - 25 in each arm. Twenty-two of 25 (88%) patients seen by intervention arm participants had a complete NV/MSK examination documented. Six of 25 (24%) patients seen by comparison arm participants had a complete NV/MSK examination documented. Elements most commonly missed in the comparison arm included documentation of ulnar pulse as well as radial, median, and ulnar nerve motor functions. CONCLUSIONS: Compared with single CBS training alone, repeated exposure to CCDSS after CBS training resulted in improved documentation of the NV/MSK status of pediatric patients with elbow fracture.

Challenges and lessons learned from clinical pharmacogenetic implementation of multiple gene-drug pairs across ambulatory care settings.

PURPOSE: Incorporating a patient's genotype into the clinical decision-making process is one approach to precision medicine. The University of Florida (UF) Health Precision Medicine Program is a pharmacist-led multidisciplinary effort that has led the clinical implementation of six gene-drug(s) pairs to date. This study focuses on the challenges encountered and lessons learned with implementing pharmacogenetic testing for three of these: CYP2D6-opioids, CYP2D6/CYP2C19-selective serotonin reuptake inhibitors, and CYP2C19-proton pump inhibitors within six pragmatic clinical trials at UF Health and partners. METHODS: We compared common measures collected within each of the pharmacogenetic implementations as well as solicited feedback from stakeholders to identify challenges, successes, and lessons learned. RESULTS: We identified several challenges related to trial design and implementation, and learned valuable lessons. Most notably, case discussions are effective for prescriber education, prescribers need clear concise guidance on genotype-based actions, having genotype results available at the time of the patient-prescriber encounter helps optimize the ability to act on them, children prefer noninvasive sample collection, and study participants are willing to answer patient-reported outcomes questionnaires if they are not overly burdensome, among others. CONCLUSION: The lessons learned from implementing three gene-drug pairs in ambulatory care settings will help shape future pharmacogenetic clinical trials and clinical implementations.

Symptom Burden and Quality of Life Over Time in Pediatric Eosinophilic Esophagitis.

OBJECTIVE: The aim of the study was to evaluate whether children with eosinophilic esophagitis (EoE) demonstrated an association between health-related quality of life (HRQoL) improvements and symptom reduction during 12 months of treatment; to examine age-related EoE discrete symptom presentation; and to describe residual symptom and HRQoL burden. METHODS: Children ages 2 to 18 years with EoE were assessed at the onset of treatment and 12 months later at 4 tertiary care centers. Continuous measures of symptoms and symptom severity were based on 8 discrete EoE symptoms. HRQoL was measured with the Pediatric Quality of Life (PedsQL) parent-proxy (PR) report, child self-report (CR), and Family Impact Module. Mixed-effects modeling was used to test changes over time for symptom burden and child and family HRQoL. RESULTS: One hundred nine children were followed (ages 2-18 years, mean age 7.6 [4.6] years, 77% boys, 87% white). Baseline symptom number mean was 3.5 (standard deviation = 2.3, range 0-8) and symptom severity mean was 5.5 (standard deviation = 4.3, range 0-24). EoE symptom number and symptom severity decreased significantly over the 12 months (P = 0.013, P < 0.001, respectively). PedsQL PR Total, Physical, Psychosocial, and Family Impact scores all improved significantly (P = 0.001, 0.012, 0.012, 0.015, respectively) but PedsQL child self-report scores did not. Symptom reduction correlated with PR PedsQL improvement (P = 0.01). Few discrete symptoms completely remitted, but lowered severity ratings indicated clinically significant improvement. CONCLUSIONS: Year-long treatment in multidisciplinary tertiary centers reduced most symptoms and improved parent-reported HRQoL in children with EoE. The frequency of residual symptoms and persistently lower HRQoL, however, underscore the chronic nature of pediatric EoE.

CYP2C19 and STAT6 Variants Influence the Outcome of Proton Pump Inhibitor Therapy in Pediatric Eosinophilic Esophagitis.

OBJECTIVE: Proton pump inhibitors (PPIs) are an effective treatment for eosinophilic esophagitis (EoE); however, only 30% to 60% of patients respond. Common genetic variants in CYP2C19 and STAT6 associate with PPI plasma concentration and magnitude of inflammatory response, respectively. Our objective was to determine if genetic variation in the genes for CYP2C19 and STAT6 influence differentiation between PPI responsive esophageal eosinophilia versus PPI nonresponsive EoE (PPI-REE, PPI-nonresponsive EoE). METHODS: Genomic DNA was isolated from 92 esophageal tissue biopsies collected from participants of a prospective clinical trial of high-dose PPI therapy for esophageal eosinophilia in children. RESULTS: Of the 92 patients examined, 57 (62%) were PPI-REE and 35 (38%) were PPI-nonresponsive EoE. Forty-six of the 92 patients were further characterized by pH probe monitoring; there was no association between reflux index and carriage of CYP2C1917 (P = 0.35). In children who received a PPI dose between ≥1.54 and ≤2.05 mg/kg/day, binary logistic regression modeling showed that carriage of CYP2C1917 associated with PPI-nonresponsive EoE (odds ratio (OR) [95% confidence interval (CI)] = 7.71 [1.21, 49.11], P = 0.031). Carriage of STAT6 allelic variant rs1059513 predicts PPI-REE (OR [95% CI] = 6.16 [1.44, 26.4], P = 0.028), whereas carriage of STAT6 rs324011 synergizes with CYP2C1917 to predict PPI-nonresponsive EoE (rs324011 OR [95% CI] = 5.56 [1.33, 20.72], P = 0.022; CYP2C1917 OR [95% CI] = 8.19[1.42, 50.57], P = 0.023). CONCLUSIONS: Common variants in CYP2C19 and STAT6 associate with a PPI-nonresponsive EoE outcome of PPI therapy for esophageal eosinophilia suggesting that response rates may be improved by adopting a genotype-guided approach to PPI dosing.

Perceived medication adherence barriers mediating effects between gastrointestinal symptoms and health-related quality of life in pediatric inflammatory bowel disease.

OBJECTIVES: The primary objective was to investigate the mediating effects of patient-perceived medication adherence barriers in the relationship between gastrointestinal symptoms and generic health-related quality of life (HRQOL) in adolescents with inflammatory bowel disease (IBD). The secondary objective explored patient health communication and gastrointestinal worry as additional mediators with medication adherence barriers in a serial multiple mediator model. METHODS: The Pediatric Quality of Life Inventory™ Gastrointestinal Symptoms, Medicines, Communication, Gastrointestinal Worry, and Generic Core Scales were completed in a 9-site study by 172 adolescents with IBD. Gastrointestinal Symptoms Scales measuring stomach pain, constipation, or diarrhea and perceived medication adherence barriers were tested for bivariate and multivariate linear associations with HRQOL. Mediational analyses were conducted to test the hypothesized mediating effects of perceived medication adherence barriers as an intervening variable between gastrointestinal symptoms and HRQOL. RESULTS: The predictive effects of gastrointestinal symptoms on HRQOL were mediated in part by perceived medication adherence barriers. Patient health communication was a significant additional mediator. In predictive analytics models utilizing multiple regression analyses, demographic variables, gastrointestinal symptoms (stomach pain, constipation, or diarrhea), and perceived medication adherence barriers significantly accounted for 45, 38, and 29 percent of the variance in HRQOL (all Ps < 0.001), respectively, demonstrating large effect sizes. CONCLUSIONS: Perceived medication adherence barriers explain in part the effects of gastrointestinal symptoms on HRQOL in adolescents with IBD. Patient health communication to healthcare providers and significant others further explain the mechanism in the relationship between gastrointestinal symptoms, perceived medication adherence barriers, and HRQOL.

Association between CYP2C19 extensive metabolizer phenotype and childhood anti-reflux surgery following failed proton pump inhibitor medication treatment.

When pediatric gastroesophageal reflux disease (GERD) that is refractory to proton pump inhibitor (PPI) medication treatment is identified in clinical practice and anti-reflux surgery (ARS) is being considered, genetic factors related to PPI metabolism by the CYP2C19 enzyme are currently not part of the clinical decision-making process. Our objective was to test the hypothesis that the distribution of the extensive metabolizer (EM) phenotypes among children undergoing ARS after failing PPI therapy would differ compared to controls (children with no history of ARS). We conducted a case-control study between children across the Nemours Health System from 2000 to 2014 who received ARS after failing PPI therapy and a control group comprised of healthy children. Our results demonstrated 2.9% of ARSs vs 20.8% of controls were poor metabolizers (PMs), 55.9% of ARSs vs 49.0% of controls were normal metabolizers (NMs), and 41.2% of ARSs vs 30.2% of controls were EMs; p = 0.035. Next, we performed a multiple-regression model to account for race as a potential confounding variable and the EM group was significantly associated with ARS compared to controls (OR 9.78, CI 1.25-76.55, p < 0.03). CONCLUSION: Among children with medically refractory GERD despite PPI therapy, carriage of CYP2C19*17 allele corresponding to the EM phenotype was associated with ARS. Prospective comparative personalized medicine effectiveness studies are needed to determine if CYP2C19 genotype-guided dosing improves response to PPI therapy without a corresponding increase in adverse effects in children. What is known: • Anti-reflux surgery (ARS) is one of the most common surgical procedures performed in children for the indication of refractory gastroesophageal reflux disease (GERD). What is new: • Individualizing PPI medication dosing based on CYP2C19 diplotype may avoid GERD treatment failures and reduce the need for anti-reflux surgery (ARS).

Electronic health record as a research tool: Frequency of exposure to targeted clinical problems and health care providers' clinical proficiency.

OBJECTIVES: The Electronic Health Record (EHR) could provide insight into possible decay in health care providers' (HCP) clinical knowledge and cognitive performance. Analyses of the contributions of variables such as frequency of exposure to targeted clinical problems could inform the development and testing of appropriate individualized interventions to mitigate these threats to quality and safety of care. MATERIALS/METHODS: Nine targeted clinical problems (TCP) were selected for further study, and de-identified, aggregated study data were obtained for one calendar year. Task analysis interviews of subspecialty physicians defined optimal management of each TCP and guided specification of quality of care metrics that could be extracted from the EHR. The Δ-t statistic, days since the provider's prior encounter with a given TCP, quantified frequency of exposure. RESULTS: Frequency of patient encounters ranged from 1566 to 220,774 visits across conditions. Mean Δ-t ranged from 1.72days to 30.79days. Maximum Δ-t ranged from 285 to 497days. The distribution of Δ-t for the TCPs generally fit a Gamma distribution (P<0.001), indicating that Δ-t conforms to a Poisson process. A quality of care metric derived for each TCP declined progressively with increasing Δ-t for 8 of the 9 TCPs, affirming that knowledge decay was detectable from EHR data. DISCUSSION/CONCLUSIONS: This project demonstrates the utility of the EHR as a research tool in studies of health care delivery in association with frequency of exposure of HCPs to TCPs. Subsequent steps in our research include multivariate modeling of clinical knowledge decay and randomized trials of pertinent preventive interventions.

Gastrointestinal Symptoms Predictors of Health-Related Quality of Life in Patients With Inflammatory Bowel Disease.

OBJECTIVES: The aim of the study was to investigate the multidimensional gastrointestinal symptoms predictors of generic health-related quality of life (HRQOL) in pediatric patients with inflammatory bowel disease from the perspectives of pediatric patients and parents. METHODS: The Pediatric Quality of Life Inventory Gastrointestinal Symptoms Scales and Pediatric Quality of Life Inventory 4.0 Generic Core Scales were completed in a 9-site study by 260 families of patients with inflammatory bowel disease. Gastrointestinal Symptoms Scales measuring stomach pain, food and drink limits, gas and bloating, constipation, blood in stool, and diarrhea were identified as clinically important symptom differentiators from healthy controls based on prior findings, and subsequently tested for bivariate and multivariate linear associations with overall HRQOL (Generic Core Scales). RESULTS: Stomach pain, food and drink limits, gas and bloating, constipation, blood in stool, and diarrhea were significantly associated with decreased HRQOL in bivariate analyses (P < 0.001). In predictive models utilizing hierarchical multiple regression analyses controlling for age, sex, and race/ethnicity, gastrointestinal symptoms accounted for an additional 40% of the variance in patient self-reported HRQOL (P < 0.001) and 37% of the variance in parent proxy-reported HRQOL (P < 0.001), reflecting large effect sizes. Stomach pain, food and drink limits, and constipation were significant individual patient-reported predictors after controlling for the other gastrointestinal symptoms in the predictive models. CONCLUSIONS: Patient-reported gastrointestinal symptoms differentially predicted HRQOL. Identifying the specific gastrointestinal symptoms from a standardized multidimensional gastrointestinal symptoms profile that are the most important predictors from the patient perspective facilitates a patient-centered approach for interventions designed to ameliorate impaired HRQOL.

Pediatric Eosinophilic Esophagitis Symptom Scores (PEESS v2.0) identify histologic and molecular correlates of the key clinical features of disease.

BACKGROUND: The Pediatric Eosinophilic Esophagitis Symptom Score (PEESS v2.0) measures patient-relevant outcomes. However, whether patient-identified domains (dysphagia, gastroesophageal reflux disease [GERD], nausea/vomiting, and pain) align with clinical symptomology and histopathologic and molecular features of eosinophilic esophagitis (EoE) is unclear. OBJECTIVE: The purpose of this study was to determine whether clinical features of EoE, measured through PEESS v2.0, associate with histopathologic and molecular features of EoE. This represents a novel approach for analysis of allergic diseases, given the availability of allergic tissue biopsy specimens. METHODS: We systematically recruited treated and untreated pediatric patients with EoE (aged 2-18 years) and examined parent proxy-reported symptoms using the PEESS v2.0. Clinical symptomology was collected by questionnaire. Esophageal biopsy samples were quantified for levels of eosinophils, eosinophil peroxidase (EPX) immunohistochemical staining, and mast cells. Molecular features were assessed by using the EoE Diagnostic Panel (94 EoE-related gene transcripts). Associations between domain scores and clinical symptoms and biological features were analyzed with Wilcoxon rank sum and Spearman correlation. RESULTS: The PEESS v2.0 domains correlated to specific parent-reported symptoms: dysphagia (P = .0012), GERD (P = .0001), and nausea/vomiting (P < .0001). Pain correlated with multiple symptoms (P < .0005). Dysphagia correlated most strongly with overall histopathology, particularly in the proximal esophagus (P ≤ .0049). Markers of esophageal activity (EPX) were significantly associated with dysphagia (strongest r = 0.37, P = .02). Eosinophil levels were more associated with pain (r = 0.27, P = .06) than dysphagia (r = 0.24, P = .13). The dysphagia domain correlated most with esophageal gene transcript levels, predominantly with mast cell-specific genes. CONCLUSION: We have (1) established a validated, parent proxy-reported measure for pediatric EoE, the PEESS v2.0; (2) verified that the parent proxy effectively captures symptoms; (3) determined that the dysphagia domain most closely aligns with symptoms and tissue-based molecular biomarkers; (4) established that symptoms correlate with EPX staining; and (5) observed association between mast cells and dysphagia.

Health-related quality of life in pediatric patients with functional and organic gastrointestinal diseases.

OBJECTIVE: To compare health-related quality of life (HRQOL) in pediatric patients with functional gastrointestinal disorders (FGIDs) and organic gastrointestinal (GI) diseases with an age-, sex-, and race/ethnicity-matched healthy sample across GI diagnostic groups and with one another. STUDY DESIGN: The Pediatric Quality of Life Inventory 4.0 Generic Core Scales were completed in a 9-site study by 689 families. Patients had 1 of 7 physician-diagnosed GI disorders: chronic constipation, functional abdominal pain, irritable bowel syndrome, functional dyspepsia, Crohn's disease, ulcerative colitis, and gastroesophageal reflux disease. The healthy control sample included 1114 families. School days missed, days in bed and needing care, parent missed workdays, work impact, and healthcare utilization were compared as well. RESULTS: Patients with an FGID or organic GI disease demonstrated lower HRQOL than the healthy controls across all dimensions (physical, emotional, social, and school; P < .001 for all), with larger effect sizes for patients with an FGID. Patients with an FGID manifested lower HRQOL than those with an organic GI disease. Patients with an FGID or organic GI disease missed more school, spent more days in bed and needing care, had greater healthcare utilization, and had parents who missed more workdays with greater work impact (P < .001 for most), with larger effect sizes for the patients with an FGID. CONCLUSION: Patients with an FGID or organic GI disease demonstrate impaired HRQOL compared with healthy children. HRQOL can be used as a common metric to compare patient outcomes in clinical research and practice both within and across groups of patients with FGIDs and organic GI diseases.

Interpretability of the PedsQL™ Gastrointestinal Symptoms Scales and Gastrointestinal Worry Scales in Pediatric Patients With Functional and Organic Gastrointestinal Diseases.

OBJECTIVE: The present study investigates the clinical interpretability of the Pediatric Quality of Life Inventory™ (PedsQL™) Gastrointestinal Symptoms Scales and Worry Scales in pediatric patients with functional gastrointestinal disorders or organic gastrointestinal diseases in comparison with healthy controls. METHODS: The PedsQL™ Gastrointestinal Scales were completed by 587 patients with gastrointestinal disorders/diseases and 685 parents, and 513 healthy children and 337 parents. Minimal important difference (MID) scores were derived from the standard error of measurement (SEM). Cut-points were derived based on one and two standard deviations (SDs) from the healthy reference means. RESULTS: The percentages of patients below the scales' cut-points were significantly greater than the healthy controls (most p values ≤ .001). Scale scores 2 SDs from the healthy reference means were within the range of scores for pediatric patients with a gastrointestinal disorder. MID values were generated using the SEM. CONCLUSIONS: The findings support the clinical interpretability of the new PedsQL™ Gastrointestinal Symptoms Scales and Worry Scales.

PedsQL™ Gastrointestinal Symptoms Scales and Gastrointestinal Worry Scales in pediatric patients with functional and organic gastrointestinal diseases in comparison to healthy controls.

OBJECTIVE: The primary objective was to compare the gastrointestinal (GI) symptoms and worry of pediatric patients with functional GI disorders (FGIDs) and organic GI diseases to healthy controls utilizing the Pediatric Quality of Life Inventory™ (PedsQL™) Gastrointestinal Symptoms and Worry Scales for patient self-reports ages 5-18 years and parent proxy-reports for ages 2-18 years. The secondary objective was to compare FGIDs and organic GI diseases to each other. METHODS: The PedsQL™ Gastrointestinal Symptoms and Worry Scales were completed in a 9-site study by 587 pediatric patients with GI disorders and 685 parents of patients. Patients had physician-diagnosed GI disorders (chronic constipation, functional abdominal pain, irritable bowel syndrome, functional dyspepsia, Crohn's disease, ulcerative colitis, and gastroesophageal reflux disease). Ten Gastrointestinal Symptoms Scales measuring Stomach Pain, Stomach Discomfort When Eating, Food and Drink Limits, Trouble Swallowing, Heartburn and Reflux, Nausea and Vomiting, Gas and Bloating, Constipation, Blood, and Diarrhea were administered along with two Gastrointestinal Worry Scales. Five hundred and thirteen healthy children and 337 parents of healthy children completed the PedsQL™ Gastrointestinal Scales in an Internet panel survey. RESULTS: The PedsQL™ Gastrointestinal Symptoms and Worry Scales distinguished between pediatric patients with FGIDs and organic GI diseases in comparison with healthy controls, supporting known-groups validity. Patients with FGIDs reported more GI symptoms and worry than patients with organic GI diseases. CONCLUSIONS: The PedsQL™ Gastrointestinal Symptoms and Worry Scales may be utilized as common metrics across pediatric patient groups with FGIDs and organic GI diseases and healthy samples to measure GI-specific symptoms in clinical research and practice.

Histologic eosinophilic gastritis is a systemic disorder associated with blood and extragastric eosinophilia, TH2 immunity, and a unique gastric transcriptome.

BACKGROUND: The definition of eosinophilic gastritis (EG) is currently limited to histologic EG based on the tissue eosinophil count. OBJECTIVE: We aimed to provide additional fundamental information about the molecular, histopathologic, and clinical characteristics of EG. METHODS: Genome-wide transcript profiles and histologic features of gastric biopsy specimens, as well as blood eosinophil counts, were analyzed in patients with EG and control subjects (n = 15 each). RESULTS: The peak gastric antrum eosinophil count was 283 ± 164 eosinophils/×400 high-power field in patients with EG and 11 ± 9 eosinophils/×400 high-power field in control subjects (P = 6.1 × 10(-7)). Patients with EG (87%) had coexisting eosinophilic inflammation in multiple gastrointestinal segments; the esophagus represented the most common secondary site. Increased peripheral blood eosinophil counts (patients with EG: 1.09 ± 0.88 × 10(3)/µL vs control subjects: 0.09 ± 0.08 10(3)/µL, P = .0027) positively correlated with peak gastric eosinophil counts (Pearson r(2) = .8102, P < .0001). MIB-1(+) (proliferating), CD117(+) (mast cells), and FOXP3(+) (regulatory T cells, activated T cells, or both) cell counts were increased in patients with EG. Transcript profiling revealed changes in 8% of the genome in gastric tissue from patients with EG. Only 7% of this EG transcriptome overlapped with the eosinophilic esophagitis transcriptome. Significantly increased IL4, IL5, IL13, IL17, CCL26, and mast cell-specific transcripts and decreased IL33 transcripts were observed. CONCLUSION: EG is a systemic disorder involving profound blood and gastrointestinal tract eosinophilia, TH2 immunity, and a conserved gastric transcriptome markedly distinct from the eosinophilic esophagitis transcriptome. The data herein define germane cellular and molecular pathways of EG and provide a basis for improving diagnosis and treatment.