The HC-Pro cistron of Triticum mosaic virus is dispensable for systemic infection in wheat but is required for symptom phenotype and efficient genome amplification.

Triticum mosaic virus (TriMV), the type species of the genus Poacevirus in the family Potyviridae, is an economically important wheat curl mite-transmitted wheat-infecting virus in the Great Plains region of the USA. In this study, the functional genomics of helper component-proteinase (HC-Pro) encoded by TriMV was examined using a reverse genetics approach. TriMV with complete deletion of HC-Pro cistron elicited systemic infection in wheat, indicating that HC-Pro cistron is dispensable for TriMV systemic infection. However, TriMV lacking HC-Pro caused delayed systemic infection with mild symptoms that resulted in little or no stunting of plants with a significant reduction in the accumulation of genomic RNA copies and coat protein (CP). Sequential deletion mutagenesis from the 5' end of HC-Pro cistron in the TriMV genome revealed that deletions within amino acids 3 to 25, except for amino acids 3 and 4, elicited mild symptoms with reduced accumulation of genomic RNA and CP. Surprisingly, TriMV with deletion of amino acids 3 to 50 or 3 to 125 in HC-Pro elicited severe symptoms with a substantial increase in genomic RNA copies but a drastic reduction in CP accumulation. Additionally, TriMV with heterologous HC-Pro from other potyvirids produced symptom phenotype and genomic RNA accumulation similar to that of TriMV without HC-Pro, suggesting that HC-Pros of other potyvirids were not effective in complementing TriMV in wheat. Our data indicate that HC-Pro is expendable for replication of TriMV but is required for efficient viral genomic RNA amplification and symptom development. The availability of TriMV with various deletions in the HC-Pro cistron will facilitate the examination of the requirement of HC-Pro for wheat curl mite transmission.

A novel blood-sensing capsule for rapid detection of upper GI bleeding: a prospective clinical trial.

BACKGROUND AND AIMS: Upper GI bleeding (UGIB) is a common medical emergency associated with high resource utilization, morbidity, and mortality. Timely EGD can be challenging from personnel, resource, and access perspectives. PillSense (EnteraSense Ltd, Galway, Ireland) is a novel swallowed bleeding sensor for the detection of UGIB, anticipated to aid in patient triage and guide clinical decision-making for individuals with suspected UGIB. METHODS: This prospective, open-label, single-arm comparative clinical trial of a novel bleeding sensor for patients with suspected UGIB was performed at a tertiary care center. The PillSense system consists of an optical sensor and an external receiver that processes and displays data from the capsule as "Blood Detected" or "No Blood Detected." Patients underwent EGD within 4 hours of capsule administration; participants were followed up for 21 days to confirm capsule passage. RESULTS: A total of 126 patients were accrued to the study (59.5% male; mean age, 62.4 ± 14.3 years). Sensitivity and specificity for detecting the presence of blood were 92.9% (P = .02) and 90.6% (P < .001), respectively. The capsule's positive and negative predictive values were 74.3% and 97.8%, and positive and negative likelihood ratios were 9.9 and .08. No adverse events or deaths occurred related to the PillSense system, and all capsules were excreted from patients on follow-up. CONCLUSIONS: The PillSense system is safe and effective for detecting the presence of blood in patients evaluated for UGIB before upper GI endoscopy. It is a rapidly deployed tool, with easy-to-interpret results that will affect the diagnosis and triage of patients with suspected UGIB. (Clinical trial registration number: NCT05385224.).

H influenzae LPS colocalization with Toll-like receptor 4 in eosinophilic esophagitis.

Background: Patients with eosinophilic esophagitis (EoE) have a unique esophageal microbiome with increased presence of Haemophilus influenzae, but its role in the disease is unclear. Objective: Microbiome-derived bacterial LPS activation of Toll-like receptors (TLR) is a potential mechanism for inducing inflammation in other chronic inflammatory diseases, but it has not been studied in EoE. Our aim was therefore to study microbiome-derived bacterial LPS activation of TLRs in EoE. Methods: We studied 10 patients with active EoE, 9 patients with inactive EoE, and 10 control patients. Esophageal biopsy samples from the controls, patients with active EoE (>15 eosinophils/hpf), and patients with inactive EoE were immunostained for the presence of H influenzae LPS, presence of TLR4, and colocalization of LPS and TLR4. Staining intensity was measured by using confocal laser microscopy and scored on a scale from 0 to 3 as the average score assigned by 2 blinded observers. Results: H influenzae LPS was detected by positive staining in 20 of the 29 patients (69.0%), including 9 of the 10 patients with active EoE (90.0%), 8 of the 9 patients with inactive EoE (89.9%), and 3 of the 10 controls (30%); its level was greater in the patients with active EoE than in the controls (P = .063). TLR4 was detected by positive staining in 19 of the 29 patients (65.5%), including 9 of the 10 patients with active EoE (90.0%), 4 of the 9 patients with inactive EoE (44.4%), and 6 of the 10 controls (60.0%); its level was higher in the patients with active EoE than in those with inactive EoE (P = .096). The result of testing for colocalization of LPS and TLR4 was positive in 8 of 10 patients with active EoE (80.0%), 1 of 9 patients with inactive EoE (11.1%), and 1 of 10 control patients (10.0%), with greater colocalization of H influenzae LPS and TLR4 staining density in the samples from patients with active EoE than in the controls or the patients with inactive EoE (P = .009 and P = .018, respectively). Conclusion: Esophageal microbiome-rich H influenzae LPS colocalizes to TLR4 in active EoE. These data lend further support to a role for the esophageal microbiome in modulating the activity of EoE.

Development of a model to identify patients who do not need oesophageal biopsies when eosinophilic oesophagitis is suspected.

BACKGROUND: Predictive models for eosinophilic oesophagitis (EoE) may not fully rule in the diagnosis. AIM: To develop a reverse model that predicts against EoE to eliminate the need for oesophageal biopsies. METHODS: In this two-centre study, a predictive model was developed (Mayo Clinic) and validated (University of North Carolina [UNC]). Cross-sectional data from consecutive adult patients without prior EoE who underwent upper enoscopy with oesophageal biopsies were used. EoE cases had ≥15 eosinophils/high-power field while controls had no eosinophils. Data were collected on patient clinical and endoscopic features. Multiple variable logistic regression was used to identify predictors of non-EoE status while maintaining specificity ≥95%. A secondary model was developed to predict against the need for endoscopy in patients suspected of having EoE without alarm symptoms. RESULTS: The Mayo and UNC cohorts consisted of 345 (EoE = 94, non-EoE = 251) and 297 patients (EoE = 84, non-EoE = 213), respectively. A primary model based on clinical and endoscopic features predicted against EoE with c-statistic 0.92 (95% CI: 0.88-0.96), specificity 95%, and sensitivity 65%. This model was validated (UNC) with c-statistic 0.87 (95% CI: 0.82-0.92). A simplified scoring system was created and a threshold of ≥12 points excluded EoE with 95% specificity and 50% sensitivity. A secondary model based on clinical characteristics alone predicted against EoE with c-statistic 0.86 (95% CI: 0.82-0.90), specificity 95% and sensitivity 39% and validated (UNC) with c-statistic 0.78 (95% CI: 0.71-0.85). CONCLUSION: A simplified scoring system accurately identified a group of patients with a low likelihood of EoE where unnecessary oesophageal biopsies can be avoided, potentially resulting in resource and cost savings.

Eosinophilic Esophagitis Histologic Scoring System: Correlation with Histologic, Endoscopic, and Symptomatic Disease and Clinical Use.

BACKGROUND: The eosinophilic esophagitis histologic scoring system (EoEHSS) was developed to enhance the diagnostic standard of peak eosinophil count (PEC) in evaluating disease activity in EoE. AIMS: (1) Correlate the EoEHSS and PEC to measures of symptomatic and endoscopic disease activity, (2) Correlate EoEHSS grade and stage subcomponents to clinical, radiology, and endoscopic markers of fibrotic disease, (3) Evaluate EoEHSS remission in asymptomatic patients with PEC < 15 eosinophils per high powered field (eos/hpf). METHODS: Secondary analysis of prospective cohort data of 22 patients with EoE that underwent dietary therapy and endoscopy at 3 time points. Active disease was defined by EoEHSS grade or stage > 0.125, symptomatic disease by EoE symptom activity index > 20, endoscopic disease by endoscopic reference score > 2, and histologic disease by PEC ≥ 15 eos/hpf. EoEHSS remission was defined by esophageal inflammation (EI) grade of 0-1, EI stage of 0, total grade ≤ 3, and total stage ≤ 3. RESULTS: EoEHSS grade and stage did not correlate with symptomatic disease but did with endoscopic and histologic disease. PEC showed similar correlation pattern. Abnormal grade and stage had strong sensitivity (87-100%) but poor specificity (11-36%) to detect symptomatic, endoscopic, and histologic disease activity. Lamina propria fibrosis was evaluated in 36% of biopsies and did not correlate with minimum esophageal diameter. Out of 14 patients who were in complete symptomatic, endoscopic, and histologic remission, 8 met criteria for EoEHSS remission. CONCLUSION: The positive and negative correlations of EoEHSS to specific measures of symptomatic, histologic, and endoscopic activity suggest that it provides complementary information in EoE.

Flexible endoscopic Zenker's diverticulotomy - A retrospective review of outcomes in 75 patients.

OBJECTIVE: Flexible endoscopic Zenker's diverticulotomy (FEZD) is a procedure performed primarily by gastroenterologists for treatment of symptomatic Zenker's diverticulum (ZD). Given the lack of prior investigations with large sample sizes, we report on one of the largest series of patients who underwent FEZD. METHODS: A review of patients who underwent FEZD at our institution from 2006 to 2021 was performed. Data were abstracted for patient demographics, clinical features, procedural characteristics, adverse events, and outcomes. RESULTS: A total of 75 patients (37 women) with mean age of 77.9 (33-102) years and mean (range) follow-up of 1.1 (0-13.2) years were identified. 67.9 % of FEZD cases were performed under general anesthesia. The mean procedure time was 37.1 min. Same day discharge and resumption of oral intake was seen in 56.4 % and 57.1 % of cases, respectively. Adverse events included intraprocedural bleeding (15.7 %) controlled with endoscopic means, infection (4.8 %) exclusively managed with antibiotics in all but one case, subcutaneous emphysema (2.4 %), and perforation (10.7 %) conservatively managed in all but one case. 97.6 % of patients had sustained subjective improvement in symptoms following their procedure. Fifteen patients (20 %) experienced recurrence after undergoing initial FEZD-26.7 % percent of whom were sufficiently treated with repeat FEZDs. Younger age was associated with recurrence (p < 0.01). CONCLUSION: FEZD is an effective, safe procedure for the management of symptomatic ZD. It is a viable alternative for patients in whom otorhinolaryngological procedures via rigid endoscopy are not an option.

Physician Assistant Students' Perception of Online Didactic Education: A Cross-Sectional Study.

PURPOSE: This study describes physician assistant students' perception toward online didactic education and highlights relationships between student characteristics and their preference for online learning. METHODS: A previously validated survey questionnaire was administered online to physician assistant students enrolled in traditional, in-person training programs across the United States. The survey consisted of five Likert-scale statements measuring perceptions of online learning and was rated on a seven-point Likert scale. Students also reported their age, gender, history of taking an online course, and preferred learning style. Mean scores were reported for agreement with each Likert-scale statement; Pearson correlation coefficients, one-way ANOVA with post hoc Tukey tests, and independent samples t-tests were used to determine relationships between student characteristics and their preference for online learning. RESULTS: A total of 391 completed surveys met the inclusion criteria for the study and were used in data analysis. The average age of respondents was 25.98 years, 81.1% (n = 317) were female, 96.2%, (n = 376) reported taking an online course previously, and preferred learning styles were reported as 36.1% (n = 141) visual, 7.7% (n = 30) auditory, 15.6% (n = 61) reading/writing, and 40.7% (n = 159) kinesthetic. Nearly a quarter of respondents indicated they preferred online courses, particularly students with a preferred learning style of reading/writing. No relationships were observed between age, gender, or history of taking an online course and preference for online education. CONCLUSION: Most physician assistant students prefer in-person learning. However, a substantial number prefer online learning, and a significant number of these students reported a preferred learning style of reading/writing. More research is necessary to give educational institutions the ability to make data-driven, student-centered program development decisions. However, data in this study indicate a need for continued development of online/hybrid physician assistant programs to better align with current student preferences.

6K1, NIa-VPg, NIa-Pro, and CP of Wheat Streak Mosaic Virus Are Collective Determinants of Wheat Streak Mosaic Disease in Wheat.

Wheat streak mosaic virus (WSMV; genus Tritimovirus, family Potyviridae) is the causal agent of the most economically important wheat streak mosaic disease of wheat (Triticum aestivum) in the Great Plains region of the United States. WSMV determinants responsible for wheat streak mosaic disease in wheat are unknown. Triticum mosaic virus (TriMV), a wheat-infecting virus, was used as an expression vector for the transient expression of each of the WSMV-encoded cistrons in wheat. WSMV-encoded 6K1, NIa-VPg, NIa-Pro, and CP cistrons in TriMV elicited symptoms specific to different stages of wheat streak mosaic disease without significantly affecting the genomic RNA accumulation. WSMV 6K1 produced early wheat streak mosaic disease-like symptoms of severe chlorotic streaks and patches. NIa-VPg and CP caused severe chlorotic streaks, followed by moderate stunting (only with NIa-VPg) of wheat, mimicking early- and mid-stage symptoms of wheat streak mosaic disease. WSMV NIa-Pro caused mild chlorotic streaks, followed by dark green leaves with severe stunting, representing the late symptoms of wheat streak mosaic disease. Collectively, these data suggest that cumulative effects of WSMV-encoded 6K1, NIa-VPg, NIa-Pro, and CP are responsible for different stages of wheat streak mosaic disease symptoms in wheat. Furthermore, deletion analysis of wheat streak mosaic disease determinants revealed that complete 6K1 and NIa-Pro, amino acids 3 to 60 and 121 to 197 of NIa-VPg, and amino acids 101 to 294 of CP are responsible for wheat streak mosaic disease-like symptoms in wheat. This study suggests that management strategies for wheat streak mosaic disease in wheat should target WSMV determinants of the disease phenotype.

Use of the Esophageal Sponge in Directing Food Reintroduction in Eosinophilic Esophagitis.

BACKGROUND & AIMS: Dietary therapy is successful in eosinophilic esophagitis (EoE) but requires multiple upper endoscopies. The aim of this study was to determine if food reintroduction in EoE can be directed by minimally-invasive esophageal sponge cytology. METHODS: In this prospective non-blinded trial, 22 responders to 6-food elimination diets underwent sequential food reintroduction guided by esophageal sponge cytology. Foods were reintroduced followed by unsedated esophageal sponge cytology assessment. A food trigger was defined by sponge cytology peak eosinophil count of ≥15 eos/high-powered field (hpf). Symptoms (EoE symptom activity index [EEsAI]), endoscopic score (EoE endoscopic reference score [EREFS]), and biopsy histology (peak eosinophil count) were collected pre-dietary therapy and post-dietary therapy, and then 4 weeks post food reintroduction. RESULTS: The EEsAI and EREFS were similar post-dietary therapy to post-food reintroduction: 12.0 (interquartile range [IQR], 0.0-27.0) vs 16.5 (IQR, 9.0-28.8) (P = .265) and 1.5 (IQR, 0.2-3.0) vs 1.0 (IQR, 0.0-2.0) (P = .185). However, the peak eosinophil count was increased post-food reintroduction compared with post-dietary therapy: 20.0 (IQR, 5.0-51.5) vs 2.0 (IQR, 1.0-4.0) (P < .001), suggesting a failure of identification of all food triggers. The peak eosinophil count was lower post-food reintroduction compared with pre-dietary therapy: 20.0 (IQR, 5.0-51.5) vs 52.0 (IQR, 30.8-76.2) (P = .008). At the post food reintroduction evaluation, sponge cytology and biopsy histology were in agreement in 59% (13/22) of cases using a cutoff of <15 eos/hpf and 68% (15/22) of cases using a cutoff of <6 eos/hpf. CONCLUSIONS: In the first study to evaluate a non-endoscopic technique in the clinical management of EoE, the esophageal sponge was moderately successful at guiding food reintroduction in EoE dietary responders in the outpatient setting. CLINICALTRIALS: gov, Number NCT02599558.

Eosinophil Peroxidase Staining Enhances the Diagnostic Utility of the Cytosponge in Eosinophilic Esophagitis.

INTRODUCTION: We aimed to assess the diagnostic utility of eosinophil peroxidase (EPX) staining on Cytosponge (CS) samples in eosinophilic esophagitis (EoE). METHODS: Esophageal biopsy (BX) samples from adult subjects with EoE were assessed using peak eosinophils per high-power field (eos/hpf), EPX, and the EoE histologic scoring system. EPX staining and eos/hpf were compared (BX vs CS). RESULTS: CS EPX positivity correlated with eos/hpf (CS [ r = 0.82, P < 0.0001]; BX [ r = 0.65, P < 0.0001]) and EoE histologic scoring system (grade [ r = 0.62, P < 0.00001]; stage [ r = 0.61, P < 0.0001]). CS EPX identified subjects with active EoE (area under the curve = 0.86, P < 0.0001). DISCUSSION: The correlation of CS EPX with eosinophilic inflammation and histologic disease severity supports its diagnostic utility in EoE.

Predictors of histologic response to dietary therapy in eosinophilic oesophagitis.

BACKGROUND: Dietary therapy successfully treats eosinophilic oesophagitis (EoE), but limited data exist on predictors of patient response. AIMS: To determine response rates and to identify predictors of histologic response to elimination diets in adults with EoE METHODS: This was a retrospective, single-centre study of adults with PPI-refractory EoE undergoing dietary therapy with six food elimination diet (SFED) or extended six food elimination diet (ExSFED) in an outpatient setting from January 2012 to January 2019. Patient demographics, radiologic and endoscopic findings, endoscopic reference (EREF) scores, histology and symptoms were evaluated before and after food elimination. Histologic response was assessed via tissue obtained from endoscopically-guided biopsy or Cytosponge. Dietary therapy adherence was assessed via structured phone interview. Multivariable logistic regression analysis was performed to identify predictors of dietary response. RESULTS: We included 68 patients, of whom 62% had a histologic response to dietary therapy (81% to SFED, 19% to ExSFED). Median duration of follow-up was 45 months (IQR, 34-53 months). On multivariable analysis, higher pre-SFED EREF score was the only variable associated with dietary non-response (OR 0.07, 95% CI 0.49, 0.98; p = 0.04). CONCLUSIONS: In adults with EoE, histologic dietary non-response to SFED was associated with a higher pre-SFED EREF score, suggesting that fixed structural disease may predict dietary non-response. Our additional observations of poor correlation between symptomatic and histologic flares, and identification of ExSFED responders, suggest that histologic confirmation should be sought before committing patients to lifelong dietary changes. We also recommend the consideration of restricting legumes and corn in SFED non-responders as ExSFED detected additional dietary responders.

Endoscopic approach to eosinophilic esophagitis: American Society for Gastrointestinal Endoscopy Consensus Conference.

Endoscopy plays a critical role in caring for and evaluating the patient with eosinophilic esophagitis (EoE). Endoscopy is essential for diagnosis, assessment of response to therapy, treatment of esophageal strictures, and ongoing monitoring of patients in histologic remission. To date, less-invasive testing for identifying or grading EoE severity has not been established, whereas diagnostic endoscopy as integral to both remains the criterion standard. Therapeutic endoscopy in patients with adverse events of EoE may also be required. In particular, dilation may be essential to treat and attenuate progression of the disease in select patients to minimize further fibrosis and stricture formation. Using a modified Delphi consensus process, a group of 20 expert clinicians and investigators in EoE were assembled to provide guidance for the use of endoscopy in EoE. Through an iterative process, the group achieved consensus on 20 statements yielding comprehensive advice on tissue-sampling standards, gross assessment of disease activity, use and performance of endoscopic dilation, and monitoring of disease, despite an absence of high-quality evidence. Key areas of controversy were identified when discussions yielded an inability to reach agreement on the merit of a statement. We expect that with ongoing research, higher-quality evidence will be obtained to enable creation of a guideline for these issues. We further anticipate that forthcoming expert-generated and agreed-on statements will provide valuable practice advice on the role and use of endoscopy in patients with EoE.

Histologic response to steroids in eosinophilic esophagitis is dependent on delivery compound.

Topical steroids are commonly used in treatment of eosinophilic esophagitis (EoE), but currently there is lack of data to clarify most effective regimen. We aimed to study the achievement of histologic remission using the same dose of budesonide in two different delivery formulations. Patients with established EoE treated with pharmacy compounded budesonide capsule or budesonide Rincinol gel (both 3 mg twice daily) were studied retrospectively. Those with pre-treatment and post-treatment histologic assessment were included with main endpoint being histologic remission. 103 patients (62 gel, 41 capsule) were included, with higher rate of histologic remission with gel (84 vs. 59%, P=0.004). A subset of patients in both groups had lack of steroid response (<50% drop in eosinophils) (15% for gel, 32% for capsule). Formulation/delivery vehicle of steroid treatments to esophageal mucosa in EoE appears important for treatment efficacy, with budesonide gel having higher likelihood of histologic remission compared to budesonide capsules in our population. A truly steroid refractory group appears likely in our population. Larger, prospective studies may help clarify best regimen of topical steroids in EoE and may work to identify patients likely to benefit from alternative therapies.

Attitudes of Dental Hygiene and Nursing Students Following a Simulation Activity.

Purpose: Interprofessional education (IPE) activities assist health care professionals outside of dentistry learn about the importance of oral care and its connection to overall health, while also encouraging the integration of dental hygienists into primary health care teams. The purpose of this study was to evaluate the effect of a simulation activity on dental hygiene and nursing students' attitudes about interprofessional collaboration (IPC).Methods: Second-year dental hygiene (n=35) and nursing students (n=45) from a community college in the Midwestern United States were recruited to participate via e-mail. Participants completed an online module about oral care and ventilator-associated pneumonia followed by the Interprofessional Education Collaborative (IPEC) Competency Self-Assessment Survey version 3 prior to participating in an IPE simulation activity. The IPEC survey measures two domains: interprofessional interaction and interprofessional values. Following the simulation activity, participants completed the survey again. A Wilcoxon signed-rank test compared pre/post-survey responses.Results: A total of 61 students completed the pre-IPE survey (73%; dental hygiene: n= 29, nursing: n=32); and a total of 38 students (47%) completed the post-IPE survey. Ten post-IPE surveys were excluded in the final analysis (dental hygiene: n=15, nursing: n=13). A significant difference was found between pre-IPE and post-IPE scores for the interprofessional interaction domain (p<.001). No difference was found for the interprofessional values domain (p<.18)Conclusion: Participants had a high regard for IPC and their attitudes improved following the simulation activity. Open-ended responses indicated an increase in knowledge of the importance of IPC and a heightened awareness of professional roles and responsibilities. Interprofessional activities are needed across the health professions curricula to provide future collaboration and quality patient care.

International Consensus Recommendations for Eosinophilic Gastrointestinal Disease Nomenclature.

BACKGROUND & AIMS: Substantial heterogeneity in terminology used for eosinophilic gastrointestinal diseases (EGIDs), particularly the catchall term "eosinophilic gastroenteritis," limits clinical and research advances. We aimed to achieve an international consensus for standardized EGID nomenclature. METHODS: This consensus process utilized Delphi methodology. An initial naming framework was proposed and refined in iterative fashion, then assessed in a first round of Delphi voting. Results were discussed in 2 consensus meetings, and the framework was updated and reassessed in a second Delphi vote, with a 70% threshold set for agreement. RESULTS: Of 91 experts participating, 85 (93%) completed the first and 82 (90%) completed the second Delphi surveys. Consensus was reached on all but 2 statements. "EGID" was the preferred umbrella term for disorders of gastrointestinal (GI) tract eosinophilic inflammation in the absence of secondary causes (100% agreement). Involved GI tract segments will be named specifically and use an "Eo" abbreviation convention: eosinophilic gastritis (now abbreviated EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC). The term "eosinophilic gastroenteritis" is no longer preferred as the overall name (96% agreement). When >2 GI tract areas are involved, the name should reflect all of the involved areas. CONCLUSIONS: This international process resulted in consensus for updated EGID nomenclature for both clinical and research use. EGID will be the umbrella term, rather than "eosinophilic gastroenteritis," and specific naming conventions by location of GI tract involvement are recommended. As more data are developed, this framework can be updated to reflect best practices and the underlying science.

Reliability and responsiveness of endoscopic disease activity assessment in eosinophilic esophagitis.

BACKGROUND AND AIMS: Endoscopic outcomes have become important measures of eosinophilic esophagitis (EoE) disease activity, including as an endpoint in randomized controlled trials (RCTs). We evaluated the operating properties of endoscopic measures for use in EoE RCTs. METHODS: Modified Research and Development/University of California Los Angeles appropriateness methods and a panel of 15 international EoE experts identified endoscopic items and definitions with face validity that were used in a 2-round voting process to define simplified (all items graded as absent or present) and expanded versions (additional grades for edema, furrows, and/or exudates) of the EoE Endoscopic Reference Score (EREFS). Inter- and intrarater reliability of these instruments (expressed as intraclass correlation coefficients [ICC]) were evaluated using paired endoscopy video assessments of 2 blinded central readers in patients before and after 8 weeks of proton pump inhibitors, swallowed topical corticosteroids, or dietary elimination. Responsiveness was measured using the standardized effect size (SES). RESULTS: The appropriateness of 41 statements relevant to EoE endoscopic activity (endoscopic items, item definitions and grading, and other considerations relevant for endoscopy) was considered. The original and expanded EREFS demonstrated moderate-to-substantial inter-rater reliability (ICCs of .472-.736 and .469-.763, respectively) and moderate-to-almost perfect intrarater reliability (ICCs of .580-.828 and .581-.828, respectively). Strictures were least reliably assessed (ICC, .072-.385). The original EREFS was highly responsive (SES, 1.126 [95% confidence interval {CI}, .757-1.534]), although both expanded versions of EREFS, scored based on worst affected area, were numerically most responsive to treatment (expanded furrows: SES, 1.229 [95% CI, .858-1.643]; all items expanded: SES, 1.252 [95% CI, .880-1.667]). The EREFS and its modifications were not more reliably scored by segment and also not more responsive when proximal and distal EREFSs were summed. CONCLUSIONS: EREFS and its modifications were reliable and responsive, and the original or expanded versions of the EREFS may be preferred in RCTs. Disease activity scored based on the worst affected area optimizes reliability and responsiveness.

Development of a core outcome set for therapeutic studies in eosinophilic esophagitis (COREOS).

BACKGROUND: End points used to determine treatment efficacy in eosinophilic esophagitis (EoE) have evolved over time. With multiple novel therapies in development for EoE, harmonization of outcomes measures will facilitate evidence synthesis and appraisal when comparing different treatments. OBJECTIVE: We sought to develop a core outcome set (COS) for controlled and observational studies of pharmacologic and diet interventions in adult and pediatric patients with EoE. METHODS: Candidate outcomes were generated from systematic literature reviews and patient engagement interviews and surveys. Consensus was established using an iterative Delphi process, with items voted on using a 9-point Likert scale and with feedback from other participants to allow score refinement. Consensus meetings were held to ratify the outcome domains of importance and the core outcome measures. Stakeholders were recruited internationally and included adult and pediatric gastroenterologists, allergists, dieticians, pathologists, psychologists, researchers, and methodologists. RESULTS: The COS consists of 4 outcome domains for controlled and observational studies: histopathology, endoscopy, patient-reported symptoms, and EoE-specific quality of life. A total of 69 stakeholders (response rate 95.8%) prioritized 42 outcomes in a 2-round Delphi process, and the final ratification meeting generated consensus on 33 outcome measures. These included measurement of the peak eosinophil count, Eosinophilic Esophagitis Histology Scoring System, Eosinophilic Esophagitis Endoscopic Reference Score, and patient-reported measures of dysphagia and quality of life. CONCLUSIONS: This interdisciplinary collaboration involving global stakeholders has produced a COS that can be applied to adult and pediatric studies of pharmacologic and diet therapies for EoE and will facilitate meaningful treatment comparisons and improve the quality of data synthesis.

Member engagement in multi-sector health care alliances.

Many communities are developing innovative forms of collaborative organizations such as multi-sector health care alliances (MHCAs) to address problems of misaligned incentives among providers, payers, and community stakeholders and improve health and health care. Member engagement is essential to the success of these organizations due to their dependence on volunteer members to develop and implement strategy and provide material and in-kind support for alliance efforts, yet relatively little research has examined how alliances can foster engagement. This study examined behavioral indicators of member engagement (e.g., recruitment and retention of organizational and individual members) and how they are related to two foundational dimensions of alliance functioning - alliance leadership and community centrality. Using three rounds of an internet-based survey of alliance members from 14 alliances, the study found that organizational recruitment and retention increased over time, from 26.6% to 41.5% and 56.0% to 65.2%, respectively. Recruitment of individuals increased over the study period (38.3% to 47.2%, while retention of individual members declined over the study period (61.0% to 53.2%). Alliance leadership was associated with lower levels of recruitment (both organizational and individual members) but higher levels of organizational retention (both organizational and individual members). Collectively, our findings suggest that behavioral aspects of alliances are more effective at retaining members than relatively stable characteristics such as size and positioning in the community. Contrasting relationships between recruitment and retention, however, suggest that different forms of leadership may be required to simultaneously attract new members while retaining existing ones.

Effectiveness and Safety of High- vs Low-Dose Swallowed Topical Steroids for Maintenance Treatment of Eosinophilic Esophagitis: A Multicenter Observational Study.

BACKGROUND & AIMS: Data evaluating efficacy of different doses of swallowed topical corticosteroids (STC) in the long-term management of eosinophilic esophagitis (EoE) are lacking. We assessed long-term effectiveness and safety of different STC doses for adults with EoE after achievement of histological remission. METHODS: We performed a retrospective multicenter study at five EoE referral centers (US and Switzerland). We analyzed data on 82 patients with EoE in histological remission and ongoing STC treatment with therapeutic adherence of ≥75% (58 males; mean age at diagnosis, 37.2±14.4 years). Patients were followed for a median of 2.2 years (interquartile range [IQR], 1.0-3.8 years). We collected data from 217 follow-up endoscopy visits. The primary endpoint was time to histological relapse. RESULTS: Histological relapse occurred in 67% of patients. Relapse rates were comparable in patients taking low dose (≤0.5 mg per day, n = 58) and high dose STC (>0.5 mg per day, n = 24) with 72 vs 54% (ns). However, histological relapse occurred significantly earlier with low dose STC (1.0 vs 1.8 years, P = .030). There was no difference regarding rates of and time to stricture formation for low vs high dose STC. Esophageal candidiasis was observed in 6% of patients (5% for low dose, 8% for high dose, ns). No dysplasia or mucosal atrophy was detected. CONCLUSION: Histological relapse frequently occurs in EoE despite ongoing STC treatment regardless of STC doses. However, relapse develops later in patients on high dose STC without an increase in side-effects. Doses higher than 0.5 mg/day may be considered for EoE maintenance treatment, but advantage over lower doses appears to be small.