EoE CONNECT, the European Registry of Clinical, Environmental, and Genetic Determinants in Eosinophilic Esophagitis:rationale, design, and study protocol of a large-scale epidemiological study in Europe

BACKGROUND: The growing prevalence of eosinophilic esophagitis (EoE) represents a considerable burden to patients and health care systems. Optimizing cost-effective management and identifying mechanisms for disease onset and progression are required. However, the paucity of large patient cohorts and heterogeneity of practice hinder the defining of optimal management of EoE. METHODS: EoE CONNECT is an ongoing, prospective registry study initiated in 2016 and currently managed by EUREOS, the European Consortium for Eosinophilic Diseases of the Gastrointestinal Tract. Patients are managed and treated by their responsible specialists independently. Data recorded using a web-based system include demographic and clinical variables; patient allergies; environmental, intrapartum, and early life exposures; and family background. Symptoms are structurally assessed at every visit; endoscopic features and histological findings are recorded for each examination. Prospective treatment data are registered sequentially, with new sequences created each time a different treatment (active principle, formulation, or dose) is administered to a patient. EoE CONNECT database is actively monitored to ensure the highest data accuracy and the highest scientific and ethical standards. RESULTS: EoE CONNECT is currently being conducted at 39 centers in Europe and enrolls patients of all ages with EoE. In its aim to increase knowledge, to date EoE CONNECT has provided evidence on the effectiveness of first- and second-line therapies for EoE in clinical practice, the ability of proton pump inhibitors to induce disease remission, and factors associated with improved response. Drug effects to reverse fibrous remodeling and endoscopic features of fibrosis in EoE have also been assessed. CONCLUSION: This prospective registry study will provide important information on the epidemiological and clinical aspects of EoE and evidence as to the real-world and long-term effectiveness and safety of therapy. These data will potentially be a vital benchmark for planning future EoE health care services in Europe

EoE CONNECT, the European Registry of Clinical, Environmental, and Genetic Determinants in Eosinophilic Esophagitis: rationale, design, and study protocol of a large-scale epidemiological study in Europe

Background: The growing prevalence of eosinophilic esophagitis (EoE) represents a considerable burden to patients and health care systems. Optimizing cost-effective management and identifying mechanisms for disease onset and progression are required. However, the paucity of large patient cohorts and heterogeneity of practice hinder the defining of optimal management of EoE. Methods: EoE CONNECT is an ongoing, prospective registry study initiated in 2016 and currently managed by EUREOS, the European Consortium for Eosinophilic Diseases of the Gastrointestinal Tract. Patients are managed and treated by their responsible specialists independently. Data recorded using a web-based system include demographic and clinical variables; patient allergies; environmental, intrapartum, and early life exposures; and family background. Symptoms are structurally assessed at every visit; endoscopic features and histological findings are recorded for each examination. Prospective treatment data are registered sequentially, with new sequences created each time a different treatment (active principle, formulation, or dose) is administered to a patient. EoE CONNECT database is actively monitored to ensure the highest data accuracy and the highest scientific and ethical standards. Results: EoE CONNECT is currently being conducted at 39 centers in Europe and enrolls patients of all ages with EoE. In its aim to increase knowledge, to date EoE CONNECT has provided evidence on the effectiveness of first- and second-line therapies for EoE in clinical practice, the ability of proton pump inhibitors to induce disease remission, and factors associated with improved response. Drug effects to reverse fibrous remodeling and endoscopic features of fibrosis in EoE have also been assessed. Conclusion: This prospective registry study will provide important information on the epidemiological and clinical aspects of EoE and evidence as to the real-world and long-term effectiveness and safety of therapy. These data will potentially be a vital benchmark for planning future EoE health care services in Europe

Accurate and timely diagnosis of Eosinophilic Esophagitis improves over time in Europe. An analysis of the EoE CONNECT Registry

BACKGROUND: Poor adherence to clinical practice guidelines for eosinophilic esophagitis (EoE) has been described and the diagnostic delay of the disease continues to be unacceptable in many settings. OBJECTIVE: To analyze the impact of improved knowledge provided by the successive international clinical practice guidelines on reducing diagnostic delay and improving the diagnostic process for European patients with EoE. METHODS: Cross‐sectional analysis of the EoE CONNECT registry based on clinical practice. Time periods defined by the publication dates of four major sets of guidelines over 10 years were considered. Patients were grouped per time period according to date of symptom onset. RESULTS: Data from 1,132 patients was analyzed and median (IQR) diagnostic delay in the whole series was 2.1 (0.7‐6.2) years. This gradually decreased over time with subsequent release of new guidelines (p < 0.001), from 12.7 years up to 2007 to 0.7 years after 2017. The proportion of patients with stricturing of mixed phenotypes at the point of EoE diagnosis also decreased over time (41.3% vs. 16%; p < 0.001), as did EREFS scores. The fibrotic sub‐score decreased from a median (IQR) of 2 (1‐2) to 0 (0‐1) when patients whose symptoms started up to 2007 and after 2017 were compared (p < 0.001). In parallel, symptoms measured with the Dysphagia Symptoms Score reduced significantly when patients with symptoms starting before 2007 and after 2012 were compared. A reduction in the number of endoscopies patients underwent before the one that achieved an EoE diagnosis, and the use of allergy testing as part of the diagnostic workout of EoE, also reduced significantly over time (p = 0.010 and p < 0.001, respectively). CONCLUSION: The diagnostic work‐up of EoE patients improved substantially over time at the European sites contributing to EoE CONNECT, with a dramatic reduction in diagnostic delay

Análisis de las características clínico-analíticas, hsitológicas y evolutivas de la infección crónica por el virus de la hepatitis B, antígeno-HBe negativo, según los niveles de GPT al diagnóstico y en la evolución

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Medicina. Fecha de lectura: 20-02-201

Hepatitis B virus e antigen-negative chronic infection. Treatment based on glutamic pyruvic transaminase and hepatitis B virus deoxyribonucleic acid cut-off values

Objectives To identify glutamic pyruvic transaminase (GPT) and hepatitis B virus DNA (HBV-DNA) cut-off values at diagnosis in patients with hepatitis B virus e antigen-negative chronic infection (HBeAg(–)), which may be predictors of clinical course, prognosis and/or the need for antiviral therapy. Methods A retrospective and observational cohort study of patients diagnosed with HBeAg(–) chronic infection (2005-2012). A normal GPT cut-off value at diagnosis that predicts abnormal GPT values in the clinical course of the infection, a baseline HBV-DNA cut-off value that predicts an increase in HBV-DNA above 2,000 IU/ml, and GPT and HBV-DNA as predictors of the need for treatment were investigated using ROC curves. Results 126 patients were enrolled (follow-up: 42.1 ± 21.5 months), 93 of which had normal GPT levels at diagnosis. In the ROC curve analysis, 900 IU/ml was found to be the HBV-DNA cut-off value that best predicted this value's increase above 2,000 IU/ml (sensitivity: 90%; specificity: 88%; PPV: 79%; NPV: 100%; diagnostic precision: 89%), while 25 mU/ml was the normal GPT cut-off value at diagnosis that best predicted subsequently elevated GPT levels (sensitivity: 95.4%; specificity: 81.6%; PPV: 67%; NPV: 96%; diagnostic precision: 80.6%). Patients with GPT 26-40 mU/ml at diagnosis presented with more complications or required more treatment than subjects with GPT ≤ 25 mU/ml (P < .05). The combined GPT and HBV-DNA values that elicited the highest treatment need were 38 mU/ml of GPT and 6,000 IU/ml of HBV-DNA (sensitivity: 75%; specificity: 93.4%; PPV: 60%; NPV: 96.6%). Conclusion HBeAg(–) patients with GPT < 25 mU/ml and HBV-DNA < 900 IU/ml at diagnosis have positive outcomes and may not require such stringent follow-up in the first years after diagnosisObjetivos Buscar puntos de corte de la glutámico-pirúvica transaminasa (GPT) y de ADN del virus de hepatitis B (ADN-VHB) al diagnóstico, en pacientes con infección crónica VHB antígeno e negativo (AgHBe(–)), que puedan ser predictores de la evolución, pronóstico y/o de la necesidad de terapia antiviral. Métodos Estudio observacional de cohortes retrospectivo de pacientes diagnosticados de infección crónica por VHB AgHBe(–) (2005-2012). Se investigó un punto de corte de GPT normal al diagnóstico que predijera la alteración de esta en la evolución, de ADN-VHB basal que predijera la elevación de este por encima de 2.000 UI/ml, y de GPT y ADN-VHB como predictores de la necesidad de tratamiento, mediante curvas ROC. Resultados Se incluyeron 126 pacientes (seguimiento: 42,1 ± 21,5 meses), de los cuales 93 tenían GPT normal al diagnóstico. En el análisis de curvas ROC el punto de corte de ADN-VHB que mejor predijo la elevación de este por encima de 2.000 UI/ml fue 900 UI/ml (sensibilidad: 90%; especificidad: 88%; VPP: 79%; VPN: 100%; precisión diagnóstica: 89%), y el que mejor predijo la alteración de GPT normal al diagnóstico posteriormente elevada fue 25 mU/ml (sensibilidad: 95,4%; especificidad: 81,6%; VPP: 67%; VPN: 96%; precisión diagnóstica: 80,6%). Los pacientes con GPT 26-40 mU/ml al diagnóstico presentaron más complicaciones o necesidad de tratamiento que aquellos con GPT ≤ 25 mU/ml (p < 0,05). La combinación de GPT y ADN-VHB que maximizó la necesidad de tratamiento fue 38 mU/ml de GPT y 6.000 UI/ml de ADN-VHB (sensibilidad: 75%; especificidad: 93,4%; VVP: 60%; VPN: 96,6%). Conclusión Los pacientes VHB AgHBe(–) con GPT < 25 mU/ml y ADN-VHB < 9.000 UI/ml al diagnóstico presentan buena evolución y podrían no requerir un seguimiento tan estrecho en los primeros años desde el diagnóstico

Efficacy of proton pump inhibitor therapy for eosinophilic oesophagitis in 630 patients:results from the EoE connect registry

Background: Proton pump inhibitors (PPIs) are the most commonly used first-line therapy for patients with eosinophilic oesophagitis (EoE). However, many aspects related to PPIs in EoE are still unknown. Aims: To assess the effectiveness of PPI therapy for EoE in real-world practice. Methods: This cross-sectional study collected data on PPI efficacy from the multicentre EoE CONNECT database. Clinical remission was defined as a decrease of 6550% in dysphagia symptom score; histological remission was defined as a peak eosinophil count below 15 eosinophils per high-power field. Factors associated with effectiveness of PPI therapy were identified by binary logistic regression multivariate analyses. Results: Overall, 630 patients (76 children) received PPI as initial therapy (n\ua0=\ua0600) or after failure to respond to other therapies (n\ua0=\ua030). PPI therapy achieved eosinophil density below 15 eosinophils per high-power field in 48.8% and a decreased symptom score in 71.0% of patients. More EoE patients with an inflammatory rather than stricturing phenotype accomplished clinico-histological remission after PPI therapy (OR 3.7; 95% CI, 1.4-9.5); as well as those who prolonged treatment length from 8 to 12\ua0weeks (OR 2.7; 95% CI, 1.3-5.3). After achieving clinico-histological remission of EoE, PPI dosage reduction was effectively maintained in 69.9% of patients, but tended to be less effective among those with a stricturing phenotype. Conclusions: Inflammatory EoE phenotype and treatment duration up to 12\ua0weeks correlated with greater chance for inducing remission of EoE. A stricturing phenotype decreased response rates to PPI therapy both initially and in the long term

Accurate and timely diagnosis of Eosinophilic Esophagitis improves over time in Europe. An analysis of the EoE CONNECT Registry

Poor adherence to clinical practice guidelines for eosinophilic esophagitis (EoE) has been described and the diagnostic delay of the disease continues to be unacceptable in many settings. To analyze the impact of improved knowledge provided by the successive international clinical practice guidelines on reducing diagnostic delay and improving the diagnostic process for European patients with EoE. Cross-sectional analysis of the EoE CONNECT registry based on clinical practice. Time periods defined by the publication dates of four major sets of guidelines over 10 years were considered. Patients were grouped per time period according to date of symptom onset. Data from 1,132 patients was analyzed and median (IQR) diagnostic delay in the whole series was 2.1 (0.7-6.2) years. This gradually decreased over time with subsequent release of new guidelines (p < 0.001), from 12.7 years up to 2007 to 0.7 years after 2017. The proportion of patients with stricturing of mixed phenotypes at the point of EoE diagnosis also decreased over time (41.3% vs. 16%; p < 0.001), as did EREFS scores. The fibrotic sub-score decreased from a median (IQR) of 2 (1-2) to 0 (0-1) when patients whose symptoms started up to 2007 and after 2017 were compared (p < 0.001). In parallel, symptoms measured with the Dysphagia Symptoms Score reduced significantly when patients with symptoms starting before 2007 and after 2012 were compared. A reduction in the number of endoscopies patients underwent before the one that achieved an EoE diagnosis, and the use of allergy testing as part of the diagnostic workout of EoE, also reduced significantly over time (p = 0.010 and p < 0.001, respectively). The diagnostic work-up of EoE patients improved substantially over time at the European sites contributing to EoE CONNECT, with a dramatic reduction in diagnostic delay