Patient-relevant outcomes of stool testing in pediatric inflammatory bowel disease.

De Ziekte van Crohn en colitis ulcerosa zijn aandoeningen van het maag- en darmstelsel, en de verzamelnaam voor deze twee aandoeningen is IBD (inflammatory bowel disease). IBD wordt gekenmerkt door het komen en gaan van darmontstekingen. Tijdens actieve ziekte moet de behandeling geïntensiveerd worden. Als dit te laat of helemaal niet gedaan wordt, dan heeft de patiënt kans op voortschrijdende darmschade. Wij onderzochten of met behulp van een ontlastingstest snel kan worden herkend of een kind IBD heeft. Door gebruik te maken van de calprotectine of calgranuline C test kan de arts eenvoudig en snel voorspellen of de kans op IBD groot of klein is. Alleen kinderen met een groot risico op IBD hoeven dan een darmkijkonderzoek (endoscopie) onder narcose te ondergaan. Als de ziekte IBD bevestigd is kan de ontlastingstest calprotectine vervolgens gebruikt worden om het beloop over de tijd te volgen. Wij ontwikkelden een methode waarbij we niet alleen op basis van gerapporteerde symptomen, maar ook op basis van de calprotectine test bepaalden of een behandeling moest worden bijgestuurd. Met deze methode, IBD-live genaamd, konden tieners met IBD op afstand gevolgd worden. Via Internet werd een symptoomscore ingevuld, en het ontlastingsmonster werd per post naar het ziekenhuislaboratorium gestuurd. Via een beveiligde portal werden zowel de patiënt als de kinderarts geïnformeerd over de actuele gezondheidssituatie. Met deze nieuwe methode kunnen tieners met IBD thuisblijven als het kan, en gaan ze naar het ziekenhuis als het moet. In de toekomst kan het monitoren op afstand mogelijk nog efficiënter worden wanneer de calprotectine uitslag nog sneller bekend is. Dit zou op korte termijn al ingevoerd kunnen worden door een calprotectine thuistest die gebruik maakt van een app op de smartphone te koppelen aan het IBD-live programma. Behandeladviezen kunnen dan nog sneller beschikbaar zijn en op deze manier krijgen tieners met IBD en kinderartsen mogelijk nog meer grip op deze chronische aandoening

Exploring the Challenges of Implementing a Web-Based Telemonitoring Strategy for Teenagers With Inflammatory Bowel Disease:Empirical Case Study

Background: We designed a telemonitoring strategy for teenagers with inflammatory bowel disease to prevent an anticipated disease flare and avert unplanned office visits and day care procedures. The strategy was evaluated in a randomized controlled trial that involved 11 Dutch pediatric gastroenterology centers, each using repeated symptom scores and stool calprotectin measurements. In the telemonitoring arm of the trial, teenagers (n=84) as well as their health providers were alerted to out-of-range results, and suggestions for change in therapy were offered. We demonstrated that the technology was a safe and cost saving alternative to health checks by the specialist at fixed intervals. Objective: The aim of this study was to evaluate whether we could move our telemonitoring strategy from a demonstration project to one that is sustained within existing sites. Methods: In this empirical case study, we used the nonadoption, abandonment, scale-up, spread, and sustainability (NASSS) framework to explore the challenges to implementing our strategy. The framework distinguishes 7 domains . (1) the illness, (2) the technology, (3) the value proposition, (4) the adopter system, (5) the organization, (6) the societal system, and (7) the time dimension. We summarized the challenges across all 7 domains and classified them as simple (+++), complicated (++), or complex (+). Technologies in which multiple domains are complicated have proven difficult to implement, whereas those with multiple complex domains may not even become mainstreamed. Results: The technology that we used and the linked program (IBD-live) allowed us to select and target the teenagers who were most likely to benefit from a face-to-face encounter with their specialist (+++). The value proposition of the technology was clear, with a distinct benefit for patients and an affordable service model, but health providers had plausible personal reasons to resist (double data entry, ++). The organization was not yet ready for the innovation, as it requires a shift to new ways of working (+). We had no concerns about reimbursement, as Dutch health insurers agreed that screen-to-screen consultations will be reimbursed at a rate equivalent to face-to-face consultations (+++). Finally, the technology was considered easy to adapt and evolve over time to meet the needs of its users (+++). Conclusions: The challenges to be addressed are merely complicated (++) rather than complex (+), which means that our program may be difficult but not impossible to sustain within existing sites. After integrating the technology and its use with local workflows first, we believe that our telemonitoring strategy will be ready for sustained adoption. In contrast with what we did ourselves, we recommend others to use the NASSS framework prospectively and in real time to predict and explore the challenges to implementing new technologies

Regulatory T Cells Facilitate Thymic Recovery After HSCT by Directly Enhancing Immigration of Donor Derived Thymic Progenitors

BACKGROUND & AIMS: An increasing number of physicians use repeated measurements of stool calprotectin to monitor intestinal inflammation in patients with inflammatory bowel diseases (IBDs). A lateral flow-based rapid test allows patients to measure their own stool calprotectin values at home. The test comes with a software application (IBDoc; Buhlmann Laboratories AG, Schonenbuch, Switzerland) that turns a smartphone camera into a results reader. We compared results from this method with those from the hospital-based reader (Quantum Blue; Buhlmann Laboratories AG) and enzyme-linked immunosorbent assay (ELISA) analysis. METHODS: In a single-center comparison study, we asked 101 participants (10 years of age or older) in the Netherlands to perform the IBDoc measurement on stool samples collected at home, from June 2015 to October 2016. Participants then sent the residual extraction fluid and a fresh specimen from the same bowel movement to our pediatric and adult IBD center at the University Medical Center Groningen, where the level of calprotectin was measured by the Quantum Blue reader and ELISA analysis, respectively. The primary outcome was the agreement of results between IBDoc and the Quantum Blue and ELISA analyses, determined by Bland-Altman plot analysis. RESULTS: We received 152 IBDoc results, 138 samples of residual extraction fluid for Quantum Blue analysis, and 170 fresh stool samples for ELISA analysis. Spearman's rank correlation coefficient was 0.94 for results obtained by IBDoc vs Quantum Blue and 0.85 for results obtained by IBDoc vs ELISA. At the low range of calprotectin level (= 100 mu g/g), and 71% of IBDoc-ELISA results were in agreement. At the high range of calprotectin level (>= 500 mu g/g), 81% of IBDoc-Quantum Blue results were within the predefined limits of agreement (+/- 200 mu g/g) and 64% of IBDoc-ELISA results were in agreement. CONCLUSIONS: Measurements of fecal levels of calprotectin made with home-based lateral flow method were in agreement with measurements made by Quantum Blue and ELISA, as long as concentrations wer

Clinical Utility of Fecal Calprotectin Monitoring in Asymptomatic Patients with Inflammatory Bowel Disease:A Systematic Review and Practical Guide

Background: In asymptomatic patients with inflammatory bowel disease (IBD), "monitoring" involves repeated testing aimed at early recognition of disease exacerbation. We aimed to determine the usefulness of repeated fecal calprotectin (FC) measurements to predict IBD relapses by a systematic literature review. Methods: An electronic search was performed in Medline, Embase, and Cochrane from inception to April 2016. Inclusion criteria were prospective studies that followed patients with IBD in remission at baseline and had at least 2 consecutive FC measurements with a test interval of 2 weeks to 6 months. Methodological assessment was based on the second Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) checklist. Results: A total of 1719 articles were identified; 193 were retrieved for full text review. Six studies met eligibility for inclusion. The time interval between FC tests varied between 1 and 3 months. Asymptomatic patients with IBD who had repeated FC measurements above the study's cutoff level had a 53% to 83% probability of developing disease relapse within the next 2 to 3 months. Patients with repeated normal FC values had a 67% to 94% probability to remain in remission in the next 2 to 3 months. The ideal FC cutoff for monitoring could not be identified because of the limited number studies meeting inclusion criteria and heterogeneity between selected studies. Conclusions: Two consecutively elevated FC values are highly associated with disease relapse, indicating a consideration to proactively optimize IBD therapy plans. More prospective data are necessary to assess whether FC monitoring improves health outcomes

Selecting children with suspected inflammatory bowel disease for endoscopy with the calgranulin C or calprotectin stool test:Protocol of the CACATU study

Introduction The introduction of the faecal calprotectin (FC) test to screen children with chronic gastrointestinal complaints has helped the clinician to decide whether or not to subject the patient to endoscopy. In spite of this, a considerable number of patients without inflammatory bowel disease (IBD) is still scoped. Faecal calgranulin C (S100A12) is a marker of intestinal inflammation that is potentially more specific for IBD than FC, as it is exclusively released by activated granulocytes. Objective To determine whether the specificity of S100A12 is superior to the specificity of FC without sacrificing sensitivity in patients with suspected IBD. Methods An international prospective cohort of children with suspected IBD will be screened with the existing FC stool test and the new S100A12 stool test. The reference standard (endoscopy with biopsies) will be applied to patients at high risk of IBD, while a secondary reference (clinical follow-up) will be applied to those at low risk of IBD. The differences in specificity and sensitivity between the two markers will be calculated. Ethics and dissemination This study is submitted to and approved by the Medical Ethics Review Committee of the University Medical Center Groningen (the Netherlands) and the Antwerp University Hospital (Belgium). The results will be disseminated through a peer-reviewed publication, conference presentation and incorporation in the upcoming National Guideline on Diagnosis and Therapy of IBD in Children

Assessing the Immunomodulatory Effect of Size on the Uptake and Immunogenicity of Influenza- and Hepatitis B Subunit Vaccines In Vitro

Viral subunit vaccines are a safer and more tolerable alternative to whole inactivated virus vaccines. However, they often come with limited efficacy, necessitating the use of adjuvants. Using free and particle-bound viral antigens, we assessed whether size affects the uptake of those antigens by human monocyte-derived dendritic cells (Mo-DCs) and whether differences in uptake affect their capacity to stimulate cytokine production by T cells. To this end, influenza antigens and hepatitis B surface antigen (HBsAg) were covalently conjugated to polystyrene particles of 500 nm and 3 μm. Cellular uptake of the antigens, either unconjugated or conjugated, and their capacity to stimulate T cells within a population of human peripheral blood mononuclear cells (PBMCs) were measured by flow cytometry. Conjugation of both antigens to particles significantly increased their uptake by Mo-DCs. Moreover, both the 500 nm and 3 μm influenza conjugates induced significantly higher numbers of cytokine-producing CD4+ T cells and induced increased production of the pro-inflammatory cytokines IFNγ and TNFα. In contrast, conjugation of HBsAg to particles did not notably affect the T cell response. In conclusion, conjugation of antigen to 500 nm and 3 μm particles leads to increased antigen uptake by human Mo-DCs, although the capacity of such conjugates to induce T cell stimulation likely depends on the immunological status of the PBMC donor