The role of regulatory B cells in allergen immunotherapy

PURPOSE OF REVIEW Allergen immunotherapy (AIT) is currently the only curative treatment available for allergic diseases, and has been used in clinical practice for over a century. Induction and maintenance of immune tolerance to nonhazardous environmental and self-antigens is essential to maintain homeostasis and prevent chronic inflammation. Regulatory B (BREG) cells are immunoregulatory cells that protect against chronic inflammatory responses primarily through production of anti-inflammatory cytokines such as IL-10, transforming growth factor-β, and IL-35. The importance of BREG cells has been extensively demonstrated in the context of autoimmune diseases. Data showing their role in the regulation of allergic responses are slowly accumulating. This review summarizes recent findings relevant to the topic of BREG cells and their potential role in AIT. RECENT FINDINGS BREG cells support AIT in models of allergic airway inflammation and intestinal inflammation through induction of regulatory T (TREG) cells. In humans BREG frequency increases during venom immunotherapy while the phenotype of allergen-specific B cells changes. Mechanisms of BREG-mediated tolerance to allergens include IL-10-mediated suppression of effector T cell, including TH2 responses, induction of TREG cells, IL-10-mediated inhibition of Dendritic cell maturation, modulation of T follicular helper responses, and production of anti-inflammatory IgG4 antibodies. SUMMARY Current evidence supports a potential role for BREG cells in induction and maintenance of allergen tolerance during AIT. A better understanding of the role of B cells and BREG cells in AIT could open potential new windows for developing targeted therapies specifically focused on promoting BREG responses during AIT

Teachers grading practice: an analysis of the reliability of teacher-assigned grade point average (GPA)

In eerder onderzoek wordt gesteld dat docenten subjectieve beoordelaars zijn die zich bij het geven van cijfers niet beperken tot het becijferen van alleen de leerlingvaardigheid, maar cijfers geven voor een mengelmoes (‘hodgepodge’) van eigenschappen: de ‘hodgepodge’hypothese. Ook zouden docenten verschillen in mildheid; de mildheidshypothese. In dit onderzoek worden deze beide hypothesen onderzocht. Voor dit onderzoek zijn bij twee steekproeven proefwerkcijfers verzameld. De eerste steekproef telt 5988 proefwerkcijfers gegeven aan 192 leerlingen gedurende één schooljaar door 64 docenten. De tweede steekproef telt 29462 proefwerkcijfers gegeven aan 306 leerlingen gedurende drie opeenvolgende schooljaren door 52 docenten. Om de beoordelingsbias te onderzoeken werden een G-studie en D-studie uitgevoerd. De resultaten geven geen overtuigend bewijs voor de twee hypotheses. In het algemeen blijkt dat rapportcijfers een redelijk betrouwbaar onderscheid maken tussen minder en meer vaardige leerlingen (Eρ2 ≥ .70) en een betrouwbare beoordeling geven over de cesuur voldoende-onvoldoende (Φλ ≈ .90). Wanneer rapportcijfers op minder dan 8 proefwerken zijn gebaseerd dan is de betrouwbaarheid lager dan het criterium .70. Een aanzienlijk deel van de onbetrouwbaarheid in beoordeling kan worden verklaard door verschillen in de kwaliteit van de proefwerken en niet door mildheid of hodgepodgegedrag in de beoordeling van docenten

Association between workarounds and medication administration errors in bar-code-assisted medication administration in hospitals

Objective: To study the association of workarounds with medication administration errors using barcode-assisted medication administration (BCMA), and to determine the frequency and types of workarounds and medication administration errors. Materials and Methods: A prospective observational study in Dutch hospitals using BCMA to administer medication. Direct observation was used to collect data. Primary outcome measure was the proportion of medication administrations with one or more medication administration errors. Secondary outcome was the frequency and types of workarounds and medication administration errors. Univariate and multivariate multilevel logistic regression analysis were used to assess the association between workarounds and medication administration errors. Descriptive statistics were used for the secondary outcomes. Results: We included 5793 medication administrations for 1230 inpatients. Workarounds were associated with medication administration errors (adjusted odds ratio 3.06 [95% CI: 2.49-3.78]). Most commonly, procedural workarounds were observed, such as not scanning at all (36%), not scanning patients because they did not wear a wristband (28%), incorrect medication scanning, multiple medication scanning, and ignoring alert signals (11%). Common types of medication administration errors were omissions (78%), administration of non-ordered drugs (8.0%), and wrong doses given (6.0%). Discussion: Workarounds are associated with medication administration errors in hospitals using BCMA. These data suggest that BCMA needs more post-implementation evaluation if it is to achieve the intended benefits for medication safety. Conclusion: In hospitals using barcode-assisted medication administration, workarounds occurred in 66% of medication administrations and were associated with large numbers of medication administration errors

Progressive myoclonus ataxia:Time for a new definition?

BACKGROUND: The clinical demarcation of the syndrome progressive myoclonus ataxia is unclear, leading to a lack of recognition and difficult differentiation from other neurological syndromes. OBJECTIVES: The objective of this study was to apply a refined definition of progressive myoclonus ataxia and describe the clinical characteristics in patients with progressive myoclonus ataxia and with isolated cortical myoclonus. METHODS: A retro- and prospective analysis was performed in our tertiary referral center between 1994 and 2014. Inclusion criteria for progressive myoclonus ataxia patients were the presence of myoclonus and ataxia with or without infrequent (all types, treatment responsive) epileptic seizures. Inclusion criteria for isolated cortical myoclonus was the presence of isolated cortical myoclonus. Clinical and electrophysiological characteristics data were systematically scored. RESULTS: A total of 14 progressive myoclonus ataxia patients (males, 7; females, 7), median age 14.5 years, and 8 isolated cortical myoclonus patients (males, 2; females, 6), median age 23.5 years, were identified. In 93% of the progressive myoclonus ataxia patients, ataxia started first (median 2 years) followed by myoclonus (4 years) and finally infrequent epilepsy (9.3 years), with a progressive course in 93%. In 64% of the progressive myoclonus ataxia patients, a genetic underlying etiology was identified, including 3 not earlier reported causative progressive myoclonus ataxia genes. In isolated cortical myoclonus patients, myoclonus started at (median) 12 years with progression over time in 63% and a single epileptic seizure in 1 patient. No genetic causes were identified. CONCLUSION: Using a refined definition, we could create a rather homogenous progressive myoclonus ataxia group. Patients with isolated cortical myoclonus have a different course and do not appear to evolve in progressive myoclonus ataxia. The refined progressive myoclonus ataxia definition is a successful first step toward creating a separate syndrome for both clinical practice and future genetic research. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society

Mechanisms and biomarkers of successful allergen-specific immunotherapy

Allergen-specific immunotherapy (AIT) is considered the only curative treatment for allergic diseases mediated by immunoglobulin E (IgE). Currently, the route of administration depends both on the different types of causal allergens and on its effectiveness and safety profile. Several studies have reported the mechanisms and changes in humoral and cellular response underlying AIT; however, the full picture remains unknown. Knowledge of who can benefit from this type of treatment is urgently needed due to the patient safety risks and costs of AIT. In vivo or in vitro biomarkers have become a strategy to predict clinical outcomes in precision medicine. There are currently no standardized biomarkers that allow determining successful responses to AIT, however, some studies have found differences between responders and nonresponders. In addition, different candidates have been postulated that may have the potential to become biomarkers. In this review, we aim to summarize the findings to date related to biomarkers in different IgE-mediated allergic diseases (respiratory, food, and venom allergy) with the potential to define who will benefit from AIT