A 24-h helpline for access to expert management advice for food allergy-related anaphylaxis in children: protocol for a pragmatic randomised controlled trial

OBJECTIVES: Anaphylaxis is an important, potentially life-threatening paediatric emergency. It is responsible for considerable morbidity and, in some cases, death. Poor outcomes may be associated with an inability to differentiate between milder and potentially more severe reactions and an associated reluctance to administer self-injectable adrenaline. This study aims to assess the effectiveness of a 24-h telephone access to specialist paediatric allergy expert advice in improving the quality of life of children and their families with potentially life-threatening food allergy (ie, anaphylaxis) compared with usual clinical care. METHODS AND ANALYSIS: Children aged less than 16 years with food allergy and who carry an adrenaline autoinjector will be recruited from the Paediatric Allergy Clinic at Cork University Hospital, Ireland and baseline disease-specific quality of life will be ascertained using the validated Food Allergy Quality of Life Questionnaire (FAQLQ). Participants will be randomised for a period of 6 months to the 24-h telephone specialist support line or usual care. The primary outcome measure of interest is a change in FAQLQ scores, which will be assessed at 0, 1 and 6 months postrandomisation. Analysis will be on an intention-to-treat basis using a 2×3 repeated measures within-between analysis of variance. Although lacking power, we will in addition assess the impact of the intervention on a range of relevant process and clinical endpoints. ETHICS AND DISSEMINATION: This trial protocol has been approved by the Clinical Research Ethics Committee of the Cork Teaching Hospitals. The findings will be presented at international scientific conferences and will be reported on in the peer-reviewed literature in early 2013

Activation and Inactivation Kinetics of Torpedo californica Acetylcholine Receptor in Reconstituted Membranes

P>Background: To date no studies have compared generic health-related quality of life (HRQL) of food allergic patients from childhood to adulthood with that of the general population or patients with other chronic diseases. The aim of this study was to compare generic HRQL of food allergic patients with the general population and other diseases. Methods: Generic HRQL questionnaires (CHQ-CF87 and RAND-36) were completed by 79 children, 74 adolescents and 72 adults with food allergy. The generic HRQL scores were compared with scores from published studies on the general population and patients with asthma, irritable bowel syndrome (IBS), diabetes mellitus (DM) and rheumatoid arthritis (RA). Results: Food allergic children and adolescents reported fewer limitations in school work due to behavioural problems (P <0.013), but food allergic adolescents and adults reported more pain (P = 0.020), poorer overall health (P <0.001), more limitations in social activities (P <0.001) and less vitality (P = 0.002) than individuals from the general population. Food allergic patients reported poorer generic HRQL than patients with DM, but better generic HRQL than patients with RA, asthma and IBS. Conclusion: HRQL is impaired in food allergic adolescents and adults, compared to the general population, and it is intermediate in magnitude between DM and RA, asthma and IBS. Children show the least impact on generic HRQL from food allergy

The impact of oral food challenges for food allergy on quality of life:a systematic review

BACKGROUND: Food allergy significantly impairs health-related quality of life (HRQL). Currently, it is still unknown whether diagnostic interventions for food allergy improve HRQL. We aim to assess the impact of diagnostic interventions for food allergy on HRQL. METHODS: A systematic search was performed in MEDLINE, Embase, Cochrane Library and CINAHL focused on patients with a (suspected) food allergy who underwent diagnostic interventions (i.e. skin prick test, specific IgE or oral food challenges (OFC)), and in whom HRQL was assessed. The mean difference between HRQL before and after the diagnostic intervention was calculated. A minimal clinically important difference of 0.5 was considered clinically relevant for the Food Allergy Quality of Life Questionnaire . RESULTS: Seven of 1465 original identified publications were included in which the impact of an OFC on HRQL was investigated (total patients n=1370). No other diagnostic interventions were investigated. Food allergy specific parent-reported HRQL improved significantly after an OFC irrespective of the outcome in children with a suspected food allergy in two publications. The change was considered clinically relevant in one of two publications. In addition, parent-reported HRQL improved after an OFC to assess the eliciting dose in children with a confirmed food allergy. The parental burden was significantly reduced after an OFC to assess resolution of food allergy. A meta-analysis could not be performed due to the limited numbers of, and considerable heterogeneity between, eligible publications. CONCLUSION: An OFC is associated with an improved food allergy specific HRQL and a reduced parental burden of food allergy. This article is protected by copyright. All rights reserved

Modeling Vesicle Traffic Reveals Unexpected Consequences for Cdc42p-Mediated Polarity Establishment

SummaryBackgroundPolarization in yeast has been proposed to involve a positive feedback loop whereby the polarity regulator Cdc42p orients actin cables, which deliver vesicles carrying Cdc42p to the polarization site. Previous mathematical models treating Cdc42p traffic as a membrane-free flux suggested that directed traffic would polarize Cdc42p, but it remained unclear whether Cdc42p would become polarized without the membrane-free simplifying assumption.ResultsWe present mathematical models that explicitly consider stochastic vesicle traffic via exocytosis and endocytosis, providing several new insights. Our findings suggest that endocytic cargo influences the timing of vesicle internalization in yeast. Moreover, our models provide quantitative support for the view that integral membrane cargo proteins would become polarized by directed vesicle traffic given the experimentally determined rates of vesicle traffic and diffusion. However, such traffic cannot effectively polarize the more rapidly diffusing Cdc42p in the model without making additional assumptions that seem implausible and lack experimental support.ConclusionsOur findings suggest that actin-directed vesicle traffic would perturb, rather than reinforce, polarization in yeast

Self-administration of adrenaline for anaphylaxis during in-hospital food challenges improves health-related quality of life

Objective To assess the impact of anaphylaxis on health-related quality of life (HRQL) and self-efficacy in food-allergic patients undergoing in-hospital food challenge. Design Secondary analysis of a randomised controlled trial. Setting Specialist allergy centre. Patients Peanut-allergic young people aged 8–16 years. Interventions Double-blind, placebo-controlled food challenge to peanut, with HRQL and self-efficacy assessed using validated questionnaire, approximately 2 weeks prior to and 2 weeks after challenge. Where possible, anaphylaxis was treated with self-injected adrenaline (epinephrine). Main outcome measures Change in HRQL and self-efficacy. Results 56 participants had reactions at food challenge, of whom 16 (29%) had anaphylaxis. Overall, there was an improvement in HRQL (mean 2.6 points (95% CI 0.3 to 4.8); p=0.030) and self-efficacy (mean 4.1 points (95% CI 2.4 to 5.9); p<0.0001), independent of whether anaphylaxis occurred. Parents also reported improved HRQL (mean 10.3 points (95% CI 5.9 to 14.7); p<0.0001). We found evidence of discordance between the improvement in HRQL and self-efficacy as reported by young people and that perceived by parents in their child. Conclusions Anaphylaxis at food challenge, followed by self-administration of injected adrenaline, was associated with an increase in HRQL and self-efficacy in young people with peanut allergy. We found no evidence that the occurrence of anaphylaxis had a detrimental effect. Young people should be encouraged to self-administer adrenaline using their autoinjector device to treat anaphylaxis at in-hospital challenge. Trial registration number NCT0214971

Peanut Allergen Threshold Study (PATS): Novel Single-dose Oral Food Challenge Study to Validate Eliciting Doses in Children with Peanut Allergy

Background: Eliciting doses (EDs) of allergenic foods can be defined by the distribution of threshold doses for subjects within a specific population. The ED05 is the dose that elicits a reaction in 5% of allergic subjects. The predicted ED05 for peanut is 1.5 mg of peanut protein (6 mg of whole peanut). Objective: We sought to validate the predicted peanut ED05 (1.5 mg) with a novel single-dose challenge. Methods: Consecutive eligible children with peanut allergy in 3 centers were prospectively invited to participate, irrespective of previous reaction severity. Predetermined criteria for objective reactions were used to identify ED05 single-dose reactors. Results: Five hundred eighteen children (mean age, 6.8 years) were eligible. No significant demographic or clinical differences were identified between 381 (74%) participants and 137 (26%) nonparticipants or between subjects recruited at each center. Three hundred seventy-eight children (206 male) completed the study. Almost half the group reported ignoring precautionary allergen labeling. Two hundred forty-five (65%) children experienced no reaction to the single dose of peanut. Sixty-seven (18%) children reported a subjective reaction without objective findings. Fifty-eight (15%) children experienced signs of a mild and transient nature that did not meet the predetermined criteria. Only 8 (2.1%; 95% CI, 0.6%–3.4%) subjects met the predetermined criteria for an objective and likely related event. No child experienced more than a mild reaction, 4 of the 8 received oral antihistamines only, and none received epinephrine. Food allergy–related quality of life improved from baseline to 1 month after challenge regardless of outcome (η2 = 0.2, P \u3c .0001). Peanut skin prick test responses and peanut- and Ara h 2-specific IgE levels were not associated with objective reactivity to peanut ED05. Conclusion: A single administration of 1.5 mg of peanut protein elicited objective reactions in fewer than the predicted 5% of patients with peanut allergy. The novel single-dose oral food challenge appears clinically safe and patient acceptable, regardless of the outcome. It identifies the most highly dose-sensitive population with food allergy not otherwise identifiable by using routinely available peanut skin prick test responses or specific IgE levels, but this single-dose approach has not yet been validated for risk assessment of individual patients

Food labeling issues for severe food allergic patients

Food allergy carries high importance and responsibility, affecting an estimated 220 million people worldwide. It is a frequent cause of food-induced anaphylaxis, a life-threatening condition requiring a toll of about one death per 50 million people a year worldwide. In order to help patients to identify allergenic foods and thus avoid anaphylactic reactions, 66 countries over the 5 continents require by law that allergenic ingredients must be declared when used in prepackaged foods. Unfortunately, the mandatory allergen list is not uniform, but varies among different countries. The widespread adoption of Precautionary Allergen Labeling (PAL) results in a proliferation of unregulated PALs with different informative statements. In this situation, the need of a scientific consensus on the definition of food allergy and the identification of a tolerable risk with routinely used detection assays, considering not only the eliciting dose but also the food source, is urgent. The aim of this manuscript is: 1) to draw a picture of the global situation in terms of PALs, and 2) to highlight new approaches that could aid in tackling the problem of regulating the labeling of allergens. These include the Voluntary Incidental Trace Allergen Labelling (VITAL) system, which intersects reference doses and labelling decisions, and a direct quantification of trace amounts of allergens at lower limit of detection (LOD) levels in the food itself through proteomics. We here highlight how, although with some limitations, the steady advances in proteomic approaches possess higher sensitivity than the recommended VITAL reference doses, allowing the identification of allergens at much lower LOD levels than VITAL. Considering that each assay used to detect allergen in food products carries method-specific issues, a more comprehensive and harmonized approach implementing both quantitative and qualitative methods could help overcoming the risk stratification approach and the overuse of PALs, offering promise as the field moves forward towards improving consumers’ quality of life

Measuring deliberate reflection in residents: validation and psychometric properties of a measurement tool

PURPOSE: Reflective capacity is the ability to understand critical analysis of knowledge and experience to achieve deeper meaning. In medicine, there is little provision for post-graduate medical education to teach deliberate reflection. The feasibility, scoring characteristics, reliability, validation, and adaptability of a modified previously validated instrument was examined for its usefulness assessing reflective capacity in residents as a step toward developing interventions for improvement. METHODS: Third-year residents and fellows from four anesthesia training programs were administered a slightly modified version of the Reflection Evaluation for Learners\u27 Enhanced Competencies Tool (REFLECT) in a prospective, observational study at the end of the 2019 academic year. Six written vignettes of imperfect anesthesia situations were created. Subjects recorded their perspectives on two randomly assigned vignettes. Responses were scored using a 5-element rubric; average scores were analyzed for psychometric properties. An independent self-report assessment method, the Cognitive Behavior Survey: Residency Level (rCBS) was used to examine construct validity. Internal consistency (ICR, Cronbach\u27s alpha) and interrater reliability (weighted kappa) were examined. Pearson correlations were used between the two measures of reflective capacity. RESULTS: 46/136 invited subjects completed 2/6 randomly assigned vignettes. Interrater agreement was high (k = 0.85). The overall average REFLECT score was 1.8 (1-4 scale) with good distribution across the range of scores. ICR for both the REFLECT score (mean 1.8, sd 0.5; α = 0.92) and the reflection scale of the rCBS (mean 4.5, sd 1.1; α = 0.94) were excellent. There was a significant correlation between REFLECT score and the rCBS reflection scale (r = .44, p \u3c 0.01). CONCLUSIONS: This study demonstrates feasibility, reliability, and sufficiently robust psychometric properties of a modified REFLECT rubric to assess graduate medical trainees\u27 reflective capacity and established construct/convergent validity to an independent measure. The instrument has the potential to assess the effectiveness of interventions intended to improve reflective capacity