Core outcome measurement set for research and clinical practice in post-COVID-19 condition (long COVID) in children and young people: an international Delphi consensus study "PC-COS Children".

The coronavirus disease 2019 (COVID-19) pandemic substantially impacted different age groups, with children and young people not exempted. Many have experienced enduring health consequences. Presently, there is no consensus on the health outcomes to assess in children and young people with post-COVID-19 condition. Furthermore, it is unclear which measurement instruments are appropriate for use in research and clinical management of children and young people with post-COVID-19. To address these unmet needs, we conducted a consensus study, aiming to develop a core outcome set (COS) and an associated core outcome measurement set (COMS) for evaluating post-COVID-19 condition in children and young people. Our methodology comprised of two phases. In phase 1 (to create a COS), we performed an extensive literature review and categorisation of outcomes, and prioritised those outcomes in a two-round online modified Delphi process followed by a consensus meeting. In phase 2 (to create the COMS), we performed another modified Delphi consensus process to evaluate measurement instruments for previously defined core outcomes from phase 1, followed by an online consensus workshop to finalise recommendations regarding the most appropriate instruments for each core outcome. In phase 1, 214 participants from 37 countries participated, with 154 (72%) contributing to both Delphi rounds. The subsequent online consensus meeting resulted in a final COS which encompassed seven critical outcomes: fatigue; post-exertion symptoms; work/occupational and study changes; as well as functional changes, symptoms, and conditions relating to cardiovascular, neuro-cognitive, gastrointestinal and physical outcomes. In phase 2, 11 international experts were involved in a modified Delphi process, selecting measurement instruments for a subsequent online consensus workshop where 30 voting participants discussed and independently scored the selected instruments. As a result of this consensus process, four instruments met a priori consensus criteria for inclusion: PedsQL multidimensional fatigue scale for "fatigue"; PedsQL gastrointestinal symptom scales for "gastrointestinal"; PedsQL cognitive functioning scale for "neurocognitive" and EQ-5D for "physical functioning". Despite proposing outcome measurement instruments for the remaining three core outcomes ("cardiovascular", "post-exertional malaise", "work/occupational and study changes"), a consensus was not achieved. Our international, consensus-based initiative presents a robust framework for evaluating post-COVID-19 condition in children and young people in research and clinical practice via a rigorously defined COS and associated COMS. It will aid in the uniform measurement and reporting of relevant health outcomes worldwide.

Evaluation of clinical outcomes of efficacy in food allergen immunotherapy trials, COFAITH EAACI task force.

Food allergy is a global public health problem that until recent years lacked any aetiological treatment supported by academy, industry and regulators. Food immunotherapy (AIT) is an evolving treatment option, supported by clinical practice and industry trial data. Recent AIT meta-analyses have highlighted the difficulty in pooling safety and efficacy data from AIT trials, due to secondary heterogeneity in the study. An EAACI task force (CO-FAITH) initiated by the Paediatric Section was created to focus on AIT efficacy outcomes for milk, egg and peanut allergy rather than in trial results. A systematic search and a narrative review of AIT controlled clinical trials and large case series was conducted. A total of 63 manuscripts met inclusion criteria, corresponding to 23, 21 and 22 studies of milk, egg and peanut AIT, respectively. The most common AIT efficacy outcome was desensitization, mostly defined as tolerating a maintenance phase dose, or reaching a particular dose upon successful exit oral food challenge (OFC). However, a large degree of heterogeneity was identified regarding the dose quantity defining this outcome. Sustained unresponsiveness and patient-reported outcomes (e.g. quality of life) were explored less frequently, and to date have been most rigorously described for peanut AIT versus other allergens. Change in allergen threshold assessed by OFC remains the most common efficacy measure, but OFC methods suffer from heterogeneity and methodological disparity. This review has identified multiple heterogeneous outcomes related to measuring the efficacy of AIT. Efforts to better standardize and harmonize which outcomes, and how to measure them must be carried out to help in the clinical development of safe and efficacious food allergy treatments.

Telemedicine with special focus on allergic diseases and asthma-Status 2022: An EAACI position paper.

Efficacious, effective and efficient communication between healthcare professionals (HCP) and patients is essential to achieve a successful therapeutic alliance. Telemedicine (TM) has been used for decades but during the COVID-19 pandemic its use has become widespread. This position paper aims to describe the terminology and most important forms of TM among HCP and patients and review the existing studies on the uses of TM for asthma and allergy. Besides, the advantages and risks of TM are discussed, concluding that TM application reduces costs and time for both, HCP and patients, but cannot completely replace face-to-face visits for physical examinations and certain tests that are critical in asthma and allergy. From an ethical point of view, it is important to identify those involved in the TM process, ensure confidentiality and use communication channels that fully guarantee the security of the information. Unmet needs and directions for the future regarding implementation, data protection, privacy regulations, methodology and efficacy are described.

EAACI guidelines on the diagnosis of IgE-mediated food allergy.

This European Academy of Allergy and Clinical Immunology guideline provides recommendations for diagnosing IgE-mediated food allergy and was developed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Food allergy diagnosis starts with an allergy-focused clinical history followed by tests to determine IgE sensitization, such as serum allergen-specific IgE (sIgE) and skin prick test (SPT), and the basophil activation test (BAT), if available. Evidence for IgE sensitization should be sought for any suspected foods. The diagnosis of allergy to some foods, such as peanut and cashew nut, is well supported by SPT and serum sIgE, whereas there are less data and the performance of these tests is poorer for other foods, such as wheat and soya. The measurement of sIgE to allergen components such as Ara h 2 from peanut, Cor a 14 from hazelnut and Ana o 3 from cashew can be useful to further support the diagnosis, especially in pollen-sensitized individuals. BAT to peanut and sesame can be used additionally. The reference standard for food allergy diagnosis is the oral food challenge (OFC). OFC should be performed in equivocal cases. For practical reasons, open challenges are suitable in most cases. Reassessment of food allergic children with allergy tests and/or OFCs periodically over time will enable reintroduction of food into the diet in the case of spontaneous acquisition of oral tolerance.

WAO consensus on DEfinition of Food Allergy SEverity (DEFASE).

Background: While several scoring systems for the severity of anaphylactic reactions have been developed, there is a lack of consensus on definition and categorisation of severity of food allergy disease as a whole. Aim: To develop an international consensus on the severity of food allergy (DEfinition of Food Allergy Severity, DEFASE) scoring system, to be used globally. Methods Phase 1: We conducted a mixed-method systematic review (SR) of 11 databases for published and unpublished literature on severity of food allergy management and set up a panel of international experts. Phase 2: Based on our findings in Phase 1, we drafted statements for a two-round modified electronic Delphi (e-Delphi) survey. A purposefully selected multidisciplinary international expert panel on food allergy (n = 60) was identified and sent a structured questionnaire, including a set of statements on different domains of food allergy severity related to symptoms, health-related quality of life, and economic impact. Participants were asked to score their agreement on each statement on a 5-point Likert scale ranging from "strongly agree" to "strongly disagree". Median scores and percentage agreements were calculated. Consensus was defined a priori as being achieved if 70% or more of panel members rated a statement as "strongly agree" to "agree" after the second round. Based on feedback, 2 additional online voting rounds were conducted. Results: We received responses from 92% of Delphi panel members in round 1 and 85% in round 2. Consensus was achieved on the overall score and in all of the 5 specific key domains as essential components of the DEFASE score. Conclusions: The DEFASE score is the first comprehensive grading of food allergy severity that considers not only the severity of a single reaction, but the whole disease spectrum. An international consensus has been achieved regarding a scoring system for food allergy disease. It offers an evaluation grid, which may help to rate the severity of food allergy. Phase 3 will involve validating the scoring system in research settings, and implementing it in clinical practice.

Managing food allergy: GA2LEN guideline 2022.

Food allergy affects approximately 2-4% of children and adults. This guideline provides recommendations for managing food allergy from the Global Allergy and Asthma European Network (GA2LEN). A multidisciplinary international Task Force developed the guideline using the Appraisal of Guidelines for Research and Evaluation (AGREE) II framework and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We reviewed the latest available evidence as of April 2021 (161 studies) and created recommendations by balancing benefits, harms, feasibility, and patient and clinician experiences. We suggest that people diagnosed with food allergy avoid triggering allergens (low certainty evidence). We suggest that infants with cow's milk allergy who need a breastmilk alternative use either hypoallergenic extensively hydrolyzed cow's milk formula or an amino acid-based formula (moderate certainty). For selected children with peanut allergy, we recommend oral immunotherapy (high certainty), though epicutaneous immunotherapy might be considered depending on individual preferences and availability (moderate certainty). We suggest considering oral immunotherapy for children with persistent severe hen's egg or cow's milk allergy (moderate certainty). There are significant gaps in evidence about safety and effectiveness of the various strategies. Research is needed to determine the best approaches to education, how to predict the risk of severe reactions, whether immunotherapy is cost-effective and whether biological therapies are effective alone or combined with allergen immunotherapy.

Measuring the Impact of Food Immunotherapy on Health-Related Quality of Life in Clinical Trials.

Food allergy is a common, and often lifelong, disorder with considerable negative impact on the quality of life of those affected and their families. While several promising immunotherapies for food allergy have either been approved or are in late-phase clinical trials based on demonstrated effectiveness at inducing desensitization, evidence of benefit in terms of improving patient-centered outcomes is inconsistent. Historically, health-related quality of life has not been prioritized as an endpoint in food immunotherapy trials and, even when included, findings have been undermined by methodological limitations of the measurement instruments used and issues with data interpretation. This review highlights the importance of measuring health-related quality of life as an endpoint in food immunotherapy trials and discusses the strengths and limitations of available evidence in this regard, with a focus on the appropriate use of assessment instruments and interpretation of findings. There remains much to learn regarding the impact of food immunotherapies on patient wellbeing, both during treatment and over the longer term. Our aim is to assist clinicians, researchers, policy makers and consumers in their interpretation of the existing literature, and to promote greater scientific rigor in the design and selection of outcome measurement frameworks for future studies evaluating the efficacy of immunotherapy treatments for food allergy.

A multi-disciplinary approach to the diagnosis and management of allergic diseases: An EAACI Task Force.

BACKGROUND: Guidelines for management of patients with allergic conditions are available, but the added value of nurses, allied healthcare professionals (AHPs), and general practitioners (GPs), in the management of allergic disease, has not been fully clarified. The European Academy of Allergy and Clinical Immunology (EAACI) appointed a task force to explore this issue. AIM: To investigate the added value of nurses, AHPs, and GPs in management of allergic diseases, in an integrated model of care. METHODS: A search was made of peer-reviewed literature published between 2010 and December 2020 (Cochrane Library, PubMed, and CINAHL) on the involvement of the various specific healthcare providers (HCPs) in the management of allergic diseases. RESULTS: Facilitative models of care for patients with allergies can be achieved if HCP collaborates in the diagnosis and management. Working in multi-disciplinary teams (MDT) can increase patients' understanding of the disease, adherence to treatment, self-care capabilities, and ultimately improve quality of life. The MDT competencies and procedures can be improved and enhanced in a climate of mutual respect and shared values, and with inclusion of patients in the planning of care. Patient-centered communication among HCPs and emphasis on the added value of each profession can create an effective integrated model of care for patients with allergic diseases. CONCLUSION: Nurses, AHPs, and GPs, both individually and in collaboration, can contribute to the improvement of the management of patients with allergic disease. The interaction between the HCPs and the patients themselves can ensure maximum support for people with allergies.

Proposal of 0.5 mg of protein/100 g of processed food as threshold for voluntary declaration of food allergen traces in processed food-A first step in an initiative to better inform patients and avoid fatal allergic reactions: A GA²LEN position paper.

BACKGROUND: Food anaphylaxis is commonly elicited by unintentional ingestion of foods containing the allergen above the tolerance threshold level of the individual. While labeling the 14 main allergens used as ingredients in food products is mandatory in the EU, there is no legal definition of declaring potential contaminants. Precautionary allergen labeling such as "may contain traces of" is often used. However, this is unsatisfactory for consumers as they get no information if the contamination is below their personal threshold. In discussions with the food industry and technologists, it was suggested to use a voluntary declaration indicating that all declared contaminants are below a threshold of 0.5 mg protein per 100 g of food. This concentration is known to be below the threshold of most patients, and it can be technically guaranteed in most food production. However, it was also important to assess that in case of accidental ingestion of contaminants below this threshold by highly allergic patients, no fatal anaphylactic reaction could occur. Therefore, we performed a systematic review to assess whether a fatal reaction to 5mg of protein or less has been reported, assuming that a maximum portion size of 1kg of a processed food exceeds any meal and thus gives a sufficient safety margin. METHODS: MEDLINE and EMBASE were searched until 24 January 2021 for provocation studies and case reports in which one of the 14 major food allergens was reported to elicit fatal or life-threatening anaphylactic reactions and assessed if these occurred below the ingestion of 5mg of protein. A Delphi process was performed to obtain an expert consensus on the results. RESULTS: In the 210 studies included, in our search, no reports of fatal anaphylactic reactions reported below 5 mg protein ingested were identified. However, in provocation studies and case reports, severe reactions below 5 mg were reported for the following allergens: eggs, fish, lupin, milk, nuts, peanuts, soy, and sesame seeds. CONCLUSION: Based on the literature studied for this review, it can be stated that cross-contamination of the 14 major food allergens below 0.5 mg/100 g is likely not to endanger most food allergic patients when a standard portion of food is consumed. We propose to use the statement "this product contains the named allergens in the list of ingredients, it may contain traces of other contaminations (to be named, e.g. nut) at concentrations less than 0.5 mg per 100 g of this product" for a voluntary declaration on processed food packages. This level of avoidance of cross-contaminations can be achieved technically for most processed foods, and the statement would be a clear and helpful message to the consumers. However, it is clearly acknowledged that a voluntary declaration is only a first step to a legally binding solution. For this, further research on threshold levels is encouraged.

Dissemination of EAACI food allergy guidelines using a flexible, practical, whole school allergy awareness toolkit.

BACKGROUND: Essential training for emergency adrenaline auto-injector administration alone provides an inadequate safeguard in school environments. Recent UK deaths have reinforced the urgency for embedding whole school (WS) allergy awareness to minimise risk. We documented the development of a practical, flexible WS Food Allergy Awareness Toolkit for UK secondary schools. METHODS: We used a multidisciplinary participatory action research methodology, involving successive modification and retesting of a pragmatic toolkit in 3 case study schools. A School Allergy Action Group drives WS risk assessment, helping schools gradually implement best practice policy in line with their particular needs. Additional schools self-piloted the resulting toolkit with only remote monitoring. School surveys, based on EAACI guidelines were developed to identify priorities and assess change. RESULTS: Effectiveness of the resulting process toolkit, now available online, was independently demonstrated via pre/post-intervention questionnaires from 24/10 pupils with food allergy (FA) and 97/6 pupils without FA, respectively. Pearson correlational analysis showed strong negative relationships between Food Allergy Quality of Life Questionnaire (FAQLQ) at T0 and School Support (SS) at T0 (r = -0.8, P<0.01), and between SS and Self-Efficacy (SE) (r = 0.73, P<0.05). Mean FAQLQ scores improved between T0 (3.3) and T1 (2.5). SE improved for those with FA (mean difference = 1.0). In those without FA, SE (mean difference = 0.9) and Attitudes and Knowledge (mean difference = 0.7) also improved. CONCLUSIONS: Full stakeholder involvement in toolkit development encourages usage and, therefore, improves WS community awareness; reduces risk of reactions; fosters a more accepting societal attitude and empowers pupils with/without allergies to self-manage effectively.

Consensus on DEfinition of Food Allergy SEverity (DEFASE) an integrated mixed methods systematic review.

BACKGROUND AND AIMS: The term "Food Allergy" refers to a complex global health problem with a wide spectrum of severity. However, a uniform definition of severe food allergy is currently missing. This systematic review is the preliminary step towards a state-of-the-art synopsis of the current evidence relating to the severity of IgE-mediated food allergy; it will inform attempts to develop a consensus to define food allergy severity by clinicians and other stakeholders. METHODS: We undertook a mixed-methods systematic review, which involved searching 11 international biomedical databases for published studies from inception to 31 December 2019. Studies were independently screened against pre-defined eligibility criteria and critically appraised by established instruments. The substantial heterogeneity of included studies precluded meta-analyses and, therefore, narrative synthesis of quantitative and qualitative data was performed. RESULTS: We found 23 studies providing eligible primary data on symptom-specific severity of food allergic reactions, and 31 previously published symptom-severity scoring systems referred to food allergic reactions. There were seven studies which assessed quality-of-life measures in patients (and family members) with different food allergy severity and two studies that investigated the economic burden of food allergy severity. Overall, the quality and the global rating of all included studies were judged as being moderate. CONCLUSIONS: There is heterogeneity among severity scoring systems used and even outcomes considered in the context of severity of food allergy. No score has been validated. Our results will be used to inform the development of an international consensus to define the severity of food allergy. SYSTEMATIC REVIEW REGISTRATION: A protocol was prospectively registered with the International Prospective Register of Systematic Reviews (PROSPERO) database with the registration number CRD42020183103 (https://www.crd.york.ac.uk/prospero/#recordDetails).

The Psychosocial Burden of Food Allergy Among Adults: A US Population-Based Study.

BACKGROUND: Food allergy (FA) affects >25 million US adults, resulting in substantial health care utilization. Data suggest that patients with FA suffer impairments in FA-related quality of life (FAQoL); however, little is known regarding psychosocial impacts of FA among US adults. OBJECTIVE: To characterize FAQoL among a large, nationally representative adult sample, and its determinants, including sociodemographic characteristics, severity, comorbid conditions, allergic symptoms, number and type of allergens, and health care utilization. METHODS: A survey was administered between October 2015 and September 2016 to a nationally representative sample of US households. Survey constructs included the Food Allergy Independent Measure (FAIM), which was developed to quantify adverse impacts of living with FA on patient quality of life. FAIM responses were analyzed from adults reporting current FA (N = 6207). Linear regression models examined associations with sociodemographic and FA characteristics. RESULTS: The overall estimated mean FAIM score was 2.87 (95% confidence interval: 2.83-2.90). FAIM scores (range = 1-7) in adjusted models were invariant by race/ethnicity, private/public insurance status, and census division. Significant differences (P < .05) by lower household income, lower age, and greater education emerged, resulting in higher FAIM scores indicating FAQoL impairment. Among major food allergens, wheat, soy, and milk allergies were each associated with the greatest increases in adjusted FAIM scores. Reporting a current epinephrine autoinjector (EAI) prescription, severe allergic reaction history, history of EAI use, FA-related emergency department visits, or more FAs were also associated with significantly higher FAIM scores. CONCLUSION: The population-level psychosocial burden of adults with FA is substantial, broadly distributed, and differs by demographic and allergic disease characteristics.

Consensus on DEfinition of Food Allergy SEverity (DEFASE): Protocol for a systematic review.

BACKGROUND AND AIMS: The term "Food Allergy" refers to a complex global health problem with a wide spectrum of severity. However, a uniform definition of severe food allergy is currently missing. This systematic review is the preliminary step towards a state-of-the-art synopsis of the current evidence relating to the severity of IgE-mediated food allergy; it will inform attempts to develop a consensus to define food allergy severity by clinicians and other stakeholders. METHODS: We will undertake a systematic review, which will involve searching international biomedical databases for published studies. Studies will be independently screened against pre-defined eligibility criteria and critically appraised by established instruments. Data will be descriptively and, if possible and applicable, quantitatively synthesised. ETHICS AND DISSEMINATION: This study does not require any specific ethical approval since it is a systematic review. We plan to report results from this systematic review in a peer reviewed journal. These results will be used to inform the development of an international consensus to define severe food allergy. Author's potential conflicts of interest are clearly stated. PROSPERO REGISTRATION NUMBER: CRD42020183103.

Effectiveness of a trauma-informed care psychoeducational program for foster carers - Evaluation of the Fostering Connections Program.

BACKGROUND: The need to improve the quality of foster care training has been highlighted and evidenced-based programs that aim to support foster carers in the care of children who have experienced trauma are warranted. OBJECTIVE: This study aimed to evaluate the effectiveness of the Fostering Connections program, a newly developed trauma-informed care program within the national child welfare agency in Ireland. PARTICIPANTS AND SETTING: The study included 79 foster carers. The Fostering Connections group-based experiential intervention was delivered over a period of 6-weeks in a community-based setting to intervention group participants. METHODS: A quasi-experimental design was used to compare the results of the intervention group (n = 49), to a control group (n = 30,) who received usual care. Standardized assessment measures were used at baseline, 6-weeks on completion, 16 weeks and 15 months post-intervention. Foster carers' knowledge of trauma-informed fostering, tolerance of misbehavior and fostering efficacy, and children's emotional and behavioral difficulties were assessed. RESULTS: Significant improvements were found in foster carers' knowledge of trauma-informed fostering (p < 0.001), tolerance of child misbehavior (p = 0.007) and fostering efficacy (p < 0.001), with effect sizes ranging from medium to large and sustained over fifteen months (ES = 0.07-0.14). Significant improvement was also found in children's emotional and behavioral difficulties at fifteen months (p = 0.019), with a small effect size (ES = 0.05). CONCLUSION: Preliminary evidence suggests that Fostering Connections is potentially an effective intervention in increasing foster carer's capacity to provide children with trauma-informed care.

Identifying and managing patients at risk of severe allergic reactions to food: Report from two iFAAM workshops.

Food allergy affects a small but important number of children and adults. Much of the morbidity associated with food allergy is driven by the fear of a severe reaction and fatalities continue to occur. Foods are the commonest cause of anaphylaxis. One of the aims of the European Union-funded Integrated Approaches to Food Allergen and Allergy Risk Management (iFAAM) project was to improve the identification and management of children and adults at risk of experiencing a severe reaction. A number of interconnected studies within the project have focused on quantifying the severity of allergic reactions; the impact of food matrix, immunological factors on severity of reactions; the impact of co-factors such as medications on the severity of reactions; utilizing single-dose challenges to understand threshold and severity of reactions; and community studies to understand the experience of patients suffering real-life allergic reactions to food. Associated studies have examined population thresholds and co-factors such as exercise and stress. This paper summarizes two workshops focused on the severity of allergic reactions to food. It outlines the related studies being undertaken in the project indicating how they are likely to impact on our ability to identify individuals at risk of severe reactions and improve their management.

Health-Related Quality of Life in Children and Adults with Primary Immunodeficiencies: A Systematic Review and Meta-Analysis.

BACKGROUND: Primary immunodeficiency diseases (PIDs) are a group of diseases that have been found to have an adverse impact on quality of life and health-related quality of life (HRQOL). OBJECTIVE: To systematically assess available evidence on the HRQOL of patients with PID. METHODS: We performed a literature search of all studies reporting HRQOL assessments in patients with PID published in English from inception to April 11, 2017, using MEDLINE and EMBASE. RESULTS: Of 1699 articles, 37 met the inclusion criteria. HRQOL was assessed by using various generic instruments. Child Health Questionnaire - Parent Form 50 and short-form 36 were the most frequently used (for children and adults, respectively). No PID-specific HRQOL instruments were used for children. HRQOL is significantly lower in adults with PID (mean score difference, -24.46; 95% CI, -34.57 to -14.34) and children (-10.06; 95% CI, -12.95 to -7.17) compared with the reference population and lower than in patients with other chronic conditions. There is a general agreement between child- and parent-reported data, although parents report child school-related HRQOL as more impaired than do children (6.19; 95% CI, 0.38 to 11.99). Most studies were of low to moderate quality and had methodological limitations. CONCLUSIONS: Available evidence suggests that patients with PID have a lower HRQOL than do healthy individuals and patients with other chronic conditions, including diabetes mellitus and juvenile idiopathic arthritis. No disease-specific instruments are available for children, and few options are available for adults. This finding highlights the need for developing PID-specific instruments that would allow for a more sensitive evaluation of PID impact on patient health and psychological well-being, school/work, and social activities.