Determining Levers of Cost-effectiveness for Screening Infants at High Risk for Peanut Sensitization Before Early Peanut Introduction

Importance Early peanut introduction reduces the risk of developing peanut allergy, especially in high-risk infants. Current US recommendations endorse screening but are not cost-effective relative to other international strategies. Objective To identify scenarios in which current early peanut introduction guidelines would be cost-effective. Design, Setting, and Participants This simulation/cohort economic evaluation used microsimulations and cohort analyses in a Markov model to evaluate the cost-effectiveness of early peanut introduction with and without peanut skin prick test (SPT) screening in high-risk infants during an 80-year horizon from a societal perspective. Data were analyzed from April to May 2019. Exposures High-risk infants with early-onset eczema and/or egg allergy underwent early peanut introduction with and without peanut SPT screening (100 000 infants per treatment strategy) using a dichotomous 8-mm SPT cutoff value (stipulated in the current US guideline). Main Outcomes and Measures Cost, quality-adjusted life-years (QALYs), net monetary benefit, peanut allergic reactions, severe allergic reactions, and deaths due to peanut allergy. Results In the simulated cohort of 200 000 infants and using the base case during the model horizon, a no-screening approach had lower mean (SD) costs ($13 449 [$38 163] vs $15 279 [$38 995]) and higher mean (SD) gain in QALYs (29.25 [3.28] vs 29.23 [3.30]) vs screening but resulted in more allergic reactions (mean [SD], 1.07 [3.15] vs 1.01 [3.02]), severe allergic reactions (mean [SD], 0.53 [1.66] vs 0.52 [1.62]), and anaphylaxis involving cardiorespiratory compromise (mean [SD], 0.50 [1.59] vs 0.49 [1.47]) per individual. In deterministic SPT sensitivity analyses at base-case sensitivity and specificity rates, screening could be cost-effective at a high disutility rate (the negative effect of a food allergic reaction) (76-148 days of life traded) for an at-home vs in-clinic reaction in combination with high baseline peanut allergy prevalence among infants at high risk for peanut allergy and not yet exposed to peanuts. If an equivalent rate and disutility of accidental and index anaphylaxis was assumed and the 8-mm SPT cutoff had 0.85 sensitivity and 0.98 specificity, screening was cost-effective at a peanut allergy prevalence of 36%. Conclusions and Relevance The results of this study suggest that the current screening approach to early peanut introduction could be cost-effective at a particular health utility for an in-clinic reaction, SPT sensitivity and specificity, and high baseline peanut allergy prevalence among high-risk infants. However, such conditions are unlikely to be plausible to realistically achieve. Further research is needed to define the health state utility associated with reaction location

A survey study of index food‐related allergic reactions and anaphylaxis management

Background:  Initial food‐allergic reactions are often poorly recognized and under‐treated. Methods:  Parents of food‐allergic children were invited to complete an online questionnaire, designed with Kids with Food Allergies Foundation , about their children’s first food‐allergic reactions resulting in urgent medical evaluation. Results:  Among 1361 reactions, 76% (95% CI 74–79%) were highly likely to represent anaphylaxis based on NIAID/FAAN criteria. Only 34% (95% CI 31–37%) of these were administered epinephrine. In 56% of these, epinephrine was administered by emergency departments; 20% by parents; 9% by paramedics; 8% by primary care physicians; and 6% by urgent care centers. In 26% of these, epinephrine was given within 15 min of the onset of symptoms; 54% within 30 min; 82% within 1 h; and 93% within 2 h. Factors associated with a decreased likelihood of receiving epinephrine for anaphylaxis included age <12 months, milk and egg triggers, and symptoms of abdominal pain and/or diarrhea. Epinephrine was more likely to be given to asthmatic children and children with peanut or tree nut ingestion prior to event. Post‐treatment, 42% of reactions likely to represent anaphylaxis were referred to allergists, 34% prescribed and/or given epinephrine auto‐injectors, 17% trained to use epinephrine auto‐injectors, and 19% given emergency action plans. Of patients treated with epinephrine, only half (47%) were prescribed epinephrine auto‐injectors. Conclusions:  Only one‐third of initial food‐allergic reactions with symptoms of anaphylaxis were recognized and treated with epinephrine. Fewer than half of patients were referred to allergists. There is still a need to increase education and awareness about food‐induced anaphylaxis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93515/1/pai1315.pd

Allergist-Reported Trends in the Practice of Food Allergen Oral Immunotherapy

Food allergen oral immunotherapy (OIT) is an experimental, immune-modifying therapy that may induce clinical desensitization in some patients. OIT is still in early phase clinical research, but some provider may offer OIT as a clinical service. To understand the current practices of allergists performing OIT an on-line survey was emailed to members of the American Academy of Allergy Asthma and Immunology. Among 442 respondents, 61 (13.8%) reported participating in OIT, including 28 in non-academic settings. Informed consent for OIT was obtained by 91.3%, IRB approval by 47.7% and Investigational New Drug (IND) approval by 38.1%. Compared to non-academic participants, more academic participants used peanut OIT, obtained IRB and IND (p <0.0001 respectively), and challenged patients prior to entry (p=0.008). More non-academic providers billed the patient or insurance for reimbursement (p<0.0001). Low reported regard for the importance for FDA approval or a standardized product (increased odds), and high regard for better safety data (decreased odds) were associated with considering to offer OIT as a service. Significant differences exist in OIT occurring in academic vs. non-academic settings. Further assessment is needed regarding the different motivations and practice styles among providers offering OIT, and those considering doing so

Anaphylaxis: Revision of the Brighton collaboration case definition

The Brighton Collaboration (BC) has formulated a number of case definitions which have primarily been applied to adverse events of special interest in the context of vaccine safety surveillance. This is a revision of the 2007 BC case definition for anaphylaxis. Recently, the BC definition has been widely used for evaluating reports of suspected anaphylaxis following COVID-19 vaccination. This has led to debate about the performance of the BC definition in comparison with those from the US National Institute of Allergy and Infectious Disease/Food Allergy Anaphylaxis Network (NIAID/FAAN) and the World Allergy Organization (WAO). BC convened an expert working group to revise the case definition based on their usual process of literature review and expert consensus. This manuscript presents the outcome of this process and proposes a revised case definition for anaphylaxis. Major and minor criteria have been re-evaluated with an emphasis on the reporting of observable clinical signs, rather than subjective symptoms, and a clearer approach to the ascertainment of levels of certainty is provided. The BC case definition has also been aligned with other contemporary and international case definitions for anaphylaxis

Outcomes reported in randomized controlled trials for mixed and non‐IgE‐mediated food allergy: Systematic review

Background Mixed and non‐IgE‐mediated food allergy is a subset of immune‐mediated adverse food reactions that can impose a major burden on the quality of life of affected patients and their families. Clinical trials to study these diseases are reliant upon consistent and valid outcome measures that are relevant to both patients and clinicians, but the degree to which such stringent outcome reporting takes place is poorly studied. Objective As part of the Core Outcome Measures for Food Allergy (COMFA) project, we identified outcomes reported in randomized clinical trials (RCT) of treatments for mixed or non‐IgE‐mediated food allergy. Design In this systematic review, we searched the Ovid, MEDLINE and Embase databases for RCTs in children or adults investigating treatments for food protein‐induced enterocolitis syndrome, food protein‐induced allergic proctocolitis, food protein‐induced enteropathy and eosinophilic gastrointestinal disorders including eosinophilic esophagitis [EoE], eosinophilic gastritis and eosinophilic colitis published until 14 October 2022. Results Twenty‐six eligible studies were identified, with 23 focused on EoE (88%). Most interventions were corticosteroids or monoclonal antibodies. All EoE studies assessed patient‐reported dysphagia, usually using a non‐validated questionnaire. Twenty‐two of 23 EoE studies used peak tissue eosinophil count as the primary outcome, usually using a non‐validated assessment method, and other immunological markers were only exploratory. Thirteen (57%) EoE studies reported endoscopic outcomes of which six used a validated scoring tool recently recommended as a core outcome for EoE trials. Funding source was not obviously associated with likelihood of an RCT reporting mechanistic versus patient‐reported outcomes. Only 3 (12%) RCTs concerned forms of food allergy other than EoE, and they reported on fecal immunological markers and patient‐reported outcomes.ConclusionsOutcomes measured in clinical trials of EoE and non‐IgE‐mediated food allergy are heterogeneous and largely non‐validated. Core outcomes for EoE have been developed and need to be used in future trials. For other forms of mixed or non‐IgE‐mediated food allergies, core outcome development is needed to support the development of effective treatments

No systemic reactions to influenza vaccination in egg-sensitized tertiary-care pediatric patients

<p>Abstract</p> <p>Background</p> <p>There are numerous, disparate guidelines for influenza vaccination in egg-allergic patients. We aimed to describe the outcome of selectively applied guidelines, based on risk-stratification, to our high risk, egg-allergic, tertiary-care pediatric population.</p> <p>Methods</p> <p>Egg allergy was confirmed with skin testing. The vaccine administered was an adjuvunated 2009 H1N1 influenza A vaccine with < 0.165 mcg/ml ovalbumin. Patients with mild egg allergy were to receive the vaccination in 1 dose, those with severe egg allergy were to receive 2 split doses, and patients with exquisite egg allergy or significant co-morbidities were to be skin tested with the vaccine (prick full strength, intradermal 1:100 of final concentration without adjuvant) and had 5 step desensitization if the testing was positive, or 1-2 step administration if negative. Patients were observed for 60 minutes after the final dose and anaphylaxis treatment was available. We report the frequency of allergic reactions.</p> <p>Results</p> <p>Ninety-nine patients were referred and 79 had positive egg testing. Asthma was present in 67% and 30% had prior anaphylaxis to egg. We vaccinated 77 of 79 patients: 71 without performing vaccine skin testing. Two refused vaccination. No patient had a systemic reaction or required treatment. Two patients experienced positive testing to the adjuvanated intradermal vaccine, but were negative without adjuvant.</p> <p>Conclusions</p> <p>Our results suggest that most egg-allergic tertiary care pediatric patients can be vaccinated with a low ovalbumin content influenza vaccine without prior vaccine testing. Vaccine skin testing, if used at all, can be reserved for special circumstances. The squalene adjuvant may cause an irritant reaction with intradermal testing.</p

Parental perception of their child's Quality of Life in children with non-Immunoglobulin-E mediated gastrointestinal allergies

BACKGROUND: Food allergy can have a significant impact on health related quality of life (HRQoL). Parental proxy questionnaires are commonly used when children are too young to complete questionnaires themselves. Little data is available on HRQoL in children with non-IgE-mediated gastrointestinal food allergy (GIFA). The aim of this study was to evaluate HRQoL in these children by parent proxy. METHODS: A cross-sectional questionnaire study was conducted with children 2-16 years old with confirmed (GIFA). Parents of these children completed the Paediatric Quality of Life Inventory (PedsQL(™) ) and the Family Impact module of the PedsQL. The PedsQL scores were compared to two published cohorts: functional abdominal pain (FAP) and IgE-mediated food allergy. RESULTS: Fifty-two parents of children with GIFA completed the PedsQL(™) parent proxy. The GIFA cohort had significantly better overall HRQoL compared to the FAP cohort, but lower emotional functioning scores. The GIFA cohort also had poorer physical QoL compared to the IgE cohort (all p<0.05). The more foods excluded, comorbidity of nasal congestion, abdominal pain, back arching, the persistence of flatus and gastrointestinal symptom severity after elimination diet were related to poorer QoL in this non-IgE cohort. Regression analyses showed that number of foods and nasal congestion significantly predicted total QoL score as perceived by parents. CONCLUSIONS: This study has shown that different areas of HRQoL of children with GIFA are affected compared to children with FAP or IgE-mediated food allergy, highlighting the need for a specific GIFA HRQoL questionnaire to better understand the impact on these children. This article is protected by copyright. All rights reserved

Excessive Media Consumption About COVID-19 is Associated With Increased State Anxiety : Outcomes of a Large Online Survey in Russia

BACKGROUND: The COVID-19 pandemic has potentially had a negative impact on the mental health and well-being of individuals and families. Anxiety levels and risk factors within particular populations are poorly described. OBJECTIVE: This study aims to evaluate confidence, understanding, trust, concerns, and levels of anxiety during the COVID-19 pandemic in the general population and assess risk factors for increased anxiety. METHODS: We launched a cross-sectional online survey of a large Russian population between April 6 and 15, 2020, using multiple social media platforms. A set of questions targeted confidence, understanding, trust, and concerns in respondents. The State-Trait Anxiety Inventory was used to measure anxiety. Multiple linear regressions were used to model predictors of COVID-19-related anxiety. RESULTS: The survey was completed by 23,756 out of 53,966 (44.0% response rate) unique visitors; of which, 21,364 were residing in 62 areas of Russia. State Anxiety Scale (S-Anxiety) scores were higher than Trait Anxiety Scale scores across all regions of Russia (median S-Anxiety score 52, IQR 44-60), exceeding published norms. Time spent following news on COVID-19 was strongly associated with an increased S-Anxiety adjusted for baseline anxiety level. One to two hours spent reading COVID-19 news was associated with a 5.46 (95% CI 5.03-5.90) point difference, 2-3 hours with a 7.06 (95% CI 6.37-7.74) point difference, and more than three hours with an 8.65 (95% CI 7.82-9.47) point difference, all compared to less than 30 minutes per day. Job loss during the pandemic was another important factor associated with higher S-Anxiety scores (3.95, 95% CI 3.31-4.58). Despite survey respondents reporting high confidence in information regarding COVID-19 as well as an understanding of health care guidance, they reported low overall trust in state and local authorities, and perception of country readiness. CONCLUSIONS: Among Russian respondents from multiple social media platforms, there was evidence of higher levels of state anxiety associated with recent job loss and increased news consumption, as well as lower than expected trust in government agencies. These findings can help inform the development of key public health messages to help reduce anxiety and raise perceived trust in governmental response to this current national emergency. Using a similar methodology, comparative surveys are ongoing in other national populations.Peer reviewe