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Introduction: Children with peanut allergy are at increased risk of developing tree nut allergies, which can be severe and for most lifelong. Introduction of peanut in the first year of life can reduce the risk of peanut allergy, however, prevention strategies for tree nut allergies have not been established. We aimed to test the efficacy and safety of a novel strategy, a supervised multi-nut oral food challenge (OFC) compared to standard care for tree nut allergy prevention in infants at high risk of developing tree nut allergy, TreEAT. Methods and analysis: TreEAT is a 2-armed, open-label, randomised, controlled trial (RCT). Infants (n=212) aged 4-11months with peanut allergy will be randomised 1:1 at peanut allergy diagnosis to either a hospital-based multi-tree nut (almond, cashew, hazelnut and walnut) OFC using multi-nut butter or standard care (home introduction of individual tree nuts). All infants will be assessed at age 18months, with questionnaires and SPT to peanut and tree nuts. Peanut and tree nut OFCs will be performed as required to determine allergy status for each nut. The primary outcome is tree nut allergy at age 18 months. Secondary outcomes include peanut allergy resolution, proportion and severity of adverse events related to tree nut ingestion, number and frequency of tree nuts ingested, quality of life and parental anxiety and allergy related healthcare visits from randomisation to 18 months of age. Analyses will be performed on an intention-to-treat basis. Ethics and dissemination TreEAT was approved by the Royal Children’s Hospital Human Research Ethics Committee (#70489). Outcomes will be presented at scientific conferences and disseminated through publication. Trial registration number: ClinicalTrials.gov ID: NCT04801823

Research Letter There are few data on long-term effects and quality of life impact of peanut OIT. PPOIT was shown to induce 8-week sustained unresponsiveness that persists to 3-years post-treatment after ad libitum peanut ingestion. PPOIT provides lasting benefits for children with peanut allergy, with long-lasting improvement in health-related quality of life.

Background: Combined treatment with probiotic and peanut oral immunotherapy (PPOIT) was shown to induce sustained unresponsiveness (SU) in a proof-of-concept randomized trial. Additional data on safety and long-term outcomes are needed. This study aimed to evaluate the safety and long-term effects of PPOIT in children with peanut allergy. Methods: Open-label study of 20 children aged 1-12 years with challenge-confirmed peanut allergy; all children received 18-months of PPOIT. Efficacy endpoints were desensitization, 8-week SU, and persistence of 8-week SU at 3-years post-treatment, assessed by double-blind placebo-controlled food challenge (cumulative 4950mg peanut protein). Treatment emergent adverse events and relationship to study treatment were recorded. Immunologic measures and health related quality of life (HRQL) were evaluated at screening, end-of-treatment and 3-years post-treatment. Results: Sixteen children (75%) completed treatment. By intention-to-treat analysis, 75% (15/20) achieved desensitization and 60% (12/20) achieved 8-week SU. Ten of 12 participants with SU at end-of-treatment consented to the 3-year SU challenge; 6 (60%) had persistence of SU. PPOIT was associated with significantly reduced peanut skin prick test wheal size and serum peanut specific-IgE levels at end-of-treatment, 12-months and 3-years post-treatment. There were no serious adverse events. HRQL scores improved (exceeding the Minimal Clinically Important Difference of 0.45) at 12-months post-treatment with benefit sustained at 3-years post-treatment. Conclusions: Eighteen months of PPOIT induced high rates of desensitization and SU, and SU persisted to 3-years post-treatment in a majority of initial responders. PPOIT led to long-lasting suppression of peanut sIgE and long-lasting clinically important improvement in HRQL.

Background: Cashew is a common cause of tree nut allergy in children. To date there have been few studies of diagnostic tests for cashew allergy, and positive predictive values (PPVs) for cashew as well as other tree nuts are largely extrapolated from studies of peanut allergy. How relevant these cutoffs are for cashew has not been formally explored. Objective: We aimed to establish skin prick test (SPT) wheal sizes that correlated to 95% PPV for a positive food challenge for cashew. Methods: We included all cashew oral food challenges (OFCs) conducted as part of the HealthNuts (n = 108; age, 4-6 years) and SchoolNuts (n = 37; age, 10-14 years) studies, both recruited from the community (population cohort). A second cohort of all cashew OFCs conducted at the Royal Children's Hospital (RCH) allergy center (n = 343) (2011-2016) and a private allergy clinic based at RCH (n = 43) was included via electronic medical record review (clinic cohort). The 95% PPV for cashew SPT was calculated for both cohorts. Results: Among the population cohort (n = 145), 62% of cashew OFCs were positive compared with 20% of the clinic cohort (n = 386). The SPT cutoff for 95% PPV derived from the population cohort was 10 mm (95% confidence interval [CI], 7.5-12.0). For the clinic cohort, the 95% PPV was 14 mm (95% CI, 9.5-unknown). An SPT wheal size of 8 mm had a PPV of 89% (95% CI, 79-95) in the population cohort and 62% (95% CI, 45-78) in the clinic cohort. Conclusion: A higher SPT wheal size may be more appropriate than the commonly used 8 mm cutoff to guide clinical decisions around when to perform OFC for cashew.

Aim To determine whether infant-feeding practices, including duration of exclusive breastfeeding and use of partially hydrolysed formula, modify the risk of developing infant food allergy. Methods In an observational population-based study, 1 year olds were recruited from community immunisation clinics in Melbourne, Australia. Parent-reported data on infant-feeding practices and potential confounders were collected prior to infant skin prick testing for four food allergens. Sensitised infants attended hospital-based oral food challenges to establish food allergy status. Multiple logistic regression was used to investigate associations between breastfeeding and formula-feeding and infant food allergy adjusting for possible confounding variables. Results A total of 5276 (74% response) infants participated. Of the 4537 for whom food allergy status was determined, 515 (11.3%) were food allergic (challenge-proven in the context of skin prick testing positive (≥2 mm)). After adjusting for confounding variables, there was no association between duration of exclusive breastfeeding and food allergy. Use of partially hydrolysed formula did not reduce the risk of food allergy compared with cow's milk formula in the general population (adjusted odds ratios 1.03 (confidence interval 0.67-1.50)). Conclusion Duration of exclusive breastfeeding and use of partially hydrolysed formula were not associated with food allergy at 1 year of age in this large population-based study. These findings have implications for population-based infant-feeding guidelines and do not support the use of partially hydrolysed formula for food allergy prevention.

Background Adolescence is well recognized as a period of increased risk for severe and fatal food-induced anaphylaxis. Current Australian adrenaline autoinjector (AAI) prescription guidelines therefore suggest that consideration be given to AAI prescription in all adolescents with a food allergy. To date, however, few studies have assessed the AAI carriage behavior of adolescents prescribed AAI devices. Objective To determine the carriage behavior of prescribed AAI devices in a population-based sample of young Australian adolescents. Methods Students aged 10 to 14 years (and their parents) from randomly selected schools in metropolitan Melbourne completed self-administered questionnaires regarding the history and management of food allergy, including prescription and carriage of AAI device in different domains of school and social life. Results A total of 9816 students completed the questionnaire (46% response): 620 students were assessed to have likely IgE-mediated food allergy and 234 (38%) of these had been prescribed an AAI. Most students (93%; 95% CI, 89%-96%) who were prescribed AAIs reported that they provided their AAI and anaphylaxis action plan to their school. Adherence to AAI carriage in other domains of social life was poor, with 49% (95% CI, 42%-56%) never carrying their AAI in 1 or more locations. Carriage of the AAI device was particularly poor when students were independent of parental supervision: 32% (95% CI, 25%-39%) never carried it when they were by themselves, 28% (95% CI, 22%-36%) never carried it while out with friends, and 36% (95% CI, 30%-43%) never carried their AAI to sporting activities. Conclusions Carriage of AAI devices is suboptimal in young adolescents prescribed AAIs, particularly when young adolescents are independent of parental supervision.

Summary Background Oral immunotherapy has attracted much interest as a potential treatment for food allergy, yet little is known about its long-term effects. We aimed to assess long-term outcomes in participants who completed a randomised, double-blind, placebo-controlled trial of combined probiotic and peanut oral immunotherapy (PPOIT), which was previously shown to induce desensitisation and 2-week sustained unresponsiveness. Methods All participants who completed the PPOIT randomised trial were eligible to participate in this follow-up study 4 years after treatment cessation. Peanut intake and adverse reactions to peanut in the 4 years after treatment cessation were systematically documented with a structured questionnaire administered by allergy nurses. Additionally, participants were invited to undergo peanut skin prick tests, measurement of peanut sIgE and sIgG4 concentrations, and double-blind placebo-controlled peanut challenge to assess 8-week sustained unresponsiveness. Findings 48 (86%) of 56 eligible participants were enrolled in the follow-up study. Mean time since stopping treatment was 4·2 years in both PPOIT (SD 0·6) and placebo (SD 0·7) participants. Participants from the PPOIT group were significantly more likely than those from the placebo group to have continued eating peanut (16 [67%] of 24 vs one [4%] of 24; absolute difference 63% [95% CI 42–83], p=0·001; number needed to treat 1·6 [95% CI 1·2–2·4]). Four PPOIT-treated participants and six placebo participants reported allergic reactions to peanut after intentional or accidental intake since stopping treatment, but none had anaphylaxis. PPOIT-treated participants had smaller wheals in peanut skin prick test (mean 8·1 mm [SD 7·7] vs 13·3 mm [7·6]; absolute difference −5·2 mm [95% CI −10·3 to 0·0]; age-adjusted and sex-adjusted p=0·035) and significantly higher peanut sIgG4:sIgE ratios than placebo participants (geometric mean 67·3 [95% CI 10·3–440·0] vs 5·2 [1·2–21·8]; p=0·031). Seven (58%) of 12 participants from the PPOIT group attained 8-week sustained unresponsiveness, compared with one (7%) of 15 participants from the placebo group (absolute difference 52% [95% CI 21–82), p=0·012; number needed to treat 1·9 [95% CI 1·2–4·8]). Interpretation PPOIT provides long-lasting clinical benefit and persistent suppression of the allergic immune response to peanut. Funding Murdoch Childrens Research Institute and Australian Food Allergy Foundation.

SummaryBackground It is controversial whether egg-allergic children should strictly avoid all forms of egg, or if regular ingestion of baked egg will either delay or hasten the resolution of egg allergy. Objective This is the first study to examine the relationship between frequency of baked egg ingestion and rate of decline in egg skin prick test size in egg-allergic children. Methodology This was a retrospective clinical cohort study. All children with challenge-proven egg allergy who attended the Royal Children's Hospital Allergy Department 1996–2005 and had at least two egg skin prick tests performed in this period were included (n = 125). Frequency of baked egg ingestion was assessed by telephone questionnaire as follows: (a) frequent (> once per week), (b) regular (> once every 3 months, up to ≤ once per week) or (c) strict avoidance (≤ once every 3 months). The relationship between frequency of baked egg ingestion and rate of decline in egg skin prick test size was examined by multiple linear regression, adjusting for potential confounders. Results Mean rate of decline in egg skin prick test size in all children was 0.7 mm/year (95% CI 0.5–1.0 mm/year). There was no evidence (P = 0.57) that the rate of decline in egg skin prick test size differed between children who undertook frequent ingestion (n = 21, mean 0.4 mm/year, 95% CI −0.3–1.2 mm/year), regular ingestion (n = 37, mean 0.9 mm/year, 95% CI 0.4–1.4 mm/year) or strict avoidance (n = 67, mean 0.7 mm/year, 95% CI 0.4–1.1 mm/year) of baked egg. Conclusions Compared with strict dietary avoidance, frequent consumption of baked egg was not associated with a different rate of decline in egg skin prick test size in egg-allergic children. Clinical Relevance Given that dietary restrictions can adversely impact on the family, it is reasonable to consider liberalizing baked egg in the diet of egg-allergic children.

BACKGROUND: Measurement of whole peanut-specific IgE (sIgE) is often used to confirm sensitization but does not reliably predict allergy. Ara h 2 is the dominant peanut allergen detected in 90% to 100% of patients with peanut allergy and could help improve diagnosis. OBJECTIVES: We sought to determine whether Ara h 2 testing might improve the accuracy of diagnosing peanut allergy and therefore circumvent the need for an oral food challenge (OFC). METHODS: Infants from the population-based HealthNuts study underwent skin prick tests to determine peanut sensitization and subsequently underwent a peanut OFC to confirm allergy status. In a stratified random sample of 200 infants (100 with peanut allergy and 100 with peanut tolerance), whole peanut sIgE and Ara h 2 sIgE levels were quantified by using fluorescence enzyme immunoassay. RESULTS: By using the previously published 95% positive predictive value of 15 kU(A)/L for whole peanut sIgE, a corresponding specificity of 98% (95% CI, 93% to 100%) was found in this study cohort. At the equivalent specificity of 98%, the sensitivity of Ara h 2 sIgE is 60% (95% CI, 50% to 70%), correctly identifying 60% of subjects with true peanut allergy compared with only 26% correctly identified by using whole peanut sIgE. We report that when using a combined approach of plasma sIgE testing for whole peanut followed by Ara h 2 for the diagnosis of peanut allergy, the number of OFCs required is reduced by almost two thirds. CONCLUSION: Ara h 2 plasma sIgE test levels provide higher diagnostic accuracy than whole peanut plasma sIgE levels and could be considered a new diagnostic tool to distinguish peanut allergy from peanut tolerance, which might reduce the need for an OFC.

In recent times, allergy has become a financial, physical andpsychological burden to the society as a whole. Allergic reactions can result in life-threatening situations causing morbidity and high economic cost. Therefore, more effective reagents are needed for allergy treatment. Literature suggests that a causal relationship exists between the intake of Omega-3/6 fatty acids such as DHA, EPA, DPA and AA and atopic individuals suffering from allergies. In an allergic cascade, cytokines IL-4 and IL-13 bind to IL-4 receptor (IL-4R), which activates the STAT6 phosphorylation pathway leading to gene activation of allergen-specific IgE production by B cells. The overall aim of this study is to characterise Omega-3/6 fatty acids and their effects on IgE production.

To determine whether infant-feeding practices, including duration of exclusive breastfeeding and use of partially hydrolysed formula, modify the risk of developing infant food allergy.In an observational population-based study, 1 year olds were recruited from community immunisation clinics in Melbourne, Australia. Parent-reported data on infant-feeding practices and potential confounders were collected prior to infant skin prick testing for four food allergens. Sensitised infants attended hospital-based oral food challenges to establish food allergy status. Multiple logistic regression was used to investigate associations between breastfeeding and formula-feeding and infant food allergy adjusting for possible confounding variables.A total of 5276 (74% response) infants participated. Of the 4537 for whom food allergy status was determined, 515 (11.3%) were food allergic (challenge-proven in the context of skin prick testing positive (≥2 mm)). After adjusting for confounding variables, there was no association between duration of exclusive breastfeeding and food allergy. Use of partially hydrolysed formula did not reduce the risk of food allergy compared with cow's milk formula in the general population (adjusted odds ratios 1.03 (confidence interval 0.67-1.50)).Duration of exclusive breastfeeding and use of partially hydrolysed formula were not associated with food allergy at 1 year of age in this large population-based study. These findings have implications for population-based infant-feeding guidelines and do not support the use of partially hydrolysed formula for food allergy prevention.

A limited number of adrenaline auto-injectors are currently available. Epipen and Anapen are available in Australia, New Zealand, UK and parts of Europe and Asia. Few studies have compared the performance of these devices.To compare the intuitiveness of use of these devices. A secondary aim was to compare the ability to recall the use of each device after a period of 3 months.A random sample of 100 subjects naïve to both the EpiPen and Anapen were recruited from staff and families attending Royal Children's Hospital, Melbourne Australia. Subjects were randomized to Anapen (n = 53) or EpiPen (n = 47) and asked to demonstrate use of a 'trainer' device (i) prior to and (ii) after receiving training in its correct use. A subset (n = 32) participated in a follow-up study to evaluate (iii) the ability to recall correct use of each device.Most subjects correctly demonstrated all steps in use of the EpiPen and Anapen both prior to (89% vs. 79%, p = 0.17) and after training on use (100% vs. 100%). However, after 3 months, significantly more participants correctly demonstrated use of EpiPen (87%) compared to Anapen (35%) (p = 0.003) and critical errors that would likely result in failure to administer adrenaline were more common with Anapen (59% vs. 13%, p = 0.01).Most study participants correctly demonstrated the use of both devices without prior training. There was greater attrition in correct use of Anapen compared to EpiPen over time. Critical errors in administration were more likely with Anapen than EpiPen.

Background: Socio-demographic predictors for the development of clinically observed, infantile eczema have not been formally examined in a large population-based study. Few studies of eczema risk factors have included current, objective eczema outcomes as well as parent-reported history. Objectives: We aimed to measure the population prevalence of infantile eczema using novel sampling methodology, and identify socio-demographic risk factors for eczema in the first year of life. Methods: A population-based cross-sectional study of infantile allergy (the HealthNuts study, n = 4972, response rate 74.1%) was conducted from 2008-2011 in Melbourne, Australia. Infants were examined for current eczema at age 12 months (mean 12.7, SD 0.7). Parents provided information about the infants' history of eczema and demographic factors. Factors associated with eczema were modelled using multinomial logistic regression. Results: The population prevalence of observed eczema at 12 months was 20.3% (95% CI 19.0, 21.5), while cumulative prevalence for parent-reported eczema was 28.0% (95% CI 26.7, 29.4). The strongest predictors of eczema were maternal eczema and asthma (multinomial (M)-OR 1.7, P < 0.001, and M-OR 1.4, P = 0.007), male sex (M-OR 1.4, P < 0.001), and East Asian ethnicity (M-OR 1.6, P < 0.001) with over 80% of infants with all risk factors exhibiting eczema. East Asian parents, particularly recent migrants, reported fewer allergies than other parents. Conclusions and Clinical Relevance: Approximately, one in three infants developed eczema by 12 months of age. East Asian infants are at increased risk of eczema despite their parents having lower rates of allergy than non-Asian parents. Gene-environment interactions may explain the differential effect seen in this minority group.

Background Food allergy has been associated with lower weight and height in cross-sectional studies in children; however, this has not been investigated in longitudinal studies to explore growth over time, and previous studies have not accounted for coexisting eczema. Objective The objective of this study was to examine the association of IgE-mediated food allergy and eczema with anthropometric measures at 1 and 4 years of age. Methods In the HealthNuts population-based cohort, infants recruited at age 1 year underwent a skin prick test to egg, peanut, and sesame; those sensitized had oral food challenges. Food challenges repeated at 4 years determined food allergy persistence or resolution. Eczema was defined as parent report of eczema diagnosis. Parent-reported weight and height and child health record data were used to calculate age- and sex-adjusted percentiles from World Health Organization charts. Multivariable linear regression models were fitted to examine the effect of food allergy and eczema on weight and height controlling for potential confounders. Results Children with both food allergy and eczema at age 1 had lower percentiles for mean weight (51.3 vs 58.3 percentile, P = .001) and height (48.4 vs 53.4, P = .028) at age 1 compared with those with neither condition. There was no difference for children with only food allergy or eczema at age 1. By age 4, children with persistent food allergy and persistent eczema, but not those with resolved food allergy, were still shorter and lighter. Conclusions Children with both food allergy and eczema were shorter and lighter throughout early childhood, with more pronounced differences in those with persistent food allergy.

Background Infant feeding guidelines have long recommended delaying introduction of solids and allergenic foods to prevent allergy in high-risk infants, despite a paucity of evidence. Objective We aimed to determine whether confirmed egg allergy in 12-month-old infants is associated with (1) duration of breast-feeding and (2) ages of introducing egg and solids. Methods In a population-based cross-sectional study (HealthNuts) parents reported on infant feeding and potential confounding factors before skin prick testing for egg white. Egg-sensitized infants were then offered an egg oral food challenge. Multiple logistic regression was used to investigate associations between diet and egg allergy adjusted for possible confounding factors. Results A total of 2589 infants (73% response) participated. Compared with introduction at 4 to 6 months, introducing egg into the diet later was associated with higher risks of egg allergy (adjusted odds ratios [ORs], 1.6 [95% CI, 1.0-2.6] and 3.4 [95% CI, 1.8-6.5] for introduction at 10-12 and after 12 months, respectively). These findings persisted even in children without risk factors (OR, 3.3 [95% CI, 1.1-9.9]; 10-12 months). At age 4 to 6 months, first exposure as cooked egg reduced the risk of egg allergy compared with first exposure as egg in baked goods (OR, 0.2 [95% CI, 0.06-0.71]). Duration of breast-feeding and age at introduction of solids were not associated with egg allergy. Conclusions Introduction of cooked egg at 4 to 6 months of age might protect against egg allergy. Changes in infant feeding guidelines could have a significant effect on childhood egg allergy and possibly food allergy more generally.

The prevalence of allergic disease has increased considerably in recent decades and Australia has one of the highest rates of allergic disease in the world. As there is currently no cure for allergic diseases, prevention offers a logical approach to addressing the rising burden of disease. The factors responsible for this escalation in prevalence remain unclear, and strategies for allergy prevention remain limited.This article discusses current recommendations for allergy prevention and highlights new insights into allergic disease.History of allergic disease in a first degree relative is currently the only useful indicator for increased risk of developing allergic disease in a child. Prevention strategies should be directed to these high risk individuals. Currently, maternal dietary restriction during pregnancy or lactation and aeroallergen avoidance are not recommended. Breastfeeding is recommended, and where not possible or insufficient, a partially hydrolysed formula should be used in high risk infants. Introduction of solids should be delayed to 4-6 months of age. There is no evidence that delaying solids beyond this age is of benefit. There is currently insufficient evidence to recommend the addition of probiotics for allergy prevention.

Allergic diseases (asthma, atopic dermatitis, allergic rhinitis and food allergy) are the commonest chronic diseases of childhood. General practitioners commonly encounter children with allergic diseases and need to be aware of when referral to a paediatric allergist should be considered. An understanding of what diagnostic tests the allergist may use in confirming the diagnosis is also necessary.This article discusses the criteria for referral to a specialist paediatric allergist and also details the tests that may be used by the allergist as part of the diagnostic work up.Management of allergic diseases requires accurate diagnosis and avoidance of offending allergens where possible. The diagnosis of an IgE mediated allergy requires both a history of symptoms on exposure to the allergen and detection of allergen specific IgE. The most commonly employed diagnostic methods in clinical allergy assessment are skin prick testing, RAST and clinical oral food challenge procedures. The use of alternative or unorthodox tests may provide misleading results and delay correct diagnosis and therefore should not be used.

Coadministration of a bacterial adjuvant with oral immunotherapy (OIT) has been suggested as a potential treatment for food allergy.To evaluate a combined therapy comprising a probiotic together with peanut OIT.We performed a double-blind, placebo-controlled randomized trial of the probiotic Lactobacillus rhamnosus CGMCC 1.3724 and peanut OIT (probiotic and peanut oral immunotherapy [PPOIT]) in children (1-10 years) with peanut allergy. The primary outcome was induction of sustained unresponsiveness 2 to 5 weeks after discontinuation of treatment (referred to as possible sustained unresponsiveness). Secondary outcomes were desensitization, peanut skin prick test, and specific IgE and specific IgG4 measurements.Sixty-two children were randomized and stratified by age (≤5 and5 years) and peanut skin test wheal size (≤10 and10 mm); 56 reached the trial's end. Baseline demographics were similar across groups. Possible sustained unresponsiveness was achieved in 82.1% receiving PPOIT and 3.6% receiving placebo (P.001). Nine children need to be treated for 7 to achieve sustained unresponsiveness (number needed to treat, 1.27; 95% CI, 1.06-1.59). Of the subjects, 89.7% receiving PPOIT and 7.1% receiving placebo were desensitized (P.001). PPOIT was associated with reduced peanut skin prick test responses and peanut-specific IgE levels and increased peanut-specific IgG4 levels (all P.001). PPOIT-treated participants reported a greater number of adverse events, mostly with maintenance home dosing.This is the first randomized placebo-controlled trial evaluating the novel coadministration of a probiotic and peanut OIT and assessing sustained unresponsiveness in children with peanut allergy. PPOIT was effective in inducing possible sustained unresponsiveness and immune changes that suggest modulation of the peanut-specific immune response. Further work is required to confirm sustained unresponsiveness after a longer period of secondary peanut elimination and to clarify the relative contributions of probiotics versus OIT.

Intense vagal discharge often follows stimulus application during electroconvulsive therapy (ECT). Related periods of asystole during ECT have been reported sporadically in psychiatric journals, but to date not in the anesthesia literature. We report here two cases of prolonged asystole that occurred in our facility in spite of the fact that published suggestions for its prevention were followed. With careful monitoring of these patients--including echocardiography for one patient--we document the onset of asystole at the exact time of ECT stimulus application. With these data, we discuss why asystole is likely to result from a direct central pathway rather than via a baroreceptor reflex, and discuss a neuroanatomic pathway potentially responsible for our findings. We also demonstrate that high-dose atropine (0.8 mg) can effectively prevent most cases of asystole in susceptible patients, and that administration of esmolol following cessation of seizures effectively reduces the elevated heart rate without causing asystole or bradycardia.

Background There is a paucity of data examining the natural history of and risk factors for egg allergy persistence, the most common IgE-mediated food allergy in infants. Objective We aimed to assess the natural history of egg allergy and identify clinical predictors for persistent egg allergy in a population-based cohort. Methods The HealthNuts study is a prospective, population-based cohort study of 5276 infants who underwent skin prick tests to 4 allergens, including egg. Infants with a detectable wheal were offered hospital-based oral food challenges (OFCs) to egg, irrespective of skin prick test wheal sizes. Infants with challenge-confirmed raw egg allergy were offered baked egg OFCs at age 1 year and follow-up at age 2 years, with repeat OFCs to raw egg. Results One hundred forty infants with challenge-confirmed egg allergy at age 1 year participated in the follow-up. Egg allergy resolved in 66 (47%) infants (95% CI, 37% to 56%) by 2 years of age; however, resolution was lower in children with baked egg allergy at age 1 year compared with baked egg tolerance (13% and 56%, respectively; adjusted odds ratio, 5.27; 95% CI, 1.36-20.50; P = .02). In the subgroup of infants who were tolerant to baked egg at age 1 year, frequent ingestion of baked egg (≥5 times per month) compared with infrequent ingestion (0-4 times per month) increased the likelihood of tolerance (adjusted odds ratio, 3.52; 95% CI, 1.38-8.98; P = .009). Mutation in the filaggrin gene was not associated with the resolution of either egg allergy or egg sensitization at age 2 years. Conclusion Phenotyping of egg allergy (baked egg tolerant vs allergic) should be considered in the management of this allergy because it has prognostic implications and eases dietary restrictions. Randomized controlled trials for egg oral immunotherapy should consider stratifying at baseline by the baked egg subphenotype to account for the differential rate of tolerance development.

Background Epidemiological evidence has shown that pediatric food allergy is more prevalent in regions further from the equator, suggesting that vitamin D insufficiency may play a role in this disease. Objective To investigate the role of vitamin D status in infantile food allergy. Methods A population sample of 5276 one-year-old infants underwent skin prick testing to peanut, egg, sesame, and cow's milk or shrimp. All those with a detectable wheal and a random sample of participants with negative skin prick test results attended a hospital-based food challenge clinic. Blood samples were available for 577 infants (344 with challenge-proven food allergy, 74 sensitized but tolerant to food challenge, 159 negative on skin prick test and food challenge). Serum 25-hydroxyvitamin D levels were measured by using liquid chromatography tandem mass spectrometry. Associations between serum 25-hydroxyvitamin D and food allergy were examined by using multiple logistic regression, adjusting for potential risk and confounding factors. Results Infants of Australian-born parents, but not of parents born overseas, with vitamin D insufficiency (≤50 nmol/L) were more likely to be peanut (adjusted odds ratio [aOR], 11.51; 95% CI, 2.01-65.79; P = .006) and/or egg (aOR, 3.79; 95% CI, 1.19-12.08; P = .025) allergic than were those with adequate vitamin D levels independent of eczema status. Among those with Australian-born parents, infants with vitamin D insufficiency were more likely to have multiple food allergies (≥2) rather than a single food allergy (aOR, 10.48; 95% CI, 1.60-68.61 vs aOR, 1.82; 95% CI, 0.38-8.77, respectively). Conclusions These results provide the first direct evidence that vitamin D sufficiency may be an important protective factor for food allergy in the first year of life.

Parents and children who have been prescribed an Epipen are often unable to demonstrate its correct administration. One contributory factor may be that doctors are unfamiliar with the EpiPen and are unable to demonstrate the correct administration of the pen to the family. The aim of this study was to determine the rate of correct EpiPen demonstration by junior and Senior Medical Staff at a major tertiary paediatric Hospital. Junior and Senior medical staff were scored on their ability to correctly use the EpiPen trainer. A 6 step scoring system was used. One-hundred doctors were recruited (Residents n = 31, Senior Residents n = 39, Fellow/Consultants n = 30). Junior and Senior Medical staff had similar scores for EpiPen demonstration, the number that needed to read the EpiPen instructions prior to use and the frequancy of accidental self-injection into the thumb. Only two doctors (2%) demonstrated all 6 administration steps correctly. The most frequent errors made were not holding the pen in place for >5 seconds (57%), failure to apply pressure to activate (21%), and self-injection into the thumb (16%). Ninety five doctors needed to read the instructions, and of these, only 39 (41%) then proceeded to correctly demonstrate the remaining 5 steps. Forty-five doctors had previously dispensed an EpiPen, but only three demonstrated its use to parents/children with a trainer. The majority of doctors do not know how to use an Epipen and are unable to provide appropriate education to parents/children. In 37% of cases, the demonstration would not have delivered adrenaline to a patient.

Background Although egg allergy is the most common food allergy in infants and young children, risk factors for egg allergy remain largely unknown. This study examined the relationship between environmental and demographic factors and egg allergy in a population-based infant cohort. Methods In a study of 5276 infants (HealthNuts), infants underwent skin prick testing (SPT) to egg white at 12 months of age. Questionnaire data on relevant exposures were obtained. 699/873 (80%) infants eligible for oral food challenge (detectable wheal on SPT) attended for formal assessment of egg allergy status; 453 had confirmed egg allergy (positive challenge and SPT ≥ 2 mm). Associations between environmental and demographic factors and egg allergy were investigated using multivariable logistic regression. Results Children with older siblings and those with a pet dog at home were less likely to develop egg allergy by 1 year of age (adjusted OR [aOR], 0.72; 95% CI, 0.62, 0.83 per sibling; and aOR, 0.72; 95% CI, 0.52, 0.99, respectively). Caesarean section delivery, antibiotic use in infancy, childcare attendance and maternal age were not associated with egg allergy. History of allergic disease in an immediate family member and having parents born in East Asia were strong risk factors for infantile egg allergy (aOR, 1.82; 95% CI, 1.40, 2.36; and aOR, 3.30; 95% CI, 2.45, 4.45, respectively). Conclusions Exposure in the first year of life to siblings and dogs may decrease the risk of subsequent egg allergy. Infants with a family history of allergy and those with parents born in East Asia are at increased risk of egg allergy.