Outpatient and primary care direct provocation challenges for antibiotic allergy in children.

OBJECTIVE: To evaluate the use of a questionnaire-based decision-making algorithm to triage children with reported antibiotic allergies to proceed directly to an oral provocation challenge. DESIGN: Cohort study. SETTING: Children aged 2-16 years attending paediatric emergency department over 1 year (1 June 2018 till 31 May 2019) or identified from four primary care centres in Sheffield with a recorded antibiotic allergy and no previous testing. PARTICIPANTS: 313 children with 325 recorded antibiotic allergies. EXPOSURE: Clinical decision-making algorithm used to either exclude, directly delabel or stratify children to oral antibiotic challenge in outpatient department or primary care practice. MAIN OUTCOME MEASURES: To assess the safety of using the questionnaire-based algorithm for proceeding to a direct oral provocation challenge.The secondary outcomes were to look for associations and predictive factors in positive challenges and to assess parent/carer acceptability of the service by using Likert Scale. RESULTS: Successful contact was made with 200 children, of which 153 children could be evaluated based on inclusion criteria, engagement and availability of medical records.15 children were directly delabelled based on history and records. 138 children underwent challenges in outpatient and primary care. 6% of challenges were reactive with a mild, delayed reaction. Overall, a delabelling rate of 91% was achieved. There were no clear predictors for a positive challenge. CONCLUSION: Our questionnaire-based algorithm for stratifying children with antibiotic allergies to proceed directly to an oral outpatient or primary care challenge was found to be safe, feasible and acceptable.

Emollients for preventing atopic eczema: Cost-effectiveness analysis of the BEEP trial.

BACKGROUND: Recent discoveries have led to the suggestion that enhancing skin barrier from birth might prevent eczema and food allergy. OBJECTIVE: To determine the cost-effectiveness of daily all-over-body application of emollient during the first year of life for preventing atopic eczema in high-risk children at 2 years from a health service perspective. We also considered a 5-year time horizon as a sensitivity analysis. METHODS: A within-trial economic evaluation using data on health resource use and quality of life captured as part of the BEEP trial alongside the trial data. Parents/carers of 1394 infants born to families at high risk of atopic disease were randomised 1:1 to the emollient group, which were advised to apply emollient (Doublebase Gel or Diprobase Cream) to their child at least once daily to the whole body during the first year of life or usual care. Both groups received advice on general skin care. The main economic outcomes were incremental cost-effectiveness ratio (ICER), defined as incremental cost per percentage decrease in risk of eczema in the primary cost-effectiveness analysis. Secondary analysis, undertaken as a cost-utility analysis, reports incremental cost per Quality-Adjusted Life Year (QALY) where child utility was elicited using the proxy CHU-9D at 2 years. RESULTS: At 2 years, the adjusted incremental cost was £87.45 (95% CI -54.31, 229.27) per participant, whilst the adjusted proportion without eczema was 0.0164 (95% CI -0.0329, 0.0656). The ICER was £5337 per percentage decrease in risk of eczema. Adjusted incremental QALYs were very slightly improved in the emollient group, 0.0010 (95% CI -0.0069, 0.0089). At 5 years, adjusted incremental costs were lower for the emollient group, -£106.89 (95% CI -354.66, 140.88) and the proportion without eczema was -0.0329 (95% CI -0.0659, 0.0002). The 5-year ICER was £3201 per percentage decrease in risk of eczema. However, when inpatient costs due to wheezing were excluded, incremental costs were lower and incremental effects greater in the usual care group. CONCLUSIONS: In line with effectiveness endpoints, advice given in the BEEP trial to apply daily emollient during infancy for eczema prevention in high-risk children does not appear cost-effective.

Phase 3 Trial of Epicutaneous Immunotherapy in Toddlers with Peanut Allergy.

BACKGROUND: No approved treatment for peanut allergy exists for children younger than 4 years of age, and the efficacy and safety of epicutaneous immunotherapy with a peanut patch in toddlers with peanut allergy are unknown. METHODS: We conducted this phase 3, multicenter, double-blind, randomized, placebo-controlled trial involving children 1 to 3 years of age with peanut allergy confirmed by a double-blind, placebo-controlled food challenge. Patients who had an eliciting dose (the dose necessary to elicit an allergic reaction) of 300 mg or less of peanut protein were assigned in a 2:1 ratio to receive epicutaneous immunotherapy delivered by means of a peanut patch (intervention group) or to receive placebo administered daily for 12 months. The primary end point was a treatment response as measured by the eliciting dose of peanut protein at 12 months. Safety was assessed according to the occurrence of adverse events during the use of the peanut patch or placebo. RESULTS: Of the 362 patients who underwent randomization, 84.8% completed the trial. The primary efficacy end point result was observed in 67.0% of children in the intervention group as compared with 33.5% of those in the placebo group (risk difference, 33.4 percentage points; 95% confidence interval, 22.4 to 44.5; P<0.001). Adverse events that occurred during the use of the intervention or placebo, irrespective of relatedness, were observed in 100% of the patients in the intervention group and 99.2% in the placebo group. Serious adverse events occurred in 8.6% of the patients in the intervention group and 2.5% of those in the placebo group; anaphylaxis occurred in 7.8% and 3.4%, respectively. Serious treatment-related adverse events occurred in 0.4% of patients in the intervention group and none in the placebo group. Treatment-related anaphylaxis occurred in 1.6% in the intervention group and none in the placebo group. CONCLUSIONS: In this trial involving children 1 to 3 years of age with peanut allergy, epicutaneous immunotherapy for 12 months was superior to placebo in desensitizing children to peanuts and increasing the peanut dose that triggered allergic symptoms. (Funded by DBV Technologies; EPITOPE ClinicalTrials.gov number, NCT03211247.).

Emollients for prevention of atopic dermatitis: 5-year findings from the BEEP randomized trial.

BACKGROUND: The effectiveness of emollients for preventing atopic dermatitis/eczema is controversial. The Barrier Enhancement for Eczema Prevention trial evaluated the effects of daily emollients during the first year of life on atopic dermatitis and atopic conditions to age 5 years. METHODS: 1394 term infants with a family history of atopic disease were randomized (1:1) to daily emollient plus standard skin-care advice (693 emollient group) or standard skin-care advice alone (701 controls). Long-term follow-up at ages 3, 4 and 5 years was via parental questionnaires. Main outcomes were parental report of a clinical diagnosis of atopic dermatitis and food allergy. RESULTS: Parents reported more frequent moisturizer application in the emollient group through to 5 years. A clinical diagnosis of atopic dermatitis between 12 and 60 months was reported for 188/608 (31%) in the emollient group and 178/631 (28%) in the control group (adjusted relative risk 1.10, 95% confidence interval 0.93 to 1.30). Although more parents in the emollient group reported food reactions in the previous year at 3 and 4 years, cumulative incidence of doctor-diagnosed food allergy by 5 years was similar between groups (92/609 [15%] emollients and 87/632 [14%] controls, adjusted relative risk 1.11, 95% confidence interval 0.84 to 1.45). Findings were similar for cumulative incidence of asthma and hay fever. CONCLUSIONS: Daily emollient application during the first year of life does not prevent atopic dermatitis, food allergy, asthma or hay fever.

BSACI guideline for the set-up of penicillin allergy de-labelling services by non-allergists working in a hospital setting.

The Standards of Care Committee of the British Society for Allergy and Clinical Immunology (BSACI) and a committee of experts and key stakeholders have developed this guideline for the evaluation and testing of patients with an unsubstantiated label of penicillin allergy. The guideline is intended for UK clinicians who are not trained in allergy or immunology, but who wish to develop a penicillin allergy de-labelling service for their patients. It is intended to supplement the BSACI 2015 guideline "Management of allergy to penicillin and other beta-lactams" and therefore does not detail the epidemiology or aetiology of penicillin allergy, as this is covered extensively in the 2015 guideline (1). The guideline is intended for use only in patients with a label of penicillin allergy and does not apply to other beta-lactam allergies. The recommendations include a checklist to identify patients at low risk of allergy and a framework for the conduct of drug provocation testing by non-allergists. There are separate sections for adults and paediatrics within the guideline, in recognition of the common differences in reported allergy history and likelihood of true allergy.

Burden of allergic disease among ethnic minority groups in high-income countries.

The COVID-19 pandemic raised acute awareness regarding inequities and inequalities and poor clinical outcomes amongst ethnic minority groups. Studies carried out in North America, the UK and Australia have shown a relatively high burden of asthma and allergies amongst ethnic minority groups. The precise reasons underpinning the high disease burden are not well understood, but it is likely that this involves complex gene-environment interaction, behavioural and cultural elements. Poor clinical outcomes have been related to multiple factors including access to health care, engagement with healthcare professionals and concordance with advice which are affected by deprivation, literacy, cultural norms and health beliefs. It is unclear at present if allergic conditions are intrinsically more severe amongst patients from ethnic minority groups. Most evidence shaping our understanding of disease pathogenesis and clinical management is biased towards data generated from white population resident in high-income countries. In conjunction with standards of care, it is prudent that a multi-pronged approach towards provision of composite, culturally tailored, supportive interventions targeting demographic variables at the individual level is needed, but this requires further research and validation. In this narrative review, we provide an overview of epidemiology, sensitization patterns, poor clinical outcomes and possible factors underpinning these observations and highlight priority areas for research.

Food protein-induced enterocolitis syndrome in the British Isles.

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a delayed type of food allergy, most often seen in infancy. We aimed to estimate its incidence, to describe common food triggers and the patient journeys of this rare but serious condition. DESIGN: We undertook a prospective epidemiological survey of FPIES using the British Paediatric Surveillance Unit. SETTING: UK and Ireland. PARTICIPANTS: A survey of all paediatricians over 13 months between January 2019 and February 2020. MAIN OUTCOME MEASURES: 204 cases were reported, 98 (48%) meeting case definition, giving an incidence of 0.006% for England based on 93 cases. RESULTS: 98 patients reported 135 trigger foods, 27% (26 of 98) had multiple food triggers. Common food triggers included cow's milk (24%, 33 of 135), fruits and vegetables (19%, 26 of 135), hen's egg (16%, 22 of 135) and fish (14%, 19 of 135). In 46% (41 of 90), the initial trigger food had been ingested three or more times before diagnosis, with a median diagnostic delay of 7.9 months (3.0, 17.3). Half (50 of 98) were admitted, yet only 5% (5 of 98) received appropriate acute treatment with ondansetron. Most cases were diagnosed by an allergy specialist (74 of 98, 76%), within a median of 7.5 (3.0, 13.3) miles from home. CONCLUSION: The incidence of FPIES was significantly lower than expected across the whole of the British Isles. Most reports were of cases local to specialist allergy centres, with delays in diagnosis. This suggests under-recognition of FPIES in frontline clinical setting where education of healthcare professionals is required to improve recognition, earlier diagnosis and treatment.

Searching for the true attrition rate of UK paediatric trainees.

OBJECTIVE: To quantitatively analyse the number of doctors leaving the paediatric specialty training (ST) programme in the UK, to assist with evidence-based workforce planning. DESIGN: Data were sought on those leaving the UK paediatrics training programme between 2014 and 2019 from Heads of Schools of Paediatrics and Freedom of Information Act requests. SETTING: Retrospective data analysis. OUTCOME MEASURES: Overall attrition rate, attrition rate across level of training, attrition rate across geographical area, recorded reason for leaving. RESULTS: All results must be interpreted with caution due to limitations in record keeping and analysis. The annual attrition rate across all ST levels between 2014 and 2019 is estimated at 3.7%-4.2% (ie, 749-845 trainees may have left the paediatric training programme over 2014-2019). No reason for leaving was recorded for three-quarters of individuals, around 630 doctors. Of those leaving paediatrics, significantly more (χ², p=0.015) did so at ST3 (20.3%) versus the next highest training year, ST2 (13.6%). CONCLUSIONS: This project seems to demonstrate worryingly poor record-keeping of the true attrition rate of paediatric trainees by organisations responsible for workforce planning, including Health Education England, the Royal College of Paediatrics and Child Health and individual paediatric schools across the UK. To allow evidence-based workforce planning for the benefit of UK children, it is vital that accurate records on trainees who leave the training programme are kept and shared across the UK.

Completion of paediatric training: trends across 2011-2017 cohorts.

OBJECTIVE: To determine trends in the demographics and destinations of doctors who have recently completed paediatric training in the UK. DESIGN: A survey was sent to all new paediatric certificate holders 1 year on from completing specialty training every year from 2011 to 2017. SETTING: Retrospective survey. OUTCOME MEASURES: Demographics, career destinations, time to complete training, working patterns, subspecialty registration, numbers of job applications, and use of the period of grace are reported. RESULTS: 1262 people who gained their paediatric certificate in the UK between 2011 and 2017 completed the survey (60.6% response rate). 58.5% (n=738) of respondents were female, and 32.4% (n=224) of women work less than full time, compared with 4.6% (n=23) of men. 85.9% (n=1056) of respondents were in a UK consultant post. 7.6% (n=94) were working overseas. 65.1% (n=722) remained in the region they trained in. 64.8% (n=1348) were registered for general paediatrics, whereas 35.2% (n=733) had subspecialised.Respondents who held a non-UK medical degree (47.5%, n=501) made more job applications on average (mean=2.2; 95% CI 2.0 to 2.5) than those with a UK degree (52.5%, n=554) (mean=1.1; 95% CI 1.0 to 1.2) (p<0.001). Average training time increased from 9.8 years (95% CI 9.4 to 10.2) to 11.3 years (95% CI 11.1 to 11.6) (p<0.001). Respondents' use of their grace period reduced from 42.7% (n=47) to 20.6% (n=29) (p<0.001). CONCLUSIONS: The data reflect the diverse paediatric workforce and doctors' working patterns following the completion of paediatric training in the UK. The trends demonstrated are vital to consider for evidence-based workforce planning.

Daily emollient during infancy for prevention of eczema: the BEEP randomised controlled trial.

BACKGROUND: Skin barrier dysfunction precedes eczema development. We tested whether daily use of emollient in the first year could prevent eczema in high-risk children. METHODS: We did a multicentre, pragmatic, parallel-group, randomised controlled trial in 12 hospitals and four primary care sites across the UK. Families were approached via antenatal or postnatal services for recruitment of term infants (at least 37 weeks' gestation) at high risk of developing eczema (ie, at least one first-degree relative with parent-reported eczema, allergic rhinitis, or asthma, diagnosed by a doctor). Term newborns with a family history of atopic disease were randomly assigned (1:1) to application of emollient daily (either Diprobase cream or DoubleBase gel) for the first year plus standard skin-care advice (emollient group) or standard skin-care advice only (control group). The randomisation schedule was created using computer-generated code (stratified by recruiting centre and number of first-degree relatives with atopic disease) and participants were assigned to groups using an internet-based randomisation system. The primary outcome was eczema at age 2 years (defined by UK working party criteria) with analysis as randomised regardless of adherence to allocation for participants with outcome data collected, and adjusting for stratification variables. This trial is registered with ISRCTN, ISRCTN21528841. Data collection for long-term follow-up is ongoing, but the trial is closed to recruitment. FINDINGS: 1394 newborns were randomly assigned to study groups between Nov 19, 2014, and Nov 18, 2016; 693 were assigned to the emollient group and 701 to the control group. Adherence in the emollient group was 88% (466 of 532) at 3 months, 82% (427 of 519) at 6 months, and 74% (375 of 506) at 12 months in those with complete questionnaire data. At age 2 years, eczema was present in 139 (23%) of 598 infants with outcome data collected in the emollient group and 150 (25%) of 612 infants in the control group (adjusted relative risk 0·95 [95% CI 0·78 to 1·16], p=0·61; adjusted risk difference -1·2% [-5·9 to 3·6]). Other eczema definitions supported the results of the primary analysis. Mean number of skin infections per child in year 1 was 0·23 (SD 0·68) in the emollient group versus 0·15 (0·46) in the control group; adjusted incidence rate ratio 1·55 (95% CI 1·15 to 2·09). INTERPRETATION: We found no evidence that daily emollient during the first year of life prevents eczema in high-risk children and some evidence to suggest an increased risk of skin infections. Our study shows that families with eczema, asthma, or allergic rhinitis should not use daily emollients to try and prevent eczema in their newborn. FUNDING: National Institute for Health Research Health Technology Assessment.

An algorithm for diagnosing IgE-mediated food allergy in study participants who do not undergo food challenge.

BACKGROUND: Food allergy diagnosis in clinical studies can be challenging. Oral food challenges (OFC) are time-consuming, carry some risk and may, therefore, not be acceptable to all study participants. OBJECTIVE: To design and evaluate an algorithm for detecting IgE-mediated food allergy in clinical study participants who do not undergo OFC. METHODS: An algorithm for trial participants in the Barrier Enhancement for Eczema Prevention (BEEP) study who were unwilling or unable to attend OFC was developed. BEEP is a pragmatic, multi-centre, randomized-controlled trial of daily emollient for the first year of life for primary prevention of eczema and food allergy in high-risk infants (ISRCTN21528841). We built on the European iFAAM consensus guidance to develop a novel food allergy diagnosis algorithm using available information on previous allergenic food ingestion, food reaction(s) and sensitization status. This was implemented by a panel of food allergy experts blind to treatment allocation and OFC outcome. We then evaluated the algorithm's performance in both BEEP and Enquiring About Tolerance (EAT) study participants who did undergo OFC. RESULTS: In 31/69 (45%) BEEP and 44/55 (80%) EAT study control group participants who had an OFC the panel felt confident enough to categorize children as "probable food allergy" or "probable no food allergy". Algorithm-derived panel decisions showed high sensitivity 94% (95%CI 68, 100) BEEP; 90% (95%CI 72, 97) EAT and moderate specificity 67% (95%CI 39, 87) BEEP; 67% (95%CI 39, 87) EAT. Sensitivity and specificity were similar when all BEEP and EAT participants with OFC outcome were included. CONCLUSION: We describe a new algorithm with high sensitivity for IgE-mediated food allergy in clinical study participants who do not undergo OFC. CLINICAL RELEVANCE: This may be a useful tool for excluding food allergy in future clinical studies where OFC is not conducted.

Perioperative anaphylaxis in children: Etiology, time sequence, and patterns of clinical reactivity.

BACKGROUND: Perioperative anaphylaxis (PA) in children is an uncommon but potentially life-threatening complication associated with anesthesia. Early identification and management of PA is essential to optimize clinical outcomes. METHODS: We performed a retrospective study of anesthesia records from pediatric patients with PA from centers in the United Kingdom, France, and the United States over a period of 10 years. Time sequence of clinical signs and physiological variables during PA were collected, along with results of allergy testing. RESULTS: Twenty-nine children with PA were included. Median age was 11 years. Based on the modified Ring and Messmer Grading Scale, severe reactions were seen in 25 (86%) members of this cohort, with 4 (14%) experiencing cardiac arrest. Life-threatening hypotension was the first clinical sign of PA in 59% of cases, followed by tachycardia and bronchospasm. In 16 (55%) cases, the initial signs of PA involved multiple organ systems. When the initial signs of PA were cardiovascular and/or respiratory, more epinephrine doses were administered. Average time from initial sign of PA to treatment with epinephrine was 6 minutes (SD: 6, range: 1-25). The causative allergen was identified in 15 patients. CONCLUSION: Severe hypotension is the most common presenting sign of PA in children. Initial cardiovascular and/or respiratory signs are associated with the need for increased epinephrine doses. Further studies should optimize the prediction, identification, and early management of PA in children.