A twenty-two-year experience with Hymenoptera venom immunotherapy in a US pediatric tertiary care center 1996-2018.

BACKGROUND: The rate of systemic reactions (SRs) to venom immunotherapy (VIT) in children has not been well evaluated. OBJECTIVE: To evaluate the rate of SRs to VIT in pediatric patients age 5 to 18 years who were treated with a standard protocol. METHODS: A retrospective chart review was conducted to identify patients who received VIT at Boston Children's Hospital from 1996 through 2018. Information on venom testing, severity of reaction to insect field sting, and SRs to VIT were retrieved. RESULTS: A total of 78 patients were included. Most had moderate to severe reactions to insect sting before VIT. The rate of SRs was 0.2% of injection visits, occurring in 9% of patients. The SRs from VIT were mild (mostly grade 1 and some grade 2), and no grades 3, 4, or 5 reactions were seen. Male sex was a significant risk factor for moderate to severe reactions to insect sting. Positive testing to vespinae was seen in 98.7% of patients, and none had exclusive sensitivity to honeybee. The severity of the initial, pre-VIT insect sting reactions in our patients did not correlate with the occurrence of SRs from VIT. Twenty-seven percent of the patients were subsequently stung while on VIT. Only 1 patient (5%) had a mild SR, while all others had only local or no reaction at all. CONCLUSION: In the largest US study evaluating the safety of VIT in children, SRs to VIT were mild, and none required epinephrine. Male sex was significantly associated with higher risk of moderate to severe reactions to insect sting. Larger multicenter studies are needed to further evaluate the rate of SRs to VIT in pediatric patients.

User-centred design for machine learning in health care: a case study from care management.

OBJECTIVES: Few machine learning (ML) models are successfully deployed in clinical practice. One of the common pitfalls across the field is inappropriate problem formulation: designing ML to fit the data rather than to address a real-world clinical pain point. METHODS: We introduce a practical toolkit for user-centred design consisting of four questions covering: (1) solvable pain points, (2) the unique value of ML (eg, automation and augmentation), (3) the actionability pathway and (4) the model's reward function. This toolkit was implemented in a series of six participatory design workshops with care managers in an academic medical centre. RESULTS: Pain points amenable to ML solutions included outpatient risk stratification and risk factor identification. The endpoint definitions, triggering frequency and evaluation metrics of the proposed risk scoring model were directly influenced by care manager workflows and real-world constraints. CONCLUSIONS: Integrating user-centred design early in the ML life cycle is key for configuring models in a clinically actionable way. This toolkit can guide problem selection and influence choices about the technical setup of the ML problem.

Long-Term Outcome of Peanut Oral Immunotherapy Facilitated Initially by Omalizumab.

BACKGROUND: We successfully used omalizumab to facilitate peanut oral immunotherapy (OIT) in children with reactivity to ≤50mg peanut protein and with high peanut IgE (median, 229 kU/L). OBJECTIVE: We report on long-term OIT outcomes in these patients, including dosing changes, adverse events, peanut immunoglobulin changes, and quality of life (QoL). METHODS: Patients were followed for up to 72 months (67 months of maintenance). Outcomes were collected on peanut dose amount, form, and frequency, as well as adverse events, (QoL), and laboratory studies. RESULTS: Of 13 patients initially enrolled, 7 patients (54%) continued on peanut OIT through month 72; 6 (46%) discontinued therapy because of adverse reactions. Maintenance peanut protein dose varied between 500 and 3500mg. Most patients consumed different peanut-containing products. All patients experienced at least 1 adverse event, and 1 patient developed eosinophilic esophagitis. Peanut-IgE, Arah1-IgE and Arah2-IgE, peanut-SPT, peanut-IgE:IgE ratio, and Arah2-IgE:Arah2-IgG4 ratio decreased on OIT. Peanut-IgG4, Arah1-IgG4, and Arah2-IgG4 initially increased on OIT and then decreased, though not falling to baseline levels. In patients who stopped OIT, there was a trend for reversal of these biomarker changes. Higher peanut-IgE and Arah2-IgE at study month 12 were associated with discontinuation. Patient and parent QoL improved from baseline, even in patients who discontinued OIT. CONCLUSIONS: Although adjunctive omalizumab allowed for faster and successful desensitization in patients with high peanut-IgE, almost half of patients discontinued OIT within 72 months because of reactions. Patients who stopped therapy had higher month 12 peanut-IgE and Arah2-IgE. It is possible that these patients might benefit from longer omalizumab administration.

Acquired Cold-Induced Urticaria in Pediatric Patients: A 22-Year Experience in a Tertiary Care Center (1996-2017).

BACKGROUND: Acquired cold-induced urticaria (ACU) has not been well evaluated in pediatrics. OBJECTIVE: To further evaluate the presentation of ACU in children and associated risk of anaphylaxis. METHODS: A retrospective chart review was performed in children 18 years or younger diagnosed with ACU at Boston Children's Hospital (US, Northeast) from 1996 to 2017. RESULTS: A total of 415 patients with ACU were identified, aged 4 months to 18.3 years at the time of diagnosis, with similar male:female distribution. Most patients had a history of atopic disease (78.3%), and 25.8% had other urticaria. Around two-third of patients experienced only localized cold-induced symptoms (grade 1), whereas 14.0% had diffuse cutaneous symptoms (grade 2) as the most severe reaction, and 18.6% experienced anaphylaxis (grade 3). Swimming triggered 77.6% of grade 3 reactions, whereas the rest were secondary to ingestion of cold food or beverages, or cold air or cold water exposure. Seven percent of subjects had more than 1 episode of anaphylaxis. Cold stimulation test (CST) was performed in 61.7% of patients, and the result was positive in 69.9% of those tested. Positive CST result was significantly associated with increased risk of anaphylaxis. There was a 11.7% rate of anaphylaxis among patients with negative CST result. Disease resolution at any point in the study period was documented in 8.9% of patients and was associated with a negative history of anaphylaxis. CONCLUSIONS: In the largest study to date on ACU, grade 3 reactions occurred in about a fifth of patients. Positive CST result was associated with a higher risk for anaphylaxis from ACU. Epinephrine prescription and patient/family counseling about risk factors for grade 3 reactions are recommended.

Systemic Reactions in Pediatric Patients Receiving Standardized Allergen Subcutaneous Immunotherapy with and without Seasonal Dose Adjustment.

BACKGROUND: The 2003 Joint Task Force on Practice Parameters recommended standardizing allergen subcutaneous immunotherapy (SCIT). Data from longitudinal surveillance survey in North America reported a systemic reaction (SR) rate of 0.1% to 0.2% of injection visits. The rate of SR to standardized SCIT in pediatric patients has not been well evaluated. OBJECTIVE: The objective of this study was to evaluate the rate of SRs to standardized SCIT in pediatric patients aged 5 to 18 years in a single tertiary care center in the United States. METHODS: A retrospective chart review was conducted in 2 groups: group 1 started SCIT within a period extending from January 2009 to June 2012, whereas group 2 started SCIT within a period extending from January 2013 to June 2016. The protocol was modified in group 2 such that updosing and maintenance doses were adjusted in the spring for tree and grass pollen and in the fall for weed pollen. RESULTS: There were a total of 128 patients in group 1 and 118 patients in group 2. The rate of SR was 0.429% in group 1 and 0.364% in group 2, which was not significant. There was no difference in the severity of SR in the 2 groups with no-fatal or near-fatal SR noted. Asthma was a significant risk factor in the younger age subgroup aged 5 to 11 years. CONCLUSIONS: Standardized SCIT appears to be associated with an SR rate of 0.429% to 0.364% of visits in pediatric patients. Protocol modification did not lead to a significant drop in SR. Larger multicenter studies are required to further evaluate the rate of SRs from standardized SCIT.