Impact of using less objective symptoms to define tolerated dose during food challenges: A data-driven approach.

BACKGROUND: Food challenges (FCs) form the basis for assessing efficacy outcomes in interventional studies of food allergy; however, different studies have used a variety of similar but not identical criteria to define a challenge reaction, including subjective (nonobjective) symptoms occurring in a single-organ system as dose limiting. OBJECTIVE: Our aim was to undertake a secondary analysis of 4 interventional studies to assess the impact of using less objective criteria to determine challenge-stop on reaction thresholds and their reproducibility. METHODS: We analyzed individual participant data, including individual participant data meta-analysis, by using 3 different published challenge-stop criteria: (1) PRACTALL consesus criteria; (2) Consortium for Food Allergy Research version 3 (CoFAR v3) with at least 1 moderate- or severe-grade symptom; or (3) CoFAR v3 with at least 2 mild symptoms occurring in different organ systems. Reproducibility of challenge threshold was also assessed in participants undergoing subsequent repeat FCs. RESULTS: Four studies, with detailed challenge data from a total of 592 participants, were included. Applying CoFAR v3 definitions for dose-limiting symptoms resulted in an underestimate of reaction thresholds compared with those in PRACTALL (P < .001) that is equivalent to almost a single dosing increment when using a semi-log dosing regimen. Reproducibility was also reduced when applying CoFAR v3 (P < .001 [n = 223]). Using the least conservative interpretation of CoFAR v3 (≥2 mild symptoms occurring in different systems) resulted in a significant overestimate of 15% when assessing oral immunotherapy efficacy. Applying a data-driven minor modification to CoFAR v3 resulted in a new set of challenge-stop criteria with validity similar to that of PRACTALL but one that is simpler to implement and in which significant gastrointestinal discomfort with observable decreased activity remains a dose-limiting symptom. CONCLUSION: The use of less objective symptoms to define challenge-stop compromises the reproducibility of the FC as a tool to assess efficacy outcomes in interventional studies, and potentially overestimates the efficacy of the intervention tested.

Complete Resection of Necrotic Bowel Improves Survival in NEC Without Compromising Enteral Autonomy.

AIMS: Controversy persists regarding operative strategy for necrotising enterocolitis (NEC). Some surgeons advocate resecting all necrotic bowel, whilst others defunction with a stoma, leaving diseased bowel in situ to preserve bowel length. We reviewed our institutional experience of both approaches. METHODS: Neonates undergoing laparotomy for NEC May 2015-2019 were identified. Data extracted from electronic records included: demographics, neonatal Sequential Organ Failure Assessment (nSOFA) score at surgery, operative findings, and procedure performed. Neonates were assigned to two groups according to operative strategy: complete resection of necrotic bowel (CR) or necrotic bowel left in situ (LIS). Primary outcome was survival, and secondary outcome was enteral autonomy. Outcomes were compared between groups. RESULTS: Fifty neonates were identified. Six were excluded: 4 with NEC totalis and 2 with no visible necrosis or histological confirmation of NEC. Of the 44 remaining neonates, 27 were in the CR group and 17 in the LIS group. 32 neonates survived to discharge (73%). On univariate analysis, survival was associated with lower nSOFA score (P = 0.003), complete resection of necrotic bowel (OR 9.0, 95% CI [1.94-41.65]), and being born outside the surgical centre (OR 5.11 [1.23-21.28]). On Cox regression multivariate analysis, complete resection was still strongly associated with survival (OR 4.87 [1.51-15.70]). 28 of the 32 survivors (88%) achieved enteral autonomy. There was no association between operative approach and enteral autonomy (P = 0.373), or time to achieve this. CONCLUSION: Complete resection of necrotic bowel during surgery for NEC significantly improves likelihood of surviving without negatively impacting remaining bowel function. LEVEL OF EVIDENCE: III.