Preventing pediatric accidental decannulation events: A quality improvement initiative.

OBJECTIVE: To describe a quality improvement (QI) method to decrease pediatric accidental decannulation (AD) in the early postoperative period for children under age 3. METHODS: A retrospective chart review was conducted on children under age 3 who underwent tracheostomy at Duke University Health System from August 1, 2013 to May 1, 2023 (n = 104). A root cause analysis was used to assess factors associated with AD following pediatric tracheostomy. Based on the factors identified by the research team, retrospective data was collected before (8/1/13 - 1/31/22) and after (2/1/22 - 5/1/23) a single practice change was implemented: using twill neck ties, rather than foam neck ties, to secure newly-placed tracheostomy tubes. Twill ties were applied intraoperatively as a visual cue to signal a recent tracheostomy for the interdisciplinary care team. The primary outcome in the pre-intervention and post-intervention period was measured as 30-day incidence of AD per 10 tracheostomy cases. RESULTS: Prior to the intervention, a total of 11 ADs occurred in 9 patients across 93 pediatric tracheostomies (1.18 AD per 10 cases). Afterward, 0 ADs occurred across 11 pediatric tracheostomies (0 AD per 10 cases). CONCLUSION: This data suggests that the twill tie intervention may prevent AD and the associated morbidity. With the twill tie initiative, we describe 11 ADs and associated risk factors and present a QI intervention that may help prevent AD and improve patient safety in the early postoperative period.

Impact of Clinical Practice Guidelines on Pediatric Tonsillectomy for Tonsillitis.

OBJECTIVE: To determine the impact of the release of updated American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNSF) Clinical Practice Guidelines (CPG) for Tonsillectomy in Children in 2019 on adherence to evidence-based practice. METHODS: Patients between ages 1 and 18 who had tonsillectomies and encounters for throat infection (tonsillitis or pharyngitis) between of February 5, 2015 and February 4, 2023 were identified by International Classification of Diseases and Current Procedural Terminology codes, excluding those with obstructive sleep-disordered breathing. Retrospective chart review was performed to determine adherence to evidence-based practice. RESULTS: There was a significant increase in adherence to evidence-based practice post-CPG release compared to pre-CPG (85.4% vs 73.1%, P = .0088). There was an observed trend for improved adherence to evidence-based practice for pediatric tonsillectomy for recurrent infection for most of the post-CPG period. There were fewer tonsillectomies performed post-CPG, despite more total encounters for throat infection. DISCUSSION: The publication of the updated AAO-HNSF CPG corresponded with improved adherence to evidence-based practice for tonsillectomy in children for recurrent infection and an observed decrease in overall rate of tonsillectomy. This suggests the CPG may be an effective quality improvement tool for reducing variation and unnecessary patient morbidity or harm. IMPLICATIONS FOR PRACTICE: These findings suggest that the updated AAO-HNSF CPG for Tonsillectomy in Children may have effectively impacted practice patterns, and further work should be done to expand their reach to other specialties and settings. Consideration should also be given to further understand any balancing factors associated with reduced tonsillectomies for recurrent infections including quality of life impact on children managed expectantly.

Identification of CDRH3 loops in the B cell receptor repertoire that can be engaged by candidate immunogens.

A major goal for the development of vaccines against rapidly mutating viruses, such as influenza or HIV, is to elicit antibodies with broad neutralization capacity. However, B cell precursors capable of maturing into broadly neutralizing antibodies (bnAbs) can be rare in the immune repertoire. Due to the stochastic nature of B cell receptor (BCR) rearrangement, a limited number of third heavy chain complementary determining region (CDRH3) sequences are identical between different individuals. Thus, in order to successfully engage broadly neutralizing antibody precursors that rely on their CDRH3 loop for antigen recognition, immunogens must be able to tolerate sequence diversity in the B cell receptor repertoire across an entire vaccinated population. Here, we present a combined experimental and computational approach to identify BCRs in the human repertoire with CDRH3 loops predicted to be engaged by a target immunogen. For a given antibody/antigen pair, deep mutational scanning was first used to measure the effect of CDRH3 loop substitution on binding. BCR sequences, isolated experimentally or generated in silico, were subsequently evaluated to identify CDRH3 loops expected to be bound by the candidate immunogen. We applied this method to characterize two HIV-1 germline-targeting immunogens and found differences in the frequencies with which they are expected to engage target B cells, thus illustrating how this approach can be used to evaluate candidate immunogens towards B cell precursors engagement and to inform immunogen optimization strategies for more effective vaccine design.

Rapid selection of HIV envelopes that bind to neutralizing antibody B cell lineage members with functional improbable mutations.

Elicitation of broadly neutralizing antibodies (bnAbs) by an HIV vaccine will involve priming the immune system to activate antibody precursors, followed by boosting immunizations to select for antibodies with functional features required for neutralization breadth. The higher the number of acquired mutations necessary for function, the more convoluted are the antibody developmental pathways. HIV bnAbs acquire a large number of somatic mutations, but not all mutations are functionally important. In this study, we identify a minimal subset of mutations sufficient for the function of the naturally occurring V3-glycan bnAb DH270.6. Using antibody library screening, candidate envelope immunogens that interact with DH270.6-like antibodies containing this set of key mutations are identified and selected in vitro. Our results demonstrate that less complex B cell evolutionary pathways than those naturally observed exist for the induction of HIV bnAbs by vaccination, and they establish rational approaches to identify boosting candidate immunogens.