Validation of a Novel Allergy-Specific Domain for the 22-Item Sino-Nasal Outcomes Test.

OBJECTIVES: To develop and assess the validity of a novel allergy-specific domain for the 22-item sino-nasal outcomes test (SNOT-22), to provide a new tool that efficiently quantifies the impact of allergic rhinitis (AR) concurrent with chronic rhinosinusitis. STUDY DESIGN: Prospective validation study. SETTING: Tertiary care hospital and community-based clinic. METHODS: Proposed items were developed based on clinician and patient input, and further assessed via factor analysis and for internal consistency (n = 1987). Items were then additionally assessed for convergent and discriminant validity (n = 415), applying data from concurrent completions of the Nasal Obstruction and Septoplasty Effectiveness Scale (NOSE), Mini-Rhinoconjunctivitis Quality-of-Life Questionnaire (MiniRQLQ), and validated global health assessments. Assessments of intra-rater reliability, responsiveness to change, and qualitative input were also performed. RESULTS: Factor analysis demonstrated that proposed allergy items mapped to a single domain. Items were internally consistent (Cronbach α: 0.80 within domain, 0.91 within all SNOT). In assessments of convergent validity, domain scores were associated with MiniRQLQ (Spearman's ρ: 0.46, 95% confidence interval [CI]: 0.30-0.59) and NOSE scores (0.36, 95% CI: 0.27-0.44). The novel items also discriminated among clinical states: a 1-point increase in domain score was associated with an 8.32 (95% CI: 5.43-12.75) increase in the odds of prompting a visit for allergy-related symptoms and a 1.52 (95% CI: 1.13-2.05) increase in the odds of positive allergy testing. Intra-rater reliability was substantial (Cohen's κ: 0.8, 95% CI: 0.8-0.9), and responsiveness to change was demonstrated (mean difference: -0.6, 95% CI: -0.8 to -0.4). CONCLUSIONS: This novel domain is a valid, efficient measure of AR alongside rhinosinusitis.

Association of Outpatient Oral Macrolide Use With Sensorineural Hearing Loss in Children, Adolescents, and Young Adults.

Importance: Prior publications have reported the sporadic development of sensorineural hearing loss (SNHL) after intravenous or high-dose macrolide therapy for adults with comorbid conditions, but investigations of the auditory effect of oral outpatient dosing for children, adolescents, and young adults have been limited. Objective: To determine whether broad-based outpatient use of oral macrolide therapy is associated with increased risk of pediatric SNHL through nationally representative analyses. Design, Setting, and Participants: A retrospective case-control study of 875 matched pairs of children, adolescents, and young adults was performed, matching on age, sex, and the time elapsed since prescription date. All eligible pediatric patients were included, with matched control participants from the TRICARE US military health insurance system who were evaluated between October 1, 2009, and September 30, 2014. Exposures: Oral outpatient macrolide treatment compared with penicillin use among pediatric patients. Main Outcomes and Measures: The clinical outcome of interest was SNHL in children, adolescents, and young adults. Multivariable conditional logistic regression was used to compare the risk of prior macrolide exposure with penicillin exposure, adjusted for other risk factors and potential confounders. Four time frames between exposure and diagnosis were additionally assessed. Results: There were 875 eligible matched pairs of children, adolescents, and young adults included. The mean (SD) age of the participants was 5.7 (4.9) years; 1082 participants were male (62%), 58 were Asian (3%), 254 were Black (15%), 1152 were White (66%), and 286 were of Native American and other (no further breakdown was available in the TRICARE database) race and ethnicity (16%). In multivariable analysis, participants who had SNHL had increased odds of having received a macrolide prescription compared with a penicillin prescription when all time frames from exposure were included (adjusted odds ratio, 1.31; 95% CI, 1.05-1.64). There were significantly higher odds of macrolide exposure than penicillin exposure when diagnosis and testing occurred more than 180 days after antibiotic exposure (adjusted odds ratio, 1.79; 95% CI, 1.23-2.60). Conclusions and Relevance: In this case-control study of a nationally representative patient population, findings suggest that children, adolescents, and young adults with SNHL had increased odds of outpatient oral macrolide use compared with penicillin use, particularly when having received a diagnosis more than 180 days after exposure. Further study of the association of macrolides with SNHL in children, adolescents, and young adults is warranted.

Impact of Powered Air-Purifying Respirator Devices on Word Recognition in Health Care Providers.

The coronavirus 2019 pandemic has increased the use of powered air-purifying respirator (PAPR) devices, which produce appreciable noise levels during filtration. Our objective was to determine if active PAPR usage significantly impairs auditory communication in health care providers. We additionally sought to assess what volume of speech presentation was required for adequate communication with providers wearing a PAPR. In subjects with normal hearing at baseline, audiometric data demonstrated a 93% (95% CI, 86%-99%) decrease in word recognition scores during active PAPR usage. Presentation at 85 to 90 dB was needed to obtain word recognition scores similar to baseline in subjects with normal hearing without a PAPR. Pure tone averages also significantly decreased with PAPR usage, by 54 dB (95% CI, 46-62). Active PAPR usage has a substantial impact on auditory perception when utilized by health care providers. The potential longer-term effect of these devices on providers with regular active usage is of interest for future study.

Radiofrequency ablation and related ultrasound-guided ablation technologies for treatment of benign and malignant thyroid disease: An international multidisciplinary consensus statement of the American Head and Neck Society Endocrine Surgery Section with the Asia Pacific Society of Thyroid Surgery, Associazione Medici Endocrinologi, British Association of Endocrine and Thyroid Surgeons, European Thyroid Association, Italian Society of Endocrine Surgery Units, Korean Society of Thyroid Radiology, Latin American Thyroid Society, and Thyroid Nodules Therapies Association.

BACKGROUND: The use of ultrasound-guided ablation procedures to treat both benign and malignant thyroid conditions is gaining increasing interest. This document has been developed as an international interdisciplinary evidence-based statement with a primary focus on radiofrequency ablation and is intended to serve as a manual for best practice application of ablation technologies. METHODS: A comprehensive literature review was conducted to guide statement development and generation of best practice recommendations. Modified Delphi method was applied to assess whether statements met consensus among the entire author panel. RESULTS: A review of the current state of ultrasound-guided ablation procedures for the treatment of benign and malignant thyroid conditions is presented. Eighteen best practice recommendations in topic areas of preprocedural evaluation, technique, postprocedural management, efficacy, potential complications, and implementation are provided. CONCLUSIONS: As ultrasound-guided ablation procedures are increasingly utilized in benign and malignant thyroid disease, evidence-based and thoughtful application of best practices is warranted.

Silencing of Oncogenic KRAS by Mutant-Selective Small Interfering RNA.

Oncogenic mutations in the KRAS gene are well-established drivers of cancer. While the recently developed KRASG12C inhibitors offer a targeted KRAS therapy and have shown success in the clinic, KRASG12C represents only 11% of all KRAS mutations. Current therapeutic approaches for all other KRAS mutations are both indirect and nonmutant-selective, largely focusing on inhibition of downstream KRAS effectors such as MAP kinases. Inhibition of KRAS downstream signaling results in a system-wide down-modulation of the respective targets, raising concerns about systemic cell toxicity. Here, we describe a custom short interfering RNA oligonucleotide (EFTX-D1) designed to preferentially bind mRNA of the most commonly occurring KRAS missense mutations in codons 12 and 13. We determined that EFTX-D1 preferentially reduced the mutant KRAS sequence versus wild-type at the levels of both transcription and translation and reversed oncogenic KRAS-induced morphologic and growth transformation. Furthermore, EFTX-D1 significantly impaired the proliferation of several KRAS mutant cancer cell lines in 2-D as well as 3-D assays. Taken together, our data indicate a novel use of RNA interference to target oncogenic KRAS-driven cancers specifically.