Continuous-wave cavity ringdown for high-sensitivity polarimetry and magnetometry measurements.

We report the development of a novel variant of cavity ringdown polarimetry using a continuous-wave laser operating at 532 nm for highly precise chiroptical activity and magnetometry measurements. The key methodology of the apparatus relies upon the external modulation of the laser frequency at the frequency splitting between non-degenerate left- and right-circularly polarized cavity modes. The method is demonstrated by the evaluation of the Verdet constants of crystalline CeF3 and fused silica, in addition to the observation of gas- and solution-phase optical rotations of selected chiral molecules. Specifically, optical rotations of (i) vapors of α-pinene and R-(+)-limonene, (ii) mutarotating D-glucose in water, and (iii) acidified L-histidine solutions are determined. The detection sensitivities for the gas- and solution-phase chiral activity measurements are ∼30 and ∼120µdeg over a 30 s detection period per cavity round trip pass, respectively. Furthermore, the measured optical rotations for R-(+)-limonene are compared with computations performed using the TURBOMOLE quantum chemistry package. The experimentally observed optically rotatory dispersion of this cyclic monoterpene was thus rationalized via a consideration of its room temperature conformer distribution as determined by the aforementioned single-point energy calculations.

The impact of digital inequities on laryngeal cancer disparities in the US.

OBJECTIVES: To develop and implement a novel, comprehensive tool, the Digital Inequity Index (DII), that quantifiably measures modern-technology access in the US to assess the impact of digital inequity on laryngeal cancer (LC) care nationwide. METHODS: DII was calculated based on 17 census-tract level variables derived from the American Community Survey and Federal Communications Commission. Variables were categorized as infrastructure-access (i.e., electronic device ownership, type of broadband, internet provider availability, income-broadband subscription ratio) or sociodemographic (i.e., education, income, disability status), ranked and then averaged into a composite score. 22,850 patients from 2008 to 2017 in SEER were assessed for regression trends in long-term follow-up, survival, prognosis, and treatment across increasing overall digital inequity, as measured by the DII. This methodology allows for us to assess the independent contribution of digital inequity adjusted for socioeconomic confounders. RESULTS: With increasing overall digital inequity, length of long-term follow-up (p < 0.001) and survival (p = 0.025) decreased. Compared to LC patients with low DII, high DII was associated with increased odds of advanced preliminary staging (OR 1.06; 95 % CI 1.03-1.08), treatment with chemotherapy (OR 1.06; 95 % CI 1.04-1.08), and radiation therapy (OR 1.02; 95 % CI 1.00-1.04), as well as decreased odds of surgical resection (OR 0.96; 95 % CI 0.94-97). CONCLUSIONS: Digital inequities are associated with detrimental trends in LC patient outcomes in the US, allowing discourse for targeted means of alleviating disparities while contextualizing national sociodemographic trends of the impact of online access on informed care.

The Impact of Digital Inequities on Esophageal Cancer Disparities in the US.

BACKGROUND: There is currently no comprehensive tool that quantifiably measures validated factors of modern technology access in the US for digital inequity impact on esophageal cancer care (EC). OBJECTIVE: To assess the influence of digital inequities on esophageal cancer disparities while accounting for traditional social determinants. METHODS: 15,656 EC patients from 2013-2017 in SEER were assessed for significant regression trends in long-term follow-up, survival, prognosis, and treatment with increasing overall digital inequity, as measured by the Digital Inequity Index (DII). The DII was calculated based on 17 census tract-level variables derived from the American Community Survey and Federal Communications Commission. Variables were categorized as infrastructure access or sociodemographic, ranked, and then averaged into a composite score. RESULTS: With increasing overall digital inequity, significant decreases in the length of long-term follow-up (p < 0.001) and survival (p < 0.001) for EC patients were observed. EC patients showed decreased odds of receiving indicated surgical resection (OR 0.97, 95% CI 0.95-99) with increasing digital inequity. They also showed increased odds of advanced preliminary staging (OR 1.02, 95% CI 1.00-1.05) and decreased odds of receiving indicated chemotherapy (OR 0.97;95% CI 0.95-99). CONCLUSIONS: Digital inequities meaningfully contribute to detrimental trends in EC patient care in the US, allowing discourse for targeted means of alleviating disparities while contextualizing national, sociodemographic trends of the impact of online access on informed care.

Perioperative outcomes in children with Hashimoto's thyroiditis undergoing total thyroidectomy.

BACKGROUND: Hashimoto's thyroiditis (HT) affects 1-2 % of the pediatric population. In adults with HT, thyroidectomy is considered challenging and prone to postoperative complications due to the chronic inflammatory process. However, the complications of thyroidectomy among children with HT have not been established. The objective of our study was to evaluate whether children with HT undergoing total thyroidectomy for presumed thyroid cancer have higher complication rates than children without HT. METHODS: A retrospective cohort study of children who underwent total thyroidectomy by high-volume pediatric otolaryngologists between 2014 and 2021. RESULTS: 111 patients met inclusion criteria, 15 of these were diagnosed with HT preoperatively. Operative time and length of admission were similar among the groups. Postoperatively, patients with HT were more likely to have low levels of parathyroid hormone (60 % vs 26 %, p = 0.014) and transient hypocalcemia compared to non-HT patients, present with symptomatic hypocalcemia (67 % vs 27 %, p = 0.006), demonstrate EKG changes (20 % vs 6.3 %, p = 0.035) within 24 h of surgery, and to require both oral and intravenous calcium supplements (80 % vs 35 %, p = 0.001 and 60 % vs 22 % p = 0.004 respectively). Persistent hypocalcemia at 6 months follow-up, and recurrent laryngeal nerve paralysis rates were similar between groups. Parathyroid tissue was found in the thyroid specimen of 9 (60 %) HT patients vs 34 (35 %) non-HT patients (p = 0.069). CONCLUSIONS: The risk of permanent complications among children with HT following thyroidectomy is low. However, patients with HT are more likely to develop symptomatic transient hypocalcemia and to require oral and intravenous calcium supplements in the immediate post-operative period compared to non-HT patients. Tailoring a perioperative treatment protocol to optimize calcium levels may be considered for children with HT.

Total Thyroidectomy and Subsequent Weight Gain in Pediatric Populations.

OBJECTIVE: To evaluate weight gain in children post-thyroidectomy and identify predictors. METHODS: Charts from patients at a tertiary health care facility who underwent total thyroidectomy from 2014 to 2020 were reviewed for Body Mass Index z-scores (BMIz) at the time of thyroidectomy and at 1 and 2-year post-operation intervals. Patient demographic information, comorbidities, pre- and postoperative thyroid stimulating hormone, and postoperative free T4 levels were also extracted. Patients with other known endocrine abnormalities, chronic kidney disease, or without sufficient follow-up were excluded. RESULTS: A total of 56 patients (ages 3-17 years old) met the inclusion criteria (n = 17 Graves' disease; n = 39 presumed cancer). Over the first year, average BMIz significantly increased in patients with Graves' disease (∆BMIz = 0.45 ± 0.77, p = 0.03), Hispanic ethnicity (∆BMIz = 0.43 ± 0.68, p = 0.004), Medicaid/no insurance coverage (∆BMIz = 0.33 ± 0.74, p = 0.038), age <13 years at thyroidectomy (∆BMIz = 0.35 ± 0.68, p = 0.016), and persistent postoperative hypothyroidism (∆BMIz = 0.41 ± 0.41, p = 0.012). These changes remained significant after the second year. Age at thyroidectomy correlated negatively with ∆BMIz only after the first year (r = -0.40, p = 0.002). Regression analysis, controlling for Graves' status, persistent postoperative hypothyroidism, and insurance coverage, identified age at thyroidectomy as a significant predictor of ∆BMIz after the first year (b = -0.06, p = 0.004) and Hispanic ethnicity as a significant predictor after the second year (b = 0.60, p = 0.003). CONCLUSION: A small increase in BMIz post-thyroidectomy was observed across several patient subgroups. Younger age at thyroidectomy and Hispanic ethnicity were associated with increased BMIz in the first 2 years post-thyroidectomy. LEVEL OF EVIDENCE: Level 4 - Historically controlled cohort Laryngoscope, 133:1518-1523, 2023.

Soothe the savage beast: Patient perceptions of the benefits of music therapy in an inpatient rehabilitation facility.

INTRODUCTION: Despite the known benefits of music therapy (MT) and its potential applications in an inpatient rehabilitation facility (IRF), there remains a lack of access to MT in a significant number of hospitals in the United States. Exploration of stakeholder (e.g., physician, therapist, and patient) perceptions as a potential barrier to uptake has been limited. OBJECTIVE: To assess the favorability of patients admitted to an IRF toward MT through the domains of knowledge, attitudes, and beliefs. We hypothesized that patient domain scores would reflect a favorable perception of MT across rehabilitation diagnoses. DESIGN: Descriptive and cross-sectional survey. SETTING: Free-standing, acute IRF. PATIENTS: A total of 119 English-speaking, adult patients across three impairment categories (general rehabilitation, spinal cord injury, and brain injury) were recruited over a 3-month period and during each patient's hospital stay. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: A modified version of the Global Complementary/Alternative and Music Therapy Assessment (GCAMTA) measured the domains of knowledge, attitudes, and beliefs. RESULTS: An overall response rate of 79.3% was achieved. Most patients (n = 95; 79.8%) scored in either the favorable or neutral ranges of the instrument. Age correlated negatively (r = -0.193, p < .05) with total score, whereas highest level of education correlated positively (rs  = 0.222, p < .05). There were no significant differences in scores across impairment categories (V = 0.068, p = .232). Knowledge scores, controlling for education and age, predicted 30.4% of the variance in attitudes and beliefs scores (R2  = 0.304, p < .001). CONCLUSIONS: It is unlikely that patient perceptions are a barrier to MT uptake. Younger, more educated patients have higher knowledge, attitudes, and beliefs about MT. Increasing patient knowledge about MT may improve their attitudes and beliefs, thereby further optimizing this therapy for widespread use.

Perioperative management in chronically anticoagulated children undergoing tonsillectomy.

BACKGROUND: When undergoing tonsillectomy, patients at high risk of thrombosis who require chronic anticoagulation therapy pose a special challenge as bleeding may occur up to 2 weeks after surgery. Because of a lack of evidence-based data, there is no consensus on the best management for such patients. The objective of our study was to review perioperative anticoagulation bridging strategies in children undergoing tonsillectomy. METHODS: The study group were a retrospective series of patients on chronic anticoagulation therapy at high risk of a thromboembolic event, who underwent tonsillectomy from 2010 to 2021. Patients whose anticoagulation treatment was discontinued because of a low risk of thromboembolic events were excluded. RESULTS: Four patients met the inclusion criteria (age range, 1.5-16.1 years). All patients were admitted prior to surgery for bridging therapy with intravenous unfractionated heparin (UFH), drip-titrated to a therapeutic dose until 4-6 h prior to surgery. The estimated blood loss during surgery was minimal in all surgeries. Unfractionated heparin was readministered according to the hospital protocol on the night of surgery and titrated to a therapeutic dose. Warfarin was restarted within 2 days postsurgery for all patients. High-risk patients were kept in hospital until postoperative day 6-8 because of concern for delayed bleeding. One patient was noticed to have blood-tinged sputum requiring no intervention; none of the patients developed early or delayed hematemesis. CONCLUSIONS: Our data show that bridging therapy with UFH has been successful in chronically anticoagulated patients undergoing tonsillectomy. These patients require multidisciplinary care for the management of their pre- and postoperative course.

Abnormal TSH Prior to Surgery in Children with Graves' Disease Predicts Abnormal TSH Following Thyroidectomy.

OBJECTIVE: To identify variables that are associated with poor compliance to thyroid hormone replacement therapy in children after total thyroidectomy. METHOD: A retrospective cohort study of children who underwent total thyroidectomy by high-volume pediatric otolaryngologists between 1/2014 and 9/2021. Postoperative poor compliance was characterized by at least three separate measurements of high TSH levels not associated with radioactive iodine treatment. RESULTS: There were 100 patients, ages 3-20 years old who met inclusion criteria; 44 patients underwent thyroidectomy for cancer diagnosis, and 56 for Graves' disease. The mean follow-up time was 36.5 months (range 3.0-95.6 months). Overall, 42 patients (42%) were found to have at least three measurements of high TSH during follow-up, and 29 patients (29%) were diagnosed with clinical hypothyroidism. Sex, race, income, insurance type, and benign versus malignant etiology for thyroidectomy were not associated with adherence to therapy. Multivariate regression analysis identified patients with Graves' disease and hyperthyroidism at the time of surgery and Hispanic ethnicity to be associated with postoperative clinical hypothyroidism (OR 9.38, 95% CI 2.16-49.2, p = 0.004 and OR 6.15, 95% CI 1.21-36.0, p = 0.033, respectively). CONCLUSIONS: Preoperative hyperthyroidism in patients with Graves' disease and Hispanic ethnicity were predictors of postoperative TSH abnormalities. Preoperative counseling for patients and their families on the implications of total thyroidectomy and the need for life-long medications postoperatively is necessary. Efforts should be made to evaluate and improve adherence to therapy pre-and postoperatively in patients with Graves' disease. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2402-2406, 2023.

Perspectives and Experiences of College-Aged Singers Regarding Voice Injury and Visiting the ENT: A Phenomenological Approach.

Among singers, stigma surrounding voice injury can affect self-esteem, self-efficacy, and self-worth and can lead to hesitancy to disclose vocal injuries for fear of damaging their career. In addition, stressors in the singer-physician relationship can work against positive interactions with physicians. To date, no study has documented the perspectives of singers about voice injury and their interactions with physicians through a qualitative approach. The purpose of this study was to a) examine the perspectives and experiences of college-aged singers regarding voice injury and visiting an ear, nose, and throat physician (ENT), and b) identify behaviors of singers and ENT physicians that establish a functional and healthy relationship with the other. Following an interpretive phenomenological design, 6 collegiate singers were interviewed using a semi-structured guide, and from the results of these interviews three emergent themes were generated: a) the emotional connection of a singer and their voice, b) the presence of stigma surrounding voice injury, and c) the barriers to effective relationships between a singer and an ENT physician.

All Tied Up: The Effect of Wearing a Necktie on Acoustic and Perceptual Measures of Male Solo Singing.

The purpose of this study was to assess acoustically (long-term average spectra and multidimensional voice profile) and perceptually (participant perceived phonatory ease and expert listening panel) the effect of wearing a necktie on male singing in a solo setting. No study to date has assessed the potential effects of wearing neckties in a solo vocal setting. Among primary results: (a) statistically significant differences in spectral energy (0-10 kHz) between performances with and without a necktie, (b) increases in mean jitter and shimmer percentage measurements of singers with a necktie, (c) significant reduction in perceived phonatory ease when singing while wearing a necktie, and (d) listener preferences for singing without a necktie. Results were discussed in terms of limitations of the study, suggestions for future research, and implications for voice pedagogy.

Fight Song on Mute: University Pep Band Member Noise Dosages and Noise-Induced Hearing Loss Knowledge.

The occurrence of noise-induced hearing loss (NIHL) can be detrimental to the future careers of student musicians. Few studies have focused on the noise exposure of student musicians within an indoor pep band as they performed during university basketball games. The purpose of this longitudinal study was to assess: (a) the status of noise dosages acquired via personal noise dosimeters from two pep band players as they performed over nine men's basketball games spanning three seasons, (b) perceived effectiveness of earplugs on the primary participants, and (c) the status of all band members' (n=72) knowledge of hearing loss and hearing loss prevention. The noise dosages accrued by primary participants in each game over the three seasons greatly exceeded the National Institute for Occupational Safety and Health's (NIOSH) recommendation regarding safe daily noise exposure time. Participants occasionally reported that the earplugs did not provide sufficient protection from noise or contributed to communication and intonation issues. Questionnaire responses from band members demonstrated a mild deficiency in hearing loss knowledge. Two-thirds of pep band members reported that they did not always wear hearing protection at pep band functions. Exceeding standard noise dosage recommendations without hearing protection potentially leaves these individuals at a high risk for permanent hearing loss.

Usability and preference of epinephrine auto-injectors: Auvi-Q and EpiPen Jr.

BACKGROUND: Despite the importance of prompt epinephrine auto-injector (EAI) treatment during anaphylaxis, proper administration technique is often lacking among patients and caregivers. OBJECTIVE: To compare usability and participant preference of Auvi-Q and EpiPen Jr EAIs in a simulated life-threatening allergic emergency-use scenario. METHODS: In this randomized, crossover, human-factors usability study, untrained adults (18-65 years) were tasked with using 0.15 mg Auvi-Q and EpiPen Jr trainers to simulate epinephrine administration to a child-sized manikin. Only written instructions on the device label and/or device voice instructions were available to participants. Endpoints included completing injection tasks per device instructions (primary endpoint), completing key injection tasks, and participant preference/ratings of devices. Completion of injection tasks were evaluated using a McNemar test for paired dichotomous data. RESULTS: Ninety-six adults were included in study analyses. Significantly more participants completed all injection tasks per device instructions with Auvi-Q (85.4%) vs EpiPen Jr (19.8%; P < .001). Significant differences were also observed for completion of key injection tasks (Auvi -Q, 94.8%; EpiPen Jr, 72.9%; P < .001). No digital/hand injection errors were seen with Auvi-Q, whereas 14 participants (14.6%) would have accidentally received a digital/hand injection with EpiPen Jr (P < .001). Overall, significantly more participants preferred Auvi-Q over EpiPen Jr (91.7% vs 6.3%; P < .001 [2.1% no preference]). Median scores for 8 EAI characteristics were also higher for Auvi-Q vs EpiPen Jr. CONCLUSION: In this study, untrained adults preferred and were more likely to use Auvi-Q correctly vs EpiPen Jr, highlighting the importance of device design for successful epinephrine administration during a life-threatening allergic emergency.

Human factors engineering validation study for a novel 0.1-mg epinephrine auto-injector.

Background: Anaphylaxis in infants and young children is increasing. Historically, epinephrine auto-injectors (EAI) were not available in a dose or platform designed for patients who weighed <15 kg, and, therefore, 0.15-mg EAIs were prescribed for these patients. Results of ultrasound studies indicate that currently marketed 0.15-mg EAIs have needle lengths that may strike bone in ∼29 to 43% of patients who weigh <15 kg and result in possible intraosseous injection. An EAI with a more weight-appropriate 0.1-mg dose and shorter needle length has been developed to potentially help minimize the risk of striking bone during epinephrine injection in patients who weigh 7.5-15 kg. Objective: A human factors usability study was completed to validate the 0.1-mg EAI user interface. Methods: This study was conducted with parents of children who were severely allergic so to evaluate simulated use of the 0.1-mg EAI by the intended user group. Fifteen participants were enrolled and received training on using the 0.1-mg EAI. Approximately 24 hours later, the participants completed a simulated emergency-use scenario by using the 0.1-mg EAI with an infant manikin. The primary end point was successful simulated administration of a meaningful epinephrine dose. Results: All the participants simulated administration of a meaningful epinephrine dose. Fourteen participants successfully used the 0.1-mg EAI per the instructions for use in the simulated emergency-use scenario. One participant did not press the EAI against the thigh for the length of time defined for this critical task; however, the EAI was pressed long enough for complete delivery of the 0.1-mg dose. Conclusion: This study validated the user interface of the 0.1-mg EAI for the intended users, uses, and use environments.

Application of human factors engineering (HFE) to the design of a naloxone auto-injector for the treatment of opioid emergencies.

The increased use of opioids for chronic treatment of pain and the resulting epidemic of opioid overdoses have created a major public health challenge. Parenteral naloxone has been used since the 1970's to treat opioid overdose. Recently, a novel naloxone auto-injector device (EVZIO, kaleo, Inc., Richmond, VA) was approved by the Food and Drug Administration. In this article, we review the Human Factors Engineering (HFE) process used in the development and testing of this novel naloxone auto-injector currently used in nonmedical settings for the emergency treatment of known or suspected opioid overdose. HFE methods were employed throughout the product development process for the naloxone auto-injector including formative and summative studies in order to optimize the auto-injector's user interface, mitigate use-related hazards and increase reliability during an opioid emergency use scenario. HFE was also used to optimize the product's design and user interface in order to reduce or prevent user confusion and misuse. The naloxone auto-injector went through a rigorous HFE process that included perceptual, cognitive, and physical action analysis; formative usability evaluations; use error analysis and summative design validation studies. Applying HFE resulted in the development of a product that is safe, fast, easy and predictably reliable to deliver a potentially life-saving dose of naloxone during an opioid overdose emergency. The naloxone auto-injector may be considered as a universal precaution option for at-risk patients prescribed opioids or those who are at increased risk for an opioid overdose emergency.

Comparative Usability Study of a Novel Auto-Injector and an Intranasal System for Naloxone Delivery.

INTRODUCTION: The standard of care for reversal of opioid-induced respiratory depression associated with opioid overdose is injectable naloxone. This study compared the usability of two naloxone delivery devices, a naloxone auto-injector (NAI) and a naloxone intranasal delivery system (NXN), in the administration of naloxone during a simulated opioid overdose emergency. NAI (EVZIO (®) ; kaleo, Inc., Richmond, VA, USA) is a Food and Drug Administration approved single-use pre-filled auto-injector containing 0.4 mg of naloxone. METHODS: Study participants were randomly assigned to administer naloxone using NAI and NXN, sequentially. The primary endpoint was successful administration of a simulated dose of naloxone into a mannequin during a simulated opioid emergency, both before and after receiving training. Secondary endpoints included using the NAI or NXN in accordance with the instructions-for-use and the comparative measurement of successful completion time of administration for both NAI and NXN. RESULTS: A total of 42 healthy participants aged 18-65 years were enrolled in the study. The proportion of participants able to successfully administer a simulated dose of naloxone was significantly greater for NAI compared to NXN both before (90.5% vs. 0.0%, respectively, P < 0.0001) and after (100% vs. 57.1%, respectively, P < 0.0001) participant training. The proportion of participants able to administer a simulated dose of naloxone in accordance with the instructions-for-use was also significantly greater for NAI compared to NXN before (85.7% vs. 0.0%, respectively, P < 0.0001) and after (100% vs. 0.0%, respectively, P < 0.0001) participant training. The average time to task completion for administration attempt before training was 0.9 ± 0.25 min for NAI versus 6.0 ± 4.76 min for NXN and after training was 0.5 ± 0.15 min for NAI versus 2.0 ± 2.15 min for NXN. CONCLUSION: Laypersons experienced substantially greater success administering a simulated dose of naloxone, both before and after training, using NAI versus NXN during a simulated opioid overdose emergency. No participants correctly used NXN without training.

Drug-device combination products in the twenty-first century: epinephrine auto-injector development using human factors engineering.

INTRODUCTION: The systematic application of human factors engineering (HFE) principles to the development of drug-device combination products, including epinephrine auto-injectors (EAIs), has the potential to improve the effectiveness and safety of drug administration. AREAS COVERED: A PubMed search was performed to assess the role of HFE in the development of drug-device combination products. The following keywords were used in different combinations: 'human factors engineering,' 'human factors,' 'medical products,' 'epinephrine/adrenaline auto-injector,' 'healthcare' and 'patient safety.' This review provides a summary of HFE principles and their application to the development of drug-device combination products as advised by the US FDA. It also describes the HFE process that was applied to the development of Auvi-Q, a novel EAI, highlighting specific steps that occurred during the product-development program. EXPERT OPINION: For drug-device combination products, device labeling and usability are critical and have the potential to impact clinical outcomes. Application of HFE principles to the development of drug-delivery devices has the potential to improve product quality and reliability, reduce risk and improve patient safety when applied early in the development process. Additional clinical and real-world studies will confirm whether the application of HFE has helped to develop an EAI that better meets the needs of patients at risk of anaphylaxis.

Design validation and labeling comprehension study for a new epinephrine autoinjector.

BACKGROUND: To facilitate the correct use of epinephrine autoinjectors (EAIs) by patients and caregivers, a novel EAI (Auvi-Q) was designed to help minimize use-related hazards. OBJECTIVE: To support validation of Auvi-Q final design and assess whether the instructions for use in the patient information leaflet (PIL) are effective in training participants on proper use of Auvi-Q. METHODS: Healthy participants, 20 adult and 20 pediatric, were assessed for their ability to complete a simulated injection by following the Auvi-Q instructions for use. Participants relied only on the contents of the PIL and other labeling features (device labeling and its instructions for use, electronic voice instructions and visual prompts). RESULTS: The mean ± SD age of the adult and pediatric participants was 39.4 ± 11.6 and 10.9 ± 2.3 years, respectively. In total, 80% of adult and 35% of pediatric participants had prior experience with EAIs. All adults and 95% of pediatric participants completed a simulated injection on the first attempt; 1 pediatric participant required parental training and a second attempt. Three adult and 4 pediatric participants exhibited a noncritical issue while successfully completing the simulated injection. Most participants agreed that the injection steps were easy to follow and the PIL facilitated understanding on using Auvi-Q safely and effectively. CONCLUSION: The PIL and other labeling features were effective in communicating instructions for successful use of Auvi-Q. This study provided validation support for the final design and anticipated instructions for use of Auvi-Q.