Better defining best-aided condition: The role of hearing aids on cochlear implantation qualification rates.

OBJECTIVE: Describe the effect of hearing aid type used during cochlear implantation evaluation on qualification rates. METHODS: Consecutive adult patients at an academic cochlear implant program undergoing cochlear implantation evaluation were identified to determine cochlear implantation qualification rate according to history of hearing aid use and type of hearing aid used during evaluation. RESULTS: 609 patients met criteria. 90.1% of patients reported prior use of a hearing aid, and 77.4% reported current use of a hearing aid. Patients were most likely to undergo cochlear implantation evaluation utilizing their own personal hearing aids exclusively (61.6%) followed by loaner hearing aids fitted at the time of the evaluation (28.2%). White patients were more likely to be tested using personal hearing aids (OR = 2.60, 95% CI 1.43 to 4.71). Married patients were more likely to be current hearing aid users (OR 1.62, 95% CI 1.04 to 2.51) and were more likely to be tested using personal hearing aids (OR = 1.68, 95% CI 1.10 to 2.56). Patients with a history of any hearing aid use (OR = 2.50, 95% CI 1.42 to 4.40) and current hearing aid use (OR = 1.62, 95% CI 1.06 to 2.49) were more likely to qualify for cochlear implantation. Patients tested using personal hearing aids were 1.5 times more likely to qualify for cochlear implantation (95% CI 0.99 to 2.27). CONCLUSION: History of hearing amplification and current amplification predict cochlear implant qualification. Hearing aids fitted at the time of cochlear implantation evaluation may result in lower qualification rates.

HIF2A gain-of-function mutation modulates the stiffness of smooth muscle cells and compromises vascular mechanics.

Heterozygous gain-of-function (GOF) mutations of hypoxia-inducible factor 2α (HIF2A), a key hypoxia-sensing regulator, are associated with erythrocytosis, thrombosis, and vascular complications that account for morbidity and mortality of patients. We demonstrated that the vascular pathology of HIF2A GOF mutations is independent of erythrocytosis. We generated HIF2A GOF-induced pluripotent stem cells (iPSCs) and differentiated them into endothelial cells (ECs) and smooth muscle cells (SMCs). Unexpectedly, HIF2A-SMCs, but not HIF2A-ECs, were phenotypically aberrant, more contractile, stiffer, and overexpressed endothelin 1 (EDN1), myosin heavy chain, elastin, and fibrillin. EDN1 inhibition and knockdown of EDN1-receptors both reduced HIF2-SMC stiffness. Hif2A GOF heterozygous mice displayed pulmonary hypertension, had SMCs with more disorganized stress fibers and higher stiffness in their pulmonary arterial smooth muscle cells, and had more deformable pulmonary arteries compared with wild-type mice. Our findings suggest that targeting these vascular aberrations could benefit patients with HIF2A GOF and conditions of augmented hypoxia signaling.

Can You Hear Me Now? The Impact of Hearing Loss on Patient Health Literacy.

OBJECTIVE: To elucidate the impact of hearing loss on patient health literacy. STUDY DESIGN: Prospective, cross-sectional study. SETTING: Academic otology practice at a university hospital. PATIENTS: Consecutive, adult, English-speaking patients. MAIN OUTCOME MEASURES: Inadequate health literacy, defined as a composite score of less than or equal to nine on the brief health literacy screen (BHLS), was compared with patient hearing data utilizing the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) hearing classification. Secondary outcome measures included comparisons of inadequate BHLS scores according to patient demographic and clinical information. RESULTS: There were 300 consecutive adult (>18 years old) patients evaluated with the BHLS at a university otology practice between February and March 2019. The median patient age was 60-years (range, 18-91 yr), a slight majority (160, 53.3%) were women, and most patients were White (241, 86.7%) and non-Hispanic (260, 91.6%). Overall, 9.7% of patients were found to have inadequate health literacy. Men had higher rates of inadequate health literacy as compared with women (13.6% versus 6.3%, odds ratio [OR] = 2.35, 95% confidence interval [CI] 1.06-5.25). Audiometric data was available for 284 (95%) patients, of which 235 (82.7%) had class A or B hearing and 49 (17.3%) had class C or D hearing. Patients with Class C or D hearing had a lower median composite BHLS score compared with patients with Class A or B hearing (11.6 versus 13.6, p < 0.0001) and an increased rate of inadequate health literacy (28.6% versus 4.7%, OR = 8.15, 95% CI 3.42-19.37). Increased age, female sex, and better hearing were independent predictors of higher BHLS scores on multivariable analysis. CONCLUSIONS: Hearing loss is an independent risk factor for inadequate health literacy. Providers should be aware of this risk and consider implementing strategies to improve counseling for this at-risk group of patients.

Crowdsourced analysis of clinical trial data to predict amyotrophic lateral sclerosis progression.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with substantial heterogeneity in its clinical presentation. This makes diagnosis and effective treatment difficult, so better tools for estimating disease progression are needed. Here, we report results from the DREAM-Phil Bowen ALS Prediction Prize4Life challenge. In this crowdsourcing competition, competitors developed algorithms for the prediction of disease progression of 1,822 ALS patients from standardized, anonymized phase 2/3 clinical trials. The two best algorithms outperformed a method designed by the challenge organizers as well as predictions by ALS clinicians. We estimate that using both winning algorithms in future trial designs could reduce the required number of patients by at least 20%. The DREAM-Phil Bowen ALS Prediction Prize4Life challenge also identified several potential nonstandard predictors of disease progression including uric acid, creatinine and surprisingly, blood pressure, shedding light on ALS pathobiology. This analysis reveals the potential of a crowdsourcing competition that uses clinical trial data for accelerating ALS research and development.