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The current study evaluates whether college students can identify characteristics of autism as diagnostic for autism, and characteristics of other disabilities as not diagnostic for autism. This study also examines metacognitive awareness of autism knowledge, evaluating whether college students can accurately calibrate their confidence in their beliefs about autistic characteristics. 283 college students completed the Autism Symptomatology Knowledge Assessment (McMahon et al. Research in Autism Spectrum Disorders 71:101499, 2020). In this assessment, participants were presented with characteristics of autism and other disabilities and asked to identify which characteristics could be used to diagnose someone with autism. For each characteristic, participants indicated how certain they were in their response. Participants more accurately categorized characteristics of autism, particularly social interaction and communication challenges, as being consistent with an autism diagnosis. Participants had more difficulty identifying that characteristics of other disabilities, especially anxiety, ADHD, and learning disabilities, were not diagnostic for autism. For autistic characteristics, participants' confidence and accuracy were positively correlated, such that participants who responded accurately were more confident in their response than those who responded inaccurately. For other disability characteristics, confidence and accuracy were typically not correlated or inversely correlated, indicating poor metacognitive awareness. College students confuse autism with other disabilities, which may have important implications in real-world contexts. Furthermore, individuals with poor metacognitive awareness of their autism knowledge may not realize that they are confusing autism with other disabilities, such that they may not seek out additional corrective information about autism., Competing Interests: Declarations Informed Consent Informed consent was obtained from all study participants. This study was approved by the university Institutional Review Board, and the study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Conflict of Interest The author declares no financial conflicts of interest., (© 2024. The Author(s).)

Purpose: Revumenib, an oral, small molecule inhibitor of the menin-lysine methyltransferase 2A (KMT2A) interaction, showed promising efficacy and safety in a phase I study of heavily pretreated patients with KMT2A -rearranged ( KMT2Ar ) acute leukemia. Here, we evaluated the activity of revumenib in individuals with relapsed/refractory (R/R) KMT2Ar acute leukemia., Methods: AUGMENT-101 is a phase I/II, open-label, dose-escalation and expansion study of revumenib conducted across 22 clinical sites in five countries (ClinicalTrials.gov identifier: NCT04065399). We report results from the phase II, registration-enabling portion. Individuals age ≥30 days with R/R KMT2Ar acute leukemia or with AML and nucleophosmin 1 ( NPM1 ) mutation were enrolled. Revumenib was administered once every 12 hours, at 163 mg (95 mg/m 2 if weight <40 kg) with a strong cytochrome P450 inhibitor, in 28-day cycles. The primary end points were the rate of complete remission (CR) or CR with partial hematologic recovery (CR + CRh) and safety. At a prespecified interim analysis, safety was assessed in all KMT2Ar treated patients; efficacy was assessed in those with centrally confirmed KMT2Ar . The separate NPM1 cohort of the trial is ongoing., Results: From October 1, 2021, to July 24, 2023, N = 94 patients (median [range] age, 37 [1.3-75] years) were treated. Grade ≥3 adverse events included febrile neutropenia (37.2%), differentiation syndrome (16.0%), and QTc prolongation (13.8%). In the efficacy-evaluable patients (n = 57), the CR + CRh rate was 22.8% (95% CI, 12.7 to 35.8), exceeding the null hypothesis of 10% ( P = .0036). Overall response rate was 63.2% (95% CI, 49.3 to 75.6), with 15 of 22 patients (68.2%) having no detectable residual disease., Conclusion: Revumenib led to high remission rates with a predictable safety profile in R/R KMT2Ar acute leukemia. To our knowledge, this trial represents the largest evaluation of a targeted therapy for these patients.

Several autism knowledge assessments include "don't know" as a response option. The inclusion of this response option may lead to systematic error, such that participants' guessing rate affects the measurement of their autism knowledge. This study examines both predictors of guessing rate for autism knowledge and predictors of autism knowledge, including guessing rate. School-based professionals (n = 396) completed the Autism Spectrum Knowledge Scale Professional Version-Revised (ASKSP-R; McClain et al, Journal of Autism and Developmental Disorders 50(3):998-1006, 2020). and the Autism Stigma and Knowledge Questionnaire (ASK-Q; Harrison et al, Journal of Autism and Developmental Disorders 47(10):3281-3295, 2017). Both assessments include "don't know" as a response option. Guessing rate was the strongest predictor of autism knowledge across both the ASKSP-R and the ASK-Q assessments. For the ASKSP-R, participants who were school psychologists, practicing for more years, had more autism-related clinical experiences, and who personally knew an autistic person had a higher guessing rate. School psychologists and participants who worked with more autistic students scored higher in autism knowledge. For the ASK-Q, participants with greater self-perceived autism knowledge had a higher guessing rate. Participants with a doctorate degree, who personally knew an autistic person, and who worked with more autistic students scored higher in autism knowledge. Guessing rate can be a source of systematic error on autism knowledge assessments. Potential solutions to correct for guessing rate are examined and recommended for future use., (© 2024. The Author(s).)

Competing Interests: KMK reports funding to his institution from National Health and Medical Research Council (NHMRC) and the Balnave's Foundation; honorarium for providing expert advice to the Coroners Court of NSW; and is an unpaid Co-Chair of the Hearing for Learning Initiative, a member of the Australian Otitis Media Guidelines Technical Advisory Group, a Committee member of the Australian Society of Otolaryngology, Head and Neck Surgery (ASOHNS), and the Chair Mina of the Royal Australasian College of Surgeons (RACS) Aboriginal and Torres Strait Islander Committee. CMM reports funding to her institution from NHMRC and the Australian Commonwealth Government and she is the Director of the HEAR Centre, a WHO Collaborating Centre, unpaid Co-Chair of the Indigenous Ear Health working group, and Co-Chair of the Innovations in Service Delivery group for the Lancet Commission on Global Hearing Loss.

Purpose: The goal of the current study was to conduct a substantive validity review of four autism knowledge assessments with prior psychometric support (Gillespie-Lynch in J Autism and Dev Disord 45(8):2553-2566, 2015; Harrison in J Autism and Dev Disord 47(10):3281-3295, 2017; McClain in J Autism and Dev Disord 50(3):998-1006, 2020; McMahon in Res Autism Spectr Disord 71:101499, 2020). 69 autism experts who served on the editorial board of one or more peer-reviewed autism journals evaluated the accuracy and ambiguity of autism knowledge questions. 34% of the questions were flagged as "potentially problematic" for accuracy, and 17% of the questions were flagged as "potentially problematic" for ambiguity. Autism expert feedback revealed three themes across ambiguous questions: (1) an oversimplification of mixed or still-evolving research literature, (2) an insufficient recognition of the heterogeneity of the autism spectrum, and (3) a lack of clarity in the question/answer prompt. Substantive validity of future autism knowledge assessments should be carefully evaluated via feedback from a diverse group of autism experts and/or potential respondents. Potentially problematic questions can be removed or modified to improve the validity of autism knowledge assessments., (© 2024. The Author(s).)

Background: Data on population-based self-reported dual vision and hearing impairment are sparse in Europe. We aimed to investigate self-reported dual sensory impairment (DSI) in European population., Methods: A standardised questionnaire was used to collect medical and socio-economic data among individuals aged 15 years or more in 29 European countries. Individuals living in collective households or in institutions were excluded from the survey., Results: Among 296 677 individuals, the survey included 153 866 respondents aged 50 years old or more. The crude prevalence of DSI was of 7.54% (7.36-7.72). Among individuals aged 60 or more, 9.23% of men and 10.94% of women had DSI. Eastern and southern countries had a higher prevalence of DSI. Multivariable analyses showed that social isolation and poor self-rated health status were associated with DSI with ORs of 2.01 (1.77-2.29) and 2.33 (2.15-2.52), while higher income was associated with lower risk of DSI (OR of 0.83 (0.78-0.89). Considering country-level socioeconomic factors, Human Development Index explained almost 38% of the variance of age-adjusted prevalence of DSI., Conclusion: There are important differences in terms of prevalence of DSI in Europe, depending on socioeconomic and medical factors. Prevention of DSI does represent an important challenge for maintaining quality of life in elderly population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Hearing loss affects approximately 1·6 billion individuals worldwide. Many cases are preventable. We aimed to estimate the annual number of new hearing loss cases that could be attributed to meningitis, otitis media, congenital rubella syndrome, cytomegalovirus, and ototoxic medications, specifically aminoglycosides, platinum-based chemotherapeutics, and antimalarials., Methods: We used a targeted and a rapid systematic literature review to calculate yearly global incidences of each cause of hearing loss. We estimated the prevalence of hearing loss for each presumed cause. For each cause, we calculated the global number of yearly hearing loss cases associated with the exposure by multiplying the estimated exposed population by the prevalence of hearing loss associated with the exposure, accounting for mortality when warranted., Findings: An estimated 257·3 million people per year are exposed to these preventable causes of hearing loss, leading to an estimated 33·8 million new cases of hearing loss worldwide per year. Most hearing loss cases were among those with exposure to ototoxic medications (19·6 million [range 12·6 million-27·9 million] from short-course aminoglycoside therapy and 12·3 million from antimalarials). We estimated that 818 000 cases of hearing loss were caused by otitis media, 346 000 by meningitis, 114 000 by cytomegalovirus, and 59 000 by congenital rubella syndrome., Interpretation: The global burden of preventable hearing loss is large. Hearing loss that is attributable to disease sequelae or ototoxic medications contributes substantially to the global burden of hearing loss. Prevention of these conditions should be a global health priority., Funding: The US National Institute on Deafness and Other Communication Disorders and the US National Institute on Aging., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Issue Addressed: Aboriginal and Torres Strait Islander child ear health is complex and multiple. We examined relationships between parent-reported sociodemographic, child health, health service access factors and ear symptoms among Aboriginal and Torres Strait Islander children aged 3 to 7 years., Methods: The Longitudinal Study of Indigenous Children is a large child cohort study with annual parent-reported data collection. Generalised linear mixed model analyses examined Wave 1 (1309 children 0-5 years; 2008) predictors of being free of parent-reported ear symptoms in both Waves 2 and 3., Results: A total of 1030 (78.7%) had no reported ear symptoms in either Wave 2 or 3. In the fully adjusted model, children who had been hospitalised in the past year (aOR = 2.16; 95% CI 1.19-3.93) and those with no ear symptoms (aOR = 2.94; 95% CI, 1.59-5.46) at Wave 1 had higher odds of no ear symptoms in both the subsequent waves. There were also relationships between parent main source of income-government pension or allowance as well as parents who reported no history of their own ear symptoms and higher odds of no ear symptoms in Waves 2 and 3 after partial adjustment for sociodemographic factors., Conclusion: These findings suggest relationships between different sociodemographic and health factors and parent-reported ear symptoms among Aboriginal and Torres Strait Islander children that warrant further investigation. So what? Children with parent-reported ear symptoms during the early years need holistic support to prevent future ear symptoms that impact health, social and educational life trajectories., (© 2023 The Authors. Health Promotion Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of Australian Health Promotion Association.)

Myelodysplastic neoplasm (MDS) is a hematopoietic stem cell disorder that may evolve into acute myeloid leukemia. Fatal infection is among the most common cause of death in MDS patients, likely due to myeloid cell cytopenia and dysfunction in these patients. Mutations in genes that encode components of the spliceosome represent the most common class of somatically acquired mutations in MDS patients. To determine the molecular underpinnings of the host defense defects in MDS patients, we investigated the MDS-associated spliceosome mutation U2AF1-S34F using a transgenic mouse model that expresses this mutant gene. We found that U2AF1-S34F causes a profound host defense defect in these mice, likely by inducing a significant neutrophil chemotaxis defect. Studies in human neutrophils suggest that this effect of U2AF1-S34F likely extends to MDS patients as well. RNA-seq analysis suggests that the expression of multiple genes that mediate cell migration are affected by this spliceosome mutation and therefore are likely drivers of this neutrophil dysfunction., (© 2023. The Author(s).)

The BCL2 inhibitor venetoclax has recently emerged as an important component of acute myeloid leukemia (AML) therapy. Notably, use of this agent has revealed a previously unrecognized form of pathogenesis characterized by monocytic disease progression. We demonstrate that this form of disease arises from a fundamentally different type of leukemia stem cell (LSC), which we designate as monocytic LSC (m-LSC), that is developmentally and clinically distinct from the more well-described primitive LSC (p-LSC). The m-LSC is distinguished by a unique immunophenotype (CD34-, CD4+, CD11b-, CD14-, CD36-), unique transcriptional state, reliance on purine metabolism, and selective sensitivity to cladribine. Critically, in some instances, m-LSC and p-LSC subtypes can co-reside in the same patient with AML and simultaneously contribute to overall tumor biology. Thus, our findings demonstrate that LSC heterogeneity has direct clinical significance and highlight the need to distinguish and target m-LSCs as a means to improve clinical outcomes with venetoclax-based regimens., Significance: These studies identify and characterize a new type of human acute myeloid LSC that is responsible for monocytic disease progression in patients with AML treated with venetoclax-based regimens. Our studies describe the phenotype, molecular properties, and drug sensitivities of this unique LSC subclass. This article is featured in Selected Articles from This Issue, p. 1949., (©2023 American Association for Cancer Research.)

Sensory deprivation can lead to cross-modal cortical changes, whereby sensory brain regions deprived of input may be recruited to perform atypical function. Enhanced cross-modal responses to visual stimuli observed in auditory cortex of postlingually deaf cochlear implant (CI) users are hypothesized to reflect increased activation of cortical language regions, but it is unclear if this cross-modal activity is "adaptive" or "mal-adaptive" for speech understanding. To determine if increased activation of language regions is correlated with better speech understanding in CI users, we assessed task-related activation and functional connectivity of auditory and visual cortices to auditory and visual speech and non-speech stimuli in CI users (n = 14) and normal-hearing listeners (n = 17) and used functional near-infrared spectroscopy to measure hemodynamic responses. We used visually presented speech and non-speech to investigate neural processes related to linguistic content and observed that CI users show beneficial cross-modal effects. Specifically, an increase in connectivity between the left auditory and visual cortices-presumed primary sites of cortical language processing-was positively correlated with CI users' abilities to understand speech in background noise. Cross-modal activity in auditory cortex of postlingually deaf CI users may reflect adaptive activity of a distributed, multimodal speech network, recruited to enhance speech understanding., (© The Author(s) 2022. Published by Oxford University Press.)

Background: Hearing loss (HL) can affect communication in complex ways. Understanding how adults with HL reflect on and conceptualise the way they listen (metacognition) is required if interventions, and the outcome measures used to evaluate them, are to address barriers to functional communication arising from HL., Objectives: This study describes how adults with HL experience and report the processes, behaviours, and components of listening, as presented in published studies., Design: Systematic review and meta-synthesis of qualitative studies., Methods: Systematic searches identified English-language, peer-reviewed journal articles reporting the results of qualitative or mixed-methods studies of adults' with HL perceived listening abilities. Medline, PsychInfo, Web of Science, Embase, and Google Scholar were searched from inception to November 2021. Handsearching reference lists of included studies identified additional studies for inclusion. The Critical Appraisal Skills Programme (CASP) qualitative checklist was used to appraise studies' methodological quality. Data from included studies were analysed using thematic meta-synthesis. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) Confidence in the Evidence from Reviews of QUALitative (CERQual) approach assessed confidence in the review findings. Two reviewers independently completed all screening and quality appraisal. Thematic meta-synthesis and GRADE CERQual assessment was completed by one reviewer and confirmed by a second reviewer. Discrepancies were resolved through discussion., Results: Data from 46 studies were included in the review. Thematic meta-synthesis identified six descriptive themes: 1) perceived listening ability; 2) external modifiers; 3) psychosocial impacts of hearing loss; 4) communication partner perspectives; 5) self-efficacy for listening; and 6) cognitive load. GRADE CERQual ratings for descriptive themes ranged from low to moderate confidence. Descriptive themes were related by analytic themes of liminality and reciprocity., Conclusions: Adults with HL provide in-depth accounts of components and processes of listening, with studies reporting both cognitive and affective experiences consistent with theoretical models of metacognition. The findings will inform content generation for a hearing-specific patient-reported outcome measure of perceived listening ability in everyday communication., Competing Interests: We declare that Dr Hughes receives funding from the National Institute for Health Research (NIHR) Applied Research Collaboration (ARC) West Midlands and UK Research and Innovation (UKRI), UK SPINE, and declares personal fees from Aparito Limited, CIS Oncology, and Astra Zeneca outside the submitted work. Dr Boisvert declares funding from Birmingham Health Partners Centre for Regulatory Science & Innovation / UK SPINE outside the submitted work. All other authors have no competing interests to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Purpose: There are currently limited objective criteria to help assist physicians in determining whether an individual patient with acute myeloid leukemia (AML) is likely to do better with induction with either standard 7 + 3 chemotherapy or targeted therapy with venetoclax plus azacitidine. The study goal was to address this need by developing exploratory clinical decision support methods., Patients and Methods: Univariable and multivariable analysis as well as comparison of a range of machine learning (ML) predictors were performed using cohorts of 120 newly diagnosed 7 + 3-treated AML patients compared with 101 venetoclax plus azacitidine-treated patients., Results: A variety of features in the two patient cohorts were identified that may potentially correlate with short- and long-term outcomes, toxicities, and other considerations. A subset of these diagnostic features was then used to develop ML-based predictors with relatively high areas under the curve of short- and long-term outcomes, hospital stays, transfusion requirements, and toxicities for individual patients treated with either venetoclax/azacitidine or 7 + 3., Conclusion: Potential ML-based approaches to clinical decision support to help guide individual patients with newly diagnosed AML to either 7 + 3 or venetoclax plus azacitidine induction therapy were identified. Larger cohorts with separate test and validation studies are necessary to confirm these initial findings., Competing Interests: Grant WellerEmployment: UnitedHealth Group, BioIntelliSense, IncStock and Other Ownership Interests: UnitedHealth Group Joseph ToninatoEmployment: Cityblock Health, UnitedHealth GroupStock and Other Ownership Interests: UnitedHealth Group, Cityblock Health Sarah StaggsResearch Funding: argenx, ElevateBio, Syros Pharmaceuticals, Kura Oncology Richard ZaneUncompensated Relationships: Riva, Arrive Health Austin GillenResearch Funding: Syros Pharmaceuticals, argenx, Kura Oncology, ElevateBio Justin DaleEmployment: UnitedHealth GroupStock and Other Ownership Interests: UnitedHealth Group Bruce GoodmanEmployment: OptumStock and Other Ownership Interests: UnitedHealth GroupResearch Funding: Optum Nazmul IslamEmployment: Optum/UnitedHealth GroupStock and Other Ownership Interests: Optum/UnitedHealth Group Christine M. McMahonConsulting or Advisory Role: Arcellx, TG Therapeutics, AbbVieResearch Funding: Syros Pharmaceuticals (Inst) Clay SmithResearch Funding: argenx, Syros Pharmaceuticals, Kura 11/21Patents, Royalties, Other Intellectual Property: Patents pending: (1) compositions and methods for reducing cancer stem cells (2) methods for treating acute myeloid leukemia (3) machine language predictor of AML patient responsiveness to treatment with venetoclax and hypomethylating agents (4) subject specific treatments for venetoclax resistant AML Shanshan PeiStock and Other Ownership Interests: CRISPR Therapeutics, Teladoc, Iterum, Abeona TherapeuticsSpeakers' Bureau: AbbViePatents, Royalties, Other Intellectual Property: A pending patent related to detecting and treating venetoclax-resistant AML patientsNo other potential conflicts of interest were reported.

Platinum-based chemotherapeutic agents cisplatin and carboplatin are widely used in cancer treatment worldwide and may result in ototoxic hearing loss. The high incidence of cancer and salient ototoxic effects of platinum-based compounds pose a global public health threat. The purpose of this study was twofold. First, to estimate the prevalence of ototoxic hearing loss associated with treatment with cisplatin and/or carboplatin via a systematic review and meta-analysis. Second, to estimate the annual global burden of ototoxic hearing loss associated with exposure to cisplatin and/or carboplatin. For the systematic review, three databases were searched (Ovid Medline, Ovid Embase, and Web of Science Core Collection) and studies that reported prevalence of objectively measured ototoxic hearing loss in cancer patients were included. A random effects meta-analysis determined pooled prevalence (95% confidence intervals [CI]) of ototoxic hearing loss overall, and estimates were stratified by treatment and patient attributes. Estimates of ototoxic hearing loss burden were created with published global estimates of incident cancers often treated with platinum-based compounds and cancer-specific treatment rates. Eighty-seven records (n = 5077 individuals) were included in the meta-analysis. Pooled prevalence of ototoxic hearing loss associated with cisplatin and/or carboplatin exposure was 43.17% [CI 37.93-48.56%]. Prevalence estimates were higher for regimens involving cisplatin (cisplatin only: 49.21% [CI 42.62-55.82%]; cisplatin & carboplatin: 56.05% [CI 45.12-66.43%]) versus carboplatin only (13.47% [CI 8.68-20.32%]). Our crude estimates of burden indicated approximately one million individuals worldwide are likely exposed to cisplatin and/or carboplatin, which would result in almost half a million cases of hearing loss per year, globally. There is an urgent need to reduce impacts of ototoxicity in cancer patients. This can be partially achieved by implementing existing strategies focused on primary, secondary, and tertiary hearing loss prevention. Primary ototoxicity prevention via otoprotectants should be a research and policy priority., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Aminoglycosides are widely used, broad-spectrum antibiotics with significant potential for ototoxicity. Global efforts to prevent ototoxicity must account for aminoglycoside overuse and non-prescription use., Objectives: The goals of this study were to a) estimate the prevalence of aminoglycoside overuse by synthesizing evidence on self-medication, over the counter (OTC) availability, and household antibiotic storage for later use, and to report the specific aminoglycosides used and the predictors of overuse, and b) leverage this information to comment on potential risk of ototoxicity., Methods: Two systematic search strings were conducted to extract peer-reviewed articles published from 2005 to 2020. The first focused on overuse of aminoglycoside antibiotics. The second focused on potentially ototoxic effects of aminoglycosides related to drug overuse., Results: A total of 26 articles were included (first search string: n = 21; second search string: n = 5). The prevalence of aminoglycoside self-medication was high and household storage and OTC availability of aminoglycosides was common. Gentamicin was the most commonly overused aminoglycoside. No studies provided information on antibiotic dosing or resultant toxicities, including ototoxicity., Conclusions: The limited available evidence indicates that antibiotic overuse (self-medication, home storage, and non-prescription availability) is relatively common, especially in low resource settings, and that aminoglycoside antibiotics comprise a variable, but concerning, proportion of non-prescribed antibiotics. Additional evidence is needed to evaluate the relationship between these dispensing patterns and ototoxicity., (Copyright © 2021. Published by Elsevier Inc.)

Objective: To describe and analyse the linguistic structure of audiological diagnoses for infants, to determine ways to optimise the delivery of diagnostic information to parents during this typically emotive time., Design: This study analysed the linguistic structure of audio-recorded infant diagnostic appointments., Study Sample: Nine appointments conducted by four experienced paediatric audiologists were analysed., Results: Diagnoses of normal hearing were delivered explicitly and in a straightforward manner. Positive aspects of this outcome were highlighted, and audiologists used the pronoun "we," conveying a feeling of teamwork. In contrast, when a hearing loss was diagnosed, the diagnosis included disfluencies and the use of hedging, although positive aspects were also emphasised. In these cases, audiologists used the pronoun "I," thereby taking ownership of the results. Differences in the topics raised by audiologists and parents highlighted a mis-match between the information provided and the information requested. Topics addressed by audiologists were primarily medical and procedural, whereas parents were concerned with causes, treatments and experiential information., Conclusions: The use of the above linguistic strategies may serve to minimise the significance and impact of the diagnosis. Whilst the data are unable to be generalised to other contexts, the study has generated in-depth and nuanced information about diagnosis delivery.

Introduction: Hearing loss in adults has a pervasive impact on health and well-being. Its effects on everyday listening and communication can directly influence participation across multiple spheres of life. These impacts, however, remain poorly assessed within clinical settings. Whilst various tests and questionnaires that measure listening and communication abilities are available, there is a lack of consensus about which measures assess the factors that are most relevant to optimising auditory rehabilitation. This study aimed to map current measures used in published studies to evaluate listening skills needed for oral communication in adults with hearing loss., Methods: A scoping review was conducted using systematic searches in Medline, EMBASE, Web of Science and Google Scholar to retrieve peer-reviewed articles that used one or more linguistic-based measure necessary to oral communication in adults with hearing loss. The range of measures identified and their frequency where charted in relation to auditory hierarchies, linguistic domains, health status domains, and associated neuropsychological and cognitive domains., Results: 9121 articles were identified and 2579 articles that reported on 6714 discrete measures were included for further analysis. The predominant linguistic-based measure reported was word or sentence identification in quiet (65.9%). In contrast, discourse-based measures were used in 2.7% of the articles included. Of the included studies, 36.6% used a self-reported instrument purporting to measures of listening for communication. Consistent with previous studies, a large number of self-reported measures were identified ( n = 139), but 60.4% of these measures were used in only one study and 80.7% were cited five times or fewer., Discussion: Current measures used in published studies to assess listening abilities relevant to oral communication target a narrow set of domains. Concepts of communicative interaction have limited representation in current measurement. The lack of measurement consensus and heterogeneity amongst the assessments limit comparisons across studies. Furthermore, extracted measures rarely consider the broader linguistic, cognitive and interactive elements of communication. Consequently, existing measures may have limited clinical application if assessing the listening-related skills required for communication in daily life, as experienced by adults with hearing loss., Competing Interests: SH receives funding from the National Institute for Health Research (NIHR) Applied Research Collaboration (ARC) West Midlands, UK Research and Innovation (UKRI) and declares personal fees from Aparito Limited and Cochlear Limited outside the submitted work. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Neal, McMahon, Hughes and Boisvert.)

Background: Hearing loss affects over 50% of people in the US across their lifespan and there is a lack of decision modeling frameworks to inform optimal hearing healthcare delivery. Our objective was to develop and validate a microsimulation model of hearing loss across the lifespan in the US., Methods: We collaborated with the Lancet Commission on Hearing Loss to outline model structure, identify input data sources, and calibrate/validate DeciBHAL-US (Decision model of the Burden of Hearing loss Across the Lifespan). We populated the model with literature-based estimates and validated the conceptual model with key informants. We validated key model endpoints to the published literature, including: 1) natural history of sensorineural hearing loss (SNHL), 2) natural history of conductive hearing loss (CHL), and 3) the hearing loss cascade of care. We reported the coefficient of variance root mean square error (CV-RMSE), considering values ≤15% to indicate adequate fit., Findings: For SNHL prevalence, the CV-RMSE for model projected male and female age-specific prevalence compared to sex-adjusted National Health and Nutrition Examination Survey (NHANES) data was 4.9 and 5.7%, respectively. Incorporating literature-based age-related decline in SNHL, we validated mean four-frequency average hearing loss in the better ear (dB) among all persons to longitudinal data (CV-RMSE=11.3%). We validated the age-stratified prevalence of CHL to adjusted NHANES data (CV-RMSE=10.9%). We incorporated age- and severity-stratified time to first hearing aid (HA) use data and HA discontinuation data (adjusted for time-period of use) and validated to NHANES estimates on the prevalence of adult HA use (CV-RMSE=10.3%)., Interpretation: Our results indicate adequate model fit to internal and external validation data. Future incorporation of cost and severity-stratified utility data will allow for cost-effectiveness analysis of US hearing healthcare interventions across the lifespan. Further research might expand the modeling framework to international settings., Funding: This study was funded by the National Institute on Deafness and Other Communication Disorders and the National Institute on Aging (3UL1-TR002553-03S3 and F30 DC019846)., Competing Interests: JRD reports grants from the National Institutes of Health, participation on the National Institute on Deafness and Other Communication Disorders Data Safety Monitoring Board (DSMB) and the National Institute on Aging ACHIEVE (Aging and Cognitive Health Evaluation in Elders) DSMB, and participation on the Board of Directors of the Hearing Health Foundation and on the Executive Council of the Acoustical Society of America. All other authors declare no competing interests., (© 2021 Published by Elsevier Ltd.)

Objectives: Children with hearing loss tend to have poorer psychosocial and quality of life outcomes than their typical-hearing (TH) peers-particularly in the areas of peer relationships and school functioning. A small number of studies for TH children have suggested that group-based music activities are beneficial for prosocial outcomes and help develop a sense of belonging. While one might question whether perceptual limitations would impede satisfactory participation in musical activities, findings from a few studies have suggested that group music activities may have similar benefits for children with hearing loss as well. It is important to note that the effect of music on psychosocial outcomes has primarily been investigated at an anecdotal level. The objective of this study was to explore the effect of a music training program on psychosocial and quality of life outcomes for children with hearing loss. It was hypothesized that music training would provide benefits for domains centered upon peer relationships and prosocial measures., Design: Fourteen children aged 6 to 9 years with prelingual sensorineural hearing loss (SNHL) participated in a 12-week music training program that consisted of group-based face-to-face music therapy supplemented by online music apps. The design was a pseudorandomized, longitudinal study (9 participants were waitlisted, initially serving as a passive control group). Psychosocial wellbeing and quality of life were assessed using a questionnaire battery comprised of the Strengths and Difficulty Questionnaire (SDQ), the Pediatric Quality of Life Inventory, the Hearing Environments and Reflection on Quality of Life (HEAR-QL), and the Glasgow Children's Benefit Inventory. For comparative purposes, responses were measured from 16 TH children that ranged in age from 6 to 9 years., Results: At baseline, children with SNHL had poorer outcomes for internalizing problems, and all measures of the HEAR-QL compared with the TH children. There were no differences for general psychosocial and physical health. After music training, SDQ internalizing problems such as peer relationships and emotional regulation were significantly reduced for the children with SNHL. There were no changes for any outcomes for the passive control group. Additional benefits were noted for emotional and learning factors on the Glasgow Children's Benefit Inventory. However, there were no significant changes for any psychosocial and quality of life outcomes as measured by the Pediatric Quality of Life Inventory or HEAR-QL instruments., Conclusions: The present study provides initial evidence that music training has a positive effect on at least some psychosocial and quality of life outcomes for children with hearing loss. As they are at a greater risk of poorer psychosocial and quality of life outcomes, these findings are cause for cautious optimism. Children with hearing loss should be encouraged to participate in group-based musical activities., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Hearing aids are costly for many Australians with hearing loss who are not eligible for public funding, and are not widely used. The purpose of this article is to describe a recent policy shift from the United States (US) that might improve access to hearing devices and services in Australia. Type of program or service: In 2017, the US legislated the Over-the-Counter Hearing Aid Act of 2017, directing the Food and Drug Administration (FDA) to develop regulations for over-the-counter sale of hearing aids for mild to moderate hearing loss., Findings: Changes in the development of hearing devices and changes to service delivery were well underway in the US prior to anticipated release of new FDA regulations, with new technology entrants in the 'hearables' market. For Australians with hearing loss not eligible for public funding, the current hearing health system is expensive and device-centred. If Australia follows suit with regulatory changes for a class of over-the-counter hearing aids, consumers are likely to benefit from access to safe and affordable devices. Additional policies to support access to hearing services are also likely to be needed., Lessons Learnt: The hearing health system in Australia will undergo tremendous change in the coming years because of the introduction of over-the-counter hearing aids in the US. For Australians to benefit, changes to regulations of devices, as well as hearing services and device provision, will be required., Competing Interests: IB has received funding from the Cochlear–Macquarie Partnership Scheme, and has been paid expenses to attend an Audiology Australia conference as a guest speaker (2018–19). AW has received grant funding from the Johns Hopkins Cochlear Center for Hearing and Public Health. FL has received consultancy fees from Cochlear Ltd, Amplifon and Boehringer Ingleheim. NR has received funding from NIH/NIA, one-time consultancy fees from Helen of Troy and is an advisory board member to audiometry company Shoebox and Neosensory.

Objectives and importance of study: The consequences of sensorineural hearing loss in young children include poor speech and language development, poor educational outcomes,and delayed socio-emotional development. For children who face socio-economic disadvantage, middle ear disease is more prevalent, access to primary health care is more difficult, and psychosocial and education supports are limited. Because of this, the consequences may be amplified. Understanding the risks associated with hearing loss and middle ear dysfunction in underserved populations can enable an earlier, more targeted and cost-effective approach to identifying those with hearing loss and effectively connecting them to systems of care., Study Type: Retrospective study., Method: This study describes the outcomes of an ear and hearing screening program for children from lower socio-economic backgrounds (n = 2489; mean age 11.0 years, standard deviation 1.74 years) in New South Wales (NSW), Australia, between 2013 and 2016. Screening was conducted in a quiet room, and the test protocol included otoscopy, 226 Hertz (Hz) tympanometry, and pure tone screening at octave frequencies from 500 Hz to 4000 Hz with a referral criterion of 20 decibels hearing level (dB HL) at any one frequency. Outcomes were categorised into 1) pass; 2) middle ear dysfunction only; and 3) did not pass hearing screen (with or without middle ear dysfunction). Multinomial logistic regression was used to investigate risk factors for hearing loss and middle ear dysfunction. The factors examined were age, gender, socio-educational advantage, quarter of year assessed, non-English speaking background (NESB), Aboriginal status and region., Results: Higher risks of middle ear dysfunction were associated with younger age and seasonal variation, with higher risk in winter and spring months (July-September and October-December, compared with January-March). There were no differences between those from NESB and those with English as a first language, between the Aboriginal population and non-Aboriginal population, or between those who resided within or outside a major city., Conclusion: More than one in 10 school-age children from lower socio-economic backgrounds experience hearing loss (11.5%). Targeted ear and hearing screening programs offer an opportunity to identify hearing loss during critical learning years and seasons, mitigating longer-term effects on education, and social and mental health., Competing Interests: None delcared.

Competing Interests: None declared.

Objective: A high prevalence of hearing loss in older adults contrasts with a small proportion of people who seek help. Emerging developments in hearing healthcare (HHC) could reduce costs but may not increase access. This study evaluated older adults' perceptions of current and future HHC services in Australia, England, US and Canada to explore potential levers and system improvements., Methods: Semi-structured focus groups (n = 47) were conducted, and data were analysed using a directed content analysis. Participants were adults 60 years and older with a) no hearing problems; b) hearing problems and hearing aid use; and c) hearing problems and no hearing aid use., Results: Perceived barriers, facilitators and preferences were largely consistent across countries, with stigma and trust in HHC being the barriers most often discussed., Conclusion: Although cost and access were consistently deemed important, there may be limited change in help-seeking and HHC uptake unless the key barriers of trust and stigma are addressed. When seeking to undertake transformative change to healthcare it is important to engage recipients of care to understand existing barriers and coproduce a user-centered solution., Competing Interests: AD has received sponsorship from GN Resound to attend conferences, a fee from Natus for lecturing, and royalties paid to Manchester University (when he was employed there) for the intellectual property for Siemen’s HearCheck Screener. KT has received fees from Lend an Ear Inc. for consultancy and developing educational presentations.

Objectives: Listening effort may be defined as the attentional and cognitive resources needed to understand an auditory message, modulated by motivation. Despite the use of hearing devices such as hearing aids or cochlear implants (CIs), the requirement for high listening effort remains a challenge for individuals with hearing loss. The Listening Effort Questionnaire-Cochlear Implant (LEQ-CI) is a hearing-specific patient-reported outcome measure (PROM), which has been designed for use in the CI candidacy and rehabilitation process to assess perceived listening effort in everyday life in adults with severe-profound hearing loss. The LEQ-CI has been developed in line with international consensus-based standards for best practice in PROM construction. The aim of this study was to improve the measurement precision of the LEQ-CI and to assess its psychometric measurement properties., Design: A field test was undertaken with 330 CI patients from five National Health Service auditory implant centers in the United Kingdom. Participants were adults (≥18 years of age), had a severe-profound hearing loss, and met the UK candidacy criteria for cochlear implantation specified by the National Institute for Health and Care Excellence (NICE). Participants completed and returned an anonymized 29-item (each with a 5- or 7-point response option), draft version of the LEQ-CI (LEQ-CI29) and a demographic questionnaire. Rasch analysis was undertaken using Winsteps software and the partial credit model to assess rating scale function and item fit. Results informed refinements to produce a 21-item version (LEQ-CI21), which underwent a further Rasch analysis., Results: The sample was predominantly female: 60.3% (n = 191). Median age of participants was 66 (range 21 to 89) years, with 7.3% (n = 24) of respondents being CI candidates and 92.7% (n = 306) being CI recipients. Mean duration of implantation was 3.8 (SD = 4.8) years. Initial Rasch analysis of the LEQ-CI29 revealed poor rating scale functioning. Collapsing the 5- and 7-point rating scales to 3- and 4-point scales and removing eight items produced a 21-item PROM (LEQ-CI21). Rasch analysis of the LEQ-CI21 showed good fit to the Rasch measurement model. No items showed misfit and dimensionality analysis supported the existence of a single Rasch dimension, defined as perceived listening effort in daily life. Person reliability was 0.91 and the person separation index was 3.28, establishing four levels of person ability. The item separation index was 9.69, confirming the item hierarchy. No items showed differential item functioning for gender or age. The item difficulty range was -0.81 to 1.05, the person ability range for nonextreme persons was -3.54 to 2.49, and the mean person ability was -0.31., Conclusions: Overall, the LEQ-CI21 was found to meet the Rasch model criteria for interval-level measurement. The LEQ-CI21 is the first PROM to be developed specifically for the measurement of perceived listening effort and one of the first patient-reported outcome measures for use with CI patients to be developed using Rasch analysis. The LEQ-CI21 has the potential to be used as a research tool and in clinical practice to evaluate perceived listening effort in daily life. Further psychometric evaluation of the LEQ-CI21 is planned., Competing Interests: This study was funded by a Pathway to Portfolio Grant, Swansea Bay University Health Board. S.E.H. is an independent consultant to Cochlear Ltd. The other authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The ability to navigate "cocktail party" situations by focusing on sounds of interest over irrelevant, background sounds is often considered in terms of cortical mechanisms. However, subcortical circuits such as the pathway underlying the medial olivocochlear (MOC) reflex modulate the activity of the inner ear itself, supporting the extraction of salient features from auditory scene prior to any cortical processing. To understand the contribution of auditory subcortical nuclei and the cochlea in complex listening tasks, we made physiological recordings along the auditory pathway while listeners engaged in detecting non(sense) words in lists of words. Both naturally spoken and intrinsically noisy, vocoded speech-filtering that mimics processing by a cochlear implant (CI)-significantly activated the MOC reflex, but this was not the case for speech in background noise, which more engaged midbrain and cortical resources. A model of the initial stages of auditory processing reproduced specific effects of each form of speech degradation, providing a rationale for goal-directed gating of the MOC reflex based on enhancing the representation of the energy envelope of the acoustic waveform. Our data reveal the coexistence of 2 strategies in the auditory system that may facilitate speech understanding in situations where the signal is either intrinsically degraded or masked by extrinsic acoustic energy. Whereas intrinsically degraded streams recruit the MOC reflex to improve representation of speech cues peripherally, extrinsically masked streams rely more on higher auditory centres to denoise signals., Competing Interests: The authors have declared that no competing interests exist.

Background: Drugs used in curative and prophylactic antimalarial treatment may be ototoxic and lead to permanent hearing loss, but there is no consensus regarding prevalence and permanence of ototoxic hearing loss caused by antimalarials. The purpose of this systematic narrative review was to synthesize current evidence on antimalarial ototoxicity in human populations., Method: Studies published between 2005 and 2018 that reported prevalence of post-treatment hearing loss in individuals treated for malaria were included., Results: Twenty-two studies including data from 21 countries were included. Primary themes of the included studies were to evaluate drug safety and/or efficacy (n = 13) or ototoxic effects of drugs (n = 9). Hearing data were measured objectively in 9 studies. Five studies focused on quinine (or derivates), 10 focused on artemisinin combination therapies, and 7 considered multiple drug combinations. There is a paucity of evidence that thoroughly reports potentially permanent ototoxic effects of antimalarials., Conclusions: Antimalarial drugs may be ototoxic in some cases. More research in human populations is needed to describe ototoxicity of current antimalarials and of future drugs that will be used/developed in response to antimalarial resistance. It is recommended that randomized trials evaluating drug safety objectively measure and report ototoxic hearing loss as an adverse event., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives estimate the prevalence of ototoxic hearing loss in drug-resistant tuberculosis (DR-TB) patients treated with aminoglycoside antibiotics via a systematic review and meta-analysis. Estimate the annual preventable cases of hearing loss in DR-TB patients and leverage findings to discuss primary, secondary and tertiary prevention. Methods studies published between 2005 and 2018 that reported prevalence of post-treatment hearing loss in DR-TB patients were included. We performed a random effects meta-analysis to determine pooled prevalence of ototoxic hearing loss overall and by medication type. Preventable hearing loss cases were estimated using World Health Organization (WHO) data on DR-TB treatment and prevalence determined by the meta-analysis. Results eighteen studies from 10 countries were included. Pooled prevalence of ototoxic hearing loss and the corresponding 95% confidence interval (CI) was 40.62% CI [32.77- 66.61%] for all drugs (kanamycin: 49.65% CI [32.77- 66.61%], amikacin: 38.93% CI [26.44-53.07%], capreomycin: 10.21% CI [4.33-22.21%]). Non-use of aminoglycosides may result in prevention of approximately 50,000 hearing loss cases annually. Conclusions aminoglycoside use results in high prevalence of ototoxic hearing loss. Widespread prevention of hearing loss can be achieved by following updated WHO guidelines for DR-TB treatment. When hearing loss cannot be avoided, secondary and tertiary prevention should be prioritized., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Participants assessed the employability of vignette characters whose presentation varied across two dimensions during a job interview: presence of autism spectrum disorder (ASD) characteristics (present, absent) and disclosure of diagnosis (ASD, ADHD, diabetes, or no disclosure). Participants more knowledgeable about ASD had more positive perceptions of vignette characters, particularly when they disclosed an ASD diagnosis and did not show ASD characteristics. Participants high in social desirability perceived vignette characters more positively. Participants expressed the most concern about job candidates showing inflexible adherence to a routine and sensory sensitivity, although such concerns may have been context-dependent due to job expectations. Overall, these results emphasize that employer factors, particularly employer knowledge of ASD and social desirability, significantly affect the perceived employability of job candidates with ASD. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Background: Most standalone real-time continuous glucose monitoring (RT-CGM) systems provide predictive low and high sensor glucose (SG) threshold alerts. The durations and risk of low and high SG excursions following Guardian™ Connect CGM system predictive threshold alerts were evaluated., Methods: Continuous glucose monitoring system data uploaded between January 2, 2017 and May 22, 2018 by 3133 individuals using multiple daily injections (MDIs) or continuous subcutaneous insulin infusion (CSII) therapy were deidentified and retrospectively analyzed. Glucose excursions were defined as SG values that went beyond a preset low or high SG threshold for ≥15 minutes. For a control group, thresholds were based on the median of the low SG threshold limit (70 mg/dL) and the high SG threshold limit (210 mg/dL) preset by all system users. During periods when alerts were not enabled, timestamps were identified when a predictive alert would have been triggered. The time before low horizon was 17.5 minutes and the time before high horizon was 15 minutes, of all users who enabled alerts. Excursions occurring after a low SG or high SG predictive alert were segmented into prevented, ≤20, 20-60, and >60 minutes., Results: Excursions were prevented after 59% and 39% of low and high SG predictive alerts, respectively. The risk of a low or high excursion occurring was 1.9 ( P < 0.001, 95% CI, 1.88-1.93) and 3.3 ( P < 0.001, 95% CI, 3.20-3.30) times greater, respectively, when alerts were not enabled., Conclusions: The predictive alerts of the RT-CGM system under study can help individuals living with diabetes prevent some real-world low and high SG excursions. This can be especially important for those unable to reach or maintain glycemic control with basic RT-CGM or CSII therapy.

Objective: We aimed to prospectively examine the relationship between vision and hearing loss and successful aging in a cohort of older adults., Study Design: We analyzed 5-year data (1997-9 to 2002-4) from 1,085 adults aged 55+ years, who were free of cancer, coronary artery disease and stroke at baseline and who had complete data on sensory loss., Main Outcome Measures: Visual impairment was defined as visual acuity <20/40 (better eye), and hearing impairment as average pure-tone air conduction threshold >25 dBHL (500-4000 Hz, better ear). Successful aging was defined as the absence of: disability, depressive symptoms, cognitive impairment, respiratory symptoms and chronic diseases (cancer, coronary artery disease and stroke) at 5-year follow-up., Results: At 5-year follow-up, 243 (22.4%) participants had died and 248 (22.9%) had aged successfully. After multivariable adjustment, participants who had either best-corrected visual impairment or bilateral hearing impairment, versus those who did not have sensory impairment at baseline, had 37% reduced odds of successful aging after 5 years: OR 0.63 (95% CI 0.43-0.94). Concurrent vision and hearing loss at baseline was not associated with 5-year aging status. Participants with moderate and severe hearing handicap at baseline had 50% and 61% reduced odds of aging successfully after 5 years, respectively., Conclusion: The presence of a single sensory impairment in older adults was associated with reduced odds of being disease-free and fully functional or having aged successfully, 5 years later. Objectively measured hearing loss and self-perceived hearing handicap, rather than vision loss, was more likely to negatively influence 5-year aging status., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The aim of this study was to assess whether a computer-based speech-in-noise auditory training (AT) program would lead to short- and long-term changes in trained and untrained measures of listening, cognition, and quality of life. A secondary aim was to assess whether directly training the underlying cognitive abilities required for speech perception in noise, using a computer-based visual training (VT) program without the auditory component, would elicit comparable outcomes as the AT program. A randomized crossover study with repeated measures was conducted with 26 adult cochlear implant users. Participants completed either 6 weeks of speech perception in noise training followed by 6 weeks of masked text recognition training, or vice versa. Outcome measures were administered twice before each training program, as well as twice after the completion of each program. The test battery was designed to evaluate whether training led to improvements in listening abilities, cognitive abilities, or quality of life. Mixed-effects models were conducted to analyze whether changes occurred on the trained tasks and on untrained outcome measures after training. Statistically significant improvements were shown for verbal recognition performance during both training programs, in particular for consonants in words, and during the first 2 weeks of training. This on-task learning, however, did not lead to clear improvements in outcomes measured beyond the training programs. This suggests that experienced cochlear implant users may not show transfer of on-task learning to untrained tasks after computer-based auditory and visual training programs such as the ones used in this study.

Hyperleukocytosis in acute myeloid leukemia (AML) is associated with inferior outcomes. There is limited high quality evidence to support the benefits of leukapheresis. We retrospectively collected data from patients with newly-diagnosed AML who presented with a white cell count (WBC) >50 × 10 9 /L to 12 centers in the United States and Europe from 2006 to 2017 and received intensive chemotherapy. Logistic regression models estimated odds ratios for 30-day mortality and achievement of composite complete remission (CRc). Cox proportional hazard models estimated hazard ratios for overall survival (OS). Among 779 patients, clinical leukostasis was reported in 27%, and leukapheresis was used in 113 patients (15%). Thirty-day mortality was 16.7% (95% CI: 13.9-19.3%). Median OS was 12.6 months (95% CI: 11.5-14.9) among all patients, and 4.5 months (95% CI: 2.7-7.1) among those ≥65 years. Use of leukapheresis did not significantly impact 30-day mortality, achievement of CRc, or OS in multivariate analysis based on available data or in analysis based on multiple imputation. Among patients with investigator-adjudicated clinical leukostasis, there were statistically significant improvements in 30-day mortality and OS with leukapheresis in unadjusted analysis, but not in multivariate analysis. Given the significant resource use, cost, and potential complications of leukapheresis, randomized studies are needed to evaluate its value.

Dietary flavonoids are vasoactive phytochemicals with promising anti-inflammatory properties. We aimed to assess the associations between baseline intakes of six commonly consumed flavonoid subclasses and 10-year incidence of age-related hearing loss. At baseline, 1691 participants aged 50+ years had information on dietary intakes and hearing status. Hearing loss was defined as the pure-tone average of frequencies 0.5, 1.0, 2.0, and 4.0 kHz > 25 dB hearing level (HL). Dietary data were collected through a semi-quantitative food frequency questionnaire. The flavonoid content of foods was estimated using US databases. During the 10-year follow-up, 260 (31.6%) new cases of hearing loss (incident) were observed. After multivariable adjustment, participants in the fourth versus first quartile (reference group) of intake of dietary isoflavone had 36% lower risk of incident hearing loss after 10 years: odds ratios (OR) 0.64 (95% confidence intervals, CI, 0.42-0.99); p-value for trend = 0.03. Nonsignificant associations were observed between the other five flavonoid subclasses and 10-year incidence of hearing loss. Our findings do not support the hypothesis that the intake of dietary flavonoids protect against long-term risk of hearing loss. The association with isoflavone intake needs to be confirmed by other population-based studies.

This study aimed to estimate the prevalence of hearing loss in the Philippines using a nationally representative sample. A cross-sectional national survey was undertaken utilizing a 3-stage stratified cluster design. Participants in the present study comprised 2275 adults and children with pure tone hearing assessment results. Prevalence of moderate or worse hearing loss, defined as 4FA ≥41 dBHL, was 7.5% in children <18 years, 14.7% in adults between 18 and 65 years, and 49.1% in adults >65 years. Factors associated with greater risk of moderate hearing loss in the better ear were presence of a middle ear condition (adjusted odds ratio = 2.39, 95% confidence interval = 1.49-3.85) and socioeconomic status (household income; adjusted odds ratio = 1.64, 95% confidence interval = 1.23-2.19). Age was also associated with increased risk, with adjusted odds ratios varying with age category. Prevalence of wax occlusion and outer and middle ear disease was 12.2% and 14.2%, respectively. Prevalence of hearing loss, outer, and middle ear disease appear comparatively high in the Philippines when compared with rates reported in high-income countries. Higher proportions of severe to profound hearing loss were also identified, indicating that there is both an increased prevalence and severity of hearing loss in this population.

Purpose A growing body of evidence suggests that long-term music training provides benefits to auditory abilities for typical-hearing adults and children. The purpose of this study was to evaluate how music training may provide perceptual benefits (such as speech-in-noise, spectral resolution, and prosody) for children with hearing loss. Method Fourteen children aged 6-9 years with prelingual sensorineural hearing loss using bilateral cochlear implants, bilateral hearing aids, or bimodal configuration participated in a 12-week music training program, with nine participants completing the full testing requirements of the music training. Activities included weekly group-based music therapy and take-home music apps three times a week. The design was a pseudorandomized, longitudinal study (half the cohort was wait-listed, initially serving as a passive control group prior to music training). The test battery consisted of tasks related to music perception, music appreciation, and speech perception. As a comparison, 16 age-matched children with typical hearing also completed this test battery, but without participation in the music training. Results There were no changes for any outcomes for the passive control group. After music training, perception of speech-in-noise, question/statement prosody, musical timbre, and spectral resolution improved significantly, as did measures of music appreciation. There were no benefits for emotional prosody or pitch perception. Conclusion The findings suggest even a modest amount of music training has benefits for music and speech outcomes. These preliminary results provide further evidence that music training is a suitable complementary means of habilitation to improve the outcomes for children with hearing loss.

Background: Cochlear implants (CIs) can provide a sound sensation for those with severe sensorineural hearing loss (SNHL), benefitting speech understanding and quality of life. Nevertheless, rates of implantation remain low, and limited research investigates journeys from traditional hearing aids to implantable devices., Method: Fifty-five adults (≥ 50 years), hearing aid users and/or CI users, General Practitioners, and Australian and United Kingdom audiologists took part in a multi-methods study. Focus groups, interviews, and surveys were thematically analysed., Results: One hundred forty-three data-capture events disclosed 2 themes: 1) "The burden of hearing loss and the impact of Cochlear Implants", and 2) "Professional Support and Practice, and HCPs Roles and Responsibilities"., Conclusions: Care experience can include convoluted, complex journeys towards cochlear implantation. The significant impact of this, as hearing loss progresses, motivates people to consider implants, but they and healthcare professionals need clear supported with defined referral pathways, and less system complexity.

Objective: School hearing screening may mitigate the effects of childhood hearing loss through early identification and intervention. This study provides an overview of existing school hearing screening programs around the world, identifies gaps in the literature, and develops priorities for future research., Data Sources: A structured search of the PubMed, Embase, and Cochrane Library databases., Review Methods: A total of 65 articles were included according to predefined inclusion criteria. Parameters of interest included age groups screened, audiometric protocols, referral criteria, use of adjunct screening tests, rescreening procedures, hearing loss prevalence, screening test sensitivity and specificity, and loss to follow-up., Conclusions: School hearing screening is mandated in few regions worldwide, and there is little accountability regarding whether testing is performed. Screening protocols differ in terms of screening tests included and thresholds used. The most common protocols included a mix of pure tone screening (0.5, 1, 2, and 4 kHz), otoscopy, and tympanometry. Estimates of region-specific disease prevalence were methodologically inaccurate, and rescreening was poorly addressed. Loss to follow-up was also a ubiquitous concern., Implications for Practice: There is an urgent need for standardized school hearing screening protocol guidelines globally, which will facilitate more accurate studies of hearing loss prevalence and determination of screening test sensitivity and specificity. In turn, these steps will increase the robustness with which we can study the effects of screening and treatment interventions, and they will support the development of guidelines on the screening, diagnostic, and rehabilitation services needed to reduce the impact of childhood hearing loss., (© The Authors 2020.)

Objectives: Hearing loss (HL) affects a significant proportion of adults aged >50 years by impairing communication and social connectedness and, due to its high prevalence, is a growing global concern. Cochlear implants (CIs) are effective devices for many people with severe or greater sensorineural HL who experience limited benefits from hearing aids. Despite this, uptake rates globally are low among adults. This multimethod, multicountry qualitative study aimed to investigate the barriers and facilitators to CI uptake among adults aged ≥50 years., Design: Adult CI and hearing aid users with postlingual severe or greater sensorineural HL, general practitioners, and audiologists were recruited in Australia using purposive sampling, and a comparative sample of audiologists was recruited in England and Wales in the United Kingdom. Participants were interviewed individually, or in a focus group, completed a demographic questionnaire and a qualitative survey. Data were analyzed using thematic analysis., Results: A total of 143 data capture events were collected from 55 participants. The main barriers to CI uptake related to patients' concerns about surgery and loss of residual hearing. Limited knowledge of CIs, eligibility criteria, and referral processes acted as barriers to CIs assessment referrals by healthcare professionals. Facilitators for CI uptake included patients' desire for improved communication and social engagement, and increased healthcare professional knowledge and awareness of CIs., Conclusions: There are numerous complex barriers and facilitators to CI uptake. Knowledge of these can inform the development of targeted strategies to increase CI referral and surgery for potential beneficiaries.

Recognition of distinct glycans is central to biology, and lectins mediate this function. Lectin glycan preferences are usually centered on specific monosaccharides. In contrast, human intelectin-1 (hItln-1, also known as Omentin-1) is a soluble lectin that binds a range of microbial sugars, including β-d-galactofuranose (β-Gal f ), d-glycerol 1-phosphate, d- glycero -d- talo -oct-2-ulosonic acid (KO), and 3-deoxy-d- manno -oct-2-ulosonic acid (KDO). Though these saccharides differ dramatically in structure, they share a common feature-an exocyclic vicinal diol. How and whether such a small fragment is sufficient for recognition was unclear. We tested several glycans with this epitope and found that l- glycero -α-d- manno -heptose and d- glycero -α-d- manno -heptose possess the critical diol motif yet bind weakly. To better understand hItln-1 recognition, we determined the structure of the hItln-1·KO complex using X-ray crystallography, and our 1.59 Å resolution structure enabled unambiguous assignment of the bound KO conformation. This carbohydrate conformation was present in >97% of the KDO/KO structures in the Protein Data Bank. Bioinformatic analysis revealed that KO and KDO adopt a common conformation, while heptoses prefer different conformers. The preferred conformers of KO and KDO favor hItln-1 engagement, but those of the heptoses do not. Natural bond orbital (NBO) calculations suggest these observed conformations, including the side chain orientations, are stabilized by not only steric but also stereoelectronic effects. Thus, our data highlight a role for stereoelectronic effects in dictating the specificity of glycan recognition by proteins. Finally, our finding that hItln-1 avoids binding prevalent glycans with a terminal 1,2-diol (e.g., N -acetyl-neuraminic acid and l- glycero -α-d- manno -heptose) suggests the lectin has evolved to recognize distinct bacterial species.

Introduction : The receptor tyrosine kinase FLT3 is the most commonly mutated gene in acute myeloid leukemia (AML). FLT3 -internal tandem duplication mutations are associated with an increased risk of relapse, and a number of small molecule inhibitors of FLT3 have been developed. The highly potent and selective FLT3 kinase inhibitor gilteritinib is the first tyrosine kinase inhibitor approved as monotherapy for the treatment of relapsed and/or refractory FLT3 -mutated AML. Areas covered : We review the biology and prognostic significance of FLT3 mutations in AML and discuss the pharmacology, clinical efficacy, and toxicity profile of gilteritinib. We also summarize important differences among the various FLT3 inhibitors that are currently approved or under development and highlight areas of ongoing research. Expert opinion : Gilteritinib has been shown to improve survival compared to salvage chemotherapy in relapsed and/or refractory FLT3 -mutated AML. Gilteritinib is orally available with a favorable toxicity profile and as such is quickly becoming the standard of care for this patient population. Ongoing clinical trials are evaluating gilteritinib in combination with frontline chemotherapy, in combination with other agents such as venetoclax and azacitidine for patients who are ineligible for standard induction therapy, and as a maintenance agent.

Gilteritinib is a potent and selective FLT3 kinase inhibitor with single-agent clinical efficacy in relapsed/refractory FLT3 -mutated acute myeloid leukemia (AML). In this context, however, gilteritinib is not curative, and response duration is limited by the development of secondary resistance. To evaluate resistance mechanisms, we analyzed baseline and progression samples from patients treated on clinical trials of gilteritinib. Targeted next-generation sequencing at the time of AML progression on gilteritinib identified treatment-emergent mutations that activate RAS/MAPK pathway signaling, most commonly in NRAS or KRAS. Less frequently, secondary FLT3 -F691L gatekeeper mutations or BCR-ABL1 fusions were identified at progression. Single-cell targeted DNA sequencing revealed diverse patterns of clonal selection and evolution in response to FLT3 inhibition, including the emergence of RAS mutations in FLT3 -mutated subclones, the expansion of alternative wild-type FLT3 subclones, or both patterns simultaneously. These data illustrate dynamic and complex changes in clonal architecture underlying response and resistance to mutation-selective tyrosine kinase inhibitor therapy in AML. SIGNIFICANCE: Comprehensive serial genotyping of AML specimens from patients treated with the selective FLT3 inhibitor gilteritinib demonstrates that complex, heterogeneous patterns of clonal selection and evolution mediate clinical resistance to tyrosine kinase inhibition in FLT3 -mutated AML. Our data support the development of combinatorial targeted therapeutic approaches for advanced AML. See related commentary by Wei and Roberts, p. 998 . This article is highlighted in the In This Issue feature, p. 983 ., (©2019 American Association for Cancer Research.)