Datopotamab-deruxtecan in early-stage breast cancer: the sequential multiple assignment randomized I-SPY2.2 phase 2 trial.

Among the goals of patient-centric care are the advancement of effective personalized treatment, while minimizing toxicity. The phase 2 I-SPY2.2 trial uses a neoadjuvant sequential therapy approach in breast cancer to further these goals, testing promising new agents while optimizing individual outcomes. Here we tested datopotamab-deruxtecan (Dato-DXd) in the I-SPY2.2 trial for patients with high-risk stage 2/3 breast cancer. I-SPY2.2 uses a sequential multiple assignment randomization trial design that includes three sequential blocks of biologically targeted neoadjuvant treatment: the experimental agent(s) (block A), a taxane-based regimen tailored to the tumor subtype (block B) and doxorubicin-cyclophosphamide (block C). Patients are randomized into arms consisting of different investigational block A treatments. Algorithms based on magnetic resonance imaging and core biopsy guide treatment redirection after each block, including the option of early surgical resection in patients predicted to have a high likelihood of pathological complete response, the primary endpoint. There are two primary efficacy analyses: after block A and across all blocks for the six prespecified breast cancer subtypes (defined by clinical hormone receptor/human epidermal growth factor receptor 2 (HER2) status and/or the response-predictive subtypes). We report results of 103 patients treated with Dato-DXd. While Dato-DXd did not meet the prespecified threshold for success (graduation) after block A in any subtype, the treatment strategy across all blocks graduated in the hormone receptor-negative HER2-Immune-DNA repair deficiency- subtype with an estimated pathological complete response rate of 41%. No new toxicities were observed, with stomatitis and ocular events occurring at low grades. Dato-DXd was particularly active in the hormone receptor-negative/HER2-Immune-DNA repair deficiency- signature, warranting further investigation, and was safe in other subtypes in patients who followed the treatment strategy. ClinicalTrials.gov registration: NCT01042379 .

Datopotamab-deruxtecan plus durvalumab in early-stage breast cancer: the sequential multiple assignment randomized I-SPY2.2 phase 2 trial.

Sequential adaptive trial designs can help accomplish the goals of personalized medicine, optimizing outcomes and avoiding unnecessary toxicity. Here we describe the results of incorporating a promising antibody-drug conjugate, datopotamab-deruxtecan (Dato-DXd) in combination with programmed cell death-ligand 1 inhibitor, durvalumab, as the first sequence of therapy in the I-SPY2.2 phase 2 neoadjuvant sequential multiple assignment randomization trial for high-risk stage 2/3 breast cancer. The trial includes three blocks of treatment, with initial randomization to different experimental agent(s) (block A), followed by a taxane-based regimen tailored to tumor subtype (block B), followed by doxorubicin-cyclophosphamide (block C). Subtype-specific algorithms based on magnetic resonance imaging volume change and core biopsy guide treatment redirection after each block, including the option of early surgical resection in patients predicted to have a high likelihood of pathologic complete response, which is the primary endpoint assessed when resection occurs. There are two primary efficacy analyses: after block A and across all blocks for six prespecified HER2-negative subtypes (defined by hormone receptor status and/or response-predictive subtypes). In total, 106 patients were treated with Dato-DXd/durvalumab in block A. In the immune-positive subtype, Dato-DXd/durvalumab exceeded the prespecified threshold for success (graduated) after block A; and across all blocks, pathologic complete response rates were equivalent to the rate expected for the standard of care (79%), but 54% achieved that result after Dato-DXd/durvalumab alone (block A) and 92% without doxorubicin-cyclophosphamide (after blocks A + B). The treatment strategy across all blocks graduated in the hormone-negative/immune-negative subtype. No new toxicities were observed. Stomatitis was the most common side effect in block A. No patients receiving block A treatment alone had adrenal insufficiency. Dato-DXd/durvalumab is a promising therapy combination that can eliminate standard chemotherapy in many patients, particularly the immune-positive subtype.ClinicalTrials.gov registration: NCT01042379 .

Development of the National Prehospital Pediatric Readiness Project assessment.

INTRODUCTION: In the United States (US), the quality of care provided to children during emergencies is highly variable. Following implementation of the National Pediatric Readiness Project (NPRP), inclusive of two national online assessments of Emergency Departments (EDs), national organizations involved in Emergency Medical Services (EMS) systems convened to launch the Prehospital Pediatric Readiness Project (PPRP). The PPRP seeks to ensure high-quality pediatric prehospital emergency care for all children. One of the first priorities of PPRP is to assess the current level of pediatric readiness in EMS systems. The development of the first comprehensive national assessment of pediatric readiness in EMS systems is described. METHODS: The 2020 joint policy statement, "Pediatric Readiness in Emergency Medical Services Systems" and the associated prehospital pediatric readiness checklist served as the foundation for the PPRP assessment. Assessment questions and scoring algorithm were developed using a modified Delphi process. The PPRP Assessment was converted into an online format comprising a website (EMSpedsReady.org), the online assessment, a personalized gap report, and non-public Tableau data-monitoring dashboards. A directory of all eligible EMS agencies in the United Staters was created to track participation. A diverse cohort of 15 EMS agencies piloted of the assessment questions and the online version of the assessment. Feedback from the pilot was integrated. CONCLUSION: The inaugural PPRP Assessment was open access May through July 2024, and the results will be used to guide future PPRP efforts.

Identifying Predictors of Positive and Negative Affect at Mid-Deployment Among Military Medical Personnel.

INTRODUCTION: Positive and negative affect influence an individual's ability to utilize available physical, psychological, and social resources to maximize responses to life events. Little research has examined the factors that influence the development of positive affect or reduction of negative affective responses among deployed military personnel. The present study aimed to investigate the relationship between deployment-related stressors and symptoms of behavioral health concerns with affectivity among deployed U.S. service members. MATERIALS AND METHODS: Participants were 1148 U.S. Air Force medical personnel deployed to Balad, Iraq, between 2004 and 2011. All participants completed self-report measures of PTSD symptoms, general military and combat exposure, stress, and affectivity. The Institutional Review Board at Wilford Hall Medical Center, the Air Force Personnel Survey Program, and the U.S. Army's Joint Combat Casualty Research Team reviewed and approved the study. RESULTS: Most respondents (89%, 1,018/1,139) reported a positive military experience, but many respondents reported exposure to a potentially traumatic event during deployment. For example, seeing dead or seriously injured Americans (47%, 523/1,123) was the most common exposure reported by participants. A large portion of personnel (21%, 232/1,089) reported clinical levels of PTSD symptoms (score of 33 or higher on the Posttraumatic Stress Disorder Checklist-Military version). Risk factors, including PTSD symptoms, combat exposure, and stress, explained 39% of the variance in negative affect, R2 = 0.39, F(1046) = 224.96, P < .001. Conversely, these risk and resilience factors, including PTSD symptoms, combat exposure, stress, and general military experiences, explained 28% of the variance in positive affect, R2 = 0.28, F(1050) = 103.79, P < .001. No significant gender differences were found between models predicting positive and negative affect. CONCLUSIONS: Negative mood states may be partly an epiphenomenon of PTSD, which has been shown to be safely and effectively treated in the deployed environment. Social support during deployments is uniquely associated with a positive mood. These findings extend beyond the military and into any high-stress occupation wherein leaders could interpret these findings as a need to build or reinforce efforts to provide opportunities to sustain healthy relationships in personnel. These critical indigenous resources support mission readiness and enable the maintenance of positive psychological health.

The perception of emotion in music by people with hearing loss and people with cochlear implants.

Music is an important part of life for many people. It can evoke a wide range of emotions, including sadness, happiness, anger, tension, relief and excitement. People with hearing loss and people with cochlear implants have reduced abilities to discriminate some of the features of musical sounds that may be involved in evoking emotions. This paper reviews these changes in perceptual abilities and describes how they affect the perception of emotion in music. For people with acquired partial hearing loss, it appears that the perception of emotion in music is almost normal, whereas congenital partial hearing loss is associated with impaired perception of music emotion. For people with cochlear implants, the ability to discriminate changes in fundamental frequency (associated with perceived pitch) is much worse than normal and musical harmony is hardly perceived. As a result, people with cochlear implants appear to judge emotion in music primarily using tempo and rhythm cues, and this limits the range of emotions that can be judged. This article is part of the theme issue 'Sensing and feeling: an integrative approach to sensory processing and emotional experience'.

Sensing and feeling: an overview.

Emotional experiences are driven, in part, by the way we process and integrate information from different sensory modalities. Understanding how perceptual and emotional systems interact to give rise to subjective feelings is an important, complex and challenging issue, requiring new approaches and integrative thinking that fuses the fundamentals of low-level sensory perception with higher-level cognitive and affective processes. The Theme Issue 'Sensing and feeling: an integrative approach to sensory processing and emotional experience' showcases fifteen theoretical, empirical, and review articles from experts working at the intersection of perception and emotion, encompassing multiple sensory systems (visual, auditory, tactile and interoceptive), clinical and non-clinical perspectives (e.g. affective disorders and hearing loss), contextual and social perspectives, and complex emotional experiences in special populations. Articles in Part 1 emphasize recent advances across fields in sensory and emotion science and give insights into future directions. Each article in Part 2 provides more detailed and specific methodological approaches or theoretical models, and focuses on basic mechanisms linking sensation to emotional experience. This article is part of the theme issue 'Sensing and feeling: an integrative approach to sensory processing and emotional experience'.

Effect of early versus late onset of partial visual loss on judgments of auditory distance.

SIGNIFICANCE: It is important to know whether early-onset vision loss and late-onset vision loss are associated with differences in the estimation of distances of sound sources within the environment. People with vision loss rely heavily on auditory cues for path planning, safe navigation, avoiding collisions, and activities of daily living. PURPOSE: Loss of vision can lead to substantial changes in auditory abilities. It is unclear whether differences in sound distance estimation exist in people with early-onset partial vision loss, late-onset partial vision loss, and normal vision. We investigated distance estimates for a range of sound sources and auditory environments in groups of participants with early- or late-onset partial visual loss and sighted controls. METHODS: Fifty-two participants heard static sounds with virtual distances ranging from 1.2 to 13.8 m within a simulated room. The room simulated either anechoic (no echoes) or reverberant environments. Stimuli were speech, music, or noise. Single sounds were presented, and participants reported the estimated distance of the sound source. Each participant took part in 480 trials. RESULTS: Analysis of variance showed significant main effects of visual status (p<0.05) environment (reverberant vs. anechoic, p<0.05) and also of the stimulus (p<0.05). Significant differences (p<0.05) were shown in the estimation of distances of sound sources between early-onset visually impaired participants and sighted controls for closer distances for all conditions except the anechoic speech condition and at middle distances for all conditions except the reverberant speech and music conditions. Late-onset visually impaired participants and sighted controls showed similar performance (p>0.05). CONCLUSIONS: The findings suggest that early-onset partial vision loss results in significant changes in judged auditory distance in different environments, especially for close and middle distances. Late-onset partial visual loss has less of an impact on the ability to estimate the distance of sound sources. The findings are consistent with a theoretical framework, the perceptual restructuring hypothesis, which was recently proposed to account for the effects of vision loss on audition.

The Impact of Graduate Record Exam Threshold Scores in Disqualifying Underrepresented Ethnic-Racial Minority Applicants for Admission to a Doctor of Physical Therapy Program.

INTRODUCTION: A growing number of graduate-level health professions education programs in the United States are discontinuing the use of the Graduate Record Exam (GRE) in their admissions requirements amidst concerns that its use puts Underrepresented Racial Minority (URRM) applicants at a disadvantage. This retrospective cross-sectional study analyzes the association between ethnic-racial selection and the reasons for disqualification among applicants to a public Doctor of Physical Therapy (DPT) program that used a minimum grade point average (GPA), and Analytic Writing and Quantitative Reasoning GRE minimum threshold scores to qualify applicants. REVIEW OF LITERATURE: There is evidence across the health professions literature that both GRE scores and GPA are associated with success on licensure examinations and academic performance. However, these variables also tend to disadvantage URRM applicants in gaining admissions to postgraduate health care fields, including physical therapy. SUBJECTS: All applicants (N = 4,797) to a single DPT program from a 9-year period were included. METHODS: Racial and ethnic self-selections, GRE scores, and prerequisite GPA were coded for each applicant and classified for meeting qualifying criteria. RESULTS: The URRM applicants were disqualified based on GRE scores alone (P < .001) and in combination of GRE and GPA at a statistically significantly (P < .001) higher rate than Overrepresented Racial Group (ORRG) applicants, although the associations were negligible or weak. CONCLUSION: Compared with ORRG applicants, URRM applicants were at a statistically significant disadvantage because of the GRE threshold scores requirement. Furthermore, this study demonstrated that use of GRE minimum threshold scores disproportionately reduced URRM applicants in the qualified applicant pool. This investigation can be used as a model to inform holistic admission decisions regarding the use of academic variables to achieve the diversity and success goals of the program.

Accuracy and Consistency of Confidence Limits for Monosyllable Identification Scores Derived Using Simulation, the Harrell-Davis Estimator, and Nonlinear Quantile Regression.

BACKGROUND: Audiological diagnosis and rehabilitation often involve the assessment of whether the maximum speech identification score (PBmax) is poorer than expected from the pure-tone average (PTA) threshold. This requires the estimation of the lower boundary of the PBmax values expected for a given PTA (one-tailed 95% confidence limit, CL). This study compares the accuracy and consistency of three methods for estimating the 95% CL. METHOD: The 95% CL values were estimated using a simulation method, the Harrell-Davis (HD) estimator, and non-linear quantile regression (nQR); the latter two are both distribution-free methods. The first two methods require the formation of sub-groups with different PTAs. Accuracy and consistency in the estimation of the 95% CL were assessed by applying each method to many random samples of 50% of the available data and using the fitted parameters to predict the data for the remaining 50%. STUDY SAMPLE: A total of 642 participants aged 17 to 84 years with sensorineural hearing loss were recruited from audiology clinics. Pure-tone audiograms were obtained and PBmax scores were measured using monosyllables at 40 dB above the speech recognition threshold or at the most comfortable level. RESULTS: For the simulation method, 6.7 to 8.2% of the PBmax values fell below the 95% CL for both ears, exceeding the target value of 5%. For the HD and nQR methods, the PBmax values fell below the estimated 95% CL for approximately 5% of the ears, indicating good accuracy. Consistency, estimated from the standard deviation of the deviations from the target value of 5%, was similar for all the methods. CONCLUSIONS: The nQR method is recommended because it has good accuracy and consistency, and it does not require the formation of arbitrary PTA sub-groups.

Confirmatory factor analysis of the Tinnitus Impact Questionnaire using data from patients seeking help for tinnitus alone or tinnitus combined with hyperacusis.

A confirmatory factor analysis (CFA) of the Tinnitus Impact Questionnaire (TIQ) was performed. In contrast to commonly used tinnitus questionnaires, the TIQ is intended solely to assess the impact of tinnitus by not including items related to hearing loss or tinnitus loudness. This was a psychometric study based on a retrospective cross-sectional analysis of clinical data. Data were available for 155 new patients who had attended a tinnitus and hyperacusis clinic in the UK within a five-month period and had completed the TIQ. The mean age was 54 years (standard deviation = 14 years). The TIQ demonstrated good internal consistency, with Cronbach's α = 0.84 and McDonald's ω = 0.89. CFA showed that two items of the TIQ had low factor loadings for both one-factor and two-factor models and their scores showed low correlations with scores for other items. Bi-factor analysis gave a better fit, indicated by a relative chi-square (χ2) of 18.5, a Root-Mean Square Error of Approximation (RMSEA) of 0.103, a Comparative Fit Index (CFI) of 0.97, a Tucker Lewis Index (TLI) of 0.92, and a Standardized Root-Mean Residual (SPMR) of 0.038. Total TIQ scores were moderately correlated with scores for the Visual Analogue Scale of effect of tinnitus on life and the Screening for Anxiety and Depression-Tinnitus questionnaire, supporting the convergent validity of the TIQ. The TIQ score was not correlated with the pure-tone average hearing threshold, indicating discriminant validity. A multiple-causes multiple-indicator (MIMIC) model showed no influences of age, gender or hearing status on TIQ item scores. The TIQ is an internally consistent tool. CFA suggests a bi-factor model with sufficient unidimensionality to support the use of the overall TIQ score for assessing the impact of tinnitus. TIQ scores are distinct from the impact of hearing impairment among patients who have tinnitus combined with hearing loss.

Serum NfL and GFAP as biomarkers of progressive neurodegeneration in TBI.

BACKGROUND: We examined spatial patterns of brain atrophy after mild, moderate, and severe traumatic brain injury (TBI), the relationship between progression of brain atrophy with initial traumatic axonal injury (TAI), cognitive outcome, and with serum biomarkers of brain injury. METHODS: A total of 143 patients with TBI and 43 controls were studied cross-sectionally and longitudinally up to 5 years with multiple assessments, which included brain magnetic resonance imaging, cognitive testing, and serum biomarkers. RESULTS: TBI patients showed progressive volume loss regardless of injury severity over several years, and TAI was independently associated with accelerated brain atrophy. Cognitive performance improved over time. Higher baseline serum neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) were associated with greater rate of brain atrophy over 5 years. DISCUSSSION: Spatial patterns of atrophy differ by injury severity and TAI is associated with the progression of brain atrophy. Serum NfL and GFAP show promise as non-invasive prognostic biomarkers of progressive neurodegeneration in TBI. HIGHLIGHTS: In this longitudinal study of patient with mild, moderate, and severe traumatic brain injury (TBI) who were assessed with paired magnetic resonance imaging (MRI), blood biomarkers, and cognitive assessments, we found that brain atrophy after TBI is progressive and continues for many years even after a mild head trauma without signs of brain injury on conventional MRI. We found that spatial pattern of brain atrophy differs between mild, moderate, and severe TBI, where in patients with mild TBI , atrophy is mainly seen in the gray matter, while in those with moderate to severe brain injury atrophy is predominantly seen in the subcortical gray matter and whiter matter. Cognitive performance improves over time after a TBI. Serum measures of neurofilament light or glial fibrillary acidic protein are associated with progression of brain atrophy after TBI.

Older Persons Participation in Hard Martial Arts: Opportunities to Improve Psychological Well-Being? A Scoping Review.

This study aims to explore the potential psychological and cognitive advantages for older individuals engaged in hard martial arts (HMA), through a comprehensive scoping review of literature up to 2023. Specifically, it examines the extent of changes in cognition, mental state, and quality of life among elderly participants of HMA. Inclusion criteria were studies conducted on healthy persons who were over 50 years of age. Only papers published in the English language were included. The search was undertaken in electronic databases and sources of grey literature. Thirteen papers with a total of 514 participants met the inclusion criteria. Improved cognition and decreased levels of anxiety and depression were emerging themes. Together, these factors contributed to the quality of life of participants. HMA was found to benefit cognitive abilities and psychological well-being, increasing quality of life more than traditional exercise alone. Findings suggested duration of training influenced change more than frequency. The limited number of studies exploring the effects of HMA on mental wellness and cognitive ability in older adults underscores the need for further research. The findings of this review suggest cognitive and quality of life improvements and reduced depression and anxiety in individuals engaging in HMA. This review serves as a foundation for soundly designed future research.

A Preliminary Analysis of the Clinical Effectiveness of Audiologist-Delivered Cognitive Behavioral Therapy Delivered via Video Calls for Rehabilitation of Misophonia, Hyperacusis, and Tinnitus.

PURPOSE: Cognitive behavioral therapy (CBT) is a key intervention for management of misophonia, hyperacusis, and tinnitus. The aim of this study was to perform a preliminary analysis comparing the scores for self-report questionnaires before and after audiologist-delivered CBT via video calls for adults with misophonia, hyperacusis, or tinnitus or a combination of these. METHOD: This was a retrospective cross-sectional study. The data for 37 consecutive patients who received CBT for misophonia, hyperacusis, or tinnitus from a private institute in the United Kingdom were analyzed. Self-report questionnaires taken as part of routine care were as follows: 4C Questionnaires for tinnitus, hyperacusis, and misophonia (4C-T, 4C-H, and 4C-M, respectively), Tinnitus Impact Questionnaire (TIQ), Hyperacusis Impact Questionnaire (HIQ), Misophonia Impact Questionnaire (MIQ), Sound Sensitivity Symptoms Questionnaire (SSSQ), and Screening for Anxiety and Depression in Tinnitus (SAD-T). Responses were also obtained to other questionnaires related to tinnitus, hyperacusis, insomnia, and anxiety and mood disorders. A linear mixed-model method was used to assess the changes in response to the questionnaires pretreatment and posttreatment. RESULTS: Pretreatment-posttreatment comparisons showed that scores for the 4C-T, 4C-H, 4C-M, TIQ, HIQ, MIQ, SSSQ, and SAD-T improved, with effect sizes of 1.4, 1.2, 1.3, 2.6, 0.9, 0.7, 0.9, and 1.4, respectively (all p < .05). CONCLUSIONS: This preliminary analysis suggests that CBT via video calls may be effective in reducing the impact of misophonia, hyperacusis, and tinnitus. However, this study did not have a control group, so its results need to be interpreted with caution.

Neuroimaging Findings in US Government Personnel and Their Family Members Involved in Anomalous Health Incidents.

Importance: US government personnel stationed internationally have reported anomalous health incidents (AHIs), with some individuals experiencing persistent debilitating symptoms. Objective: To assess the potential presence of magnetic resonance imaging (MRI)-detectable brain lesions in participants with AHIs, with respect to a well-matched control group. Design, Setting, and Participants: This exploratory study was conducted at the National Institutes of Health (NIH) Clinical Center and the NIH MRI Research Facility between June 2018 and November 2022. Eighty-one participants with AHIs and 48 age- and sex-matched control participants, 29 of whom had similar employment as the AHI group, were assessed with clinical, volumetric, and functional MRI. A high-quality diffusion MRI scan and a second volumetric scan were also acquired during a different session. The structural MRI acquisition protocol was optimized to achieve high reproducibility. Forty-nine participants with AHIs had at least 1 additional imaging session approximately 6 to 12 months from the first visit. Exposure: AHIs. Main Outcomes and Measures: Group-level quantitative metrics obtained from multiple modalities: (1) volumetric measurement, voxel-wise and region of interest (ROI)-wise; (2) diffusion MRI-derived metrics, voxel-wise and ROI-wise; and (3) ROI-wise within-network resting-state functional connectivity using functional MRI. Exploratory data analyses used both standard, nonparametric tests and bayesian multilevel modeling. Results: Among the 81 participants with AHIs, the mean (SD) age was 42 (9) years and 49% were female; among the 48 control participants, the mean (SD) age was 43 (11) years and 42% were female. Imaging scans were performed as early as 14 days after experiencing AHIs with a median delay period of 80 (IQR, 36-544) days. After adjustment for multiple comparisons, no significant differences between participants with AHIs and control participants were found for any MRI modality. At an unadjusted threshold (P < .05), compared with control participants, participants with AHIs had lower intranetwork connectivity in the salience networks, a larger corpus callosum, and diffusion MRI differences in the corpus callosum, superior longitudinal fasciculus, cingulum, inferior cerebellar peduncle, and amygdala. The structural MRI measurements were highly reproducible (median coefficient of variation <1% across all global volumetric ROIs and <1.5% for all white matter ROIs for diffusion metrics). Even individuals with large differences from control participants exhibited stable longitudinal results (typically, <±1% across visits), suggesting the absence of evolving lesions. The relationships between the imaging and clinical variables were weak (median Spearman ρ = 0.10). The study did not replicate the results of a previously published investigation of AHIs. Conclusions and Relevance: In this exploratory neuroimaging study, there were no significant differences in imaging measures of brain structure or function between individuals reporting AHIs and matched control participants after adjustment for multiple comparisons.

Clinical, Biomarker, and Research Tests Among US Government Personnel and Their Family Members Involved in Anomalous Health Incidents.

Importance: Since 2015, US government and related personnel have reported dizziness, pain, visual problems, and cognitive dysfunction after experiencing intrusive sounds and head pressure. The US government has labeled these anomalous health incidents (AHIs). Objective: To assess whether participants with AHIs differ significantly from US government control participants with respect to clinical, research, and biomarker assessments. Design, Setting, and Participants: Exploratory study conducted between June 2018 and July 2022 at the National Institutes of Health Clinical Center, involving 86 US government staff and family members with AHIs from Cuba, Austria, China, and other locations as well as 30 US government control participants. Exposures: AHIs. Main Outcomes and Measures: Participants were assessed with extensive clinical, auditory, vestibular, balance, visual, neuropsychological, and blood biomarkers (glial fibrillary acidic protein and neurofilament light) testing. The patients were analyzed based on the risk characteristics of the AHI identifying concerning cases as well as geographic location. Results: Eighty-six participants with AHIs (42 women and 44 men; mean [SD] age, 42.1 [9.1] years) and 30 vocationally matched government control participants (11 women and 19 men; mean [SD] age, 43.8 [10.1] years) were included in the analyses. Participants with AHIs were evaluated a median of 76 days (IQR, 30-537) from the most recent incident. In general, there were no significant differences between participants with AHIs and control participants in most tests of auditory, vestibular, cognitive, or visual function as well as levels of the blood biomarkers. Participants with AHIs had significantly increased fatigue, depression, posttraumatic stress, imbalance, and neurobehavioral symptoms compared with the control participants. There were no differences in these findings based on the risk characteristics of the incident or geographic location of the AHIs. Twenty-four patients (28%) with AHI presented with functional neurological disorders. Conclusions and Relevance: In this exploratory study, there were no significant differences between individuals reporting AHIs and matched control participants with respect to most clinical, research, and biomarker measures, except for objective and self-reported measures of imbalance and symptoms of fatigue, posttraumatic stress, and depression. This study did not replicate the findings of previous studies, although differences in the populations included and the timing of assessments limit direct comparisons.

The Cambridge aided loudness profile (CALP): item choices and data for unaided listening by young and older normal-hearing listeners and older hearing-impaired listeners.

OBJECTIVE: To develop an improved version of the profile of aided loudness (PAL), intended for assessment of the appropriateness of the loudness of everyday sounds. DESIGN: Initially, 16 participants with a range of ages and degrees of hearing loss indicated whether they encountered each situation described in the PAL and how specific they considered the description to be. Based on the responses, most situations from the PAL were eliminated and new situations were introduced, giving the Cambridge Aided Loudness Profile (CALP). The CALP was administered to 80 young and 22 older participants with normal hearing, who rated the loudness of each situation and satisfaction with this loudness (as for the original PAL). Satisfaction was strongly negatively correlated with loudness, suggesting that satisfaction was largely based on loudness. The CALP was then administered to 32 new young normal-hearing participants and 49 older participants with hearing loss, most of whom used hearing aids, who rated loudness and the appropriateness of loudness. RESULTS: Some situations were rated as loud but appropriate in loudness, indicating that the CALP can distinguish these aspects. CONCLUSIONS: The CALP questions were understood by all participants. The CALP may be useful for assessing the appropriateness of loudness.

Development of New Open-Set Speech Material for Use in Clinical Audiology with Speakers of British English.

BACKGROUND: The Chear open-set performance test (COPT), which uses a carrier phrase followed by a monosyllabic test word, is intended for clinical assessment of speech recognition, evaluation of hearing-device performance, and the fine-tuning of hearing devices for speakers of British English. This paper assesses practice effects, test-retest reliability, and the variability across lists of the COPT. METHOD: In experiment 1, 16 normal-hearing participants were tested using an initial version of the COPT, at three speech-to-noise ratios (SNRs). Experiment 2 used revised COPT lists, with items swapped between lists to reduce differences in difficulty across lists. In experiment 3, test-retest repeatability was assessed for stimuli presented in quiet, using 15 participants with sensorineural hearing loss. RESULTS: After administration of a single practice list, no practice effects were evident. The critical difference between scores for two lists was about 2 words (out of 15) or 5 phonemes (out of 50). The mean estimated SNR required for 74% words correct was -0.56 dB, with a standard deviation across lists of 0.16 dB. For the participants with hearing loss tested in quiet, the critical difference between scores for two lists was about 3 words (out of 15) or 6 phonemes (out of 50).

Sensitivity of Methods for Diagnosing Noise-Induced Hearing Loss in Cases of Exposures Including Intense Low-Frequency Noise.

Exposure to intense low-frequency sounds, for example inside tanks and armoured vehicles, can lead to noise-induced hearing loss (NIHL) with a variable audiometric pattern, including low- and mid-frequency hearing loss. It is not known how well existing methods for diagnosing NIHL apply in such cases. Here, the audiograms of 68 military personnel (mostly veterans) who had been exposed to intense low-frequency noise (together with other types of noise) and who had low-frequency hearing loss (defined as a pure-tone average loss at 0.25, 0.5 and 1 kHz ≥20 dB) were used to assess the sensitivity of three diagnostic methods: the method of Coles, Lutman and Buffin, denoted CLB, which depends on the identification of a notch or bulge in the audiogram near 4 kHz, and two methods specifically intended for diagnosing NIHL sustained during military service, the rM-NIHL method, which depends on the identification of a notch or bulge in the audiogram near 4 kHz and/or a hearing loss at high frequencies greater than expected from age alone, and the MLP(18) method based on a multi-layer perceptron. The proportion of individuals receiving a positive diagnosis for either or both ears, which provides an approximate measure of sensitivity, was 0.40 for the CLB method, 0.79 for the rM-NIHL method and 1.0 for the MLP(18) method. It is concluded that the MLP(18) method is suitable for diagnosing NIHL sustained during military service whether or not the exposure includes intense low-frequency sounds.

Confirmatory factor analysis of the Hyperacusis Impact Questionnaire, Sound Sensitivity Symptoms Questionnaire, and Screening for Anxiety and Depression in Tinnitus, including preliminary analyses of the parent versions for use with children.

BACKGROUND: We previously reported the results of exploratory factor analysis (EFA) of the Hyperacusis Impact Questionnaire (HIQ), the Sound Sensitivity Symptoms Questionnaire (SSSD) and the Screening for Anxiety and Depression in Tinnitus (SAD-T). Confirmatory Factor Analysis (CFA) is necessary to confirm the latent constructs determined using EFA. CFA should use different samples but with similar characteristics to those used for EFA. PURPOSE: The aim was to use CFA to confirm latent constructs derived using EFA of the HIQ, SSSQ and SAD-T. We further evaluated the psychometric properties of parent versions of these questionnaires (indicated by -P), which are intended for use with children. RESEARCH DESIGN: This was a retrospective cross-sectional study. STUDY SAMPLE: Data for 323 consecutive adults and 49 children who attended a Tinnitus and Hyperacusis Therapy Clinic in the UK within a six-month period were included. DATA COLLECTION AND ANALYSIS: Data were collected retrospectively from the records of patients held at the audiology department. CFA with the weighted least-squares mean and variance-adjusted estimator was applied to assess the previously proposed factor structures of the HIQ, SSSQ and SAD-T. The internal consistency of the scales was assessed via Cronbach's alpha (α). The items of the HIQ, SSSQ and SAD-T were tested for measurement invariance regarding age and gender using the multiple indicator multiple cause (MIMIC) model. RESULTS: All questionnaires showed good to excellent internal consistency, with α = 0.93 for the HIQ, 0.87 for the SSSQ, and 0.91 for the SAD-T. The parent versions showed acceptable to good internal consistency, with α = 0.88 for the HIQ-P, 0.71 for the SSSQ-P, and 0.86 for the SAD-T-P. CFA showed that the HIQ, SSSQ, and SAD-T were all one-factor questionnaires and the factors generally were similar to those obtained for the EFA. The MIMIC model showed that all three questionnaires can be considered as measurement invariant, with scores similar across genders and ages. CONCLUSIONS: The HIQ, SSSQ and SAD-T are internally consistent one-factor questionnaires that can be used in clinical and research settings to assess the impact of hyperacusis, the severity of sound sensitivity symptoms, and to screen for anxiety and depression symptoms. Future studies should further explore the psychometric properties of the parent versions of the HIQ and SSSQ and SAD-T.