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States that although abnormal T-cell subsets correlate with the progression of human immunodeficiency virus (HIV)-related disease, approximately 5 percent of healthy persons have abnormal T-cell values. Needless anxiety this has provoked among persons so labeled; Impact of such labeling on insurance in California; Ways to establish that a healthy person with abnormal T-cell subsets is not infected with HIV or AIDS.

Background: We previously reported that olaparib led to significantly longer imaging-based progression-free survival than the physician's choice of enzalutamide or abiraterone among men with metastatic castration-resistant prostate cancer who had qualifying alterations in homologous recombination repair genes and whose disease had progressed during previous treatment with a next-generation hormonal agent. The results of the final analysis of overall survival have not yet been reported.Methods: In an open-label, phase 3 trial, we randomly assigned patients in a 2:1 ratio to receive olaparib (256 patients) or the physician's choice of enzalutamide or abiraterone plus prednisone as the control therapy (131 patients). Cohort A included 245 patients with at least one alteration in BRCA1, BRCA2, or ATM, and cohort B included 142 patients with at least one alteration in any of the other 12 prespecified genes. Crossover to olaparib was allowed after imaging-based disease progression for patients who met certain criteria. Overall survival in cohort A, a key secondary end point, was analyzed with the use of an alpha-controlled, stratified log-rank test at a data maturity of approximately 60%. The primary and other key secondary end points were reported previously.Results: The median duration of overall survival in cohort A was 19.1 months with olaparib and 14.7 months with control therapy (hazard ratio for death, 0.69; 95% confidence interval [CI], 0.50 to 0.97; P = 0.02). In cohort B, the median duration of overall survival was 14.1 months with olaparib and 11.5 months with control therapy. In the overall population (cohorts A and B), the corresponding durations were 17.3 months and 14.0 months. Overall, 86 of 131 patients (66%) in the control group crossed over to receive olaparib (56 of 83 patients [67%] in cohort A). A sensitivity analysis that adjusted for crossover to olaparib showed hazard ratios for death of 0.42 (95% CI, 0.19 to 0.91) in cohort A, 0.83 (95% CI, 0.11 to 5.98) in cohort B, and 0.55 (95% CI, 0.29 to 1.06) in the overall population.Conclusions: Among men with metastatic castration-resistant prostate cancer who had tumors with at least one alteration in BRCA1, BRCA2, or ATM and whose disease had progressed during previous treatment with a next-generation hormonal agent, those who were initially assigned to receive olaparib had a significantly longer duration of overall survival than those who were assigned to receive enzalutamide or abiraterone plus prednisone as the control therapy, despite substantial crossover from control therapy to olaparib. (Funded by AstraZeneca and Merck Sharp and Dohme; PROfound ClinicalTrials.gov number, NCT02987543.). [ABSTRACT FROM AUTHOR]

Background: Multiple loss-of-function alterations in genes that are involved in DNA repair, including homologous recombination repair, are associated with response to poly(adenosine diphosphate-ribose) polymerase (PARP) inhibition in patients with prostate and other cancers.Methods: We conducted a randomized, open-label, phase 3 trial evaluating the PARP inhibitor olaparib in men with metastatic castration-resistant prostate cancer who had disease progression while receiving a new hormonal agent (e.g., enzalutamide or abiraterone). All the men had a qualifying alteration in prespecified genes with a direct or indirect role in homologous recombination repair. Cohort A (245 patients) had at least one alteration in BRCA1, BRCA2, or ATM; cohort B (142 patients) had alterations in any of 12 other prespecified genes, prospectively and centrally determined from tumor tissue. Patients were randomly assigned (in a 2:1 ratio) to receive olaparib or the physician's choice of enzalutamide or abiraterone (control). The primary end point was imaging-based progression-free survival in cohort A according to blinded independent central review.Results: In cohort A, imaging-based progression-free survival was significantly longer in the olaparib group than in the control group (median, 7.4 months vs. 3.6 months; hazard ratio for progression or death, 0.34; 95% confidence interval, 0.25 to 0.47; P<0.001); a significant benefit was also observed with respect to the confirmed objective response rate and the time to pain progression. The median overall survival in cohort A was 18.5 months in the olaparib group and 15.1 months in the control group; 81% of the patients in the control group who had progression crossed over to receive olaparib. A significant benefit for olaparib was also seen for imaging-based progression-free survival in the overall population (cohorts A and B). Anemia and nausea were the main toxic effects in patients who received olaparib.Conclusions: In men with metastatic castration-resistant prostate cancer who had disease progression while receiving enzalutamide or abiraterone and who had alterations in genes with a role in homologous recombination repair, olaparib was associated with longer progression-free survival and better measures of response and patient-reported end points than either enzalutamide or abiraterone. (Funded by AstraZeneca and Merck Sharp & Dohme; PROfound ClinicalTrials.gov number, NCT02987543.). [ABSTRACT FROM AUTHOR]

Abstract: Objective: With more children receiving cochlear implants at an early age, there is a need for evaluation and assessment of early auditory behavior. We present the translation of the LittlEARS® Auditory Questionnaire into Hebrew and into Arabic. First the validation of the LittlEARS® Auditory Questionnaire in normal hearing children was evaluated. Second, the auditory behavior and the progress in hearing skills of a group of children with cochlear implants were assessed. Methods: A “back-translation” method was used to translate and adapt the LittlEARS® Auditory Questionnaire into Hebrew and into Arabic. Normal hearing participants included 70 Hebrew speaking and 97 Arabic speaking parents of children from 1 to 24 months of age with normal hearing. An additional group of 42 parents of children with cochlear implants with a hearing age of up to 24 months completed the LittlEARS® Auditory Questionnaire. 27 of them completed the questionnaire more than once at intervals, so that change and development could be recorded. Scores on the LittlEARS® Auditory Questionnaire were compared to results of SIR and CAP scales and other available auditory data. Results: The results of the first study show that the curves found for the Hebrew and the Arabic translations of the LittlEARS® Auditory Questionnaire are essentially similar to those previously found for other languages. These curves reflect the age dependency of auditory skills. Furthermore, in the group with cochlear implants the developmental pattern was different than that of the normal hearing group, with an initial steep increase and a later slower improvement. This trend appeared both in curves of groups and in curves of individuals (individuals whose parents completed the questionnaire at several points in time). There was a high correlation between scores on the LittlEARS® Auditory Questionnaire and results of other audiologic tests, showing validity of results with the LittlEARS® Auditory Questionnaire. Conclusion: Both the Hebrew and Arabic versions of the LittlEARS® Auditory Questionnaire were found to be reliable and valid tools for assessment of the development of auditory behavior in children up to the age of 24 months. Furthermore, the LittlEARS® Auditory Questionnaire in both languages is useful in monitoring the progress of children with cochlear implant. [Copyright &y& Elsevier]

Purpose: Bilingual children often demonstrate a high rate of disfluencies, which might impact the diagnostic evaluation of fluency disorders; however, research on the rates and types of disfluencies in bilinguals' two languages is limited. The purpose of this research is to profile disfluencies of two types, stuttering-like disfluencies (SLDs) and other disfluencies (ODs), in the speech of Russian-Hebrew bilingual typically developing children, focusing on cross-linguistic differences and the effect of language proficiency in both languages., Method: Spontaneous narratives based on the Frog, Where Are You? (Mayer, 1969) picture book were collected in both languages from 40 bilingual Russian-Hebrew children aged 5;6-6;6 (years;months). The transcribed narratives were coded for SLD (sound, syllable, and monosyllabic word repetitions) and OD (multisyllabic word/phrase repetitions, interjections, and revisions), and their frequencies per 100 syllables were calculated., Results: Overall, most children had a percentage of SLD and OD below the cutoff point and within the existing criteria for stuttering diagnosis established based on monolingual data, but several children exceeded this stuttering criterion. Monosyllabic word repetitions (part of SLD) and interjections (part of OD) were more frequent in Hebrew than in Russian. Lower proficiency was associated with a higher percentage of monosyllabic word repetitions and of interjections in both languages., Conclusions: Bilingual disfluency criteria are needed, since based on the existing monolingual criteria, some children might be erroneously assessed as children who stutter, thus leading to overdiagnosis. The results support the claim that proficiency is an important factor in the production of disfluencies.

Introduction: Vestibular Schwannoma, a benign slow growing tumor on the eight cranial nerve, will eventually cause in most patients, a severe sensory neural hearing loss in the ipsilateral ear. Patients with asymmetric hearing loss experience difficulties in hearing in the presence of noise, in sound localization and an increase in listening effort, especially if contralateral hearing loss exists. Cochlear implant is the treatment of choice for hearing rehabilitation in severe to profound sensorineural hearing loss. This treatment was shown to be effective in patients with vestibular schwannoma whether they were treated by surgery, radiation or conservative surveillance only. In this case report we present 2 patients with stable growth of over 10 years, who presented with a severe decrease in hearing loss on the ipsilateral side and a known contralateral moderate loss. Both underwent cochlear implant with no other intervention and demonstrated great speech perception results and continue to use the implant regularly for several years. The cochlear implant is an effective tool for hearing rehabilitation for patients with a stable vestibular schwannoma under conservative surveillance. It is of grave importance to properly educate these patients on hearing rehabilitation and recommend cochlear implant for appropriate patients.

Purpose: The aim of this study was to assess the perceptions of audiology students and preceptors regarding changes in the practicum as a result of COVID-19., Method: This study was conducted during two different periods, with Internet questionnaires posted on social media forums. Preceptors and newly graduated clinicians were recruited in 2019 for a study prior to COVID-19, and students and preceptors were recruited for comparison during COVID-19. Four groups participated in this study: (a) 101 students who were enrolled in the second, third, or fourth year of an Israeli communication disorders Bachelor of Arts (BA) program during the pandemic; (b) 94 newly graduated audiologists with a BA degree from an Israeli communication disorders program granted in the last 3 years (before COVID-19); (c) 18 audiologist preceptors who supervised audiology practicum in an Israeli communication disorders BA programs (before COVID-19); and (d) 20 audiologist preceptors who, during COVID-19, were supervising an audiology practicum in Israel. Perceptions of the various groups were compared., Results: Although perceptions of preceptors and students regarding the practicum were revealed to be similar, perceptions of the practicum before COVID-19 underwent changes in the course of the pandemic. In evaluating the COVID-19 experience, both preceptors and students agreed that more hours of practicum were needed, as well as more variety in types of cases and exposure to varied placements., Conclusion: Academic programs and employers should consider implications of changes implemented in the practicum due to COVID-19, which can be addressed either in continuing education and/or by additional supervision in the future workplace., Supplemental Material: https://doi.org/10.23641/asha.19855639.

Background: Phase III randomized trial data have confirmed the activity for olaparib in homologous recombination repair (HRR) mutated metastatic castration-resistant prostate cancer (mCRPC) post next-generation hormonal agent (NHA) progression. Preclinical data have suggested the potential for a combined effect between olaparib and NHAs irrespective of whether an HRR gene alteration was present. NCT01972217 was a randomised double-blind Phase II study which evaluated olaparib and abiraterone versus placebo and abiraterone in mCRPC patients who had received prior chemotherapy containing docetaxel. The study showed that radiologic progression was significantly delayed by the combination of olaparib and abiraterone regardless of homologous recombination repair mutation (HRRm) status. The study utilized tumour, blood (germline), and circulating tumour DNA (ctDNA) analysis to profile patient HRRm status, but tumour tissue provision was not mandated, leading to relatively low tissue acquisition and DNA sequencing success rates not representative of real-world testing., Patients and Methods: Further analysis of germline and ctDNA samples has been performed for the trial to characterize HRRm status more fully and robustly analyse patient response to treatment., Results: Germline and plasma testing increased the HRRm characterized population from 27% to 68% of 142 randomized patients. Tumour-derived variants were detectable with high confidence in 78% of patients with a baseline plasma sample (71% of randomized patients). There was high concordance across methodologies (plasma vs. tumour; plasma vs. germline). The HR for the exploratory analysis of radiographic progression-free survival was 0.54 (95% CI: 0.32-0.93) in favour of olaparib and abiraterone in the updated HRR wild type (HRRwt) group ( n = 73) and 0.62 (95% CI: 0.23-1.65) in the HRRm group ( n = 23)., Conclusion: Our results confirm the value of plasma testing for HRRm status when there is insufficient high-quality tissue for multi-gene molecular testing. We show that patients with mCRPC benefit from the combination of olaparib and abiraterone treatment regardless of HRRm status. The combination is currently being further investigated in the Phase III PROpel trial.

Hypothesis: Hearing via soft tissue stimulation involves an osseous pathway., Background: A recent study that measured both hearing thresholds and skull vibrations found that vibratory stimulation of soft tissue led to hearing sensation that correlated with skull vibrations, supporting the hypothesis of an osseous pathway. It is possible, however, that a lower application force of the vibrator on the stimulated soft tissue would not be sufficient to elicit skull vibration suggesting hearing via a nonosseous pathway. The purpose of the present study was to confirm the osseous pathway by measuring skull vibrations and behavioral thresholds using a low application force on a layer of ultrasound gel. Gel was used to mimic soft tissue because of its similar acoustic impedance and to control for variability between participants., Methods: Hearing thresholds and the skull vibrations of five patients who were implanted with bone-anchored implants were assessed in two conditions when the bone vibrator was applied on the forehead: 1) direct application with 5N force; 2) through a layer of ultrasound gel with minimal application force. Skull vibrations were measured in both conditions by a laser Doppler vibrometer focused on the bone-anchored implant., Results: Skull vibrations were present even when minimal application force was applied on soft tissue. The difference in skull vibrations when the vibrator was directly on the forehead compared with the gel condition was consistent with the variability in hearing thresholds between the two conditions., Conclusion: These results reinforce the hypothesis that skull vibrations are involved in hearing when sound is transmitted via either soft tissue or bone., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2020, Otology & Neurotology, Inc.)

To gain insight into the broader implications of the occlusion effect (OE-difference between unoccluded and occluded external canal thresholds), the OE in response to pure tones at 0.5, 1.0, 2.0 and 4.0 kHz to two bone conduction sites (mastoid and forehead) and two soft tissue conduction (STC) sites (under the chin and at the neck) were assessed. The OE was present at the soft tissue sites and at the bone conduction sites, with no statistical difference between them. The OE was significantly greater at lower frequencies, and negligible at higher frequencies. It seems that the vibrations induced in the soft tissues (STC) during stimulation at the soft tissue sites are conducted not only to the inner ear and elicit hearing, but also reach the walls of the external canal and initiate air pressures in the occluded canal which drive the tympanic membrane and excite the inner ear, leading to hearing. Use of a stethoscope by the internist to hear intrinsic body sounds (heartbeat, blood flow) serves as a clear demonstration of STC and its relation to hearing.