Providing Mindful and Informed Health Care for Patients Who Are LGBTQ+: Perspectives for Clinical Audiology.

PURPOSE: More than 7% of the U.S. population identifies as LGBTQ+ (lesbian, gay, bisexual, transgender, queer, and other identities), meaning clinical audiologists in all settings are likely to encounter LGBTQ+ patients seeking audiological services. This conceptual clinical focus article (a) introduces contemporary LGBTQ+ terms, definitions, and pertinent issues; (b) summarizes the current state of knowledge on barriers to equitable hearing health care access and utilization for people who identify as LGBTQ+; (c) explores the legal, ethical, and moral obligations for audiologists to provide equitable care to people who identify as LGBTQ+; and (d) provides resources to continue to learn about salient LGBTQ+ issues. CONCLUSIONS: This clinical focus article provides actionable guidance to clinical audiologists on providing inclusive equitable care to LGBTQ+ patients. Practical actionable guidance on how clinical audiologists can make their clinical practice more inclusive for their patients who identify as LGBTQ+ is provided.

Audiologists' perceived value of ototoxicity management and barriers to implementation for at-risk cancer patients in VA: the OtoMIC survey.

PURPOSE: Platinum-based chemotherapies used to treat many types of cancers are ototoxic. Ototoxicity management (OtoM) to mitigate the ototoxic outcomes of cancer survivors is recommended practice yet it is not a standard part of oncologic care. Although more than 10,000 patients each year are treated with platinum-based chemotherapies at the US Veterans Health Administration (VA), the current state of OtoM in VA is not well-defined. This study reports on a national survey of VA audiologists' perceptions regarding OtoM in cancer patients. METHODS: A 26-item online survey was administered to VA audiologists and service chiefs across the VA's 18 regional systems of care. Descriptive statistics and deductive thematic analysis were used to analyze the data. RESULTS: The 61 respondents included at least one from each VA region. All reported they felt some form of OtoM was necessary for at-risk cancer patients. A pre-treatment baseline, the ability to detect ototoxicity early, and management of ototoxic effects both during and after treatment were considered high value objectives of OtoM by respondents. Roughly half reported routinely providing these services for patients receiving cisplatin and carboplatin. Respondents disagreed regarding appropriate hearing testing schedules and how to co-manage OtoM responsibilities with oncology. They identified barriers to care that conformed to three themes: care and referral coordination with oncology, audiology workload, and lack of protocols. CONCLUSIONS: Although VA audiologists value providing OtoM for cancer patients, only about half perform OtoM for highly ototoxic treatment regimens. The OtoMIC survey provides clinician perspectives to benchmark and address OtoM care gaps. IMPLICATIONS FOR CANCER SURVIVORS: Collaboration between oncology and audiology is needed to improve current OtoM processes, so that cancer survivors can have more control over their long term hearing health.

Mild hearing loss in C57BL6/J mice after exposure to antiretroviral compounds during gestation and nursing.

OBJECTIVE: There is evidence of ototoxicity from antiretrovirals (ARVs), and ARV therapy in pregnant/nursing mothers can expose offspring to these compounds. The current work modelled whether exposure to ARVs in utero and during nursing altered the functioning of the auditory system in offspring mice. DESIGN: The females of seven breeding pairs of C57BL6/J mice were given daily doses of ARVs lamivudine and tenofovir disoproxil fumarate by oral gavage during gestation and nursing. Three breeder females were given equivalent volumes of water as controls. At wean age (3 weeks after birth), the offspring mice were tested with auditory brainstem responses (ABRs). At the conclusion of the experiment, the offspring mice's cochleae were examined for hair cell counts. STUDY SAMPLE: Ten breeder female C57BL6/J mice and 69 offspring mice. RESULTS: The offspring mice exposed to ARVs during development showed higher ABR thresholds than the control offspring. No differences were found in supra-threshold ABRs. There was no evidence of missing hair cells. CONCLUSIONS: Hearing impairment may be a possible consequence of exposure to ARVs during gestation and development. Because the threshold differences were not large, if they are occurring in humans, it is unlikely they would be identified in any hearing screening tests.

Hearing Loss in Offspring Exposed to Antiretrovirals During Pregnancy and Breastfeeding.

Over 27 million people worldwide currently receive daily antiretroviral therapy for the management of HIV/AIDS. In order to prevent the continued spread of HIV, the World Health Organization (WHO) recommends the use of highly active antiretroviral therapy by pregnant and nursing women. There is currently little research into the auditory effects of this therapy on children exposed during pregnancy and breastfeeding, and research to date on the direct effects of antiretroviral exposure on the auditory system is inconclusive. The current study examined the effects of WHO-recommended first-line antiretrovirals in a well-controlled animal model to evaluate the potential for auditory damage and dysfunction following these exposures. Female breeding mice were each exposed to one of four antiretroviral cocktails or a vehicle control once daily during pregnancy and breastfeeding. Offspring of these mice had their auditory status evaluated after weaning using auditory brainstem responses and distortion-product otoacoustic emissions (DPOAEs). Auditory brainstem response thresholds following antiretroviral exposure during gestation and breastfeeding showed elevated thresholds and increased wave latencies in offspring of exposed mice when compared to unexposed controls, but no corresponding decrease in DPOAE amplitude. These differences in threshold were small and so may explain the lack of identified hearing loss in antiretroviral-exposed children during hearing screenings at birth. Minimal degrees of hearing impairment in children have been correlated with decreased academic performance and impaired auditory processing, and so these findings, if also seen in human children, suggest significant implications for children exposed to antiretrovirals during development despite passing hearing screenings at birth.

Cochlear Preconditioning as a Modulator of Susceptibility to Hearing Loss.

Significance: Acquired sensorineural hearing loss is a major public health problem worldwide. The leading causes of sensorineural hearing loss are noise, aging, and ototoxic medications, with the key underlying pathology being damage to the cochlea. The review focuses on the phenomenon of preconditioning, in which the susceptibility to cochlear injury is reduced by exposing the ear to a stressful stimulus. Recent Advances: Cochlear conditioning has focused on the use of mono-modal conditioning, specifically conditioning the cochlea with moderate noise exposures before a traumatic exposure that causes permanent hearing loss. Recently, cross-modal conditioning has been explored more thoroughly, to prevent not only noise-induced hearing loss, but also age-related and drug-induced hearing losses. Critical Issues: Noise exposures that cause only temporary threshold shifts (TTSs) can cause long-term synaptopathy, injury to the synapses between the inner hair cells and spiral ganglion cells. This discovery has the potential to significantly alter the field of cochlear preconditioning with noise. Further, cochlear preconditioning can be the gateway to the development of clinically deployable therapeutics. Therefore, understanding the underlying mechanisms of conditioning is crucial for optimizing clinical protection against sensorineural hearing loss. Future Directions: Before the discovery of synaptopathy, noise exposures that caused only TTSs were believed to be either harmless or potentially beneficial. Any considerations of preconditioning with noise must consider the potential for injury to the synapses. Further, the discovery of different methods to precondition the cochlea against injury will yield new avenues for protection against hearing loss in the vulnerable populations. Antioxid. Redox Signal. 36, 1215-1228.

Changing the time intervals between cisplatin cycles alter its ototoxic side effect.

Various methods have been tested and deployed clinically to identify and minimize cisplatin ototoxicity. Upon early identification of hearing loss, one of the possible approaches to reducing future ototoxicity is to increase the gaps or breaks between cycles or doses of cisplatin. However, recent findings about the retention of cisplatin in the cochlea and the potential for its long-term ototoxic effects call into question whether such an approach is effective in reducing hearing loss. The current study was undertaken to determine whether increasing the rest intervals between cycles of cisplatin altered the resulting ototoxicity. CBA/CaJ mice were exposed to a cumulative dose of 48 mg/kg cisplatin delivered in three cycles of 16 mg/kg (4 mg/kg per day for 4 consecutive days). The cycles were separated by either 10, 17, or 87 days to determine if the inter-cycle rest intervals affected resulting ototoxicity. Ototoxicity was measured using auditory brainstem response threshold shifts and hair cell losses. Results indicated that longer intervals between cycles of cisplatin led to lower threshold shifts and outer hair cell lesions. The results support the principle that 'slowing down' cisplatin dosing by increasing rest intervals between doses can reduce the ototoxic side effect. Further testing is needed to optimize the timing and to determine the impact of longer inter-cycle intervals on cisplatin's anti-tumor efficacy.

The Impact of Speech Recognition Testing on State Anxiety in Young, Middle-Age, and Older Adults.

Purpose This study assessed state anxiety as a function of speech recognition testing using three clinical measures of speech in noise and one clinical measure of dichotic speech recognition. Method Thirty young adults, 30 middle-age adults, and 25 older adults participated. State anxiety was measured pre- and post-speech recognition testing using the State-Trait Anxiety Inventory. Speech recognition was measured with the Revised Speech Perception in Noise Test, the Quick Speech-in-Noise Test, the Words-in-Noise Test, and the Dichotic Digits Test (DDT). Results Speech recognition performance was as expected: Older adults performed significantly poorer on all measures as compared to the young adults and significantly poorer on the Revised Speech Perception in Noise Test, the Quick Speech-in-Noise Test, and the Words-in-Noise Test as compared to the middle-age adults. On average, State-Trait Anxiety Inventory scores increased posttesting, with the middle-age adults exhibiting significantly greater increases in state anxiety as compared to the young and older adults. Increases in state anxiety were significantly greater for the DDT relative to the speech-in-noise tests for the middle-age adults only. Poorer DDT recognition performance was associated with higher levels of state anxiety. Conclusions Increases in state anxiety were observed after speech-in-noise and dichotic listening testing for all groups, with significant increases seen for the young and middle-age adults. Although the exact mechanisms could not be determined, multiple factors likely influenced the observed increases in state anxiety, including task difficulty, individual proficiency, and age.

Cisplatin-induced threshold shift in the CBA/CaJ, C57BL/6J, BALB/cJ mouse models of hearing loss.

The development of a clinically-relevant rodent model of cisplatin-induced hearing loss presents the challenges of finding the cumulative dose, dosing schedule, and rodent strain to induce a consistent level of threshold shift with low mortality. This study was undertaken to model hearing loss at 16, 32, and 48 mg/kg cumulative doses of cisplatin in the CBA/CaJ, C57BL/6J, and BALB/cJ mouse strains. Mice were exposed to three cycles of 16 mg/kg cisplatin, for a cumulative dose of 48 mg/kg. Equal numbers of male and female mice were used in each strain, and the cisplatin was delivered in three different dosing schedules: a single bolus dose of 16 mg/kg followed by 20 days of recovery, 8 mg/kg doses delivered every ten days, and 4 mg/kg delivered daily for four consecutive days followed by 17 days of recovery. Auditory brainstem response threshold shifts indicated increased hearing loss with increasing cumulative dose in all strains and dosing schedules. The BALB/cJ experienced the largest threshold shifts, and the C57BL/6J the smallest. However, the BALB/cJ mice had the lowest mortality (0%) of the strains. The dosing schedule had minimal effects on threshold shift, but did affect mortality, with the 16 mg/kg single dose inducing more mortality than the other two schedules. In the BALB/cJ mice, the males experienced more threshold shift than the females. The results mirror past work comparing the three strains' susceptibility to kanamycin ototoxicity, with highest pigmentation showing the lowest acute susceptibility to cisplatin-induced hearing loss, and the albino strain showing the highest susceptibility.

Chronotolerance for cisplatin ototoxicity in the rat.

Cisplatin is a potent chemotherapeutic compound for which ototoxicity is a significant side effect. Cisplatin has shown sensitivity to circadian time, in that cisplatin is most effective as an anti-tumor compound, and least nephrotoxic, when given in the active (dark) period of the light-dark cycle in rodents. The objective of the study was to determine the sensitivity of cisplatin ototoxicity to circadian time. Fifty-seven Fischer 344/NHsd rats were exposed to 12 mg/kg cisplatin by intra-peritoneal injection at one of six time points on a 12 h light-12 h dark cycle: 2, 6, or 10 h after light onset or 2, 6, or 10 h after light offset. Cochlear injury was evaluated using auditory brainstem response threshold shifts and postmortem outer hair cell counts. All animals experienced threshold shift in the highest frequencies tested (30 and 40 kHz). The animals exposed to cisplatin at 6 h after light onset (the inactive period) had significantly higher mid-frequency threshold shifts and outer hair cell losses than the groups exposed during the dark hours. The results indicate that cisplatin is less likely to cause ototoxicity in the Fischer 344/NHsd rat when given during the active period. This finding is consistent with the lower nephrotoxicity that has been detected in cisplatin-exposed animals treated during the dark hours, and the magnitude of differences in threshold shifts between the light and dark exposure indicates that circadian timing has a significant impact on susceptibility to cisplatin ototoxicity.

Long-Term Synergistic Interaction of Cisplatin- and Noise-Induced Hearing Losses.

OBJECTIVE: Past experiments in the literature have shown that cisplatin interacts synergistically with noise to create hearing loss. Much of the previous work on the synergistic interaction of noise and cisplatin tested exposures that occurred very close together in time. The present study assessed whether rats that have been exposed to cisplatin continue to show increased susceptibility to noise-induced hearing loss months after conclusion of the cisplatin exposure. DESIGN: Thirty-two Fischer 344/NHsd rats were exposed to one of five conditions: (1) cisplatin exposure followed by immediate cochlear tissue harvest, (2) cisplatin exposure and a 20-week monitoring period before tissue harvest, (3) cisplatin exposure followed immediately by noise exposure, (4) cisplatin exposure followed by noise exposure 16 weeks later, and (5) noise exposure without cisplatin exposure. The cisplatin exposure was an 8-week interval in which cisplatin was given every 2 weeks. Cochlear injury was evaluated using auditory brainstem response thresholds, P1 wave amplitudes, and postmortem outer hair cell counts. RESULTS: The 8-week cisplatin exposure induced little threshold shift or P1 amplitude loss, and a small lesion of missing outer hair cells in the basal half of the cochlea. The rats exposed to noise immediately after the cisplatin exposure interval showed a synergistic interaction of cisplatin and noise. The group exposed to noise 16 weeks after the cisplatin exposure interval also showed more severe threshold shift and outer hair cell loss than control subjects. The controls exposed to cisplatin and monitored for 20 weeks showed little threshold shift or outer hair cell loss, but did show P1 wave amplitude changes over the 20-week monitoring period. CONCLUSIONS: The results from the groups exposed to cisplatin followed by noise, combined with the findings from the cisplatin- and noise-only groups, suggest that the cisplatin induced cochlear injuries that were not severe enough to result in threshold shift, but left the cochlea in a state of heightened susceptibility to future injury. The heightened susceptibility to noise injury was still present 16 weeks after the conclusion of the cisplatin exposure.

A low-dose regimen of cisplatin before high-dose cisplatin potentiates ototoxicity.

OBJECTIVES/HYPOTHESIS: Cochlear preconditioning with low doses of kanamycin or noise can reduce susceptibility to noise- and ototoxic drug-induced hearing loss. The current study was undertaken to investigate whether a preconditioning regimen of low-dose cisplatin would alter susceptibility to ototoxicity induced by a single large dose of cisplatin. STUDY DESIGN: In vivo study using an animal model. METHODS: Twenty-six Fischer 344/NHsd rats were used in the study. The low-dose regimen consisted of cisplatin (2 or 3 mg/kg) given every 2 weeks by intraperitoneal injection. Control animals received injections of saline on the same schedule as the cisplatin injections. Four injections were done in total. Following the preconditioning interval, seven of the animals were sacrificed for hair cell analyses. The remaining 19 animals were exposed to 12 mg/kg cisplatin by intraperitoneal infusion to induce cochlear injury. Auditory brainstem response (ABR) thresholds were measured 3 days after cisplatin, and the cochleae from the 19 animals were harvested and analyzed. RESULTS: Statistical analyses revealed no threshold shifts, but mild outer hair cell losses, after the low-dose regimen. ABR threshold shifts in the rats exposed to the 12 mg/kg cisplatin dose were significantly higher at day 3 in the animals that underwent preconditioning with low-dose cisplatin. Outer hair cell losses were also greater in the preconditioned animals. CONCLUSIONS: Preconditioning with low-dose cisplatin, using the protocol applied in the current experiment, created potentiation of cisplatin ototoxicity, rather than protection from it. There are numerous possible explanations for this effect that should be considered. LEVEL OF EVIDENCE: NA.