Prevalence of ototoxic medication use among older adults in Beaver Dam, Wisconsin.
ABSTRACT: BACKGROUND AND PURPOSE:Drug-related ototoxicity may exacerbate presbycusis (age-related hearing loss); yet, few data are available on the prevalence of ototoxic medication use by older adults. The purposes of this study were to assess the impact of aging and ototoxicity on hearing loss, the prevalence of ototoxic medication use, and select characteristics associated with ototoxic medication use among older adults. METHODS:Cross-sectional analyses were conducted using select variables extracted from the baseline and 10-year follow-up assessments of the two population-based epidemiological studies to compare two points in time. RESULTS:Ninety-one percent of the sample was taking a medication reported to be ototoxic. Nonsteroidal anti-inflammatory drugs were the most commonly used (75.2%), followed by acetaminophen (39.9%) and diuretics (35.6%). Hypertension, diabetes, cardiovascular disease, and history of smoking were associated with ototoxic medication use. Participants with hearing loss were taking a significantly greater number of ototoxic medications than those without hearing loss. CONCLUSION:Known ototoxic medications are widely used. Any subsequent ototoxicity may interact with age changes and a more severe hearing loss than that associated with only age. IMPLICATIONS FOR PRACTICE:Nurse practitioners should inform older adults about the possibility of drug-related ototoxicity and monitor hearing acuity of all older adults taking known ototoxic medications.
Project description:Therapeutic drugs with ototoxic side effects cause significant hearing loss for thousands of patients annually. Two major classes of ototoxic drugs are cisplatin and the aminoglycoside antibiotics, both of which are toxic to mechanosensory hair cells, the receptor cells of the inner ear. A critical need exists for therapies that protect the inner ear without inhibiting the therapeutic efficacy of these drugs. The induction of heat shock proteins (HSPs) inhibits both aminoglycoside- and cisplatin-induced hair cell death and hearing loss. We hypothesized that exposure to sound that is titrated to stress the inner ear without causing permanent damage would induce HSPs in the cochlea and inhibit ototoxic drug–induced hearing loss. We developed a sound exposure protocol that induces HSPs without causing permanent hearing loss. We used this protocol in conjunction with a newly developed mouse model of cisplatin ototoxicity and found that preconditioning mouse inner ears with sound has a robust protective effect against cisplatin-induced hearing loss and hair cell death. Sound therapy also provided protection against aminoglycoside-induced hearing loss. These data indicate that sound preconditioning protects against both classes of ototoxic drugs, and they suggest that sound therapy holds promise for preventing hearing loss in patients receiving these drugs.
Project description:Aminoglycoside-induced cochlear ototoxicity causes hair cell (HC) loss and results in hearing impairment in patients. Previous studies have developed the concept of an ototoxicity-sensitive period during which the cochleae of young mice are more vulnerable to auditory trauma than adults. Here, we compared neomycin-induced ototoxicity at the following four developmental ages in mice: postnatal day (P)1-P7, P8-P14, P15-P21, and P60-P66. We found that when neomycin was administered between P8 and P14, the auditory brainstem response threshold increase was significantly higher at low frequencies and HC loss was significantly greater in the apical turn of the cochlea compared to neomycin administration during the other age ranges. Quantitative real-time PCR (qPCR) data revealed that the expression of apoptotic markers, including Casp3 and Casp9, was significantly higher when neomycin was injected from P8 to P14, while the expression of the X-linked inhibitor of apoptosis protein (XIAP) gene was significantly higher when neomycin was injected from P60 to P66. Because XIAP expression was low during the neomycin-sensitive period, we overexpressed XIAP in mice and found that it could protect against neomycin-induced hearing loss at low frequencies and HC loss in the apical turn of the cochlea. Altogether, our findings demonstrate a protective role for XIAP against neomycin-induced hearing loss and HC loss in the apical turn of the cochlea during the ototoxic-sensitive period, and suggest that apoptotic factors mediate the effect of neomycin during the ototoxic-sensitive period.
Project description:Taking a genome-wide association study approach, we identified inherited genetic variations in ACYP2 associated with cisplatin-related ototoxicity (rs1872328: P = 3.9 × 10(-8), hazard ratio = 4.5) in 238 children with newly diagnosed brain tumors, with independent replication in 68 similarly treated children. The ACYP2 risk variant strongly predisposed these patients to precipitous hearing loss and was related to ototoxicity severity. These results point to new biology underlying the ototoxic effects of platinum agents.
Project description:BACKGROUND:To confirm levels and detection timing of circulating microRNAs (miRNAs) in the serum of a mouse model for diagnosis of ototoxicity, circulating miR-205 in the serum was evaluated to reflect damages in the cochlear microstructure and compared to a kidney injury model. METHOD:A microarray for miRNAs in the serum was performed to assess the ototoxic effects of kanamycin-furosemide. Changes in the levels for the selected miRNAs (miR-205, miR-183, and miR-103) were compared in the serum and microstructures of the cochlea (stria vascularis, organ of Corti, and modiolus) between the ototoxicity and normal mouse groups. An acute kidney injury (AKI) mouse model was used to assess changes in miR-205 levels in the kidney by ototoxic drugs. RESULTS:In the mouse model for ototoxicity, the serum levels of circulating miR-205 peaked on day 3 and were sustained from days 7?14. Furthermore, miR-205 expression was highly expressed in the organ of Corti at day 5, continued to be expressed in the modiolus at high levels until day 14, and was finally also in the stria vascularis. The serum miR-205 in the AKI mice did not change significantly compared to the normal group. Conclusions Circulating miR-205 from the cochlea, after ototoxic damage, migrates through the blood vessels to organs, which is then finally found in blood. In conditions of hearing impairment with ototoxic medications, detection of circulating miR-205 in the blood can be used to determine the extent of hearing loss. In the future, inner ear damage can be identified by simply performing a blood test before the hearing impairment due to ototoxic drugs.
Project description:Ototoxicity is a significant side effect of a number of drugs, including the aminoglycoside antibiotics and platinum-based chemotherapeutic agents that are used to treat life-threatening illnesses. Although much progress has been made, the mechanisms that lead to ototoxic loss of inner ear sensory hair cells (HCs) remains incompletely understood. Given the critical role of protein phosphorylation in intracellular processes, including both damage and survival signaling, we screened a library of kinase inhibitors targeting members of all the major families in the kinome. Micro-explants from the organ of Corti of mice in which only the sensory cells express GFP were exposed to 200 ?M of the ototoxic aminoglycoside gentamicin with or without three dosages of each kinase inhibitor. The loss of sensory cells was compared to that seen with gentamicin alone, or without treatment. Of the 160 inhibitors, 15 exhibited a statistically significant protective effect, while 3 significantly enhanced HC loss. The results confirm some previous studies of kinase involvement in HC damage and survival, and also highlight several novel potential kinase pathway contributions to ototoxicity.
Project description:BACKGROUND:Cisplatin is one of the most ototoxic chemotherapy drugs, resulting in a permanent and irreversible hearing loss in up to 50% of patients. Cisplatin and gentamicin are thought to damage hearing through a common mechanism, involving reactive oxygen species in the inner ear. Aspirin has been shown to minimise gentamicin-induced ototoxicity. We, therefore, tested the hypothesis that aspirin could also reduce ototoxicity from cisplatin-based chemotherapy. METHODS:A total of 94 patients receiving cisplatin-based chemotherapy for multiple cancer types were recruited into a phase II, double-blind, placebo-controlled trial and randomised in a ratio of 1:1 to receive aspirin 975 mg tid and omeprazole 20 mg od, or matched placebos from the day before, to 2 days after, their cisplatin dose(s), for each treatment cycle. Patients underwent pure tone audiometry before and at 7 and 90 days after their final cisplatin dose. The primary end-point was combined hearing loss (cHL), the summed hearing loss at 6 kHz and 8 kHz, in both ears. RESULTS:Although aspirin was well tolerated, it did not protect hearing in patients receiving cisplatin (p-value = 0.233, 20% one-sided level of significance). In the aspirin arm, patients demonstrated mean cHL of 49 dB (standard deviation [SD] 61.41) following cisplatin compared with placebo patients who demonstrated mean cHL of 36 dB (SD 50.85). Women had greater average hearing loss than men, and patients treated for head and neck malignancy experienced the greatest cHL. CONCLUSIONS:Aspirin did not protect from cisplatin-related ototoxicity. Cisplatin and gentamicin may therefore have distinct ototoxic mechanisms, or cisplatin-induced ototoxicity may be refractory to the aspirin regimen used here.
Project description:OBJECTIVES:Integrating audiological management into the care pathways of clinical specialties that prescribe ototoxic medications for essential, often life-preserving medical care that is critical for early hearing loss identification and remediation. Research shows that successful implementation of a new health service or intervention requires alignment of goals among provider groups, institutional leadership and patients. Thoughtful consideration of the physician's viewpoints about ototoxicity and its implications for treatment planning is, therefore, important for the implementation and enduring success of an ototoxicity monitoring programme (OMP). DESIGN:This discussion paper uses qualitative methods to explore the perspectives of four physicians on OMP provision in their patient populations. STUDY SAMPLE:Three pulmonologists and one oncologist completed the written survey or survey-based interview described in this report. RESULTS:Each physician indicated that (i) ototoxicity is a potential problem for their patients; (ii) monitoring hearing is important to ensure good quality of life among their patients and (iii) treatment modification would be considered if an alternative treatment option were available. The physicians differed in their approaches to ototoxicity monitoring, from routine referrals to audiology, to relying on patient self-referral. CONCLUSION:Physician provider input is needed to optimise monitoring schedules and OMP care coordination with audiology.
Project description:BACKGROUND:Chemical exposure leading to ototoxicity is a fresh challenge for occupational healthcare in South Africa. OBJECTIVES:The critical question is: 'what is known about occupational ototoxic chemicals with or without noise exposure in South Africa?' METHOD:This qualitative, mapping study was completed with published (peer-reviewed) and grey literature from 1979-2019. Data was analysed using the Preferred Reporting Items for Systematic reviews and Meta-Analyses: extension for Scoping Reviews and the Nursing and Allied Health Resources Section subcommittee on Mapping the Literature of Nursing and Allied Health (adapted). Numerical analysis of article type was completed, but the primary focus was on capturing patterns/trends using thematic analysis and ideology critique. RESULTS:The African Journal of Disability, African Journal of Primary Health Care and Family Medicine, South African Medical Journal, The South African Journal of Communication Disorders [SAJCD] and Health SA Gesondheid) were included with the SAJCD containing one relevant item and seventeen other items were analysed. Research focusses on the mining sector (gold) in Gauteng, and ototoxic medication (tuberculosis and/or human immunodeficiency virus) take precedence. In KwaZulu-Natal, the focus is on commerce and industry across formal and informal sectors. There are no governmental policies that refer to chemical ototoxicity. Occupational hearing loss is configured exclusively on the meme that noise exposure is the only toxin. CONCLUSION:Chemical exposures are only just beginning to be recognised as ototoxic in South Africa. Hearing conservation programmes should always serve the workers' interests and never bow down to the econometric interests of employers.
Project description:BACKGROUND:Tuberculosis (TB) affects millions of people worldwide and is treated with medication including aminoglycosides and polypeptides. Individuals respond differently to medications as a result of their genetic inheritance. These differences in genetic inheritance can result in the underdosing or overdosing of medication, which may affect the efficacy or, in the case of aminoglycosides and polypeptides used in the treatment of all forms of TB, result in ototoxicity. When ototoxicity is detected, physicians should adjust dosages to minimize further ototoxicity and hearing loss; however, there are no suitable grading systems to define significant hearing loss. OBJECTIVE:The aim of this study was to develop a standardized grading system by making use of an electronic health (eHealth) platform to ensure that a user-friendly method was available to interpret hearing test results, calculate significant hearing loss, and provide recommendations with regard to dosage adjustments and management. It further aimed to establish the sensitivity of the newly developed grading scale. METHODS:This grading system was developed in South Africa based on data that were obtained from an audiology and pharmacokinetic study on patients with drug-resistant TB (DR-TB) at two DR-TB units at state-run hospitals. This feasibility study employed a prospective, cross-sectional, exploratory, descriptive case series research design, with a total of 22 participants. Participants underwent audiological and pharmacological assessments at baseline and every 2 weeks for the first 3 months of treatment. Various professionals (8 in total) were subsequently involved in the development of the eHealth system, including a software engineer, four audiologists, a pharmacist, a medical doctor, and a nurse. The app underwent 14 modifications that involved aspects of data storage, ease of usability, grades, and the risk factor checklist. RESULTS:An ototoxicity grading system within a mobile app for use by doctors, nurses, and audiologists was developed for patients with DR-TB. The purpose of this user-friendly ototoxicity calculator, OtoCalc, is to (1) assist health professionals in assessing patients for ototoxicity, (2) establish the clinical significance of ototoxicity by calculating the grade of hearing loss, (3) monitor the progression of hearing loss, and (4) enable systematic referral and management of patients according to their needs. CONCLUSIONS:This newly developed system is more sensitive than the existing grading methods for determining ototoxicity in patients with DR-TB. This app needs to be trialed in a larger sample to establish data security, ease of use, and suitability within this population.
Project description:Objective:The ototoxicity of povidone-iodine has been documented in animal studies. However, there is limited evidence of these ototoxic effects in humans. This is the first report to show the ototoxic effects of povidone-iodine in a human subject. Patient:A 36-year-old woman came to our hospital complaining of left unilateral persistent hearing loss. One month before presentation, her child had accidentally struck her on her left ear. She applied approximately three drops of povidone-iodine (10% weight/volume) into her left auditory canal. Immediately after application, she felt severe pain and vertigo. An audiogram revealed severe left unilateral sensorineural hearing loss. Magnetic resonance imaging showed mild enhancement of the left vestibule and basal turn of the left cochlea. Conclusions:Even a single application of povidone-iodine could cause significant hearing loss and disequilibrium. It should, therefore, be used with caution.