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Cisplatin is a cornerstone agent in the treatment of head and neck squamous cell carcinoma. Nonetheless, cisplatin is associated with significant ototoxicity, leading to substantial irreversible hearing loss. Pharmacogenetic testing offers a potential strategy to identify patients at risk, allowing for personalized treatment plans that could mitigate this adverse event and reduce related costs. This study aimed to evaluate the economic impact of pharmacogenomic screening. A cost-minimization analysis was conducted using a decision-analytic model incorporating Bayesian inference through Metropolis-Hastings algorithm. Probabilities of ototoxicity were derived from existing literature. The costs of standard treatment were compared with those of a genotype-guided approach, assessing potential cost savings related to the need for audiological interventions. In 250 patients, the genotype-guided approach reduced the incidence of moderate-to-severe ototoxicity from 29% to 18% among low-risk patients while avoiding cisplatin in high-risk individuals. The total savings over 10 years were estimated at US$13,077.73 (Credible Interval US$11,026.07 to US$14,147.61), driven primarily by reduced costs for audiological interventions. The break-even point for cost-effectiveness was achieved when at least 275 patients were tested annually. Sensitivity analyses demonstrated that the cost savings remained robust under variations in patient volume and testing costs. Implementing pharmacogenomic screening in the management of head and neck squamous cell carcinoma patients treated with cisplatin may offer significant economic benefits. Personalized treatment plans based on genetic risk for ototoxicity could potentially not only enhance patient-related outcomes but also contribute to more efficient use of healthcare resources. Prospective, randomized evaluations would be ideal to confirm these findings.

Background Radiation therapy (RT) plays a significant role in the multimodal management of primary brain tumors, improving oncological outcomes. However, despite advances such as Intensity-Modulated Radiation Therapy (IMRT), photon-based RT inevitably exposes normal organs to low-dose radiation, leading to long-term functional morbidities like cognitive decline, endocrine dysfunction, auditory toxicity. These late effects are particularly concerning in patients with favorable prognoses and protracted survival. Proton beam therapy (PBT), owing to its unique physical properties, holds promise for better functional preservation, but robust clinical data in adults are lacking. Methods The PRIDE study is a prospective, open-label, phase 3 randomized controlled trial enrolling adults aged 18–70 years undergoing focal cranial RT with conventional fractionation for primary brain tumors with expected survival > 5 years at Tata Memorial Centre, Mumbai. Participants will be randomized 1:1 to receive either photon-IMRT (standard arm) or PBT (experimental arm), stratified by age, tumor type, proximity to the hypothalamic-pituitary axis, and radiation dose. The primary endpoint is 5-year functional survival, defined as survival without functional deterioration (neurocognitive decline, significant ototoxicity, new or worsening endocrine dysfunction, neurological impairment, severe radio-necrosis, disease progression, or death). Secondary endpoints include patient-reported quality of life and health economic analysis. Survival outcomes will be analyzed using Kaplan-Meier methods with log-rank test. Neurocognitive and quality-of-life data will be evaluated using linear mixed-effects and non-parametric tests. A total of 156 patients will be enrolled, accounting for 20% attrition, to detect a 25% absolute improvement in 5-year functional survival favoring PBT (65% vs 40%, HR 0.47, α=0.05, power=80%). An interim analysis has been planned using the O'Brien-Fleming rule after 50% of the events (n=28). Discussion This trial will provide level 1 evidence investigating the role of PBT in functional outcomes among adults with primary brain tumors. If study endpoint is achieved, PBT will be considered as standard of care guiding contemporary neuro-oncology practice. Registration The trial has been approved by the Institutional Ethics Committee of Tata Memorial Centre, Mumbai. The trial has been registered with the Clinical Trial Registry of India (CTRI/2025/03/082568) and Clinicaltrials.gov (study identifier NCT06831461).

Background/Objectives: Sensorineural hearing loss (SNHL) is a chronic condition with no established pharmacological treatment. Recent advances in drug-based therapies offer promising opportunities to prevent or treat SNHL. This scoping review summarizes the current landscape of pharmacotherapeutics for SNHL. Methods: This scoping review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). A literature search of PubMed, Google Scholar, Embase, Scopus, and Web of Science was conducted in 2024 using keywords related to SNHL and pharmacotherapeutics. A review protocol was preregistered on the Open Science Framework. A systematic search of five electronic databases identified published studies from 2004 to 2024 on pharmacological treatments for SNHL in human participants, as well as ongoing clinical trials. Interventions were categorized by mechanism of action: antioxidant therapy, steroid-based combination therapy, hematologic-based therapy, pathway modulator therapy, regenerative therapy, and gene therapy. A narrative synthesis approach was used to map key trends across treatment types, study designs, and outcomes. Results: Sixty-six records met the inclusion criteria, including 48 published studies and 18 ongoing or recently completed clinical trial records. Antioxidants, corticosteroids, hematologic agents, and pathway modulators have demonstrated potential in preventing or treating SNHL caused by cisplatin, aminoglycosides, noise-induced ototoxicity, and intraoperative cochlear implantation trauma. Emerging regenerative and gene therapies show promise as future pharmacologic treatment options. Conclusions: Pharmacologic therapies for SNHL are promising but remain constrained by small sample sizes, heterogeneous study designs, and drug delivery challenges across the blood–labyrinth barrier. Future research should prioritize multicenter randomized trials, optimized delivery strategies, and integration of precision medicine approaches.

Background High-grade open fractures carry a significant risk of osteomyelitis, despite advancements in surgical techniques and treatment protocols. The use of prophylactic, adjuvant local antibiotics is controversially discussed in the literature. CERAMENT®G (BONESUPPORT™) is a novel synthetic bone substitute that effectively elutes gentamicin. This report presents the largest and longest follow-up data collected over the past decade, comparing these findings to our previous findings to identify long-term complications, as well as comparing the outcome against other forms of local antibiotic prophylaxis. Methods A retrospective, descriptive analysis was conducted on patients with Gustilo–Anderson IIIb fractures treated with CERAMENT®G as an adjunct to the conventional fix-and-flap approach from June 2013 to August 2021. Patient demographics, orthoplastic interventions, microbiological findings, and the latest outcome data—including union rates, infection rates, mortality, and amputation outcomes—were extracted from electronic records up to April 2024. Results Seventy-six patients with 78 fractures were included, with a mean follow-up period of 88.7 months. The primary union was achieved in 65 cases (83.3%), and secondary union following bone grafting was achieved in 5 of 13 non-union cases. Three mortalities were identified. Four cases required amputation due to osteomyelitis, flap failure leading to soft tissue infection, failure in bone reconstruction, and chronic pain. Superficial infections occurred in 33 cases (42.3%), and osteomyelitis in 4 cases (5.1%). No local or systemic adverse reactions, including ototoxicity, were reported. Conclusion CERAMENT®G is a safe and effective option for local antibiotic delivery in high-grade open fractures as an adjunct to systemic antibiotic prophylaxis. Its adjunctive use significantly reduced the risk of osteomyelitis compared to systemic prophylaxis alone and was superior to PMMA beads alone.

Introduction The animal studies raise concerns about the possible ototoxicity of phenolic chemicals. Therefore, we conducted an epidemiologic study to examine the associations of phenols and parabens with hearing impairment. Materials and methods Bisphenol A (BPA), benzophenone-3 (BP-3), and triclosan (TCS) were measured in urine samples in the National Health and Nutrition Examination Survey (NHANES) 2003–06 and 2009–12. Methyl paraben (MPB) and propyl paraben (PPB) were measured in urine samples in NHANES 2005–06 and 2009–12. Hearing impairment was defined as a hearing threshold of more than 25 dB at each hearing frequency in the better ear. Tests for linear trend were conducted using the median concentrations of urinary phenols or parabens in each quartile as a continuous variable. Results A total of 1809 participants (women = 52.0%) aged 20 and above were included in the final analysis (For MPB and PPB, the sample size was 1188). After adjusting for potential confounders, we found positive associations between BPA and hearing impairment at 3 K ( p -trend = 0.04); between TCS and hearing impairment at 6 K ( p -trend = 0.03); However, the odds ratio (OR) for the highest compared with the lowest quartile of both BPA and TCS did not reach statistical significance. In contrast, we found unexpected negative associations between BP-3 and hearing impairment at 0.5 K ( p -trend = 0.04), 1 K ( p -trend = 0.02), 2 K ( p -trend <0.01), 6 K ( p -trend = 0.03), and 8 K Hz ( p -trend = 0.02), respectively. Conclusions The present study offers limited evidence that background phenol and paraben exposures are ototoxicants for the United States adult population.

Background Vancomycin therapeutic drug monitoring (TDM) is commonly performed to ensure safe and effective use of the antibiotic. Aim of Study To evaluate appropriateness of vancomycin TDM and its outcomes in Singapore General Hospital. Method A retrospective, cross-sectional study was conducted between 1 January 2014 and 28 February 2014 involving patients who received ≥ 1 dose of intravenous vancomycin with TDM. Patient demographics and relevant vancomycin TDM data were collected from medical records. Results Of 746 vancomycin troughs measured among 234 patients, 459 troughs (61.5%) were taken inappropriately, with a median time of 2.6 h (interquartile range 1.1–4.3) before the next scheduled dose. Inappropriate interpretation of vancomycin troughs resulted in 41 unnecessary dose suspensions, 24 dose changes, and 102 unchanged vancomycin doses. The cost incurred due to inappropriate interpretation and measurement after discontinuation of treatment was US$7286. No differences in rates of vancomycin related nephrotoxicity, ototoxicity, recurrent infection, development of infection secondary to vancomycin resistant microorganism and mortality were observed (p > 0.05). Conclusion This study highlighted a high incidence of inappropriate vancomycin TDM which has led to increased healthcare cost.

Background Aminoglycosides used in the treatment of Multidrug-Resistant Tuberculosis (MDR-TB) are known to result in hearing loss. The effects of an acquired hearing loss with an MDR-TB diagnosis may have an increased adverse impact on the overall quality of life of an individual; however, there is minimal research in the area. Objectives This study explores the psychological and emotional impact of hearing loss in adults with MDR-TB; and describes the experiences of the social, economic, and vocational impact of hearing loss in adults with MDR-TB. Method A qualitative research study was conducted on 10 participants, with a confirmed diagnosis of MDR-TB and hearing loss. The researcher used a semi-structured questionnaire to collect data during face-to-face, audio-recorded interviews. Results Hearing loss in patients diagnosed with MDR-TB has a significant adverse impact on the lived experiences of patients. Stigma, discrimination, psychological distress, adverse changes in family status and family relationships, financial constraints, and social challenges were some of the common issues reported by participants. Unemployment posed a significant challenge, resulting in participants having no economic stability because of MDR-TB, which was then worsened by the hearing loss; consequently, generating a great deal of stress. Participants reported feelings of worthlessness, a loss of identity, lack of motivation, feelings of embarrassment, and loss of independence. Conclusion There is a significant irreversible social, psychological, and economic impact of hearing loss that has a direct impact on the lived experiences of MDR-TB patients and their families even after cure of MDR-TB. There is a need for improved treatment methods with psychosocial intervention strategies that equip patients to alleviate the adverse effects they experience.

Loss of balance is often due to loss of vestibular hair cells. In mammals, regeneration of functional hair cells in the mature sensory epithelium is limited; therefore, loss of sensory cells can lead to debilitating balance problems. Delivery of the transcription factor atonal (atoh1) after aminoglycoside ototoxicity has previously been shown to induce the transdifferentiation of supporting cells into new hair cells and restore function. A problem with mouse aminoglycoside models is that the partial loss of hair cells seen in human disease is difficult to establish consistently. To more closely mirror human clinical balance dysfunction, we have used systemic application of 3,3′-iminodipropionitrile (IDPN), a vestibulotoxic nitrile compound known to cause vestibular hair cell loss, to induce a consistent partial loss of vestibular hair cells. To determine if balance function could be restored, we delivered atoh1 using a new adenovirus vector, based on Ad28. The Ad28 adenovector is based on a human serotype with a low seroprevalence that appears to target gene delivery to vestibular supporting cells. To further provide cell type selectivity of gene delivery, we expressed atoh1 using the supporting cell-specific glial fibrillary acid protein promoter. Delivery of this vector to IDPN-damaged vestibular organs resulted in a significant recovery of vestibular hair cells and restoration of balance, as measured by time on rotarod compared with untreated controls.

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.

Cisplatin is a widely used chemotherapy drug in the treatment of pediatric solid tumors, but it is associated with significant rates of ototoxicity (medication-induced hearing loss). A genetic test has recently been developed that can help predict the likelihood that a cisplatin-treated pediatric patient will develop ototoxicity. This study estimates the potential economic impact of this test. Assuming that an alternative, non-preferred, medication to cisplatin exists that it is as efficacious as cisplatin but without the risk of hearing loss, and that the alternative treatment is no more expensive than current practice, we have estimated that administering this genetic test to every pediatric cancer patient for whom cisplatin is first-line therapy could potentially avoid an average of $71 168 in societal costs per tested patient. This translates into a potential present value savings of over $2.4 million annually in British Columbia and over $19.6 million in Canada.