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People with misophonia experience strong negative emotional responses to sounds and associated stimuli-mostly human produced-to an extent that it may cause impairment in social functioning. The exact nature of the disorder remains a matter of ongoing research and debate. Here, we investigated the genetic etiology of misophonia to understand contributing genetic factors and shed light on individual differences in characteristics that are related to the disorder. For misophonia, we used an unpublished genome-wide association study (GWAS) from genetic service provider 23andMe, Inc., on a self-report item probing a single common misophonic symptom: the occurrence of rage when others produce eating sounds. First, we used gene-based and functional annotation analyses to explore neurobiological determinants of the rage-related misophonia symptom. Next, we calculated genetic correlations ( ) of this rage-related misophonia symptom GWAS with a wide range of traits and disorders from audiology (tinnitus, hearing performance, and hearing trauma), psychiatry, neurology, and personality traits. The rage-related misophonia symptom was significantly correlated with tinnitus, major depression disorder (MDD), post-traumatic stress disorder (PTSD), and generalized anxiety disorder (GAD; 0.12 < < 0.22). Stronger genetic correlations (0.21 < < 0.42) were observed for two clusters of personality traits: a guilt/neuroticism and an irritability/sensitivity cluster. Our results showed no genetic correlation with attention deficit and hyperactivity disorder, obsessive-compulsive disorder, and psychotic disorders. A negative correlation with autism spectrum disorder (ASD) was found, which may be surprising given the previously reported comorbidities and the sensory sensitivity reported in ASD. Clustering algorithms showed that rage-related misophonia consistently clustered with MDD, generalized anxiety, PTSD, and related personality traits. We conclude that-based on the genetics of a common misophonia symptom-misophonia most strongly clusters with psychiatric disorders and a personality profile consistent with anxiety and PTSD.

The results from different Cochrane studies justify considerable professional equipoise concerning different treatment options for tinnitus. In case of professional equipoise, Shared Decision Making (SDM) is an indispensable tool for guiding patients to the intervention that best fits their needs. To improve SDM we developed a method to assess the accuracy and utility of decisions made by tinnitus patients when freely choosing between different treatment options during their patient journey. The different treatment options were audiological care and psychosocial counseling. We developed a statistical model by combining Signal Detection Theory (SDT) with the Health Belief Model (HBM). HBM states that perceived severity of an illness is strongly related to sick-role behavior. As proxies for perceived severity, we selected hearing loss and Tinnitus Handicap Inventory (THI) score at baseline. Next, we used these proxies as predictors in linear regression models based on SDT to determine the likelihood ratio of true positive decisions (choosing a treatment option and experiencing an improvement of more than 7 points in THI-score) and false positive decisions (choosing a treatment option and experiencing an improvement of less than 7 points in THI-score) for audiological care and psychosocial counseling, respectively. Data was gathered in a prospective cohort of 145 adults referred for tinnitus care to an outpatient audiology clinic in the Netherlands. The participants were asked to decide freely on uptake of audiological care (provision of hearing aids with or without a sound generator) and uptake of psychosocial counseling. Logistic regression with Bayesian inference was used to determine the cumulative distribution functions and the probability density functions of true positive decisions and false positive decisions as function of hearing loss and baseline THI-score for both treatment options, respectively. With the cumulative distribution functions, we determined the accuracy of the decisions. With the probability density functions we calculated the likelihood ratios of true positive decisions versus false positive decisions as function of hearing loss and baseline THI-score. These likelihood ratio functions allow assessment of the utility of the decisions by relating a decision criterion to perceived benefits and costs. Baseline THI-score drives decisions about psychosocial counseling and hearing loss drives decisions about audiological care. Decisions about psychosocial counseling are more accurate than decisions about audiological care. Both decisions have a low accuracy (0.255 for audiological care and  - 0.429 for psychosocial counseling), however. For decisions about audiological care the unbiased decision criterion is 37 dB(HL), meaning that a lenient decision criterion (likelihood ratio < 1) is adopted by patients with a hearing loss below 37 dB and a strict criterion (likelihood ratio > 1) by patients with a hearing loss exceeding 37 dB. For psychosocial counseling uptake the decision criterion is always strict, regardless of baseline THI-score. The distributions of the populations, that do and do not experience a clinically important change in THI-score, have unequal variances for psychosocial counseling, while they have almost equal variances for audiological care. Combining SDT and HBM can help assess accuracy and utility of patient decisions and thus may provide valuable information that can help to improve SDM by combining patient related outcome measures, decision drivers, and perceived benefits and costs of a treatment.

Tinnitus affects approximately 14% of the population. Its symptomatology is versatile, ranging from mild annoyance to anxiety and depression. Current multidisciplinary treatments (psychological, audiological, and combinations) focus on impact reduction and acceptance. Shared decision making (SDM) promotes patients and health care professionals making treatment choices together based on the best available evidence. In the case of professional equipoise (no clear clinical evidence for superiority of a treatment), knowledge about individual factors influencing the outcome of patient decisions can be of utmost importance in informing the SDM process. A statistical model that was developed in previous work to analyze tinnitus patient decisions, was extended to analyze how patient characteristics on sex, age, and laterality of tinnitus affect the accuracy and utility of decisions concerning audiological care and cognitive behavioral therapy (CBT) based psychosocial counseling. For each group, we calculated Receiver-Operator-Characteristic curves and likelihood ratio curves as function of hearing loss and pre-treatment tinnitus impact to assess accuracy and utility of decisions for audiological care and CBT-based counseling, respectively. The largest effect was found for sex differences. The results indicated that males used a strict decision criterion when deciding about psychosocial counseling, while females used a strict decision criterion for decisions about audiological care. The likelihood ratios of a successful treatment versus unsuccessful treatment are smaller than 1 for psychosocial counseling for females and for audiological care for males. The likelihood ratios of success are approximately 2 and almost 7 for audiological care for females and psychosocial counseling for males, respectively. For age differences, older participants adopted a more lenient decision criterion for audiological care across most of the hearing loss range, while younger participants adopt a stricter decision criterion up to hearing losses of approximately 75 dB(HL). For psychosocial counseling, older participants adopted an unbiased criterion and younger participants a strict decision criterion. For the younger group, psychological counseling seems more likely to be successful compared to the older group. When considering laterality, for audiological care the group with unilateral tinnitus adopted a strict decision criterion for the whole range of hearing loss, while the group with bilateral tinnitus adopted a strict decision criterion for hearing losses above approximately 70 dB(HL). For decisions about psychosocial counseling, the unilateral tinnitus group adopt a strict decision criterion for baseline THI-scores between approximately 25 and 90 points. The bilateral tinnitus group adopted an unbiased to strict decision criterion for psychosocial counseling for the entire baseline THI-score range. These findings underscore the importance of personalized treatment approaches based on specific patient characteristics and the need for further research to test and improve these findings. Especially males may be more strongly advised to take up psychosocial counseling and females may be more strongly advised to take up audiological care. For age and laterality, the results are more diffuse.

Cisplatin-induced hearing loss (CIHL) in pediatric cancer patients is an irreversible and highly prevalent adverse effect with a devastating impact on quality of life. Sodium thiosulfate (STS) has recently been approved for systemic administration as an otoprotective agent in children. However, implementation of systemic STS has its challenges, and there is currently limited evidence to support local STS for children. This review investigates the potential value of locally administered otoprotective agents other than STS with a focus on future pediatric implementation. We conducted a systematic review on the efficacy and safety of locally applied non-STS otoprotective agents in settings. This included a summary of investigated drug delivery methods and administration routes. We identified 70 preclinical and eight clinical studies. Agents were categorized based on their biological mechanisms: anti-inflammatory, chemical deactivators, calcium blockers, biologicals, and miscellaneous mechanisms. Preclinical studies investigated 45 different agents. Dexamethasone and -acetylcysteine were identified as efficacious agents recurrently and progressed to clinical trials. Dexamethasone was investigated in three randomized clinical trials (RCTs) and three non-randomized clinical studies and showed statistically significant but not clinically relevant benefit in two trials. -acetylcysteine was investigated in two clinical trials and one RCT and was minimally effective in the RCT and in one clinical study. Our review did not identify available studies of local alternative otoprotective agents that could reliably replace systemic STS in terms of safety and efficacy for pediatric patients. Further research on the optimal dosage, delivery method, and timing of otoprotective agents is needed.

IntroductionCisplatin is a widely used chemotherapeutic anti-cancer drug. However, high-dose cisplatin is also known for its dose-limiting toxicities, including irreversible cisplatin-induced hearing loss (CIHL). Sodium thiosulphate (STS) can bind to cisplatin to form an inactive and harmless complex. A topical application is desired, allowing cisplatin to retain its systemic anti-cancer effect.Methods and analysisThe SOUND trial is an investigator-initiated randomised controlled multicentre phase III trial to study the efficacy of transtympanic administration of STS against CIHL in a cohort of 100 patients with head and neck cancer treated with cisplatin at a dose of ≥200 mg/m2. Each subject will receive transtympanic STS injections in one ear, chosen by randomisation, before each cisplatin infusion. The contralateral ear serves as an internal control. The primary objective is efficacy (ie, clinically relevant benefit) of transtympanic STS injections against CIHL, defined as a difference in threshold shift of ≥10 decibels between baseline and 3 months after treatment in favour of the STS-treated ear. Secondary objectives include the difference in mean threshold shifts on frequencies essential for speech and extended high frequencies, as well as the difference between both ears in the gradation of hearing loss as defined by ototoxicity grading scales.Ethics and disseminationThe medical ethics committee in the Netherlands approved the trial (Clinical Trials Information System (CTIS) 2023-503313-30-00). The results will be disseminated through the CTIS and peer-reviewed scientific journals.Trial registration numberCTIS 2023-503313-30-00 approved by Medical Research Ethics Committee NedMec.

Background Literature on the effects of prenatal exposure to platinum-based chemotherapy on the auditory capacity of the offspring is scarce. The current study aims to describe the occurrence of hearing impairment in a well-documented series of children who underwent audiological testing. Methods An international, descriptive multicentre study using oncological, obstetrical, and neonatal data registered by the International Network of Cancer Infertility and Pregnancy database, was performed. The offspring (aged ≥ 4 years) underwent pure tone audiometry. Audiological outcomes were registered after expert review, using international standardized audiological grading as developed for platinum exposed childhood cancer patients: the Muenster criteria and the International Society for Paediatric Oncology classification. Platinum-induced hearing loss was defined as bilateral hearing loss, starting at 8 kHz and without middle ear problems confirmed by tympanometry or otoscopy. Findings Twenty-five children were included of which 17 children (68%) had been exposed to cisplatin and 8 (32%) to carboplatin, none to both. Median gestational age at start maternal treatment was 22 weeks (range, 14–31). Median gestational age at delivery was 35 weeks (range, 31–39), and median birth weight was 2345 g (range, 1526–3360). Neonatal hearing screening, performed in 10 children (40%), showed no hearing loss. At a median age of 6.0 years (range, 4.0–28 . 0), 6 children (24%) revealed bilateral hearing loss, using cut-off values of Muenster grade ≥ 2b and SIOP grade ≥ 2. Interpretation Antenatal exposure to platinum-based chemotherapy is associated with hearing loss in a subset of the offspring. Prospective longitudinal standardized surveillance of auditory function is advised, starting after birth.

A cochlear implant (CI) is a prosthesis that allows people with severe to profound hearing loss to understand speech in quiet settings. However, listening to music presents a challenge to most CI users; they often do not enjoy music or avoid it altogether. The Musi-CI training course was developed for CI users with the goal of reducing music aversion and improving music enjoyment. A consortium was established consisting of a professional musician with CI, CI rehabilitation professionals and researchers. Participatory action research (PAR) was applied to develop and evaluate the training experiences, collaborating with 37 CI users during three cycles of eight training sessions, each held over a period of 3 months. Input and feedback were collected after each training session using questionnaires, observations and focus group interviews. Almost all participants (86%) completed the training. After completing the training a large majority of participants reported increased music appreciation, increased social participation in musical settings and a positive impact on general auditory perception. The resulting Musi-CI training programme focuses on music listening skills, self-efficacy, and self-motivation. It consists of exercises intended to strengthen attention and working memory, to improve beat and rhythm perception (with online rhythm exercises) and exercises to distinguish timbre of instruments and emotion in music. A Melody Game was developed to improve pitch and melodic contour discrimination.

Some children with central nervous system (CNS) and solid tumors are at risk to develop ototoxicity during treatment. Up to now, several risk factors have been identified that may contribute to ototoxicity, such as platinum derivates, cranial irradiation, and brain surgery. Comedication, like antibiotics and diuretics, is known to enhance ototoxicity, but their independent influence has not been investigated in childhood cancer patients. Recommendations for hearing loss screening are missing or vary highly across treatment protocols. Additionally, adherence to existing screening guidelines is not always optimal. Currently, knowledge is lacking on the prevalence of ototoxicity. The aim of the Study on Prevalence and Determinants of Ototoxicity During Treatment of Childhood Cancer (SOUND) is to determine the feasibility of audiological testing and to determine the prevalence and determinants of ototoxicity during treatment for childhood cancer in a national cohort of patients with solid and CNS tumors. The SOUND study is a prospective cohort study in the national childhood cancer center in the Netherlands. The study aims to include all children aged 0 to 19 years with a newly diagnosed CNS or solid tumor. Part of these patients will get audiological examination as part of their standard of care (stratum 1). Patients in which audiological examination is not the standard of care will be invited for inclusion in stratum 2. Age-dependent audiological assessments will be pursued before the start of treatment and within 3 months after the end of treatment. Apart from hearing loss, we will investigate the feasibility to screen patients for tinnitus and vertigo prevalence after cancer treatment. This study will also determine the independent contribution of antibiotics and diuretics on ototoxicity. This study was approved by the Medical Research Ethics Committee Utrecht (Identifier 20-417/M). Currently, we are in the process of recruitment for this study. The SOUND study will raise awareness about the presence of ototoxicity during the treatment of children with CNS or solid tumors. It will give insight into the prevalence and independent clinical and cotreatment-related determinants of ototoxicity. This is important for the identification of future high-risk patients. Thereby, the study will provide a basis for the selection of patients who will benefit from innovative otoprotective intervention trials during childhood cancer treatment that are currently being prepared. Netherlands Trial Register NL8881; https://www.trialregister.nl/trial/8881. DERR1-10.2196/34297.

Purpose: The frequency and patterns of HL in a HNRMS survivor cohort were investigated. A dose–effect relationship between the dose to the cochlea and HL was explored. Methods: Dutch survivors treated for HNRMS between 1993 and 2017 with no relapse and at least two years after the end of treatment were eligible for inclusion. The survivors were evaluated for HL with pure-tone audiometry. HL was graded according to the Muenster, Common Terminology Criteria for Adverse Events (CTCAE) v4.03 and International Society for Paediatric Oncology (SIOP) classification. We defined deleterious HL as Muenster ≥ 2b, CTCAE ≥ 2, and SIOP ≥ 2. Mixed-effects logistic regression was used to search for the dose–effect relationship between the irradiation dose to the cochlea and the occurrence of HL. Results: Forty-two HNRMS survivors underwent pure-tone audiometry. The Muenster, CTCAE and SIOP classification showed that 19.0% (n = 8), 14.2% (n = 6) and 11.9% (n = 5) of survivors suffered from HL, respectively. A low-frequency HL pattern with normal hearing or milder hearing loss in the higher frequencies was seen in four survivors. The maximum cochlear irradiation dose was significantly associated with HL (≥Muenster 2b) (p = 0.047). In our series, HL (≥Muenster 2b) was especially observed when the maximum dose to the cochlea exceeded 19 Gy. Conclusion: HL occurred in up to 19% of survivors of HNRMS. More research is needed on HL patterns in HNRMS survivors and on radiotherapy dose–effect relationships.