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Background: Pulmonary infections by gram-negative organisms are important in cystic fibrosis (CF). Aminoglycosides (AG) are often part of the treatment regimen. However, they are a well-known cause of ototoxicity. Even minimal hearing impairment in children could have a future impact on functional well-being.We aimed to investigate the progression of sensorineural hearing loss (SNHL) over several years in pediatric CF patients, and to identify risk factors, such as the use of AG, including both intravenous (IV) and inhaled AG. Methods: Retrospective analyses of patient records from children and adolescents followed up at the CF clinic of the Antwerp University Hospital, Belgium, were performed. We collected data on age, sex, pure-tone audiometry, and the use of AG. Descriptive and binary logistic regression analyses, and if indicated generalized estimating equations (GEE) analyses were performed. Results: Forty pediatric patients were enrolled in the study taking part from 2013 to 2020. Pure-tone audiometry revealed an important rate of SNHL over several years, with a prevalence of 29 % for high-frequency SNHL (i.e. 8 kHz). Increasing age was identified as a significant risk factor for the development of SNHL at 8 kHz if 5 or more IV AG courses (p = 0.01) were reported or when IV AG were combined with inhaled AG (p = 0.002). Conclusions: Age combined with the use of IV AG (≥5 courses or in combination with inhaled AG) are predictive for developing high-frequency SNHL (i.e. 8 kHz). We suggest routine annual hearing screening (incl. high-frequency thresholds) in CF patients, starting from childhood.

Abstract Background Chronic tinnitus is a highly prevalent symptom, with many patients reporting considerable effects of tinnitus on quality of life. No clear evidence-based treatment options are currently available. While counseling-based methods are valuable in some cases, they are not sufficiently effective for all tinnitus patients. Neuromodulation techniques such as high-definition transcranial direct current stimulation (HD-tDCS) are proposed to have positive effects on tinnitus severity but, to date, these effects have not been proven conclusively. The proposed trial will investigate the hypothesis that chronic tinnitus patients receiving HD-tDCS will report a positive effect on the impact of tinnitus on daily life, as compared to patients receiving sham stimulation. Methods This study proposes a randomized, double-blind, placebo-controlled trial with parallel group design. A total of 100 chronic tinnitus patients will be randomly allocated to an experimental group or a sham group, with allocation stratified according to gender and tinnitus severity. Patient and researcher will be blinded to the patient’s allocation. Patients will undergo six sessions of sequential dual-site HD-tDCS of the left temporal area and the right dorsolateral prefrontal cortex. Evaluations will take place at baseline, immediately following treatment, and at three and six months after the start of the therapy. The primary outcome measure is the change in Tinnitus Functional Index (TFI) score. Secondary outcome measures include audiological measurements, cortical auditory evoked potentials, the Repeatable Battery for the Assessment of Neuropsychological Status adjusted for hearing-impaired individuals (RBANS-H), and supplementary questionnaires probing tinnitus severity and additional symptoms. By use of a linear regression model, the effects of HD-tDCS compared to sham stimulation will be assessed. Discussion The objective of this study is to evaluate whether HD-tDCS can reduce the impact of tinnitus on daily life in chronic tinnitus patients. To date, published trials on the effects of HD-tDCS on tinnitus suffer from a lack of standardization and few randomized controlled trials exist. The proposed study will be the first adequately powered trial to investigate the effects of sequential dual-site HD-tDCS on tinnitus severity. Trial registration ClinicalTrials.gov, NCT03754127. Registered on 22 November 2018.

A convivência entre marcapassos e desfibriladores está em vias de desaparecimento, mas ainda se impoe em alguns casos particulares. Este trabalho faz o balanço entre as compatibilidades e as incompatibilidades dos modelos recentes. O presente relato de caso refere-se a um paciente no qual o desfibrilador foi escolhido e posicionado atrás do grande peitoral esquerdo, de modo a separá-lo de um marcapasso de dupla-câmara implantado anteriormente. A programaçao de ambos, que eram da mesma marca, pôde ser efetuada pelo mesmo programador, mediante subterfúgios. Nenhuma interferência sobreveio entre os dois aparelhos, sendo necessário apenas corrigir algumas incompatibilidades na programaçao do marcapasso, passíveis de comprometer o funcionamento do desfibrilador.

Objective: To investigate retrospectively the frequency of usage of bimodal stimulation among cochlear implant (CI) users, as well its clinical benefit relative to unilateral use., Design: All subjects had been monitored with the clinical Minimal Outcome Measurements test battery., Study Samples: 103 adults with bilateral postlingual profound sensorineural hearing loss and unilateral CI use were extracted from the local database. These were divided into two groups: those who only used a CI and those who used bimodal stimulation., Results: The preoperative contralateral residual hearing in the bimodal group was significantly better than that of the CI-only group. In both groups, speech perception in quiet and in noise improved after CI, with no significant difference between postoperative unimodal conditions. For the bimodal group, an additional significant improvement was found for the bimodal condition compared to the unimodal., Conclusion: Given the observed auditory benefit of bimodal stimulation in comparison to unimodal stimulation and given the finding that degree of residual hearing is not correlated with bimodal benefits, it is recommended to encourage CI recipients to continue contralateral HA use after CI. As a result of expanding CI criteria worldwide, the population of bimodal users is expected to grow in the near future.

Purpose: Recent literature suggests that tinnitus can impact cognition, but results were varied due to a diversity in investigated aspects of cognition and utilized tests, as well as the possible influence of confounding factors. The purpose of this study was to assess the impact of tinnitus loudness on cognition by use of a within-subjects design in patients with a cochlear implant (CI). In this population, tinnitus loudness can be modulated by switching the CI on or off as CI is known to highly suppress tinnitus., Methods: A total of 18 CI users completed two versions of the Repeatable Battery for Assessment of Neuropsychological Status for Hearing Impaired individuals (RBANS-H), once in unaided condition and once in best aided condition. Tinnitus suppression was defined as a difference in score on a visual-analogue scale (VAS) of at least one point out of ten between these two conditions., Results: No significant differences in RBANS-H scores were found between the suppression and no suppression group, nor for the suppression group alone. No significant correlations between tinnitus loudness and RBANS-H were found, neither for the suppression group alone, nor for the group as a whole., Conclusion: The current study shows no significant effect of tinnitus loudness on cognition, which contradicts previous literature. This discrepancy could be explained by the use of a within-subjects design, which controls for confounding factors. Future research should include a larger and more diverse study sample to draw definitive conclusions on this topic., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: This scoping review aims to assess whether the severity or distress of subjective tinnitus is negatively associated or correlated with the level of health-related quality of life (HRQoL). A second objective is to examine whether tinnitus patients score differently on HRQoL questionnaires in comparison to subjects without tinnitus and whether HRQoL differs between specific subgroups of tinnitus., Methods: This scoping review adheres to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines (PRISMA guidelines): the statement and extension for scoping reviews (PRISMA-ScR). The following databases were consulted (on the 20th of October 2023): PubMed, Cochrane Library, Web of Science, and Scopus. The search string was composed of the terms tinnitus, HRQoL, and synonyms. A double-blinded screening for eligibility was performed, first on the title and abstract and subsequently on the full-text articles. Studies were considered eligible if they looked at HRQoL questionnaire results for adult patients (> 18 years) reporting chronic (> 3 months), subjective tinnitus as a primary complaint., Results: In total, 37 studies with a total sample size of 33,900 participants were included in this scoping review, with some studies answering multiple study objectives. Seventeen studies demonstrated the presence of a significant negative correlation between tinnitus-related distress and HRQoL. Two studies indicated that HRQoL is mediated by tinnitus-related distress. Eighteen studies found that, in general, patients with tinnitus scored significantly lower on HRQoL questionnaires in comparison to subjects without tinnitus. Nineteen studies demonstrated that subgroups of patients with more severe tinnitus complaints or specific additional complaints scored worse on HRQoL questionnaires., Conclusion: Based on the current literature, chronic subjective tinnitus-related distress has a significant impact on health-related quality of life. In addition, subjects without tinnitus generally score significantly higher on HRQoL questionnaires than patients with tinnitus. The heterogeneity in outcome measures between studies precludes meta-analysis. Increased homogeneity in the choice of HRQoL questionnaires would make a comparison between studies possible, which would give valuable information on both a clinical and an economic level, guiding future tinnitus treatment., Registration: The protocol for the scoping review is registered at Open Science Framework: https://doi.org/10.17605/OSF.IO/F5S9C ., (© 2024. The Author(s) under exclusive licence to Association for Research in Otolaryngology.)

Background: Pulmonary infections by gram-negative organisms are important in cystic fibrosis (CF). Aminoglycosides (AG) are often part of the treatment regimen. However, they are a well-known cause of ototoxicity. Even minimal hearing impairment in children could have a future impact on functional well-being.We aimed to investigate the progression of sensorineural hearing loss (SNHL) over several years in pediatric CF patients, and to identify risk factors, such as the use of AG, including both intravenous (IV) and inhaled AG., Methods: Retrospective analyses of patient records from children and adolescents followed up at the CF clinic of the Antwerp University Hospital, Belgium, were performed. We collected data on age, sex, pure-tone audiometry, and the use of AG. Descriptive and binary logistic regression analyses, and if indicated generalized estimating equations (GEE) analyses were performed., Results: Forty pediatric patients were enrolled in the study taking part from 2013 to 2020. Pure-tone audiometry revealed an important rate of SNHL over several years, with a prevalence of 29 % for high-frequency SNHL (i.e. 8 kHz). Increasing age was identified as a significant risk factor for the development of SNHL at 8 kHz if 5 or more IV AG courses (p = 0.01) were reported or when IV AG were combined with inhaled AG (p = 0.002)., Conclusions: Age combined with the use of IV AG (≥5 courses or in combination with inhaled AG) are predictive for developing high-frequency SNHL (i.e. 8 kHz). We suggest routine annual hearing screening (incl. high-frequency thresholds) in CF patients, starting from childhood., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objectives: To estimate the prevalence of tinnitus and hyperacusis in children aged 9-12 years in Flanders, as well as to explore the associations with hearing abilities and listening behaviours., Design: A cross-sectional survey was undertaken in four different Flemish schools. The questionnaire was distributed among 415 children, with a response rate of 97.3%., Results: The prevalence of permanent tinnitus was 10.5% and of hyperacusis was 3.3%. The hyperacusis prevalence was higher in girls (p < .05). Some children reported effects of tinnitus in terms of anxiety (20.1%), sleep (36.5%), and concentration (24.8%). When listening to personal listening devices, 33.5% of the children reported to listen for at least 1 h at 60% or higher of the volume range. Moreover, 54.9% of children stated to never wear hearing protection., Conclusions: Tinnitus and hyperacusis are prevalent in children aged 9-12 years. Some of these children might be overlooked and, as such, not receiving the required follow-up or counselling. Development of guidelines for the assessment of these auditory symptoms in children would help to determine the prevalence numbers with greater accuracy. Sensibility campaigns for safe listening are warranted, as more than half of the children never use hearing protection., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: The antibacterial activity of graphene oxide (GO) has been widely explored and tested against various pathogenic bacterial strains. Although antimicrobial activity of GO against planktonic bacterial cells was demonstrated, its bacteriostatic and bactericidal effect alone is not sufficient to damage sedentary and well protected bacterial cells inside biofilms. Thus, to be utilized as an effective antibacterial agent, it is necessary to improve the antibacterial activity of GO either by integration with other nanomaterials or by attachment of antimicrobial agents. In this study, antimicrobial peptide polymyxin B (PMB) was adsorbed onto the surface of pristine GO and GO functionalized with triethylene glycol., Methods: The antibacterial effects of the resulting materials were examined by evaluating minimum inhibitory concentration, minimum bactericidal concentration, time kill assay, live/dead viability staining and scanning electron microscopy., Results and Discussion: PMB adsorption significantly enhanced the bacteriostatic and bactericidal activity of GO against both planktonic cells and bacterial cells in biofilms. Furthermore, the coatings of PMB-adsorbed GO applied to catheter tubes strongly mitigated biofilm formation, by preventing bacterial adhesion and killing the bacterial cells that managed to attach. The presented results suggest that antibacterial peptide absorption can significantly enhance the antibacterial activity of GO and the resulting material can be effectively used not only against planktonic bacteria but also against infectious biofilms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pandit, Jacquemin, Zhang, Gao, Nishina, Meyer, Mijakovic, Bianco and Pang.)

Background:  Exploding head syndrome (EHS) is characterized by hearing a sudden loud noise or experiencing a sense of explosion in head during the transition of sleep-wake or wake-sleep. The experience of EHS shares similarities with tinnitus, where an individual perceives a sound without any external sound source. To the authors' knowledge, the possible relationship between EHS and tinnitus has not been explored., Purpose:  Preliminary assessment of prevalence of EHS and its related factors among patients seeking help for tinnitus and/or hyperacusis., Research Design:  Retrospective cross-sectional study., Study Sample:  A total of 148 consecutive patients who sought help for tinnitus and/or hyperacusis at an audiology clinic in the United Kingdom., Data Collection and Analysis:  The data regarding demographics, medical history, audiological measures, and self-report questionnaires were collected retrospectively from the patients' records. Audiological measures comprised of pure-tone audiometry and uncomfortable loudness levels. The self-report questionnaires which were administered as a part of standard care comprised of the Tinnitus Handicap Inventory, numeric rating scale of tinnitus loudness, annoyance, and effect on life, hyperacusis questionnaire, Insomnia Severity Index, Generalized Anxiety Disorder scale 7, and Patient Health Questionnaire (PHQ-9). To establish presence of EHS, participants were asked "Do you ever hear a sudden, loud noise, or feel a sense of explosion in your head at night?", Results:  EHS was reported by 8.1% of patients with tinnitus and/or hyperacusis (12 out of 148). The patients with and without EHS were compared, but no significant relationships were found, between the presence of EHS and age, gender, tinnitus/hyperacusis distress, symptoms of anxiety or depression, sleep difficulties, or audiological measures., Conclusion:  The prevalence of EHS in a tinnitus and hyperacusis population is similar to that in the general population. While there does not seem to be any association with sleep or mental factors, this might be due to the limited variability in our clinical sample (i.e., most patients exhibited high level of distress regardless of EHS). Replication of the results in a larger sample with more variety of symptom severity is warranted., Competing Interests: None declared., (American Academy of Audiology. This article is published by Thieme.)

In this work, the mechanisms of radical generation on different functionalized graphene oxide (GO) conjugates under near-infrared (NIR) light irradiation are investigated. The GO conjugates are designed to understand how chemical functionalization can influence the generation of radicals. Both pristine and functionalized GO are irradiated by a NIR laser, and the production of different reactive oxygen species (ROS) is investigated using fluorimetry and electron paramagnetic resonance to describe the type of radicals present on the surface of GO. The mechanism of ROS formation involves a charge transfer from the material to the oxygen present in the media, via the production of superoxide and singlet oxygen. Cytotoxicity and effects of ROS generation are then evaluated using breast cancer cells, evidencing a concentration dependent cell death associated to the heat and ROS. The study provides new hints to understand the photogeneration of radicals on the surface of GO upon near infrared irradiation, as well as, to assess the impact on these radicals in the context of a combined drug delivery system and phototherapeutic approach. These discoveries open the way for a better control of phototherapy-based treatments employing graphene-based materials., (© 2023 The Authors. Small published by Wiley-VCH GmbH.)

Introduction: Severe hearing loss is a sensory deficit with considerable impact on the patient's daily life and on society. Previous research has established occupational obstacles in professionally active patients with hearing loss. However, studies investigating the impact of severe hearing loss and cochlear implantation (CI) on work performance using a quantitative and longitudinal study design and validated questionnaires are lacking. This study aims to answer the following research question: 'What is the impact of unilateral and bilateral severe hearing loss and CI on the cost for society, health state, employment, productivity and social well-being?'. We hypothesise hearing impairment to influence work performance. After establishing the impact, we will be able to enhance the support of hearing impaired patients to maintain employed., Methods and Analysis: A total of 200 professionally active adults between 18 and 65 years old with severe hearing loss will be included for assessment at baseline and reassessment at 3, 6 and 12 months. The following four study groups are included: bilateral severely hearing impaired participants without CI (1) and with CI (2) and unilateral severely hearing impaired participants in acute (3) and chronic (4) setting. The primary outcome of this study is the change in index score on the Work Limitations Questionnaire, which evaluates the degree of limitations and health-related productivity loss. Secondary outcome measures include audiometric and cognitive evaluations and validated questionnaires evaluating employment, work productivity, quality of life and direct healthcare costs. Linear mixed models will assess the evolution in time and the difference in evolution between groups., Ethics and Dissemination: This study protocol (project ID 2021-0306) received ethical approval from the ethics committee of the Antwerp University Hospital on 22 November 2021. Our findings will be disseminated by peer-reviewed publications and conference presentations., Trial Registration Number: NCT05196022., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Hyperacusis is a reduced tolerance to sounds that often co-occurs with tinnitus. Both symptoms have convergent as well as divergent characteristics. Somatic modulation, changes in pitch or loudness during certain movements, is common in patients with a primary complaint of tinnitus. However, thus far, this is not documented in patients with hyperacusis., Objectives: This study aimed to examine the influence of somatic manoeuvres on the perception of external sounds in patients with a primary complaint of hyperacusis., Methodology: In this prospective cross-sectional pilot study, 18 patients with a primary complaint of hyperacusis were recruited at the Tinnitus Treatment and Research Center Antwerp (TINTRA). While patients listened to a 1 kHz broadband noise of 30 dB sensation level, six neck manoeuvres (flexion, extension, lateroflexion left/right, traction and compression), three jaw manoeuvres (protrusion, laterotrusion left/right) and one placebo manoeuvre (hand on head) were performed. The primary outcome measure was the change in the perception of the presented sound in terms of loudness and intrusiveness between baseline and each modulation measured by a visual analogue scale (VAS)., Results: No overall significant changes were found; however, individual results indicated that five patients presented a clinically relevant change of more than three points out of ten on VAS in terms of hyperacusis after at least one of the executed somatic manoeuvres., Conclusions: This pilot study did not demonstrate an overall significant change in hyperacusis after somatic manoeuvres but does not rule out the possibility of somatic modulation in some hyperacusis patients., Trial Registration: The protocol of this prospective cross-sectional pilot study was registered on clinicaltrials.gov with registration number NCT04693819., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Tinnitus is a highly prevalent symptom affecting 10%-20% of the adult population. Most patients with tinnitus have chronic tinnitus, which can directly or indirectly disrupt their daily life and negatively affect the health-related quality of life. Therefore, patients with tinnitus are frequently in need of costly and time-consuming treatments. As an answer, telerehabilitation interventions are on a rise to promote self-management in patients with tinnitus and reduce their dependency on in-person care., Objective: This systematic review aimed to provide an overview of the research concerning the effectiveness of telerehabilitation interventions for self-management of tinnitus., Methods: This systematic review adheres to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Studies were eligible for inclusion if study participants were adult patients with complaints of primary subjective tinnitus and the study intervention comprised any possible telerehabilitation form for the self-management of tinnitus complaints. A search for eligible studies was conducted on PubMed, ScienceDirect, Scopus, Web of Science, and Cochrane Library. The Cochrane Risk of Bias 2 tool was used to the assess risk of bias., Results: In total, 29 articles were found eligible, and of these, 5 (17%) studied multiple telerehabilitation forms. Internet-based cognitive behavioral treatment with guidance by a psychologist or audiologist was examined in 17 studies (n=1767), internet-based cognitive behavioral treatment without guidance was examined in 4 studies (n=940), self-help manuals were examined in 1 study (n=72), technological self-help devices were examined in 2 studies (n=82), smartphone apps were examined in 8 studies (n=284), and other internet-based interventions were examined in 2 studies (n=130). These rehabilitation categories were proven to be effective in decreasing tinnitus severity and relieving tinnitus distress as measured by tinnitus questionnaires such as Tinnitus Functional Index, Tinnitus Handicap Inventory, or Tinnitus Reactions Questionnaire. However, dropout rates were often high (range 4%-71.4%). All studies reported between some concerns and high concerns of risk of bias, resulting in low to moderate certainty levels., Conclusions: Overall, there is low to moderate quality evidence that telerehabilitation interventions effectively reduce tinnitus severity and distress. These interventions form a possible tool to improve the self-management capacities of the patient and the accessibility of tinnitus care as a replacement or an addition to in-person care. Nevertheless, barriers such as lack of time, engagement, motivation, and openness of the patient causing high dropout should be considered., Trial Registration: PROSPERO International Prospective Register of Systematic Reviews CRD42021285450; https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=285450., (©Sara Demoen, Antonios Chalimourdas, Annick Timmermans, Vincent Van Rompaey, Olivier M Vanderveken, Laure Jacquemin, Winfried Schlee, Wim Marneffe, Janis Luyten, Annick Gilles, Sarah Michiels. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 09.02.2023.)

MoS 2 has been increasingly used in place of graphene as a flexible and multifunctional 2D material in many biomedical applications such as cancer detection and drug delivery, which makes it crucial to evaluate downstream compatibility in human immune cells. Molybdenum is a component of stainless-steel stent implants and has previously been implicated in stent hypersensitivity. In view of this, it is important to ascertain the effect of MoS 2 on allergy-relevant cells. Basophils are a less commonly used immune cell type. Unlike mast cells, basophils can be easily derived from primary human blood and can act as a sentinel for allergy. However, merely testing any one type of MoS 2 in basophils could result in different biological results. We thus decided to compare 2D MoS 2 from the two companies BeDimensional© (BD) and Biograph Solutions (BS), manufactured with two different but commonly exploited methods (BD, deoxycholate surfactant in a high-pressure liquid exfoliation, and BS using glycine in ball-milling exfoliation) to elucidate immunological end-points common to both MoS 2 and to demonstrate the need for biological verification for end-users who may require a change of supplier. We report higher histamine production in human basophils with MoS 2 . No effects on either surface basophil activation markers CD63 and CD203c or reactive oxygen species (ROS) production and cell viability were observed. However, different cytokine production patterns were evidenced. IL-6 and IL-1β but not TNF and GM-CSF were increased for both MoS 2 . BS-MoS 2 increased IL-4, while BD-MoS 2 decreased IL-4 and increased IL-13. Molybdate ion itself only increased IL-1β and IL-4. Deoxycholate surfactant decreased viability at 18 h and increased ROS upon basophil activation. Therefore, these results demonstrate the safety of MoS 2 in human basophils in general and highlight the importance of considering manufacturer additives and variability when selecting and investigating 2D materials such as MoS 2 ., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Nanoscale graphene-based materials (GBMs) enable targeting subcellular structures of the nervous system, a feature crucial for the successful engineering of alternative nanocarriers to deliver drugs and to treat neurodisorders. Among GBMs, graphene oxide (GO) nanoflakes, showing good dispersibility in water solution and being rich of functionalizable oxygen groups, are ideal core structures for carrying biological active molecules to the brain, such as the neuropeptide Y (NPY). In addition, when unconjugated, these nanomaterials have been reported to modulate neuronal function per se . Although some GBM-based nanocarriers have been tested both in vitro and in vivo, a thorough characterization of covalent binding impact on the biological properties of the carried molecule and/or of the nanomaterial is still missing. Here, a copper(I)-catalyzed alkyne-azide cycloaddition strategy was employed to synthesize the GO-NPY complex. By investigating through electrophysiology the impact of these conjugates on the activity of hippocampal neurons, we show that the covalent modification of the nanomaterial, while making GO an inert platform for the vectorized delivery, enhances the duration of NPY pharmacological activity. These findings support the future use of GO for the development of smart platforms for nervous system drug delivery., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Transcranial direct current stimulation (tDCS) has been proposed as a potential intervention for subjective tinnitus, but supporting evidence remains limited. We aimed to investigate the effect of anodal high-definition tDCS of the left temporal area and right dorsolateral prefrontal cortex on tinnitus severity. This double-blind randomized controlled trial included 77 patients (age range 18-79, 43 male) with chronic subjective tinnitus as their primary complaint. Thirty-eight subjects received six consecutive sessions of dual-site sequential high-definition-tDCS with electrodes positioned over the left temporal area and right dorsolateral prefrontal cortex. Both areas were stimulated for 15 min per session, with total stimulation time amounting to 30 min. Thirty-nine subjects received sham stimulation. The primary outcome measure was the change in tinnitus severity, as evaluated by the Tinnitus Functional Index, from baseline to a follow-up visit at 8 ± 2 weeks after treatment completion. Secondary outcomes included changes in perceived tinnitus loudness, as measured with a visual analogue scale and a tinnitus matching procedure, as well as scores on the Hospital Anxiety and Depression Scale, and the Hyperacusis Questionnaire. No differences in Tinnitus Functional Index change scores were identified between the active treatment and sham control groups (linear regression: P = 0.86). The Tinnitus Functional Index scores decreased significantly over time in both groups (P = 0.0012), indicating the presence of a considerable placebo effect. These change scores were significantly influenced by sex (linear regression: P = 0.037) and baseline symptoms of anxiety (linear regression: P = 0.049) in both groups. In general, Tinnitus Functional Index scores decreased more profoundly in males and in subjects with a higher degree of anxiety at baseline. None of the included secondary measures differed significantly between experimental arms. Our results suggest that dual-site sequential high-definition-tDCS of the left temporal area and right dorsolateral prefrontal cortex does not alleviate tinnitus severity. Interestingly, in our study population, fluctuations in tinnitus severity were influenced by gender and concurrent mental condition. It is therefore important to take these factors into account when conducting or planning randomized controlled trials in tinnitus populations., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Objective: As tinnitus is often associated with hearing loss, hearing aids have been proposed for tinnitus relief in literature for more than 70 years. There is a need for recent literature to be reviewed and guide decision making in tinnitus management. This scoping review aims to provide an update of the available evidence on hearing aids for tinnitus, focussing on the effect of sound amplification or combination devices (i.e. amplification and sound generation within one device)., Design: Research studies were included if they investigated hearing aids or combination devices for tinnitus and were published after 2011., Study Sample: A total of 28 primary research studies were selected., Results: Positive results of hearing aids in tinnitus patients were shown in 68% of the studies, whereas 14% demonstrated no change in tinnitus distress. However, the quality of the evidence across studies was variable., Conclusions: Scientific support for hearing aids and combination devices for tinnitus relief was found. The standalone effect of sound amplification and the added value of sound generators and adjustment of sound processing strategies needs further investigation. Stronger methodology in future studies is needed to reach consensus on how to optimise hearing solutions in a multidisciplinary approach.

Objectives: Transcranial direct current stimulation (tDCS) of the right dorsolateral prefrontal cortex has been hypothesized to reduce tinnitus severity by modifying cortical activity in brain regions associated with the perception of tinnitus. However, individual response to tDCS has proven to be variable. We investigated the feasibility of using random forest classification to predict the response to high-definition (HD) tDCS for tinnitus relief., Design: A retrospective analysis was performed on a dataset consisting of 99 patients with subjective tinnitus receiving six consecutive sessions of HD-tDCS at the Antwerp University Hospital. A baseline assessment consisted of pure-tone audiometry and a set of questionnaires including the Tinnitus Functional Index (TFI), Hospital Anxiety and Depression Scale, and Edinburgh Handedness Inventory. Random forest classification was applied to predict, based on baseline questionnaire scores and hearing levels, whether each individual responded positively to the treatment (defined as a decrease of at least 13 points on the TFI). Further testing of the model was performed on an independent cohort of 32 patients obtained from the tinnitus center at the University of Regensburg., Results: Twenty-four participants responded positively to the HD-tDCS treatment. The random forest classifier predicted treatment response with an accuracy of 85.71% (100% sensitivity, 81.48% specificity), significantly outperforming a more traditional logistic regression approach. Performance of the classifier on an independent cohort was slightly but not significantly above chance level (71.88% accuracy, 66.67% sensitivity, 73.08% specificity). Feature importance analyses revealed that baseline tinnitus severity, co-occurrence of depressive symptoms and handedness were the most important predictors of treatment response. Baseline TFI scores were significantly higher in responders than in nonresponders., Conclusions: The proposed random forest classifier predicted treatment response with a high accuracy, significantly outperforming a more traditional statistical approach. Machine learning methods to predict treatment response might ultimately be used in a clinical setting to guide targeted treatment recommendations for individual tinnitus patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 The Authors. Ear & Hearing is published on behalf of the American Auditory Society, by Wolters Kluwer Health, Inc.)

Purpose: To document whether patients with and without hyperacusis differ from each other on demographic, audiological, and clinical characteristics., Methods: Based on the Hyperacusis Questionnaire's (HQ) cut-off (HQ > 28), a total of 2301 participants were divided into patients with and without hyperacusis. Demographic data, scores on self-reported questionnaires [Tinnitus Functional Index (TFI), Visual Analogue Scale of tinnitus loudness (VAS loudness ), Hospital Anxiety Depression Scale (HADS)], and audiological parameters were retrospectively analysed to determine differential factors between the two groups., Results: In total, 10.9% of the patients was classified as hyperacusis patients (n = 251). They reported a significant, higher tinnitus severity (mean difference of 19 points on TFI) and mental distress (mean difference of 4 points on the HADS subscales) (p < 0.001) than patients without hyperacusis. Moreover, this group consisted of more women (45% % in hyperacusis group vs. 35% in non-hyperacusis group) and women scored significantly higher on the HQ (p < 0.001) and TFI (p < 0.01)., Conclusion: Patients with hyperacusis have distinctive characteristics. The presence of hyperacusis in combination with tinnitus can indicate a higher need for psychoeducation. Patients that present themselves with hyperacusis without tinnitus complaints remain a minority, yet might be underdiagnosed. Hence, future studies should disentangle tinnitus from hyperacusis. In clinical practice, greater efforts are required to increase knowledge about hyperacusis as a primary or secondary complaint and to provide individualized treatment for these patients., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The current limited understanding of tinnitus neurophysiology is one of the major obstacles in developing effective treatments for chronic tinnitus. As such, there is an urgent need for knowledge on underlying neural and/or neurobehavioral correlates that might function as potential biomarkers for tinnitus. We aimed to develop a model for the detection of tinnitus cases based on such potential biomarkers. In a first step, data from twenty patients suffering from chronic tinnitus, but no concurrent hearing loss or psychological complaints, were compared to data from twenty matched controls. Cortical auditory evoked potentials (CAEP) were elicited using a standard oddball paradigm. Source estimation and brain signal variability were analyzed to investigate putative differences between tinnitus patients and controls. Other examinations included standard audiometry, speech understanding in quiet and noisy conditions, and cognitive testing using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The P300 component, a response to unexpected but relevant stimuli, was significantly reduced in the tinnitus group. Source estimation revealed that the response of tinnitus patients was characterized by a decreased activity in temporal cortex, parahippocampus and insula. Brain signal variability on fine time scales was significantly higher in the tinnitus group, suggesting that tinnitus patients rely more strongly on local information processing. Furthermore, tinnitus was associated with a decreased cognitive performance, especially on tasks measuring delayed memory. In a second step, a logistic regression model was constructed based on CAEP activity, brain signal variability and RBANS scores. This model performed significantly above chance level when detecting tinnitus cases in an unseen dataset (accuracy of 75%, area under the ROC curve of 0.86). The successful classification between tinnitus cases and controls demonstrates the potential value of the proposed combination of biomarkers. Moreover, the identified associations between tinnitus, auditory evoked activity and cognitive performance point towards a significant contribution of top-down information processing in the perception of tinnitus., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: To evaluate the effects of a single psycho-educational session on tinnitus burden in chronic tinnitus patients. The session is organized at a tertiary referral center for otologic disorders at the University Hospital Antwerp as a group session (maximum of 10-15 patients a time) lasting for approximately 3-4 h. The session focusses on different aspects of tinnitus., Methods: The current manuscript reports on 96 patients who completed the Tinnitus Functional Index (TFI), Visual Analogue Scale for mean loudness (VAS), Hyperacusis Questionnaire (HQ), and the Hospital Anxiety and Depression Scale (HADS) prior to treatment and at 6-month follow-up. The TFI was chosen as the primary outcome. Paired-samples T tests were performed to evaluate therapy effect at 6-month follow-up. In addition, a logistic regression model revealed baseline TFI/VAS scores and duration of tinnitus as contributing factors to a significant decrease of the TFI., Results: The TFI total score showed a significant decrease (p < 0.001) at the 6-month follow-up time point. At follow-up, 75% of patients reported their tinnitus to be under control not requiring any additional treatment. The logistic regression model showed that patients with higher baseline TFI scores, lower baseline mean VAS loudness ratings, and shorter tinnitus duration were more likely to show clinically significant improvement on the TFI scale., Conclusions: Tinnitus Retraining Therapy or Cognitive Behavioural Therapy are effective, though very time-consuming and expensive treatments. A single psycho-educational group session was shown to be highly effective in decreasing the tinnitus burden, which increases feasibility and cost-effectiveness., Trial Registration: Not applicable as this is a retrospective reporting of tinnitus outcome in the daily clinical practice, not a clinical trial., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Tinnitus is a highly prevalent symptom, affecting 10-15% of the adult population. Tinnitus influenced by alterations in somatosensory afference from the neck or jaw is referred to as somatic tinnitus (ST). ST is known to respond positively to physiotherapy treatment; however, it is challenging to motivate patients to systematically perform home exercises correctly, and the necessary tinnitus counselling is often lacking. The aim of this study is twofold, namely to investigate both the effectiveness and cost-effectiveness of a blended physiotherapy program for ST, including a smartphone application designed to increase exercise therapy compliance and provide tinnitus counselling., Methods: This study is designed as a single-blind two-arm 1:1 randomised controlled trial (RCT). Adult patients diagnosed with ST, without psychiatric comorbidities and with experience in using a smartphone, will be recruited at the Ear Nose Throat (ENT) department of the Antwerp University Hospital (UZA). Patients will be randomised into two groups. The experimental group will receive the blended physiotherapy program comprising six in-clinic physiotherapy sessions over a period of 12 weeks (1x/2 weeks) and an exercise and counselling program provided by the smartphone application. The control group will receive the standard care program comprising twelve weekly in-clinic physiotherapy sessions. Each physiotherapy session has a duration of 30 min. The primary outcome measure is the change in Tinnitus Functional Index (TFI) score. Additionally, a cost-effectiveness analysis will be performed from a societal perspective considering both direct and indirect costs. There will be follow-up assessments at one and 3 months after the final treatment session., Discussion: Our study is the first to combine both tinnitus counselling and neck/jaw treatment provided by a digital application in a blended physiotherapy program. This, in order to empower ST patients to improve and better manage their own health and, possibly, reduce economic costs by alleviating the tinnitus burden that ST patients experience. The strengths of the planned RCT are the high-quality methodological design, the large sample size and the expertise of the involved multidisciplinary research team., Trial Registration: Clinicaltrials.gov NCT05245318 . Registered on 26 January 2022., (© 2022. The Author(s).)

Tinnitus is a common experience which can have a severe impact on ones quality of life. Whilst there have been reports of historical references to tinnitus, there has not been an international cross-sectional analysis of the vocabulary used for tinnitus. In this study, with 227 respondents (of which 53.3% experiencing tinnitus themselves), we report such an analysis of 252 words or phrases, from 42 languages and 48 countries. The results indicate that the majority of vocabulary used has a negative connotation (63%), though a small minority are positive (4%). Many words used for tinnitus in different languages are onomatopoeic-thus mimicking aspects of the percept experienced-or describe the sound (in total 42% of the vocabulary). The involvement of the ear is implied in some terminology, though other vocabulary expresses the impact. Participants experiencing tinnitus significantly differed on the codes for their proposed words or phrases ( p < 0.001), with the code "internal suffering or irritation or intrusion" being more prevalent and the code "relate to ear" and "sound is phantom or not real or imagined" being less prevalent in this group. This research has implications not only for the vocabulary used for tinnitus in Patient Reported Outcome Measures but also, and importantly, for understanding the vocabulary and lived experiences of people with tinnitus by healthcare professionals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Baguley, Caimino, Gilles and Jacquemin.)

Background: Successful orofacial treatment can reduce tinnitus severity in patients with somatic tinnitus (ST). However, it is still unclear to what extent the degree of reduction in temporomandibular disorders (TMD) actually contributes to the decrease in tinnitus severity after orofacial treatment. Therefore, the aim of this study was to analyze the mediating effect of reduction in TMD pain on the improvement of tinnitus severity after multidisciplinary orofacial treatment., Methods: A total of 80 patients with moderate to severe ST attributed to the temporomandibular region, were recruited from a tertiary tinnitus clinic. At baseline, patients were randomly assigned to the orofacial treatment group or to the control group. Both groups received a minimum of information and advice regarding their tinnitus complaints. The orofacial treatment group received orofacial physical therapy complemented with occlusal splints when needed, while the control group received no other treatment. A mediation analysis was performed according to the steps described by Baron and Kenny and the proportion of the mediating effect was calculated for the potential mediator: "change in TMD pain," measured by a one-point decrease in TMD pain screener score., Results: Our analysis showed that 35% of the observed decrease in tinnitus severity can be attributed to a reduction in TMD pain. A significant total effect of orofacial treatment compared with control on the change in tinnitus functional index (TFI) score was found (B = 0.253 p = 0.025 Cl for B = 1.265-18.576). Orofacial treatment was also significantly related to the change in TMD pain (Exp (B) = 2.800, p = 0.034 Cl for Exp B 1.081-7.251). Additionally, the change in TMD pain screener score was significantly related to the change in TFI score (B = -0.273 p = 0.016 Cl for B = -19.875 to -2.119)., Conclusion: Reduction of TMD pain is a mediating factor in the decrease of tinnitus severity after multidisciplinary orofacial treatment., Practical Implications: Orofacial treatment can be used to decrease tinnitus severity in patients with TMD related somatic tinnitus., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2022, Otology & Neurotology, Inc.)

Purpose: Meaningfully grouping individuals with tinnitus who share a common characteristics (ie, subgrouping, phenotyping) may help tailor interventions to certain tinnitus subgroups and hence reduce outcome variability. The purpose of this study was to test if the presence of tinnitus subgroups are discernible based on hearing-related comorbidities, and to identify predictors of tinnitus severity for each subgroup identified., Methods: An exploratory cross-sectional study was used. The study was nested within an online survey distributed worldwide to investigate tinnitus experiences during the COVID-19 pandemic. The main outcome measure was the tinnitus Handicap Inventory- Screening Version., Results: From the 3400 respondents, 2980 were eligible adults with tinnitus with an average age of 58 years (SD = 14.7) and 49% (n = 1457) being female. A three-cluster solution identified distinct subgroups, namely, those with tinnitus-only (n = 1306; 44%), those presenting with tinnitus, hyperacusis, hearing loss and/or misophonia (n = 795; 27%), and those with tinnitus and hearing loss (n = 879; 29%). Those with tinnitus and hyperacusis reported the highest tinnitus severity (M = 20.3; SD = 10.5) and those with tinnitus and no hearing loss had the lowest tinnitus severity (M = 15.7; SD = 10.4). Younger age and the presence of mental health problems predicted greater tinnitus severity for all groups (β ≤ -0.1, P ≤ .016)., Conclusion: Further exploration of these potential subtypes are needed in both further research and clinical practice by initially triaging tinnitus patients prior to their clinical appointments based on the presence of hearing-related comorbidities. Unique management pathways and interventions could be tailored for each tinnitus subgroup., (© 2021 John Wiley & Sons Ltd.)

Background: The Marie-Skłodowska-Curie Actions' (MSCA) Innovative Training Network (ITN) is a doctoral training programme jointly implemented by academic institutions and industries from countries across Europe and beyond. To our knowledge no study has examined the experience of students participating in MSCA-ITNs. This study aims to evaluate and report MSCA-ITN Early Stage Researcher (ESR) experiences. Methods: The Innovative Training Network - Evaluation Questionnaire (ITN-EQ) was developed to assess supervision, training, collaborations and experiences of ESRs and forwarded to two tinnitus-related ITNs and seven ITNs of other disciplines. Results: Key advantages identified included better career prospects, multidisciplinary research opportunities/collaborations, international exposure, personal/professional development, plus generous salaries and research budgets. However, lack of a common EU framework resulted in the experience being largely dependent on the host institution, country and supervisor. Moreover, managing the dual requirements of ITNs and host institutions while completing a three-year PhD seemed challenging for most ESRs. ESR involvement in workshop and training school planning was desirable. More than 80% of ESRs rated the overall ITN experience favourably and 98.3% would recommend the same to prospective PhD students. Conclusions: This report could provide valuable insights in planning and management of future ITNs and could assist prospective students in their decision of joining an ITN for their PhD., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Biswas R et al.)

Objective: COVID-19 patients may develop coagulopathy, which is associated with poor prognosis and high risk of thrombosis. The main objective of this work was to evaluate the prevalence of deep venous thrombosis of lower limbs (DVT) through ultrasonography in patients infected with COVID-19 admitted to conventional units at our hospital with 5 days of monitoring. The secondary objective was to determine if D-dimer levels, body mass index, and C-reactive protein were associated with DVT., Methods: A total of 72 patients, with a mean age of 65 ± 12.3 years, infected with COVID-19 were admitted to three conventional units at our institution; 28 patients were women. A COVID-19 diagnosis was made by a transcriptase polymerase chain reaction by means of nasopharyngeal swab or by chest computer tomography without iodine contrast media. Demographics, comorbidities, and laboratory parameters were collected. A preventive anticoagulation treatment was established on admission with low-molecular-weight heparin. A complete venous duplex ultrasound (DU) test of lower limbs was performed on day (D) 0 and D5. A pulmonary computer tomography angiogram with iodine contrast media was required when pulmonary embolism was suspected., Results: On D0, the DU showed acute DVT in seven patients (9.75%). A pulmonary computer tomography angiogram was performed in 12 patients (16.65%), 3 (25%) of whom had an acute pulmonary embolism. On D0, acute DVT was not significantly associated with C-reactive protein (mean 101 ± 98.6 in the group without DVT vs 67.6 ± 58.4 mg/L, P = .43) or body mass index (27.7 ± 5.04 vs 28.1 ± 2.65 kg/m 2 , P = .54). However, we found a significant association between acute DVT and D-dimer levels (1536 ± 2347 vs 9652 ± 10,205 ng/mL, P < .01). Among the patients included on D0, only 32 had a DU on D5. Forty of them (55.55%) were not examined for the following reasons: 7 (9.7%) were previously diagnosed with venous thromboembolism on D0 and therefore were excluded on D5, 8 (11%) were transferred to the intensive care unit, 10 (14%) were discharged from the hospital, 5 (7%) died, and 10 (13.9%) were excluded because of technical issues. On D5, five (15.6%) patients had acute DVT in addition to those found on D0; three were distal and two proximal despite preventive anticoagulation with low-molecular-weight heparin., Conclusions: Hospitalized non-intensive care unit patients with COVID-19 pneumonia have a high frequency of venous thrombotic events justifying screening with DU., (Copyright © 2020 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Tinnitus severity has been exacerbated because of the COVID-19 pandemic and those with tinnitus require additional support. Such support should be informed by patient preferences and needs. The objective of this study was to gather information from individuals with tinnitus living in Europe to inform stakeholders of the (a) support they needed in relation to changes associated with the COVID-19 pandemic and (b) suggestions regarding tinnitus care for the future., Methods: A cross-sectional mixed method study design was used using closed and open-ended questions via an online survey. Data were gathered from 710 adults experiencing tinnitus in Western Europe, with the majority living in The Netherlands, Belgium and Sweden. Data were analysed using qualitative content analysis and descriptive statistics., Results: Those with tinnitus indicated the following support needs during the pandemic (a) support for tinnitus, (b) support for hearing-related difficulties, (c) social support and (d) pandemic-related support. Five directions for future tinnitus care were provided, namely, (a) need for understanding professional support and access to multidisciplinary experts, (b) greater range of therapies and resources, (c) access to more information about tinnitus, (d) prioritising tinnitus research and (e) more support for hearing protection and hearing loss prevention., Conclusions: The findings point to the need for accessible (remote), patient-centred, suitable and evidence-based tinnitus care. Insights from the current study can be used by various stakeholders including clinical practitioners and tinnitus support services to ensure those with tinnitus have access to the help and support required in order to reduce service provision insufficiencies., (© 2021 John Wiley & Sons Ltd.)

Tinnitus can be a burdensome condition on both individual and societal levels. Many aspects of this condition remain elusive, including its underlying mechanisms, ultimately hindering the development of a cure. Interdisciplinary approaches are required to overcome long-established research challenges. This review summarizes current knowledge in various tinnitus-relevant research fields including tinnitus generating mechanisms, heterogeneity, epidemiology, assessment, and treatment development, in an effort to highlight the main challenges and provide suggestions for future research to overcome them. Four common themes across different areas were identified as future research direction: (1) Further establishment of multicenter and multidisciplinary collaborations; (2) Systematic reviews and syntheses of existing knowledge; (3) Standardization of research methods including tinnitus assessment, data acquisition, and data analysis protocols; (4) The design of studies with large sample sizes and the creation of large tinnitus-specific databases that would allow in-depth exploration of tinnitus heterogeneity., Competing Interests: KA is employed by Cochlear Company. MJ is employed by WS Audiology. CC is employed by Oticon A/S. These relationships have not influenced the work reported in this paper. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Simoes, Daoud, Shabbir, Amanat, Assouly, Biswas, Casolani, Dode, Enzler, Jacquemin, Joergensen, Kok, Liyanage, Lourenco, Makani, Mehdi, Ramadhani, Riha, Santacruz, Schiller, Schoisswohl, Trpchevska and Genitsaridi.)

Background: Transcranial Direct Current Stimulation (tDCS) aims to induce cortical plasticity by modulating the activity of brain structures. The broad stimulation pattern, which is one of the main limitations of tDCS, can be overcome with the recently developed technique called High-Definition tDCS (HD-tDCS)., Objective: Investigation of the effect of HD-tDCS on tinnitus in a large patient cohort., Methods: This prospective study included 117 patients with chronic, subjective, non-pulsatile tinnitus who received six sessions of anodal HD-tDCS of the right Dorsolateral Prefrontal Cortex (DLPFC). Therapy effects were assessed by use of a set of standardized tinnitus questionnaires filled out at the pre-therapy (T pre ), post-therapy (T 3w ) and follow-up visit (T 10w ). Besides collecting the questionnaire data, the perceived effect (i.e., self-report) was also documented at T 10w ., Results: The Tinnitus Functional Index (TFI) and Tinnitus Questionnaire (TQ) total scores improved significantly over time (p TFI <0.01; p TQ <0.01), with the following significant post hoc comparisons: T pre vs. T 10w (p TFI <0.05; p TQ <0.05) and T 3w vs. T 10w (p TFI <0.01; p TQ <0.01). The percentage of patients reporting an improvement of their tinnitus at T 10w was 47%. Further analysis revealed a significant effect of gender with female patients showing a larger improvement on the TFI and TQ (p TFI <0.01; p TQ <0.05)., Conclusions: The current study reported the effects of HD-tDCS in a large tinnitus population. HD-tDCS of the right DLPFC resulted in a significant improvement of the tinnitus perception, with a larger improvement for the female tinnitus patients., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Subjective tinnitus, the perception of sound in the absence of any sound source, is routinely assessed using questionnaires. The subjective nature of these tools hampers objective evaluation of tinnitus presence, severity and treatment effects. Late auditory evoked potentials (LAEPs) might be considered as a potential biomarker for assessing tinnitus complaints. Using a multivariate meta-analytic model including data from twenty-one studies, we determined the LAEP components differing systematically between tinnitus patients and controls. Results from this model indicate that amplitude of the P300 component is lower in tinnitus patients (standardized mean difference (SMD) = -0.83, p < 0.01), while latency of this component is abnormally prolonged in this population (SMD = 0.97, p < 0.01). No other investigated LAEP components were found to differ between tinnitus and non-tinnitus subjects. Additional sensitivity analyses regarding differences in experimental conditions confirmed the robustness of these results. Differences in age and hearing levels between the two experimental groups might have a considerable impact on LAEP outcomes and should be carefully considered in future studies. Although we established consistent differences in the P300 component between tinnitus patients and controls, we could not identify any evidence that this component might covary with tinnitus severity. We conclude that out of several commonly assessed LAEP components, only the P300 can be considered as a potential biomarker for subjective tinnitus, although more research is needed to determine its relationship with subjective tinnitus measures. Future trials investigating experimental tinnitus therapies should consider including P300 measurements in the evaluation of treatment effect., Competing Interests: The authors have declared that no competing interests exist.

Introduction: The COVID-19 pandemic has disrupted delivery of healthcare, economic activity, and affected social interactions. Identifying and supporting those most affected by the pandemic is required. The purpose of this study was to determine the impact of the pandemic on individuals with tinnitus and to identify mediating factors. Methods: This is a mixed-methods exploratory cross-sectional study, using data collected via an online survey from 3,103 individuals with tinnitus from 48 countries. The greatest representation was from North America (49%) and Europe (47%) and other countries were only marginally represented. Results: Although the study was aimed at those with pre-existing tinnitus, 7 individuals reported having COVID-19 initiated tinnitus. Having COVID-19 symptoms exacerbated tinnitus in 40% of respondents, made no change in 54%, and improved tinnitus in 6%. Other mediating factors such as the social and emotional consequences of the pandemic made pre-existing tinnitus more bothersome for 32% of the respondents, particularly for females and younger adults, better for 1%, and caused no change to tinnitus for 67%. Pre-existing tinnitus was significantly exacerbated for those self-isolating, experiencing loneliness, sleeping poorly, and with reduced levels of exercise. Increased depression, anxiety, irritability, and financial worries further significantly contributed to tinnitus being more bothersome during the pandemic period. Conclusions: These findings have implications for tinnitus management, because they highlight the diverse response both internal and external factors have on tinnitus levels. Clinical services should be mindful that tinnitus may be caused by contracting COVID-19 and pre-existing tinnitus may be exacerbated, although in the majority of respondents there was no change. Additional support should be offered where tinnitus severity has increased due to the health, social, and/or emotional effects of the COVID-19 pandemic. Tinnitus may be more bothersome for those experiencing loneliness, having fewer social interactions, and who are more anxious or worried., (Copyright © 2020 Beukes, Baguley, Jacquemin, Lourenco, Allen, Onozuka, Stockdale, Kaldo, Andersson and Manchaiah.)

Introduction: Subjective tinnitus that is influenced by the somatosensory system is called somatosensory tinnitus (ST). When ST is related to the temporomandibular area, multidisciplinary orofacial treatment can reduce tinnitus severity. It is, however, unknown if we can predict this positive outcome. The aim of this study is to look for prognostic indicators that can predict a positive outcome after multidisciplinary orofacial treatment in patients with ST., Methods: Patients were included when they were diagnosed with temporomandibular-related ST and received a maximum of 18 sessions of orofacial treatment during a 9-week program. Predictors for positive treatment outcome were identified using univariate and multiple logistic regression analyses with the Tinnitus Questionnaire (TQ) and the Tinnitus Functional Index (TFI) as dependent variables., Results: The results of 101 patients were included in the analysis. Immediately after multidisciplinary orofacial treatment, a clinically relevant decrease in TQ score was significantly associated with "shorter duration of tinnitus" [odds ratio (OR) 0.99], "higher initial score on the TQ somatic subscale" (OR 1.52), and "painful palpation of the temporomandibular joint (TMJ)" (OR 2.46). After 9 weeks of follow-up, the "higher initial score on the TQ somatic subscale" remained as the sole predictor (OR 1.44). A clinically relevant decrease on TFI after 9 weeks of follow-up was predicted by "female gender" (OR 2.70), "younger age" (OR 0.96), "shorter duration of the tinnitus" (OR 0.99), "lower pressure pain thresholds (PPT) on TMJ" (OR 0.99), "lower PPT on sternocleidomastoid origin" (OR 0.99), and "better speech in noise perception" (OR 0.88). A multivariate model comprising "shorter duration of tinnitus" and "higher initial score on the somatic subscale of the TQ" correctly predicts the clinically relevant decrease in TQ score after treatment in 68.5%. A second multivariate model comprising "female gender," "younger age," and "shorter duration of the tinnitus" correctly predicts a clinically significant decrease on TFI after follow-up in 68.1%., Conclusion: We were able to identify various prognostic indicators. "Younger female patients" with a "shorter duration of tinnitus" and a "higher initial score on the TQ somatic subscale" appear to have the best prognosis after multimodal orofacial therapy., (Copyright © 2020 van der Wal, Van de Heyning, Gilles, Jacquemin, Topsakal, Van Rompaey, Braem, Visscher, Truijen, Michiels and De Hertogh.)

Introduction: To date, guidelines recommend the use of a stepped care approach to treat tinnitus. The current clinical management of tinnitus frequently consists of audiologic interventions and tinnitus retraining therapy (TRT) or cognitive behavioral therapy (CBT). Due to the high heterogeneity of the tinnitus population and comorbidity of tinnitus with insomnia, anxiety, and depression, these interventions may not be sufficient for every patient. The current study aims to determine whether a bimodal therapy for chronic, subjective tinnitus consisting of the combination of TRT and eye movement desensitization reprocessing (EMDR) results in a clinically significant different efficacy in comparison with the prevailing bimodal TRT and CBT therapy., Methods: Patients were randomized in two treatment groups. The experimental group received the bimodal therapy TRT/EMDR and the active control group received the bimodal therapy TRT/CBT. Evaluations took place at baseline (T 0 ), at the end of the treatment (T 1 ), and 3 months after therapy (T 2 ). The tinnitus functional index (TFI) was used as primary outcome measurement. Secondary outcome measurements were the visual analog scale of tinnitus loudness (VAS Loudness ), tinnitus questionnaire (TQ), hospital anxiety and depression scale (HADS), hyperacusis questionnaire (HQ), global perceived effect (GPE), and psychoacoustic measurements., Findings: The TFI showed clinically significant improvement in both bimodal therapies (mean decrease 15.1 in TRT/CBT; p < 0.001 vs. 16.2 in TRT/EMDR; p < 0.001). The total score on the TQ, HADS, HQ, and VAS Loudness all demonstrated significant decrease after treatment and follow-up ( p < 0.001) in the experimental and the active control group. GPE-measurements revealed that more than 80% (i.e., 84% in TRT/CBT vs. 80% in TRT/EMDR) of the patients experienced substantial improvement of tinnitus at follow up. Treatment outcome remained stable after 3 month follow-up and no adverse events were observed., Conclusion: Both psychotherapeutic protocols result in a clinically significant improvement for patients with chronic subjective tinnitus. No significant different efficacy was found for the TRT/EMDR treatment compared to the combination of TRT and CBT., Clinical Trial Registration: ClinicalTrials.gov, ID: NCT03114878. April 14, 2017., (Copyright © 2020 Luyten, Jacquemin, Van Looveren, Declau, Fransen, Cardon, De Bodt, Topsakal, Van de Heyning, Van Rompaey and Gilles.)

The SARS-Cov-2 pandemic has spread worldwide during 2020, setting up an uncertain start of this decade. The measures to contain infection taken by many governments have been extremely severe by imposing home lockdown and industrial production shutdown, making this the biggest crisis since the second world war. Additionally, the continuous colonization of wild natural lands may touch unknown virus reservoirs, causing the spread of epidemics. Apart from SARS-Cov-2, the recent history has seen the spread of several viral pandemics such as H2N2 and H3N3 flu, HIV, and SARS, while MERS and Ebola viruses are considered still in a prepandemic phase. Hard nanomaterials (HNMs) have been recently used as antimicrobial agents, potentially being next-generation drugs to fight viral infections. HNMs can block infection at early (disinfection, entrance inhibition) and middle (inside the host cells) stages and are also able to mitigate the immune response. This review is focused on the application of HNMs as antiviral agents. In particular, mechanisms of actions, biological outputs, and limitations for each HNM will be systematically presented and analyzed from a material chemistry point-of-view. The antiviral activity will be discussed in the context of the different pandemic viruses. We acknowledge that HNM antiviral research is still at its early stage, however, we believe that this field will rapidly blossom in the next period.

Introduction: Tinnitus is a complex symptom requiring a thorough multidisciplinary assessment to construct an individual's tinnitus profile. The Antwerp University Hospital hosts a tertiary tinnitus clinic providing intensive, multidisciplinary tinnitus care in the form of combinational psychological treatment with either Tinnitus Retraining Therapy (TRT)/Cognitive Behavioral Therapy (CBT) or TRT/eye movement desensitization and reprocessing therapy (EMDR), high-definition transcranial direct current stimulation (HD-tDCS), and physical therapy treatment (in cases of somatic influence of the neck or the temporomandibular area). Several factors may contribute to therapy effect of which the role of gender has recently gained more interest. As such, the current manuscript explores gender differences in the outcome of different tinnitus treatments., Methods: Data on treatment outcome of four distinct tinnitus treatments (1. HD-tDCS; 2. orofacial physical therapy; 3. combination TRT + CBT; and 4. combination TRT + EMDR) were pooled and compared. Treatment outcome was assessed via the Tinnitus Functional Index (TFI). Participants completed the TFI at baseline, immediately after treatment and after 9 weeks (±3 weeks) follow-up. To explore the effect of gender on different treatment outcomes, a linear mixed model was designed including Time point , Gender , and Therapy Group as fixed factors as well as all interactions between these factors., Results: TFI scores improved significantly over time regardless of therapy group ( p < 0.0001). A mean TFI decrease of at least 13 points was obtained by all participants except by those in the HD-tDCS. Significant interactions between Gender and Time point were identified in all groups except for the TRT +EMDR group. Female subjects improved more extensively than males in the HD-tDCS ( p = 0.0009) and orofacial therapy group ( p = 0.0299). Contrarily, in the TRT +CBT group, male participants showed a significant improvement whereas the mean TFI scores of female subjects remained on baseline levels ( p = 0.0138)., Conclusion: Our data suggest that male and female tinnitus patients seem to react differently to different therapy options. We strongly encourage further prospective studies to discern the relevance of gender in therapy outcome., (Copyright © 2020 Van der Wal, Luyten, Cardon, Jacquemin, Vanderveken, Topsakal, Van de Heyning, De Hertogh, Van Looveren, Van Rompaey, Michiels and Gilles.)

Background: Patients with familial hypercholesterolemia (FH) are prone to develop acute myocardial infarction (AMI) at a younger age., Objectives: The aim of the present study was to assess 5-year outcomes after AMI according to the presence of FH in a large multicenter cohort of patients., Methods: The French registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction consists of nationwide surveys recruiting patients over a 1- to 2-month period every 5 years. Patients recruited in 2005 and 2010 were followed up to 5 years., Results: Of 5147 patients discharged alive and in whom FH status could be assessed, 2.8% had probable/definite FH, using an adapted Dutch Lipid Clinic score. They were 12 years younger, on average, than non-FH patients. Before adjustment, their 5-year survival and event-free survival did not differ from non-FH patients. After adjustment, however, both mortality (hazard ratio [HR] 1.82, 95% confidence interval [CI] 1.15-2.89; P = .011) and the combined endpoint of death, AMI, or stroke (HR 2.22, 95% CI: 1.51-3.26; P < .001) were higher in FH patients. The higher risk in FH patients was also present in patients receiving high-intensity lipid-lowering therapy at discharge: adjusted HR for mortality 2.29, 95% CI: 1.18 to 4.47, P = .015; HR for cardiovascular events 2.57, 95% CI: 1.48 to 4.48, P = .001. Concordant results were observed in propensity score-marched cohorts., Conclusions: The risk of long-term mortality and cardiovascular events is twice as high in FH than in non-FH patients, when adjusted on baseline characteristics, even for those receiving high-intensity lipid-lowering therapy. Additional therapeutic measures are needed in these patients., (Copyright © 2020. Published by Elsevier Inc.)

Background: Tinnitus, or ringing in the ears, is a perception of sound in the absence of overt acoustic stimulation. In some cases, tinnitus can be influenced by temporomandibular somatosensory input, then called temporomandibular somatosensory tinnitus (TST). It is, however, not entirely known if orofacial treatment can decrease tinnitus severity. The purpose of this study was to evaluate the effect of orofacial treatment on tinnitus complaints in patients with TST., Methods: Adult patients with TST were included, and all patients received information and advice about tinnitus and conservative orofacial treatment consisting of physical therapy, and, in case of grinding, occlusal splints were applied. Included patients were randomly assigned to an early start group and a delayed start group according to our delayed treatment design., Results: In total, 40 patients were included in each group. The treatment effect on tinnitus severity was investigated using the tinnitus questionnaire (TQ) and Tinnitus Functional Index (TFI). Regarding the TQ score, no clinically relevant reductions were observed, and no significant differences in the decrease were observed between the early start group and delayed start group. Contrarily, a significantly higher percentage of patients showed a decrease in the TQ degree in the early start group compared to the delayed start group (30.0% versus 2.8%, p = 0.006). The TFI score did show a significantly greater and clinically relevant reduction in the early start group compared to the delayed start group ( p = 0.042)., Conclusion: A multidisciplinary non-invasive orofacial treatment was able to reduce tinnitus severity in patients with temporomandibular related somatosensory tinnitus.

Objective: Cochlear implantation results in restoration of hearing, potential cortical reorganisation and the reallocation of attentional resources to the auditory system. Hence, the distorted cortical activity of patients with profound sensorineural hearing loss may be partially reversed. The measurement of auditory event-related potentials (ERPs) forms a promising electrophysiological evaluation of the central auditory nervous system. In particular, the P3 component is hypothesised to be a differential indicator of subjective auditory discrimination. This overview discusses the association between the cortical P3 component and the performance on auditory tests in post-lingually deaf adults using a CI. Moreover, the current article proposes important guidelines on eliciting, recording and analysing ERPs in CI users. Design: The literature search was conducted in PubMed. Study sample: Articles were included if they focussed on the relationship between P3 and auditory performance of an adult CI population. Results: The higher-order processing of speech in quiet and in noise of adult CI users is correlated with the ERP components, including the P3, shedding light on neurophysiological foundations for auditory performance differences. Conclusions: There is a need for replicating studies with larger sample sizes to fully comprehend the relationship between P3 and the auditory performance of CI users.

Objective: Many tinnitus patients report cognitive deficits such as concentration and attention difficulties. The aim of this study was to comprehensively assess cognitive functioning in tinnitus patients using a standardized test battery, the repeatable battery for the assessment of neuropsychological status adjusted for hearing impaired individuals (RBANS-H)., Study Design: Cross-sectional study., Setting: Tertiary referral center., Participants: Twenty-eight chronic tinnitus patients and 28 control participants, matched for sex, age, hearing loss, and education level., Intervention: Diagnostic., Main Outcome Measures: All participants completed the RBANS-H, which includes subtests probing immediate and delayed memory, visuospatial capabilities, language, and attention. The tinnitus patients completed the tinnitus functional index (TFI), a visual analogue scale (VAS) measuring subjective mean tinnitus loudness and the hyperacusis questionnaire (HQ)., Results: The total RBANS-H scores did not differ between tinnitus patients and controls. However, on the language subscale, mean scores of the tinnitus group (97.6 ± 11.0) were significantly lower than those of controls (104.4 ± 12.0), with correction for sex, age, hearing level, and education level (general linear model: p = 0.034). Post hoc t tests revealed a specific deficit concerning the semantic fluency subtest (tinnitus: 19.5 ± 6.2; control: 23.1 ± 5.9; p = 0.015). VAS scores for tinnitus loudness were negatively correlated to scores on the RBANS-H attention subscale (r = -0.48, p = 0.012)., Conclusions: The current study successfully employed the RBANS-H to provide a broader view on cognitive functioning in tinnitus patients. The results showed a specific negative influence of tinnitus on verbal fluency, which could be related to a deficit in executive cognitive control. Moreover, patients experiencing louder tinnitus performed worse on specific subtests concerning attention.

Objective: Treatment effect in tinnitus research is commonly evaluated by use of self-report questionnaires. As this is a solely subjective assessment method, the need for an objective measurement is paramount to genuinely evaluate the effects of therapeutic interventions. The current study explores the value of event-related potentials (ERPs) in the evaluation of high-definition transcranial direct current stimulation (HD-tDCS) for tinnitus treatment., Study Design: Prospective exploratory study., Setting: Tertiary referral center., Patients: Twenty-two chronic tinnitus patients., Intervention: HD-tDCS., Main Outcome Measures: ERPs., Results: The results show a significant shortening of the N1, P2, N2, and P3 latencies after HD-tDCS treatment. Moreover, the increased amplitude of the P2 and N2 peaks result in more salient and clear peaks, with the amplitude of N2 being significant larger after HD-tDCS. However, the ERP changes are not significantly correlated with the change in tinnitus functional index (TFI) total score., Conclusions: The current study was the first to explore ERPs as objective measure in a study with HD-tDCS in tinnitus patients. Adding ERPs to the outcome measures in tinnitus research may lead to a better understanding of the therapeutic effect in the future. The results showed a shortening of ERP latencies and an increased N2 amplitude, possibly reflecting more effective sound processing with higher recruitment of synchronized neurons in the auditory cortex. Future studies should elaborate on these results, by collecting control data and adding a sham group, to provide a better insight in the underlying mechanism of the ERP changes after tinnitus treatment.

Background: Complete alleviation of tinnitus perception is rarely achieved by current therapeutic interventions. However, adequate therapy may induce a small or large decrement of the tinnitus. The assessment of the therapeutic effect is challenging due to large interindividual variability. Multiple tinnitus questionnaires are available to describe functional effects of tinnitus pre and post-therapeutic intervention, of which the Tinnitus Functional Index (TFI) and Tinnitus Questionnaire (TQ) are two very commonly used questionnaires by clinicians and researchers., Objective: To recommend either TFI or TQ as an outcome measure for the investigation of tinnitus treatments by investigating the consistency between the TFI and TQ, as well as comparing the responsiveness of both scales after therapeutic intervention., Methods: Data from the validated Dutch versions of the TFI and the TQ of 100 chronic subjective tinnitus patients who underwent 6 sessions of neuromodulation at the Antwerp University Hospital were included. The patients reported their perceived effect and filled out the TFI and TQ at the pre-therapy, post-therapy and follow-up visit (i.e. ± seven weeks post-therapy). The intra-class correlation (ICC) was determined, measuring consistency between the TFI and TQ. Furthermore, the responsiveness was compared by use of mixed effects analysis. Finally, the agreement between the total scores of the questionnaires and the perceived effect was evaluated by use of their receiver operating characteristic (ROC) curve., Results: The total scores of the TFI and TQ showed a good agreement at pre-therapy (ICC = .82) and post-therapy visit (ICC = 0.82). The ICC indicated a lower, but still good agreement at follow-up (ICC = 0.79). Furthermore, the total scores of the TFI and TQ significantly changed over time (pTFI < .05; p TQ  < .05). In the patients who verbally reported at follow-up visit that their tinnitus complaints decreased after treatment, the percentage of patients showing a clinically significant decrease on the TFI (i.e. a decrease of ≥13 points) and the TQ (i.e. decrease of ≥12 points) was 50% and 33% respectively, however, not statically significant different (p = .13). Finally, the analysis of the agreement between the perceived effect and the clinically significant improvement on the questionnaires showed a kappa-value of 0.36 for the TFI and 0.29 for the TQ., Conclusion: The TFI and TQ have high convergent validity and are both suitable as an outcome measure to quantify a change in the self-perceived tinnitus burden. The TFI is shorter and shows a slightly higher agreement with the self-reported perceived effect. Therefore, this comparison is in favor of the TFI for research purposes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Chronic tinnitus is a highly prevalent symptom, with many patients reporting considerable effects of tinnitus on quality of life. No clear evidence-based treatment options are currently available. While counseling-based methods are valuable in some cases, they are not sufficiently effective for all tinnitus patients. Neuromodulation techniques such as high-definition transcranial direct current stimulation (HD-tDCS) are proposed to have positive effects on tinnitus severity but, to date, these effects have not been proven conclusively. The proposed trial will investigate the hypothesis that chronic tinnitus patients receiving HD-tDCS will report a positive effect on the impact of tinnitus on daily life, as compared to patients receiving sham stimulation., Methods: This study proposes a randomized, double-blind, placebo-controlled trial with parallel group design. A total of 100 chronic tinnitus patients will be randomly allocated to an experimental group or a sham group, with allocation stratified according to gender and tinnitus severity. Patient and researcher will be blinded to the patient's allocation. Patients will undergo six sessions of sequential dual-site HD-tDCS of the left temporal area and the right dorsolateral prefrontal cortex. Evaluations will take place at baseline, immediately following treatment, and at three and six months after the start of the therapy. The primary outcome measure is the change in Tinnitus Functional Index (TFI) score. Secondary outcome measures include audiological measurements, cortical auditory evoked potentials, the Repeatable Battery for the Assessment of Neuropsychological Status adjusted for hearing-impaired individuals (RBANS-H), and supplementary questionnaires probing tinnitus severity and additional symptoms. By use of a linear regression model, the effects of HD-tDCS compared to sham stimulation will be assessed., Discussion: The objective of this study is to evaluate whether HD-tDCS can reduce the impact of tinnitus on daily life in chronic tinnitus patients. To date, published trials on the effects of HD-tDCS on tinnitus suffer from a lack of standardization and few randomized controlled trials exist. The proposed study will be the first adequately powered trial to investigate the effects of sequential dual-site HD-tDCS on tinnitus severity., Trial Registration: ClinicalTrials.gov, NCT03754127 . Registered on 22 November 2018.