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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.

Aims: To investigate whether temporomandibular disorders treatment can positively influence tinnitus complaints., Methods: Four online databases (PubMed, Web of Science, Scopus, and the Cochrane Library) were searched up to August 2018 for relevant studies. Two independent reviewers extracted the data and performed a risk of bias assessment., Results: A total of 11 studies were included. These studies showed an overall positive effect of the combination of splint therapy and exercise treatment on tinnitus severity and intensity (as measured on a visual analog or numeric rating scale), as well as on global perceived effect. One study specified that the treatment effect was only present in patients with severe to very severe tinnitus, while the others found an effect in the overall study group. The risk of bias in the included studies was high, mainly due to lack of statistical analyses between groups and before vs after treatment, incomplete presentation of the data, and selective reporting. Additionally, most included studies showed a lack of information concerning blinding of the subjects, therapists, and investigators. The heterogeneity of the inclusion criteria, outcome measurements, and treatments made data pooling and meta-analysis impossible., Conclusion: There is low-quality evidence for a positive effect of conservative temporomandibular disorders treatment on tinnitus complaints. The combination of splint therapy and exercise treatment is currently the best investigated treatment approach, showing a decrease in tinnitus severity and intensity. Despite the low level of evidence and the methodologic issues in the included studies, it is noteworthy that all included studies show positive treatment effects.

Background: Patients suffering from chronic, subjective tinnitus are on a quest to find a cure or any form of alleviation for their persistent complaint. Current recommended therapy forms provide psychotherapeutic interventions that are intended to train the patient how to deal with the tinnitus sound. Pharmaceutical managements are used to reduce secondary effects of the tinnitus sound such as sleep deprivation, emotional and concentration difficulties, but these treatments do not cure the tinnitus. Recent studies have shown that Tinnitus Retraining Therapy (TRT) significantly improves the quality of life for tinnitus patients. Furthermore, several studies have reported that cognitive behavioral therapy (CBT) relieves a substantial amount of distress by changing dysfunctional cognitions. However, when the tinnitus causes great interference with daily functioning, these treatment methods are not always sufficiently effective. Recent insights show that Eye Movement Desensitization Reprocessing (EMDR) is a highly effective therapy for medically unexplained symptoms such as chronic pain and phantom pain. In scientific research, tinnitus is compared to phantom limb pain. Starting from tinnitus as a phantom percept we therefore aim to demonstrate that the operating mechanisms of EMDR may also be an effective treatment method for patients with subjective tinnitus. The aim of this randomized controlled study with blind evaluator is to examine the effect of EMDR compared to CBT in chronic tinnitus patients. To our knowledge, there are no other studies that evaluate both methods simultaneously., Methods/design: A total of 166 patients with subjective, chronic, non-pulsatile tinnitus will be randomized in two treatment groups: TRT + CBT versus TRT + EMDR. The experimental group will receive the bimodal therapy TRT/EMDR and the active control group will receive the bimodal therapy TRT/CBT. Evaluations will take place at baseline before therapy, at the end of the treatment and 3 months after therapy. The score on the Tinnitus Functional Index (TFI) will be used as the primary outcome measurement. Secondary outcome measurements are the Visual Analogue Scale of Loudness (VAS), Tinnitus Questionnaire (TQ), Hospital Anxiety and Depression Scale (HADS), Hyperacusis Questionnaire (HQ), psychoacoustic measurements and event-related potentials (ERP)., Discussion: The objective is to evaluate whether the bimodal therapy TRT and EMDR can provide faster and/or more relief from the annoyance experienced in chronic tinnitus patients' daily lives compared to the bimodal therapy TRT and CBT. So far there has been no prospective, randomized controlled, clinical trial with blind evaluator that compares CBT and EMDR as a treatment for tinnitus., Trial Registration: ClinicalTrials.gov, ID: NCT03114878 . April 14, 2017.

Background: Tinnitus is a highly prevalent symptom affecting 10-15% of the adult population. It often affects patient quality of life and frequently causes distress. When subjective tinnitus can be elicited by the somatosensory system of the cervical spine or temporomandibular area it is termed somatic tinnitus. The first aim of the current study is to investigate the effect of the best evidence conservative temporomandibular disorder (TMD) treatment on tinnitus in patients with co-existence of tinnitus and TMD or oral parafunctions compared to no treatment. The second aim is to identify a subgroup of patients with tinnitus that benefits from the conservative temporomandibular joint treatment., Methods and Design: This study is a randomised controlled trial with a delayed treatment design. Patients with a TMD (TMD pain screener ≥ 3 points) or oral parafunctions (such as clenching and bruxism), who are suffering from moderate to severe subjective tinnitus (Tinnitus Functional Index (TFI) between 25 and 90 points), will be recruited from the tertiary tinnitus clinic of the University Hospital of Antwerp, Edegem, Belgium. Patients will be excluded in case of clear otological or neurological causes of the tinnitus, progressive middle ear pathology, intracranial pathology, traumatic cervical spine or temporomandibular injury in the past 6 months, severe depression as diagnosed by a psychologist, tumours, previous surgery in the orofacial area, substance abuse that may affect the outcome measures, any contra-indication for physical therapy treatment directed to the orofacial area or when they received TMD treatment in the past 2 months. After screening for eligibility, baseline data among which scores on the TFI, tinnitus questionnaire (TQ), mean tinnitus loudness as measured with visual analogue scale (VAS), TMD pain screener, and a set of temporomandibular joint tests will be collected. Patients will be randomised in an early-start group and in a delayed-start group of therapy by 9 weeks. Patients will receive conservative TMD treatment with a maximum of 18 sessions within 9 weeks. At baseline (week 0), at the start of therapy (weeks 0 or 9), 9 weeks after therapy (weeks 9 or 18), and at follow-up (weeks 18 or 27) data from the TFI, TQ, VAS mean tinnitus loudness and the TMD pain screener will be collected., Discussion: Herein, we aim to improve the quality of care for patients with tinnitus attributed to TMD or oral parafunctions. By evaluating the effect of state-of-the-art TMD treatment on tinnitus complaints, we can investigate the usefulness of TMD treatment in patients with somatic tinnitus., Trial Registration: 3 July 2017, version 1 of the protocol, ClinicalTrials.gov NCT03209297 .

Background: Contradictory results have been reported for transcranial direct current stimulation (tDCS) as treatment for tinnitus. The recently developed high-definition tDCS (HD tDCS) uses smaller electrodes to limit the excitation to the desired brain areas., Objective: The current study consisted of a retrospective part and a prospective part, aiming to compare 2 tDCS electrode placements and to explore effects of HD tDCS by matched pairs analyses., Methods: Two groups of 39 patients received tDCS of the dorsolateral prefrontal cortex (DLPFC) or tDCS of the right supraorbital-left temporal area (RSO-LTA). Therapeutic effects were assessed with the tinnitus functional index (TFI), a visual analogue scale (VAS) for tinnitus loudness, and the hyperacusis questionnaire (HQ) filled out at 3 visits: pretherapy, posttherapy, and follow-up. With a new group of patients and in a similar way, the effects of HD tDCS of the right DLPFC were assessed, with the tinnitus questionnaire (TQ) and the hospital anxiety and depression scale (HADS) added., Results: TFI total scores improved significantly after both tDCS and HD tDCS (DLPFC: P < .01; RSO-LTA: P < .01; HD tDCS: P = .05). In 32% of the patients, we observed a clinically significant improvement in TFI. The 2 tDCS groups and the HD tDCS group showed no differences on the evolution of outcomes over time (TFI: P = .16; HQ: P = .85; VAS: P = .20)., Conclusions: TDCS and HD tDCS resulted in a clinically significant improvement in TFI in 32% of the patients, with the 3 stimulation positions having similar results. Future research should focus on long-term effects of electrical stimulation.

Background: Transcatheter aortic valve replacement (TAVR) is standard therapy for patients with severe aortic stenosis who are at high surgical risk. However, national data regarding procedural characteristics and clinical outcomes over time are limited., Objectives: The aim of this study was to assess nationwide performance trends and clinical outcomes of TAVR during a 6-year period., Methods: TAVRs performed in 48 centers across France between January 2013 and December 2015 were prospectively included in the FRANCE TAVI (French Transcatheter Aortic Valve Implantation) registry. Findings were further compared with those reported from the FRANCE 2 (French Aortic National CoreValve and Edwards 2) registry, which captured all TAVRs performed from January 2010 to January 2012 across 34 centers., Results: A total of 12,804 patients from FRANCE TAVI and 4,165 patients from FRANCE 2 were included in this analysis. The median age of patients was 84.6 years, and 49.7% were men. FRANCE TAVI participants were older but at lower surgical risk (median logistic European System for Cardiac Operative Risk Evaluation [EuroSCORE]: 15.0% vs. 18.4%; p < 0.001). More than 80% of patients in FRANCE TAVI underwent transfemoral TAVR. Transesophageal echocardiography guidance decreased from 60.7% to 32.3% of cases, whereas more recent procedures were increasingly performed in hybrid operating rooms (15.8% vs. 35.7%). Rates of Valve Academic Research Consortium-defined device success increased from 95.3% in FRANCE 2 to 96.8% in FRANCE TAVI (p < 0.001). In-hospital and 30-day mortality rates were 4.4% and 5.4%, respectively, in FRANCE TAVI compared with 8.2% and 10.1%, respectively, in FRANCE 2 (p < 0.001 for both). Stroke and potentially life-threatening complications, such as annulus rupture or aortic dissection, remained stable over time, whereas rates of cardiac tamponade and pacemaker implantation significantly increased., Conclusions: The FRANCE TAVI registry provided reassuring data regarding trends in TAVR performance in an all-comers population on a national scale. Nonetheless, given that TAVR indications are likely to expand to patients at lower surgical risk, concerns remain regarding potentially life-threatening complications and pacemaker implantation. (Registry of Aortic Valve Bioprostheses Established by Catheter [FRANCE TAVI]; NCT01777828)., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Few clinical trials have focused on populations with a history of distant myocardial infarction (MI). The PEGASUS trial assessed the impact of dual antiplatelet therapy in such patients, selected by enrichment criteria of high cardiovascular risk. Whether the PEGASUS population reflects the risk of a broader post-MI population is questionable. We analyzed whether 4-year mortality of a routine-practice population would differ according to the inclusion and exclusion criteria used in PEGASUS., Methods: FAST-MI is a nationwide French registry recruiting acute MI patients in November 2005; 2490 patients alive and without recurrent MI at one year were classified into three groups: Group 1 ("PEGASUS-like" population; n=1395; 56%), Group 2 (population having ≥1 exclusion criterion for the trial; n=677; 27%), and group 3 (population meeting neither the PEGASUS inclusion nor exclusion criteria; n=418, 17%)., Results: Group 1 patients were older than Group 3 patients, with higher GRACE scores, more comorbidity, and less STEMI, but were younger than the PEGASUS trial population. Enrichment criteria successfully defined a population at higher risk: 4-year survival 83% in Group 1, 97% in Group 2, and 68% in Group 3 (P<0.001). Among risk-enrichment criteria, age alone was highly discriminant: in PEGASUS-like patients, survival was 78% in those ≥65 versus 94% in those <65years., Conclusions: Enrichment criteria used in PEGAGUS succeed in defining a population at increased risk in patients with prior MI, age being the most discriminant factor. The trial population, however, was notably younger and more masculine than the corresponding real-life population in France. Clinicaltrials.govnumber:NCT00673036., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: The aim of this study was to analyse the factors that influenced speech recognition scores in quiet conditions and speech reception threshold levels (SRT) in fixed noise conditions, after cochlear implant (CI) surgery in adults with postlinguistic deafness., Study Design: Combined retrospective and prospective study in a tertiary referral centre., Methods: We included 66 patients that received implants between 2002 and 2013. We retrospectively collected speech recognition scores and 14 demographic, audiological, and technical factors, including gender, age at implantation, aetiology, hearing loss progression, preoperative Pure Tone Average (PTA), hearing loss onset age and duration, duration and use of hearing aids (HAs); implantation in the best or worst ear; implantation on the right or left side; use of HA after implantation; and the duration and type of CI. We prospectively tested a subgroup of 21 patients for SRT in fixed noise., Results: The hearing loss duration significantly affected speech recognition scores in quiet conditions (H (4) = 10.567, p =0.032) and SRTs in fixed noise conditions (rs = 0.466, p = 0.033). The PTA of the better ear significantly affected only the SRT in fixed noise conditions (rs = 0.57 1, p = 0.007)., Conclusion: The duration of hearing loss and the PTA of the best ear had significant effects on the outcomes of speech recognition and SRT in quiet and fixed noise conditions, respectively. These findings are important for counselling CI candidates. Further studies in larger study populations are warranted.

The aim of this article is to compare two different sets of optimal conditions for twin-screw extraction of xylans and define their influence on the purification steps, combining ultrafiltration and industrial chromatography. Two xylan extracts were obtained by twin-screw extrusion of straw and bran. Condition 1 used a high straw/bran ratio (equal to 6) and high sodium hydroxide content, and condition 2 used a lower straw/bran ratio (equal to 2) and low sodium hydroxide content. Arabinoxylan extraction yields are slightly higher for conditions with low straw content (5.1% versus 4.4%). Nevertheless, these recovery yields remain between 9% and 10%. Ultrafiltration is as efficient as evaporation for polysaccharide concentration, with lower energy consumption, but also demineralizes the solution. The combination of ultrafiltration and chromatography gives partial purification of the extract with a final arabinoxylan purity ranging from 16% to 26%. This is slightly higher than by direct precipitation, but limited because all the large molecules such as proteins and lignins were retained by ultrafiltration., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Percutaneous coronary intervention (PCI) as a treatment of coronary artery disease can be a simple, rapid procedure with a clear benefit for the patient, but it could also become a complex procedure with fatal consequences. These complications depend on the lesion itself, material used and also on operating staff. In this case we report a coronary artery dissection of the circumflex (CX) artery caused by inflation of an oversized balloon. We discuss here the management and evolution of this complication., (2014 BMJ Publishing Group Ltd.)

Aims: Proof-of-concept evidence suggests that mechanical ischaemic post-conditioning (PostC) reduces infarct size when applied immediately after culprit coronary artery re-opening in ST-elevation myocardial infarction (STEMI) patients with thrombolysis in myocardial infarction 0-1 (TIMI 0-1) flow grade at admission. Whether PostC might also be protective in patients with a TIMI 2-3 flow grade on admission (corresponding to a delayed application of the post-conditioning algorithm) remains undetermined., Methods and Results: In this multi-centre, randomized, single-blinded, controlled study, STEMI patients with a 2-3 TIMI coronary flow grade at admission underwent direct stenting of the culprit lesion, followed (PostC group) or not (control group) by four cycles of (1 min inflation/1 min deflation) of the angioplasty balloon to trigger post-conditioning. Infarct size was assessed both by cardiac magnetic resonance at Day 5 (primary endpoint) and cardiac enzymes release (secondary endpoint). Ninety-nine patients were prospectively enrolled. Baseline characteristics were comparable between control and PostC groups. Despite comparable size of area at risk (AAR) (38 ± 12 vs. 38 ± 13% of the LV circumference, respectively, P = 0.89) and similar time from onset to intervention (249 ± 148 vs. 263 ± 209 min, respectively, P = 0.93) in the two groups, PostC did not significantly reduce cardiac magnetic resonance infarct size (23 ± 17 and 21 ± 18 g in the treated vs. control group, respectively, P = 0.64). Similar results were found when using creatine kinase and troponin I release, even after adjustment for the size of the AAR., Conclusion: This study shows that infarct size reduction by mechanical ischaemic PostC is lost when applied to patients with a TIMI 2-3 flow grade at admission. This indicates that the timing of the protective intervention with respect to the onset of reperfusion is a key factor for preventing lethal reperfusion injury in STEMI patients., Clinical Trial Number: NCT01483755., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Objective of the Study: Bivalirudin, a direct thrombin inhibitor, demonstrated an improvement in the prognosis of acute coronary syndromes by a decrease in major bleeding complications. This observational study evaluated inhospital outcome of patients with acute myocardial infarction treated by prehospital bivalirudin before primary angioplasty., Patients and Methods: We included, from June 2010 to June 2012, all patients with acute myocardial infarction receiving prehospital bivalirudin with bolus of 0.75mg/kg followed by an infusion of 1.75mg/kg per hour until the arrival in the catheterization laboratory. Bivalirudin was possibly continued after primary angioplasty., Results: We included 152 patients aged 57.6±11.6 years. A prehospital 60mg loading dose of prasugrel was given in 77% of patients. Coronary angiography with radial access (77.6%) was performed before a successful angioplasty in 97.3% of cases. The bivalirudin infusion was continued after the procedure in 81.6% of patients. Inhospital outcome showed two deaths (1.3%) and two re-infarctions (1.3%) of which one was related to the single acute stent thrombosis (0.6%). Major bleeding complications were limited irrespective of the Gusto (0.6%), Timi (0.6%) or Horizons-MI (4.6%) classification. Bleeding complications rate was similar when bivalirudin was followed or not after primary angioplasty., Conclusion: The use of bivalirudin in the prehospital setting for primary angioplasty seems to be effective and safe about ischemic and bleeding complications during the inhospital outcome., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Background: The value of prehospital initiation of glycoprotein IIb/IIIa inhibitors remains a controversial issue. We sought to investigate whether in-ambulance initiation of abciximab in patients with ST-segment elevation myocardial infarction (STEMI) improves ST-segment elevation resolution (STR) after primary percutaneous coronary intervention (PCI)., Methods and Results: MISTRAL (Myocardial Infarction with ST-elevation Treated by Primary Percutaneous Intervention Facilitated by Early Reopro Administration in Alsace) is a prospective, randomized, double-blind study. Two hundred and fifty-six patients with acute STEMI were allocated to receive abciximab either in the ambulance (ambulance group, n=127) or in the catheterization laboratory (hospital group, n=129). The primary end point was complete (>70%) STR after PCI. Complete STR was not significantly different between the 2 groups (before PCI, 21.6% versus 15.5%, P=0.28; after PCI, 70.3% versus 65.8%, P=0.49). Thrombolysis In Myocardial Infarction (TIMI) 2 to 3 flow rates before PCI tended to be higher in the ambulance group (46.8% versus 35%, P=0.08) but not after PCI (70.3% versus 65.8%, P=0.49). Slow flow tended to be lower (5.6% versus 13.4%, P=0.07), and distal embolization occurred significantly less often in the ambulance group (8.1% versus 21.1%, P=0.008). One- and 6-month major adverse cardiac event rates were low and similar in both groups., Conclusions: Early ambulance administration of abciximab in STEMI did not improve either STR or TIMI flow rate after PCI. However, it tended to improve TIMI flow pre-PCI and decreased distal embolization during procedure. Larger studies are needed to confirm these results.

First devoted to research and its applications in chemistry and microbiology, the institute was created in 1894. Its founder, Georges Jacquemin was the son of the professor of chemistry of the school of pharmacy of Nancy. He was first a student in pharmacy but he did not finish the last examinations... Three years ago, he created or participated to the creation of the Institut La Claire, near Morteau in the Jura, with same activities. The Institut Jacquemin settled in special houses and laboratories where were studied and prepared numerous chemical and biological products, particularly selected yeasts used in wine-making, brewery, cider-making, also phytosanitary chemical products and, in 1902, Ferment Jacquemin which was a depurative and was considered as a drug. Georges Jacquemin died in 1925 but his institute remainded in activity with his coworkers until 1967 and closed totally only in 1976.

Aims of the Study: The study evaluated in-hospital and long-term outcome of patients less than 50 years old with myocardial infarction within 12 hours after symptom onset treated by coronary angioplasty., Patients and Method: This is a retrospective study with survival analysis by Kaplan-Meier method in patients included from December 2003 to February 2008., Results: We included 93 patients aged 42,8+/-5,2 years old with smoking estimated at 27,7+/-12,7 pack-years. Thirty-one patients (33,3%) were dyslipidemic and 36 patients had family history of coronary artery disease. Thirty patients (32,3%) had an anterior myocardial infarction and four patients (4.4%) had Killip greater than 2. Coronary angioplasty was performed within 4.5+/-3.0 hours after symptom onset with TIMI 3 final flow in the culprit vessel in 96.8%. One patient died from cardiogenic shock. With a follow-up of 85 patients during 20.0+/-15.6 months, the survival without death was 98.2% and survival without major cardiac complication was 87.9% at 24 months. Seventy-two patients (85.7%) were taking a betablocker, 81 patients (96.4%) aspirin, 75 patients (89.3%) a statin and 64 patients (76.2%) an angiotensin-converting inhibitor. Only 50 patients (58.8%) were nonsmokers., Conclusion: Thus, young smokers with acute MI treated by coronary angioplasty have a good prognosis during in-hospital stay and long-term outcome. Secondary medical treatment prevention is well followed but there is a low rate of smoking cessation., (Copyright 2010. Published by Elsevier SAS.)

Objectives: We investigated whether maintenance therapy with clopidogrel 150 mg/day produces greater platelet inhibition than the standard 75-mg/day dose and whether the higher maintenance dose increases platelet inhibition in low responders to clopidogrel 75 mg/day., Background: Patients show interindividual variability in their platelet response to clopidogrel. Low responders could potentially obtain greater clinical benefit from greater doses of clopidogrel., Methods: One hundred fifty-three elective percutaneous coronary intervention patients were randomized to clopidogrel 150 mg/day (n = 58) or 75 mg/day (n = 95) for 4 weeks, with vasodilator-stimulated phosphoprotein assay-guided switching to clopidogrel 150 mg/day after 2 weeks in low responders (platelet reactivity index >or=69%). All patients received aspirin 75 mg/day., Results: After 2 weeks, clopidogrel 150 mg/day produced a significantly lower platelet reactivity index than clopidogrel 75 mg/day (43.9 +/- 17.3% vs. 58.6 +/- 17.7%; p < 0.0001). The proportion of low responders was significantly lower in patients randomized to clopidogrel 150 mg/day than in those randomized to clopidogrel 75 mg/day (8.6% vs. 33.7%; p = 0.0004). In the clopidogrel 75 mg/day group, 64.5% (20 of 31) of low responders became responders after switching to clopidogrel 150 mg/day for 2 weeks. No major bleeds occurred during the study; the incidence of minor bleeds was similar in each treatment group., Conclusions: In elective percutaneous coronary intervention patients, a 150-mg/day clopidogrel maintenance dose produces greater inhibition of platelet function than clopidogrel 75 mg/day. In low responders to clopidogrel 75 mg/day, switching to clopidogrel 150 mg/day overcomes low responsiveness in a majority of patients. These findings warrant further clinical evaluation. (VASP-02; EudraCT number: 2004-005230-40).

Among 10% of all patients presenting with non ST elevation acute coronary syndromes (ACS), coronary angiography do not show non lesions at all (50%) or mild atheromatous stenosis (50%). ACS without angiographic stenosis are more prevalent in female sex and young patients but can be seen in older ones and in men. Pathogenic mechanisms include acute evolution of vulnerable non-significant plaques and endothelial dysfunction. In hospital and mean term prognosis is not as benign as expected. Six months deaths and myocardial infarction incidence is around 6%. Numerous rehospitalizations due to ischemic recurrences are also very often seen. Therefore, such surprising coronary angiograms do not preclude a fair follow-up. These patients need a careful therapeutic strategy.

This study evaluated the hospital outcome of octogenarian patients treated by primary angioplasty for acute myocardial infarction less than 12 hours. The long-term mortality and social outcome were evaluated, social outcome was based on IADL and IADL-E scales corresponding to physical autonomy and level of dependence. We included from 1999 to 2005 47 old patients of 83.5+/-3.2 years. The reperfusion of the obstructed coronary artery was obtained in 45 patients (95.7%) with TIMI 3 flow. Hospital mortality was 25.5% and 4.2% without hemodynamic complication. A multivariate analysis identified a Killip score>1 as predictive factor of hospital mortality (OR=8.9 and p=0.05). The long-term survival without death with a follow-up of 26.3+/-18.3 months was 82.2% at 24 months and 70.6% at 48 months according to the Kaplan-Meier method. In an multivariate analysis, hospitalization exit without aspirine was associated with a higher long term mortality (OR=34.8 and p=0.04). According to the evolution of scores of IADL and IADL-E scales, patients had an excellent autonomy and good capacities before the infarction and they kept them on the long term. Thus octogenarians with acute myocardial infarction treated by primary angioplasty have a high in hospital and long term mortality but the survivors preserve an excellent daily autonomy.

Acute myocardial infarction is a rare complication of dobutamine stress echocardiography (DSE). We report the case of a 60-year-old man with moderate apical sequela of a myocardial infarction (MI) which had an inferior MI complicated with cardiogenic shock and circulatory arrest two hours after a positive DSE in that very circulatory topography. Emergency coronarography objectivizes a dissection of the circumflex artery. The patient required a circulatory assistance device. He survived the episode and left the hospital with 50% left ventricular ejection fraction.

Objective: To evaluate the results and the feasibility of the technique of percutaneous closing of patent foramen oval (PFO) with Atrial Septal Aneurysm (ASA) among young patients having presented a cryptogenic cerebral ischemia., Patients and Methods: Eighteen patients: 14 cryptogenic stroke and 4 TIA with a broad PFO (rank III) and an important ASA (excursion higher than 15 mm) at transesophageal echocardiography (TEE). The average age is 48.2 years: man 61%, women 39%. The patients have little cardiovascular risk factor (0.83/patient) and 38% presented recurrent thromboembolic events. Percutaneous closing is carried out under general anaesthesia with TEE and Amplatzer devices implantation. A control TEE is carried out 6 months after closing., Results: No complication occurred at the time of the procedures. After 72 hours, one patient presented a major complication: one arteriovenous fistula requiring a surgery. Five patients presented a minor complication: two non complicated femoral hematoma, two atrial arrhytmias and one asymptomatic secondary displacement of the device without need for surgery. Seven-teen patients had TEE at six months: the shunt disappeared for 95% from the patients, no thrombus was found. No recurrent thromboembolic event appeared for the 18 patients (median follow-up 19.2 months)., Conclusion: The installation of a technique of percutaneous closing of the PFO+ASA is safe and effective.