After four years of the COST TINNET Action we're presenting the final report about the TINNET objectives:
The TINNET working group 1 "clinical working group" of the TINNET action concentrated on the objective “Clinical and audiological assessment of tinnitus patients according to common standards”.
1. The leaders of the group were Prof. Rilana Cima (Netherlands) and Dr. Haula Haider (Portugal).
The group performed two important steps towards reaching the goals of the objective: First, they systematically analyzed the current situation in the European countries. Second, the group developed harmonized European guidelines for the assessment and treatment of tinnitus.
1) A European survey among experts in the field was carried out to review the existing guidelines systematically and assess the current state of the art with respect to assessment and treatment of tinnitus.
The roadmap of the working group was published 2016 in ENT & Audiology News:Cima R, Haider H. Clinical WG1. Establishing a standard for tinnitus: patient assessment and characterisation, ENT & Audiology News, 2016; 24 (6):p.71-100.
The results of the systematic review on the currently available tinnitus guidelines is published in Frontiers in Psychology. Fuller, T. E., Haider, H. F., Kikidis, D., Lapira, A., Mazurek, B., Norena, A., ... & Brueggemann, P. G. (2017). Different teams, same conclusions? A systematic review of existing clinical guidelines for the assessment and treatment of tinnitus in adults. Frontiers in psychology, 8, 206.
https://www.frontiersin.org/articles/10.3389/fpsyg.2017.00206/full
2) Using a Delphi consensus methodology, working group 1 achieved to develop a harmonized and adaptive clinical European guideline.The "Multidisciplinary European Guideline for Tinnitus: Diagnostics, Assessment and Treatment" have been presented to the scientific community at the TRI/TINNET international tinnitus conference in Regensburg in March 2018. The manuscript is currently prepared for peer-reviewed publication.
The guidelines were presented in session III of the TRI/TINNET conference. Link to the scientific program of the conference:
http://2018.tri-conf.org/images/tri-conference/Final-Scientific-Program.pdf
The TINNET working group 2, "database working group" of the TINNET action concentrated on objective 2, "Establishment and Data management in a central database and identification of subtype candidates". The leaders of the group were Prof. Berthold Langguth (Germany) and Prof. Michael Landgrebe (Germany).
There have been two main goals for the database working group:First of all, a database had to be implemented that can fulfill the needs for an international database used by several researcher groups simultaneously and data collected. Second, the data needed to be analyzed in order to identify meaning patient subgroups.
The goals and the working plan of the database working group was described and published here: Langguth B., Database WG2. The Tinnitus Patient Database in the TINNET Project, ENT & Audiology News, 2016; 24 (6):p.71-100. https://www.entandaudiologynews.com/features/audiology-features/post/database-wg2-the-tinnitus-patient-database-in-the-tinnet-cost-action-bm1306
1) The first goal of the working group was achieved within the first year of the TINNET action and the data could be collected during the rest of the project period. The URL of the database is https://www.tinnitus-database.de/welcome
At the current state (April 2018) there are data sets from 5'125 tinnitus patients from 12 different centres in the database.
2) For the second goal, a large-scale analysis of the dataset was calculated.Latent class analysis was used to identify patient subgroups with distinct hearing profiles. The results were published 2017: Langguth, B., Landgrebe, M., Schlee, W., Schecklmann, M., Vielsmeier, V., Steffens, T., Staudinger, S., Frick, H., Frick, U. (2017). Different Patterns of hearing loss among Tinnitus Patients: a latent class analysis of a large sample. Frontiers in Neurology, 8. https://www.frontiersin.org/articles/10.3389/fneur.2017.00046/full
In cooperation with the largest online patient forum for tinnitus (www.tinnitustalk.com) the working group compared the group of patients seeking help in the internet or with a smartphone app, compared to patients seeking help in a University clinic. The differences between these patient groups are published here: Probst, T., Pryss, R. C., Langguth, B., Spiliopoulou, M., Landgrebe, M., Vesala, M., Harrison, S., Schobel, J., Reichert, M., Stach, M., Schlee, W.(2017). Outpatient Tinnitus Clinic, Self-Help Web Platform, or Mobile Application to Recruit Tinnitus Study Samples? Frontiers in Aging Neuroscience, 9.
https://www.frontiersin.org/articles/10.3389/fnagi.2017.00113/full
The TINNET working group 3 "neuroimaging working group" of the TINNET action concentrated on objective 3, “Developing standards for neuroimaging studies and probing the neurobiological entity of the defined subtypes by large-scale analyses of neuroimaging data”. The leaders of the group were Prof. Pim van Dijk (Netherlands) and Prof. Sven Vanneste (Belgium/US).
The most frequently used neuroimaging methods in tinnitus research are Electroencephalography (EEG), Magnetoencephalography (MEG) and Magnetic Resonance Imaging (MRI). The group managed to develop standardized guidelines for all these measurement techniques.
The project goals and how the group’s aims to achieve them was published 2016 in ENT & Audiology news: Van Dijk P, Vanneste S., Neuroimaging WG3. Neuroimaging as a window on the heterogeneity of tinnitus, ENT & Audiology News, 2016; 24 (6):p.71-100. https://www.entandaudiologynews.com/features/audiology-features/post/neuroimaging-wg3-neuroimaging-as-a-window-on-the-heterogeneity-of-tinnitus
The standardized guidelines for EEG and MEG recordings have been finalized already in 2016 and are published on the TINNET webpage under: http://www.tinnet.tinnitusresearch.net/images/Standardisation_Report_V5.pdf. The guidelines contain general and specific topics for EEG and MEG research are discussed and recommendations are given. Literature suggestions for further reading is also included. Additionally, a checklist has been compiled with decisions and considerations that should be made before the start of the study. The authors of these guidelines are Peyman Adjamian, Winfried Schlee, Elisabeth Wallhäuser-Franke, Martin Meyer, Eugen Diesch and the Neuroimaging working group.
The standardized guidelines for MRI studies on tinnitus have been developed by the group using a Delphi consensus methodology.The work was finished early 2018 and presented at the TRI/TINNET conference in March 2018 in Regensburg on poster no. 304: "Consensus on MRI studies in tinnitus: a TINNET Delphi Study" by Peyman Adjamian, Deborah Hall, Emile de Kleine, Audrey Maudoux, Paolo Toffanin and the TINNET MRI study group.
Resting state recordings are used across all neuroimaging methods in tinnitus research.During the resting state recordings, patients are usually asked to “do nothing” and not to deliberately engage in thoughts about their tinnitus. The thoughts of the participants during the experiment are certainly not under the control of the researcher – but they can have an impact on the brain recordings. The TINNET neuroimaging group therefore decided to design a “TINNET resting-state questionnaire” to assess the thoughts of the tinnitus patients during the recordings: http://www.tinnet.tinnitusresearch.net/images/TRSQ_ver1.pdf
A large number of publications has been published by the group which are listed in the "Action publications" of this report.
The TINNET working group 4 "genetics working group" of the TINNET action concentrated on objective 4, “Identifying the involvement of genetic factors in the pathogenesis of the different subtypes of tinnitus”. The leaders of the group were Dr. Antonio Lopez-Escamez (Spain) and Prof. Christopher Cederroth (Sweden).
The scientific knowledge on the genetics of tinnitus is very limited and before the start of the TINNET project there was no coordinated research effort on the genetics of tinnitus at all. The TINNET working group 4 aimed to change this situation and kick-started several collaborative research projects to improve the scientific understanding on the genetic contributions of tinnitus and prepare a fertile ground for genetic research on tinnitus by developing standards and recommendations.
An outline of the aims and early achievements of the group was published in ENT&Audiology news: Cederroth CR, Lopez-Escamez JA., Genetics WG4. Improving diagnosis and drug development through the genetic understanding of tinnitus subtypes: a TINNET endeavour,ENT & Audiology News, 2016; 24 (6):p.71-100. https://www.entandaudiologynews.com/features/audiology-features/post/genetics-wg4-improving-diagnosis-and-drug-development-through-the-genetic-understanding-of-tinnitus-subtypes-a-tinnet-endeavour
As a first step, the group analyzed the current situation and proposed various strategies to investigate the genetic underpinnings of tinnitus. This work was already published in 2016: Lopez-Escapes, J. A., Bibas, T., Cima, R. F., ... & Cederroth, C. R. (2016). Genetics of tinnitus: an emerging area for molecular diagnosis and drug development. Frontiers in Neuroscience, 10. http://journal.frontiersin.org/article/10.3389/fnins.2016.00377/full
As a second step, members of the group investigated the glutamate aspartate transporter (GLAST) with the hypothesis that loss of GLAST function could sensitize the ear to tinnitus-inducing agents like salicylate and found strong support for it: Yu, H., Patel, K. V., Han, C., Fabella, B., Canlon, B., Someya, S., & Cederroth, C. R. (2016). GLAST Deficiency in Mice Exacerbates Gap Detection Deficits in a Model of Salicylate-Induced Tinnitus. Frontiers in Behavioral Neuroscience, 10. http://journal.frontiersin.org/article/10.3389/fnbeh.2016.00158/full
With a joint research effort of the group it was possible to analyze the genetic susceptibility of tinnitus in a large swedish cohort of 10'464 concordant and discordant twins.This analysis showed that heritability for bilateral tinnitus is higher than for unilateral tinnitus, and that heritability is higher in men than in women. The paper was published 2017 in Genetics in Medicine: Maas, I. L., Brüggemann, P., Requena, T., Bulla, J., ... & Cederroth, C. R. (2017). Genetic susceptibility to bilateral tinnitus in a Swedish twin cohort. Genetics in Medicine, 19(9), 1007.https://www.nature.com/articles/gim20174
The results of the TINNET genetic working group were also discussed in a broader perspective in an additional article.Importantly, in this article the leaders of the working group compared the heritability of tinnitus to the know heritability of other disorders: Cederroth, C. R., Kähler, A. K., Sullivan, P. F., & Lopez-Escamez, J. A. (2017). Genetics of Tinnitus: Time to Biobank Phantom Sounds. Frontiers in genetics, 8, 110. https://www.frontiersin.org/articles/10.3389/fgene.2017.00110/full
Finally, all the experiences and results of the working group have been condensed to formulate a set of recommendations on the collection and storage of genetic studies in tinnitus research, which can be the foundation for many future studies on the genetic contribution of tinnitus. The paper will appear in Ear and Hearing (manuscript number EANDH-D-17-00348R2) and was accepted in April 2018 entitled: "Recommendations on collecting and storing samples for genetic studies in hearing and tinnitus research".
The TINNET working group 5 "outcome measurement working group" of the TINNET action concentrated on objective 5, “Development of standards for outcome measurements in clinical trials and central data collection”. The leaders of the group were Prof. Deborah Hall (UK) and Dr. Alain Londero (France).
A Roadmap for the development of standards for outcome assessments in clinical trials was developed by the group and is published here: Hall DA, Haier H, Kikidis D, Mielczarek M, Mazurek B, Szczepek AJ, Cederroth CR (2015a). Toward a Global Consensus on Outcome Measures for Clinical Trials in Tinnitus: Report From the First International Meeting of the COMiT Initiative, November 14, 2014, Amsterdam, The Netherlands. Trends in Hearing 19, 1-7. https://comum.rcaap.pt/bitstream/10400.26/9078/1/Trends%20Hear%20(1).pdf
Also, a description of the goals of the working group and how the group aims to achieve the goals was published in ENT & Audiology News: Londero A., Outcome measurements WG5. Developing a Core Outcome Set of measures for tinnitus, ENT & Audiology News, 2016; 24 (6):p.71-100.https://www.entandaudiologynews.com/features/audiology-features/post/outcome-measurements-wg5-developing-a-core-outcome-set-of-measures-for-tinnitus
Since then, the group registered their work on the central database of the EU FP7 funded COMET initiative(http://www.comet-initiative.org) as well as registered and initiated two reviews of current practice
- Hall D, Szczepek A, Kennedy V, Kottapalli S, Haider H (2015b). Current reported outcome domains in studies of adults with a focus on the treatment of tinnitus. PROSPERO 2015:CRD42015017525.
- Haider H, Hall D. 2015. Dimensions of tinnitus-related complaints by patients and their significant others. PROSPERO 2015:CRD42015020629.
Both projects are finished and published:
- Hall, D. A., Szczepek, A. J., Kennedy, V., & Haider, H. (2015).Current-reported outcome domains in studies of adults with a focus on the treatment of tinnitus: protocol for a systematic review.BMJ open, 5(11), e009091. http://bmjopen.bmj.com/content/5/11/e009091.full.pdf+html
- Hall, D. A., Haider, H., Szczepek, A. J., Lau, P., Rabau, S., Jones-Diette, J., ... & Fuller, T. (2016). Systematic review of outcome domains and instruments used in clinical trials of tinnitus treatments in adults.Trials, 17(1), 1. http://trialsjournal.biomedcentral.com/articles/10.1186/s13063-016-1399-9
Furthermore, the group developed two important guidelines that are published on the TINNET website:
1) TINNET Recommendations for standardised outcomes in clinical trials of tinnitus:
http://www.tinnet.tinnitusresearch.net/images/pdf/WG5/20171126-TINNET-Outcomes-recommendations.pdf
2) TINNET Recommendations for designing and reporting trials of clinical efficiacy:
http://www.tinnet.tinnitusresearch.net/images/pdf/WG5/TINNET-WG5-recommendations_v1.1.pdf
The group published a long list of additional peer-reviewed articles, which are summarized under the publications sections of this report.
