Low Evidence for Tinnitus Risk Factors: A Systematic Review and Meta-analysis.

AIMS/HYPOTHESIS: Identifying risk factors for tinnitus could facilitate not only the recommendations for prevention measures, but also identifying potential pathways for new interventions. This study reports the first comprehensive systematic review of analytical observational studies able to provide information about causality (i.e., case-control and cohort designs). METHODS: A literature search of four electronic databases identified epidemiological studies published on tinnitus and different exposures. Independent raters screened all studies, extracted data, and evaluated study quality using the Newcastle-Ottawa Scale. Reported relative risks (RR), hazard ratios (HR), odds ratios (OR), and prevalence ratios (PR) with 95% confidence intervals (CI) were used to compute crude estimates of RR for tinnitus risk factors. RESULTS: From 2389 records identified, a total of 374 articles were read as full text (24 reviews, 301 cross-sectional studies, 42 cohort studies, and 7 case-control studies). However, from 49 case-control and cohort studies, only 25 adequately reported risk ratios. Using the findings from these studies, positive causal associations were found for various hearing-related factors (i.e., unspecified hearing loss, sensorineural hearing loss, occupational noise exposure, ototoxic platinum therapy, and otitis media). Evidence was also found for a number of non-otological risk factors including temporo-mandibular joint disorder, depression, chronic obstructive pulmonary disease, and hyperlipidemia. Negative associations indicating preventative effects were found for diabetes and high alcohol consumption. No associations were found for low alcohol consumption, body mass index, head injury, heart failure, hypertension, leisure noise exposure, migraine, rheumatoid arthritis, sex, smoking, stroke, and whiplash. However, with the exception of unspecified hearing loss, these findings resulted from pooling no more than 4 studies, illustrating that the vast majority of the associations still remain inconclusive. CONCLUSIONS: These systematic review and meta-analysis confirm a number of otological and non-otological risk factors for tinnitus. By highlighting major gaps in knowledge, our synthesis can help provide direction for future research that will shed light on the pathophysiology, improve management strategies, and inform more effective preventions.

An Albanian translation of a questionnaire for self-reported tinnitus assessment.

OBJECTIVE: To our knowledge, there is no published study investigating the characteristics of people experiencing tinnitus in Albania. Such a study would be important, providing the basis for further research in this region and contributing to a wider understanding of tinnitus heterogeneity across different geographic locations. The main objective of this study was to develop an Albanian translation of a standardised questionnaire for tinnitus research, namely the European School for Interdisciplinary Tinnitus Research-Screening Questionnaire (ESIT-SQ). A secondary objective was to assess its applicability and usefulness by conducting an exploratory survey on a small sample of the Albanian tinnitus population. DESIGN AND STUDY SAMPLE: Three translators were recruited to create the Albanian ESIT-SQ translation following good practice guidelines. Using this questionnaire, data from 107 patients attending otolaryngology clinics in Albania were collected. RESULTS: Participants reporting various degrees of tinnitus symptom severity had distinct phenotypic characteristics. Application of a random forest approach on this preliminary dataset showed that self-reported hearing difficulty, and tinnitus duration, pitch and temporal manifestation were important variables for predicting tinnitus symptom severity. CONCLUSIONS: Our study provided an Albanian translation of the ESIT-SQ and demonstrated that it is a useful tool for tinnitus profiling and subgrouping.

Corrigendum: Multidisciplinary Tinnitus Research: Challenges and Future Directions From the Perspective of Early Stage Researchers.

[This corrects the article DOI: 10.3389/fnagi.2021.647285.].

Modifiable lifestyle-related risk factors for tinnitus in the general population: An overview of smoking, alcohol, body mass index and caffeine intake.

INTRODUCTION: Tinnitus is a symptom and not a disease in its own right. A number of medical conditions are known to increase the risk of developing tinnitus. Most known risk factors are otological or neurological, but general health and lifestyle can also precipitate the condition. Understanding these modifiable risk factors can help to identify vulnerable groups and can inform preventive actions to reduce likelihood of developing tinnitus. Smoking, alcohol consumption, body mass index (BMI) and caffeine intake are all lifestyle risk factors hypothesized to be related to tinnitus. Nonetheless, research findings in support of those relationships are somewhat mixed. METHODS: A systematic review was conducted to identify all relevant studies on the specific risk factors. Findings were summarized using a narrative synthesis and meta-analysis, where possible. RESULTS: Overall 384 studies were included, mostly using cross-sectional designs. Findings indicated significantly increased risk of tinnitus among current (based on 26 studies) and ever smokers (based on 16 studies) and among obese people (based on seven studies), but no effect of alcohol consumption (based on 11 studies). With respect to caffeine intake or coffee drinking, only three studies examined this risk factor and so we were unable to draw conclusions. CONCLUSION: Our results contribute to quantifying the relationship between tinnitus and specific lifestyle-related risk factors, and we highlight some of the gaps and inconsistencies across published studies.

The spatial percept of tinnitus is associated with hearing asymmetry: Subgroup comparisons.

The spatial percept of tinnitus is hypothesized as an important variable for tinnitus subtyping. Hearing asymmetry often associates with tinnitus laterality, but not always. One of the methodological limitations for cross-study comparisons is how the variables for hearing asymmetry and tinnitus spatial perception are defined. In this study, data from two independent datasets were combined (n=833 adults, age ranging from 20 to 91 years, 404 males, 429 females) to investigate characteristics of subgroups with different tinnitus spatial perception focusing on hearing asymmetry. Three principle findings emerged. First, a hearing asymmetry variable emphasizing the maximum interaural difference most strongly discriminated unilateral from bilateral tinnitus. Merging lateralized bilateral tinnitus (perceived in both ears but worse in one side) with unilateral tinnitus weakened this relationship. Second, there was an association between unilateral tinnitus and ipsilateral asymmetric hearing. Third, unilateral and bilateral tinnitus were phenotypically distinct, with unilateral tinnitus being characterized by older age, asymmetric hearing, more often wearing one hearing aid, older age at tinnitus onset, shorter tinnitus duration, and higher percentage of time being annoyed by tinnitus. We recommend that careful consideration is given to the definitions of hearing asymmetry and tinnitus spatial perception in order to improve the comparability of findings across studies.

Multidisciplinary Tinnitus Research: Challenges and Future Directions From the Perspective of Early Stage Researchers.

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.

Doctoral Studies as part of an Innovative Training Network (ITN): Early Stage Researcher (ESR) experiences.

Background: The Marie-Sklodowska-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.

A Review and a Framework of Variables for Defining and Characterizing Tinnitus Subphenotypes.

Tinnitus patients can present with various characteristics, such as those related to the tinnitus perception, symptom severity, and pattern of comorbidities. It is speculated that this phenotypic heterogeneity is associated with differences in the underlying pathophysiology and personal reaction to the condition. However, there is as yet no established protocol for tinnitus profiling or subtyping, hindering progress in treatment development. This review summarizes data on variables that have been used in studies investigating phenotypic differences in subgroups of tinnitus, including variables used to both define and compare subgroups. A PubMed search led to the identification of 64 eligible articles. In most studies, variables for subgrouping were chosen by the researchers (hypothesis-driven approach). Other approaches included application of unsupervised machine-learning techniques for the definition of subgroups (data-driven), and subgroup definition based on the response to a tinnitus treatment (treatment response). A framework of 94 variable concepts was created to summarize variables used across all studies. Frequency statistics for the use of each variable concept are presented, demonstrating those most and least commonly assessed. This review highlights the high dimensionality of tinnitus heterogeneity. The framework of variables can contribute to the design of future studies, helping to decide on tinnitus assessment and subgrouping.

Impact of Temporomandibular Joint Complaints on Tinnitus-Related Distress.

There is increasing evidence of associations between the presence of temporomandibular joint (TMJ) disorders and tinnitus. It has been recently proposed that tinnitus patients with TMJ complaints could constitute a subtype, meaning a subgroup of tinnitus patients responsive to specific treatments. Tinnitus patients with TMJ complaints are often young women with somatosensory features of their tinnitus. Here, we investigate the socio-economic factors, phenotypic characteristics and psychological variables of tinnitus subjects from the Swedish Tinnitus Outreach Project, with (n = 486) or without (n = 1,996) TMJ complaints. The prevalence of TMJ complaints was greater in tinnitus subjects with severe tinnitus (36%) when compared to those with any tinnitus (19%), strongly indicating the contribution of TMJ problems to the severity of tinnitus. Comparing subgroups with or without TMJ complaints in the whole sample, differences were found regarding a large number of socioeconomic, phenotypic, and psychological characteristics. Subjects with TMJ complaints were more often women, more often reported stress as the cause of tinnitus, were more severely affected by tinnitus, scored worse in measures of psychological well-being and life quality, and were more often affected by problems tolerating sounds, headache, vertigo/dizziness, and neck pain. In addition, they more often reported pulsating and tonal tinnitus, somatic modulation of tinnitus, and aggravation of tinnitus by loud sounds and stress. When focusing the analysis in subjects with tinnitus as a big problem using the Tinnitus Functional Index cut-off ≥ 48, or with severe tinnitus according to the Tinnitus Handicap Inventory cut-off ≥ 58, the impact of somatosensory modulations and stress on tinnitus were greater in subjects with TMJ complaints in comparison to those without. In light of these results, we hypothesize that stress could contribute to the co-occurrence of TMJ problems and tinnitus and also to the development of severe tinnitus. Our study supports the need of involving dental care and stress management in the holistic treatment of patients with severe tinnitus.

Standardised profiling for tinnitus research: The European School for Interdisciplinary Tinnitus Research Screening Questionnaire (ESIT-SQ).

BACKGROUND: The heterogeneity of tinnitus is substantial. Its numerous pathophysiological mechanisms and clinical manifestations have hampered fundamental and treatment research significantly. A decade ago, the Tinnitus Research Initiative introduced the Tinnitus Sample Case History Questionnaire, a case history instrument for standardised collection of information about the characteristics of the tinnitus patient. Since then, a number of studies have been published which characterise individuals and groups using data collected with this questionnaire. However, its use has been restricted to a clinical setting and to the evaluation of people with tinnitus only. In addition, it is limited in the ability to capture relevant comorbidities and evaluate their temporal relationship with tinnitus. METHOD: Here we present a new case history instrument which is comprehensive in scope and can be answered by people with and without tinnitus alike. This 'European School for Interdisciplinary Tinnitus Research Screening Questionnaire' (ESIT-SQ) was developed with specific attention to questions about potential risk factors for tinnitus (including demographics, lifestyle, general medical and otological histories), and tinnitus characteristics (including perceptual characteristics, modulating factors, and associations with co-existing conditions). It was first developed in English, then translated into Dutch, German, Italian, Polish, Spanish, and Swedish, thus having broad applicability and supporting international collaboration. CONCLUSIONS: With respect to better understanding tinnitus profiles, we anticipate the ESIT-SQ to be a starting point for comprehensive multi-variate analyses of tinnitus. Data collected with the ESIT-SQ can allow establishment of patterns that distinguish tinnitus from non-tinnitus, and definition of common sets of tinnitus characteristics which might be indicated by the presence of otological or comorbid systemic diseases for which tinnitus is a known symptom.