Tinnitus is defined as the conscious awareness of a tonal or composite noise in the absence of a corresponding external acoustic source. This international multicentre, parallel-arm, superiority, randomised controlled trial investigated whether combination therapies are superior to single interventions in the treatment of chronic subjective tinnitus. Tinnitus patients were recruited from five clinical sites across the EU and randomly assigned using a web-based system, stratified by their hearing and distress level, to single or combination treatment of 12 weeks. Cognitive-behavioural therapy, hearing aids, app-based structured counselling, or app-based sound therapy were administered either alone or as a combination of two treatments resulting in ten treatment arms. App-based treatments were delivered without direct contact or guidance from clinicians. The primary outcome was the difference in the change from baseline to week 12 in the total score of the Tinnitus Handicap Inventory (THI) between single and combination treatments in the intention-to-treat population. All statistical analysis were performed blinded to treatment allocation. 674 patients of both sexes aged between 18 and 80 years were screened for eligibility. 461 participants (190 females) with chronic subjective tinnitus and at least mild tinnitus handicap were enroled, 230 of which were randomly assigned to single and 231 to combination treatment. Least-squares mean changes from baseline to week 12 were −11.7 for single treatment (95% confidence interval [CI], −14.4 to −9.0) and −14.9 for combination treatments (95% CI, −17.7 to −12.1), with a statistically significant group difference ( p = 0.034). Cognitive-behavioural therapy and hearing aids alone had large effect sizes, which could not be further increased by combination treatment. No serious adverse events occurred. In this trial involving patients with chronic tinnitus, all treatment arms showed improvement in THI scores from baseline to week 12. Combination treatments showed a stronger clinical effect than single treatment, however, no clear synergistic effect was observed when combining treatments. Instead, we observed a compensatory effect, where a more effective treatment offsets the clinical effects of a less effective treatment. ClinicalTrials.gov Identifier: NCT04663828.

High comorbidity rates, especially mental–physical comorbidity, constitute an increasing health care burden, with women and men being differentially affected. To gain an overview of comorbidity rates stratified by sex across a range of different conditions, this study examines comorbidity patterns within and between cardiovascular, pulmonary, skin, endocrine, digestive, urogenital, musculoskeletal, neurological diseases, and psychiatric conditions. Self-report data from the LifeGene cohort of 31,825 participants from the general Swedish population (62.5% female, 18–84 years) were analyzed. Pairwise comorbidity rates of 54 self-reported conditions in women and men and adjusted odds ratios (ORs) for their comparison were calculated. Overall, the rate of pairwise disease combinations with significant comorbidity was higher in women than men (14.36% vs. 9.40%). Among psychiatric conditions, this rate was considerably high, with 41.76% in women and 39.01% in men. The highest percentages of elevated mental–physical comorbidity in women were found for musculoskeletal diseases (21.43%), digestive diseases (20.71%), and skin diseases (13.39%); in men, for musculoskeletal diseases (14.29%), neurological diseases (11.22%), and digestive diseases (10%). Implications include the need for integrating mental and physical health care services and a shift from a disease-centered to an individualized, patient-centered focus in clinical care.

Background: Tinnitus severity is generally assessed by psychometric and audiological instruments. However, no objective measure exists to evaluate the subjective discomfort and suffering caused by this hearing phenomenon. The objective of this work was to determine the possible blood parameters for diagnostics and therapy. Methods: We measured tinnitus distress by using the Tinnitus Questionnaire (TQ) and collected tinnitus-related audiological measures, namely the hearing threshold (HT), tinnitus loudness (TL), and sensation level (SL, i.e., the tinnitus loudness/hearing threshold at a tinnitus frequency). Blood samples were taken from 200 outpatients of the Tinnitus Centre of the Charité, and 46 routine blood count parameters were examined. The possible interactions were determined by (robust) linear models. Results: Tinnitus distress and audiological measurements were largely uncorrelated but could partly be predicted by selected blood parameters. First, the erythrocyte counts predicted tinnitus distress to a small extent. Second, the levels of vitamin D3 explained about 6% of tinnitus loudness and, age-dependently, the hearing threshold variability. Last, the levels of uric acid explained about 5% of the sensation level variability. Conclusions: Tinnitus is a multidimensional phenomenon. The marginal influences of blood markers suggest the possible roles of inflammation and oxidative stress produced by psychological or somatic burdens. Clinically, a vitamin D substitution (in older patients) might have a hearing-protective effect.

Tinnitus is associated with a variety of aetiologies, phenotypes, and underlying pathophysiological mechanisms, and available treatments have limited efficacy. A combination of treatments, addressing various aspects of tinnitus, might provide a viable and superior treatment strategy. In this international multicentre, parallel-arm, superiority, randomised controlled trial, patients with chronic subjective tinnitus were recruited from five clinical sites across the EU as part of the interdisciplinary collaborative UNITI project. Patients were randomly assigned using a web-based system, stratified by their hearing and distress level, to single or combination treatment of 12 weeks. Cognitive-behavioural therapy, hearing aids, structured counselling, and sound therapy were administered either alone or as a combination of two treatments resulting in ten treatment arms. The primary outcome was the difference in the change from baseline to week 12 in the total score of the Tinnitus Handicap Inventory (THI) between single and combination treatments in the intention-to-treat population. All statistical analysis were performed blinded to treatment allocation. 674 patients of both sexes aged between 18 and 80 years were screened for eligibility. 461 participants (190 females) with chronic subjective tinnitus and at least mild tinnitus handicap were enrolled, 230 of which were randomly assigned to single and 231 to combination treatment. Least-squares mean changes from baseline to week 12 were -11.7 for single treatment (95% confidence interval [CI], -14.4 to -9.0) and -14.9 for combination treatments (95% CI, -17.7 to -12.1), with a statistically significant group difference ( p =0.034). Cognitive-behavioural therapy and hearing aids alone had large effect sizes, which could not be further increased by combination treatment. No serious adverse events occurred. In this trial involving patients with chronic tinnitus, all treatment arms showed improvement in THI scores from baseline to week 12. Combination treatments showed a stronger clinical effect than single treatment, however, no clear synergistic effect was observed when combining treatments. We observed rather a compensatory effect, where a more effective treatment offsets the clinical effects of a less effective treatment. ClinicalTrials.gov Identifier: NCT04663828 .

Background: Clinical management of tinnitus remains challenging due to unclear etiology and diverse phenotypic manifestations. To quantify its associated burden, a variety of patient-reported outcome measures (PROMs) are used. This study aims to comprehensively evaluate the content overlap of items between eight PROMs commonly used in tinnitus research. Methods: A two-stage, blinded multi-rater process was used to analyze the content of all 199 items from the International Tinnitus Inventory (ITI), Subjective Tinnitus Severity Scale (STSS), Tinnitus Functional Index (TFI), Tinnitus Handicap Inventory (THI), Tinnitus Handicap Questionnaire (THQ), Tinnitus Primary Function Questionnaire (TPFQ), Tinnitus Questionnaire (TQ), and Tinnitus Reaction Questionnaire (TRQ). The Jaccard Index was used to measure pairwise content overlap between scales. Results: The analysis revealed 83 distinct symptoms. “Concentration” was the most frequently captured symptom (in seven scales), whereas 41 symptoms (49.4%) were unique to one scale. The TQ exhibited the highest number of unique symptoms (52.5%), while the THI had the least (4%). The Jaccard Index identified very weak/weak scale overlap between the PROMs. The highest overlap was observed between TFI and THI (0.35). The TFI had the highest mean overlap (0.26), coming closest to the content measured by all other PROMs. Conclusion: The results demonstrate high heterogeneity and limited content overlap among tinnitus burden PROMs, similar to other conditions. The findings suggest that tinnitus burden is not measured as a unified construct across questionnaires, thus, researchers and clinicians should carefully consider the specific symptoms measured when selecting instruments for treatment evaluation and comparison.