The statistical analysis plan for the unification of treatments and interventions for tinnitus patients randomized clinical trial (UNITI-RCT).

BACKGROUND: Tinnitus is a leading cause of disease burden globally. Several therapeutic strategies are recommended in guidelines for the reduction of tinnitus distress; however, little is known about the potentially increased effectiveness of a combination of treatments and personalized treatments for each tinnitus patient. METHODS: Within the Unification of Treatments and Interventions for Tinnitus Patients project, a multicenter, randomized clinical trial is conducted with the aim to compare the effectiveness of single treatments and combined treatments on tinnitus distress (UNITI-RCT). Five different tinnitus centers across Europe aim to treat chronic tinnitus patients with either cognitive behavioral therapy, sound therapy, structured counseling, or hearing aids alone, or with a combination of two of these treatments, resulting in four treatment arms with single treatment and six treatment arms with combinational treatment. This statistical analysis plan describes the statistical methods to be deployed in the UNITI-RCT. DISCUSSION: The UNITI-RCT trial will provide important evidence about whether a combination of treatments is superior to a single treatment alone in the management of chronic tinnitus patients. This pre-specified statistical analysis plan details the methodology for the analysis of the UNITI trial results. TRIAL REGISTRATION: ClinicalTrials.gov NCT04663828 . The trial is ongoing. Date of registration: December 11, 2020. All patients that finished their treatment before 19 December 2022 are included in the main RCT analysis.

Unification of Treatments and Interventions for Tinnitus Patients (UNITI): a study protocol for a multi-center randomized clinical trial.

BACKGROUND: Tinnitus represents a relatively common condition in the global population accompanied by various comorbidities and severe burden in many cases. Nevertheless, there is currently no general treatment or cure, presumable due to the heterogeneity of tinnitus with its wide variety of etiologies and tinnitus phenotypes. Hence, most treatment studies merely demonstrated improvement in a subgroup of tinnitus patients. The majority of studies are characterized by small sample sizes, unstandardized treatments and assessments, or applications of interventions targeting only a single organ level. Combinatory treatment approaches, potentially targeting multiple systems as well as treatment personalization, might provide remedy and enhance treatment responses. The aim of the present study is to systematically examine established tinnitus therapies both alone and in combination in a large sample of tinnitus patients. Further, it wants to provide the basis for personalized treatment approaches by evaluating a specific decision support system developed as part of an EU-funded collaborative project (Unification of treatments and interventions for tinnitus patients; UNITI project). METHODS/STUDY DESIGN: This is a multi-center parallel-arm randomized clinical trial conducted at five different clinical sites over the EU. The effect of four different tinnitus therapy approaches (sound therapy, structured counseling, hearing aids, cognitive behavioral therapy) applied over a time period of 12 weeks as a single or rather a combinatory treatment in a total number of 500 chronic tinnitus patients will be investigated. Assessments and interventions are harmonized over the involved clinical sites. The primary outcome measure focuses on the domain tinnitus distress assessed via the Tinnitus Handicap Inventory. DISCUSSION: Results and conclusions from the current study might not only provide an essential contribution to combinatory and personalized treatment approaches in tinnitus but could also provide more profound insights in the heterogeneity of tinnitus, representing an important step towards a cure for tinnitus. TRIAL REGISTRATION: ClinicalTrials.gov NCT04663828 . Registered on 11 December 2020.

Hearing Aid Fitting in Tinnitus: A Scoping Review of Methodological Aspects and Effect on Tinnitus Distress and Perception.

Current evidence on efficacy of hearing aids (HAs) on tinnitus perception and annoyance is considered insufficient due to the heterogeneity of tinnitus characteristics and of methods used in the relevant clinical studies. This is a scoping review focused on the methodological aspects of clinical studies evaluating the value of HA fitting as part of tinnitus management over the past 10 years. Thirty-four studies were included in the review, showing important heterogeneity in almost all aspects of inclusion criteria, comparators, outcome measures, follow-up time and HA fitting procedures. Although all studies show that HA fitting has a positive impact on tinnitus perception in patients with hearing loss, the methodological heterogeneity does not allow robust conclusions. Future studies taking into account the different nature and goals of each tinnitus therapeutic modality and adapting their methods, endpoints and timelines according to them could lay the groundwork for obtaining high-quality evidence on whether and how HA fitting shall be implemented in tinnitus management strategies.

Methodological Aspects of Randomized Controlled Trials for Tinnitus: A Systematic Review and How a Decision Support System Could Overcome Barriers.

Although a wide range of tinnitus management interventions is currently under research and a variety of therapeutic interventions have already been applied in clinical practice, no optimal and universal tinnitus treatment has been reached yet. This fact is to some extent a consequence of the high heterogeneity of the methodologies used in tinnitus related clinical studies. In this manuscript, we have identified, summarized, and critically appraised tinnitus-related randomized clinical trials since 2010, aiming at systematically mapping the research conducted in this area. The results of our analysis of the 73 included randomized clinical trials provide important insight on the identification of limitations of previous works, methodological pitfalls or gaps in current knowledge, a prerequisite for the adequate interpretation of current literature and execution of future studies.

Audiological findings in professionals exposed to music and their relation with tinnitus.

Professional musicians are at high risk of developing tinnitus due to their over-exposure to music at both occupational and recreational level. This is a 5-year long prospective case series study performed in the Musicians/Performing Arts Medicine Clinic of the 1st Otorhinolaryngology Department of the National and Kapodistrian University of Athens. A total of 274 professional musicians underwent thorough medical history, history of music exposure, assessment of the impact their hearing status has on their professional life (Musicians Hearing Handicap Index), behavioral (Pure Tone Audiometry, standard and extended high frequency) and objective audiometric tests (TEOAE and DPOAE). Standard pure tone audiometry thresholds were correlated with the presence of tinnitus only at high frequencies. Musicians with tinnitus had a clinical and significant higher MHHI score and the incidence of tinnitus was significantly higher in participants suffering from musculoskeletal disease and those with abnormal PTA. Participants' hours of practice were similar in those with tinnitus and those without. The tinnitus group (and in order of descending effect size) had significantly worse thresholds in high frequency audiometry (≥3000Hz) as well as lower signal to noise ratios in DPOAE at almost all frequencies and in TEOAE at high frequencies (2.8 and 4kHz). A subgroup analysis of the musicians with normal PTA, showed that those with tinnitus showed elevated thresholds in the extended high frequency. In conclusion, tinnitus occurrence in musicians with normal audiogram is potentially correlated with high frequency hearing loss and impaired otoacoustic emissions and these two examinations should be considered in this group.

Musicians' Hearing Handicap Index: A New Questionnaire to Assess the Impact of Hearing Impairment in Musicians and Other Music Professionals.

Purpose We aimed to develop and validate the Musicians' Hearing Handicap Index (MHHI), a new self-evaluation tool for quantifying occupation-related auditory difficulties in music professionals. Although pure-tone audiometry is often considered the "gold standard" and is usually employed as the main instrument for hearing assessment, it cannot fully describe the impact of hearing dysfunction. The MHHI is an attempt to complement the hearing impairment assessment toolbox and is based on a unique approach to quantify the effects of hearing-related symptoms or hearing loss on the performance of musicians and other music industry professionals. Method An initial set of 143 questionnaire items was successively refined through a series of critical appraisals, modifications, and suggestions. This yielded an intermediate questionnaire consisting of 43 items, which was administered to 204 musicians and sound engineers. After exploratory factor analysis, the final form of the MHHI questionnaire was obtained, consisting of 29 items. The questionnaire's test-retest reliability, internal consistency, discriminating power, content validity, criterion validity, and aspects of construct validity and inherent conceptual structure were assessed. Results Exploratory factor analysis revealed a combination of four common factors for the 29 validated questionnaire items. They were named "impact on social and working lives," "difficulties in performance and sound perception," "communication difficulties," and "emotional distress." The MHHI was shown to be a valid and reliable instrument to assess musicians' and sound engineers' occupational difficulties due to hearing impairment and related symptoms. Conclusion The ability of the MHHI to discriminate between groups of music professionals with different auditory symptoms or pure-tone audiometry thresholds suggests that auditory symptoms might influence a professional's performance to an extent that cannot be assessed by a pure-tone audiogram.

Multi-objective evolutionary emergency response optimization for major accidents.

Emergency response planning in case of a major accident (hazardous material event, nuclear accident) is very important for the protection of the public and workers' safety and health. In this context, several protective actions can be performed, such as, evacuation of an area; protection of the population in buildings; and use of personal protective equipment. The best solution is not unique when multiple criteria are taken into consideration (e.g. health consequences, social disruption, economic cost). This paper presents a methodology for multi-objective optimization of emergency response planning in case of a major accident. The emergency policy with regards to protective actions to be implemented is optimized. An evolutionary algorithm has been used as the optimization tool. Case studies demonstrating the methodology and its application in emergency response decision-making in case of accidents related to hazardous materials installations are presented. However, the methodology with appropriate modification is suitable for supporting decisions in assessing emergency response procedures in other cases (nuclear accidents, transportation of hazardous materials) or for land-use planning issues.

Statistical analysis of incidents reported in the Greek Petrochemical Industry for the period 1997-2003.

This paper makes an analysis of all reported accidents and incidents in the Greek Petrochemical Industry for the period spanning from 1997 to 2003. The work performed is related to the analysis of important parameters of the incidents, their inclusion in a database adequately designed for the purposes of this analysis and an importance assessment of this reporting scheme. Indeed, various stakeholders have highlighted the importance of a reporting system for industrial accidents and incidents. The European Union has established for this purpose the Major Accident Reporting System (MARS) for the reporting of major accidents in the Member States. However, major accidents are not the only measure that can characterize the safety status of an establishment; neither are the former the only events from which important lessons can be learned. Near misses, industrial incidents without major consequences, as well as occupational accidents could equally supply with important findings the interested analyst, while statistical analysis of these incidents could give significant insight in the understanding and the prevention of similar incidents or major accidents in the future. This analysis could be more significant, if each industrial sector was separately analyzed, as the authors do for the petrochemical sector in the present article.