Effect of electrical stimulation with a cochlear implant on tinnitus impact: protocol of an individual patient data meta-analysis

INTRODUCTION: Tinnitus is the perception of sound without an external stimulus, often experienced as a ringing, buzzing sound. While several studies have shown a reduction in tinnitus distress following cochlear implantation, others showed an increase or no change after implantation. At this stage, clinicians have little certainty when counselling their patients prior to implantation regarding tinnitus post-implantation. To help clinicians to counsel cochlear implant (CI) candidates on the risk of developing or improving tinnitus after implantation, we aim to assess the effect of electrical stimulation with a CI on tinnitus impact for individual adult patients with tinnitus. We will also apply prediction models to individual patient data (IPD) of clinical trials to find predictive factors of the effect of electrical stimulation on tinnitus impact. METHOD AND ANALYSIS: The IPD meta-analysis is a follow-up project of the systematic review on cochlear implantation in patients with tinnitus as a primary complaint. First, the systematic searches will be updated to date. Methodological quality of eligible studies will be assessed using the Risk of Bias In Non-randomised Studies of Intervention tool (ROBINS-I). Based on a data-sharing agreement, authors of the eligible studies will be invited to share their deidentified and complete IPD. The primary outcome is the effect of electrical stimulation with a CI on tinnitus impact 1 month or more post-implantation. IPD meta-analysis will be used to assess the primary outcome, while differentiating the tinnitus impact questionnaires. Second, linear regression analyses will be used to model the effect of electrical stimulation on tinnitus impact based on relevant predictors. ETHICS AND DISSEMINATION: The Medical Research Involving Human Subject Act does not apply, and ethical approval is not required. The study results will be made accessible to the public in a peer-review open access journal. PROSPERO REGISTRATION NUMBER: CRD42022319367, review ongoing

Treatment of Tinnitus in Children-A Systematic Review

Objectives: To systematically review studies on the effect of treatment of subjective tinnitus in children. Data Sources: We searched for studies in MEDLINE and EMBASE databases, after which additional studies were hand searched using Scopus databases. The methods are described in the study protocol, which has been registered in the PROSPERO register. PRISMA guidelines were followed in the reporting of this study. Eligibility Criteria: We considered for inclusion randomized controlled trials (RCTs), observational studies, case reports, and case series, with tinnitus as primary outcome in children (0-18 years old) with acute or chronic subjective tinnitus. We excluded studies in which both children and adults participated but outcomes were not specifically reported for children, as well as animal studies, studies with a non-original study design and studies about children with pulsatile or objective tinnitus. Data Selection: Two reviewers independently assessed studies for eligibility and quality, collected and extracted data. Statistical analyses were performed in case of homogeneous outcomes. Results: The search yielded a total of 4,447 studies. Of these, 147 eligible studies were selected. One case report and five observational studies met the eligibility criteria. Three studies applied counseling and (simplified-)TRT and reported improvement in tinnitus outcome in 68 out of 82 children after 3-6 months of treatment. Two studies used pharmacological treatments and reported improvement in 74 out of 86 patients after 10 days to 3 months of treatment. One study reported the outcome of biofeedback therapy, describing an improvement in tinnitus loudness and annoyance after 2 months of treatment. Conclusion: Due to the high risk of bias of the included studies, we cannot determine the effectiveness of the treatment of subjective tinnitus in children. Also, owing to brief follow-up periods, it is not possible to draw conclusions regarding long-term effects. Randomized controlled trials with longer follow-up periods are necessary to provide substantial evidence of the effects of therapies for children affected by tinnitus. https://www.crd.york.ac.uk/prospero/ Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, identifier [CRD42020178134]

Coping in Chronic Tinnitus Patients

Background: Tinnitus is the perception of sound without an external stimulus. A large part of the adult population experiences this symptom but never seeks professional help, where others have devastating complaints in daily life. This suggests that the impact of tinnitus varies among patients and may be influenced by coping strategies and multiple psychological factors. Method: Cross- sectional study of patients visiting the tertiary tinnitus referral center of the University Medical Center Utrecht, the Netherlands. Three hundred and twenty-one consecutive chronic tinnitus patients were evaluated by the tinnitus care group Utrecht from 6-2007 till 11-2012 of which 308 patients were included. Patients completed two tinnitus distress questionnaires (THI, TQ), a coping questionnaire (CISS) as well as a psychopathological questionnaire (SCL-90-R). Results: Emotional-orientated coping and distraction-orientated coping strategies were significantly correlated with the experienced tinnitus burden. Also a significant negative correlation with task orientated coping was found. The effect size was small. Tinnitus distress also had a significant positive correlation with anxiety, agoraphobia, depression, insufficiency of handling, distrust & personal sensitivity, hostility and sleeping problems. Conclusion: Patients with higher tinnitus handicap scores demonstrated the use different coping strategies than the patients with lower distress scores. This insight in coping strategies in a group of patients with high tinnitus burden is useful for counseling patients. As tinnitus coping strategy might be related to the extent and success of habituation, this outcome could be of interest to optimize tinnitus treatments in the near future

Correlation Between Chronic Tinnitus Distress and Symptoms of Depression: A Systematic Review

OBJECTIVES: In this systematic review, we aim to evaluate the evidence regarding the correlation between tinnitus distress and the severity of depressive symptoms in patients with chronic tinnitus. Also, the prevalence of clinically relevant depressive symptoms scores in patients with chronic tinnitus was evaluated. METHODS: We performed a systematic review in PubMed, EMBASE, and the Cochrane library in June 2021 using the terms "depression" and "tinnitus," and their synonyms, following PRISMA guidelines. Studies were selected on relevance and critically appraised regarding risk of bias using the Newcastle-Ottowa Quality Assessment Scale. RESULTS: A total of 1,912 articles were screened on title and abstract after the removal of the duplicates. Eventually, 33 (1.5%) articles were included for the final analysis. Only cross-sectional cohort studies and case-control studies with a low level of evidence and a high risk of bias due to the study design and patient selection were found. Statistically significant correlations between the experienced tinnitus distress and depressive symptoms were reported in 31 out of 33 studies. Clinically relevant depression scores had a prevalence of 4.6-41.7%. CONCLUSIONS: In this systematic review, in which mostly cross-sectional studies were included, a statistically significant correlation was found between the experienced tinnitus distress and the reported severity of symptoms of depression in patients with chronic tinnitus. A wide range of clinically relevant depression scores were reported in included studies. Due to the high risk of bias of included studies it is not possible to provide a definite answer on the existence of this relationship. Future population-based studies are necessary to provide more clarity

Congenital Anomalies of the Ossicular Chain: Surgical and Audiological Outcomes

Objectives: In this study, we aim to analyze audiometric outcomes of middle ear surgery in patients with congenital middle ear anomalies. Methods: In this single center retrospective cohort study, audiological outcomes were extracted from patient files. Patients with a congenital middle ear anomaly treated surgically in a tertiary referral center between June 2015 and December 2020 were included. Pre- and postoperative short- and long-term audiometric data (at ≥3 and ≥10 months respectively) were compared to analyze hearing outcomes. Results: Eighteen ears (15 patients) were treated surgically with an exploratory tympanotomy. At short term follow up statistically significant improvements in air conduction thresholds and air-bone gaps were found. Hearing improved in 94.4% (17/18) of operated ears. Successful outcome, defined as an air-bone gap closure to within 20 dB after surgery, was reached in 44.4% (8/18). Serviceable hearing (air conduction ≤30 dB) was reached in 55.6% (10/18). Negative outcome (any significant deterioration in hearing) occurred in 1 patient: in this ear otitis media occurred during the postoperative course. At long term follow up, available for 50% of the cohort, hearing remained stable in 5 ears, improved in 1 ear and deteriorated in 3, all of which underwent revision surgery. Sensorineural hearing loss due to surgery, or other complications, were not encountered. Conclusion: middle ear surgery was found to be an effective treatment option to improve hearing in this cohort of patients with congenital middle ear anomalies. Surgical goals of obtained gain in air conduction thresholds and serviceable hearing levels were met by most patients without the occurrence of any iatrogenic sensorineural hearing loss

Genetic outcomes in children with developmental language disorder: a systematic review

IntroductionDevelopmental language disorder (DLD) is a common childhood condition negatively influencing communication and psychosocial development. An increasing number of pathogenic variants or chromosomal anomalies possibly related to DLD have been identified. To provide a base for accurate clinical genetic diagnostic work-up for DLD patients, understanding the specific genetic background is crucial. This study aims to give a systematic literature overview of pathogenic variants or chromosomal anomalies causative for DLD in children.MethodsWe conducted a systematic search in PubMed and Embase on available literature related to the genetic background of diagnosed DLD in children. Included papers were critically appraised before data extraction. An additional search in OMIM was performed to see if the described DLD genes are associated with a broader clinical spectrum.ResultsThe search resulted in 15,842 papers. After assessing eligibility, 47 studies remained, of which 25 studies related to sex chromosome aneuploidies and 15 papers concerned other chromosomal anomalies (SCAs) and/or Copy Number Variants (CNVs), including del15q13.1–13.3 and del16p11.2. The remaining 7 studies displayed a variety of gene variants. 45 (candidate) genes related to language development, including FOXP2, GRIN2A, ERC1, and ATP2C2. After an additional search in the OMIM database, 22 of these genes were associated with a genetic disorder with a broader clinical spectrum, including intellectual disability, epilepsy, and/or autism.ConclusionOur study illustrates that DLD can be related to SCAs and specific CNV's. The reported (candidate) genes (n = 45) in the latter category reflect the genetic heterogeneity and support DLD without any comorbidities and syndromic language disorder have an overlapping genetic etiology

Development and internal validation of a prediction model for the presence of tinnitus in a Dutch population-based cohort

OBJECTIVES: In this study we aim to develop and internally validate a prediction model on tinnitus experience in a representative sample of the Dutch general population. METHODS: We developed a multivariable prediction model using elastic net logistic regression with data from the Dutch Lifelines Cohort Study. This is a multigenerational cohort study on adults who are located in the northern parts of the Netherlands. The model was internally validated using 10-fold cross-validation. The outcome of the model was tinnitus presence, for which we used 24 candidate predictors on different domains (among others demographic, hearing specific, and mental health variables). We assessed the overall predictive performance, discrimination, and calibration of the model. RESULTS: Data on 122.884 different participants were included, of which 7,965 (6.5%, 0 missing) experienced tinnitus. Nine variables were included in the final model: sex, hearing aids, hearing limitations, arterial blood pressure, quality of sleep, general health, symptom checklist of somatic complaints, cardiovascular risk factors, and age. In the final model, the Brier score was 0.056 and 0.787 in internal validation. CONCLUSION: We developed and internally validated a prediction model on tinnitus presence in a multigenerational cohort of the Dutch general population. From the 24 candidate predictors, the final model included nine predictors

Assessing the feasibility of a randomised controlled trial examining the effect of hearing aids on cognitive decline in elderly individuals: a study protocol

Introduction Hearing loss is one of the leading potentially modifiable risk factors for dementia. There is growing evidence suggesting that treating hearing loss with hearing aids could be a relatively low-cost intervention in reducing cognitive decline and the risk of dementia in the long term. However, given the current constraints of the limited evidence, it is premature to draw definitive conclusions about the effect of hearing aids on cognitive functioning. More long-term randomised studies examining this effect would be recommended. Prior to embarking on large-scale lengthy randomised controlled trials (RCTs), it is imperative to determine the viability of such studies. Therefore, the purpose of the current study is to assess the feasibility of a RCT that investigates the effect of hearing aids on cognitive functioning in elderly hearing impaired individuals. Methods and analysis In this randomised controlled feasibility trial, 24 individuals aged 65 years or older with mild to moderate hearing loss (≥35–<50 dB pure tone average (0.5–4 kHz) unilateral or bilateral) will be included and randomised towards a hearing aid intervention or no intervention. At baseline and at 6-month follow-up, a test battery consisting of cognitive tests and questionnaires will be administered to both groups. The primary outcome of the study is the willingness of hearing impaired individuals to be randomised for hearing amplification in a study regarding cognition. The secondary outcomes are the feasibility of the test battery and the therapy compliance of hearing aid use. Ethics and dissemination This research protocol was approved by the Institutional Review Board of the University Medical Centre Utrecht (NL80594.041.22, V.3, January 2023). The trial results will be made accessible to the public in a peer-reviewed journal

Selective Reporting of Outcomes in Tinnitus Trials: Comparison of Trial Registries With Corresponding Publications

Objectives: We aimed to study the prevalence of selective reporting of primary and secondary outcomes in tinnitus trials and to examine if selective reporting of outcome measures is influenced by the nature and direction of its results. Background: Selective reporting of outcome measures has been reported in several biomedical fields and can influence the clinical usefulness and implementation of outcomes of clinical trials. It is reported as one of the obstacles in finding an effective intervention for tinnitus. Methods: ClinicalTrials.gov (CT.gov) was used to identify all registered interventional tinnitus trials up to December 2015. A standardized search was used to find corresponding publications up to March 2018. The prespecified outcomes in CT.gov were compared with the outcomes reported in corresponding publication(s). The effects of the (lack of) statistical significance of trial results and the effects of funding source on record adherence were evaluated. Changes in registration elements were assessed with the Archive site of CT.gov. Results: We found corresponding publications for 60 (64.5%) of 93 eligible tinnitus trials registered in CT.gov. Of all the publications, five (7.5%) fully reported outcome measures entirely in line with the prespecified outcome measures. Discrepancies between the prespecified and reported outcomes were found in a total of 51 (76.1%) of the studies for primary outcomes, whereas 62 (92.5%) of the studies had discrepancies in secondary outcomes. In secondary outcomes, statistical significance of trial results influenced CT.gov record adherence. In addition, there was a statistically significant difference in the rate of discrepancy in industry-funded [n = 98 (87.5%) discrepant outcomes] and non-industry funded trials [n = 172 (74.5%) discrepant outcomes] (p = 0.01). Finally, 15 (25.9%) trialists made modifications in registered outcome measures during or after the trial period. Conclusion: Tinnitus trials suffer from substantial outcome reporting bias. Awareness of its presence must be raised to limit the obstacles of finding an effective intervention for tinnitus

Analysis and comparison of clinical practice guidelines regarding treatment recommendations for chronic tinnitus in adults: a systematic review

OBJECTIVES: To determine if, and to what extent, published clinical practice guidelines for the treatment of chronic tinnitus vary in their recommendations. DESIGN: Systematic review of guidelines. DATA SOURCES: PubMed, EMBASE and GIN electronic databases were searched in March 2022 and the search was updated in June 2023. ELIGIBILITY CRITERIA: We included clinical practice guidelines that gave recommendations on the treatment of tinnitus. No language restrictions were applied. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted the data and used the AGREE checklist to report on reporting. RESULTS: A total of 10 guidelines were identified and included, published between 2011 and 2021. Recommendations for 13 types of tinnitus treatments were compared. Large differences in guideline development and methodology were found. Seven of the 10 guidelines included a systematic search of the literature to identify the available evidence. Six of the 10 guidelines used a framework for the development of the guideline. Reporting was poor in multiple guidelines. Counselling and cognitive behavioural therapy were the only treatments that were recommended for treating tinnitus associated distress by all guidelines that reported on these topics. Tinnitus retraining therapy, sound therapy, hearing aids and cochlear implantation were not unanimously recommended either due to the lack of evidence, a high risk of bias or judgement of no beneficial effect of the specific treatment. CONCLUSIONS: There were notable differences with respect to whether guidelines considered the available evidence sufficient enough to make a recommendation. Notably, we identified substantial differences in the rigour of guideline design and development. Reporting was poor in many guidelines. Future guidelines could benefit from the use of reporting tools to improve reporting and transparency and the inclusion of guideline experts and patients to improve the quality of clinical practice guidelines on tinnitus