Betahistine for tinnitus (Protocol)

Background: Tinnitus describes 'ringing', 'whooshing' or 'hissing' sounds that are heard in the absence of any corresponding external sound. Between 5% and 43% of people experience this symptom and for some it has a significant negative impact on their quality of life. Tinnitus can be managed through education and advice, prescription devices that improve hearing, over-the-counter devices that generate background sounds, psychological therapy and relaxation therapy. Drug therapies are used to manage complaints associated with tinnitus such as sleep difficulties, anxiety or depression. No drug therapies exist that manage the tinnitus itself. Nonetheless, betahistine is often prescribed for tinnitus. The purpose of this review is to evaluate the evidence from high-quality clinical trials to work out the effect of betahistine on people's tinnitus. We particularly wanted to look at the effect of betahistine on tinnitus loudness and the side effects of betahistine.Study characteristics: Our review identified five randomised controlled trials with a total of 303 to 305 participants who suffered from tinnitus. These studies compared participants receiving betahistine to those receiving a placebo. Four study designs allocated participants into parallel groups. In one study, participants consented to take all study medications in a pre-defined sequence. The outcomes that we evaluated included tinnitus loudness and intrusiveness, tinnitus symptoms and side effects.Key results: The included studies did not show differences in tinnitus loudness, severity of tinnitus symptoms or side effects between participants receiving betahistine and participants receiving a placebo. No significant side effects were reported. We had planned to evaluate changes in tinnitus intrusiveness, depression and anxiety and quality of life, but these were not measured. The evidence suggests that betahistine is generally well tolerated with a similar risk of side effects to placebo.Quality of the evidence: The quality of the evidence ranged from moderate to very low. The risk of bias in all of the included studies was unclear. The results were drawn from one or two studies only. In some studies, the participants that were included did not fully represent the entire population of people with tinnitus and so we cannot draw general conclusions

The chemical defensome of five model teleost fish

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Eide, M., Zhang, X., Karlsen, O. A., Goldstone, J., Stegeman, J., Jonassen, I., & Goksoyr, A. The chemical defensome of five model teleost fish. Scientific Reports, 11(1), (2021): 10546, https://doi.org/10.1038/s41598-021-89948-0.How an organism copes with chemicals is largely determined by the genes and proteins that collectively function to defend against, detoxify and eliminate chemical stressors. This integrative network includes receptors and transcription factors, biotransformation enzymes, transporters, antioxidants, and metal- and heat-responsive genes, and is collectively known as the chemical defensome. Teleost fish is the largest group of vertebrate species and can provide valuable insights into the evolution and functional diversity of defensome genes. We have previously shown that the xenosensing pregnane x receptor (pxr, nr1i2) is lost in many teleost species, including Atlantic cod (Gadus morhua) and three-spined stickleback (Gasterosteus aculeatus), but it is not known if compensatory mechanisms or signaling pathways have evolved in its absence. In this study, we compared the genes comprising the chemical defensome of five fish species that span the teleosteii evolutionary branch often used as model species in toxicological studies and environmental monitoring programs: zebrafish (Danio rerio), medaka (Oryzias latipes), Atlantic killifish (Fundulus heteroclitus), Atlantic cod, and three-spined stickleback. Genome mining revealed evolved differences in the number and composition of defensome genes that can have implication for how these species sense and respond to environmental pollutants, but we did not observe any candidates of compensatory mechanisms or pathways in cod and stickleback in the absence of pxr. The results indicate that knowledge regarding the diversity and function of the defensome will be important for toxicological testing and risk assessment studies.The work was supported by the Norwegian Research Council as part of the iCOD and iCOD 2.0 projects (Grant Nos. 192441/I30 and 244654/E40), and the dCod 1.0 project (Grant No. 248840) which is part of Centre for Digital Life Norway. The American collaborators were funded by the National Institute of Health (USA) NIH P42ES007381 (Boston University Superfund Center to JJS and JVG), NIH R21HD073805 (JVG) and NHI R01ES029917 (JVG) grants. The Ocean Outlook exchange program funded the trans-Atlantic collaboration

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

Benefit-Harm Analysis for Informed Decision Making on Participating in Colorectal Cancer Screening: A Modeling Study

OBJECTIVES To facilitate informed decision making on participating in colorectal cancer (CRC) screening, we assessed the benefit-harm balance of CRC screening for a wide range of subgroups over different time horizons. METHODS The study combined incidence proportions of benefits and harms of (not) participating in CRC screening estimated by the Adenoma and Serrated pathway to CAncer microsimulation model, a preference eliciting survey, and benefit-harm balance modeling combining all outcomes to determine the net health benefit of CRC screening over 10, 20, and 30 years. Probability of net health benefit was estimated for 210 different subgroups based on age, sex, previous participation in CRC screening, and lifestyle. RESULTS CRC screening was net beneficial in 183 of 210 subgroups over 30 years (median probability [MP] of 0.79, interquartile range [IQR] of 0.69-0.85) across subgroups. Net health benefit was greater for men (MP 0.82; IQR 0.69-0.89) than women (MP 0.76; IQR 0.67-0.83) and for those without history of participation in previous screenings (MP 0.84; IQR 0.80-0.89) compared with those with (MP 0.69; IQR 0.59-0.75). Net health benefit decreased with increasing age, from MP of 0.84 (IQR 0.80-0.86) at age 55 to 0.61 (IQR 0.56-0.71) at age 75. Shorter time horizons led to lower benefit, with MP of 0.70 (IQR 0.62-0.80) over 20 years and 0.54 (IQR 0.48-0.67) over 10 years. CONCLUSIONS Our benefit-harm analysis provides information about net health benefit of screening participation, based on important characteristics and preferences of individuals, which could assist screening invitees in making informed decisions on screening participation

Investigating the prevalence and impact of device-related problems associated with hearing aid use

OBJECTIVE : To explore the prevalence of device-related problems associated with hearing aid use, participants’ help-seeking behaviours for these problems, and factors associated with hearing aid problems. DESIGN : A prospective convenience cohort design surveying 413 adult hearing aid users (34–97 years of age) recruited from seven clinics across Australia. RESULTS : Almost all participants (98%) indicated that they were experiencing at least one of the hearing aid problems included on the survey. The number of hearing aid related problems reported by participants ranged from 0 to 25 (of a possible 26), with a mean of 10 problems (SD = 5). The three most reported problems were related to difficulty hearing in noisy environments, hearing in windy environments, and understanding certain voices. Participants had reported less than half (46.33%) of the total problems identified to their clinic (range = 0–100%, mean = 43.40, SD = 13.92). Participants who reported experiencing a greater number of hearing aid problems also reported lower levels of hearing aid benefit, and satisfaction with their hearing aids. CONCLUSIONS : The majority of hearing aid owners experience problems with their hearing aids. Addressing these problems would likely contribute to improved hearing aid outcomes.Portions of this article were presented at the ACAud National Congress 2017, Adelaide, SA, August 2017, at the Audiology Australia Chapter conferences in Perth, Adelaide and Hobart, November 2017, at the HAASA National Conference, Sydney NSW, May 2018, and at the Audiology Australia National Congress, Sydney NSW, May 2018.Australian Postgraduate Award scholarship through The University of Western Australia.http://www.tandfonline.com/loi/iija20hj2021Speech-Language Pathology and Audiolog

Analysis of a cochlear implant database : changes in tinnitus prevalence and distress after cochlear implantation

The aim of this study was to estimate the prevalence and distress of tinnitus pre- and post-cochlear implantation in patients with bilateral severe to profound hearing loss. In this retrospective study, we included patients from a cochlear implant clinic in Perth, Western Australia. Pre- and post-cochlear implantation data from 300 implant recipients were collected on self-reported presence of tinnitus, tinnitus distress using the Tinnitus Reaction Questionnaire (TRQ), hearing-related quality of life using the Abbreviated Profile of Hearing Aid Benefit (APHAB), and consonant-nucleus vowel-consonant (CNC) word recognition test scores. Retrospectively, patients were grouped into those with or without tinnitus, and the grade of tinnitus distress. The potential factors associated with post-implantation changes in the presence of tinnitus and its distress were evaluated. Tinnitus prevalence was 55.8% pre-operatively and 44.3% post-implantation with a median TRQ score respectively of 12.0 (IQR: 1.0–28.0) and 3.5 (IQR: 0.0–16.2) points. Among the 96 patients experiencing tinnitus pre-implantation, 14.6% patients experienced moderate to catastrophic tinnitus distress pre-implantation compared to 6.3% post-implantation. To conclude, the pre- and post-implantation median TRQ score for the cohort population showed that tinnitus was a “slight” handicap. Tinnitus prevalence and its associated tinnitus distress decreased post-implantation. Patients with tinnitus post-implantation were significantly younger and had less severe pre-implantation hearing loss in the non-implanted ear than patients without tinnitus. Further research is needed to understand the factors influencing changes in tinnitus.https://journals.sagepub.com/home/tiahj2023Speech-Language Pathology and Audiolog

The impact of tinnitus on adult cochlear implant recipients: A mixed-method approach

BackgroundTinnitus is a common problem in patients with a cochlear implant (CI). Between 4% and 25% of CI recipients experience a moderate to severe tinnitus handicap. However, apart from handicap scores, little is known about the real-life impact tinnitus has on those with CIs. We aimed to explore the impact of tinnitus on adult CI recipients, situations impacting tinnitus, tinnitus-related difficulties and their management strategies, using an exploratory sequential mixed-method approach. MethodsA 2-week web-based forum was conducted using Cochlear Ltd.’s online platform, Cochlear Conversation. A thematic analysis was conducted on the data from the forum discussion to develop key themes and sub-themes. To quantify themes and sub-themes identified, a survey was developed in English with face validity using cognitive interviews, then translated into French, German and Dutch and disseminated on the Cochlear Conversation platform, in six countries (Australia, France, Germany, New Zealand, the Netherlands and United Kingdom). Participants were adult CI recipients experiencing tinnitus who received a Cochlear Ltd. CI after 18 years of age. ResultsFour key themes were identified using thematic analysis of the discussion forum: tinnitus experience, situations impacting tinnitus, difficulties associated with tinnitus and tinnitus management. Among the 414 participants of the survey, tinnitus burden on average was a moderate problem without their sound processor and not a problem with the sound processor on. Fatigue, stress, concentration, group conversation and hearing difficulties were the most frequently reported difficulties and was reported to intensify when not wearing the sound processor. For most CI recipients, tinnitus seemed to increase when performing a hearing test, during a CI programming session, or when tired, stressed, or sick. To manage their tinnitus, participants reported turning on their sound processor and avoiding noisy environments. ConclusionThe qualitative analysis showed that tinnitus can affect everyday life of CI recipients in various ways and highlighted the heterogeneity in their tinnitus experiences. The survey findings extended this to show that tinnitus impact, related difficulties, and management strategies often depend on sound processor use. This exploratory sequential mixed-method study provided a better understanding of the potential benefits of sound processor use, and thus of intracochlear electrical stimulation, on the impact of tinnitus

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IMPORTANCE The cost of bilateral cochlear implantation (BCI) is usually not reimbursed by insurance companies because of a lack of well-designed studies reporting the benefits of a second cochlear implant. OBJECTIVE To determine the benefits of simultaneous BCI compared with unilateral cochlear implantation (UCI) in adults with postlingual deafness. DESIGN, SETTING, AND PARTICIPANTS A multicenter randomized clinical trial was performed. The study took place in 5 Dutch tertiary referral centers: the University Medical Centers of Utrecht, Maastricht, Groningen, Leiden, and Nijmegen. Forty patients eligible for cochlear implantation met the study criteria and were included from January 12, 2010, through November 2, 2012. The main inclusion criteria were postlingual onset of hearing loss, age of 18 to 70 years, duration of hearing loss of less than 20 years, and a marginal hearing aid benefit. Two participants withdrew from the study before implantation. Nineteen participants were randomized to undergo UCI and 19 to undergo BCI. INTERVENTIONS The BCI group received 2 cochlear implants during 1 surgery. The UCI group received 1 cochlear implant. MAIN OUTCOMES AND MEASURES The primary outcome was the Utrecht Sentence Test with Adaptive Randomized Roving levels (speech in noise, both presented from straight ahead). Secondary outcomes were consonant-vowel-consonant words in silence, speech-intelligibility test with spatially separated sources (speech in noise from different directions), sound localization, and quality of hearing questionnaires. Before any data were collected, the hypothesis was that the BCI group would perform better on the objective and subjective tests that concerned speech intelligibility in noise and spatial hearing. RESULTS Thirty-eight patients were included in the study. Fifteen patients in the BCI group used hearing aids before implantation compared with 19 in the UCI group. Otherwise, there were no significant differences between the groups' baseline characteristics. At 1-year follow-up, there were no significant differences between groups on the Utrecht Sentence Test with Adaptive Randomized Roving levels (9.1 dB, UCI group; 8.2 dB, BCI group; P = .39) or the consonant-vowel-consonant test (median percentage correct score 85.0% in the UCI group and 86.8% in the BCI group; P = .21). The BCI group performed significantly better than the UCI group when noise came from different directions (median speech reception threshold in noise, 14.4 dB, BCI group; 5.6 dB, BCI group; P <.001). The BCI group was better able to localize sounds (median correct score of 50.0% at 60 degrees, UCI group; 96.7%, BCI group; P CONCLUSIONS AND RELEVANCE This randomized clinical trial demonstrates a significant benefit of simultaneous BCI above UCI in daily listening situations for adults with postlingual deafness

Accuracy of routine laboratory tests to predict mortality and deterioration to severe or critical COVID-19 in people with SARS-CoV-2

Objectives This is a protocol for a Cochrane Review (diagnostic). The objectives are as follows:  To assess the accuracy of routine blood-based laboratory tests to predict mortality and deterioration to severe or critical (from mild or moderate) COVID-19 in people with SARS-CoV-2 infection. Secondary objectives Where data are available, we will investigate whether prognostic accuracy varies according to a specific measurement or test, reference standard, timing of outcome verification, sample type, study design, and setting, including prevalence of the target condition (either by stratified analysis or meta-regression)