Effectiveness and cost effectiveness of digital hearing aids in patients with tinnitus and hearing loss: a randomised feasibility trial (THE HUSH Trial).

BACKGROUND: Education and advice is provided for tinnitus management in all UK audiology clinics. Sound therapy, including provision of hearing aids may be offered, but this is often dependent on a clinician's decision rather than UK policy. This inconsistent management reflects a lack of evidence around the effectiveness of hearing aids for tinnitus. This open-label, two-arm multicentre randomised controlled feasibility trial gathered data around recruitment, acceptability and outcome assessments to determine the feasibility of conducting a large randomised controlled trial investigating the effectiveness of hearing aids for tinnitus management. METHODS: Adults referred to audiology for tinnitus, with an aidable hearing loss were recruited at five UK audiology clinics. They were randomised 1:1 to either education and advice (treatment as usual (TAU), n = 41) or TAU plus hearing aids (n = 42). Outcomes were collected by questionnaires 12 weeks after randomisation. After participation, interviews were conducted with a subset of both participants and clinicians from each trial centre. RESULTS: Eighty three participants from five sites were randomised. Non-aidable hearing loss was the main reason for ineligibility to participate in the trial reported by the sites. Seventy three percent of participants returned the 12-week questionnaires, with return rates by site ranging from 61 to 100%. Fifteen out of 33 participants (45%) reported using hearing aids for the clinician-recommended time, or longer, during the day. The Tinnitus Functional Index (TFI) was the outcome measure most responsive to change. The majority of participants also agreed it was relevant to their tinnitus and hearing loss. Qualitative data demonstrated that the trial was acceptable to participants. Feedback from clinicians revealed a potential lack of equipoise. It also highlighted the differences in referral and treatment pathways between departments and differences in audiometric criteria for fitting hearing aids. Health economic measures were well completed for those returned. No change in health-related quality of life was observed. Costs were higher in the intervention arm, but self-reports of healthcare service use indicated participant confusion in treatment pathways. CONCLUSIONS: This feasibility trial is the first step towards obtaining high quality evidence to determine potential clinical effectiveness and cost effectiveness of hearing aids for tinnitus versus usual care. A definitive trial was deemed to be feasible, with some modifications based on feasibility findings and using the TFI as the primary outcome. This trial was funded by the National Institute for Health Research, Research for Patient Benefit Programme (PB-PG-0816-20,014) and registered with ISRCTN (ISRCTN14218416).

Substitution of a triazole for the central olefin in biologically active stilbenes.

The stilbene moiety is commonly found in natural products and these compounds display an extraordinary range of biological activity. Efforts to derive useful drugs from stilbenes must address the potential liabilities of this structure, including a propensity for cis/trans isomerization. To identify olefin replacements that address this limitation while preserving biological activity we have prepared analogues of two bioactive stilbenes, a pawhuskin and a schweinfurthin, where a 1,2,3-triazole ring formally replaces the stilbene double bond. The new schweinfurthin analogue (23) has been tested for anti-proliferative activity against 60 cell lines, and shows a strong correlation of bioactivity when compared to the compound that inspired its synthesis (22).

Surrounded by Sound: The Impact of Tinnitus on Musicians.

AIM: To investigate the impact of tinnitus on professional musicians in the UK. BACKGROUND: Tinnitus is the experience of sound when an external source is absent, primarily associated with the ageing process, hearing loss, and noise exposure. Amongst populations exposed to industrial noise, noise exposure and noise-induced hearing loss (NIHL) have been found to be the factors most associated with tinnitus. The risk of NIHL amongst professional musicians is greater than that amongst the general population, meaning they may be at increased risk of tinnitus. METHODS: Seventy-four professional musicians completed an online survey involving closed and open-ended questions, and completed the Tinnitus fuctional Index (TFI) questionnaire. Descriptive statistics and thematic analysis of open-ended qualitative responses were used to analyse the data. RESULTS: Three themes were generated from the analysis of the responses to the open-ended questions. These themes were: (1) the impact of tinnitus on the lives of professional musicians, (2) professional musician experience of tinnitus services, support, and hearing health and safety, and (3) the support professional musicians want. The mean global TFI score for professional musicians was 39.05, interpreted as tinnitus being a moderate problem. Comparisons with general population data revealed lower TFI scores for the TFI subscales of 'sense of control' and 'intrusiveness' for professional musicians and higher for auditory difficulties associated with tinnitus amongst professional musicians. CONCLUSION: Tinnitus can negatively impact on professional musicians' lives. There is a need for bespoke self-help groups, awareness raising, and education to prevent tinnitus and promote hearing health among musicians.

Investigating tinnitus subgroups based on hearing-related difficulties.

PURPOSE: Meaningfully grouping individuals with tinnitus who share a common characteristics (ie, subgrouping, phenotyping) may help tailor interventions to certain tinnitus subgroups and hence reduce outcome variability. The purpose of this study was to test if the presence of tinnitus subgroups are discernible based on hearing-related comorbidities, and to identify predictors of tinnitus severity for each subgroup identified. METHODS: An exploratory cross-sectional study was used. The study was nested within an online survey distributed worldwide to investigate tinnitus experiences during the COVID-19 pandemic. The main outcome measure was the tinnitus Handicap Inventory- Screening Version. RESULTS: From the 3400 respondents, 2980 were eligible adults with tinnitus with an average age of 58 years (SD = 14.7) and 49% (n = 1457) being female. A three-cluster solution identified distinct subgroups, namely, those with tinnitus-only (n = 1306; 44%), those presenting with tinnitus, hyperacusis, hearing loss and/or misophonia (n = 795; 27%), and those with tinnitus and hearing loss (n = 879; 29%). Those with tinnitus and hyperacusis reported the highest tinnitus severity (M = 20.3; SD = 10.5) and those with tinnitus and no hearing loss had the lowest tinnitus severity (M = 15.7; SD = 10.4). Younger age and the presence of mental health problems predicted greater tinnitus severity for all groups (ß ≤ -0.1, P ≤ .016). CONCLUSION: Further exploration of these potential subtypes are needed in both further research and clinical practice by initially triaging tinnitus patients prior to their clinical appointments based on the presence of hearing-related comorbidities. Unique management pathways and interventions could be tailored for each tinnitus subgroup.

A Delphi survey to determine a definition and description of hyperacusis by clinician consensus.

OBJECTIVE: There is currently no singularly accepted definition of hyperacusis. The aim of this study was to determine a definition and description of hyperacusis by clinician consensus. DESIGN: A three-round Delphi survey involving hearing healthcare professionals built towards clinical consensus on a definition of hyperacusis. Round 1 involved three open-ended questions about hyperacusis. Seventy-nine statements were generated on descriptions, impact, sounds, and potential features of hyperacusis. Agreement on the relevance of each statement to defining or describing hyperacusis was then measured in Rounds 2 and 3. General consensus was defined a priori as ≥70% agreement, or ≥90 for clinical decision making. STUDY SAMPLE: Forty-five hearing healthcare professionals were recruited to take part in this study. Forty-one completed Round 1, 36 completed Round 2, and 33 completed Round 3. RESULTS: Consensus was reached on 42/79 statements. From these a consensus definition includes "A reduced tolerance to sound(s) that are perceived as normal to the majority of the population or were perceived as normal to the person before their onset of hyperacusis". A consensus description of hyperacusis was also determined. CONCLUSIONS: This consensus definition of hyperacusis will help to determine the scope of clinical practice guidelines and influence needed research on hyperacusis.

Natural history of tinnitus in adults: a cross-sectional and longitudinal analysis.

OBJECTIVE: To assess incidence and changes in tinnitus and bothersome tinnitus as well as associated risk factors in a large sample of UK adults. DESIGN: Prospective cohort study. SETTING: UK. PARTICIPANTS: For cross-sectional analysis, a group of 168 348 participants aged between 40 and 69 years with hearing and tinnitus data from the UK Biobank resource. Longitudinal analysis included a subset of 4746 people who attended a 4-year retest assessment. MAIN OUTCOME MEASURES: Presence and bothersomeness of tinnitus. RESULTS: 17.7% and 5.8% of participants reported tinnitus or bothersome tinnitus, respectively. The 4-year incidence of tinnitus was 8.7%. Multivariate logistic regression models suggested that age, hearing difficulties, work noise exposure, ototoxic medication and neuroticism were all positively associated with both tinnitus and bothersome tinnitus. Reduced odds of tinnitus, but not bothersome tinnitus, was seen in alcohol drinkers versus non-drinkers. Male gender was associated with increased odds of tinnitus, while female gender was associated with increased odds of bothersome tinnitus. At follow-up, of those originally reporting tinnitus, 18.3% reported no tinnitus. Of those still reporting tinnitus, 9% reported improvement and 9% reported tinnitus becoming more bothersome, with the rest unchanged. Male gender and alcohol consumption were associated with tinnitus being reported less bothersome, and hearing difficulties were associated with the odds of tinnitus being reported as more bothersome. CONCLUSIONS: This study is one of the few to provide data on the natural history of tinnitus in a non-clinical population, suggesting that resolution is relatively uncommon, with improvement and worsening of symptoms equally likely. There was limited evidence for any modifiable lifestyle factors being associated with changes in tinnitus symptoms. In view of the largely persistent nature of tinnitus, public health strategies should focus on: (1) primary prevention and (2) managing symptoms in people that have tinnitus and monitoring changes in bothersomeness.

Changes in Tinnitus Experiences During the COVID-19 Pandemic.

Introduction: The COVID-19 pandemic has disrupted delivery of healthcare, economic activity, and affected social interactions. Identifying and supporting those most affected by the pandemic is required. The purpose of this study was to determine the impact of the pandemic on individuals with tinnitus and to identify mediating factors. Methods: This is a mixed-methods exploratory cross-sectional study, using data collected via an online survey from 3,103 individuals with tinnitus from 48 countries. The greatest representation was from North America (49%) and Europe (47%) and other countries were only marginally represented. Results: Although the study was aimed at those with pre-existing tinnitus, 7 individuals reported having COVID-19 initiated tinnitus. Having COVID-19 symptoms exacerbated tinnitus in 40% of respondents, made no change in 54%, and improved tinnitus in 6%. Other mediating factors such as the social and emotional consequences of the pandemic made pre-existing tinnitus more bothersome for 32% of the respondents, particularly for females and younger adults, better for 1%, and caused no change to tinnitus for 67%. Pre-existing tinnitus was significantly exacerbated for those self-isolating, experiencing loneliness, sleeping poorly, and with reduced levels of exercise. Increased depression, anxiety, irritability, and financial worries further significantly contributed to tinnitus being more bothersome during the pandemic period. Conclusions: These findings have implications for tinnitus management, because they highlight the diverse response both internal and external factors have on tinnitus levels. Clinical services should be mindful that tinnitus may be caused by contracting COVID-19 and pre-existing tinnitus may be exacerbated, although in the majority of respondents there was no change. Additional support should be offered where tinnitus severity has increased due to the health, social, and/or emotional effects of the COVID-19 pandemic. Tinnitus may be more bothersome for those experiencing loneliness, having fewer social interactions, and who are more anxious or worried.

The TinMan study: feasibility trial of a psychologically informed, audiologist-delivered, manualised intervention for tinnitus.

OBJECTIVE: To develop a manualised psychological treatment for tinnitus that could enhance audiologist usual care, and to test feasibility of evaluating it in a randomised controlled trial. DESIGN: Feasibility trial, random allocation of patients to manualised treatment or treatment as usual, and mixed-methods evaluation. Study sample: Senior audiologists, and adults with chronic tinnitus. RESULTS: Recruitment reached 63% after 6 months (feasibility pre-defined as 65%). Only nine patients (47%) were retained for the duration of the trial. Patients reported that the treatment was acceptable and helped reassure them about their tinnitus. Audiologists reported mixed feelings about the kinds of techniques that are presented to them as 'psychologically informed'. Audiologists also reported lacking confidence because the training they had was brief, and stated that more formal supervision would have been helpful to check adherence to the treatment manual. CONCLUSIONS: The study indicate potential barriers to audiologist use of the manual, and that a clinical trial of the intervention is not yet feasible. However, positive indications from outcome measures suggest that further development work would be worthwhile. Refinements to the manual are indicated, and training and supervision arrangements to better support audiologists to use the intervention in the clinic are required. Trial Registration: ISRCTN13059163.

Protocol for a multi-centre randomised controlled stand-alone feasibility trial to assess potential effectiveness and cost-effectiveness of digital hearing aids in patients with tinnitus and hearing loss (the HUSH trial).

BACKGROUND: The most common management strategy for tinnitus provided in the UK audiology clinics is education and advice. This may also be combined with some form of sound therapy (e.g. digital hearing aids). While education and advice is generally provided by all clinics, there is a marked variability in provision of hearing aids that depends very much on clinical decisions. A recent Cochrane review concluded a lack of evidence to support or refute hearing aid use as a routine intervention for people with tinnitus and hearing loss. This lack of evidence is reflected in the inconsistency of tinnitus management in the UK. The aim of the HUSH trial is to determine the feasibility of conducting a definitive randomised controlled trial (RCT) of the effectiveness and cost-effectiveness of hearing aids for adults with tinnitus and hearing loss. METHODS: This is a multicentre randomised controlled feasibility trial. Up to 100 adults, aged 18 and over, presenting to 5 UK audiology clinics with a complaint of tinnitus and measurable hearing loss are being randomised to receive either (i) education and advice (treatment as usual) or (ii) education and advice with digital hearing aids. Feasibility outcomes are being collected around recruitment, retention, patient and healthcare professional acceptability and clinical outcome assessment. Outcomes are being collected via postal questionnaire at 12 weeks post baseline. A nested interview study will supplement clinical and other outcome data, providing a detailed understanding of participants' and audiologists' experience of both tinnitus management and the research processes. DISCUSSION: This feasibility trial will help us to (i) determine if it is feasible to conduct a multicentre RCT comparing treatment as usual and treatment as usual plus digital hearing aids; (ii) optimise the design of a future definitive, multicentre RCT; and (iii) inform which outcome(s) is/are relevant for patients. This work presents an important first step in determining the effectiveness of hearing aids as a tinnitus management strategy. TRIAL REGISTRATION: ISRCTN, ISRCTN14218416. Registered on 30 July 2018.

Soldiering on: a survey on the lived experience of tinnitus in aged military veterans in the UK.

Tinnitus has long been interrogated as a medical conundrum, with little discourse between medicine and other disciplines. It involves the perception of sound in the ears or head without any external sound source, most likely a natural consequence of some form of hearing loss. For many people, tinnitus is bothersome and associated with various problems such as insomnia, difficulty concentrating and impaired listening ability. Nevertheless, with little attention from humanities or the social sciences, our understanding of the wider perspectives and psychosocial context of adults with tinnitus is limited, especially among UK military veterans. The aim of this study was to explore the impact of tinnitus on aged UK veterans, and to consider the support they receive and require to live well with tinnitus. In all, 120 aged UK veterans took part in this study. Data revealed similarities and differences between UK veteran and other study populations. For example, tinnitus symptom severity was higher in aged veterans than a general (younger) research population, particularly so on measures of intrusiveness and the effect of tinnitus on listening ability. Veterans had mixed views on social support. Many did not want to talk about tinnitus with others and/or did not want to burden their family, preferring to deal with their tinnitus 'backstage'. Others appreciated empathy or sympathy; many implied a desire that their family and/or friends could better understand their experience of living with tinnitus and the problems it caused them. These complexities support a need for cross-disciplinary work to understand and respond to tinnitus-related problems in veterans.

Why Is There No Cure for Tinnitus?

Tinnitus is unusual for such a common symptom in that there are few treatment options and those that are available are aimed at reducing the impact rather than specifically addressing the tinnitus percept. In particular, there is no drug recommended specifically for the management of tinnitus. Whilst some of the currently available interventions are effective at improving quality of life and reducing tinnitus-associated psychological distress, most show little if any effect on the primary symptom of subjective tinnitus loudness. Studies of the delivery of tinnitus services have demonstrated considerable end-user dissatisfaction and a marked disconnect between the aims of healthcare providers and those of tinnitus patients: patients want their tinnitus loudness reduced and would prefer a pharmacological solution over other modalities. Several studies have shown that tinnitus confers a significant financial burden on healthcare systems and an even greater economic impact on society as a whole. Market research has demonstrated a strong commercial opportunity for an effective pharmacological treatment for tinnitus, but the amount of tinnitus research and financial investment is small compared to other chronic health conditions. There is no single reason for this situation, but rather a series of impediments: tinnitus prevalence is unclear with published figures varying from 5.1 to 42.7%; there is a lack of a clear tinnitus definition and there are multiple subtypes of tinnitus, potentially requiring different treatments; there is a dearth of biomarkers and objective measures for tinnitus; treatment research is associated with a very large placebo effect; the pathophysiology of tinnitus is unclear; animal models are available but research in animals frequently fails to correlate with human studies; there is no clear definition of what constitutes meaningful change or "cure"; the pharmaceutical industry cannot see a clear pathway to distribute their products as many tinnitus clinicians are non-prescribing audiologists. To try and clarify this situation, highlight important areas for research and prevent wasteful duplication of effort, the British Tinnitus Association (BTA) has developed a Map of Tinnitus. This is a repository of evidence-based tinnitus knowledge, designed to be free to access, intuitive, easy to use, adaptable and expandable.

Mobile Apps for Management of Tinnitus: Users' Survey, Quality Assessment, and Content Analysis.

BACKGROUND: Tinnitus is the perception of a sound without any outside source. It affects 6 million people in the United Kingdom. Sound therapy is a core component of many tinnitus management programs. Potential mechanisms of benefit include making tinnitus less noticeable, habituation, distracting attention from tinnitus, relaxation, and promoting neuroplastic changes within the brain. In recent years, there has been a substantial increase in the use of mobile technology. This provided an additional medium through which people with tinnitus can access different tinnitus management options, including sound therapy. OBJECTIVE: The aim of this study was to (1) generate the list of apps that people use for management of their tinnitus, (2) explore reasons for app use and nonuse, (3) perform quality assessment of the most cited apps, and (4) perform content analysis to explore and describe options and management techniques available in the most cited apps. METHODS: A Web-based survey consisting of 33 open and closed questions captured (1) demographic information, information about tinnitus, and hearing loss and (2) mobile app-specific information about the motivation to use an app, the apps which respondents used for tinnitus, important factors when choosing an app, devices used to access apps, and reasons for not using apps. The quality of the most cited apps was assessed using the Mobile Apps Rating Scale (MARS). Content and features of the most cited apps were analyzed. RESULTS: Data from 643 respondents were analyzed. The majority of respondents (482/643, 75.0%) had never used an app for management of tinnitus mainly because of lack of awareness (381/643, 59.3%). The list of the 55 apps that people use for their tinnitus was generated. These included apps that were developed specifically for the management of tinnitus; however, the majority of cited apps were developed for other problems (eg, sleep, depression or anxiety, and relaxation). Quality assessment of the 18 most popular apps using MARS resulted in a range of mean scores from 1.6 to 4.2 (out of 5). In line with the current model of tinnitus management, sound was the main focus of the majority of the apps. Other components included relaxation exercises, elements of cognitive behavioral therapy, information and education, and hypnosis. CONCLUSIONS: People used apps for the management of their tinnitus; however, this was done mostly as a self-help option, without conjunction with management provided by hearing health care professionals. Further research should consider the place for apps in tinnitus management (stand-alone self-management intervention vs part of the management by a hearing professional). As the content of the apps varies with respect to sound options, information, and management strategies, it seems that the choice of the best management app should be guided by individual patient's needs and preferences.

Promotion and views on tinnitus self-help within United Kingdom national health service audiology departments.

Self-help has the potential to provide low-cost and effective ways of improving access to psychological support for people with tinnitus. When developing and evaluating resources it is important to consider issues that may influence successful implementation. This Survey explored clinicians' use and views on self-help, and barriers to implementation. An online survey was distributed to 220 UK audiology departments. One-hundred and twenty-four clinicians responded to the survey (91 audiologists, 32 hearing therapists, 1 clinical psychologist), each representing a different tinnitus department. Two-thirds of respondents reported providing or recommending self-help resources. Potential benefits were patient empowerment and providing a means of engaging patients in their care. Almost half of respondents felt that there is insufficient training or guidance for clinicians on using or promoting self-help. Clinicians felt that for patients with low-level tinnitus severity, self-help may reduce the number of audiology appointments required. For patients with more complex needs self-help may be useful to engage with between clinical appointments. Further research is needed to determine effectiveness, who benefits, and by what mechanism, before clinicians can confidently recommend or implement self-help. Clinicians will benefit from formal guidance on promoting and supporting use of self-help for tinnitus.

Tinnitus services in the United Kingdom: a survey of patient experiences.

BACKGROUND: Tinnitus service provision in the United Kingdom has been investigated from the healthcare provider's perspective demonstrating considerable regional variation particularly regarding availability of psychological treatments. An audiological-based tinnitus service, however, was reportedly available for all tinnitus patients in the UK. The aim of the current study was to define and evaluate nationwide tinnitus healthcare services from the patients' viewpoint. METHODS: Secondary analyses were performed on data from a 33-item questionnaire provided by the British Tinnitus Association. The questionnaire had been distributed via email and social media. RESULTS: Responses from 937 participants who had or had previously experienced tinnitus were analysed. All but one person had at some time consulted their GP. About one in five received medication in primary care. The majority were referred to secondary care, generally an ENT surgeon or audiovestibular physician; some were referred directly to audiological services. In secondary care the majority underwent audiometric testing and over half underwent MRI scanning. Drugs were prescribed less frequently in secondary care. About one third of patients were referred onwards from diagnostic services in secondary care to receive therapeutic interventions for tinnitus. Therapy was generally delivered by an audiologist or hearing therapist. Just under two fifths of people discharged from secondary care returned to their GP, with most returning within one year. Over a third of this group were re-referred to secondary care. Few patients saw a psychologist (2.6%) though some psychological treatments were delivered by appropriately trained audiologists. Negative counselling from healthcare professionals in both primary and secondary care settings was reported. CONCLUSIONS: Although the UK has developed a national service for patients with tinnitus many people find it difficult to access, being blocked at the primary care level or after secondary care diagnostic services. Many of those discharged from secondary care return to their GP within a short space of time and are re-referred to secondary care creating an unsatisfactory and expensive revolving-door pattern of healthcare. Despite psychological treatment modalities having the best evidence base for successful tinnitus management, only a minority of tinnitus patients ever get to meet a psychologist.

Patients' and Clinicians' Views of the Psychological Components of Tinnitus Treatment That Could Inform Audiologists' Usual Care: A Delphi Survey.

OBJECTIVES: The aim of this study was to determine which components of psychological therapies are most important and appropriate to inform audiologists' usual care for people with tinnitus. DESIGN: A 39-member panel of patients, audiologists, hearing therapists, and psychologists completed a three-round Delphi survey to reach consensus on essential components of audiologist-delivered psychologically informed care for tinnitus. RESULTS: Consensus (≥80% agreement) was reached on including 76 of 160 components. No components reached consensus for exclusion. The components reaching consensus were predominantly common therapeutic skills such as Socratic questioning and active listening, rather than specific techniques, for example, graded exposure therapy or cognitive restructuring. Consensus on educational components to include largely concerned psychological models of tinnitus rather than neurophysiological information. CONCLUSIONS: The results of this Delphi survey provide a tool to develop audiologists' usual tinnitus care using components that both patients and clinicians agree are important and appropriate to be delivered by an audiologist for adults with tinnitus-related distress. Research is now necessary to test the added effects of these components when delivered by audiologists.

Synthesis of amide isosteres of schweinfurthin-based stilbenes.

The schweinfurthins are plant-derived stilbenes with an intriguing profile of anti-cancer activity. To obtain analogues of the schweinfurthins that might preserve the biological activity but have greater water solubility, a formal replacement of the central olefin with an amide has been explored. Two pairs of amides have been prepared, each containing the same hexahydroxanthene "left half" joined through an amide linkage to two different "right halves." In each series, the amide has been inserted in both possible orientations, placing the carbonyl group on the tricyclic ABC ring system and the amine on the D-ring, or placing the amine on the hexahydroxanthene and the carbonyl group on the D-ring. The four new schweinfurthin analogues have been tested in the NCI 60 cell line screen, and in both cases the more active isomer carried the carbonyl group on the C-ring.

An economic evaluation of the healthcare cost of tinnitus management in the UK.

BACKGROUND: There is no standard treatment pathway for tinnitus patients in the UK. Possible therapies include education and reassurance, cognitive behavioural therapies, modified tinnitus retraining therapy (education and sound enrichment), or amplification of external sound using hearing aids. However, the effectiveness of most therapies is somewhat controversial. As health services come under economic pressure to deploy resources more effectively there is an increasing need to demonstrate the value of tinnitus therapies, and how value may be continuously enhanced. The objective of this project was to map out existing clinical practice, estimate the NHS costs associated with the management approaches used, and obtain initial indicative estimates of cost-effectiveness. METHODS: Current treatment pathways, costs and health outcomes were determined from the tinnitus literature, national statistics, a patient survey, and expert opinion. These were used to create an Excel-based economic model of therapy options for tinnitus patients. The probabilities associated with the likelihood of an individual patient receiving a particular combination of therapies was used to calculate the average cost of treatment per patient, average health outcome per patient measured in QALYs gained, and cost-effectiveness, measured by the average cost per QALY gained. RESULTS: The average cost of tinnitus treatment per patient per year is GB£717, equating to an NHS healthcare bill of GB£750 million per year. Across all pathways, tinnitus therapy costs £10,600 per QALY gained. Results were relatively insensitive to restrictions on access to cognitive behaviour therapy, and a subsequent reliance on other therapies. CONCLUSIONS: NHS provisions for tinnitus are cost-effective against the National Institute for Health and Care Excellence cost-effective threshold. Most interventions help, but education alone offers very small QALY gains. The most cost-effective therapies in the model were delivered within audiology.

Selective opioid growth factor receptor antagonists based on a stilbene isostere.

As part of an ongoing drug development effort aimed at selective opioid receptor ligands based on the pawhuskin natural products we have synthesized a small set of amide isosteres. These amides were centered on lead compounds which are selective antagonists for the delta and kappa opioid receptors. The amide isomers revealed here show dramatically different activity from the parent stilbene compounds. Three of the isomers synthesized showed antagonist activity for the opioid growth factor (OGF)/opioid growth factor receptor (OGFR) axis which is involved in cellular and organ growth control. This cellular signaling mechanism is targeted by "low-dose" naltrexone therapy which is being tested clinically for multiple sclerosis, Crohn's disease, cancer, and wound healing disorders. The compounds described here are the first selective small molecule ligands for the OGF/OGFR system and will serve as important leads and probes for further study.

A psychologically informed, audiologist-delivered, manualised intervention for tinnitus: protocol for a randomised controlled feasibility trial (Tin Man study).

BACKGROUND: Chronic tinnitus is a common incurable condition often associated with depression, anxiety, insomnia and reduced quality of life. Within National Health Service (NHS) audiology in the United Kingdom (UK), no standard protocol currently exists for the treatment of tinnitus. Counselling is only available in less than half of audiology departments, and there is no agreed standard for what constitutes tinnitus counselling. There is substantial evidence from systematic reviews for the clinical benefit of cognitive behaviour therapy (CBT) for tinnitus delivered by clinical psychologists or psychiatrists, but no studies have sufficiently evidenced the NHS model of tinnitus care where management is increasingly being delivered by audiology professionals. In a pilot randomised controlled trial (RCT), this study aims to evaluate the feasibility of comparing a psychologically informed guidance manual developed to support audiologist management of tinnitus with usual treatment. METHODS/DESIGN: Phase 1 consisted of three development stages: (1) a scoping review to generate a comprehensive set of tinnitus counselling components, (2) a Delphi survey involving expert patients (n = 18) and clinicians (n = 21) to establish consensus on the essential core attributes of tinnitus counselling, and (3) incorporation of these elements into a manualised care protocol. In phase 2, following training in a dedicated workshop, the manualised intervention will be delivered by three experienced audiologists across three different sites. Patients (n = 30) will be randomly allocated to receive either (1) psychologically informed management from an audiologist trained to deliver the manualised intervention or (2) treatment as usual (TAU) from an audiologist who has not received this training. Quantitative outcome measures will be administered at baseline, discharge and 6-month follow-up. Qualitative interviews with participating patients and clinicians will be conducted to gather perspectives on the feasibility and acceptability of the manualised intervention. DISCUSSION: The feasibility of proceeding to a definitive RCT will be assessed via compliance with the manual, willingness to be randomised, number of eligible participants, rate of recruitment, retention and collection of quantitative outcome measures. This research offers an important first step to an evidence-based, standardised and accessible approach to tinnitus care. TRIAL REGISTRATION: ISRCTN13059163. Date of registration: 6 May 2016.