Validation of a new questionnaire measure of tinnitus functioning and disability for use in the UK: the Tinnitus Functional Index (TFI)

The Tinnitus Functional Index (TFI) was developed in the USA as a standard for assessing the functional impact of tinnitus based on eight tinnitus-related domains. The finalised 25-item version was never formally validated. This PhD seeks to assess the psychometric properties of the questionnaire and evaluate its suitability as the tool of choice for use in the diagnostic and outcome assessment of tinnitus for clinical and research purposes in the UK. The primary objectives were to (i) determine whether the TFI is reliable, (ii) verify its factor structure, and (iii) evaluate its responsiveness to treatment-related change. These objectives were evaluated in two UK studies. The first was a prospective multi-centre longitudinal validation study in which 255 NHS patients were recruited from audiology clinics to complete the TFI over four different time points in a nine-month period. The second was a retrospective analysis of data collected on the TFI and a battery of other health questionnaires from 294 members of the general public who had previously participated in two-centre randomised controlled trial of a novel tinnitus device. Approaches to psychometric analysis included classical and modern test theories, including Rasch measurement theory. Both approaches led to similar conclusions. Seven of the eight subscales were reliable and valid in both studies, although not as sensitive as the original developers proposed. Classical testing showed the auditory subscale to be reasonably reliable, but Rasch modelling indicated that it did not measure the functional impact of tinnitus. The overall factor structure was not confirmed. The sleep and auditory subscales did not relate to the other subscales and did not fit the model. My recommendation is to calculate the composite TFI score using only six subscales. The sleep subscale should be scored separately and the auditory subscale should not be used

A narrative synthesis of research evidence for tinnitus-related complaints as reported by patients and their significant others

Background: There are a large number of assessment tools for tinnitus, with little consensus on what it is important to measure and no preference for a minimum reporting standard. The item content of tinnitus assessment tools should seek to capture relevant impacts of tinnitus on everyday life, but no-one has yet synthesised information about the range of tinnitus complaints. This review is thus the first comprehensive and authoritative collection and synthesis of what adults with tinnitus and their significant others report as problems in their everyday lives caused by tinnitus. Methods: Electronic searches were conducted in PubMed, Embase, CINAHL, as well as grey literature sources to identify publications from January 1980 to June 2015 in which participants were enrolled because tinnitus was their primary complaint. A manual search of seven relevant journals updated the search to December 2017. Of the 3,699 titles identified overall, 84 records (reporting 86 studies) met our inclusion criteria and were taken through to data collection. Coders collated generic and tinnitus specific complaints reported by people with tinnitus. All relevant data items were then analyzed using an iterative approach to narrative synthesis to form domain groupings representing complaints of tinnitus, which were compared patients and significant others. Results: From the 86 studies analyzed using data collected from 16,381 patients, 42 discrete complaints were identified spanning physical and psychological health, quality of life and negative attributes of the tinnitus sound. This diversity was not captured by any individual study alone. There was good convergence between complaints collected using open- and closed-format questions, with the exception of general moods and perceptual attributes of tinnitus (location, loudness, pitch and unpleasantness); reported only using closed questions. Just two studies addressed data from the perspective of significant others (n=79), but there was substantial correspondence with the patient framework, especially regarding relationships and social life. Conclusions: Our findings contribute fundamental new knowledge and a unique resource that enables investigators to appreciate the broad impacts of tinnitus on an individual. Our findings can also be used to guide questions during diagnostic assessment, to evaluate existing tinnitus-specific HR-QoL questionnaires and develop new ones, where necessary

Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol

Background: Abiraterone acetate plus prednisolone (herein referred to as abiraterone) or enzalutamide added at the start of androgen deprivation therapy improves outcomes for patients with metastatic prostate cancer. Here, we aimed to evaluate long-term outcomes and test whether combining enzalutamide with abiraterone and androgen deprivation therapy improves survival. Methods: We analysed two open-label, randomised, controlled, phase 3 trials of the STAMPEDE platform protocol, with no overlapping controls, conducted at 117 sites in the UK and Switzerland. Eligible patients (no age restriction) had metastatic, histologically-confirmed prostate adenocarcinoma; a WHO performance status of 0–2; and adequate haematological, renal, and liver function. Patients were randomly assigned (1:1) using a computerised algorithm and a minimisation technique to either standard of care (androgen deprivation therapy; docetaxel 75 mg/m2 intravenously for six cycles with prednisolone 10 mg orally once per day allowed from Dec 17, 2015) or standard of care plus abiraterone acetate 1000 mg and prednisolone 5 mg (in the abiraterone trial) orally or abiraterone acetate and prednisolone plus enzalutamide 160 mg orally once a day (in the abiraterone and enzalutamide trial). Patients were stratified by centre, age, WHO performance status, type of androgen deprivation therapy, use of aspirin or non-steroidal anti-inflammatory drugs, pelvic nodal status, planned radiotherapy, and planned docetaxel use. The primary outcome was overall survival assessed in the intention-to-treat population. Safety was assessed in all patients who started treatment. A fixed-effects meta-analysis of individual patient data was used to compare differences in survival between the two trials. STAMPEDE is registered with ClinicalTrials.gov (NCT00268476) and ISRCTN (ISRCTN78818544). Findings: Between Nov 15, 2011, and Jan 17, 2014, 1003 patients were randomly assigned to standard of care (n=502) or standard of care plus abiraterone (n=501) in the abiraterone trial. Between July 29, 2014, and March 31, 2016, 916 patients were randomly assigned to standard of care (n=454) or standard of care plus abiraterone and enzalutamide (n=462) in the abiraterone and enzalutamide trial. Median follow-up was 96 months (IQR 86–107) in the abiraterone trial and 72 months (61–74) in the abiraterone and enzalutamide trial. In the abiraterone trial, median overall survival was 76·6 months (95% CI 67·8–86·9) in the abiraterone group versus 45·7 months (41·6–52·0) in the standard of care group (hazard ratio [HR] 0·62 [95% CI 0·53–0·73]; p<0·0001). In the abiraterone and enzalutamide trial, median overall survival was 73·1 months (61·9–81·3) in the abiraterone and enzalutamide group versus 51·8 months (45·3–59·0) in the standard of care group (HR 0·65 [0·55–0·77]; p<0·0001). We found no difference in the treatment effect between these two trials (interaction HR 1·05 [0·83–1·32]; pinteraction=0·71) or between-trial heterogeneity (I2 p=0·70). In the first 5 years of treatment, grade 3–5 toxic effects were higher when abiraterone was added to standard of care (271 [54%] of 498 vs 192 [38%] of 502 with standard of care) and the highest toxic effects were seen when abiraterone and enzalutamide were added to standard of care (302 [68%] of 445 vs 204 [45%] of 454 with standard of care). Cardiac causes were the most common cause of death due to adverse events (five [1%] with standard of care plus abiraterone and enzalutamide [two attributed to treatment] and one (<1%) with standard of care in the abiraterone trial). Interpretation: Enzalutamide and abiraterone should not be combined for patients with prostate cancer starting long-term androgen deprivation therapy. Clinically important improvements in survival from addition of abiraterone to androgen deprivation therapy are maintained for longer than 7 years. Funding: Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Janssen, and Astellas

Validation of a new questionnaire measure of tinnitus functioning and disability for use in the UK: the Tinnitus Functional Index (TFI)

The Tinnitus Functional Index (TFI) was developed in the USA as a standard for assessing the functional impact of tinnitus based on eight tinnitus-related domains. The finalised 25-item version was never formally validated. This PhD seeks to assess the psychometric properties of the questionnaire and evaluate its suitability as the tool of choice for use in the diagnostic and outcome assessment of tinnitus for clinical and research purposes in the UK. The primary objectives were to (i) determine whether the TFI is reliable, (ii) verify its factor structure, and (iii) evaluate its responsiveness to treatment-related change. These objectives were evaluated in two UK studies. The first was a prospective multi-centre longitudinal validation study in which 255 NHS patients were recruited from audiology clinics to complete the TFI over four different time points in a nine-month period. The second was a retrospective analysis of data collected on the TFI and a battery of other health questionnaires from 294 members of the general public who had previously participated in two-centre randomised controlled trial of a novel tinnitus device. Approaches to psychometric analysis included classical and modern test theories, including Rasch measurement theory. Both approaches led to similar conclusions. Seven of the eight subscales were reliable and valid in both studies, although not as sensitive as the original developers proposed. Classical testing showed the auditory subscale to be reasonably reliable, but Rasch modelling indicated that it did not measure the functional impact of tinnitus. The overall factor structure was not confirmed. The sleep and auditory subscales did not relate to the other subscales and did not fit the model. My recommendation is to calculate the composite TFI score using only six subscales. The sleep subscale should be scored separately and the auditory subscale should not be used

Tuotantoprosessin kehittäminen Case Vähälä Logistics Oy

Opinnäytetyön tarkoituksena oli tutkia voiteluaineiden noutojakeluprosessia Vähälä Logistics Oy:ssä. Vähälä Logistics Oy on osa valtakunnallista Kiitolinjaketjua, jossa se vastaa Oulun ja Lapin läänin sekä Keski-Suomen kappaletavaraliikenteestä. Työssä tutkittiin mahdollisuuksia tuotantoprosessin läpimenoajan lyhentämiseksi ja voiteluaineiden lajitteluun liittyvää resursointia. Tutkimus rajattiin koskemaan Oulun terminaalissa tapahtuvaa lajittelua. Teoriaosuudessa käytiin yleisesti läpi prosessi ja prosessien kehittämisen vaiheet. Teoriaosuuden tiedot kerättiin kirjallisuudesta ja internetistä. Tutkimusosuudessa prosessi kuvattiin sanallisesti ja prosessikaaviota hyväksi käyttäen. Tietoa kerättiin edelleen kirjallisuudesta, internetistä ja haastattelemalla prosessissa työskenteleviä ja siitä tietoisia henkilöitä. Kuvauksessa kiinnitettiin huomioita prosessin kriittisiin tekijöihin. Prosessikuvauksen analysoinnilla pyrittiin löytämään päällekäisiä vastuita ja kiinnittämään huomiota poikkeamiin. Prosessikuvauksesta kävi ilmi, että voiteluaineiden lajittelu viivästyy ruuhkautuneen lajittelupaikan vuoksi. Tähän johtavia syitä pohditiin ja pyrittiin antamaan toimenpide-ehdotuksia viivästysten välttämiseen.The purpose of this thesis was to examine the lubricant pick up and distribution process in Vähälä Logistics Oy. Vähälä Logistics is part of the nationwide Kiitolinja chain, in which it is responsible for Oulu and Lapland County and Central Finland parcelled goods traffic. The study examined the possibilities of the production lead time reduction and lubricants' sorting resourcing. The study focused on sorting in the terminal of Oulu. The theoretical part describes the process and the process development stages. The theory part's information was gathered from literature and the Internet. The research section described the process in words and by using a process diagram. Information was gathered from literature, the Internet and by interviewing the people aware of the process. The process description aimed at finding the critical points of the process and the duplication in responsibilities and paying attention to the deviations. The process description revealed that sorting of lubricants is delayed due to congested sorting place. Causes for this were discussed, and proposals for measures to avoid delays were make

The COMiT’ID Study:Developing Core Outcome Domains Sets for Clinical Trials of Sound-, Psychology-, and Pharmacology-Based Interventions for Chronic Subjective Tinnitus in Adults

Subjective tinnitus is a chronic heterogeneous condition that is typically managed using intervention approaches based on sound devices, psychologically informed therapies, or pharmaceutical products. For clinical trials, there are currently no common standards for assessing or reporting intervention efficacy. This article reports on the first of two steps to establish a common standard, which identifies what specific tinnitus-related complaints (‘outcome domains’) are critical and important to assess in all clinical trials to determine whether an intervention has worked. Using purposive sampling, 719 international healthcare users with tinnitus, healthcare professionals, clinical researchers, commercial representatives and funders were recruited. Eligibility was primarily determined by experience of one of the three interventions of interest. Following recommended procedures for gaining consensus, three intervention-specific, three-round, Delphi surveys were delivered online. Each Delphi survey was followed by an in-person consensus meeting. Viewpoints and votes involved all stakeholder groups, with approximately a 1:1 ratio of healthcare users to professionals. ‘Tinnitus intrusiveness’ was voted in for all three interventions. For sound-based interventions, the minimum set included ‘ability to ignore’, ‘concentration’, ‘quality of sleep’, and ‘sense of control’. For psychology-based interventions, the minimum set included ‘acceptance of tinnitus’, ‘mood’, ‘negative thoughts and beliefs’, and ‘sense of control’. For pharmacology-based interventions, ‘tinnitus loudness’ was the only additional core outcome domain. The second step will next identify how those outcome domains should best be measured. The uptake of these intervention-specific standards in clinical trials will improve research quality, enhance clinical decision-making and facilitate meta-analysis in systematic reviews

An evaluation of the content and quality of tinnitus information on websites preferred by General Practitioners

<p>Abstract</p> <p>Background</p> <p>Tinnitus is a prevalent and complex medical complaint often co-morbid with stress, anxiety, insomnia, depression, and cognitive or communication difficulties. Its chronicity places a major burden on primary and secondary healthcare services. In our recent national survey of General Practitioners (GPs) from across England, many reported that their awareness of tinnitus was limited and as a result were dissatisfied with the service they currently provide. GPs identified 10 online sources of information they currently use in clinical practice, but welcomed further concise and accurate information on tinnitus assessment and management. The purpose of this study was to assess the content, reliability, and quality of the information related to primary care tinnitus assessment and management on these 10 websites.</p> <p>Methods</p> <p>Tinnitus related content on each website was assessed using a summative content analysis approach. Reliability and quality of the information was assessed using the DISCERN questionnaire.</p> <p>Results</p> <p>Quality of information was rated using the validated DISCERN questionnaire. Significant inter-rater reliability was confirmed by Kendall’s coefficient of concordance (<it>Wt</it>) which ranged from 0.48 to 0.92 across websites. The website Map of Medicine achieved the highest overall DISCERN score. However, for information on treatment choice, the British Tinnitus Association was rated best. Content analysis revealed that all websites lacked a number of details relating to either tinnitus assessment or management options.</p> <p>Conclusions</p> <p>No single website provides comprehensive information for GPs on tinnitus assessment and management and so GPs may need to refer to more than one if they want to maximise their coverage of the topic. From those preferred by GPs we recommend several specific websites as the current ‘best’ sources. Our findings should guide healthcare website providers to improve the quality and inclusiveness of the information they publish on tinnitus. In the case of one website, our preliminary findings are already doing so. Such developments will in turn help facilitate best practice in primary care.</p