Designing clinical trials for assessing the effectiveness of interventions for tinnitus

In the face of finite resources, allocations of research and healthcare funding are dependent upon high-quality evidence. Historically, tinnitus has been the poor cousin of hearing science, with low-quality clinical research providing unreliable estimates of effect, and with devices marketed for tinnitus without strong evidence for those product claims. However, the tinnitus field is changing. Key opinion leaders have recently made calls to the field to improve the design, implementation and reporting of clinical trials, and there is growing intersectoral collaboration. The Tonndorf Lecture presented at the 1st World Tinnitus Congress and 12th International Tinnitus Seminar in Warsaw, Poland provided an opportunity to reflect on the present and future progress of tinnitus research and treatment and what is needed for the field to achieve success. The content of that lecture is summarised in this review article. The main debate concerns the selection and reporting of outcomes in clinical trials of tinnitus. Comprehensive reviews of the literature confirm the diversity of the personal impact of tinnitus, and illustrate a lack of consensus in what aspects of tinnitus should be assessed and reported in a clinical trial. An innovative project is described which engages the global tinnitus community (patients and professionals alike) in working together. This project seeks to improve future tinnitus research by creating an evidence-based consensus about minimum reporting standards for outcomes in clinical trials of a tinnitus intervention. The output will be a core set of important and critical outcomes to be measured and reported in all clinical trials

In the Gray Zone in the Fragile X Gene: What are the Key Unanswered Clinical and Biological Questions?

Smaller expansions (41–54 CGG repeats) in the fragile X mental retardation 1 (FMR1) gene are termed “gray zone” alleles. Only recently has interest in these expansions increased due to reporting of phenotypes unique to gray zone carriers or similar to those seen in individuals with larger expansions. As minimal research has focused on gray zone expansions, this paper asks several questions related to this topic. These include the following: What is the definition of the gray zone? Is there a risk of developing neurological signs in these carriers? Are there secondary gene effects that impact gray zone alleles or a biologic advantage to carrying these repeats? How do we counsel patients with gray zone expansions? The answers to these questions will help to determine the significance of these expansions and provide needed information to the research community and clinicians

Tinnitus in Adults, a Health Problem: Implications for the Society and the Scientific Community

Tinnitus is a phantom sound perceived in the absence of external acoustic stimulation, which is only heard by the affected person. It is described in a variety of ways and can be a single sound or combination of different sounds. Tinnitus is related to many other conditions and has an impact in the quality of life of the affected person. However, pathophysiological mechanisms underlying tinnitus and their basic biological remains unknown. One of the major challenges, concerning the heterogeneity of the tinnitus condition, is the lack of standardization in research and clinical management. For this, the TINNET, a European Cost Action for research, has the main objective to develop better strategies for diagnosis and management. The establishment of guidelines for clinical diagnosis, treatment, neuroimaging assessments and outcome assessment, through the identification of clinically meaningful tinnitus subtypes, provides an important basis for the standardization of clinical research and management of tinnitus

Subtyping somatic tinnitus: a cross-sectional UK cohort study of demographic, clinical and audiological characteristics

Somatic tinnitus is the ability to modulate the psychoacoustic features of tinnitus by somatic manoeuvres. The condition is still not fully understood and further identification of this subtype is essential, particularly for the purpose of establishing protocols for both its diagnosis and treatment. This study aimed to investigate the characteristics of somatic tinnitus within a large UK cohort using a largely unselected sample. We believe this to be relatively unique in comparison to current literature on the topic. This was investigated by using a total of 608 participant assessments from a set of recognised tinnitus and audiology measures. Results from a set of chi-square tests of association found that amongst the individuals with somatic tinnitus, a higher proportion had pulsatile tinnitus (different from heartbeat), were under the age of 40, reported variation in the loudness of their tinnitus and reported temporomandibular joint (TMJ) disorder. The same pattern of results was confirmed using a multivariate analysis of the data based on logistic regression. These findings have strong implications towards the profiling of somatic tinnitus as a distinct subtype of general tinnitus

Domains relating to the everyday impact of hearing loss, as reported by patients or their communication partner(s): protocol for a systematic review

INTRODUCTION: Hearing loss is a highly prevalent condition that affects around 1 in 6 people in the UK alone. This number is predicted to rise by the year 2031 to a staggering 14.5 million people due to the ageing population of the UK. Currently, the most common intervention for hearing loss is amplification with hearing aid(s) which serve to address the issue of audibility due to hearing loss, but cannot reverse its effects. The consequences of hearing loss are multifaceted, as it is a complex condition that can detrimentally affect various aspects of an individual's life, including communication and personal relationships. The scope of these reported issues is so broad that it calls on the need for patient-centred management plans that are tailored to each patient as well as appropriate measures to assess intervention benefit. It is unclear whether current outcome instruments adequately match what patients report as the most important problems for them. METHODS AND ANALYSIS: The systematic review aims to capture existing knowledge about patients and their communication partner's perspective on the everyday impact of hearing loss. Methods are defined according to the Preferred Reporting Items for Systematic reviews and Meta-analyses for Protocols (PRISMA-P) 2015. ETHICS AND DISSEMINATION: No ethical issues are foreseen. Findings will be reported in student's thesis as well as at national and international ENT/audiology conferences and in a peer-reviewed journal. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42015024914

Presentation modality influences behavioral measures of alerting, orienting, and executive control

The Attention Network Test (ANT) uses visual stimuli to separately assess the attentional skills of alerting (improved performance following a warning cue), spatial orienting (an additional benefit when the warning cue also cues target location), and executive control (impaired performance when a target stimulus contains conflicting information). This study contrasted performance on auditory and visual versions of the ANT to determine whether the measures it obtains are influenced by presentation modality. Forty healthy volunteers completed both auditory and visual tests. Reaction-time measures of executive control were of a similar magnitude and significantly correlated, suggesting that executive control might be a supramodal resource. Measures of alerting were also comparable across tasks. In contrast, spatial-orienting benefits were obtained only in the visual task. Auditory spatial cues did not improve response times to auditory targets presented at the cued location. The different spatial-orienting measures could reflect either separate orienting resources for each perceptual modality, or an interaction between a supramodal orienting resource and modality-specific perceptual processing

The human 'pitch center' responds differently to iterated noise and Huggins pitch

A magnetoencephalographic marker for pitch analysis (the pitch onset response) has been reported for different types of pitch-evoking stimuli, irrespective of whether the acoustic cues for pitch are monaurally or binaurally produced. It is claimed that the pitch onset response reflects a common cortical representation for pitch, putatively in lateral Heschl's gyrus. The result of this functional MRI study sheds doubt on this assertion. We report a direct comparison between iterated ripple noise and Huggins pitch in which we reveal a different pattern of auditory cortical activation associated with each pitch stimulus, even when individual variability in structure-function relations is accounted for. Our results suggest it may be premature to assume that lateral Heschl's gyrus is a universal pitch center

Ergonomic redesign using quality improvement for pre-hospital care of acute myocardial infarction

Context: Frontline emergency ambulance clinicians collaborated in a national quality improvement (QI) initiative to improve pre-hospital care for patients with acute myocardial infarction (AMI). Problem: The National Ambulance Clinical Performance Indicator (CPI) care bundle for AMI (consisting of aspirin, GTN, pain assessment and administration of analgesia) highlighted a consistent shortfall in patient pain assessment and inadequate provision of analgesia. Ineffective pain management in AMI has negative physiological and psychological effects that can be detrimental to patient outcomes. The aim is to increase the delivery of the entire AMI care bundle to 90% by March 2012 Assessment of problem and analysis of its causes: We explored barriers to effective pain management using process maps, cause-and-effect diagrams and thematic analysis of audio recordings from QI collaborative workshops and semi-structured interviews. We found that ergonomic factors (interaction between human and system factors), which included ineffective and inefficient pain assessment methods, ineffective feedback processes and poor access to analgesia were root causes for suboptimal pain management in AMI. Intervention: Through collaboration with frontline ambulance clinicians, solutions were found to overcome these root causes. These included: •Provider prompts (e.g. aide memoires and checklists) to prompt care bundle delivery. •Modified pain assessment tools (integrating Wong-baker faces, numerical verbal scores from 0 to 10 and descriptive intensity scales). •Individual clinical feedback by a clinical leader. •The introduction of small nitrous oxide canisters to increase availability and administration of analgesia earlier in the care pathway. Strategy for change: We used Plan-Do-Study-Act (PDSA) cycles to improve processes of care in AMI. Once improvements developed through PDSA cycles were identified, these were spread to county divisions and then trust-wide. Results were shared through QI workshops, face-to-face dialogue, e-forums, bulletins, newsletters and magazines locally and nationally. Measurement of improvement: Statistical Process Control (SPC) control methods were used to evaluate the effects of changes implemented. Improvements in the delivery of analgesia and the entire care bundle were achieved through initial awareness raising and implementation of system changes; e.g. provider prompts and revised pain assessment tool etc. We have already seen improvements in performance in the delivery of analgesia and also the care bundle as a whole. Effects of changes: An increase in pain assessment and the delivery of analgesia for patients experiencing AMI will help improve patient outcomes. The preliminary results of this study show improvement in the pain management in AMI. The sustainability of improvements recognised so far, and any variations that may occur as a consequence of subsequent interventions, continue to be monitored. Lessons learnt: A deeper understanding of the current system of care has been achieved by adopting a collaborative approach using QI methods focusing on ergonomics. Greater efforts earlier in the project to nurture a culture for improvement and to foster ownership and support from senior executives could have been an additional facilitator for these activities. Message for others: Systems of care can be ergonomically designed using QI methods to foster an environment that minimises opportunities for mistakes, accidental slips, lapses as well as routine (i.e. purposeful) and exceptional (i.e. unavoidable) violations in pre-hospital pain management

Acoustic, psychophysical, and neuroimaging measurements of the effectiveness of active cancellation during auditory functional magnetic resonance imaging

Functional magnetic resonance imaging (fMRI) is one of the principal neuroimaging techniques for studying human audition, but it generates an intense background sound which hinders listening performance and confounds measures of the auditory response. This paper reports the perceptual effects of an active noise control (ANC) system that operates in the electromagnetically hostile and physically compact neuroimaging environment to provide significant noise reduction, without interfering with image quality. Cancellation was first evaluated at 600 Hz, corresponding to the dominant peak in the power spectrum of the background sound and at which cancellation is maximally effective. Microphone measurements at the ear demonstrated 35 dB of acoustic attenuation [from 93 to 58 dB sound pressure level (SPL)], while masked detection thresholds improved by 20 dB (from 74 to 54 dB SPL). Considerable perceptual benefits were also obtained across other frequencies, including those corresponding to dips in the spectrum of the background sound. Cancellation also improved the statistical detection of sound-related cortical activation, especially for sounds presented at low intensities. These results confirm that ANC offers substantial benefits for fMRI research

Spatially Extended fMRI Signal Response to Stimulus in Non-Functionally Relevant Regions of the Human Brain: Preliminary Results

The blood-oxygenation level dependent (BOLD) haemodynamic response function (HDR) in functional magnetic resonance imaging (fMRI) is a delayed and indirect marker of brain activity. In this single case study a small BOLD response synchronised with the stimulus paradigm is found globally, i.e. in all areas outside those of expected activation in a single subject study. The nature of the global response has similar shape properties to the archetypal BOLD HDR, with an early positive signal and a late negative response typical of the negative overshoot. Fitting Poisson curves to these responses showed that voxels were potentially split into two sets: one with dominantly positive signal and the other predominantly negative. A description, quantification and mapping of the global BOLD response is provided along with a 2 × 2 classification table test to demonstrate existence with very high statistical confidence. Potential explanations of the global response are proposed in terms of 1) global HDR balancing; 2) resting state network modulation; and 3) biological systems synchronised with the stimulus cycle. Whilst these widespread and low-level patterns seem unlikely to provide additional information for determining activation in functional neuroimaging studies as conceived in the last 15 years, knowledge of their properties may assist more comprehensive accounts of brain connectivity in the future