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Tinnitus is the perception of a phantom sound and the patient's reaction to it. Although much progress has been made, tinnitus remains a scientific and clinical enigma of high prevalence and high economic burden, with an estimated prevalence of 10%-20% among the adult population. The EU is funding a new collaborative project entitled "Unification of Treatments and Interventions for Tinnitus Patients" (UNITI, grant no. Erastin2 ic50 848261) under its Horizon 2020 framework. The main goal of the UNITI project is to set the ground for a predictive computational model based on existing and longitudinal data attempting to address the question of which treatment or combination of treatments is optimal for a specific patient group based on certain parameters. Clinical, epidemiological, genetic and audiological data, including signals reflecting ear-brain communication, as well as patients' medical history, will be analyzed making use of existing databases. Predictive factors for different patient groups will be extracted and theil Therapy (CBT), hearing aids, sound stimulation, and structured counseling. The consortium will also make use of e/m-health applications for the treatment and assessment of tinnitus. (4) Decision Support System An innovative Decision Support System will be implemented, integrating all available parameters (epidemiological, clinical, audiometry, genetics, socioeconomic and medical history) to suggest specific examinations and the optimal intervention strategy based on the collected data. (5) Financial estimation analysis A cost-effectiveness analysis for the respective interventions will be calculated to investigate the economic effects of the interventions based on quality-adjusted life years. In this paper, we will present the UNITI project, the scientific questions that it aims to address, the research consortium, and the organizational structure.To evaluate efficacy and safety of BGG492 (selurampanel; an orally active, competitive AMPA glutamate receptor antagonist) in patients with moderate-to-catastrophic chronic subjective tinnitus. Study (NCT01302873) enrolled patients with subjective tinnitus based on THI severity grade 3, 4 or 5 (moderate, severe or catastrophic), and those with chronic (>6 and less then 36 months) tinnitus. Primary endpoints were clinical status of tinnitus using TBF-12 and tinnitus loudness using VAS after multiple dose 2-week BGG492 treatment. Safety was assessed by recording all adverse events (AEs). After a single dose of BGG492 VAS scores for tinnitus loudness (P=0.012) and tinnitus annoyance (P=0.004) were significantly reduced vs placebo. After 2 weeks treatment a significantly greater proportion of patients showed improvement of ≥4 points from baseline in TBF-12 (stringent responder definition) with BGG492 vs placebo (26.7% [n=23] vs 14% [n=12], respectively; odds ratio [OR] (90% CI)2.30 (1.10, 4.83); P=0.064), fulfilling proof-of-concept achievement criteria. No notable difference in proportion of responders to BGG492 vs placebo was observed as assessed using VAS (26.7% [n=23] vs 27.6% [n=24], respectively; OR (90% CI)0.94 (0.52, 1.67); P=0.848). Dizziness was the most frequently reported AE in 50% [n=21] and 31.5% [n=17] patients on BGG492 100 and 50mg TID, respectively vs 9.6% [n=9] on placebo. In conclusion, BGG492 showed reduction of both tinnitus loudness and annoyance after a single dose and reduction of tinnitus handicap after 2 weeks of treatment in patients with chronic subjective tinnitus, thereby supporting further clinical investigation of AMPA receptor antagonists with an improved benefit/risk ratio. A dose of 100mg TID BGG492 showed higher efficacy but somewhat lower tolerability compared to 50mg TID.While tinnitus is known to compromise the perception of speech, it is unclear if the same holds for extralinguistic speaker information. Furthermore, research with simple tone stimuli showed that unilateral tinnitus binds spatial attention, thereby impeding the detection of auditory changes in the non-affected ear. Using dichotic listening tasks, we tested left-ear tinnitus patients and control patients for their ability to ignore speech and speaker information in the task-irrelevant ear. To this end they heard vowel-consonant-vowel (VCV) syllables simultaneously spoken by gender-ambiguous voices in one ear and male or female voices in the contralateral ear. They selectively attended to speech (Exp. 1) or speaker (Exp. 2) information in a designated target ear, by classifying either the consonant (/b/ or /g/) in VCV syllables or voice gender (male or female) while ignoring distractor voices in the other ear. While performance was comparable across groups in the gender task, tinnitus patients responded slower than controls in the consonant task, with no effect of target ear. This suggests that tinnitus hampers phonetic perception in speech, while preserving the processing of extralinguistic speaker information. These findings support the growing evidence for speech perception impairments in tinnitus.Distress is a domain-general symptom that accompanies several disorders, including tinnitus. Based on previous studies, we know that distress is encoded by changes in functional connectivity between cortical and subcortical regions. However, how distress relates to large-scale brain networks is not yet clear. In the current study, we investigate the relationship between distress and the efficiency of a network by examining its topological properties using resting state fMRI collected from 90 chronic tinnitus patients. The present results indicate that distress negatively correlates with path length and positively correlates with clustering coefficient, small-worldness, and efficiency of information transfer. Specifically, path analysis showed that the relationship between distress and efficiency is significantly mediated by the resilience of the feeder connections and the centrality of the rich-club connections. In other words, the higher the network efficiency, the lower the resilience of the feeder connections and the centrality of the rich-club connections, which in turn reflects in higher distress in tinnitus patients. This indicates a reorganization of the network towards a paradoxically more efficient topology in patients with high distress, potentially explaining their increased rumination on the tinnitus percept itself.
Read More: https://www.selleckchem.com/products/erastin2.html
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