Abstract Tinnitus is a very frequent symptom affecting 10% of the general population. It corresponds to the perception of an internal noise that can severely impair the quality of life. Tinnitus ...management requires a multidisciplinary approach in which neuromodulation and neurosurgery tend to play major roles. Classification of tinnitus separates objective tinnitus (i.e., tinnitus that can be heard or recorded) from the more frequent subjective tinnitus (i.e., tinnitus only perceived by the patient). Objective tinnitus is either pulsatile synchronous with heartbeat or asynchronous. In the former, appropriate radiological testing should search for a vascular abnormality as well as other neurological diseases (intracranial hypertension, Arnold-Chiari malformation, vascular loops, etc.). Asynchronous objective tinnitus generally corresponds to muscular contractions that require specific management. The pathophysiology of subjective tinnitus is more complex, showing strong analogies with postamputation pain syndromes. After peripheral middle ear or inner ear damage, auditory deafferentation could result in hyperactivity and/or functional reorganization within central auditory and nonauditory structures. This could explain the persistence of tinnitus after total hearing amputation (e.g., translabyrinthine approach for vestibular schwannoma) and associated symptoms such as hyperacusis or anxiety and depression. This central model finds strong support in animal experiments and in functional neuroimagery (PET, fMRI, MEG). Since no etiologically based therapies are currently available, severe subjective tinnitus management only targets tinnitus tolerance with sound enrichment or cognitive behavior therapy. However, in the near future better knowledge of tinnitus pathophysiology and innovative therapeutic tools could emerge from neuromodulation techniques such as repeated transcranial magnetic or epidural electric stimulation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The aim of this study was to evaluate the ovarian function in women who received or not gonadotropin-releasing hormone (GnRH) analogue co-treatment compared to the control group that did not receive ...it.
This study analyzed 124 patients affected by hematological diseases between 1998 and 2007. The data were analyzed using R (v 2.9.1).
In the women treated with GnRH analogue, the authors found 33% post-treatment secondary amenorrhea and 6% had a pregnancy post-treatment, while in the other group the prevalence were respectively 49% and 4% (p n.s.). Moreover, in multivariate analysis the authors found bone marrow transplantation to be a risk factor for secondary amenorrhea, while the association of chemotherapy with radiotherapy was a protective factor (p < 0.05). Finally, none of the considered factors were predictive of pregnancy achievement post-treatment.
The authors found no statistical evidence to support that Gn-RH analogue treatment preserves ovarian follicular reserve during hematologic cancer treatment, but more evidence must be obtained.
There is no evidence-based guidance to facilitate design decisions for confirmatory trials or systematic reviews investigating treatment efficacy for adults with tinnitus. This systematic review ...therefore seeks to ascertain the current status of trial designs by identifying and evaluating the reporting of outcome domains and instruments in the treatment of adults with tinnitus.
Records were identified by searching PubMed, EMBASE CINAHL, EBSCO, and CENTRAL clinical trial registries (ClinicalTrials.gov, ISRCTN, ICTRP) and the Cochrane Database of Systematic Reviews. Eligible records were those published from 1 July 2006 to 12 March 2015. Included studies were those reporting adults aged 18 years or older who reported tinnitus as a primary complaint, and who were enrolled into a randomised controlled trial, a before and after study, a non-randomised controlled trial, a case-controlled study or a cohort study, and written in English. Studies with fewer than 20 participants were excluded.
Two hundred and twenty-eight studies were included. Thirty-five different primary outcome domains were identified spanning seven categories (tinnitus percept, impact of tinnitus, co-occurring complaints, quality of life, body structures and function, treatment-related outcomes and unclear or not specified). Over half the studies (55 %) did not clearly define the complaint of interest. Tinnitus loudness was the domain most often reported (14 %), followed by tinnitus distress (7 %). Seventy-eight different primary outcome instruments were identified. Instruments assessing multiple attributes of the impact of tinnitus were most common (34 %). Overall, 24 different patient-reported tools were used, predominantly the Tinnitus Handicap Inventory (15 %). Loudness was measured in diverse ways including a numerical rating scale (8 %), loudness matching (4 %), minimum masking level (1 %) and loudness discomfort level (1 %). Ten percent of studies did not clearly report the instrument used.
Our findings indicate poor appreciation of the basic principles of good trial design, particularly the importance of specifying what aspect of therapeutic benefit is the main outcome. No single outcome was reported in all studies and there was a broad diversity of outcome instruments.
The systematic review protocol is registered on PROSPERO (International Prospective Register of Systematic Reviews): CRD42015017525 . Registered on 12 March 2015 revised on 15 March 2016.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The heterogeneity of tinnitus is substantial. Its numerous pathophysiological mechanisms and clinical manifestations have hampered fundamental and treatment research significantly. A decade ago, the ...Tinnitus Research Initiative introduced the Tinnitus Sample Case History Questionnaire, a case history instrument for standardised collection of information about the characteristics of the tinnitus patient. Since then, a number of studies have been published which characterise individuals and groups using data collected with this questionnaire. However, its use has been restricted to a clinical setting and to the evaluation of people with tinnitus only. In addition, it is limited in the ability to capture relevant comorbidities and evaluate their temporal relationship with tinnitus.
Here we present a new case history instrument which is comprehensive in scope and can be answered by people with and without tinnitus alike. This ‘European School for Interdisciplinary Tinnitus Research Screening Questionnaire’ (ESIT-SQ) was developed with specific attention to questions about potential risk factors for tinnitus (including demographics, lifestyle, general medical and otological histories), and tinnitus characteristics (including perceptual characteristics, modulating factors, and associations with co-existing conditions). It was first developed in English, then translated into Dutch, German, Italian, Polish, Spanish, and Swedish, thus having broad applicability and supporting international collaboration.
With respect to better understanding tinnitus profiles, we anticipate the ESIT-SQ to be a starting point for comprehensive multi-variate analyses of tinnitus. Data collected with the ESIT-SQ can allow establishment of patterns that distinguish tinnitus from non-tinnitus, and definition of common sets of tinnitus characteristics which might be indicated by the presence of otological or comorbid systemic diseases for which tinnitus is a known symptom.
•ESIT-SQ: a self-report tinnitus-relevant history questionnaire.•39 questions relevant for tinnitus profiling: 17 general and 22 tinnitus-specific.•Available in Dutch, English, German, Italian, Polish, Spanish and Swedish.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Résumé Au cours de la dernière décennie, un très grand nombre de travaux de stimulation magnétique transcrânienne (ou transcranial magnetic stimulation , TMS) ont été effectués, comprenant notamment ...l’élaboration de nouveaux paradigmes de stimulation, l’intégration des données d’imagerie et le couplage de techniques de TMS et d’EEG ou de neuroimagerie. Aussi, devant l’accumulation de ces données difficiles à synthétiser, plusieurs sociétés savantes francophones ont mandaté un groupe d’experts français afin de réaliser une analyse exhaustive de la littérature concernant la TMS. Ce texte de consensus reprend l’ensemble des conclusions de ce groupe d’experts sur les mécanismes d’action, les règles de sécurité et les indications thérapeutiques de la TMS, notamment répétitive (rTMS). Des séances de TMS ont été réalisées chez des milliers de sujets sains ou des patients souffrant de diverses maladies neurologiques ou psychiatriques, permettant une meilleure évaluation des risques relatifs liés à cette technique. Le nombre d’effets secondaires rapportés est extrêmement faible, la complication la plus sérieuse étant la survenue de crises d’épilepsie. Dans la plupart des crises rapportées, les paramètres de stimulation ne suivaient pas les recommandations précédemment publiées (Wassermann, 1998) 430 et souvent il existait un traitement médicamenteux qui pouvait abaisser le seuil épileptogène. Les recommandations sur la sécurité d’utilisation de la TMS/rTMS ont été récemment actualisées (Rossi et al., 2009) 348 , fixant les contre-indications et établissant de nouvelles limites concernant les différents paramètres de stimulation. Concernant les règles de sécurité, les recommandations que nous proposons pour un public francophone sont donc en grande partie fondées sur ce précédent article avec quelques adaptations. La question des indications thérapeutiques de la rTMS n’avait jamais fait en revanche l’objet d’un travail de synthèse. Nous avons abordé les pathologies suivantes : douleurs chroniques, mouvements anormaux, accidents vasculaires cérébraux, épilepsie, acouphènes et pathologies psychiatriques. Il y a déjà pour certaines d’entre elles (douleurs neuropathiques chroniques, épisodes dépressifs majeurs, hallucinations auditives), un niveau de preuves suffisant des études publiées, pour retenir une indication thérapeutique de la rTMS en pratique clinique. Ces indications devraient encore se développer dans les prochaines années et les paramètres de stimulation optimaux à utiliser en fonction de ces indications devraient également se préciser.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Tinnitus - the perception of sound in one or both ears or in the head when no external sound is present - can be disabling and is especially difficult to treat. Repetitive transcranial magnetic ...stimulation (rTMS) is a noninvasive technique for activating or inactivating specific areas of the cortex. The aim of this study was to assess the feasibility of magnetic neurostimulation of the primary and secondary auditory cortex in the treatment of disabling chronic tinnitus.
Thirteen patients with tinnitus refractory to several conventional treatments underwent transcranial magnetic stimulation guided by functional magnetic resonance imaging (fMRI). We compared two types of stimulation of targets in the auditory cortex, identified by fMRI: 3-second pulses at high frequency (10 Hz) and 20-minute stimulations at a lower frequency (1 Hz).
Brief high-frequency pulses of cortical magnetic stimulation (10 Hz) were not effective. On the other hand, prolonged low frequency (1 Hz) stimulation was effective in 62.5% of patients; the effect appeared 48 h after treatment and lasted for approximately 5 days.
RTMS may be a new noninvasive technique for studying the cortical plasticity associated with the pathophysiologic mechanisms of chronic tinnitus and may lead to new treatment strategies for patients with disabling tinnitus resistant to all treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
It is still debated if pre-existing minority drug-resistant HIV-1 variants (MVs) affect the virological outcomes of first-line NNRTI-containing ART.
This Europe-wide case-control study included ...ART-naive subjects infected with drug-susceptible HIV-1 as revealed by population sequencing, who achieved virological suppression on first-line ART including one NNRTI. Cases experienced virological failure and controls were subjects from the same cohort whose viraemia remained suppressed at a matched time since initiation of ART. Blinded, centralized 454 pyrosequencing with parallel bioinformatic analysis in two laboratories was used to identify MVs in the 1%-25% frequency range. ORs of virological failure according to MV detection were estimated by logistic regression.
Two hundred and sixty samples (76 cases and 184 controls), mostly subtype B (73.5%), were used for the analysis. Identical MVs were detected in the two laboratories. 31.6% of cases and 16.8% of controls harboured pre-existing MVs. Detection of at least one MV versus no MVs was associated with an increased risk of virological failure (OR = 2.75, 95% CI = 1.35-5.60, P = 0.005); similar associations were observed for at least one MV versus no NRTI MVs (OR = 2.27, 95% CI = 0.76-6.77, P = 0.140) and at least one MV versus no NNRTI MVs (OR = 2.41, 95% CI = 1.12-5.18, P = 0.024). A dose-effect relationship between virological failure and mutational load was found.
Pre-existing MVs more than double the risk of virological failure to first-line NNRTI-based ART.
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