Emerging pharmacotherapy of tinnitus

Tinnitus, the perception of sound in the absence of an auditory stimulus, is perceived by about 1 in 10 adults, and for at least 1 in 100, tinnitus severely affects their quality of life. Because tinnitus is frequently associated with irritability, agitation, stress, insomnia, anxiety and depression, the social and economic burdens of tinnitus can be enormous. No curative treatments are available. However, tinnitus symptoms can be alleviated to some extent. The most widespread management therapies consist of auditory stimulation and cognitive behavioral treatment, aiming at improving habituation and coping strategies. Available clinical trials vary in methodological rigor and have been performed for a considerable number of different drugs. None of the investigated drugs have demonstrated providing replicable long-term reduction of tinnitus impact in the majority of patients in excess of placebo effects. Accordingly, there are no FDA or European Medicines Agency approved drugs for the treatment of tinnitus. However, in spite of the lack of evidence, a large variety of different compounds are prescribed off-label. Therefore, more effective pharmacotherapies for this huge and still growing market are desperately needed and even a drug that produces only a small but significant effect would have an enormous therapeutic impact. This review describes current and emerging pharmacotherapies with current difficulties and limitations. In addition, it provides an estimate of the tinnitus market. Finally, it describes recent advances in the tinnitus field which may help overcome obstacles faced in the pharmacological treatment of tinnitus. These include incomplete knowledge of tinnitus pathophysiology, lack of well-established animal models, heterogeneity of different forms of tinnitus, difficulties in tinnitus assessment and outcome measurement and variability in clinical trial methodology. © 2009 Informa UK Ltd.Fil: Langguth, Berthold. Universitat Regensburg; AlemaniaFil: Salvi, Richard. State University of New York; Estados UnidosFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentin

Temporomandibular Joint Disorder Complaints in Tinnitus: Further Hints for a Putative Tinnitus Subtype

OBJECTIVE: Tinnitus is considered to be highly heterogeneous with respect to its etiology, its comorbidities and the response to specific interventions. Subtyping is recommended, but it remains to be determined which criteria are useful, since it has not yet been clearly demonstrated whether and to which extent etiologic factors, comorbid states and interventional response are related to each other and are thus applicable for subtyping tinnitus. Analyzing the Tinnitus Research Initiative Database we differentiated patients according to presence or absence of comorbid temporomandibular joint (TMJ) disorder complaints and compared the two groups with respect to etiologic factors. METHODS: 1204 Tinnitus patients from the Tinnitus Research Initiative (TRI) Database with and without subjective TMJ complaints were compared with respect to demographic, tinnitus and audiological characteristics, questionnaires, and numeric ratings. Data were analysed according to a predefined statistical analysis plan. RESULTS: Tinnitus patients with TMJ complaints (22% of the whole group) were significantly younger, had a lower age at tinnitus onset, and were more frequently female. They could modulate or mask their tinnitus more frequently by somatic maneuvers and by music or sound stimulation. Groups did not significantly differ for tinnitus duration, type of onset (gradual/abrupt), onset related events (whiplash etc.), character (pulsatile or not), hyperacusis, hearing impairment, tinnitus distress, depression, quality of life and subjective ratings (loudness etc.). CONCLUSION: Replicating previous work in tinnitus patients with TMJ complaints, classical risk factors for tinnitus like older age and male gender are less relevant in tinnitus patients with TMJ complaints. By demonstrating group differences for modulation of tinnitus by movements and sounds our data further support the notion that tinnitus with TMJ complaints represents a subgroup of tinnitus with clinical features that are highly relevant for specific therapeutic management

Phototherapy and exchange transfusion for neonatal hyperbilirubinaemia

The purpose of this document is to address the current lack of consensus  regarding the management of hyperbilirubinaemia in neonates in South Africa. If left untreated, severe neonatal hyperbilirubinaemia may cause kernicterus and ultimately death and the severity of neonatal jaundice is often underestimated clinically. However, if phototherapy is instituted  timeously and at the correct intensity an exchange transfusion can usually be avoided. The literature describing intervention thresholds for  phototherapy and exchange transfusion in both term and preterm infants is therefore reviewed and specific intervention thresholds that can be used throughout South Africa are proposed and presented graphically. A simplified version for use in a primary care setting is also presented. All academic heads of neonatology departments throughout South Africa were consulted in the process of drawing up this document and consensus was achieved

Fitting model of ABR age dependency in a clinical population of normal hearing children

The purpose of this study was to present a simple and powerful fitting model that describes age-dependent changes of auditory brainstem responses (ABR) in a clinical population of normal hearing children. A total of 175 children (younger than 200 weeks postconceptional age) were referred for audiologic assessment with normal ABR results. ABR parameters of normal hearing children between 2003 and 2008 were included. The results of the right ears recorded at 90 dB nHL were analyzed. A simple and accurate fitting model was formulated based on these data. A very similar age-dependent effect was found for peaks III and V, and I–III and I–V intervals; latencies decrease as postconceptional age increases. It shows that the total age-dependent effect will be completed after 1.5–2 years. The age-dependent effect can be modeled by a relatively simple and accurate exponential function. This fitting model can be easily implemented to analyze ABR results of infants in daily clinical practice. We speculate about the underlying physiological processes

Perinatal determinants of germ-cell testicular cancer in relation to histological subtypes

We aimed to investigate the role of perinatal determinants on the risk for germ-cell testicular cancer, with respect to the aetiological heterogeneity between seminomas and non-seminomas. A case–control study of 628 case patients with testicular cancer (308 seminomas and 320 non-seminomas) and 2309 individually matched controls was nested within a cohort of boys born from 1920 to 1980 in two Swedish regions (Uppsala-Örebro Health Care Region and Stockholm). Cases were diagnosed from 1958 to 1998 and were identified through the Swedish National Cancer Registry. Perinatal information on cases and controls was collected through charts available at maternity wards. Gestational duration, categorised in three categories (<37, 37–41, >41 weeks), was negatively associated with the risk for testicular cancer (P value for linear trend=0.008). A protective effect of long gestational duration and an increased risk for high birth weight were found for seminomas. Non-seminomas were associated with short gestational duration, particularly among those with low birth order (odds ratio: 3.02, 95% confidence intervals: 1.53–5.97) and high maternal age (odds ratio: 2.33, 95% confidence intervals: 1.19–4.55). No significant differences were found in tests for heterogeneity between the two histological groups. Our data support the hypothesis that intrauterine environment affects the risk for germ-cell testicular cancer. Seminomas and non-seminomas seemed to have similar risk patterns, although they are not entirely congruent

Mining and analysis of audiology data to find significant factors associated with tinnitus masker

Objectives: The objective of this research is to find the factors associated with tinnitus masker from the literature, and by using the large amount of audiology data available from a large NHS (National Health Services, UK) hearing aid clinic. The factors evaluated were hearing impairment, age, gender, hearing aid type, mould and clinical comments. Design: The research includes literature survey for factors associated with tinnitus masker, and performs the analysis of audiology data using statistical and data mining techniques. Setting: This research uses a large audiology data but it also faced the problem of limited data for tinnitus. Participants: It uses 1,316 records for tinnitus and other diagnoses, and 10,437 records of clinical comments from a hearing aid clinic. Primary and secondary outcome measures: The research is looking for variables associated with tinnitus masker, and in future, these variables can be combined into a single model to develop a decision support system to predict about tinnitus masker for a patient. Results: The results demonstrated that tinnitus maskers are more likely to be fit to individuals with milder forms of hearing loss, and the factors age, gender, type of hearing aid and mould were all found significantly associated with tinnitus masker. In particular, those patients having Age<=55 years were more likely to wear a tinnitus masker, as well as those with milder forms of hearing loss. ITE (in the ear) hearing aids were also found associated with tinnitus masker. A feedback on the results of association of mould with tinnitus masker from a professional audiologist of a large NHS (National Health Services, UK) was also taken to better understand them. The results were obtained with different accuracy for different techniques. For example, the chi-squared test results were obtained with 95% accuracy, for Support and Confidence only those results were retained which had more than 1% Support and 80% Confidence. Conclusions: The variables audiograms, age, gender, hearing aid type and mould were found associated with the choice of tinnitus masker in the literature and by using statistical and data mining techniques. The further work in this research would lead to the development of a decision support system for tinnitus masker with an explanation that how that decision was obtained

Supplementation of a western diet with golden kiwifruits (Actinidia chinensis var.'Hort 16A':) effects on biomarkers of oxidation damage and antioxidant protection

<p>Abstract</p> <p>Background</p> <p>The health positive effects of diets high in fruits and vegetables are generally not replicated in supplementation trials with isolated antioxidants and vitamins, and as a consequence the emphasis of chronic disease prevention has shifted to whole foods and whole food products.</p> <p>Methods</p> <p>We carried out a human intervention trial with the golden kiwifruit, Actinidia chinensis, measuring markers of antioxidant status, DNA stability, plasma lipids, and platelet aggregation. Our hypothesis was that supplementation of a normal diet with kiwifruits would have an effect on biomarkers of oxidative status. Healthy volunteers supplemented a normal diet with either one or two golden kiwifruits per day in a cross-over study lasting 2 × 4 weeks. Plasma levels of vitamin C, and carotenoids, and the ferric reducing activity of plasma (FRAP) were measured. Malondialdehyde was assessed as a biomarker of lipid oxidation. Effects on DNA damage in circulating lymphocytes were estimated using the comet assay with enzyme modification to measure specific lesions; another modification allowed estimation of DNA repair.</p> <p>Results</p> <p>Plasma vitamin C increased after supplementation as did resistance towards H₂O₂-induced DNA damage. Purine oxidation in lymphocyte DNA decreased significantly after one kiwifruit per day, pyrimidine oxidation decreased after two fruits per day. Neither DNA base excision nor nucleotide excision repair was influenced by kiwifruit consumption. Malondialdehyde was not affected, but plasma triglycerides decreased. Whole blood platelet aggregation was decreased by kiwifruit supplementation.</p> <p>Conclusion</p> <p>Golden kiwifruit consumption strengthens resistance towards endogenous oxidative damage.</p

Histological confirmation of breast cancer registration and self-reporting in England and Wales: a cohort study within the UK Collaborative Trial of Ovarian Cancer Screening

In research studies, accurate information of cancer diagnosis is crucial. In women with breast cancer (BC), we compare cancer registration (CR) in England/Wales and self-reporting with independent confirmation