Prevention of cisplatin-induced hearing loss in children: Informing the design of future clinical trials.

Cisplatin is an essential chemotherapeutic agent in the treatment of many pediatric cancers. Unfortunately, cisplatin-induced hearing loss (CIHL) is a common, clinically significant side effect with life-long ramifications, particularly for young children. ACCL05C1 and ACCL0431 are two recently completed Childrens Oncology Group studies focused on the measurement and prevention of CIHL. The purpose of this paper was to gain insights from ACCL05C1 and ACCL0431, the first published cooperative group studies dedicated solely to CIHL, to inform the design of future pediatric otoprotection trials. Use of otoprotective agents is an attractive strategy for preventing CIHL, but their successful development must overcome a unique constellation of methodological challenges related to translating preclinical research into clinical trials that are feasible, evaluate practical interventions, and limit risk. Issues particularly important for children include use of appropriate methods for hearing assessment and CIHL severity grading, and use of trial designs that are well-informed by preclinical models and suitable for relatively small sample sizes. Increasing interest has made available new funding opportunities for expanding this urgently needed research

Determination and evaluation of clinically efficient stopping criteria for the multiple auditory steady-state response technique

Background: Although the auditory steady-state response (ASSR) technique utilizes objective statistical detection algorithms to estimate behavioural hearing thresholds, the audiologist still has to decide when to terminate ASSR recordings introducing once more a certain degree of subjectivity. Aims: The present study aimed at establishing clinically efficient stopping criteria for a multiple 80-Hz ASSR system. Methods: In Experiment 1, data of 31 normal hearing subjects were analyzed off-line to propose stopping rules. Consequently, ASSR recordings will be stopped when (1) all 8 responses reach significance and significance can be maintained for 8 consecutive sweeps; (2) the mean noise levels were ≤ 4 nV (if at this “≤ 4-nV” criterion, p-values were between 0.05 and 0.1, measurements were extended only once by 8 sweeps); and (3) a maximum amount of 48 sweeps was attained. In Experiment 2, these stopping criteria were applied on 10 normal hearing and 10 hearing-impaired adults to asses the efficiency. Results: The application of these stopping rules resulted in ASSR threshold values that were comparable to other multiple-ASSR research with normal hearing and hearing-impaired adults. Furthermore, in 80% of the cases, ASSR thresholds could be obtained within a time-frame of 1 hour. Investigating the significant response-amplitudes of the hearing-impaired adults through cumulative curves indicated that probably a higher noise-stop criterion than “≤ 4 nV” can be used. Conclusions: The proposed stopping rules can be used in adults to determine accurate ASSR thresholds within an acceptable time-frame of about 1 hour. However, additional research with infants and adults with varying degrees and configurations of hearing loss is needed to optimize these criteria

The psychophysics of absolute threshold and signal duration: A probabilistic approach

The absolute threshold for a tone depends on its duration; longer tones have lower thresholds. This effect has traditionally been explained in terms of ?temporal integration? involving the summation of energy or perceptual information over time. An alternative probabilistic explanation of the process is formulated in terms of simple equations that predict not only the time=duration dependence but also the shape of the psychometric function at absolute threshold. It also predicts a tight relationship between these two functions. Measurements made using listeners with either normal or impaired hearing show that the probabilistic equations adequately fit observed threshold-duration functions and psychometric functions. The mathematical formulation implies that absolute threshold can be construed as a two-valued function: (a) gain and (b) sensory threshold, and both parameters can be estimated from threshold-duration data. Sensorineural hearing impairment is sometimes associated with a smaller threshold=duration effect and sometimes with steeper psychometric functions. The equations explain why these two effects are expected to be linked. The probabilistic approach has the potential to discriminate between hearing deficits involving gain reduction and those resulting from a raised sensory threshold

Modelling costs and outcomes of newborn hearing screening: The economic part of a German health technology assessment project

The prevalence of newborn hearing disorders is 1-3 per 1000. Crucial for later outcome are correct diagnosis and effective treatment in the first year of life. With BERA and TEOAE low-risk techniques for early detection are available. Universal screening is recommended but not realised in most European health care systems. Objective of the study was to examine the scientific evidence of newborn hearing screening, thus to compare cost-effectiveness of different programmes, differentiated by type of strategy (risk screening, universal screening, no screening). Methods: In an interdisciplinary health technology assessment project all relevant studies on newborn hearing screening were identified and data on medical outcome, costs and cost-effectiveness extracted. A Markov model was designed to calculate cost-effectiveness ratios. Results: Economic data were extracted from 20 relevant publications. In the model total costs for screening of 100.000 newborns with a time horizon of ten years were calculated: 2.0 Mio . for universal screening (U), 1.0 Mio. for risk screening (R) and 0.6 Mio. for no screening (N). The costs per child detected: 13,395 (U) respectively 6,715 (R) and 4,125 (N). Conclusions: A remarkable small number of economic publications mainly of low methodo-logical quality was found. In our own model we found reasonable cost-effectiveness ratios also for universal screening. Considering the outcome advantages of higher numbers of cases detected a universal newborn hearing screening is recommended. --

Auditory and cognitive performance in elderly musicians and nonmusicians

Musicians represent a model for examining brain and behavioral plasticity in terms of cognitive and auditory profile, but few studies have investigated whether elderly musicians have better auditory and cognitive abilities than nonmusicians. The aim of the present study was to examine whether being a professional musician attenuates the normal age-related changes in hearing and cognition. Elderly musicians still active in their profession were compared with nonmusicians on auditory performance (absolute threshold, frequency intensity, duration and spectral shape discrimination, gap and sinusoidal amplitude-modulation detection), and on simple (short-term memory) and more complex and higher-order (working memory [WM] and visuospatial abilities) cognitive tasks. The sample consisted of adults at least 65 years of age. The results showed that older musicians had similar absolute thresholds but better supra-threshold discrimination abilities than nonmusicians in four of the six auditory tasks administered. They also had a better WM performance, and stronger visuospatial abilities than nonmusicians. No differences were found between the two groups\u2019 short-term memory. Frequency discrimination and gap detection for the auditory measures, and WM complex span tasks and one of the visuospatial tasks for the cognitive ones proved to be very good classifiers of the musicians. These findings suggest that life-long music training may be associated with enhanced auditory and cognitive performance, including complex cognitive skills, in advanced age. However, whether this music training represents a protective factor or not needs further investigation

Adverse Events among HIV/MDR-TB Co-Infected Patients Receiving Antiretroviral and Second Line Anti-TB Treatment in Mumbai, India.

Significant adverse events (AE) have been reported in patients receiving medications for multidrug- and extensively-drug-resistant tuberculosis (MDR-TB & XDR-TB). However, there is little prospective data on AE in MDR- or XDR-TB/HIV co-infected patients on antituberculosis and antiretroviral therapy (ART) in programmatic settings

Frontal brain asymmetries as effective parameters to assess the quality of audiovisual stimuli perception in adult and young cochlear implant users

How is music perceived by cochlear implant (CI) users? This question arises as "the next step" given the impressive performance obtained by these patients in language perception. Furthermore, how can music perception be evaluated beyond self-report rating, in order to obtain measurable data? To address this question, estimation of the frontal electroencephalographic (EEG) alpha activity imbalance, acquired through a 19-channel EEG cap, appears to be a suitable instrument to measure the approach/withdrawal (AW index) reaction to external stimuli. Specifically, a greater value of AW indicates an increased propensity to stimulus approach, and vice versa a lower one a tendency to withdraw from the stimulus. Additionally, due to prelingually and postlingually deafened pathology acquisition, children and adults, respectively, would probably differ in music perception. The aim of the present study was to investigate children and adult CI users, in unilateral (UCI) and bilateral (BCI) implantation conditions, during three experimental situations of music exposure (normal, distorted and mute). Additionally, a study of functional connectivity patterns within cerebral networks was performed to investigate functioning patterns in different experimental populations. As a general result, congruency among patterns between BCI patients and control (CTRL) subjects was seen, characterised by lowest values for the distorted condition (vs. normal and mute conditions) in the AW index and in the connectivity analysis. Additionally, the normal and distorted conditions were significantly different in CI and CTRL adults, and in CTRL children, but not in CI children. These results suggest a higher capacity of discrimination and approach motivation towards normal music in CTRL and BCI subjects, but not for UCI patients. Therefore, for perception of music CTRL and BCI participants appear more similar than UCI subjects, as estimated by measurable and not self-reported parameters

Cochlear implant programming: a global survey on the state of the art

The programming of CIs is essential for good performance. However, no Good Clinical Practice guidelines exist. This paper reports on the results of an inventory of the current practice worldwide. A questionnaire was distributed to 47 CI centers. They follow 47600 recipients in 17 countries and 5 continents. The results were discussed during a debate. Sixty-two percent of the results were verified through individual interviews during the following months. Most centers (72%) participated in a cross-sectional study logging 5 consecutive fitting sessions in 5 different recipients. Data indicate that general practice starts with a single switch-on session, followed by three monthly sessions, three quarterly sessions, and then annual sessions, all containing one hour of programming and testing. The main focus lies on setting maximum and, to a lesser extent, minimum current levels per electrode. These levels are often determined on a few electrodes and then extrapolated. They are mainly based on subjective loudness perception by the CI user and, to a lesser extent, on pure tone and speech audiometry. Objective measures play a small role as indication of the global MAP profile. Other MAP parameters are rarely modified. Measurable targets are only defined for pure tone audiometry. Huge variation exists between centers on all aspects of the fitting practice