COAST (Cisplatin ototoxicity attenuated by aspirin trial): A phase II double-blind, randomised controlled trial to establish if aspirin reduces cisplatin induced hearing-loss.

BACKGROUND: Cisplatin is one of the most ototoxic chemotherapy drugs, resulting in a permanent and irreversible hearing loss in up to 50% of patients. Cisplatin and gentamicin are thought to damage hearing through a common mechanism, involving reactive oxygen species in the inner ear. Aspirin has been shown to minimise gentamicin-induced ototoxicity. We, therefore, tested the hypothesis that aspirin could also reduce ototoxicity from cisplatin-based chemotherapy. METHODS: A total of 94 patients receiving cisplatin-based chemotherapy for multiple cancer types were recruited into a phase II, double-blind, placebo-controlled trial and randomised in a ratio of 1:1 to receive aspirin 975 mg tid and omeprazole 20 mg od, or matched placebos from the day before, to 2 days after, their cisplatin dose(s), for each treatment cycle. Patients underwent pure tone audiometry before and at 7 and 90 days after their final cisplatin dose. The primary end-point was combined hearing loss (cHL), the summed hearing loss at 6 kHz and 8 kHz, in both ears. RESULTS: Although aspirin was well tolerated, it did not protect hearing in patients receiving cisplatin (p-value = 0.233, 20% one-sided level of significance). In the aspirin arm, patients demonstrated mean cHL of 49 dB (standard deviation [SD] 61.41) following cisplatin compared with placebo patients who demonstrated mean cHL of 36 dB (SD 50.85). Women had greater average hearing loss than men, and patients treated for head and neck malignancy experienced the greatest cHL. CONCLUSIONS: Aspirin did not protect from cisplatin-related ototoxicity. Cisplatin and gentamicin may therefore have distinct ototoxic mechanisms, or cisplatin-induced ototoxicity may be refractory to the aspirin regimen used here.

The choice of distracting task can affect the quality of auditory evoked potentials recorded for clinical assessment.

Auditory evoked potential (AEP) recordings often require subjects to ignore the stimuli and stay awake. In the present experiment, early (ABR), middle (MLR), and late latency (LLR) AEPs were recorded to compare the effect of five different distracting tasks: (1) doing nothing eyes open, (2) reading, (3) watching a movie, (4) solving a three-digit sum, and (5) doing nothing eyes closed (or counting the stimuli for LLR). Results showed that neither the amplitudes nor the latencies of the ABR, MLR, or LLR were affected by task. However, the amount of pre-stimulus activity (noise) or amplitude rejection was significantly and differently affected by the distracting task. For the ABR, the math task was the noisiest but, for the MLR, the amount of noise was greater when watching a movie. As for the LLR, reading and watching a movie yielded the lowest percentage of rejected traces. In conclusion, the choice of distracting task depends on the AEP being measured and should be chosen to improve the quality of the AEP traces and thus reduce recording time.

Does long-term unilateral deafness change auditory evoked potential asymmetries?

OBJECTIVE: To investigate the long-term cortical changes in auditory evoked potential (AEP) asymmetries associated with profound unilateral deafness. METHODS: Electroencephalographic (EEG) recordings from 68 channels were used to measure auditory cortex responses to monaural stimulation from 7 unilaterally deaf patients and 7 audiogram-matched controls. Source localization of the AEP N100 response was carried out and regional source waveform amplitude and latency asymmetries were analysed for activity in the N100 latency range and for the middle latency response (MLR) range. RESULTS: Asymmetry indices (contralateral-ipsilateral)/(contralateral+ipsilateral) showed that matched control subjects, like normally hearing participants, produced activity in the N100 latency range that was more contralaterally dominant for left compared to right ear stimulation. Contrary to expectation, source waveforms and asymmetry indices in the MLR and N100 latency range were similar for unilaterally deaf patients, their matched controls and a group of normally hearing participants. CONCLUSIONS: Regional source waveform analysis revealed no evidence of systematic cortical changes in hemispheric asymmetries associated with long-term unilateral deafness. It is possible that a reorganization of cortical asymmetries to a 'normal' pattern had taken place in the years between deafness and testing. SIGNIFICANCE: Electrophysiological measures of auditory hemispheric asymmetries do not suggest long-term cortical reorganisation as a result of profound unilateral deafness.

Universal newborn screening for permanent childhood hearing impairment: an 8-year follow-up of a controlled trial.

An 8-year follow-up study of the birth cohort of babies enrolled in the Wessex controlled trial of universal newborn screening (UNS) for permanent childhood hearing impairment (PCHI) was undertaken to establish whether UNS would increase the proportion of all true cases of PCHI in children aged 7-9 years who are referred early. The proportion referred before 6 months of age increased from 11 of 35 (31%) children with true PCHI born during periods without UNS to 23 of 31 (74%) born during periods with UNS (difference 43%, 95% CI 19-60). UNS leads to early referral of PCHI.