Effects of low-dose metformin and rosiglitazone on biochemical, clinical, metabolic and biophysical outcomes in polycystic ovary syndrome.

The aim of this study was to compare the effect of low-dose metformin and rosiglitazone on clinical, biochemical, ultrasound features and endothelial function in patients with polycystic ovary syndrome (PCOS). After randomisation, a group of 17 women received metformin 500 mg b.d. (MG) and a group of 18 received rosiglitazone 4 mg o.d. (RG) for 3 months. Serum FSH, LH, testosterone, fasting glucose, insulin, IGF-1, IGFBP-3, CRP were measured at baseline and follow-up. Ovarian scan and microcirculation studies were also performed. It was found that there was a reduction in hyperandrogenaemia, insulin resistance, lipidaemia, CRP levels, ovarian volume and number of follicles in both groups. No improvement in endothelial- dependent function was noted but a significant improvement in endothelial-independent function in rosiglitazone group. It was concluded that low-dose therapeutic regimen with rosiglitazone and metformin, has comparable beneficial impacts on metabolic, hormonal and morphological features of PCOS but no obvious effect on vascular parameters in a population of predominantly mild PCOS.

Outcomes and efficacy of newborn hearing screening: strengths and weaknesses (success or failure?).

OBJECTIVE: To assess the outcomes of neonatal hearing screening with regard to the final diagnosis in a very large number of newborns and investigate related strengths and weaknesses of the program. SUBJECTS: In this study, 76,560 newborns were assessed. METHOD: All neonates were assessed using transient evoked otoacoustic emissions (TEOAEs). RESULTS: From the 76,560 neonates screened, 1,564 (2%) failed the test. According to the screening protocol, all parents of failed neonates were asked to bring their children 1 month following discharge to repeat the test. Of the 541 (34.6%) newborns who repeated the test, 303 (56%) were found normal and 238 (44%) again failed TEOAE. The latter children were referred to two special public centers for full audiology evaluation. In addition, 124 neonates were also referred due to other reasons revealed in the screening process (family history, high levels of bilirubin, etc.). Of the 362 children who were referred to the two special audiology centers, 113 (31.2%) were evaluated by these two centers. In addition, 42 children who had failed initial screening and did not show up for a follow-up appointment to repeat TEOAE were also assessed in the same centers. Of the 155 children who had a special audiologic evaluation, 56 (36.1%) were found to have hearing loss (HL) and 99 (63.9%) normal hearing. In detail, 28 had bilateral sensorineural HL greater than 40 dB, 10 had unilateral sensorineural HL greater than 40 dB, and 18 had otitis media with effusion or other conductive HL. CONCLUSIONS: Derived from the present study: 1) repeated testing of "failed" newborns in the maternity hospital and before discharge leads to an acceptable referral rate of 2%; 2) the 1-month follow-up of "failed" newborns further limits the false positive results but leads to high rate of newborns lost to follow-up; 3) a dedicated secretariat system should be implemented to follow-up each "failed" newborn and remind parents about their follow-up appointments; and 4) additional measures such as detailed educational material and parental friendly approach should also be implemented.

Neurotoxicity of vincristine on the medial olivocochlear bundle.

OBJECTIVE: Vincristine is a well known neurotoxic chemotherapeutic agent. Dose dependent and cumulative peripheral neuropathy is the main dose limiting side effect of chemotherapy with vincristine. The mechanisms responsible for the neurotoxic effects of vincristine have not yet been fully understood. This prospective study was directed at determining whether vincristine treatment interferes with the function of the medial olivocochlear bundle. DESIGN: Fifteen children suffering from leukemia were subjected to tympanogram, stapedial muscle reflex, pure tone audiometry and transient evoked otoacoustic emissions (TEOAEs) in the absence and presence of contralateral white noise on day 1 and on day 22 of treatment with vincristine. The function of the medial olivocochlear bundle was assessed by the phenomenon of suppression of otoacoustic emissions by contralateral application of white noise. RESULTS: The study revealed a statistically significant decrease of contralateral suppression amplitudes in all cases after three sessions of chemotherapy with vincristine. On the contrary no alterations were observed in pure tone audiometry thresholds. A non-significant decrease of the mean TEOAEs' amplitudes was also noted. When analyzed by frequency, however, this decrease reached the level of statistical significance at two frequencies. CONCLUSION: Vincristine treatment seems to exert a neurotoxic effect on the efferent olivocochlear system, which takes place early in the course of chemotherapy. This is a new aspect to be added to the possible mechanisms underlying the toxicity of vincristine in the auditory periphery. Whether changes in efferent function might contribute to understanding the mechanisms of neurotoxicity caused by vincristine, or find any clinical application as a predictor or early detector of neurological side effects of vincristine still remains to be seen.

IgE sensitization, respiratory allergy symptoms, and heritability independently increase the risk of otitis media with effusion.

BACKGROUND AND AIMS: Epidemiological evidence examining the role of atopy and/or allergy in the pathogenesis of otitis media with effusion (OME) is inconclusive. The aim of this study was to assess any increased risk for OME attributable to allergy-related factors, in a well-characterized population using a case-control design and multivariate analysis. SUBJECTS AND METHODS: Eighty-eight 1-7-year-old children with OME, diagnosed by clinical and tympanometric evaluation and 80 matched controls were enrolled. A standardized questionnaire was completed, in order to assess factors related to OME and allergy-related symptoms and diagnoses using strict clinical definitions. Specific IgE was measured by skin-prick tests and/or CAP-FEIA. RESULTS: The patient and control groups were well matched. Factors conferring increased risk for OME in the univariate analysis included IgE sensitization, dyspnea, wheezing, asthma, paroxysmal sneezing, rhinitis, eczema, 'any allergic disease,' family history of otitis media, and family history of allergy. After multivariate analysis IgE sensitization, wheezing, nasal obstruction, family history of otitis, and child-care attendance remained as independent risk factors for development of OME. CONCLUSION: IgE sensitization and respiratory allergy symptoms are independent risk factors for the development of OME, suggesting that both immunological and mechanical pathways may contribute to the development of the disease. Otitis heritability provides additional risk, as well as frequent exposure to viral upper respiratory tract infections in children attending daycare. Treatment and/or prevention of OME using anti-allergic medications should be further examined.

Transient otoacoustic emissions in the detection of olivocochlear bundle maturation.

OBJECTIVE: The medial olivocochlear bundle, forms a neural pathway connecting the superior olivary complex to the outer hair cells of mainly the contralateral cochlea. Although the biological significance of the bundle remains ambiguous, it is clear that activation of medial olivocochlear fibers alters cochlear output and this can be experimentally evident through a series of changes on otoacoustic emissions, called otoacoustic emission suppression. The aim of this study is to observe the maturation of the medial olivocochlear bundle by measuring the suppression effects on transient otoacoustic emissions. METHODS: The study population consisted of 27 premature babies (53 ears) from the P&A Kyriakou Neonatal Intensive Care Unit (conceptional age: 31-36 weeks) and 43 fullterm babies (61 ears) (conceptional age: 37-42 weeks) from the same unit. The ILO-92 system is used to deliver both the linear clicks to the ear examined (producing the emissions) and the white noise to the contralateral ear. The mode used is based on the alternating on and off presence of the white noise in the contralateral ear. RESULTS: 12/53 (22%) ears of preterm babies presented suppression > or =1 dB. 32/61 (52.4%) ears of fullterm babies presented suppression > or =1 dB. The mean suppression for the ears of premature infants was 0.52 dB, (+/-0.1 S.E.M.). The mean suppression for the ears of fullterm infants was 0.90 dB, (+/-0.09 S.E.M.). At the second half of the time window, suppression of fullterms rises above 1 dB (a pattern similar to that of adults), whereas it remains below 1 dB for preterms. CONCLUSIONS: Suppression of otoacoustic emissions helps us to study the function of the medial olivocochlear bundle in different populations. It appears in premature babies but becomes stronger as the postconceptional age advances.

The effect of treatment with vincristine on transient evoked and distortion product otoacoustic emissions.

OBJECTIVE: Vincristine chemotherapy is mainly associated with neurotoxic effects. The ototoxicity of vincristine has been related to high dosage, while low and moderate doses do not seem to induce significant hearing impairment when measured by pure tone or speech audiometry. Otoacoustic emissions have been reported to be more sensitive in early detection of ototoxicity than conventional pure tone audiometry. The present study was directed at determining whether vincristine treatment interferes with outer hair cell function in the absence of measurable changes in pure tone audiometry. METHODS: We studied prospectively a cohort of ten children suffering from leukemia. All children were subjected to tympanogram, stapedial muscle reflex, pure tone audiometry, transient evoked (TEOAEs) and distortion product (DPOAEs) otoacoustic emissions on day 1 and on day 22 of treatment with vincristine. TEOAEs were analyzed in terms of emission level and reproducibility as a function of frequency. DPOAEs were obtained as DP-grams and were analyzed in terms of amplitude. RESULTS: The analyzed parameters of TEOAEs and DPOAEs revealed a declining tendency, although changes did not reach statistical significance. Pure tone audiometry and stapedial reflex thresholds were not altered. CONCLUSION: For the population of this study, vincristine did not seem to cause significant alterations of otoacoustic emissions' recordings and consequently significant outer hair cell damage.

Etiological diagnosis of bilateral, sensorineural hearing impairment in a pediatric Greek population.

Early diagnosis, evaluation and treatment of childhood deafness are essential for a child's normal growth. Etiological diagnosis of hearing loss makes prevention, family scheduling and more effective therapy feasible goals. Etiological assessment of sensorineural deafness still remains difficult although recently with the progress of genetics it has become more efficient. In this retrospective study, the etiology of bilateral, sensorineural hearing loss with indication for hearing aids has been studied in 153 hearing impaired children. Etiological diagnosis was based on family and patient record, physical, audiological and laboratory examinations. Among the 94 children who completed the diagnostic protocol etiological groups revealed the following distribution: non-hereditary acquired hearing impairment was present in 36 children (38%) and hereditary was present in 44 (47%) children. The etiology remained unknown in 14 (15%) children. Non-syndromic autosomal dominant type accounted for 13 (29% of hereditary hearing loss) children, non-syndromic autosomal recessive type for 21 (48%) children and syndromic deafness for 10 (23%) children. Modern diagnostic methods, such as genetic testing, help diminish the number of cases with hearing impairment of unknown etiology, for the benefit of children who receive early and appropriate medical, audiologic, genetic and educational counseling based on the etiology of their hearing loss.

Hearing evaluation with distortion-product otoacoustic emissions in young patients undergoing haemodialysis.

Sensorineural hearing loss is frequently reported in young patients with chronic renal failure having haemodialysis. The effect of a single session of haemodialysis on hearing acuity was assessed prospectively in nine children with end-stage renal disease using pure-tone audiometry (PTA) and distortion-product otoacoustic emissions (DPOAEs). Results were compared with those obtained from nine audiologically normal healthy children also tested with PTA and DPOAEs twice during a 4-h interval. Sensorineural hearing loss of unknown aetiology was found in 55.5% of renal patients, mainly in the higher frequencies. Patients on HD had mean PTA thresholds significantly poorer than those of the control group in the frequency range 1000-12 000Hz (P < 0.05). Their mean DPOAE amplitudes were significantly lower in all frequencies > 1184 Hz (P < 0.05). Furthermore, patients' ears with normal PTA thresholds between 250 and 4000 Hz also had decreased DPOAE amplitudes. No significant changes in PTA thresholds or DPOAE amplitudes were encountered in renal patients before and after a HD session (P > 0.05). Changes in PTA thresholds or DPOAE amplitudes were not significantly different than those in the control group (P > 0.05). In conclusion, sensorineural hearing loss of unknown origin, especially in high frequencies, is frequent in young renal patients under HD and single HD sessions do not seem to alter the hearing acuity of these patients. DPOAEs seem to be more sensitive to incipient cochlear damage than behaviour thresholds in monitoring renal patients.

The change in the acoustic admittance phase angle: a study in children suffering from acute otitis media.

Middle ear mechanics, in normal and in pathological conditions, is the subject of this research, with acoustic impedance measurements as the cornerstone. Previous studies have established the importance of admittance-phase tympanograms, mainly in frequencies higher than the conventional 226 Hz. The purpose of the present study was to record how acute otitis media (AOM) affects the middle ear system and function by evaluating the recordings of the change in phase angle parameter (deltatheta) provided by an automated tympanometer using the sweep-frequency technique. Multifrequency and conventional tympanograms were obtained from 70 children suffering from AOM on consecutive visits. Values of deltatheta from these subjects were compared to normative data previously acquired in our Department. It appears that changes in the mechanical status of the middle ear after AOM are reflected in abnormal deltatheta values, despite the normal findings of conventional tympanometry. A positive history of AOM did not seem to influence the behaviour of the middle ear. In most cases, abnormal deltatheta values coexisted with abnormal values of resonance frequency (RF), i.e. the frequency at which mass and stiffness of the middle ear are in balance, and total susceptance (deltaB) reaches 0mmhos and the converse. The deltatheta seems to be an important indicator of middle ear mechanical status that can record changes occurring in the system after AOM and undetected by low probe-tone tympanometry.

Hearing loss in speech-language delayed children.

An infant begins to communicate with his/her environment from the first months of life. However, true words do not appear until the age of 12-15 months, following a rather predictable sequence. Delay or failure of normal language development is not a rare situation in childhood and may be due to a variety of reasons. Among these, hearing undoubtedly plays a leading part in the language acquisition process. The purpose of this study was to assess the percentage of hearing-impaired children in a group of phenotypically healthy children presenting with speech-language delay. Between March 1993 and March 1999, 726 speech-language delayed children were examined in our department. In 72 of them, various diseases or syndromes had already been diagnosed and so they were excluded from the study. The remaining 654 apparently healthy children entered the study and underwent a thorough audiological assessment for determination of their hearing thresholds. Eighty-seven children (13.3%) showed various degrees of hearing loss. Most of them (55 children, 8.4%) suffered from sensorineural hearing impairment, while in 32 children (4.9%) a conductive hearing loss was discovered. The increased prevalence of hearing impairment found in our population mandates a thorough hearing evaluation for every case of speech-language delay, even for those children who show no evidence of other handicaps. This will help in the early diagnosis of hearing loss, allowing proper management to be instituted as early as possible.

Evoked otoacoustic emissions--an approach for monitoring cisplatin induced ototoxicity in children.

OBJECTIVES: Cisplatin chemotherapy is associated with an increased risk of ototoxic changes. The incidence of hearing loss after the 1st cisplatin-infusion session is only scarcely mentioned in the international literature. With increasing survival rates, prevention and/or early detection of ototoxicity are important for providing management options. The predictive value of pure-tone audiometry in early detection of ototoxicity has been questioned, particularly in the higher frequencies. Otoacoustic emissions appear to be more sensitive to cochlear insult than the conventional pure-tone audiometry. The aims of our study was (a) to define the extent of hearing damage in children after the 1st cisplatin-infusion session (50 mg/m(2)); and (b) to compare the efficacy of otoacoustic emissions (transient evoked otoacoustic emissions, distortion-product otoacoustic emissions) with that of pure-tone audiometry as methods of audiological monitoring. METHODS: Baseline audiometric (0.25-8 kHz) and otoacoustic emission testing (transient evoked otoacoustic emissions, distortion-product otoacoustic emissions) was conducted in 19 children, 12 of whom met the criteria for inclusion in the final study. Comparisons were performed between baseline measurements and those recorded after the 1st cisplatin course. Transient evoked otoacoustic emissions were analyzed in terms of emission level and reproducibility as a function of frequency (0.8-4 kHz). Distortion-product otoacoustic emissions were obtained as DP-grams and I/Q functions at 4,6 and 8 kHz. The DP-gram amplitude, the dynamic range and the detection thresholds from the I/Q functions were determined for each child. RESULTS: Threshold changes from baseline were founded to be statistically significant from 4-8 kHz in 50% of the children (P<0.01). Transient evoked otoacoustic emissions revealed a significant decrease in the emission level and in the reproducibility at the highest frequency tested (4 kHz, P<0.01), reflecting the results seen in pure-tone audiometry. Distortion-product otoacoustic emissions demonstrated a significant threshold shift, a reduced dynamic range and a decreased amplitude in the frequencies >3 kHz (P<0.05). Furthermore, DP-gram amplitude also reduced significantly at 3 kHz (P<0.05) without any similar change in pure-tone audiometry. CONCLUSIONS: A significant high-frequency hearing loss is identified in children even after one low-dose cisplatin-infusion session. As ototoxicity screening tools DP-grams were extremely sensitive and superior to pure-tone audiometry and/or transient evoked otoacoustic emissions. Their use is recommended for regular monitoring of cochlear function, aiming in prevention of permanent damage. Some suggestions for reducing the potential for cisplatin ototoxicity (chemoprotective agents, gene therapy, inhibition of apoptosis) are also discussed.

Incidence of hearing loss among children presented with speech-language delay.

Infants' first attempts to communicate with their environment begin shortly after birth. However, real words appear by age of 12-15 months. Any delay in expressing their needs verbally beyond this age is defined as speech delay and may be associated with a variety of pathological conditions. The aim of this study is to investigate the incidence of hearing impairment in those children presented with speech delay. Ninety-one speech-delayed children were audiologically assessed between March 1993 and March 1995. In 25 out of 91 children (27.4%) a moderate to severe hearing loss was detected, either sensorineural or conductive. The increased incidence of hearing impairment found in this group mandates a thorough hearing evaluation for any case of speech-language delay.

Towards a universal newborn hearing screening.

Hearing loss is a common problem which, if remaining undetected during early childhood, could affect the patient's linguistic and mental abilities permanently. Although recommended, mass hearing screening has so far been problematic or even impossible due to several reasons. The available otoacoustic emission devices appear to be effective tools for universal hearing screening. The aim of this study is to evaluate the reliability and practicability of a new device for recording click-evoked otoacoustic emissions (cEOEs) on a pediatric population. Sixty children aged between 6 days and 14 years were evaluated audiologically both by auditory brainstem responses (ABR) and otoacoustic emissions. The latter were obtained by using the well-known ILO88v3.92 otoacoustic analyser and a new, portable device ('Echocheck', Otodynamics Ltd, UK). Sensitivity and specificity of cEOEs recorded by 'Echocheck'was found to be 93% and 91%, respectively, when compared to ABR results. Additionally, 'Echocheck' recordings were proved to be much easier to perform, needing considerably less time in comparison with those of the ILO88 system. In our opinion, 'Echocheck' as well as all similar portable devices--screeners--may represent a much-desired solution for implementing universal hearing screening programmes.

Pneumococcal acute otitis media in children.

OBJECTIVES: To evaluate the clinical and laboratory findings of Streptococcus pneumoniae acute otitis media in children during a 1 year period. METHODS: From October 1995 to September 1996, 113 children aged 2 months to 14 years (median 18 months), with S. pneumoniae acute otitis media were studied. Susceptibility testing was performed by the Kirby-Bauer method and the E-test, and serotyping by the Quellung reaction. RESULTS: E-test assays detected five isolates (4.4%) to be highly resistant to penicillin and 13 (11.5%) that had intermediate resistance. All isolates were found to be susceptible to vancomycin, rifampicin and cefotaxime. In total, 25 isolates (22.1%) were resistant to one or more drugs. Fifty per cent of the penicillin-resistant or intermediately resistant S. pneumoniae isolates were resistant to multiple drugs, whereas only 2.1% of the penicillin-susceptible isolates were resistant to multiple drugs. The predominating serogroups of the isolates with reduced susceptibility to penicillin were the 19 (61.1%), 9 (16.7%), 23 (11.1%), 6 (5.5%) and 14 (5.5%) whereas those of the susceptible isolates were the 19 (26.3%), 14 (13.7%), 3 (11.6%), 6 (11.6%), 9 (8.4%), 1 (5.3%) and 12 (5.3%). CONCLUSIONS: Streptococcus pneumoniae isolates from children with acute otitis media were penicillin-insensitive in 15.9%. The multiresistant S. pneumoniae isolates belonged to serogroups: 19 (45.4%), 9 (27.3%), 6 (18.2%) and 23 (9.1%).

Otoacoustic emissions--an approach for monitoring aminoglycoside induced ototoxicity in children.

OBJECTIVES: The early detection of hearing impairment caused by ototoxic drugs, such as aminoglycosides, has been the aim of research world-wide. Histopathological studies have shown that the outer hair cells are the most susceptible cochlear components to injury from ototoxic drugs like aminoglycosides. Otoacoustic emissions reflect the functional status of the outer hair cells and constitute the only non-invasive means of objective cochlear investigation. The aim of this study was to evaluate the potential of otoacoustic emissions in early identification of aminoglycoside-induced cochlear dysfunction. In addition, a comparison with pure-tone audiometry or auditory brainstem responses was performed in order to determine if this test might provide a more reliable method of monitoring early ototoxic insults to the cochlea. METHODS: Twenty four children receiving gentamicin (4 mg/kg once daily) for 6-29 days were included in the study. Eleven children received gentamicin for up to 7 days (group A), while 13 underwent longer-term therapy lasting 8-29 days (group B). Hearing was serially monitored using transient evoked otoacoustic emissions and pure-tone audiometry (0.25-12 kHz) or auditory brainstem responses for younger or uncooperative children. Transient evoked otoacoustic emissions data were analysed in terms of emission amplitude and response reproducibility as a function of frequency. RESULTS: All patients yielded a normal baseline audiometric assessment upon hospital admission. For group A patients no significant changes in hearing levels were observed either by pure-tone audiometry (P = 0.2), auditory brainstem responses (P = 0.3) or transient evoked otoacoustic emissions (mean response: P = 0.06, reproducibility by frequency: P > 0.05). For group B patients no significant changes in hearing levels measured by pure-tone audiometry (P = 0.1) or auditory brainstem responses (P = 0.4) were observed. Transient evoked otoacoustic emissions however revealed a statistically significant decrease in the mean response level (P = 0.017) and in the reproducibility over the whole frequency spectrum (1 kHz: P = 0.0057, 2 kHz: P = 0.0247, 3 kHz: P = 0.0134, 4 kHz: P = 0.0049, 5 kHz: P = 0.0019). CONCLUSIONS: The findings suggest that transient evoked otoacoustic emissions are an extremely sensitive measure of the early effects of aminoglycoside-induced injury to the peripheral auditory system. Therefore, their use is recommended for regular monitoring of cochlear function, in the presence of potentially toxic factors, aiming at prevention of permanent damage.

Multiple-frequency tympanometry in children with acute otitis media.

Multiple-frequency tympanometry (MFT) is a sweep-frequency method of acoustic immittance measurement, recently introduced in clinical practice. It provides values for the resonant frequency of the middle ear system. The purpose of this study was to use MFT to collect information about the mechanoacoustical changes occurring to the middle ear system after acute otitis media and to compare it with the results of conventional, low probe-tone tympanometry. Children with acute otitis media were followed up with both methods for 1 month after an episode of acute infection. Also, children with normal hearing were studied to establish normative data. Resonant frequency of the middle ear was found to be lower than normal even 1 month past the initial episode, for all types of 226-Hz tympanograms. MFT seemed to record changes in the middle ear after acute otitis media that 226-Hz tympanometry was unable to detect, implying persistence of pathology. More extended research will illuminate the clinical value of this method in the follow-up of acute otitis media.

Prognostic value of multiple-frequency tympanometry in acute otitis media.

Multiple-frequency tympanometry (MFT) and conventional 226-Hz tympanometry were performed in 86 ears of children affected by acute otitis media (AOM) after therapy. In a 3-month follow-up period, the recurrence rate of AOM and persistence of middle-ear effusion in these children were evaluated in comparison with the early results of the two methods, as well as the relation of MFT findings to the possibility of development of AOM sequelae. It seems that abnormal resonant frequency values and recordings by MFT right after an episode of AOM indicate persistence of changes in the mass and stiffness balance of the middle ear, not demonstrated by conventional tympanometry, that could be responsible for a higher probability of AOM sequelae.

Otoacoustic emission-based hearing screening of a Greek NICU population.

The pressing need for early identification of hearing-disabled children has led to the development of several neonatal hearing screening programmes world-wide. Today otoacoustic emissions represent a widely used methodology for identification of neonatal hearing impairment. The purpose of the present study is to determine the sensitivity and specificity of click-evoked otoacoustic emissions (cEOAEs) in a Greek NICU population and compare the cEOAE data to the final hearing status of these children. A total of 438 ears of 223 neonates at high risk for hearing impairment were tested with both brainstem response audiometry (ABR) and cEOAEs. In 107 neonates the final hearing status was determined by using behavioural and playtone audiometry, at an age greater than 2 1/2 years. The sensitivity and specificity of the cEOAEs were found to be 90 and 92.4% when compared to ABR results and 90.9 and 91.1% when compared to the children's hearing status, respectively. Click-EOAEs have been proved to be highly effective in determining whether or not hearing impairment really exists. Since conventional ABR does not meet the requirements for large scale screening programmes, the cEOAEs represent a reliable alternative.