Identification of neonatal hearing impairment: experimental protocol and database management.

OBJECTIVE: The purposes of this article are to describe the overall protocol for the Identification of Neonatal Hearing Impairment (INHI) project and to describe the management of the data collected as part of this project. A well-defined protocol and database management techniques were needed to ensure that data were 1) collected accurately and in the same way across sites; 2) maintained in a database that could be used to provide feedback to individual sites regarding enrollment and the extent to which the protocol was complete on individual subjects; and 3) available to answer project questions. This article describes techniques that were used to meet these needs. DESIGN: This study was a prospective, randomized study that was designed to evaluate auditory brain stem responses, transient evoked otoacoustic emissions, and distortion product otoacoustic emissions as hearing-screening tools, and to relate neonatal test findings to hearing status, defined by visual reinforcement audiometry at 8 to 12 mo of age. Measures of middle-ear function also were obtained at some sites as part of the neonatal test battery. In addition, other clinical and demographic data were gathered to determine the extent to which factors, other than auditory status, influenced test behavior. Three groups were evaluated: neonatal intensive care unit (NICU) infants (those who spent 3 or more days in a NICU), well babies with risk factors for hearing loss, and well babies without risk factors. Six centers participated in the trial. The testers for the project included audiologists, technicians, audiology graduate students, and medical research staff. The same computerized neonatal test program was applied at each center. This program generated the neonatal test database automatically. Clinical and demographic data were collected by means of concise data collection forms and were entered into a database at each site. After the neonatal test, subjects from the NICU and at-risk well babies were evaluated with visual reinforcement audiometry starting at 8 to 12 mo of age. All data were electronically transmitted to the core site where they were merged into one overall database. This database was exercised to provide feedback and to identify discrepancies throughout the course of the study. In its final form, it served as the database on which all analyses were performed. RESULTS AND CONCLUSION: The protocol was a departure from typical hearing screening procedures in terms of 1) its regimented application of three screening measures; 2) the detailed information that was obtained regarding subject clinical and demographic factors; and 3) its application of the same procedures across six centers having diverse geographic location and subject demographics. A learning curve for successfully executing the study protocols was observed. Throughout the study, monthly reports were generated to monitor subject enrollment, check for data completeness, and to perform data integrity checks. In combination with monthly data reports and checks that occurred throughout the progression of the study, miscellaneous data audits were performed to check accuracy of neonatal testing programs and to cross-check information entered in the clinical and demographic database. The data management techniques used in this project helped to ensure the quality of the data collection process and also allowed for detailed analyses once data were collected. This was particularly important because it enabled us to evaluate not only the performance of individual measures as screening tools, but also permitted an evaluation of the influence of other variables on screening test results.

Characteristics of transient evoked otoacoustic emissions in normal-hearing and hearing-impaired children.

OBJECTIVE: Transient evoked otoacoustic emissions (TEOAEs) were measured in children with normal hearing and in children with hearing loss to investigate the characteristics of TEOAEs as they relate to overall amplitude and amplitude spectra of evoking stimuli, and to audiometric status. DESIGN: Three parameters of response measure (signal to noise ratio, amplitude and reproducibility) were assessed to determine accuracy of identification of varying degrees of hearing loss for broadband clicks, frequency-specific click bands and tone bursts. Forty-four children (66 ears) between 4 and 13 yr of age were evaluated for participation in the study. Fifty-nine ears with intact tympanic membranes were included in the final analyses: 14 ears with normal hearing and 45 ears with hearing loss. RESULTS: Children with normal hearing had robust responses that displayed nonlinear growth functions for broadband clicks and for tone bursts. Children with hearing loss had responses that decreased rapidly with decreasing stimulus level, if emissions were present at all. Data were analyzed using clinical decision analysis and receiver operator characteristic curves. Broadband clicks presented at 80 and 86 dB peSPL identified a hearing loss > or = 30 dB HL with a high degree of accuracy. Click responses filtered into octave bands centered at 500 and 1000 Hz did not improve classification of hearing loss, in fact, the 500 Hz band was particularly inaccurate. Results for click responses filtered into half-octave bands centered at 2000 and 4000 Hz were comparable with those for the broadband click, although the 2000 Hz band was superior for identification of hearing loss > or = 20 dB HL for an 80 dB peSPL click, and > or = 30 dB HL for an 86 dB peSPL click. Results for tone bursts centered at 500, 1000, 2000 and 4000 Hz, presented at 80 dB peSPL, were similar to results of the filtered click bands. Accuracy for identifying hearing loss increased with increasing center frequency. The 2000 and 4000 Hz tone bursts provided the best separation between normal-hearing and hearing-impaired ears, with 4000 Hz being slightly better. CONCLUSIONS: Data from this study suggest that TEOAEs in children can separate ears with normal hearing from those with hearing loss using a variety of stimulus and response conditions. Moreover, by using multiple stimulus levels it may be possible to distinguish between mild and moderate hearing losses.

Effects of contralateral acoustic stimulation on spontaneous otoacoustic emissions.

Spontaneous otoacoustic emissions (SOAEs) were measured in the ear canal of adult humans prior to, during, and following presentation of tonal and broadband stimuli to the contralateral ear. Tones were presented at a fixed level at ten frequencies relative to the SOAE. Broadband noise was presented at eight levels, from 6 to 76 dB SPL. Shifts in SOAE frequency and amplitude were observed for some subjects, for some tone conditions. Frequency shifts were always positive, whereas amplitude shifts were variable. No apparent pattern of tuning was seen, such that tones with a particular frequency relationship to the SOAEs induced greater changes in the SOAEs. Systematic changes in frequency and amplitude of SOAEs were observed for increasing level of broadband noise for all subjects. Results are discussed with respect to possible mechanism(s) responsible for the alterations in SOAEs: Transcranial conduction; the olivocochlear system; and/or the middle-ear reflex arc.

Voluntary contraction of middle ear muscles: effects on input impedance, energy reflectance and spontaneous otoacoustic emissions.

Two types of measurements were performed on a subject able to voluntarily contract her middle ear muscles (MEM). First, wideband measurements (0-11 kHz) of middle ear input impedance and energy reflectance were obtained when the subject was relaxed and when she contracted her MEM. The changes in impedance observed with voluntary MEM contraction were similar to those reported in the literature for acoustically-elicited MEM contractions. The energy reflectance increased for frequencies below about 4 kHz. Second, the effects of voluntary MEM contraction on the frequencies and levels of spontaneous otoacoustic emissions (SOAEs) were measured and compared to effects evoked by contralateral acoustic stimulation. Effects on SOAEs appear to be a more sensitive indicator of MEM activity than changes in impedance, and the effects due to voluntary MEM contraction were qualitatively similar to those evoked by contralateral acoustic stimulation. These results suggest that in subjects with normally-functioning middle ears, only some effects on otoacoustic emissions caused by contralateral stimuli whose levels are below the contralateral acoustic reflex threshold can be unequivocally attributed to the action of cochlear efferents. The temporal aspects of SOAE frequency shifts caused by voluntary contraction of MEM show that voluntary contraction fatigues rapidly over a time period of tens of seconds.

Oxathiin carboxanilide, a potent inhibitor of human immunodeficiency virus reproduction.

Oxathiin carboxanilide (OC), NSC 615985, a compound originally synthesized as a potential fungicide, was demonstrated to be highly active in preventing human immunodeficiency virus (HIV)-induced cell killing and in inhibiting HIV reproduction. Virus-infected CD4+ lymphocytes were completely protected by 0.5 microM OC, whereas no toxicity was observed at concentrations below 50 microM OC. Production of infectious virus, viral p24 antigen, and virion reverse transcriptase were reduced by OC at concentrations that prevented viral cell killing. A variety of CD4+ T-cell lines were protected by OC from HIV cytopathicity, and OC inhibited two distinct strains of HIV-1. However, HIV-2 infections were unaffected by OC. OC had no direct effect on virions of HIV or on the enzymatic activities of HIV reverse transcriptase or HIV protease. Time-limited treatments of cells with OC before, during, or after exposure of cells to virus failed to protect cells from the eventual cytopathic effects of HIV, and OC failed to inhibit the production of virus from cells in which infection was established or from chronically infected cells. We conclude that the highly active OC has a reversible effect on some early stage of HIV-1 reproduction and cytopathicity. Pilot in vivo experiments showed that circulating concentrations of OC exceeding 1 microM could be achieved and sustained in hamsters for at least a week with no remarkable toxicological sequelae. OC represents a new class of anti-HIV agents that are promising candidates for drug development.