Implementation and evaluation of a rural community-based pediatric hearing screening program integrating in-person and tele-diagnostic auditory brainstem response (ABR).

BACKGROUND: In an attempt to reach remote rural areas, this study explores a community-based, pediatric hearing screening program in villages, integrating two models of diagnostic ABR testing; one using a tele-medicine approach and the other a traditional in-person testing at a tertiary care hospital. METHODS: Village health workers (VHWs) underwent a five day training program on conducting Distortion Product Oto Acoustic Emissions (DPOAE) screening and assisting in tele-ABR. VHWs conducted DPOAE screening in 91 villages and hamlets in two administrative units (blocks) of a district in South India. A two-step DPOAE screening was carried out by VHWs in the homes of infants and children under five years of age in the selected villages. Those with 'refer' results in 2nd screening were recommended for a follow-up diagnostic ABR testing in person (Group A) at the tertiary care hospital or via tele-medicine (Group B). The overall outcome of the community-based hearing screening program was analyzed with respect to coverage, refer rate, follow-up rate for 2nd screenings and diagnostic testing. A comparison of the outcomes of tele-versus in-person diagnostic ABR follow-up was carried out. RESULTS: Six VHWs who fulfilled the post training evaluation criteria were recruited for the screening program. VHWs screened 1335 children in Group A and 1480 children in Group B. The refer rate for 2nd screening was very low (0.8%); the follow-up rate for 2nd screening was between 80 and 97% across the different age groups. Integration of tele-ABR resulted in 11% improvement in follow-up compared to in-person ABR at a tertiary care hospital. CONCLUSIONS: Non-availability of audiologists and limited infrastructure in rural areas has prevented the establishment of large scale hearing screening programs. In existing programs, considerable challenges with respect to follow-up for diagnostic testing was reported, due to patients being submitted to traveling long distance to access services and potential wage losses during that time. In this program model, integration of a tele-ABR diagnostic follow-up improved follow-up in comparison to in-person follow-up. VHWs were successfully trained to conduct accurate screenings in rural communities. The very low refer rate, and improved follow-up rate reflect the success of this community-based hearing screening program.

Cost and outcome of a community-based paediatric hearing screening programme in rural India with application of tele-audiology for follow-up diagnostic hearing assessment.

OBJECTIVE: This study evaluated the cost and outcome of a community-based hearing screening programme in which village health workers (VHWs) screened children in their homes using a two-step DPOAE screening protocol. Children referred in a second screening underwent tele diagnostic ABR testing in a mobile tele-van using satellite connectivity or at local centre using broadband internet at the rural location. DESIGN: Economic analysis was carried out to estimate cost incurred and outcome achieved for hearing screening, follow-up diagnostic assessment and identification of hearing loss. Two-way sensitivity analysis determined the most beneficial cost-outcome. STUDY SAMPLE: 1335 children under 5 years of age underwent screening by VHWs. RESULTS: Nineteen of the 22 children referred completed the tele diagnostic evaluation. Five children were identified with hearing loss. The cost-outcomes were better when using broadband internet for tele-diagnostics. The use of least expensive human resources and equipment yielded the lowest cost per child screened (Rs.1526; $23; €21). When follow-up expenses were thus maximised, the cost per child was reduced considerably for diagnostic hearing assessment (Rs.102,065; $1532; €1368) and for the cost per child identified (Rs.388,237; $5826; €5204). CONCLUSION: Settings with constrained resources can benefit from a community-based programme integrated with tele diagnostics.

The Audiology of Otosclerosis.

Diagnostic audiologic procedures for otosclerosis are effective tools in identifying this condition. Audiometric data usually demonstrate a conductive hearing loss at the early stages of otosclerosis. Modern middle ear analysis procedures are becoming more popular in the better diagnosis of otosclerosis. In clinical practice, cochlear otosclerosis can also be observed. Audiologic rehabilitation of otosclerosis includes fitting of hearing aids and implantable hearing devices. Current hearing technology enables patients who do not pursue surgical correction to function well and significantly improve their communication and quality of life. Otosclerosis may also be associated with annoying tinnitus, and tinnitus management is important in the rehabilitation process.

Validation of DPOAE screening conducted by village health workers in a rural community with real-time click evoked tele-auditory brainstem response.

OBJECTIVE: This study assessed the validity of DPOAE screening conducted by village health workers (VHWs) in a rural community. Real-time click evoked tele-auditory brainstem response (tele-ABR) was used as the gold standard to establish validity. DESIGN: A cross-sectional design was utilised to compare the results of screening by VHWs to those obtained via tele-ABR. Study samples: One hundred and nineteen subjects (0 to 5 years) were selected randomly from a sample of 2880 infants and young children who received DPOAE screening by VHWs. METHOD: Real time tele-ABR was conducted by using satellite or broadband internet connectivity at the village. An audiologist located at the tertiary care hospital conducted tele-ABR testing through a remote computing paradigm. Tele-ABR was recorded using standard recording parameters recommended for infants and young children. Wave morphology, repeatability and peak latency data were used for ABR analysis. RESULTS: Tele-ABR and DPOAE findings were compared for 197 ears. The sensitivity of DPOAE screening conducted by the VHW was 75%, and specificity was 91%. The negative and positive predictive values were 98.8% and 27.2%, respectively. CONCLUSIONS: The validity of DPOAE screening conducted by trained VHW was acceptable. This study supports the engagement of grass-root workers in community-based hearing health care provision.

Hearing and Balance Disorders in the State of Hawai'i: Demographics and Demand for Services.

Hearing and balance disorders affect people of all ages. Among children, hearing loss affects speech and language development, academic performance, and psychosocial development. Hearing loss in adults negatively impacts work productivity, cognitive function, and psychosocial status. Prevalence of hearing loss in children in Hawai'i is higher than the national average. Research indicates that hearing loss is a prevalent condition among veterans and advanced age adults. This is of particular concern in Hawai'i as the state is home to many military training facilities and has a large elderly population. In contrast to the higher than average prevalence of hearing loss in Hawai'i, there is a relatively small number of practicing audiologists in the state. Audiologists are independent doctoral level professionals responsible for the assessment and non-medical management of hearing impairment, vestibular disorders, auditory processing disorder, auditory neuropathy, tinnitus, and related disorders. Currently, there is no formal audiology training program in Hawai'i to meet the needs for current or future hearing health professionals. The Department of Communication Sciences and Disorders at the University of Hawai'i at Manoa is developing a proposal for a Doctor of Audiology (Au.D.) program to provide a comprehensive doctoral-level audiology curriculum and clinical training in order to graduate audiologists with knowledge and skills needed to serve people with hearing and balance disorders in Hawai'i. This review article describes the current status of hearing and balance disorders and services in Hawai'i and stresses the importance of early identification and intervention in remediating their effects in all ages, with a focus on the need for expanding hearing health services in Hawai'i.

Crosscheck Principle in Pediatric Audiology Today: A 40-Year Perspective.

The crosscheck principle is just as important in pediatric audiology as it was when first described 40 years ago. That is, no auditory test result should be accepted and used in the diagnosis of hearing loss until it is confirmed or crosschecked by one or more independent measures. Exclusive reliance on only one or two tests, even objective auditory measures, may result in a auditory diagnosis that is not clear or perhaps incorrect. On the other hand, close and careful analysis of findings for a test battery consisting of objective procedures and behavioral tests whenever feasible usually leads to prompt and accurate diagnosis of auditory dysfunction. This paper provides a concise review of the crosscheck principle from its introduction to its clinical application today. The review concludes with a description of a modern test battery for pediatric hearing assessment that supplements traditional behavioral tests with a variety of independent objective procedures including aural immittance measures, otoacoustic emissions, and auditory evoked responses.

Parents' perceptions of tele-audiological testing in a rural hearing screening program in South India.

INTRODUCTION: Tele-diagnostic audiological testing in a hearing screening program for infants and young children is a novel practice, and this study is the first to explore its application in a rural community. It is important to understand parental perceptions and confidence when introducing a new process such as tele-audiological diagnostic testing in rural areas. METHOD: A questionnaire with 17 rater-administered items was designed to elicit comments concerning the quality of tele-hearing testing and video-conferencing, access to tele-hearing testing, and parents' attitudes regarding tele-hearing testing in the village. The questionnaire was administered by an audiologist not involved in tele-diagnostic testing to avoid bias. RESULTS: Parents perceived tele-hearing testing as equal in quality to in-person testing. Technical factors such as good video-conferencing quality and logistical factors such as ease of access due to reasonable travel time to testing facility could have influenced these perceptions. CONCLUSIONS: While these results show tele-hearing testing is an acceptable alternative, occasional poor signal quality should be addressed prior to large-scale implementation.

Newborn hearing screening at a community-based obstetric unit: Screening and diagnostic outcomes.

OBJECTIVE: Postnatal visits at community-based midwife obstetric units (MOUs) have been proposed as an alternative primary healthcare screening platform in South Africa. This study evaluated the outcomes of distortion product otoacoustic emissions (DPOAEs) and automated auditory brainstem response (AABR) screening conducted by a dedicated non-professional screener at a community-based MOU in the Western Cape, South Africa. METHODS: Universal newborn hearing screening (UNHS) at a community-based MOU was evaluated over a 16-month period. A dedicated non-professional screener was trained to follow a two-stage screening protocol targeting bilateral hearing loss. A two group comparative design was used alternating AABR (Maico MB11 BERAphone™()) and DPOAE (Bio-logic AuDX I) technology on a daily basis. Infants referring the initial screen received a follow-up appointment in two days' time and were rescreened with the same technology used at their first screen. Those referring the second stage were booked for diagnostic assessments. RESULTS: 7452 infants were screened including 47.9% (n=3573) with DPOAE and 52.1% (n=3879) with AABR technology. Mean age at first stage screen was 6.1 days. The initial bilateral referral rate was significantly lower for AABR (4.6%) compared to DPOAE (7.0%) and dropped to 0.3% and 0.7% respectively following the second stage screenings. First rescreen and initial diagnostic follow-up rates of 90% and 92.3% were obtained for the DPOAE group and 86.6% and 90% for the AABR group. Follow-up rates showed no significant difference between technology groups. Diagnostic assessment revealed a higher prevalence rate for bilateral SNHL among the AABR group (1/1000) compared to the DPOAE group (0.3/1000). Screening technology had no significant influence on daily screening capacity (23 AABR/day; 24 DPOAE/day). CONCLUSIONS: Postnatal visits at community-based MOUs create a useful platform for hearing screening and follow-up. AABR technology with negligible disposable costs provides opportunity for AABR screening to be utilised in community-based programmes. AABR screening offers lower initial referral rates and a higher true positive rate compared to DPOAE.

Pure-tone audiometry outside a sound booth using earphone attentuation, integrated noise monitoring, and automation.

OBJECTIVE: Accessibility of audiometry is hindered by the cost of sound booths and shortage of hearing health personnel. This study investigated the validity of an automated mobile diagnostic audiometer with increased attenuation and real-time noise monitoring for clinical testing outside a sound booth. DESIGN: Attenuation characteristics and reference ambient noise levels for the computer-based audiometer (KUDUwave) was evaluated alongside the validity of environmental noise monitoring. Clinical validity was determined by comparing air- and bone-conduction thresholds obtained inside and outside the sound booth (23 subjects). STUDY SAMPLE: Twenty-three normal-hearing subjects (age range, 20-75 years; average age 35.5) and a sub group of 11 subjects to establish test-retest reliability. RESULTS: Improved passive attenuation and valid environmental noise monitoring was demonstrated. Clinically, air-conduction thresholds inside and outside the sound booth, corresponded within 5 dB or less > 90% of instances (mean absolute difference 3.3 ± 3.2 SD). Bone conduction thresholds corresponded within 5 dB or less in 80% of comparisons between test environments, with a mean absolute difference of 4.6 dB (3.7 SD). Threshold differences were not statistically significant. Mean absolute test-retest differences outside the sound booth was similar to those in the booth. CONCLUSION: Diagnostic pure-tone audiometry outside a sound booth, using automated testing, improved passive attenuation, and real-time environmental noise monitoring demonstrated reliable hearing assessments.

Outcomes with OAE and AABR screening in the first 48 h--Implications for newborn hearing screening in developing countries.

OBJECTIVE: Early discharge of newborns (<24h after birth) from birthing centres is an important barrier to successful newborn hearing screening (NHS) in developing countries. This study evaluated the outcome of NHS within the first 48 h using an automated auditory brainstem response (AABR) device without the need for costly disposables typically required, and transient evoked otoacoustic emissions (TEOAE). METHODS: NHS was performed on 150 healthy newborns (300 ears) with TEOAE and AABR techniques before discharge at a hospital. A three-stage screening protocol was implemented consisting of an initial screen with TEOAE (GSI AUDIOscreener+) and AABR (BERAphone(®) MB 11). Infants were screened at several time points as early as possible after birth. Infants were only re-screened if either screening technique (TEOAE or AABR) initially yielded a refer outcome. The same audiologist performed all TEOAE and AABR screenings. RESULTS: Over the three-stage screen AABR had a significantly lower refer rate of 16.7% (24/144 subjects) compared to TEOAE (37.9%; 55/145 subjects). Screening refer rate showed a progressive decrease with increasing age. For both TEOAE and AABR, refer rate per ear screened 24h post birth was significantly lower than for those screened before 24h. For infants screened before 12h post birth, the AABR refer rate per ear (51.1%) was significantly lower than the TEOAE refer rate (68.9%). Overall AABR refer rate per ear was similar for infants screened between 24 to 36 h (20.2%) and 36 to 48 h (18.9%) but significantly lower than for TEOAE (40.7% and 41.9%, respectively). Lowest initial refer rates per ear (TEOAE 25.8%, AABR 3.2%) were obtained after 48 h post birth. CONCLUSION: In light of the early post birth discharge typical in developing countries like South Africa, in-hospital screening with AABR technology is significantly more effective than TEOAEs. AABR screening with a device like the MB 11 is particularly appropriate because disposable costs are negligible.

Tele-ABR using a satellite connection in a mobile van for newborn hearing testing.

We assessed the feasibility of conducting Auditory Brainstem Response (ABR) testing in a mobile van with satellite connectivity, with the help of trained health workers. ABR recordings in newborn babies made by telemedicine were compared with recordings made face to face. The auditory evoked response equipment was controlled by an audiologist at a nearby hospital. Videoconferencing was used during the testing process to monitor patient preparation by the village health worker. A total of 24 newborns (13 male and 11 female) aged 8-30 days underwent ABR in face-to-face and tele-mode. There was no significant difference between peak V latency measured at three intensity levels in the two modes. Agreement between the two methods of measurement was examined with a Bland-Altman plot. Almost all points were within the limits of agreement, suggesting no bias in the telemedicine measurements. Real-time tele-ABR testing as a component of newborn hearing screening is feasible in a mobile van using satellite link with the assistance of village health workers.

Asynchronous video-otoscopy with a telehealth facilitator.

OBJECTIVE: The study investigated whether video-otoscopic images taken by a telehealth clinic facilitator are sufficient for accurate asynchronous diagnosis by an otolaryngologist within a heterogeneous population. SUBJECTS AND METHODS: A within-subject comparative design was used with 61 adults recruited from patients of a primary healthcare clinic. The telehealth clinic facilitator had no formal healthcare training. On-site otoscopic examination performed by the otolaryngologist was considered the gold standard diagnosis. A single video-otoscopic image was recorded by the otolaryngologist and facilitator from each ear, and the images were uploaded to a secure server. Images were assigned random numbers by another investigator, and 6 weeks later the otolaryngologist accessed the server, rated each image, and made a diagnosis without participant demographic or medical history. RESULTS: A greater percentage of images acquired by the otolaryngologist (83.6%) were graded as acceptable and excellent, compared with images recorded by the facilitator (75.4%). Diagnosis could not be made from 10.0% of the video-otoscopic images recorded by the facilitator compared with 4.2% taken by the otolaryngologist. A moderate concordance was measured between asynchronous diagnosis made from video-otoscopic images acquired by the otolaryngologist and facilitator (κ=0.596). The sensitivity for video-otoscopic images acquired by the otolaryngologist and the facilitator was 0.80 and 0.91, respectively. Specificity for images acquired by the otolaryngologist and the facilitator was 0.85 and 0.89, respectively, with a diagnostic odds ratio of 41.0 using images acquired by the otolaryngologist and 46.0 using images acquired by the facilitator. CONCLUSIONS: A trained telehealth facilitator can provide a platform for asynchronous diagnosis of otological status using video-otoscopy in underserved primary healthcare settings.

Validity of diagnostic pure-tone audiometry without a sound-treated environment in older adults.

OBJECTIVE: To investigate the validity of diagnostic pure-tone audiometry in a natural environment using a computer-operated audiometer with insert earphones covered by circumaural earcups incorporating real-time monitoring of environmental noise. DESIGN: A within-subject repeated measures design was employed to compare air (250 to 8000 Hz) and bone (250 to 4000 Hz) conduction pure-tone thresholds, measured in retirement facilities, with thresholds measured in a sound-treated booth. STUDY SAMPLE: One hundred and forty-seven adults (average age 76 ± 5.7 years) were evaluated. Pure-tone averages were ≥ 25 dB in 59%, mildly (> 40 dB) elevated in 23%, and moderately (> 55 dB) elevated in 6% of ears. RESULTS: Air-conduction thresholds (n = 2259) corresponded within 0 to 5 dB in 95% of all comparisons between the two test environments. Bone-conduction thresholds (n = 1669) corresponded within 0 to 5 dB in 86% of comparisons. Average threshold differences (- 0.6 to 1.1) and standard deviations (3.3 to 5.9) were within typical test-retest reliability limits. Thresholds recorded showed no statistically significant differences (paired samples t-test:p > 0.01) except at 8000 Hz in the left ear. CONCLUSION: Valid diagnostic pure-tone audiometry can be performed in a natural environment with recently developed technology, offering the possibility of access to diagnostic audiometry in communities where sound-treated booths are unavailable.

Diagnostic pure-tone audiometry in schools: mobile testing without a sound-treated environment.

PURPOSE: To validate diagnostic pure-tone audiometry in schools without a sound-treated environment using an audiometer that incorporates insert earphones covered by circumaural earcups and real-time environmental noise monitoring. RESEARCH DESIGN: A within-subject repeated measures design was employed to compare air (250 to 8000 Hz) and bone (250 to 4000 Hz) conduction pure-tone thresholds measured in natural school environments with thresholds measured in a sound-treated booth. STUDY SAMPLE: 149 children (54% female) with an average age of 6.9 yr (SD = 0.6; range = 5-8). RESULTS: Average difference between the booth and natural environment thresholds was 0.0 dB (SD = 3.6) for air conduction and 0.1 dB (SD = 3.1) for bone conduction. Average absolute difference between the booth and natural environment was 2.1 dB (SD = 2.9) for air conduction and 1.6 dB (SD = 2.7) for bone conduction. Almost all air- (96%) and bone-conduction (97%) threshold comparisons between the natural and booth test environments were within 0 to 5 dB. No statistically significant differences between thresholds recorded in the natural and booth environments for air- and bone-conduction audiometry were found (p > 0.01). CONCLUSIONS: Diagnostic air- and bone-conduction audiometry in schools, without a sound-treated room, is possible with sufficient earphone attenuation and real-time monitoring of environmental noise. Audiological diagnosis on-site for school screening may address concerns of false-positive referrals and poor follow-up compliance and allow for direct referral to audiological and/or medical intervention.

Effects of advancing age and hearing loss on gaps-in-noise test performance.

PURPOSE: The present study evaluated the effects of advancing age and sensorineural hearing loss (SNHL) on approximate temporal gap detection thresholds obtained from the Gaps-in-Noise (GIN; Musiek et al., 2005) test. METHOD: Approximate thresholds from the GIN test were compared among 3 groups of participants (older adults with SNHL, older adults with essentially normal hearing, and young adults with normal hearing). Analyses of variance and regression modeling were used to determine the effect of age and audibility on GIN performance. Comparisons of thresholds obtained from the 4 test lists of the GIN were also conducted. RESULTS: Approximate gap thresholds differed significantly across all groups, with the poorest thresholds found in older adults with SNHL and with the best thresholds found in young adults with normal hearing. The strongest predictor of decreases in GIN performance was increased Audibility Index score, but a significant independent effect of age was also documented. Test list influenced GIN performance only in the group of young adults with normal hearing. CONCLUSIONS: The GIN test is a promising clinical measure of temporal resolution. Findings from the present study suggest that age and audibility influence GIN performance and may affect test analysis and interpretation with published normative data.

Digital music exposure reliably induces temporary threshold shift in normal-hearing human subjects.

OBJECTIVES: One of the challenges for evaluating new otoprotective agents for potential benefit in human populations is the availability of an established clinical paradigm with real-world relevance. These studies were explicitly designed to develop a real-world digital music exposure that reliably induces temporary threshold shift (TTS) in normal-hearing human subjects. DESIGN: Thirty-three subjects participated in studies that measured effects of digital music player use on hearing. Subjects selected either rock or pop music, which was then presented at 93 to 95 (n = 10), 98 to 100 (n = 11), or 100 to 102 (n = 12) dBA in-ear exposure level for a period of 4 hr. Audiograms and distortion product otoacoustic emissions (DPOAEs) were measured before and after music exposure. Postmusic tests were initiated 15 min, 1 hr 15 min, 2 hr 15 min, and 3 hr 15 min after the exposure ended. Additional tests were conducted the following day and 1 week later. RESULTS: Changes in thresholds after the lowest-level exposure were difficult to distinguish from test-retest variability; however, TTS was reliably detected after higher levels of sound exposure. Changes in audiometric thresholds had a "notch" configuration, with the largest changes observed at 4 kHz (mean = 6.3 ± 3.9 dB; range = 0-14 dB). Recovery was largely complete within the first 4 hr postexposure, and all subjects showed complete recovery of both thresholds and DPOAE measures when tested 1 week postexposure. CONCLUSIONS: These data provide insight into the variability of TTS induced by music-player use in a healthy, normal-hearing, young adult population, with music playlist, level, and duration carefully controlled. These data confirm the likelihood of temporary changes in auditory function after digital music-player use. Such data are essential for the development of a human clinical trial protocol that provides a highly powered design for evaluating novel therapeutics in human clinical trials. Care must be taken to fully inform potential subjects in future TTS studies, including protective agent evaluations, that some noise exposures have resulted in neural degeneration in animal models, even when both audiometric thresholds and DPOAE levels returned to pre-exposure values.

Psychosocial status of children with auditory processing disorder.

BACKGROUND: Children with hearing loss often exhibit reduced psychosocial status compared to children with normal hearing. It is reasonable to assume that psychosocial function may also be affected in children diagnosed with auditory processing disorder (APD). However, there are no published studies specifically addressing the psychosocial health of children with APD. PURPOSE: This investigation examined relationships between APD and psychosocial status, with an aim to examine nonauditory factors that may influence quality of life of children diagnosed with APD. RESEARCH DESIGN: A two-matched group design was employed. Participants and their mothers completed appropriate versions of the Dartmouth Primary Care Cooperative Information Project Charts for Adolescents (COOP-A), the Behavioral Assessment System for Children, Second Edition (BASC-2), and the Social Skills Rating System (SSRS). STUDY SAMPLE: Participants consisted of 19 children (aged 9.5-17.8 yr; mean = 11.9) diagnosed with APD and 20 gender- and age-matched (mean = 12.8 yr) children with no evidence of APD by history or audiological assessment. Primary caretakers (mothers) of the participants also completed psychosocial questionnaires according to their perception of their participating child's function. DATA COLLECTION AND ANALYSIS: Data were collected at a single visit, following APD diagnosis. Data from each questionnaire were analyzed using appropriate statistical methods for two-group comparisons. RESULTS: Analysis of child reports revealed significantly greater psychosocial difficulty in the APD group on subscales of the COOP-A and BASC-2. Increased problems in the APD group were also reported by parents on subscales of the COOP-A, BASC-2, and SSRS. Eta-squared values for all significant findings indicated moderate to large effect sizes, suggesting findings may be generalized to other children in this age group. No between-group differences were found on any subscale for APD children with or without a confirmed or suspected language disorder. CONCLUSION: We found that children with APD exhibit increased psychosocial difficulty in several areas compared to children without APD.

Efficacy of a community-based infant hearing screening program utilizing existing clinic personnel in Western Cape, South Africa.

OBJECTIVE: Screening programs at primary health care immunization clinics have been proposed as an alternative to hospital-based programs in South Africa. The objective of this study was to evaluate the first systematic community-based infant hearing screening program in a developing South African community in the Western Cape. METHODS: A community-based universal infant hearing screening program initiated at eight primary health care clinics in the Cape Metropolitan area was evaluated over a 19-month research period. During this time 6227 infants that were candidates for screening attended their 6, 10 or 14-week immunization visit at the relevant clinic. Clinic nurses were trained as screening personnel. A two-stage distortion product otoacoustic emissions screening protocol was utilized. The target disorder was uni- or bilateral hearing loss and infants referring the first screen were scheduled for a 4-week follow-up visit at the clinic. Diagnostic audiological and medical evaluations were scheduled at referral hospitals when indicated. The study evaluated the efficacy of the program based on coverage, referral and follow-up rates and diagnostic outcomes according to guidelines specified by the Health Professions Council of South Africa 2007 Position Statement. RESULTS: Overall coverage rate across the eight clinics was 32.4% with 2018 infants (aged 0-14 weeks) screened. The mean age of the sample at first stage screen was 3.9 weeks of age and 13.5 weeks of age for first hospital visit. Overall first stage screen referral rate was 9.5% with 62 subjects (3%) referred for diagnostic services at hospital level after a follow-up screen. The average follow-up rate for rescreens at clinic level was 85.1% and for initial diagnostic assessments at hospital level it was 91.8%. Prevalence rates were 4.5/1000 with significant hearing loss, including sensorineural (1.5/1000) and conductive (3/1000) losses, and 12.9/1000 for subjects with middle ear effusion. CONCLUSIONS: The community-based infant hearing screening program was valuable in attaining high follow-up return rates but reaching sufficient coverage may require dedicated screening personnel as opposed to existing nursing personnel.

III. Identification of novel CXCR3 chemokine receptor antagonists with a pyrazinyl-piperazinyl-piperidine scaffold.

The SAR of a novel pyrazinyl-piperazinyl-piperidine scaffold with CXCR3 receptor antagonist activity was explored. Optimization of the DMPK profile and reduction of hERG inhibition is described. Compound 16e with single-digit CXCR3 affinity, good rat PK and hERG profiles has been identified as a lead for further study.

II. SAR studies of pyridyl-piperazinyl-piperidine derivatives as CXCR3 chemokine antagonists.

The structure-human CXCR3 binding affinity relationship of a series of pyridyl-piperazinyl-piperidine derivatives was explored. The optimization campaign highlighted the pronounced effect of 2'-piperazine substitution on CXCR3 receptor affinity. Analog 18j, harboring a 2'(S)-ethylpiperazine moiety, exhibited a human CXCR3 IC(50) of 0.2 nM.