Research Report 2008–2009

The NHMRC Clinical Trials Centre at the University of Sydney runs large multicentre investigator-initiated clinical trials, takes part in trials of national and international collaborative trial groups and contributes expertise to trials run by others. It also: • undertakes research into trial methods and is recognised through publications as a leader in trial methodology • reviews and synthesises evidence from completed trials, and is at the forefront of developments in methods, such as prospective meta-analysis • advises on trial design and operation, and randomises patients and analyses data for other groups conducting trials, particularly through its Outreach program • takes a lead in proposing new directions for trial research in Australia, particularly with regard to integrating clinical trials with national policy and clinical practice • offers placements for postgraduate students in all of these areas • runs short courses in the design and conduct of clinical trials as part of its undertaking to train people for Australian medical research. Core funding is provided by the NHMRC, and specific projects are funded by government, public and private institutions and the pharmaceutical industry. The CTC is at two sites in Camperdown in inner Sydney — the Medical Foundation Building on Parramatta Road and on Mallett Street. This report covers the CTC’s achievements for the biennium 2008–200

Incidence and clinical value of prolonged I–V interval in NICU infants after failing neonatal hearing screening

Infants admitted to neonatal intensive care units (NICUs) have a higher incidence of perinatal complications and delayed maturational processes. Parameters of the auditory brainstem response (ABR) were analyzed to study the prevalence of delayed auditory maturation or neural pathology. The prevalence of prolonged I–V interval as a measure of delayed maturation and the correlation with ABR thresholds were investigated. All infants admitted to the NICU Sophia Children’s Hospital between 2004 and 2009 who had been referred for ABR measurement after failing neonatal hearing screening with automated auditory brainstem response (AABR) were included. The ABR parameters were retrospectively analyzed. Between 2004 and 2009, 103 infants were included: 46 girls and 57 boys. In 58.3% (60 infants) of our population, the I–V interval was recordable in at least one ear at first diagnostic ABR measurement. In 4.9%, the I–V interval was severely prolonged. The median ABR threshold of infants with a normal or mildly prolonged I–V interval was 50 dB. The median ABR threshold of infants with a severely prolonged I–V interval was 30 dB. In conclusion, in case both peak I and V were measurable, we found only a limited (4.9%) incidence of severely prolonged I–V interval (≥0.8 ms) in this high-risk NICU population. A mild delay in maturation is a more probable explanation than major audiologic or neural pathology, as ABR thresholds were near normal in these infants

Diagnosis and management strategies in congenital atresia of the external auditory canal.

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Audiometric Analyses Confirm a Cochlear Component, Disproportional to Age, in Stapedial Otosclerosis

OBJECTIVE:: To report the preoperative audiometric profile of surgically confirmed otosclerosis. STUDY DESIGN:: Retrospective, multicenter study. SETTING:: Four tertiary referral centers. PATIENTS:: One thousand sixty-four surgically confirmed patients with otosclerosis. INTERVENTIONS:: Therapeutic ear surgery for hearing improvement. MAIN OUTCOME MEASURES:: Preoperative audiometric air conduction (AC) and bone conduction (BC) hearing thresholds were obtained retrospectively for 1064 patients with otosclerosis. A cross-sectional multiple linear regression analysis was performed on audiometric data of affected ears. Influences of age and sex were analyzed and age-related typical audiograms were created. Bone conduction thresholds were corrected for Carhart effect and presbyacusis; in addition, we tested to see if separate cochlear otosclerosis component existed. Corrected thresholds were than analyzed separately for progression of cochlear otosclerosis. RESULTS:: The study population consisted of 35% men and 65% women (mean age, 44 yr). The mean pure-tone average at 0.5, 1, and 2 kHz was 57 dB hearing level. Multiple linear regression analysis showed significant progression for all measured AC and BC thresholds. The average annual threshold deterioration for AC was 0.45 dB/yr and the annual threshold deterioration for BC was 0.37 dB/yr. The average annual gap expansion was 0.08 dB/year. The corrected BC thresholds for Carhart effect and presbyacusis remained significantly different from zero, but only showed progression at2kHz. CONCLUSION:: The preoperative audiological profile of otosclerosis is described. There is a significant sensorineural component in patients with otosclerosis planned for stapedotomy, which is worse than age-related hearing loss by itself. Deterioration rates of AC and BC thresholds have been reported, which can be helpful in clinical practice and might also guide the characterization of allegedly different phenotypes for familial and sporadic otosclerosis

Prevalence of otosclerosis in an unselected series of temporal bones

Background: Histologic otosclerosis is a disease process without clinical symptoms or manifestations that can be discovered only by sectioning of the temporal bone at autopsy. Clinical otosclerosis is otosclerosis at a site where it causes conductive hearing loss by interfering with the motion of the stapes or of the round window membrane. Various authors have studied the prevalence of histologic otosclerosis on laboratory collections of temporal bones. Some 12% to 15% of temporal bones with histologic otosclerosis have demonstrated stapedial fixation. Using these figures for calculating the prevalence of clinical otosclerosis gives an extrapolated clinical prevalence of 0.99% to 1.2%. This does not correlate well with the clinical data on otosclerotic families, from which a clinical prevalence of 0.3% has been estimated. Objective: To study the prevalence of histologic otosclerosis in an unselected series of temporal bones, Study Design: During a 1-year period, 118 consecutive pairs of temporal bones of deceased patients at a tertiary care center were collected to determine the prevalence of otosclerosis. Although histology remains the gold standard for evaluation of otosclerosis, the gross observation of temporal bone slices combined with microradiography was used to screen for otosclerotic lesions more rapidly and with a lower cost/benefit ratio. The temporal bones, which were suspected of having otosclerosis with these techniques, were further analyzed by conventional histology. Results: 2.5% of the 236 temporal bones (or 3.4% of patients) studied demonstrated histologic otosclerosis. Conclusions: Although the prevalence of 2.5% is much lower than previously published figures on histologic otosclerosis, the extrapolated data (extrapolated clinical prevalence = 0.30% to 0.38%) correlate well with clinical studies of otosclerotic families. The previous studies based on laboratory collections were likely biased by hearing loss or other otologic diseases