Safety, tolerability, and effect of a single aural dose of Dornase alfa at the time of ventilation tube surgery for otitis media: A Phase 1b double randomized control trial.

BACKGROUND: One third of children require repeat ventilation tube insertion (VTI) for otitis media. Disease recurrence is associated with persistent middle ear bacterial biofilms. With demonstration that Dornase alfa (a DNase) disrupts middle ear effusion biofilms ex vivo, we identified potential for this as an anti-biofilm therapy to prevent repeat VTI. First, safety and tolerability needed to be measured. METHODS: This was a phase 1B double-blinded randomized control trial conducted in Western Australia. Children between 6 months and 5 years undergoing VTI for bilateral middle ear effusion were recruited between 2012 and 2014 and followed for two years. Children's ears were randomized to receive either Dornase alfa (1 mg/mL) or 0.9 % sodium chloride (placebo) at time of surgery. Children were followed up at 2 weeks post-VTI and at 3-monthly intervals for 2 years. Outcomes assessed were: 1) safety and tolerability, 2) otorrhoea frequency, 3) blocked or extruded ventilation tube (VT) frequency, 4) time to blockage or extrusion, 5) time to infection recurrence and/or need for repeat VTI. RESULTS: Sixty children (mean age 2.3 years) were enrolled with 87 % reaching study endpoint. Treatment did not change otorrhoea frequency. Hearing improved in all children following VTI, with no indication of ototoxicity. Dornase alfa had some effect on increasing time until VT extrusion (p = 0.099); and blockage and/or extrusion (p = 0.122). Frequency of recurrence and time until recurrence were similar. Fourteen children required repeat VTI within the follow-up period. CONCLUSION: A single application of Dornase alfa into the middle ear at time of VTI was safe, non-ototoxic, and well-tolerated. TRIAL REGISTRATION: ACTRN12623000504617.

Does otitis media in early childhood affect later behavioural development? Results from the Western Australian Pregnancy Cohort (Raine) Study.

OBJECTIVES: To examine the relationship between early life episodes of otitis media and later behavioural development with adjustment for confounders. DESIGN: Longitudinal cohort study. SETTING: The Western Australian Pregnancy Cohort (Raine) Study recruited 2900 pregnant women from King Edward Memorial Hospital (KEMH) in Perth, Western Australia, between 1989 and 1991. PARTICIPANTS: Data from the children born were collected at both the Year 3 and Year 5 follow-up. At Year 3, n = 611 were diagnosed with recurrent otitis media through parent-report and clinical examination. At Year 5, n = 299 were considered exposed to otitis media based upon tympanometry results. MAIN OUTCOME MEASURES: Performance in the Child Behaviour Checklist (CBCL), a questionnaire completed by the primary caregiver at Year 10. RESULTS: Significant associations were found between recurrent otitis media at Year 3 and internalising behaviours (P = .011), and the somatic (P = .011), withdrawn (P = .014), attention (P = .003) and thought problems domains (P = .021), and the total CBCL score (P = .010). A significant association was also found between exposure to otitis media at Year 5 and externalising behaviours (P = .026). CONCLUSIONS: A modest association was seen between recurrent otitis media at Year 3 and exposure to otitis media at Year 5 and a number of behaviour domains at Year 10.

Associations between cardiovascular disease and its risk factors with hearing loss-A cross-sectional analysis.

OBJECTIVES: To investigate the relationship between hearing loss and cardiovascular disease risk factors. DESIGN: Cross-sectional study. METHODS: Participants were recruited between May 2010 and December 2015 and answered a health and risk factor questionnaire. Physical and biochemical assessments were performed. SETTING: A community-based population. PARTICIPANTS: A total of 5107 participants born within the years 1946-1964 enrolled in the Busselton Healthy Ageing Study. MAIN OUTCOME MEASURES: Hearing was assessed behaviourally through the best ear pure-tone average (500, 1000, 2000, 4000 Hz), low-frequency average (250, 500, 1000 Hz) and high-frequency average (4000, 8000 Hz). Self-reported hearing loss, tinnitus and hyperacusis were assessed via questionnaire. Cardiovascular risk factors were assessed via a patient-completed questionnaire and objective measurements including blood pressure, body mass index, waist circumference, lipid profile and glycated haemoglobin. RESULTS: Of the participants, 54% were female, with the mean age of 58 years (range 45-69 years). Age, sex and family history of hearing loss were consistently strong determinants of hearing loss outcomes. After adjusting for these, obesity, current smoking, peripheral arterial disease and history of cardiovascular disease were significantly associated with pure-tone, low-frequency and high-frequency hearing loss. In addition, high blood pressure, triglyceride and glycated haemoglobin were significantly associated with low-frequency hearing loss. There was a graded association between hearing loss and Framingham Risk Score for cardiovascular risk (P<0.001). CONCLUSIONS: Established cardiovascular disease and individual and combined cardiovascular disease risk factors were found to be associated with hearing loss. Future research should prospectively investigate whether targeting cardiovascular disease can prevent hearing loss.

A population-based study of the association between dysglycaemia and hearing loss in middle age.

AIMS: To investigate the independent associations between hearing loss and dysglycaemia in a sample of middle-aged adults, including separate analysis of those aged < 60 years. METHODS: The first 2023 participants in the cross-sectional Busselton Health Ageing Survey were assessed for hearing loss ≥ 26 dB (better ear) for four-frequency average (4FA) of pure-tone thresholds at 500, 1000, 2000 and 4000 Hz, and high-frequency average (HFA) of pure-tone thresholds at 4000 and 8000 Hz. RESULTS: Valid data from 1864 participants in the Busselton Health Ageing Survey [92.1%; mean ± sd age 56.2 ± 5.5 years, 46.0% men, 120 (7.0%) with diabetes, 274 (14.7%) with prediabetes] were analysed, of whom 103 (5.5%) had four-frequency average hearing loss and 561 (30.1%) had high-frequency average hearing loss. In multivariable analyses, glycaemic status was not independently associated with four-frequency or high-frequency average hearing loss. In the 1286 participants aged < 60 years, there was no relationship between dysglycaemia and high-frequency average hearing loss, but the prevalence of four-frequency average hearing loss increased from 2.3% (95% CI 1.5-3.4) in participants with normoglycaemia to 5.7% (95% CI 3.0-10.6) in those with prediabetes and 10.2% (4.2-21.5) in those with diabetes (trend P = 0.003). In multivariable analysis with normoglycaemia as reference, the odds ratios for four-frequency average hearing loss were 2.84 (95% CI 1.29-6.27) for prediabetes and 5.93 (95% CI 1.67-21.05) for diabetes (P ≤ 0.01) in the < 60 year age group. CONCLUSIONS: There was progressively increasing mid-range hearing loss with worsening glucose tolerance in younger individuals, suggesting dysglycaemia-associated early-onset presbycusis.

Protective benefit of predominant breastfeeding against otitis media may be limited to early childhood: results from a prospective birth cohort study.

OBJECTIVES: To examine the long-term effects of predominant breastfeeding on incidence of otitis media. DESIGN: Prospective birth cohort study. SETTING: The West Australian Pregnancy Cohort (Raine) Study recruited 2900 mothers through antenatal clinics at the major tertiary obstetric hospital in Perth, Western Australia, between 1989 and 1992. PARTICIPANTS: In total, 2237 children participated in a 6-year cohort follow-up, and a subset of 1344 were given ear and hearing assessments. MAIN OUTCOME MEASURES: OM diagnosis at 6 years of age (diagnosed by low-compliance tympanograms, 0-0.1 mmho). This was compared to OM diagnosed at the 3-year cohort follow-up using parent-report measures. Main exposure measures were duration of predominant breastfeeding (defined as the age other milk was introduced) and duration of partial (any) breastfeeding (defined as the age breastfeeding was stopped). RESULTS: There was a significant, independent association between predominant breastfeeding (OR = 1.33 [1.04, 1.69]; P = 0.02) and OM, and breastfeeding duration (OR = 1.35 [1.08, 1.68]; P = 0.01) with OM at 3 years of age. However, at 6 years of age, this relationship was no longer statistically significant (predominant breastfeeding OR = 0.78 [0.48, 1.06]; P = 0.09; duration of breastfeeding, OR = 1.34 [0.81, 2.23]; P = 0.25). CONCLUSIONS: Our findings are in line with a number of epidemiological studies which show a positive association between breastfeeding and OM in early childhood. However, the long-term follow-up of these children revealed that by 6 years of age, there was no significant influence of breastfeeding on presence of OM. These results suggest that the protective effect of predominant breastfeeding for at least 6 months does not extend to school-age children, where other social and environmental factors may be stronger predictors of OM.

The relationship between hearing impairment and cognitive function: a meta-analysis in adults.

OBJECTIVE: Hearing loss affects over 1.23 billion people globally. It has been proposed that hearing impairment negatively impacts on cognition. Some studies have demonstrated a faster rate of decline in cognition, and increased risk of incident all-cause dementia. This finding is not ubiquitous. This study used meta-analysis to examine the evidence-base regarding the relationship between hearing and cognition. DESIGN: A systematic review of the literature and meta-analyses of study findings were conducted. Published and grey literature was reviewed. Papers were included if they studied the relationship between hearing and cognition in adults with and without hearing impairment. MAIN OUTCOME MEASURES: Meta-analyses examined evidence for and against seven questions. Is cognition poorer in individuals with normal hearing compared to (i) untreated or (ii) treated hearing impairment, is cognition associated with degree of hearing impairment in (iii) untreated and/or (iv) treated hearing, is cognition (v) different in untreated compared to treated hearing impairment, (vii) does cognition improve after intervention, and (vii) how is hearing impairment differentially associated with cognitive ability across six domains of cognition? RESULTS: The 33 included studies contributed 40 samples, with a total of 602 participants with untreated hearing impairment, 672 participants with treated hearing impairment, 176 healthy controls, and 4260 individuals with a range of hearing impairment with/without treatment. The results demonstrated that cognition is significantly poorer in (i) individuals with untreated hearing and remains poorer in (ii) treated hearing impairment compared to normal hearers. The degree of cognitive deficit is significantly associated with the degree of hearing impairment in both (iii) untreated and (iv) treated hearing impairment. Furthermore, (v) hearing intervention significantly improves cognition. Finally, (vii) hearing impairment impacted on all domains of cognition. CONCLUSIONS: This meta-analysis suggests that hearing impairment is associated with cognitive problems. However, due to diversity within studies, small sample sizes, the failure to control for premorbid and other health factors, this conclusion may be premature.