ETD Collection

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Author: search.filters.author.Hollander, Cara

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    The pharmacokinetics and pharmacodynamics of kanamycin and capreomycin in patients with drug resistant-tuberculosis and the relationship between hearing levels: a feasibility study
    (2018) Hollander, Cara
    Individuals respond differently to medication as a result of their genetic inheritance. These differences can result in the under- or over-dosing of medication, which may affect the efficacy or in the case of aminoglycosides (kanamycin) and polypeptides (capreomycin), result in toxicity. In South Africa, administration of the standardised Drug Resistant -Tuberculosis (DR-TB) medication regimen is simplified across four weight bands. These bands accommodate the formulations available in the country while complying with international requirements for minimum, maximum and average dose per kilogram. There is a dearth of information on the ideal concentration, pharmacokinetics, and pharmacodynamics of kanamycin (KM) and capreomycin (CM) in patients with DR-TB and relationship of this on hearing levels. Thus, this study aimed to establish the feasibility of investigating the pharmacokinetics and pharmacodynamics of kanamycin and capreomycin in patients with DR-TB and the relationship between hearing levels. This feasibility study employed a prospective, cross-sectional, exploratory, descriptive and case series research design. A total of 22 participants (mean age 33.78 years, ±7.3) participated in this multi-site study at Helen Joseph (HJH) and South Rand Hospitals (SRH). The majority of the paryicpants were females (68%, n=15). Participants underwent audiological (otoscopy, tympanometry, ultra high frequency DPOAEs, ultra high frequency pure tone audiometry) and pharmacological assessments at baseline and every two weeks for the first three months of treatment. Creatinine clearance was measured, and the overall outcome of treatment was evaluated in relation to the pharmacokinetics. Results revealed high-frequency hearing loss with both kanamycin and capreomycin, specifically in the ultra-high frequencies (9kHz to 16kHz). Clinically significant ultra-high frequency loss noted was with pure tone audiometry from week four after the initiation of treatment, and from week six in the high frequencies (6kHz to 8kHz). Pharmacokinetic measurements showed erratic levels of kanamycin and capreomycin, with considerable differences among individuals, specifically with the peak readings. Mean peak levels for kanamycin were within the target range yet were subtherapeutic for the capreomycin participants. Kanamycin also correlated to more reduced kidney function when compared to capreomycin. Participants’ culture converted within the first two months from baseline, however, long-term culture results are unknown. Trough levels were also below 10 μg/ml and not within a toxic range, despite the hearing loss detected. This research identified many challenges with regard to establishing the feasibility of investigating the pharmacokinetics and pharmacodynamics of kanamycin and capreomycin in patients with DR-TB and the relationship between hearing levels. Participant enrolment was poor, with high attrition. This study also highlighted the need for a standardised ototoxicity monitoring protocol designed for this population which led to the development of ‘Ototcalc’: an ototoxicity calculator in the form of a mobile application designed to assist healthcare professionals in the classification of significant ototoxicity as well as with management recommendations. With the considerations identified in this study to further enhance the feasibility, the pharmacokinetics and pharmacodynamics of kanamycin and capreomycin are recommended for further exploration in relation to toxicity and efficacy with a larger sample, combined with the use of ‘Otocalc’.
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    The effects of aircraft noise on the auditory language processing abilities of English first language primary school learners.
    (2012-05-14) Hollander, Cara
    The purpose of the research was to investigate the effects of aircraft noise on the auditory language processing abilities of English First Language (EFL) primary school learners. Schools located in close proximity to airports are exposed to extremely high levels of chronic, yet intermittent noise. These levels have been shown to cause cognitive, health and hearing problems. However, it is unsure whether this long term exposure to these noise levels may cause auditory language processing problems when hearing is normal, which could result in decreased academic performance. This study utilised a non-experimental, cross sectional and descriptive design, as well as a post-hoc design. Seventy children attending schools that are exposed to high levels of noise were matched according to socio-demographic characteristics to seventy children in quieter schools. All the schools were situated in Durban, South Africa, while the noisy schools were located 1.7 km and 1.9 km from the airport and the quieter schools were 4.6km and 3.5km from the airport. All participants are EFL, have attended the respective schools from grade 1, have hearing within normal limits, are in grade 6 or 7, are 12 years or younger, and have no pre-diagnosed learning, auditory or attention problems. Audiological screening and auditory language processing assessments (subtests of the TAPS, PhAB and the Dollaghan and Campbell task) were undertaken. This study utilised various types of statistical analyses, including descriptive methods, Pearson’s chi-squared tests, Fisher’s tests, three-way ANOVAs, Cramer’s V tests and Cohen’s D tests. The results from the schools that are exposed to noise have scored below average in all the auditory processing subtests. This study aimed to provide evidence that not only can hearing be affected by noise, but so too can the processing of sounds, even when hearing is normal. The results of this study are hoped to serve as a motivation for the provision of speech-language therapy and audiology posts within mainstream legislation with regard to schools due to the large amount of children with auditory language processing difficulties in both noisy and quieter schools, as well as for noise treatment surrounding airports and appropriate to zoning of schools around airports to help and prevent this chronic noise interrupting the development of auditory language processing abilities and thus in turn affecting learning.