Thesis (MSc(Med)(Pharmacy))-- University of Limpopo, 2013. / Neonates, particularly when premature, are prone to more infections due to being immunocompromised. Sixty percent of preterm neonates receive at least one antibiotic and 43% of the antibiotics administered to these neonates are aminoglycosides (AGs). This class of antibiotics is concentration dependent thus achieving a therapeutic maximum concentration of amikacin in plasma is associated with a significant decrease in the rate of mortality due to infection in critical ill patients. Amikacin has a very narrow therapeutic range and can cause side effects such as nephrotoxicity and ototoxicity. Neonates are a high risk population and the internal and external risk factors necessitate close monitoring in this population. The main aim of the study was to determine a possible correlation between amikacin serum concentrations and ototoxicity in neonates by using otoacoustic emissions (OAEs). The study was done at the Neonatal Intensive Care Unit of Dr George Mukhari Hospital (DGMH), a public sector academic hospital in Ga-Rankuwa, west of Pretoria in the Gauteng Province. A descriptive quantitative study with a correlation research design was used for the study. The correlation design was between the amikacin peak and trough levels and otoacoustic emission amplitudes measured at four different frequencies. Although the clinical therapeutic range for amikacin trough level is less than 10 mcg/mL, for the purpose of the study trough levels higher than 2 mcg/mL were used as a referral end point for OAEs. Over the period of five months, 83 neonates receiving amikacin therapy were recruited. Data were obtained from 55 (66%) of these recruited neonates. Kinetic-only data were obtained from 33 neonates and kinetic-and-audiology data from 22 neonates. The total population group had a mean gestational age (GA) of approximately 33 weeks with a mean weight of 1.91kg. This group received a mean maintenance dose of 19.59 mg/kg per day. Their glomerular filtration rate (GFR) was within limits and the mean was 19.58 mL/min per 1.73m2. Pharmacokinetic (PK) calculations revealed Determination of the correlation between amikacin serum concentrations and ototoxicity in neonates using otoacoustic emissions: A multidisciplinary approach at Dr George Mukhari Academic Hospital: Gauteng Province xix a mean true peak value of 47.45 mcg/mL which was higher than the recommended range of 30 to 40 mcg/mL. The reference half-life is between 4 and 8 hours, but was much longer at 10.93 hours. With regards to the volume of distribution (Vd), it was towards the upper limit, calculated at 0.665 L/kg. The interquartile range (IQR) for the whole population (n = 55) showed that 50% of the true trough levels ranged between 2.07 and 6.15 mcg/mL with true peak levels between 36.14 and 53.43 mcg/mL. The kinetics-only group had a mean GA of 33 weeks with a mean weight of 1.84 kg. This group received a mean maintenance dose of 19.84 mg/kg and had a GFR of 19.51 mL/min per 1.73m2. A mean peak of 45.67 mcg/mL and a mean trough of 7.07 mcg/L, both much higher than desired. The mean half-life was much higher than the reference range at 12.88 hours and the volume of distribution within range but towards the upper limit. The kinetic-and-audiology group had a mean GA of 33 weeks with a mean weight of 2 kg. This group received a mean maintenance dose of 20.12 mg/kg and had a GFR of 139.71 mL/min per 1.73m2. A mean peak of 50.13 mcg/mL and a mean trough of 5 mcg/L, both much higher than desired. The half-life was toward the upper limit and the volume of distribution within range. During the ototoxic monitoring, a DPOAE assessment was completed at baseline for the sub-population of 22 patients. These baselines were determined within 24 hours from when the patient was identified and consent obtained. A follow-up DPOAE was performed on the day of the third MD and therapeutic drug monitoring (TDM). Distortion product otoacoustic emissions (DPOAEs) were obtained at four different frequencies for each ear, namely at 2, 4, 6 and 8 kHz. Trough levels above 2 mcg/mL, but below the accepted therapeutic level of 10 mcg/mL, affected seven neonates ears (left and/or right), thus 32% of the sub-population. Three neonates (n = 22; 14%) had trough levels above 10 mcg/mL and reflected a change in outer hair cell function at some to all the frequency levels. Peak levels above 50 mcg/mL affected eight neonates’ ears (left and/or right), accounting for 36% of the sub- Determination of the correlation between amikacin serum concentrations and ototoxicity in neonates using otoacoustic emissions: A multidisciplinary approach at Dr George Mukhari Academic Hospital: Gauteng Province xx population. A total of six patients had both ears affected with peak and trough levels, thus 27.3% of the sub-population. This study indicated that outer hair cell (OHC) function is affected from baseline to follow-up audiology in neonatal patients treated with amikacin. A multidisciplinary approach between pharmacists, audiologists and doctors is imperative to reduce the morbidity in vulnerable population groups. Diagnostic OAE and PKs for ototoxic medications should be further investigated in a larger study population. Keywords: neonates, aminoglycoside, amikacin, ototoxicity, outer hair cell, otoacoustic emission

Thesis (Ph. D.)--Columbia University, 1912. / Vita.

Thesis (Ph. D.)--Columbia University, 1912. / Vita.

Thesis (MSc(Med)(Pharmacy))-- University of Limpopo, 2012. / i THE ROLE OF COUNSELLING, MONITORING OF SERUM CARBAMAZEPINE CONCENTRATION, AND OF COMPLIANCE IN EPILEPSY CONTROL Non-compliance with the patient’s prescribed medication regimen has been identified in several publications as a major factor responsible for insufficient seizure control. Non-compliance is also held by some workers in this field to be closely interlinked with inadequate serum anti-epileptic drug concentration. The early identification of non-compliance may therefore play an important role in epilepsy therapy. A study was undertaken at Kalafong Hospital to explore the efficacy of monitoring serum carbamazepine concentration in order to detect compliance or otherwise. Intrinsic in such study was exploration of the role played by counselling in the promotion of compliance. Samples of blood were drawn from 78 outpatient volunteers at intervals as close to 28 days as possible, and the serum carbamazepine concentration of these samples was then determined by means of the TDx FLx System (ABBOTT). Items such as conscientious attendance at the Kalafong epilepsy clinics (“visits”), serum carbamazepine concentration, patient’s age, gender and weight, concomitant drug interactions, occurrence of epileptic seizures and dosage of Tegretol®CR were examined to ascertain whether they could be correlated with compliance and used as indicators thereof. It was, however, constantly borne in mind that these are not the only elements of compliance; other factors such as difficult fundamental behavioural changes, such as avoiding stress, may also play a part. Conscientious attendance at Kalafong epilepsy clinics (“visits”) was found to be a usable (albeit not strong) indicator of compliance. Serum carbamazepine concentration was used as another, with, however, reservations arising from the relationship between the patient’s actual compliance on the one hand, and whether v the daily dosage was sub-therapeutic or excessive on the other. The statistical agreement between visits and these concentration values was, however, very poor (8.2%). Using visits as an indicator, 66.7% of the participants were assessed as compliant. Using ‘compliant concentration’, only 25.6% were assessed as compliant. The data acquired during the study was, unfortunately, too variable to warrant anything more than descriptive statistical treatment. To a large extent this was because the participants were out-patients, not in-patients over whom strict therapeutic control could be exercised. Age, gender and patient’s weight were not significantly linked to compliance. The correlation between expected and measured serum carbamazepine concentrations was not statistically significant (p = 0.062). The Kalafong data in respect of seizures indicate that the relationship between seizures and compliance is not a simple one and that the occurrence or otherwise of break-through seizures should not be used as an indicator of compliance, as has indeed been done by other research workers. Drug interaction was as expected in 20 of the 26 patients concerned, this agreement being statistically significant (p = 0.0074). Improved compliance was the outcome expected from counselling but it was not possible to quantify the enhancement of compliance achieved, if any. Conventional verbal counselling, particularly when not done in the patient’s mother tongue and supported by interventions such as visual counselling material, may not be adequate.

Thesis (M.S.)--Oregon State University, 2007. / Printout. Includes bibliographical references (leaves 92-98). Also available on the World Wide Web.

No description available.

162 leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (M.D.)--University of Adelaide, Dept. of Surgery, 1972

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Fig. C-14 in back pocket / xi, 171, xxxix leaves : ill. ; 25 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.) from the Dept. of Microbiology, University of Adelaide, 1973

Thesis (M.D.) -- University of Adelaide, Dept. of Surgery, 1972.