3. Electronic Theses and Dissertations (ETDs) - All submissions

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    A characterization and validation of the pyrogenic models and thermotric methids used for pharmacognostic evaluation of antipyretic medicine
    (2018) Dangarembizi, Rachael
    The development of safe and effective antipyretic and anti-inflammatory drugs remains an important focus of the pharmacological industry. Despite reports that rectal thermometry causes stress-induced hyperthermia in rodents, it remains the most commonly used method for measuring core body temperature during antipyretic drug-testing. The impact of the stressinduced hyperthermia on the accuracy and reliability of thermal responses reported in pharmacological studies investigating the efficacy of antipyretic drugs remains unclear. Additionally, the sickness response to Brewer’s yeast, the pyrogen recommended for inducing fever during antipyretic testing, remains largely uncharacterised and its mechanisms unknown. I used intra-abdominally implanted temperature-sensitive radiotelemeters to measure changes in the abdominal temperature of both normothermic and febrile rats injected with Brewer’s yeast, and exposed to rectal temperature measurement at hourly intervals for five hours. My results show that rectal temperature measurement is associated with a reproducible, nondecremental rise in abdominal temperature (0.6 - 0.8 °C) in normothermic rats. The hyperthermia was muted in febrile rats and was not blunted by the common habituation procedure. A comparison of temperatures measured using rectal thermometry with those measured using biotelemetry showed that rectal temperatures recorded using a thermocouple probe could be up to 0.5 °C lower or 0.7 °C greater than abdominal temperatures recorded using an abdominally implanted telemeter. The differences in thermal responses exhibited by normothermic vs febrile rats, coupled with the under- or overestimation of core body temperatures when one uses thermocouple probes supports my hypothesis that the procedure of rectal thermometry may affect the accuracy of thermal responses observed during antipyretic drug-testing. Having examined the methods used for temperature measurement, my second objective was to characterise the sickness response to the recommended and commonly used pyrogen for antipyretic screening; Saccharomyces cerevisiae (Brewer’s yeast). I measured the change in abdominal temperature, nocturnal activity, food intake and body mass gain in male Sprague Dawley rats injected subcutaneously with one of three doses of Brewer’s yeast (0.4, 0.2 and 4 g/kg). I further characterised the spatiotemporal activation of inflammatory mediators in the periphery (tumor necrosis factor alpha and interleukin (IL)-6) and in the brain (nuclear factor (NF) for interleukin 6, NF-kB, cyclooxygenase-2 (COX-2) and the signal transducer and activator of transcription (STAT)-3 in the vascular organ of the lamina terminalis (OVLT). Lastly, I measured the expression of hypothalamic inflammatory genes including: cytokines (IL-1b, IL-6, TNF-a), enzymes (COX-2 and microsomal prostaglandin synthase (mPGES)) and regulators of transcription factors (NF-kB inhibitor alpha (IkBa) and suppressor of cytokine signalling 3 (SOCS3)). My results show that Brewer’s yeast dose-dependently induces fever, lethargy, anorexia and body mass stunting. However, the sickness response to the high dose of Brewer’s yeast; the dose commonly used during antipyretic screening, was associated with an initial short-lived hypothermia, lengthy fevers, excessive peripheral and central inflammation and the development of an abscess. My last objective was to investigate if zymosan, a cell wall moiety of Brewer’s yeast could be used as an alternative pyrogen during antipyretic drug testing. Using the same methods as outlined for my second study, I therefore characterised the sickness responses and activation of inflammatory mediators associated with subcutaneous injection of two doses of zymosan (300 mg/kg and 30 mg/kg). My results show that zymosan dose-dependently induces fever, lethargy, anorexia and body mass stunting and that zymosan activates the same suite of inflammatory mediators as Brewer’s yeast albeit on a more moderate scale. Thus, zymosan could be used as a pyrogen for simulating fungal infections during antipyretic drug testing. In conclusion, the studies undertaken as part of my PhD have shown that among the methods and models currently recommended for use during antipyretic drug testing, rectal thermometry is associated with stress and hyperthermia which can potentially affect the accuracy and reliability of observations and conclusions drawn on the efficacy of test drugs. Additionally, at the recommended doses, Brewer’s yeast induces fever and sickness behaviours albeit with undesirable animal welfare challenges such as hypothermia, excessive inflammation and a lengthy sickness response due to the development of an abscess. However, zymosan is suitable for use as alternative to Brewer’s yeast as it is capable of inducing fever, sickness behaviours and inflammation of a moderate magnitude, which would allow pharmacological interventions without inducing animal suffering related to an excessive and prolonged inflammation.
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    The needs of family members accompanying patients into a trauma casuality
    (2014-08-26) Johnson, Meghan
    Introduction and Background Trauma Casualty is an environment of constant unpredictability which has an impact on the both the casualty staff, the patient and family. Family members are usually not prepared for the sudden crisis of having a loved one injured. The Trauma Nurse therefore, has a very important role with regards to meeting the needs of the family of patients brought into the unit. The needs of family members in the Intensive Care or Critical Care setting has been extensively researched using the critical care family needs inventory (CCFNI), however very little has been researched in the setting of a trauma or emergency setting. The needs of family members in the emergency setting has been researched in Australia, but no work has been done in South Africa. There is, therefore, a need for research in this area. Purpose of the study The aim of the study was to determine the needs of family members accompanying patients into trauma casualty, in order of importance as perceived by them, and to determine if these needs are being met. Identification of needs will inform the role of the nurse with regard to holistic nursing care including care of the family of the patient. Research Method The study made use of a quantitative descriptive exploratory design. The population (n=97) included family members of patients brought into casualty. The sample size was determined in consultation with a statistician from the Medical Research Council. The inclusion Criteria incorporated family members, over the age of 18, who were willing to complete a self administered questionnaire. Family members of patients who had died in the unit were excluded. An Australian developed instrument, using a Likert Scale to categorise and quantify needs statements, was used. The tool was validated by review of a panel of experts and an inter rater agreement of 90% established. The tool was adapted for the South African context and validated on a subscale level using the Cronbach Alpha correlation test. Five major themes make up the critical care family needs inventory, these consist of “Meaning”, “Proximity”, “Communication”, “Comfort”, and “Support”. Two questionnaires were used, comprised of the same needs statements, however CCFNI-1 was used to determine the level of importance of needs statements, while CCFNI-2 sought to determine the level of satisfaction of needs met. The study setting made use of a Level 1 Trauma Casualty in a Public Tertiary Academic Hospital, in which the pilot study was conducted before data collection in the same setting. The data analysis process made use of descriptive statistics. After cleaning and coding, the data were exported to STATA statistical software for values to be calculated and interpreted. Data were analysed in three steps, namely analysis of demographic data, thematic organisation of analysed data and content analysis of open ended questions. Main Findings The main findings highlighted the importance of needs relating to the themes “Meaning” and “Communication”, while satisfaction was highest in the theme “Meaning”. A concerning finding was the low level of satisfaction with needs being met related to communication.
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    The profile of deliberate self-poisoning cases presenting at the emergency department of Pelonomi Regional Hospital
    (2014-04-24) Benedict, Matthew Olukayode Abiodun
    Background Deliberate self-poisoning (DSP) remains a common method employed for suicide worldwide. Despite its frequent occurrence and the high cost required in its management, only few studies have been carried out on this subject in South Africa. Inadequate research into DSP in South Africa is a great concern as this may inadvertently result in an inadequate knowledge of health professionals on the general approach to victims presenting at emergency departments. This may consequently result in a poor clinical outcome of these cases. This study was aimed at determining the demographics of DSP cases presenting to the emergency department (ED) of Pelonomi hospital and also to enquire into the drugs/agents commonly used, reasons for DSP and the clinical outcome of these cases. Method This was a retrospective, descriptive study which was carried out by going through the hospital clinical records covering a period of eighteen months (1st January 2010 – 30th June 2011). The demographics and deliberate self-poisoning-related information were then collected, using a data collection form. The data was thereafter analysed by using descriptive statistics, calculated for continuous data. Frequencies and percentages were calculated for categorical data. Results Of the 212 DSP cases reviewed, 66% were female. Most patients (86.8%) were single and 65.6% were unemployed. DSP occurred more in the age-group of 20-39 years (68.8%). Majority of the DSP cases (84.4%) occurred in areas associated with poor socio-economic status.Paracetamol was the drug used by majority of these patients (21.7%) for DSP. Other common agents/drugs used were antidepressants (9.4%), antiretrovirals (ARVs) (9.9%) and household chemicals (19.3%). 85 patients (40.1%) took more than one drug/agent. Out of the 81 patients who had the reason for their poisoning stated, 40 patients had relationship disharmony (32 unmarried, 8 married). 15 patients had family issues which mainly resulted from conflicts with parents and grandparents. The medical reasons found amongst 5 patients were HIV infection, cancer and dental problems. Unemployment and post traumatic stress disorder following rape were the other reasons for DSP. The psychosocial problems of 10 patients were not specified. Majority of the patients (59.9%) were discharged in stable conditions. Low GCS (≤8) and hypothermia were common clinical features occurring amongst patients that got admitted. Conclusion DSP is still a common phenomenon, majorly amongst females in the age-group of 20-39 years, with poor quality of life. Relationship disharmony is the most common reason for poisoning. Drug/agents used can only be curtailed to a minimal extent. Prevention through early detection of vulnerable patients and early psychological management should be our goal.
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    A review of indications for endotracheal intubation in a private emergency centre in Pretoria
    (2012-07-12) Groenewald, Anita
    There is no clear list of indications for endotracheal intubation in the emergency centre. Current indications are derived from studies done in other disciplines, such as anaesthesiology (1, 2). The emergency centre is unique due to the presence of clinically undifferentiated patients as well as the urgency accompanying the management of critically ill or injured patients. A consensus statement for South African emergency centres was developed using a modified Delphi approach. The statement makes recommendations for a list of indications for endotracheal intubation in the emergency centre. This retrospective record review looks at indications used for endotracheal intubation in a private emergency centre during 2006. These indications were then measured against the consensus document derived from indications suggested by experts. The study evaluated 183 critically ill or injured patients during the study period of which 56 were intubated. Of all the critically ill or injured patients, only three were not intubated that should have been, according to the consensus document. The study found that the emergency doctors in the specific emergency centre used similar indications to intubate as suggested by the consensus document.
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    An analysis of paramedic out-of-hospital endotracheal intubation success in Johannesburg, South Africa
    (2012-01-19) Botha, Martin John
    Study objective: The aim of this study was to describe and analyse the success of endotracheal tube (ETT) placement when performed by paramedics in the out-of-hospital setting in Johannesburg, South Africa. Design: A prospective, observational study design with a consecutive convenience sample was used to analyse the prevalence of unrecognised mal-positioned ETTs by ALS paramedics. Setting: The ETT position was evaluated by the receiving medical practitioner in patients arriving at eight different urban, public and private, Johannesburg emergency departments (EDs) after being intubated by paramedics from multiple, both public and private – emergency medical services (EMS) agencies out-of-hospital. The study is set in a developing context where EMS systems vary considerably in terms of clinical governance, paramedic experience and qualification, and resources. Patients: All patients who arrived at Johannesburg EDs who had been intubated by paramedics out-of-hospital regardless of indication, aetiology or age, were included in the convenience sample. Methods: The main outcome measure was the unrecognized misplaced intubation rate which was recorded via routine methods by the receiving medical practitioner immediately upon arrival of the intubated patient at the ED. Findings were compared with international values. The use of endotracheal intubation confirmatory devices, both by paramedics and ED medical practitioners, was also reported. Main results: Of the 100 patients who were intubated out-of-hospital, 2 (2%; 95 CI 0.4% – 7.7%, p < 0.0001) arrived with unrecognised oesophageal ETT misplacements, and the ETT cuff was found to be in the pharynx, above the vocal cords in 1% of the sample. Thus, unrecognised mal-positioned intubations were detected in a total of 3 of 100 cases (3%; 95 CI 0.8% – 9.2%, p < 0.0001). Right main bronchus positioning occurred in 9 (9%) of cases. Paramedics reported the use of auscultation of the chest and stomach in 98% of the sample to confirm ETT placement, direct laryngoscopy in 22%, end-tidal carbon dioxide detection (ETCO2) in 19%, and pulse oximetry in 12% of patients. None of the misplaced ETTs had ETCO2 verification used out-of-hospital. ETT confirmation strategies by ED medical practitioners included auscultation of the chest and stomach in 97% of cases, direct laryngoscopy in 33%, and use of capnography to detect ETCO2 in only 4% of out-of-hospital intubated patients. Conclusions: This, the first known study to evaluate endotracheal intubation placement by EMS personnel in South Africa, found an overall 3% rate of misplaced ETTs (2 oesophageal and 1 hypopharyngeal), similar to several previous investigations, and much less than earlier studies. The findings of this study have important implications for South African EMS policy and practice. Based on the findings of this study, it seems reasonable to recommend that in a resource-limited, developing country where expensive ETCO2 is not readily available, the out-of-hospital ETT position should, at very least, be confirmed via auscultation, direct laryngoscopy and subjective clinical methods. Despite showing a statistically significant reduction in ETT misplacement rates when compared to international studies in similar settings, the results of this Johannesburg study are alarming and cause for concern, since any misplacement of an ETT in a critically ill or injured patient is calamitous with the potential for increased morbidity and mortality.
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