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Item Open Access Factors influencing the utilization of biological medicines in the Free State (South Africa)(University of the Free State, 2019-06) Mocke-Richter, M.; Walubo, A.English: Biological Medicines are substances derived from animal or other biological origin, and are used to treat, diagnose or prevent mainly inflammatory diseases and cancer. The use thereof has grown worldwide and is aimed at improving the quality of life of patients. However, in South Africa access to Biological Medicines remains limited. Unfortunately, the use of Biological Medicines has presented challenges with regard to the requirements for appropriate therapeutic responses and their side-effects. In order to obtain an appropriate therapeutic response, appropriate patients have to be selected and continuously monitored during therapy. The two-fold aim of the study was to identify the factors influencing the utilization of Biological Medicines in the Free State (South Africa), and to develop a framework for the use of Biological Medicines in South Africa. Therefore the objective of the study was to determine perception, knowledge of and training in Biological Medicines by clinicians who have been practising for two years or less since graduating and to identify the factors that might influence the prescribing of Biological Medicines by some doctors in the Free State. It was also important to evaluate patient knowledge and experience with Biological Medicines and identify the factors (age, gender, race, disease, patient perception, and adverse effects) that might influence patient compliance with Biological Medicines in some institutions in South Africa. The abovementioned helped to develop a framework for the use of Biological Medicines in South Africa. A cross sectional study design was used. The literature review was used as the foundation to compile the questionnaires. The study consists of three different questionnaires, one for the newly qualified doctors; one for the specialists who prescribed Biological Medicines as well as the one for the patients who used Biological Medicines. The Delphi survey consisted of the data generated through the previous phases of the study, which consisted of literature cited, as well as three different questionnaires. For the purpose of this study, the Delphi method was used as a tool for achieving consensus, where experts validated some of the aspects and criteria with the view to draft a framework. As it was, out of the 79 newly qualified doctors in the Mangaung district (Bloemfontein) in the Free State, 79,7% (n = 63) completed the questionnaire. There were 17 specialists that prescribed Biological Medicines in the Free State, and 70,6% (n = 12) of them completed the questionnaire. Biological Medicines do not have more adverse effects than pharmaceutical agents. As it was, out of the 38 patients that used Biological Medicines and were identified by the clinicians, 81,6% completed the questionnaire. In the Delphi questionnaire study, there were 15 panel members that responded out of 20 who received the invitation. In conclusion, there was a general lack of knowledge on Biological Medicines among newly qualified doctors; therefore, there was a need to educate these young doctors about Biological Medicines, and to offer support in the form of a framework on the use of Biological Medicines to ensure that current patients benefit. The clinicians have limited knowledge of the pharmacology of Biological Medicines and therefore there is still much to be learned about the adverse effects of Biological Medicines. Furthermore, there is a need to educate the prescribers, and to offer support in the form of a framework on the use of Biological Medicines to ensure that current patients benefit and also to improve the procurement process to obtain Biological Medicines. It was established that Biological Medicines are improving the quality of life of patients. Seen from above, Biological Medicines have so far had a positive impact on patient lives; therefore, there was a need expressed to make Biological Medicines more available to patients who need it. The framework containing the findings of the research will be brought to the attention of the Biological Medicine Committee of South Africa, the Medicine Control Council, as well as the National Department of Health. It will furthermore be recommended that the framework that was developed may be adapted by the health care professionals who prescribe Biological Medicines. The research findings were submitted to academic journals with a view to publication, as well as presented at conferences.Item Open Access An integrated framework for the treatment of substance addiction and dependency in the Free State(University of the Free State, 2009-11) Van Zyl, Paulina Maria; Gagiano, C. A.; Mollentze, W.; Snyman, J.; Joubert, G.English:Background: Historically characterized by a high prevalence of alcohol addiction and dependency, South Africa has in recent years experienced an unprecedented increase in illicit drug use, linked to organized criminal activities. While internationally, the role of pharmacotherapy in the multi-disciplinary treatment of addiction/dependency becomes more important based on an increasing body of evidence revealing the biological nature of the condition, major transformation in the Health and Social delivery systems are taking place locally. Aim: The study aims to provide a critical analysis of current treatment practices regarding pharmacotherapy for drug addiction/dependency in the Free State against the background of the biological processes involved in the addiction/dependency state as well as aspects of health service delivery that may influence the use of pharmacotherapy. The analysis forms the basis for the development of a framework for the treatment of substance addiction and dependence regarding pharmacotherapy, taking into account the findings of the literature study and local context. Material and Methods: Both quantitative and qualitative methods were used. A questionnaire and structured interview were conducted with 121 health care professionals that could reasonably be expected to be confronted by patients with addiction and dependency. The population included a randomized sample of general practitioners selected from regional, district and basic environments in the Free State; purposely selected representatives of state hospitals and private treatment centres, as well as private psychiatrists and therapists in the corresponding towns. Results: Help-seeking for addiction occurs in a distinguishable pattern across the various professional groups. Private general medical practitioners are an important conduit into treatment for alcohol addiction and dependency. Depending on the local organization of services, they are also actively involved in the medical treatment of addiction and dependency cases. Private psychiatrists exclusively deal with dual diagnosis patients and are exposed to a wider range of addiction/dependency cases. State hospital service delivery varies from comprehensive services to no services. Perceptions regarding access to state hospitals and the quality of services in state hospitals are poor, while private services are generally regarded as costly, yet effective. Medical Scheme policies play an important role in determining access to facilities and services and dictate the individual prescriber‟s approach to pharmacotherapy. Respondents regarded the role of pharmacotherapy as essential in withdrawal and neuropsychological support, yet less important in relapse prevention. Convention mainly determines the withdrawal regimens used by respondents, with a number of area-dependent exceptions. Recognition of the neurotoxic nature of the withdrawal state is not universally reflected in the selection of pharmacotherapeutic agents in withdrawal regimens. Only disulfiram is commonly used for relapse prevention and its use is limited by high cost. Besides financial status, the decision to prescribe these drugs is based on the patient‟s motivation or willpower. Conclusion: A basic lack of recognition of the biological basis of addiction and dependency exists in the current legislation, in the organization of services and in the management of addiction/dependency. Medical intervention in addiction/dependency typically occurs late and follows an intermittent course with short-term goals. Recommendations: An integrated framework was developed and needs to be considered for implementation at both organizational and treatment practice levels in the region with the primary objective to improve treatment outcomes. Rational prescribing of pharmacotherapy requires an expansion of medication options and improved screening methods to allow individualized treatment, a biological imperative for successful treatment. At the same time standardization of evidence-based best treatment practices should be implemented. The role of private general practitioners as primary gatekeepers of the health system should be restored to provide a platform for accessible medical treatment of addiction and dependency.Item Open Access Development of a model to characterize the effect of Phela on selected immune markers in immune-suppressed rats(University of the Free State, 2015-05) Lekhooa, 'Makhotso Rose; Walubo, A.The therapeutic potential of several plant species and necessity for scientific validation of the use of plant derived medicines has prompted interest in field of traditional medicines. According to the WHO, in Africa alone, up to 80% of the population use herbal medicines to meet their primary health care needs and most of them have not been scientifically tested. Understanding the mechanism of action of herbal medicines is necessary for their proper use with regard to indications and limitations. One of South African traditional herbal medicines, Phela is currently being developed for use in immune compromised patients; hence there is a need to establish its mechanism of immunomodulation. Unfortunately, there is no appropriate animal model for the testing of immune-boosters. The current models involve either in vitro or ex vivo models. Furthermore, an ideal model would be a disease specific model, but this would not tell much about the mechanism of action, and would call for testing of every product in each disease model. As such, based on the understanding of the model of immune response in particular diseases, an in vivo model in which the cell mediated, humoral or non-specific immune response can be studied is more appropriate. Hence an animal model by which to evaluate purported immune boosters and traditional medicine to understand their mechanism of action on the immune system is essential. Here, it was proposed to undertake a study to develop a rat model by which to characterize the effect of Phela on selected immune markers in immune-suppressed rats. The above mentioned aim was achieved through six objectives outlined below. Firstly, an HPLC method with two detectors was applied to ensure consistency of all batches of Phela that were used throughout the study before undertaking an in vivo study. Two mark peaks were observed after analysis of Phela by HPLC-DAD. Phela fingerprint was confirmed by comparing the current results from both methods with those obtained previously. Secondly, an HPLC-UV assay was developed, validated and applied for the simultaneous determination of cyclophosphamide and dexamethasone concentration in rat plasma. The retention time was at 4.2, 5.7 and 8.1 minutes for cyclophosphamide, dexamethasone and internal standard, respectively. The method was linear with regression and correlation coefficients of y = 0.04x+0.11 and 0.999 for cyclophosphamide, and y = 0.32x–1.52 and 0.998 for dexamethasone, and their respective recoveries of 102 – 108 % and 99 – 107 %. The drugs were stable at -20 °C up to a month. Thereafter, the slide-a-lyzer technique was used to rule out potential interactions of Phela with the immunesuppresants [cyclosporine, cyclophosphamide and dexamethasone] before co-administration in rats experiment. Despite wide variations, the results indicated that there was no significant difference between the free fractions of drug-only group when compared with drug+Phela group. As thus, the above mentioned drugs could be co-administered with Phela without interference. In order to develop an animal model, three rat experiments were undertaken. For the first experiment, rats were treated with three escalading doses of Phela for three weeks, along with levamisole a known immune stimulant and a control group. Five rats were sacrificed once weekly per group. Physiological function tests and immune markers (CD4, CD8, IgG, IgM, IL-2 and IL-10) concentration was determined. Phela caused increase in white cell count, which correlates with elevated lymphocyte sub-sets (i.e. CD4 and CD8 count) after treatment with all three doses and this observation peaked by day 14 of treatment. Moreover, Phela led to ample stimulation of the immune system as indicated by increased CD4 cell count and IL-2 at doses of 5 and 15.4 mg/kg. This selective effect implies that Phela can be indicated in diseases that interfere with CD4 and IL-2 count, but this needed to be confirmed in a diseased model. The 15.4 mg/kg dose was selected to be used in subsequent studies. For the second experiment, the aim was to determine the optimum dose and time it takes to achieve optimum immune suppression by known immune suppressants; cyclosporine, cyclophosphamide and dexamethasone. Different groups of twelve rats each were treated with cyclosporine, cyclophosphamide and dexamethasone only, along with a control group in each case. Physiological and immune tests described in the first experiment were also done. As expected, the animals exhibited abnormal physiological function tests in association with progressive immunesuppression. Cyclosporine inhibited the cell mediated immunity, while cyclophosphamide suppressed the humoral immunity and the suppressive effect of dexamethasone was multi-systemic. In all cases, the immunesuppression continued up to the end of the study period. The optimum dose and time of each drug was established. This implies that a rat model of drug induced immune suppression was successfully developed. This rat model was to be validated when the immune suppressed rat model was co-administered with a test drug, in this case Phela, to understand its mechanism of immune modulation which is described in the experiment that follows. The aim of the third experiment was to apply the rat model to establish the mechanism of action of a purported immune booster Phela on the immune system. Different groups of fifteen rats each were pre-treated with cyclosporine, cyclophosphamide or dexamethasone only to induce immunesuppression. Thereafter, the control-groups continued on the immunesuppresant only and the test groups we co-treated with an immunesuppresants (CsA/CP/Dex) and Phela for 21 days. Tests described in the first experiment were similarly done. Phela stopped the progression of immunesuppression in rats treated with cyclosporine as indicated by the reversal and/or resistance to CsA induced changes in the WCC, neutrophils, lymphocytes, CD4, CD8 cells and IL-2 count. Furthermore, Phela prevented progression of CP-induced body and thymus weight loss, suppression of IgG and IgM, and minimal effect on CD4 and CD8 cell count. Observations from the results indicated that the mechanism of immunomodulation of Phela in rats is cell mediated. Therefore, Phela would be candidate for testing against diseases or disorders associated with suppressed CMI, such as HIV/AIDS and Tuberculosis. In conclusion, a rat immunesuppression model has been successfully developed and applied to establish the mechanism of immunomodulation of Phela in rats. Characterizing the mechanism of Phela in rats has indicated the scope of its application for use during diseases with a loss of cell mediated immunity. This model is a necessity in South Africa and across the world at large where many traditional herbal medicines and their products are purported as immune stimulants but lack proof of indication and a scope of application. Furthermore, this model is a tool and/approach that can be used to scientifically validate any immune stimulant and/or traditional medicine to establish its mechanism of action on the immune system, describing its limitations and contra-indications thereof. Lastly, the rat model was applied using Phela a known South African immune stimulant to establish its mechanism of.