Browsing by Author "Mathibe, Lehlohonolo John."

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Comparison of the costs of treating prostate cancer with standard chemotherapy regimens versus targeted nuclear medicines.
(2020) Gabela, Nomaswazi Cordelia.; Mathibe, Lehlohonolo John.
Background: Healthcare costs for the treatment of mCRPC continue to rise year on year. However, with the advent of targeted Nuclear medicine and continued treatment with standard chemotherapy regimen for the treatment of mCRPC the costs are still not known. Aim: We sought to compare the costs of treating mCRPC with standard chemotherapy regimen versus targeted Nuclear Medicine. Methods: We conducted a retrospective and prospective inferential study on patients, diagnosed with mCRPC, aged >18 years at Steve Biko Academic Hospital (SBAH), Pretoria and Inkosi Albert Luthuli Central Hospital (IALCH) in Durban, South Africa. The patients were referred to the treatment centres between the periods 1 January 2017 and 24 November 2019. We employed the International Classification of Diseases, 10th Revision Code system to identify mCRPC patients and match them with their Medical Record Number using MediTechTM computer Software program at IALCH, and a thorough patient file audit at SBAH was used to identify patients who were treated for mCRPC in this hospital during the study period. Treatment, Imaging, Screening, Out-patient and hospitalisation costs were extracted from the MediTechTM system using the Activity Based Costing Model and costs were compared to the costs derived from the patient files for the Nuclear Medicine patients. Results: A total of 60 patients (n=49, Chemotherapy Cohort, and n=11, Nuclear Medicine Cohort) with mCRPC, Mean ages at diagnosis 66 and 61 years respectively. The most common chemotherapy used were Bicalutamide, Goserelin and Docetaxel, compared to one comparator LuPSMA-Radioligand. The total healthcare costs for Chemotherapy were estimated at 500 000USD ($), whilst the costs for Lu-PSMA-Radioligand averaged 184 000USD ($). Imaging costs for chemotherapy were 37% higher than Lu-PSMA costs, in- hospital and out-patient costs accounted for 88% of the total healthcare costs. 2 Conclusions: For the treatment of metastatic resistant Prostate Cancer, patients treated with Chemotherapy regimen incur more cost for chemotherapy (43%) and imaging (37%) than patients treated with targeted nuclear medicine. Chemotherapy treated patients experience more in-patient and out-patient days compared to patients treated with targeted nuclear medicine. There are significantly more chemotherapy cycles and drug combinations that contribute to the higher chemotherapy costs.
Cost saving from the use of generic medicines for the treatment of the most common non-communicable diseases in adults in South Africa.
Redhi, Dhirendra Gyanasivan.; Mathibe, Lehlohonolo John.
Access to quality and affordable healthcare is a worldwide problem. Making healthcare affordable to the ordinary South African is a priority of the national government and therefore the use of generic medicine is encouraged. Generic medicines are manufactured by pharmaceutical companies without a licence from the innovator company, and are expected to work physiologically in the same manner as the innovator, based on their bioequivalence. These medicines normally cost less than innovator medicines. One method of reducing the costs of healthcare is by the introduction of generic medicine for the treatment of non-communicable diseases. This cross-sectional retrospective study investigated the potential savings from the use of generic medicine for the treatment of the most common non-communicable diseases of adults in South Africa. Five of the most common non-communicable chronic diseases in South Africa were extracted from the Council for Medical Schemes chronic disease list. The innovator drug, along with available generic drugs, was selected and an algorithm was designed to compare the single exit price differences for a treatment period of 30 days. To assess the price changes over a period of time, the innovator and generic medicine prices were compared in 2006 and 2014. This study has shown that there was a major saving potential from the use of generic medicines over innovator medicines for the treatment of the most common non-communicable diseases in adults in South Africa. This has been proven by comparing the single exit price of innovator medicines against that of generic alternatives. However, these findings confirm that medicine prices between innovator and generic brands vary extensively. A major saving of 97.14% for furosemide, 97.11% for prednisone and 95.70% for glibenclamide existed when generic medicines were used. Minor savings of 8.06% for budesonide and 12.68% for metformin existed when generic medicines were used instead of the innovator product. Secondly, this study has shown that over a period of eight years, most generic drug prices have increased in line with the South Africa’s nominal inflation rate, except for the methotrexate which increased by 75.70%, while simvastatin 10mg and 20mg generics decreased by 69.95% and 72.32% respectively. These results confirm the recommendations that generic medicine can be utilised effectively to ensure accessibility and affordable quality healthcare to all. However, constant monitoring of price changes is needed to ensure that above inflation increases do not erode affordability of quality healthcare achieved with the use of generic medicines.
Effects of Z-venusol and other pure compounds from medicinal plants on prostate, cervical and breast cancer cells.
(2017) Mathibe, Lehlohonolo John.; Naidoo, Strinivasen.; Botha, Julia Hilary.
Introduction According to recent World Health Organisation (WHO) estimates, cancer causes more deaths than coronary heart diseases globally (GLOBOCAN, 2012). While communicable diseases such as HIV/AIDS continue to burden African populations, cancer is increasingly recognised as a critical public and private health problem in Africa (Igene, 2008). It is estimated that by 2030, about 112 921 new cases of cancer will be diagnosed in South Africa (Singh et al., 2015). This would represent a 50% increase of new cancer cases as compared to 2012’s estimates by the WHO. Although there is little doubt about the incidences of cancer, there are, unfortunately, divergent theories in as far as tumourigenesis and the aetiology of cancer. Some researchers hold the view that cancer originates from malignant transformation of normal tissue progenitor and stem cells (Reya et al., 2001). Others believe that cancer is as a result of mature cells that have undergone de-differentiation (Sell, 2004). Notably, latest research has shown that there is a strong association between tissue-specific cancer risk and the lifetime cumulative number of cell divisions of tissue or organ-specific stem cells (Tomasetti & Vogelstein, 2015). Although there are still differing views on the origins of cancer, it is widely accepted that this devastating disease occurs as a result of abnormal cell development and is characterised by uncontrollable cell proliferation. The majority of currently-available cancer treatments target cell proliferation. However, the effectiveness of many cytotoxic drugs, including those that were discovered from plants, is limited by their serious side-effects and cost (Abratt, 2016). Chemotherapeutic agents that were originally discovered from medicinal plants include vinblastine (isolated from Catharanthus roseus), etoposide (isolated from Podophyllum peltatum), paclitaxel (isolated from Taxus brevifolia) and topotecan and camptothecin (isolated from Camptotheca acumenata). Thus, medicinal plants continue to play a critical role in the management of diseases in the world. In Africa, decoctions, which contain extracts from various medicinal plants (Bruneton, 1995; Balunas & Kinghorn, 2005), are widely used for traditional management of many diseases including cancer. However, apart from subjective oral evidence regarding the effectiveness of extracts from various plants, the identity of ingredients, as well as the science and pharmacology of active compounds found in numerous popular concoctions and decoctions are not known. Objectives The main objectives of this study were:  To assess anti-proliferative potential of three plant-derived-compounds, i.e. hypoxoside, ent-Beyer-15-en-19-ol and Z-venusol on human cancer cells, namely DU-145 (prostate), HeLa (cervical) and MCF-7 (breast) in vitro.  To determine the type of cell death, i.e. whether a compound with potential causes apoptotic or necrotic cell death on both human cancer and normal cell lines (such as MCF-12, HMECs and dMVECs).  To investigate how a potential compound exerts its cytotoxicity. Materials and Methods Initially dimethylthiazol-diphenyltetrazolium bromide (MTT) assays were conducted to find the concentrations which may inhibit proliferation in prostate (DU-145), cervical (HeLa) and breast (MCF-7) cancer cells. Normal human cell lines, which were used for control purposes, were the primary human mammary epithelial cells (HMECs), MCF-12 and the dermal microvascular endothelial cells (dMVECs). Initially, cells were exposed for 48 hr to hypoxoside, ent-Beyer-15-en-19-ol and Z-venusol, which were isolated from Hypoxis hemerocallidea, Helichrysum tenax, and Gunnera perpensa, respectively. The concentrations ranged from 2.34 μg/mL to 2400 μg/mL, dissolved in cell specific media. In subsequent experiments, the more sensitive sulforhodamine B (SRB) methodology was used, and cells were exposed to Z-venusol for 24 hr, 48 hr and 72 hr, to much lower concentrations, which ranged from 1.9 μg/mL to 240 μg/mL dissolved in dimethyl sulphoxide (DMSO). To investigate possible pathways of observed cell death, two assays were conducted. These were the fluorescein isothiocyanate (FITC) Annexin V apoptosis detection assay (using the FACS Calibur “JO” E5637 flow cytometer for analysis), and the lactate dehydrogenase (LDH) assay. To explore possible mechanism(s) of action, the activities of interleukin-6 (IL-6) and cyclic adenosine monophosphate (cAMP) were assessed. To investigate the activity of IL-6, cells were exposed for 48 hr to various working concentrations of Z-venusol; that is, 37.5 μg/mL and 75 μg/mL. To investigate the activity of direct cAMP, cells were exposed for 48 hr to various working concentrations of Z-venusol; that is, 37.5 μg/mL, 75 μg/mL, and 150 μg/mL. Absorbance, which is inversely proportional to the concentration of cAMP in both the samples and the standards, was measured using a BioRad (Model 3550) microplate reader. Epinephrine (10 μM) and propranolol (10 μM), were used separately and in combination, added to the highest concentration of Z-venusol for comparison. Main Results & Discussion Hypoxoside resulted in a statistically significant (p < 0.001) 38% and 77% increases in proliferation in MCF-7s at concentrations of hypoxoside 1200 μg/mL and 2400 μg/mL, respectively, after 48 hr exposure. In support of the current findings, Xulu (2013) also reported that hypoxoside, and its active derivative known as rooperol, significantly increases cell proliferation of both cancer and normal mammary cells in vitro (Xulu, 2013). This was considered an undesirable finding with regards to the aim of finding a cure for cancer. Therefore, no further test were carried out on this compound beyond the initial screening stages. The highest concentration (i.e., 2400 μg/mL) of the second compound, that is ent-Beyer-15- en-19-ol, decreased proliferation in prostate cancer cells (DU-145) and in breast cancer cells (MCF-7) by 6% and 19%, respectively. Interestingly, much lower concentrations, i.e. 4.7 μg/mL and 9.4 μg/mL, of ent-beyer-15-en-19-ol significantly (p < 0.05) decreased cell proliferation in cervical cancer cells (HeLa) by 37% and 41%, respectively. The differences in expression of vimentin gene, which is over-expressed in HeLa cells and suppressed in MCF- 7s and DU-145s may explain why this compound showed significant activity only in the cervical cancer cells (Oshima, 2002; Satelli & Li, 2011). More importantly, the ability of this compound to significantly inhibit cell proliferation in the HeLa cell line by almost 50% at lower concentrations offers an opportunity for further studies. The findings with regards to the third compound, i.e. Z-venusol, were the most exciting. Hence investigations on it were developed beyond the screening stages. This compound demonstrated a statistically significant, concentration-dependent, apoptotic inhibitory effect on the proliferation of MCF-7 cells, with an IC50 of 53.7 μg/mL after 72 hr exposure, while the highest concentration (250 μg/mL) resulted in 69% inhibition. Both the FITC Annexin V and LDH results suggested that apoptosis contributed to most of the effects observed. Further, there was non-significant inhibition (20%) of HMEC proliferation observed when the concentration of Z-venusol was increased beyond 16.6 μg/mL. The highest concentration of Z-venusol used in this study resulted in a statistically significant (p < 0.001) 51% inhibition of IL-6 activity in the MCF-7 after 48 hr exposure. None of the Z-venusol concentrations, either alone or in combination with epinephrine, an agonist of the adrenergic receptors, showed any statistically significant effect on the levels of cAMP in the MCF-7s. Surprisingly, there was a significant (p ≤ 0.028) 34% elevation of cAMP levels in cells which were exposed to a combination of Zvenusol and propranolol. If Z-venusol was ever able to be used clinically, there might be a need to increase the dose high enough for the attainment of desired therapeutic effects with minimal cytotoxicity on normal cells, because its potency is much lower than that of cisplatin. Increasing Z-venusol to a therapeutically-effective concentration would be possible as there was no plateauing-off of inhibition of proliferation in MCF-7s. It was only in primary normal human mammary epithelial cells (HMECs) that formation of “plateaus” was observed. Favourably, this selective plateauing-effect might allow the ‘gold-standard’ attainment of the desired cytotoxic effect on cancer cells while preserving normal cells at higher concentrations. There are no studies with which to directly compare the findings of this study. However, reports on effects of the extracts of G. perpensa on various other cancer cell lines provide an opportunity for comparison. For instance, the results of this research support the findings of Simelane and colleagues. They recently reported that G. perpensa extracts caused an inhibition of proliferation of hepatocellular carcinoma cells (HepG2) with an IC50 of 222.33 μg/mL and human embryonic kidney 293 (HEK293) cells, with an IC50 of 279.43 μg/mL both after 48 hr of treatment (Simelane et al., 2012). Conclusion Z-venusol, unlike other compounds studied, has a firm potential to play a role in the treatment of cancer in the future. Its mechanism of action involves IL-6 signaling, which may trigger other downstream mediators and may also involve cAMP “cross-talk”. Recommendations More basic science investigations using other hormone-dependent and highly invasive breast cancer cell lines such as the triple-negative MB-231 cells are needed. In vivo studies, such as using the nude mice model, are needed to confirm the in vitro results and to provide an insight into the benefits of Z-venusol in living systems.
Pharmacoeconomic implications of interchangeable use of oral NSAIDS for pain management at a district hospital.
(2015) Nkosi, Makhipha Johannes.; Mathibe, Lehlohonolo John.
Background: Ibuprofen, diclofenac and aspirin belong to the same class of drugs called NSAIDs, but are used interchangeably at Tonga Hospital. The problem with this approach is that it may lead to preventable misguided and increased spending on pharmaceuticals. Aim: To investigate the pharmacoeconomic implications of interchangeable use of oral NSAIDs for pain management at a district hospital. Setting: This study was conducted at a district hospital in the Tonga village in the Nkomazi municipality, Mpumalanga Province, South Africa. Methods: A quantitative retrospective descriptive study, using existing patient records as well as medicine stock control records, was conducted to investigate the cost-effectiveness of oral NSAIDs when used interchangeably in the management of pain in adult patients at a district hospital. Results: The total number of patients included in this study was 211 in a split of 104 in 2013 and 107 in 2014. The mean ages of all the patients who participated in our study in 2013 and 2014 were 36 and 35 years respectively and there were more females than males. Most patients who presented at Tonga Hospital for pain management were suffering from minor bodily/joint pains (36.0%, n=76), whereas the least number of patients were suffering from bone fractures (10.9%, n=23). Our study found that most patients (31.3%; n=66) treated with ibuprofen were suffering from minor bodily/joint pains, whereas the least number of patients (1.4%; n=3) treated with diclofenac were suffering from inflammatory conditions. Females were the largest users of NSAIDs (both ibuprofen and diclofenac) in Tonga Hospital when compared with males. Patients between the ages of 19-35 years were the most prevalent (28.4%, n=60) who were treated with ibuprofen when compared with patients 18 years and below (9.5%, n=20). Also, patients who were 18 years and younger and treated with diclofenac were the least number of patients (1.4%, n=3). The highest total NSAID stock volumes issued from July to December of 2013 and 2014 combined was ibuprofen (36978 packs) when compared with diclofenac (11127 packs). The stock volumes for both ibuprofen and diclofenac were higher in July, with 8170 for Ibuprofen and 2099 for diclofenac. Diclofenac stock volumes fell to their lowest (1583) in September, whereas Ibuprofen stock volumes fell to their lowest (4478) in December. The fall in stock volumes issued might be attributable to many factors including but not limited to non-delivery by the supplier or non-ordering by the pharmacy staff. In all instances ibuprofen stock volumes issued were higher than that of diclofenac. The acquisition cost of ibuprofen when calculated as mean price per tablet during 2013 to 2014 was consistently lower, with an average price of (0.285 ZAR) when compared with diclofenac (0.995 ZAR). 0.3% of the population of Nkomazi east, on average, gets treatment of ibuprofen daily whereas 0.01% of the population gets treatment of diclofenac daily. The mean cost per defined daily dose was consistently lower for ibuprofen in both 2013 (0.84 ZAR) and 2014 (0.87 ZAR) when compared with diclofenac in 2013 (2.94 ZAR) and 2014 (3.03 ZAR). The sensitivity analysis points in favour of ibuprofen over diclofenac as indicated when increasing or decreasing the mean price per tablet by 50% of either ibuprofen or diclofenac. Conclusion: This study found that the acquisition costs of NSAIDs in relation to the mean price per pack of oral tablets had been consistently higher for diclofenac than they were for ibuprofen in Tonga Hospital. Therefore, the use of ibuprofen oral tablets in the management of pain at a district hospital is cost-effective when compared with diclofenac oral tablets.