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Masters Degrees (Pharmaceutical Sciences)

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    Nanoencapsulation of novel pyrazolone-based compounds to enhance solubility and biological activity.
    (2022) Igbokwe, Nkeiruka Nkeonyere.; Faya, Mbuso.; Karpoormath, Rajshekhar.
    The biological activity of pyrazolone-based derivatives has been thoroughly documented; nonetheless, low stability and water solubility are their main drawbacks, preventing effective translation to clinical application. Based on this, two previously reported weakly soluble pyrazolone-based compounds, PBC-301 and PBC-302, were encapsulated using PLGA: poloxamer complex to improve their solubility and further examine the influence of solubility augmentation on their biological activities. We first developed and validated a simple, accurate RP HPLC-PDA method for detecting, measuring, and standardising the compounds in nanoformulations to achieve this wide goal. Efficient separation and quantification were carried out using Shim-pack GIST C18 (5 𝜇m 150 × 4.6 mm) column, maintained at 25 ℃ with isocratic elution using acetonitrile and acidified water (0.1% Trifluoracetic acid) (75:25 v/v) at 0.5 mL/min flow rate. The injection volume was 20 𝜇L, and eluents were detected at 333 nm at a retention time of 4.82 mins. Method validation was done following ICH guidelines. Results demonstrated that the method is specific, precise, and accurate within the recommended limits. The method showed good linearity with a 0.9994 correlation coefficient over a concentration range of 2.5-50 𝜇g/ml. The method efficiently detected and quantified the novel pyrazolone compound in the nanosuspension. The obtained nanoformulations PBC-PLGA 301 and PBC-PLGA 302 were characterised using various in vitro techniques. Size, PDI and ZP of the optimised nanoformulations were 166.6 ± 7.12 nm, 0.129 ± 0.042, -14.14 ± 2.90 mV for PBC-PLGA 301 and 192.5 ± 1.08 nm, 0.132 ± 0.025, -10.77 ± 1.515 mV for PBC-PLGA 302 with the encapsulation efficiency being 84.20 ± 0.930 and 81.5 ± 2.051, respectively. The compound release from the nanovesicles followed a sustained release pattern, with PBC-PLGA 301 and PBC-PLGA 302 attaining a cumulative release of approximately 37% and 53% in 48 hours. The biological activity assays showed a better-enhanced activity with the nanoformulations compared to the non-encapsulated PBC 301 and PBC-302. In vitro antibacterial activity revealed that the compound-loaded nanovesicles have better activity against the two gram-positive bacteria S. aureus and Methicillin-resistant S. aureus compared to the standard drug vancomycin and the non-encapsulated compound. On the other, the cell penetration assay further revealed that the compound-loaded nanovesicles achieved greater than 90% propidium iodide penetration (translating to cell death) at the reported MIC well for S. aureus while showing 86% and 89% cell penetration for Methicillin-resistant S. aureus. Also, the nanoformulations showed improved radical scavenging activity in a concentration-dependent manner, with PBC-PLGA 301 exhibiting the best antioxidant activity against DPPH, FRAP and nitric oxide compared to the standard antioxidant-gallic acid and the non-encapsulated compounds. In conclusion, the aqueous solubility of the two pyrazolone compounds, PBC-301 and PBC-302, was greatly enhanced by their encapsulation into a nanosystem, resulting in improved biological activities. Therefore, the nanoformulations of the pyrazolone-based derivatives can be exploited as potential pharmaceutical agents to fight bacterial infections and other diseases triggered by oxidative stress, cancer, and hepatic and vascular diseases. The data from this study has resulted in two first-authored research publications.
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    Erythromycin, Roxithromycin, Azithromycin and Clarithromycin targeting the SARS-COV-2 spike protein: a molecular dynamics study.
    (2022) Naidoo, Eustacia.; Faya, Andile Kennedy Mbuso.
    The Covid-19 global pandemic has taken the lives of many people and has left the health sector in ruins. There is a desperate need for the scientific and medical community to pose new strategies to combat this virus. One way is repurposing of already existing drugs for the safe treatment of Covid-19. In view of the above facts, the present research project work was planned and aimed to identify the mechanism of inhibition of macrolides by evaluating them in silico against the SARS-CoV-2 spike protein. We performed molecular dynamics and molecular docking studies on the following macrolide antibiotics: azithromycin, erythromycin, clarithromycin and roxithromycin, and we compared these with the results achieved from our controls (Ivermectin and Remdesivir). Our ligands were prepared using chemdraw and chimera software. Protein data bank was used to retrieve the four receptors: 3CLpro (6LU7), native human ACE2 (1R42), RdRp (6M71) and spike RBD-ACE2 (6LZG)). AutoDock Vina software was used to perform all docking experiments. Fitting analyses were performed using PyMOL and Biovia Discovery Studio. GROMACS was used for molecular dynamics studies to determine RMSD (Root Mean Square Deviation) and RMSF (Root Mean Square Fluctuation) values. We then went on to determine the intermolecular hydrogen bonding present, as well as the distances of the ligand whilst inside the pocket. Our findings revealed that all the macrolide antibiotics portrayed similar results with each other, as well as with each of our controls (Ivermectin and Remdesivir). Each of the macrolide antibiotics showed strong binding with each of the four receptors. However, azithromycin showed the greatest binding potential (-7.9 kcal/mol) relative to the two controls (Ivermectin (-10.4 kcal/mol) and Remdesivir (-8.5 kcal/mol)). Azithromycin-ACE2 complex showed the least deviation to the ACE2 protein and is therefore the most similar. The average RMSF values shows that there are potential interactions of azithromycin with the receptor protein (ACE2). Covid-19 emerged in 2019, and to this date, 2022, there is no known cures. There have been vaccines like Johnson and Johnson and Pfizer which have been tried and tested and has shown to reduce severity of disease and minimize fatality. However, due to the new emerging strains, there is a continuous need for new therapeutic interventions. Azithromycin has also showed similar results to both Ivermectin and Remdesivir (controls), showing great binding affinity for the ACE-2 receptor. Our analysis based on molecular dynamics simulation and MM-PBSA binding free energy calculation suggests that azithromycin, erythromycin, clarithromycin and roxithromycin could serve as SARS-CoV-2 inhibitors, hence an alternative solution to treat COVID-19 upon further clinical validation.
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    O-alkylated/acylated coumarin analogues: synthesis, anti-diabetic evaluation and docking studies.
    (2016) Ngcoya, Nomandla Innocentia.; Singh, Parvesh.
    Diabetes mellitus (DM) represents a group of chronic disorders with diverse multiple etiology. It is characterized by high blood glucose (hyperglycemia) resulting from the malfunctioning in insulin secretion and/or insulin action, leading to impaired metabolism of carbohydrates, lipids and proteins in the body. According to 2013 WHO report, approximately 4.9 million people have died thus far and around 415 million are currently suffering from DM worldwide. Different approaches such as anti-diabetic drugs, insulin injection, and lifestyle modification are currently being used to control/treat diabetes. However, these techniques are not so effective and suffer a number of limitations which is why the development of novel potent anti-diabetic drugs is highly anticipated. Recent literature review revealed that the coumarins have potential to act as anti-diabetic agents with excellent pharmacological profile. Hence, the aim of this project was to synthesize variedly substituted coumarin analogues and to test their anti-diabetic potential under in vitro conditions. Accordingly, three 4-methylcoumarins bearing hydroxyl moiety were synthesized using substituted phenols and a β-ketoester using the Pechmann reaction. The hydroxyl group of synthesized coumarins was then engaged in further transformations by its alkylation and acylation using a variety of alkyl/acyl halides under basic conditions. The synthesized compounds were structurally characterized using different spectroscopic techniques viz. proton nuclear magnetic resonance spectroscopy (1H NMR, FT-IR and HR-MS). 2D NMR such as heteronuclear multiple bond correlation (HMBC), heteronuclear single quantum coherence spectroscopy (HSQC) and correlation spectroscopy (COSY) were also conducted to assign each proton and carbon resonances of the compounds synthesized. All the synthesized compounds were tested in vitro for their anti-diabetic activity using the standard drug (acarbose) as a control. Some of the coumarin derivatives exhibited excellent anti-diabetic activity, even better than the standard drug, based on the IC50 data. The effect of alkyl chain length and electronic nature (electron-donating/withdrawing) of substituents attached to coumarin ring on the anti-diabetic activity was monitored, and a detailed structure activity relationship (SAR) was established. The in vitro anti-oxidant activity of compounds further revealed the importance of hydroxyl (-OH) groups in coumarins for their antioxidant activity. The alkylation or acylation of coumarins significantly reduced their antioxidant activity. On the other hand, the attachment of nitro (-NO2) group to the aromatic ring of coumarin, impressively increased the antioxidant activity. Molecular docking simulations were finally conducted to predict the binding propensities of the compounds in the binding site of -glucosidase, an enzyme that regulates the sugar level in the body. Since, the X-ray data for this protein is not available in protein data bank, its 3D model was generated using homology modelling technique. The predicted free binding energies predicted these compounds to be good inhibitors for the protein. Docking data suggested the importance of both the hydrogen bonding and hydrophobic forces in their host-guest relationship.
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    The pharmacological management of Autism Spectrum Disorder in children.
    (2022) Maniram, Jennal.; Oosthuizen, Frasia.; Karrim, Saira Banu.
    Background Autism Spectrum Disorder (ASD) is a developmental disorder that affects individuals from early childhood. The pharmacological management of ASD in children remains a challenge due to limited effective management options and the absence of approved drugs to manage the core symptoms. This study aimed to review pharmacological treatment options used in the management of ASD in children at a public hospital in KwaZulu-Natal by identifying pharmacological agents prescribed and determining the role and impact on treatment outcomes. Additionally, the study aimed to review effective pharmacological management options employed in managing the core symptoms and comorbidities of ASD on an international scale by conducting a systematic review. Method A quantitative retrospective study was conducted by reviewing patient files of children diagnosed with ASD, meeting the inclusion criteria. A descriptive analysis was done to identify prescribing trends and therapeutic outcomes. A systematic review was also conducted to identify pharmacotherapeutic options for the management of ASD in children and adolescents. A systematic search for studies from January 2012 to January 2022 was performed using four databases, which included: PubMed, Scopus, Science Direct, and PsycInfo. A narrative synthesis was used for data analysis. Results A total of 181 children met the inclusion criteria for the study. Risperidone was the most frequently prescribed drug (88%) for the management of comorbidities and/or core symptoms of ASD. Attention deficit hyperactivity disorder (54%), irritability or aggression (25%), and sleep dysregulation (22%) were frequent ASD comorbidities that warranted pharmacotherapy. Drugs prescribed to manage ASD comorbidities included methylphenidate, melatonin, sodium valproate, risperidone, oxybutynin, carbamazepine, and others. Risperidone and non-pharmacological therapies played a prominent role in targeting the core symptoms of ASD. In 41% of patients, there was a positive response to treatment and 20% of patients experienced improvements in the core symptoms of ASD. The systematic review provides a comprehensive list of effective management options for ASD comorbidities and core symptoms from 33 included studies. Risperidone, aripiprazole, methylphenidate, guanfacine, levetiracetam, and atomoxetine are examples of effective pharmacological drugs against ASD comorbidities. Effective drugs for the management of ASD core symptoms include but are not limited to, bumetanide, fluoxetine, intranasal oxytocin, intranasal vasopressin, and prednisolone. Conclusion Pharmacotherapy plays an important role in managing the comorbidities of ASD, however, the use of drugs in the management of ASD core symptoms is limited at the public hospital in KwaZulu-Natal. The systematic review successfully summarised the pharmacological advancements made in the past decade and includes promising therapeutic options that manage the core symptoms and comorbidities of ASD.
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    Drug utilization review of analgesics in the management of pain in accordance with the South African Standard Treatment Guidelines at a hospital level in Limpopo, South Africa.
    (2022) Rikhotso, Muhluri Alvinah.; Bangalee, Varsha.; Suleman, Fatima.
    Background One of the aims of the National Drug Policy (NDP) of South Africa was to promote the rational use of medicines and to achieve this goal, the Essential Medicines Programme (formerly EMP), which included an Essential Medicines List (EML) and Standard Treatment Guidelines (STGs), was developed. The STGs offer guidance on the rational use of medicines for the most common conditions including pain management. A perceived marked increase in the use of tramadol for pain management requires that research be undertaken to confirm if there is use of tramadol outside of prescribed guidelines, and to determine the contributing factors for this. Study aim The overall aim of the research was to review the use of analgesics in the management of pain in terms of compliance with STGs by prescribers and to determine the cost implication of failure to follow STGs in pain management for the district hospital. Prescriber awareness and use of the guidelines for pain management and the associated cost implications of nonadherence to guidelines was also assessed. Finally the study sought to ascertain prescriber experience on the misuse of tramadol when treating patients for pain. Methods This was a quantitative study in which the records of patients admitted and being treated for chronic mild to moderate pain at a district hospital in Limpopo from the 1st of April to the 30th of September 2021 were reviewed to determine whether the Hospital Level Adults STG/EML (2019) was followed when patients commenced with treatment. An Excel spreadsheet was used to record patient demographics; diagnosis; pain medication prescribed; dosage regimen; prescriber post and prescriber compliance with recommended STG. The treatment regimens for pain that were captured included paracetamol; ibuprofen; and tramadol as single prescribed therapies as well as combinations of paracetamol and ibuprofen; paracetamol and tramadol; and a combination of all three, viz. paracetamol, ibuprofen and tramadol. The recorded prescriptions were assessed for compliance in terms of the stepwise process of pain management as outlined in the Hospital Level Adults STG/EML (2019). Descriptive statistics and Excel were used for data analysis. The cost of analgesics was obtained from the Limpopo Province Pharmaceutical Depot (LPPD). A questionnaire was used to determine prescribers’ awareness of STGs, compliance with guidelines for the management of chronic mild to moderate pain, and awareness of the cost implications of non-compliance among prescribers assigned to the general ward for the period of data collection. Full ethical approval was obtained before commencement with the study. Results A total of 224 prescriptions were recorded for the 6-month period. Patients initiated on paracetamol as first-line treatment for pain were 129 (57.5 %). Nineteen patients (8.5%) were initiated on tramadol and 54 patients (24 %) on paracetamol and tramadol. Patients initiated on paracetamol and ibuprofen were 12 (5.4%); those on ibuprofen were 3 (1.3%) and 7 (3%) were switched between pain regimens. The prescription compliance rate in terms of the stepwise process of pain management as outlined in the STGs/EML was 90.6% and 9.4% were noncompliant. The total cost for both compliant and non-compliant prescriptions was R1128,10. Compliance to STGs when prescribing analgesics as reported by prescribers was 33%. Half of the prescribers (50%) stated that they only follow guidelines occasionally. Only 33% followed STGs when prescribing tramadol although 83% stated that they prescribe paracetamol for pain. All prescribers had encountered tramadol misuse by patients but only 50% monitored patients after the medicine was prescribed. The study found that 67% of prescribers had poor knowledge of the cost implication associated with non-compliance to STG. Conclusion This study has identified that there is a prescription compliance rate of 90.6% among prescribers in prescribing analgesics according to the STG/EML. There is however still room for improvement because non-compliance to guidelines has cost implications. In the South African setting where there are resource constraints, compliance is critical for the purpose of efficient use of health care resources. There is also a need for educating prescribers on the importance of compliance to guidelines.
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    The effect of consignment on the price of pharmaceuticals and liquidity in a private hospital in Mombasa, Kenya.
    (2022) Ganiwalla, Shaheed Imtiaz.; Bangalee, Varsha.
    Background A well-structured procurement system will enable the acquisition of quality products in the correct quantity, at the right time, and the right cost. There are several procurement methods available for organizations’ to choose from, and each method will alter the organizations financial position in its unique way. Bomu Hospital transitioned from a tenderbased procurement system to a consignment model in 2020. Aim and Objectives This study aims to assess the impact of consignment on the financial health of Bomu Hospital. Specific objectives include: i) to determine the effect of consignment on the cost price of pharmaceuticals, ii) to assess the effect of consignment on the liquidity ratio, iii) to evaluate the effect of combining a tender and consignment system on the cost price of pharmaceuticals, and iv) to compare the mean adjusted cost price of pharmaceuticals with the Management Sciences for Health International Medical Products Price Guide 2015. Methodology The study used a retrospective pre-post observational design. Medicine purchase price data was collected from the 2019 tender document, 2020 consignment supplier invoices, and the 2022 tenders-for-consignment document. Liquidity was assessed by comparing the institution's cash flow statements from 2019 and 2020. Descriptive and inferential statistics were used to determine the effect of the two procurement systems on the purchase price of pharmaceuticals and its effect on the liquidity. Results The dataset included 65 products listed by proprietary name. Quantitative analysis of the purchase price obtained through tenders in 2019 and consignment in 2020 shows that the price increased by a median of 4.78% [IQR = -5.66% - 12.71%] (p=0.48). However, when tenders-for-consignment were introduced, the price reduced by a median of 7.71% [IQR = -11.72% - 1.935%] (p=0.65). Consignment resulted in a direct cash savings of KES 4,427,266.10 in one year. The median price ratio was 4.4319 [IQR = 0.8496-12.6193]. Conclusion Consignment offers substantial savings through reduced capital expenditure. However, eliminating competition results in higher purchase prices that can harm the affordability of medicines. Comparatively, tenders provide the best prices because of competition between suppliers. Combining both results in substantial savings for the institution without negatively impacting the cost of medicines.
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    Assessment of factors affecting adherence to chronic medicines among stable patients registered onto the Centralized Chronic Medicines Dispensing and Distribution (CCMDD) programme: the case of eThekwini Metropolitan Health District, South Africa.
    (2018) Naidoo, Mary-Anne.; Nlooto, Manimbulu.
    Background Globally more deaths are due to chronic disease compared to infectious disease. In South Africa, the number of patients has been increasing over the years for those who have been diagnosed with chronic diseases and thus requiring chronic treatment. The Centralized Chronic Medicine Dispensing and Distribution (CCMDD) programme is a national programme with the aim to improve patients access to medicines in the public health sector. To establish the implications of factors that affect patient adherence to chronic medication on the CCMDD programme in eThekwini Metropolitan Health district. Methods A descriptive cross-sectional study was conducted among stable chronic patients on the CCMDD programme in five public health facilities in eThekwini Metropolitan Health District South Africa between May and August 2017. The researcher administered face-to-face interviews were carried out using a semi-structured questionnaire with open and closed-ended questions. Results Most patients reported never experiencing out of stock of medicines at PUPs (365/417, 87 .5%, 95%CI [84.1-90.5]) and never received an incomplete parcel (324/417, 77.7%, 95%CI [73.7-81.7]). Many respondents rated their relationship with CCMDD as good (221/417, 53.0%, 95%CI [48.12-57.79]); they were satisfied to collect their medicines without counselling at PUPs (411/417, 98.6%, 95%CI [97.47-99.73]) and rarely experienced challenges with the CCMDD programme (345/417, 82.7%, 95%CI [79.07-86.33]). Majority ofrespondents reported a waiting time less than 30 minutes (411/417, 98.6%, 95%CI [97.47-99.3]) after CCMDD programme implementation compared to two hours (398/417, 95.4%, 95%CI [93.39-97.41]) before CCMDD program implementation. Most respondents (370/417, 88.7%, 95%CI [85.66-91.74]) reported not missing their appointment for collection of their medicines. Conclusion Most respondents reported neither experiencing medicine stock-outs nor receiving incomplete medicine parcels, they had a good relationship with the CCMDD programme, were satisfied with no counselling at the PUPs and rarely experienced challenges. Majority respondents reported a significant decrease in the waiting time for the collection of their medicines after CCMDD programme implementation. Missed appointments for collection of medicine parcels were significantly low among study participants. These findings can suggest high levels of adherence to such a programme.
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    Evaluating the impact of Single Exit Pricing (SEP) on medicine product withdrawal from the private health care market in South Africa.
    (2019) Naidoo, Kasturie.; Fatima, Suleman.
    Introduction: The introduction of medicine pricing policies in South Africa in the form of Single Exit Pricing (SEP), provided a mechanism to improve medicine price transparency and reduce both medicine price and inflation. However regulating medicine prices may have had further unforeseen effects on the availability of medicine. This research presents the impact of medicine price controls in the form of SEP on medicine product discontinuations from the private health care market in South Africa Aim The aim of this study is to evaluate the impact of SEP legislation on the availability of medicines in the private health sector market in South Africa, in terms of withdrawal of medicines from the market and rationale for withdrawal. Methods A descriptive, quantitative analysis of all registered medicines on the South African market by Stock Keeping Units (SKUs) to establish medicine products withdrawn from the market by SKU during a 14 year period from 2001 to 2014. Results A total number of 152 manufacturers discontinued 3691 SKUs between 2001 and 2014. The mean number of discontinuations per generic manufacturer was 22.34 (sd= 58.11), while innovator manufacturers discontinued a mean of 27.61 (sd= 41.89). The 2002 saw the largest number of SKUs being commercially withdrawn n=603, followed by 2003 (n=463) and 2004 (n=407). There was a negative correlation between number of discontinued SKUs per year and SEP increase; with a Pearson’s correlation coefficient (r) = -0.414 (p=0.14). Discussion Medicine pricing policies may have a dual impact in the market. Policies are typically aimed to make medicines more affordable to the patient; however pricing policies may have a negative effect on medicine availability. The results show that the SEP and transparent pricing policy may have had an impact on SKU withdrawal from the market. Lower prices and control of annual increases on medicines may have led to SKUs exiting the market. Conclusion The result of reduced product availability in the market and its impact to the cost and quality of healthcare to the patient needs to be regularly monitored and evaluated to ascertain if direct price regulations are achieving the intended outcomes as well as evaluate other intended or unintended effects in pharmaceutical market dynamics.
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    Assessment of factors affecting adherence to chronic medicines among stable patients registered onto the Centralized Chronic Medicines Dispensing and Distribution (CCMDD) programme: the case of eThekwini Metropolitan Health District, South Africa.
    (2018) Naidoo Pillay, Mary-Anne.; Nlooto, Manimbulu.
    Abstract Background Globally more deaths are due to chronic disease compared to infectious disease. In South Africa, the number of patients has been increasing over the years for those who have been diagnosed with chronic diseases and thus requiring chronic treatment. The Centralized Chronic Medicine Dispensing and Distribution (CCMDD) programme is a national programme with the aim to improve patients access to medicines in the public health sector. To establish the implications of factors that affect patient adherence to chronic medication on the CCMDD programme in eThekwini Metropolitan Health district. Methods A descriptive cross-sectional study was conducted among stable chronic patients on the CCMDD programme in five public health facilities in eThekwini Metropolitan Health District South Africa between May and August 2017. The researcher administered face-to-face interviews were carried out using a semi-structured questionnaire with open and closed-ended questions. Results Most patients reported never experiencing out of stock of medicines at PUPs (365/417, 87 .5%, 95%CI [84.1-90.5]) and never received an incomplete parcel (324/417, 77.7%, 95%CI [73.7-81.7]). Many respondents rated their relationship with CCMDD as good (221/417, 53.0%, 95%CI [48.12-57.79]); they were satisfied to collect their medicines without counselling at PUPs (411/417, 98.6%, 95%CI [97.47-99.73]) and rarely experienced challenges with the CCMDD programme (345/417, 82.7%, 95%CI [79.07-86.33]). Majority ofrespondents reported a waiting time less than 30 minutes (411/417, 98.6%, 95%CI [97.47-99.3]) after CCMDD programme implementation compared to two hours (398/417, 95.4%, 95%CI [93.39-97.41]) before CCMDD program implementation. Most respondents (370/417, 88.7%, 95%CI [85.66-91.74]) reported not missing their appointment for collection of their medicines. Conclusion Most respondents reported neither experiencing medicine stock-outs nor receiving incomplete medicine parcels, they had a good relationship with the CCMDD programme, were satisfied with no counselling at the PUPs and rarely experienced challenges. Majority respondents reported a significant decrease in the waiting time for the collection of their medicines after CCMDD programme implementation. Missed appointments for collection of medicine parcels were significantly low among study participants. These findings can suggest high levels of adherence to such a programme.
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    Evaluating the impact of Single Exit Pricing (SEP) on medicine product withdrawal from the private health care market in South Africa.
    (2019) Naidoo, Kasturie.; Suleman, Fatima.
    ABSTRACT / SUMMARY Introduction The introduction of medicine pricing policies in South Africa in the form of Single Exit Pricing (SEP), provided a mechanism to improve medicine price transparency and reduce both medicine price and inflation. However regulating medicine prices may have had further unforeseen effects on the availability of medicine. This research presents the impact of medicine price controls in the form of SEP on medicine product discontinuations from the private health care market in South Africa Aim The aim of this study is to evaluate the impact of SEP legislation on the availability of medicines in the private health sector market in South Africa, in terms of withdrawal of medicines from the market and rationale for withdrawal. Methods A descriptive, quantitative analysis of all registered medicines on the South African market by Stock Keeping Units (SKUs) to establish medicine products withdrawn from the market by SKU during a 14 year period from 2001 to 2014. Results A total number of 152 manufacturers discontinued 3691 SKUs between 2001 and 2014. The mean number of discontinuations per generic manufacturer was 22.34 (sd= 58.11), while innovator manufacturers discontinued a mean of 27.61 (sd= 41.89). The 2002 saw the largest number of SKUs being commercially withdrawn n=603, ` 2 followed by 2003 (n=463) and 2004 (n=407). There was a negative correlation between number of discontinued SKUs per year and SEP increase; with a Pearson’s correlation coefficient (r) = -0.414 (p=0.14). Discussion Medicine pricing policies may have a dual impact in the market. Policies are typically aimed to make medicines more affordable to the patient; however pricing policies may have a negative effect on medicine availability. The results show that the SEP and transparent pricing policy may have had an impact on SKU withdrawal from the market. Lower prices and control of annual increases on medicines may have led to SKUs exiting the market. Conclusion The result of reduced product availability in the market and its impact to the cost and quality of healthcare to the patient needs to be regularly monitored and evaluated to ascertain if direct price regulations are achieving the intended outcomes as well as evaluate other intended or unintended effects in pharmaceutical market dynamics.
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    Direct treatment costs of invasive candidiasis in Haematology patients at a South African private hospital.
    (2019) Cruickshank, Rozlyn.; Suleman, Fatima.
    ABSTRACT Background: Haematology patients are at a high risk of developing invasive candidiasis (IC). Fluconazole has been the mainstay of prophylaxis and treatment but recently a newer class of therapeutic options, the echinocandins, has seen a considerable improvement in treatment success. However, these agents are associated with substantial acquisition costs when compared to fluconazole. Objective: This study analysed the direct treatment costs of invasive candidiasis in haematology patients. Methods: This is a retrospective, single-centre economic analysis of haematology patients with IC, at a private hospital in Durban, KwaZulu-Natal province, South Africa.. The direct medical costs related to managing IC were analysed. These included antifungal administration costs, hospital ward costs, haematologist consultation costs and laboratory costs for blood cultures. Adult patients (≥18 years old) diagnosed with a haematology disorder and a positive blood culture for Candida who were prescribed fluconazole and/or an echinocandin as treatment were included in the study, patients in the three groups were analysed separately and compared. Results: There was a statistically significant difference for duration of antifungal treatment (p = 0.013) and antifungal administration costs (p = 0.003) between the three groups. Median overall direct treatment costs per patient were, ZAR110 365 for patients treated with fluconazole, ZAR219 915 for patients receiving an echinocandin and ZAR181 502 (for patients treated with both the antifungals. Overall hospital stay was the biggest cost contributor to the overall cost of treatment. Conclusion: The results of this cost analysis found that treatment with fluconazole only is considerably less expensive, almost half of the mean daily treatment cost, when compared to an echinocandin only and treatment using both agents is still less expensive than an echinocandin as first line therapy. 1
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    Comparative chemistry of COA® herbal medicine and herbal extracts of azadirachta indica and carica papaya.
    (2019) Nwabuife, Joshua Chukwufumnanya.; Manimbulu, Nlooto.; Karpoormath, Rajshekhar.
    Natural products have indeed endowed man with a variety of efficacious benefit combinations which can be dated to origin of the universe. The essence of herbs in the mitigation of human indisposition cannot be overstressed. The plant kingdom is believed to be a dockyard of never-ending genesis of active compounds paramount for the prophylaxis and mitigation of countless communicable and non-communicable disease conditions of mankind. Orthodox therapeutic substances used for basic medical care necessity, in recent times, have caught the attention of researchers; the rationale for this may be explained by the increased use of chemically derived therapeutic agents having adverse effects and negative clinical outcomes. This has seen the good turn of people to natural products such as COA® herbal medicine produced in Ghana and used by people in South Africa. However, the phytochemistry of COA® herbal medicine may not be well known. This study was aimed to establish the differences and similarities of phytochemical compounds found in COA® herbal medicine and two of its constituent plants (Azadirachta indica and Carica papaya Linn.) collected in Cape Coast (Ghana), Durban and Port Shepstone (South Africa). Method An experimental study was conducted in the pharmaceutical chemistry laboratory, discipline of pharmaceutical sciences, School of Health Sciences and in the chemistry laboratory, School of Chemistry and Physics, University of KwaZulu – Natal. A phytochemical screening and Gas Chromatography–Mass Spectrometry (GC-MS) were carried out using hexane, ethanol, ethyl acetate and dichloromethane extracts to establish the similarities and disparities between the COA® herbal medicine and leaf extracts of Azadirachta indica and Carica papaya Linn. collected in Ghana and South Africa. The mass spectra of the compounds found in the analyzed extracts were matched with the National Institute of Standards and Technology (NIST) library. Results The results of the phytochemical screening revealed the presence of alkaloids, anthraquinones, flavonoids, saponins, tannins, terpenoids and steroids, cardiac glucosides. GC–MS results revealed the presence of common phytochemical compounds such as Phyto acetate, Octadecanoic acid, Pentadecanoic acid, Stigmast-5-en-3-ol, Stigmast-5,22-dien-3-ol, in COA® herbal medicine and leaf extracts of Azadirachta indica and Carica papaya Linn. collected in Ghana and South Africa. However, this study confirmed the differences in phytochemical compounds from leaf extracts of Azadirachta indica and Carica papaya Linn. collected in Ghana and South Africa. Conclusion This study found that there were similarities between COA® herbal medicine and leaf extracts of Azadirachta indica and Carica papaya Linn. However, differences in phytochemical compounds were observed between leaf extracts of Azadirachta indica and Carica papaya Linn. collected in Ghana and South Africa.
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    Cytochrome p450 monooxygenase cyp139 family involved in the synthesis of secondary metabolites in mycobacterial species.
    (2019) Syed, Puleng Rosinah.; Karpoormath, Rajshekhar.
    Tuberculosis (TB) is one of the top infectious diseases causing numerous human deaths in the world. Despite enormous efforts, the physiology of the causative agent, Mycobacterium tuberculosis, is still poorly understood. To contribute to better understanding the physiological capacity of these microbes, we have carried out extensive in silico analyses of the 1111 mycobacterial species genomes focusing on revealing the role of the orphan cytochrome P450 monooxygenase (CYP) CYP139 family. We have found that CYP139 members are present in 894 species belonging to three mycobacterial groups: M. tuberculosis complex (850-species), Mycobacterium avium complex (34-species), and non-tuberculosis mycobacteria (10-species), with all CYP139 members belonging to the subfamily “A”. CYP139 members have unique amino acid patterns at the CXG motif. Amino acid conservation analysis placed this family in the 8th among CYP families belonging to different biological domains and kingdoms. Biosynthetic gene cluster analyses have revealed that 92% of CYP139As might be associated with producing different secondary metabolites. Such enhanced secondary metabolic potentials with the involvement of CYP139A members might have provided mycobacterial species with advantageous traits in diverse niches competing with other microbial or viral agents, and might help these microbes infect hosts by interfering with the hosts’ metabolism and immune system.
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    Prescription pattern monitoring of outpatient pediatric patients.
    (2019) Tsegay, Zerisenay.; Oosthuizen, Frasia.; Ojewole, Elizabeth Bolanle.
    Prescribing for paediatric patients can be challenging for prescribers as children are especially vulnerable to harmful effects of drugs due to differences in pharmacokinetics and pharmacodynamics as well as the limited availability of licensed drugs in their appropriate dosage forms. The World Health Organisation has estimated that over 50% of drugs globally are prescribed inappropriately. Prescription pattern monitoring studies (PPMS) are tools for assessing the prescribing, dispensing and administering of drugs. They help in explaining the extent and profile of drug use, trends, and quality of drugs and compliance of prescribing with standard treatment guidelines (STGs) and essential medicines list (EML). Regular assessment of prescribing practice and evaluation for compliance in reference with treatment guidelines is crucial in promoting rational drug use and identifying problems related to drug therapy. This study was therefore conducted to monitor the prescription patterns in paediatric outpatients and to determine the level of compliance of prescribed treatments against the South African 2017 paediatric STGs/EML at a public sector tertiary hospital located in KwaZulu-Natal, South Africa. Methods This was a retrospective descriptive study, based on systematic sampling of paediatric patient files visiting the outpatient department. Paediatric outpatient files containing prescriptions dated between June 1, 2016 and May 30, 2017 were used. A systematic sampling technique was used to minimize bias in the selection process and to ensure equal representation of samples. Data regarding patient demographic characteristics, diagnosis and disease condition as well as details of the treatments prescribed (drug name, dose, dosage form, frequency and duration of treatment) were extracted from patient files and captured using MS Excel 2016. The data were analysed using the following statistical packages; the Statistical Package for Social Sciences® (SPSS®) version 25 and Minitab® version 18. Compliance was determined using the loose criteria model, a method adopted from a report by the Ministry of Health and Social Services of Namibia and the Systems for Improved Access to Pharmaceuticals and Services (SIAPS). Where applicable, associations were carried out and a p-value ˂ 0.05 was estimated as statistically significant. Results A total of 327 patient files were evaluated, of which 193 (59.02%) were for male patients and 134 (40.98%) female patients. The total number of drugs prescribed was 845 constituted by 29 drug groups, of which antibiotics 155/845 (18.34%), emollients 118/845 (13.96%) and analgesics 117/845 (13.85%) were most predominantly prescribed. Of the 155 antibiotics, penicillins 55/155 (35.48%), penicillins combined with beta-lactamase inhibitors 40/155 (25.81%) and cephalosporins 39/155 (25.16%) were most commonly used. The percentage of encounters with antibiotics was 35.47% and the average number of drugs per prescription was 2.58. Out of the overall 845 drugs prescribed, 354 (41.89%) were generic drugs prescribed from the paediatric EML while 491 (58.11%) were non-generic drugs prescribed using trade names. Out of the total of 419 disease conditions assessed, 134 disease conditions were identified as most commonly diagnosed. Majority of the patients 100/134 (74.63%) did not have comorbidities, while 34/134 (25.37%) had co-occurring conditions ranging from 2 - 4 diseases. Male patients 19/34 (55.88%) presented slightly higher number of comorbidities compared to female patients 15/34 (44.12%). In order to determine compliance, disease conditions which were not listed in the 2017 paediatric STGs were excluded, resulting in 275 disease conditions. Treatments prescribed for 219/275 (79.64%) disease conditions were in accordance with the South African paediatric STGs, while treatments prescribed for 56/275 (20.36%) disease conditions did not comply with the STG recommendations. Conclusion There was a high level of antibiotic prescribing among the paediatric outpatients, and penicillins were the most often prescribed. The average number of drugs per prescription identified in this study was higher than that recommended by the World Health Organization. Overall, majority of the treatments prescribed conformed with the recommendations of the South African 2017 paediatric STGs, however extent of generic prescribing was low. There is a need for training of prescribers and healthcare professionals, especially regarding generic prescribing in order to promote appropriate use of drugs and overall patient safety.
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    Cost-analysis of Misoprostol and Mifepristone versus Misoprostol and Methotrexate when used for medical termination of pregnancy in women of gestational age of 7 weeks and less at Embhuleni Hospital in Elukwatini, Mpumalanga.
    (2019) Siyaya, Thembelihle Nomsa Qiosandra.; McGee, Shelley.; Suleman, Fatima.
    Background: The purpose of the Republic of South Africa Choice on Termination of Pregnancy Act 92 of 1996 is to provide a safe and effective alternative to the rife illegal abortions taking place in South Africa. The Department of Health’s standard treatment guidelines recommend a regimen of 200mg Mifepristone orally stat followed by 800mcg of Misoprostol sublingually after 24 to 48 hours (for up to 9 weeks or 63 days gestation) for termination pregnancy. Mifepristone has a relatively high cost and cost-effective alternatives would be beneficial to alleviate the strain on the National Healthcare budget caused by the official termination of pregnancy regimen. Aim: To perform a budget impact analysis and calculate potential savings if Methotrexate/Misoprostol combination is used for termination of pregnancy in women of gestational age less than or equal to 7 weeks compared to the current regimen of Mifepristone/misoprostol Setting: This study was undertaken at Embhuleni hospital, a 220-bed district hospital located in the Chief Albert Luthuli sub-district in Mpumalanga. Method: Three hundred and twelve (n=312) medical records of patients who visited the Choice of Termination of Pregnancy clinic during the 2017/2018 financial year, were retrieved and analyzed. Only medical termination of pregnancy medicines cost was considered. The total cost for the medicine (Misoprostol and Mifepristone) used to bring about an abortion was calculated using the information gathered from personal details and treatment regimen. Tender prices for 2017 were used for the medicines on national tender. Results: The current regimen of misoprostol/mifepristone costs R289.25 per case. The total cost incurred by the hospital in the 2017/2018 financial year for this medicine regimen was R90, 246.00 for a total of 312 patients. The proposed regimen comprising of methotrexate tablets and misoprostol costs R32.50 per patient whilst the total cost of using methotrexate injection and misoprostol tablets is R61.61 per patient. The current regimen impacted the medicine budget by 0.95% (0.51% if used for women of gestational age 7 weeks or less), 0.05% using the Methotrexate (MXT) tablets and 0.11% using the MXT injection. The alternative regimens were still cost-saving when tested through a sensitivity analysis. Conclusion: Both MXT injection and tablets are registered in South Africa and have local manufacturers and distributors. Currently in the public sector, Mpumalanga Department of Health formulary, the MXT 2.5mg tablets are on tender. If MTX tablets had been used, the total cost savings would have been 48% and 43% for the injection. In order to bring about change which will recommend for the indications of MXT to include Medical termination of pregnancy. More studies need to be done across the country to determine the overall financial impact the current regimen has and how much money could be saved from amending the guidelines to include the cost-effective regimen of MXT and misoprostol in combination. This study was not without limitations, it studied only the medicine required to bring about an abortion, for a more comprehensive budget impact analysis more variables will need to be considered.
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    Knowledge, attitudes and practices of veterinarians on antibiotic use, resistance and its containment in South Africa.
    (2021) Maruve, Simbai Allen.; Essack, Sabiha Yusuf.; Nlooto, Manimbulu.
    The inappropriate use of antibiotics in the veterinary sector has led to antibiotic resistance (ABR), which negatively impacts animal health and welfare and indirectly on human health. Understanding the knowledge, attitudes, and practices on antibiotic use, ABR, and its containment amongst veterinarians is critical to optimize antibiotic use and contain resistance. A quantitative questionnaire based online survey was conducted amongst members of professional veterinary associations. The questionnaire consisted of four sections focusing on socio-demographic characteristics, knowledge, attitudes, and practices (KAP) of participants on antibiotic use, ABR, and its containment in the South African veterinary sector. The Independent t-test, analysis of variance (ANOVA), and Chi-square test were used to establish associations among selected socio-demographic variables and selected KAP parameters. A total of 130 responses were received from 2178 animal health professionals, yielding a response rate of 6 %, with 102 complete responses constituting the final sample size. Self-reported knowledge on antibiotic stewardship, antibiotic resistance mechanisms, and pharmacology was good at 96 (94.1%), 91 (89.2%), and 70 (68.6%), respectively. More than half the respondents (60 [58.8%]) were confident that the veterinary training they received prepared them quite a bit/very much on rational antibiotic use. Most respondents (81 [79.4%]) believed that antibiotics were sometimes prescribed for suspected but not confirmed infections. The majority of the respondents (77 [75.5%]) were quite concerned/very concerned about antibiotic resistant infections, compared to 19 (18.7%) of clients expressing the same concern. Veterinary guidelines for appropriate use of antibiotics were sometimes read by respondents (45 [44.1%]). A little more than half of the veterinarians (54 [52.9%]) often/always discussed antibiotic resistance with their clients. Most respondents identified broadspectrum antibiotics such as amoxicillin-clavulanate and metronidazole as first-line treatment at 62 (60.8%) and 64 (62.7%) respectively. Notably, most of the veterinarians (61 [59.8%]) also lacked an antibiotic stewardship programme at their practice. The cost of diagnostics (90 [88.2%]), time to results of diagnostics (83 [81.4%]), and client expectations of receiving antibiotics (74 [72.5%]) were cited amongst barriers to the implementation of an antibiotic stewardship programme. Place of practice was significantly associated (p=0.004) with possession of knowledge about antibiotic resistance. Veterinarians in urban practice were more knowledgeable about antibiotic resistance than those in rural practice. Place of practice was also significantly associated (p=0.035) with discussions on antibiotic resistance with clients. More veterinarians in rural practice frequently carried out such discussions than their urban counterparts. There is a need for education and training to address gaps in KAP. There is also a need for the development and implementation of antibiotic stewardship programmes in veterinary practice. Cost effective diagnostic tests with shorter turnaround time might assist in achieving such. The programmes might encourage microbiology informed therapy and the use of guidelines for appropriate antibiotic use.
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    Awareness, attitudes, and experiences of patients taking antiretrovirals towards adverse drug reactions at a public health facility in KwaZulu-Natal.
    (2020) Tlaila, Malebogo.; Ojewole, Elizabeth Bolanle.
    Adverse drug reactions (ADRs) are undesirable side effects that occur even when a drug is administered at the proper dose and correctly for an appropriate indication. Given the high prevalence of Human Immuno-deficiency Virus (HIV) in South Africa, more than 3 million people are reported to be taking antiretrovirals (ARVs). Therefore, patients taking ARVs may also be taking other medicines due to other existing diseases such as diabetes, hypertension, and tuberculosis. The concurrent use of other medicines with ARVs may increase the potential of ADRs, snowballing to increased numbers of hospitalisations and contributing to mortality rates. The study investigated awareness, attitudes, and experiences of ADRs among patients taking ARVs. This was a descriptive cross-sectional study using a questionnaire that contained closeended questions to which patients responded. The study was conducted at a selected public hospital in KwaZulu-Natal. Questionnaires were available in both English and isiZulu and were hand delivered to patients. Ethical approval was obtained prior to commencement of this study. The participants were recruited by a random systematic selection by choosing every second participant. Both verbal and written consents were obtained before handing out questionnaires for participation. Statistical Package for Social Sciences (SPSS®) version of 25 was used to capture and analyse data. Categorical measurements were summarised using frequencies and proportions. Out of 200 questionnaires, a total of 174 patients responded, which delivered an 87% response rate. Of the 174 respondents, 55% (n=96) were females and 45% (n=78) were males. About 8% (n=13) of respondents were aware of ADRs, 55% (n=94) of drug–drug interactions and 12% (n=20) had reported ADRs. About 13% (n=22) respondents reported having hypertension, 7% (n=4) respondents reported diabetes and 1% (n=2) respondents reported tuberculosis. Almost 65% (n=114) respondents took the fixed drug combination, 17% (n=30) respondents took lamivudine and zidovudine combination, and 2.3% (n=4) respondents took ritonavir and atazanavir combinations. About 5% (n=8) respondents experienced vomiting, 1.7% (n=3) of respondents experienced diarrhoea and 1.1% (n=2) respondents experienced rashes. Most patients on ARVs and anti-TB medicines can experience reduced hearing or deafness, particularly in patients using medicines such as Kanamycin. Most medicines metabolised by CYP450, such as rifampicin and lopinavir/ritonavir combination, where rifampicin lowers ritonavir blood serum levels therefore requiring a boost of ritonavir. Patients should therefore be made aware of ADRs of ARVs, particularly those that may arise due to drug-drug interactions among the patients that have coexisting diseases. Patients should also be counselled to report ADRs, to obtain the ADR form, complete it and ensure they submit the ADR reports the healthcare professionals as well as the pharmacovigilance centre. The awareness of ADRs among patients taking ARVs could be improved by providing quality training and in-depth counselling of the patients during their visit to the hospital in order to ensure optimal therapy and patients safety.
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    Development of a tool to assess knowledge, awareness and perception of prostate cancer amongst women in Ghana.
    (2020) Wiafe, Ebenezer.; Oosthuizen, Frasia.; Bangalee, Varsha.; Mensah, Kofi Boama.
    Background and Objectives: The incidence of prostate cancer in developing countries is less than 30%, yet it has the disease's highest mortality. To address the mortality, strategies to increase awareness of the disease have been proposed, including the recommendation for women's active involvement. This is because women act as family health advocates, advisors, managers, and promoters. Therefore, it is essential to gather evidence on women's awareness of prostate cancer. Also, in Ghana, there is a lack of evidence about women's awareness of prostate cancer. However, there are about 50 indigenous Ghanaian languages, with Akan been the most spoken language. Providing a valid and reliable Akan version of a modified tool for assessing Ghanaian women's awareness of prostate cancer is vital. The study aim was (1) to conduct a mixed-methods systematic review on the awareness of women regarding prostate cancer, and (2) to translate, validate, and conduct a reliability assessment of a questionnaire for studying the knowledge, awareness, and perception of prostate cancer in Ghanaian market women. Methods: The Joanna Briggs Institute manual was employed in the development of a mixed methods systematic review protocol. The protocol was then used to conduct a systematic review of the awareness of women on prostate cancer. MEDLINE (EBSCOhost), CINAHL (EBSCOhost), PsycINFO (EBSCOhost), Web of Science, and EMBASE (Ovid) were searched based on the inclusion criteria for studies conducted between 1999 to 2019. Also, questionnaires on prostate cancer awareness were adopted from other studies, modified, and translated to Akan using the forward and backward translation protocols. The Akan questionnaire was certified, validated, and a reliability assessment was performed by measuring average scores, content validity index, and Cronbach’s alpha, respectively. Study participants for the validation and reliability study were recruited using a simple random sampling technique. Results: A total of 2201 articles were identified from the search, of which seven were included in the review. The selected studies' results indicated moderate knowledge on signs and symptoms; and causes and risk factors of prostate cancer. An inadequate level of knowledge about prostate cancer screening tools was recorded among women. An Akan questionnaire was adequately developed and certified. The average scores for all parameters employed in the face validation were greater than 4. The content validity index was within the range of 0.90 - 0.99 whilst Cronbach’s alpha within the range of 0.7808 - 0.9209. Conclusion: The selected studies indicated moderate awareness about prostate cancer among women. The selected studies for the review were few; hence this hinders the generalizability and transferability of the results. More studies should be conducted on prostate cancer awareness among women to promote their role in disease prevention. The Akan questionnaire for assessing women's awareness of prostate cancer was adequate, reliable, and valid for the Ghanaian or Akan speaking people.