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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, Andile Kennedy 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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    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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    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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    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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    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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    Retail pharmacy prescription medicines availability, prices, and affordability in Eswatini.
    (2021) Shambira, Garikai.; Suleman, Fatima.
    Background: The low availability of medicines in public health outlets coupled with unaffordable prices in the private sector can be a major barrier to medicines’ access. Patients in Eswatini may be forced to buy medicines from the private sector due to the chronic medicines shortages in Eswatini public health facilities. The extent to which they can afford to do so is unknown. Aim: To determine the availability, prices paid by patients and affordability of medicines, in the retail pharmacies in Eswatini and to compare the results regionally. Setting: Retail pharmacy sector in the 4 administrative regions of Eswatini. Methods: Data on availability, prices and affordability to patients for two products namely the originator brand (OB) and the lowest-priced generic equivalent (LPG) for 50 medicines were collected using the standardised World Health Organization/ Health Action International methodology. The data collection was conducted in 32 retail pharmacies in the 4 regions of Eswatini. Prices for each medicine were compared with South Africa. Results: The overall mean availability of all medicines in selected retail pharmacy outlets was (38.5%; SD=20.4%) for OBs and (80.9%; SD=19.0%) for LPGs. The overall median price ratio (MPR) in the surveyed pharmacies was 18.61 for the OBs and 4.67 for LPGs. Most standard treatments with LPGs cost less than a day’s wage whilst OB’s cost more than a day’s wages. The differences between Eswatini and South African prices were statistically significant. Conclusion: There is a need to develop medicines pricing policies and price monitoring tools in the whole pharmaceutical chain in Eswatini to measure and monitor availability, affordability, and accessibility of medicines to the general populace.
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    Molecular epidemiology of antibiotic-resistant Enterococcus spp. from farm-to-fork in intensive pig production in KwaZulu-Natal, South Africa.
    (2021) Badul, Sasha.; Essack, Sabiha Yusuf.; Bester, Linda Antionette.; Amoako, Daniel Gyamfi.; Akebe, Luther King Abia.
    Background: Substantial antibiotic use and high population densities in intensive farming systems results in the emergence and spread of antibiotic-resistant commensals and pathogens. This study investigated the molecular epidemiology of antibiotic resistance (ABR) and virulence in Enterococcus spp. from pigs in an intensive food production continuum from farm-to-fork in the uMgungundlovu district, Kwa-Zulu Natal. Methods: A total of 174 samples obtained along the pig farm-to-fork continuum (farm, transport, abattoir, and retail meat) were subjected to the quantification and putative identification of Enterococcus spp. using the IDEXX Enterolert® method and selective media, respectively. Up to three presumptive enterococcal colonies were picked per sampling point for molecular confirmation by real-time PCR, targeting the genus- and species-specific (tuf and sodA) genes, respectively. Antibiotic resistance profiles were determined by the Kirby-Bauer disk diffusion method against a panel of antibiotics for Enterococcus spp. recommended by the WHO-AGISAR using EUCAST guidelines. Selected antibiotic resistance and virulence genes were detected by real-time PCR. Clonal relatedness between isolates across the continuum was evaluated by REP-PCR. Results: A total of 284 isolates constituted the final sample. Real-time PCR confirmed 79.2% of the isolates as E. faecalis, 6.7% as E. faecium, 2.5% as E. casseliflavus, 0.4% as E. gallinarum, and 11.2% as other Enterococcus spp. Antibiotic susceptibility testing revealed resistance to sulfamethoxazole-trimethoprim (78.8%), tetracycline (76.9%), erythromycin (68.1%), streptomycin (62.6%), chloramphenicol (27.0%), ciprofloxacin (8.5%), gentamicin (8.1%), and levofloxacin (5.6%) but no vancomycin, teicoplanin, tigecycline or linezolid resistance was detected. E. faecium displayed 44.4% resistance to quinupristin-dalfopristin. A total of 78% of enterococcal isolates were MDR. Phenotypic resistance to tetracycline, aminoglycosides, and macrolides was corroborated by the presence of the tetM, aph(3’)-IIIa, and ermB genes in 99.1%, 96.1%, and 88.3% of the isolates, respectively. The most commonly detected virulence genes were: gelE, efaAfs, and cpd in 89.1%, 78.5%, and 77.1% of isolates conferring autolysin and biofilm formation capabilities, cell adhesion, and conjugative plasmid accumulation, respectively. Clonality evaluated by REP-PCR revealed that E. faecalis isolates belonged to diverse clones along the continuum with major REP-types, largely consisting of isolates from the same sampling source but different sampling rounds (on the farm). E. faecium isolates revealed a less diverse profile. There was minimal evidence of clonal transmission across the continuum. Conclusion: Multi-drug resistant Enterococcus spp. were isolated along the farm-to-fork continuum. Isolates harboured a diversity of antibiotic resistance and virulence genes in different combinations forming reservoirs for the potential transfer of these genes from pigs to occupationally exposed workers and consumers via direct contact with animals and animal products/food, respectively. The results highlight the need for more robust guidelines for antibiotic use in intensive farming practices and the necessity of including Enterococcus spp. as an indicator in antibiotic resistance surveillance systems in food animals.
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    Awareness and knowledge of doctors, pharmacists and nurses on adverse drug reaction reporting systems in Namibia.
    (2020) Ndlovu, Garnet.; Oosthuizen, Frasia.; Bangalee, Varsha.
    Objective Reporting of adverse drug reactions (ADRs) in Namibian public health facilities is routinely done through safety yellow forms which are forwarded to the Therapeutics Information and Pharmacovigilance Centre (TIPC) for further assessment and possible interventions. This study investigated the awareness and knowledge of healthcare practitioners (HCPs) regarding the ADR reporting system in the country. Methods A cross-sectional study was conducted via a self-administered questionnaire at two state hospitals in Namibia; one located in the Khomas region and the other located in the Hardap region. The questionnaire was distributed to HCPs in current practice dealing directly with medication and it included a combination of open-ended, closed-ended and multiple-choice questions. Questionnaires were distributed in hard copy form during the period of 1 October 2019 up until 15 December 2019. Data was coded and transcribed into Microsoft® Excel® 2016 and analysed with SPSS® for IOS version 24. Results One-hundred and three completed questionnaires were received. Sixty-eight percent of the respondents were nurses, 24.3% were medical doctors and 7.8% were pharmacists. The majority of HCPs (73.8% and 56.3% respectively) were able to define the terms “adverse drug reaction” and “pharmacovigilance” correctly while only 41.7% correctly defined “spontaneous reporting”. The majority of HCPs (60.2%) have identified an ADR in practice; however only 36.9% reported this following the approved process. Only 48.5% of HCPs were aware of the safety yellow form for ADRs and 63.1% of HCPs did not know where to obtain the form. Furthermore only 37.9% of HCPs knew the name of the drug regulatory authority in Namibia. Conclusion Awareness and knowledge of ADR reporting systems by HCPs in Namibia is insufficient. While HCPs deem it necessary to report ADRs, reporting is unacceptably low leading to serious concerns regarding continuous monitoring of drug safety. Pharmacists showed better awareness compared to other HCPs and can, therefore, be best utilised as focal points in pharmacovigilance protraction. Mass awareness programs by the TIPC and other stakeholders need to be established to expand pharmacovigilance among HCPs.
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    A comparison study between public and private healthcare sector medicine prices in South Africa.
    (2020) Thaver, Tarryn.; Padayachee, Neelaveni.; Bangalee, Varsha.
    Introduction The adoption of medicine pricing regulations was established to counter the on-going global struggle of high medicine prices. South Africa’s healthcare is divided into the private and public sector and each sector functions utilizing different medicine pricing systems i.e. the tender and single exit price (SEP) system. The National Health Insurance (NHI), in its pilot phase in SA, may declare new system changes and improvements. Therefore, increased data on current medicine pricing systems are necessary particularly to assist the NHI process. Aim The overall aim of this study was to compare the medicine prices procured in the public tender system with the private SEP system. Objectives The objectives of the study were to compare pricing trends, determine price differentials, and equate the average price index of a basket of medicines between the public and private healthcare sectors in South Africa. Methods A pricing list consisting of 32 essential medicines available in both the public and private healthcare systems of South Africa was chosen for this study. The price of medicines for the private sector were obtained from the Medicine Price Registry- Open Up website for the period 2014–2018. Public sector medicine prices were obtained from the Department of Health website for the corresponding period. Observations and pricing trends were identified and analysed using Microsoft Excel version 2016. Key Findings A total of 74 medicine brands were analysed in the study. It was found that the prices across both sectors had increased over time, however, the majority of brands (87%) displayed higher prices in the private sector in comparison to the public sector. The price differential between the private and public sector medicines yielded positive values with the median of 252.30%. Conclusion The study found vast price differences between each pricing system due to the different methodologies practiced. Some of the methods and procedures utilized are known, however, both systems lack complete transparency in the processes applied. Therefore, more transparent medicine pricing systems need to be considered for the future of South Africa’s healthcare system as the country transitions toward universal health coverage.
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    Matching a chelator (DOTA) with ions for radio-pharmaceutical applications using DFT study.
    (2016) Frimpong, Ebenezer Kwabena.; Honarparvar, Bahareh.; Skelton, Adam Arnold.
    Organometallic chelators can be potentially used for radiometal-based pharmaceuticals. The bifunctional chelator, which is covalently bound to a lead compound, forms a stable chelator―ion complex to deliver an isotope, as a labelling agent, towards a specific in vivo target. The quest to find the optimal match between chelators and radiometal ions is of interest in the field of radio pharmaceuticals. A loss of radiometal ion from a chelator without reaching to its specific target organ in vivo could be disastrous to the body. The present project is focused on the complexation of 1, 4, 7, 10-tetraazacyclododecane-1, 4, and 7, 10-tetraacetic acid (DOTA) with alkali metals and radiometal ions. Herein, we investigated DOTA―alkali metal ions complexes with density functional theory using B3LYP and ωB97XD functionals and the 6-311+G(2d,2p) basis set for Li+, Na+ and K+ and Def2-TZVPD for Rb+. Conformational possibilities, starting from x-ray crystal structures and considering a different number of arms (2, 3 and 4) interacting with the ions were explored. Interaction and relaxation energies, thermochemical parameters, HOMO/LUMO energies, ΔEHOMO-LUMO and chemical hardness indicate the decrease in the stability of DOTA―ions down the alkali metal series. Natural bond orbital analysis reveals charge transfer between DOTA and alkali metals. Regarding radiometal ions, the geometries for the various complexes were consistent with experimentally reported binding constants. NBO analysis indicates charge transfer from the chelator to the radio metals resulting in reduced positive atomic charge values for all the ions. DOTA―Ga3+, DOTA―In3+ and DOTA―Sc3+ complexes recorded higher ΔELUMO-HOMO energies and chemical hardness values. The DOTA―Cu2+ complex was the least stable among the selected complexes. This study serves as a guide to researchers in the field of organometallic chelators, particularly; radio-pharmaceuticals in finding the efficient optimal match between chelators and different metal ions.
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    The impact of the introduction of generics and generic references pricing and candesartan and rosuvastatin utilisation, price and expenditure in South Africa.
    (2017) De Jager, Hendrik Petrus.; Suleman, Fatima.
    Rationale for the study The growth of pharmaceutical expenditure as a percentage of total health care expenditure has stagnated, both locally and globally, despite increasing consumption. Two factors that contributed to the stagnation are the introduction of generic medicines after patent expiry, and the introduction of cost-containment policies, like generic reference pricing. The introduction of generic medicines offer the opportunity to reduce medicine expenditure because of a switch in utilisation from expensive brand-name originator products to more cost-effective generic alternatives. Reference pricing is a policy where therapeutically similar medicines are grouped together, and a maximum reimbursement rate is set for the group. If a patient chooses to use a product more expensive than the reference price, they have to pay the difference in price. In the South African context, generically similar products are grouped together and the reimbursement rate is set at the average price of the generically equivalent products. Aims and objectives The aim of the study is to determine the impact of the introduction of generics and generic reference pricing on two active ingredients, candesartan and rosuvastatin, which recently lost their patent protection, in the South African private health care sector, for the period January 2012 to December 2015. To achieve this aim, three objectives were identified: 1. To measure the impact on medicine utilisation after the introduction of generics and generic reference pricing on candesartan and rosuvastatin. 2. To measure the impact on the average medicine price after the introduction of generics and generic reference pricing on candesartan and rosuvastatin. 3. To measure the impact on medicine expenditure after the introduction of generics and generic reference pricing on candesartan and rosuvastatin. Method Medicine claims for candesartan and rosuvastatin was obtained from a Pharmacy Benefit Manager in South Africa. The claims covered a 48-month period from January 2012 to December 2015 and provided a pre- and post-reference price period for analysis. Medicine utilisation was measured as the number of Defined Daily Doses dispensed per 100 000 beneficiaries. Medicine price and expenditure was calculated as the average per Defined Daily Dose. Results Candesartan experienced an average 7.0% year-on-year decline in utilisation and rosuvastatin a 5.0% increase. Utilisation of generic medicines was 59.3% of the total volume in the final year of the study for candesartan and 76.4% for rosuvastatin. The introduction of generic alternatives resulted in a 31.0% reduction in the average price per Defined Daily Dose for candesartan and a 13.9% reduction for rosuvastatin. Medicine expenditure reduced by an additional 34.6% and 20.9% for candesartan and rosuvastatin respectively, because of the introduction of generic reference pricing. The total saving because of the introduction of generics and generic reference pricing was 54.8% for candesartan and 31.9% for rosuvastatin. Conclusion The introduction of generics and generic reference pricing did not have an impact on overall medicine utilisation, but reduced the price and expenditure of both candesartan and rosuvastatin.
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    Trend analysis of antibiotic resistance in KwaZulu-Natal : a retrospective study 2011- 2015.
    (2017) Patel, Miriam.; Essack, Sabiha Yusuf.; Mlisana, Koleka Patience.
    Objective: Antimicrobial resistance is a global phenomenon which is limiting treatment options for common infections resulting in poor clinical outcomes, increased mortality and increased cost of healthcare. Antibiotic resistance trends in pathogen-drug combinations stipulated in the Global Antimicrobial Surveillance System (GLASS) of the World Health Organization were investigated for the period 2011-2015 in the province of KwaZulu Natal, South Africa. Methods: Antibiotic susceptibility data from blood, urine, faecal and urethral/cervical samples was retrospectively analyzed from six public hospitals. Pathogens included Escherichia coli, Streptococcus pneumoniae, Klebsiella pneumoniae, Salmonella spp., Acinetobacter baumannii, Staphylococcus aureus, Shigella spp. and N. gonorrhoea. Results were analyzed as MIC50, MIC90, percentage resistance, incidence of monitored infections in the population and proportion of nonsusceptible infections per pathogen. Results were also evaluated against South African treatment guidelines. Significant differences in resistance proportions by year were identified using the Pearson χ2 test. Comparison of MIC50 were analysed using the equality-of-medians test. Findings: Urine samples were most abundant (61.22%, n= 33 018) and E. coli (52%) was the most common pathogen. Most isolates were multi-drug resistant. Resistance to third and fourth generation cephalosporins and fluoroquinolones increased in K. pneumoniae, E. coli and Shigella spp. over the 5- year period. Notable changes in resistance were: K. pneumoniae from blood samples to carbapenems (1 – 26%, p< 0.001) and A. baumannii to carbapenems (69% - 50%, p-value not available). Susceptibility to antibiotics recommended in treatment guidelines was >50% for most pathogen-drug combinations. Conclusion: The results of this study show that antibiotic resistance in hospitals in KwaZulu-Natal generally increased from 2011 to 2015, although some pathogen-drug combinations showed a plateau or decline in resistance necessitating a review of the existing treatment guidelines. To our knowledge, this is the first South African report on ABR using GLASS metrics. There is a need for more extensive research in order to build an accurate, comparable picture of ABR in South Africa.
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    Experiences of Implanon NXT® users at public health facilities in South Africa.
    (2018) Prosad, Shimona.; Ojewole, Elizabeth Bolanle.
    Background and aim: Implanon NXT® was introduced in South Africa (SA) in the public health sector in February 2014. There exist concerns with premature Implanon NXT® user discontinuation in SA however, the true extent remains unknown due to delayed monitoring systems and limited empirical data. This study aimed to evaluate the experiences of Implanon NXT® among users in the public health sector in SA. Methods: A retrospective study was conducted and entailed analysis of secondary data attained from the National Department of Health Pharmacovigilance Centre for Public Health Programmes using reports submitted from 1 April 2015 to 11 September 2017. A total of 3743 cases were extracted and analysed using SPSS®. Tests of association were performed using demographics, adverse drug reactions and discontinuation variables. Chi square test and Mann Whitney U-Test were performed to test differences between Gauteng and KwaZulu-Natal (KZN). Results: The 20-24-year olds were the most frequent Implanon NXT® users (25.70%; 962/3743). Of the 36.57% (1369/3743) cases which reported adverse drug reactions (ADRs), menorrhagia (52.01%;712/1369), headache (20.45%;280/1369) and dizziness (11.18%;153/1369) were the most frequent ADRs. Discontinuation was reported by 63.56% (2379/3743) of case reports and premature discontinuation was reported by 81.1% (1210/1492). The common reasons for discontinuation were menorrhagia (34.27%;728/2124), expiry (29.57%;628/2124) and headache (10.26%;218/2124). Overall, ADRs were found to be the main reason for discontinuation (83.99%; 1784/2124). Pregnancies reported with Implanon NXT® occurred in 4.97% (68/1369) of case reports and efavirenz-based therapy was suspected to be associated with pregnancy in Implanon NXT® users (p<0.001). The common ADRs and reasons for discontinuation of Implanon NXT® reported in Gauteng was consistent with the national data while drug interaction and pregnancy were commonly reported in KZN. Premature discontinuation of Implanon NXT® was higher in Gauteng (82.6%, 252/305) than KZN (76.7%, 23/30). Conclusion: Young women were frequent users of Implanon NXT® . Menorrhagia was the predominantly reported ADR among all the users. A high frequency of discontinuation was identified, and ADRs were mainly responsible for discontinuation. The frequency of failure was small and efavirenz was suspected to be associated. The experiences of Implanon NXT® users differed between KZN and Gauteng which emphasizes tailored strategies need to be considered. Users’ counselling, adverse drug reaction treatment and management, monitoring and evaluation are recommended to address high discontinuation in SA.
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    Thiobarbituric acid a useful scaffold for medicinal chemistry.
    (2018) Noki, Sikabwe.; Albericio, Fernando.; Garcia-de-la-Torre, Beatriz.
    Due to the growth number of infectious diseases, a huge demand of new antimicrobial agents are required. In this regard, Thiobarbituric acid (TBA) moieties were explored. As its name indicates, TBA is the sulfur version of the barbituric acid. The work in barbituric moieties dated long ago in 1864 by Baeyer, when it was reported that these barbituric derivatives can be used as anesthetics, sedative or anticonvulsive agents. In the present work and taking advantage that TBA structure shows several points where diversity can be introduced, therefore several functionalities were introduced in the TBA analogues and their antimicrobial properties were studied in Gram-positive and Gram-negative bacteria. (Chapter 1) These are the chemical modifications explored: i) N- substitution, where this site can be substituted with a symmetrical substituents; ii) reaction at C-5 position owing to the high acidity of the protons which includes acylation, acetylation, Schiff bases, Knoevenagel condensation thioamide and enamine formation. The antimicrobial activity screening for the synthesized compounds were against Gram-positive (S. aureus and B. subtilus) and Gram negative (E. coli and P. aeruginosa) bacteria. Among all thiobabituric derivatives synthesized, Boc-Phe-TBA showed a promising activity, which confirms that TBA could be an excellent scaffold when combined with N-protected amino acids for developing antimicrobial compounds. (Chapter 2) The characterization of 20 thiobarbituric derivatives was carried out in different spectroscopy techniques such as: Nuclear Magnetic Resonance (NMR), Ultra violet spectroscopy, Infra-Red spectroscopy and single X-ray crystallography. In NMR characterization the acetylation of TBA was the most interesting due to the fact that this type of compound have the tendency of forming Enol and Keto tautomerism. This was proved by NMR and also by theoretical calculation, and the results confirm that the 1H NMR for this compound (A01)showed resonance at 17.72 ppm (singlet) for OH. This indicate that the enol form is more stable than the keto form. In UV characterization due to the fact TBA derivatives are not known aromatic and yet they are UV active. Therefore the absorption of few TBA derivatives were study in different solvents hence these showed absorption iv at maximum wavelength (max) in the range of 322 – 285 nm respectively. For IR characterization, these derivatives (A01, A02, A03, A04, A06, A10, A12, A13, A14 and A17) were evaluated, and showed absorption stretching frequency of thiocarbonyl (C=S) in three different ranges, 1395– 1570 cm-1 , 1260– 11420 cm-1 and 940 – 1140 cm-1 . For X- ray crystallography, crystals of A01, A02, A06, A13, A17 and A18 were obtained by hot recrystallization from ethanol and the intramolecular H-Bonding formation was observed in all cases, intermolecular H-bonding was observed for A17. (Chapter 3)
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    Evaluation of the pharmacokinetics of ketamine for the treatment of major depressive disorder.
    (2018) Naidoo, Vivian Campbell.; Baijnath, Sooraj.; Naicker, Tricia.; Naidoo, Panjasaram.; Kruger, Hendrik Gerhardus.
    Recent reports have demonstrated ketamine’s potential use in the treatment of major depressive disorder (MDD), as it elicits potent antidepressant effects via a different mechanism compared to conventional antidepressants. Ketamine’s hypothesized antidepressant effect is elicited by a neurochemical cascade involving the antagonization of the N-methyl-D-aspartate (NMDA) receptors and the subsequent activation of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors; resulting in the disinhibition of glutamate signalling due to the suppression of tonic glutamate input into the GABAergic interneurons, providing rapid symptomatic relief as opposed to the two-week delay with conventional treatments. There is a large escalation in the number of individuals being diagnosed with treatment resistant depression (TRD) even after numerous trials on conventional antidepressant therapy. Health care professionals are now resorting to unconventional treatments, such as ketamine’s off-label use, to achieve therapeutic outcomes and provide symptomatic relief. MDD’s increasing prevalence has been associated with significant public health costs and morbidity rates and therefore alternative, effective treatments are now essential. Many reports have been published on the intranasal (IN) efficacy of ketamine in the treatment of major depressive disorder, however there have been no studies investigating the effects on the route of administration in drug delivery to the brain. The purpose of this study was to investigate pharmacokinetics of ketamine following oral, intraperitoneal and intranasal administration. A dose of 15mg/kg (body weight) was administered to healthy male Sprague-Dawley rats, and ketamine concentrations were quantified in both plasma and brain tissue homogenates at time intervals of 5, 15, 30, 60, 120, 240 minutes post-treatment. The results showed that with intraperitoneal administration, concentrations of 524,58 ng/mL and 352,06 ng/mL, were achieved in plasma and brain tissue, respectively. Surprisingly, IN administration which is believed to favour drug delivery to the brain only exhibited moderate levels post administration; whereas, oral administration produced significantly lower levels due to extensive first-pass metabolism of ketamine in the liver and intestines. These results show that parenteral administration should be used for the administration of ketamine in the treatment of MDD. The findings of the study provide a platform for future investigations assessing alternative routes of administration of ketamine; and its use in clinical practice for the treatment of MDD. This paves the way forward to optimize treatment and provide symptomatic relief were conventional antidepressants have failed those suffering with MDD.
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    LC-MS/MS method development and validation for simultaneous quantification of first-line HIV drugs and second-line TB drugs in rat plasma.
    (2018) Malinga, Thembeka Hlengiwe.; Govender, Thavendran.; Baijnath, Sooraj.; Naicker, Tricia.; Kruger, Hendrik Gerhardus.
    Tuberculosis (TB) and human immunodeficiency virus (HIV) co-infection continues to be a major public health concern, worldwide. HIV infection has increased the TB incidence over the past twenty years, making it hard to eliminate TB. At the same time, TB continues to be responsible for approximately 30% of deaths among HIV-infected individuals. Emtricitabine (FTC), efavirenz (EFV), and tenofovir (TFV) are constituents of a one-day-pill, AtriplaTM, which was approved in 2006 by the Food and Drug Administration (FDA). AtriplaTM is a triple combination anti-HIV drug that provides an efficient dosing plan. Streptomycin (STR), kanamycin (KAN), and ofloxacin (OFL) are second-line anti-TB drugs used to treat multidrug-resistant/ extensively drug-resistant tuberculosis (MDR/XDR-TB). The worldwide increase in the prevalence of anti-TB drugs resistance is of concern to researchers since it remains one of the most significant threats to the community. Co-prescription of anti-HIV and anti-TB drugs poses a challenge of drug-drug interactions, which causes adverse effects. Therapeutic drug monitoring (TDM) seems to be the tool for a solution to these problems since it personalizes doses thus reducing drug toxicity. LC-MS/MS methods with short run times are required to produce effective TDM studies. Therefore, this study aimed to evaluate the new Ascentis Express column technologies [pentafluorophenylpropyl (F5), octadecyl (C18), biphenyl, and reversed phase amide (RP-Amide)] and their applicability to the simultaneous quantification of current first-line anti-HIV treatment Atripla. It also aimed to develop, optimize and validate a liquid-chromatography tandem mass spectrometry (LC-MS/MS) methods for the simultaneous quantification of anti-HIV drugs (FTC, EFV, and TFV) and second-line anti-TB drugs (STR, KAN, and OFL) in rat plasma for the usage of TDM. The currently used HPLC columns have longer run times making them impractical in a point of care environment since the number of patients and diseases is globally increasing. There are also no or very few studies regarding the LC-MS/MS method of simultaneous HIV and TB drugs for HIV positive TB patients. The biphenyl column showed consistency and optimum performance with regard to the number of theoretical plates, resolution and peak asymmetry factor. It showed good separation and overall effectiveness. However, this does not rule out other columns for other purposes intended to be accomplished. The LC-MS/MS method developed for the simultaneous quantification of anti-HIV drugs and second-line anti-TB drugs was short to eleven minutes and met all the recommendations by the European Medicines Agency (EMA) guidelines for bioanalytical method validation. The new HPLC column matrices (F5, C18, biphenyl, and RP-Amide) offer various benefits such as the potential of saving solvents and short runtimes, essential in TDM studies. Therefore, the usage of the new HPLC column technologies iv will be beneficial in a point of care environment in terms of saving time and money. The LC-MS/MS method validated in this study can be used in clinical trials and in the simultaneous determination of the effective plasma concentrations of anti-TB and anti-HIV drugs, making it a strong candidate for TDM in a point of care setting.
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    Design, synthesis and biological evaluation of antimicrobial agents: bromopyrrole-cinnamaldehyde hybrids.
    (2018) Dlungele, Andile Princess.; Karpoormath, Rajshekhar.
    Antimicrobial resistance threatens the effective prevention and treatment of an increasing range of Infections. The ongoing discovery of newer antimicrobial resistance has been a driving energy in the design, synthesis and development of newer antimicrobial agents. As a contribution to these efforts, we synthesized novel Bromopyrrole-Cinnamaldehyde Hybrids compounds. A series of fifteen Bromopyrrole-Cinnamaldehyde Hybrids molecules were synthesized by molecular hybridization approach. In vitro anti-mycobacterial activity of synthesized compounds was evaluated against Mycobacterium tuberculosis H37Rv strain. Among the series, 4(b-e) exhibited activity (MIC >20 μM; IC50 = >20 μM) furthermore the sythesised hybrids displayed promising activity against tested fungal strains, in particular for clinical isolate of C. neoformans with MIC values ranging from 12.5 – 25 μg/mL. All synthesized compounds were confirmed by melting point, FT-IR, 1H-NMR and 13C-NMR spectroscopy. The yield of these compounds obtained ranged from 40% to 80%.
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    Antimicrobial resistance and antibiotic stewardship: knowledge, attitudes and perceptions amongst final-year undergraduate health professional students in a South African university.
    (2016) Singh, Shanay.; Essack, Sabiha Yusuf.
    Antimicrobial resistance (AMR) is a major threat to human health. The World Health Organization (WHO) and subsequently the South African Department of Health have developed detailed plans to combat AMR including recommendations to implement Antibiotic Stewardship (ABS) in the curricula of healthcare students. A number of studies have measured the knowledge, attitudes and perceptions (KAP) of healthcare students globally. However, in South Africa, no multidisciplinary studies have been performed. This study thus ascertained KAP on AMR and antibiotic stewardship amongst final year medical, nursing and pharmacy students at a South African university by means of a cross-sectional questionnaire based survey. A total of 132 questionnaires were completed (response rate 33%), with individual response rates of 63% (n=63), 86% (n=46) and 9% (n=23) for pharmacy, nursing and medical students respectively. The mean correct knowledge score was 88.9%, with significantly lower scores seen for nursing students when compared to other two groups. The perceived seriousness of AMR at international, national and local levels was also significantly lower amongst nursing students. Only a third of all students and 45% of nursing students agreed that use of antibiotics contributes to AMR. Large percentages of nursing and medical students prefer to take antibiotics for viral illnesses whilst, 76% of all students consult a doctor before starting an antibiotic. Several knowledge gaps were identified, as well as key differences between the student groups. Curriculum review to educate students about their role in contributing to AMR and antimicrobial stewardship is imperative as sub-optimal KAP are likely to lead to negative patient outcomes.
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    A price and availability survey of essential medicines in Harare Province, Zimbabwe.
    (2015) Marume, Amos.; Bangalee, Varsha.
    Access to essential medicines is both a fundamental basic right and necessity for everyone, thus governments should make concerted efforts to ensure that all have access to safe, quality and comparative cost-effective medicines. Efforts aimed at identifying factors hindering full access are key in informing relevant policy makers. Thus in pursuant of making significant contributions to the above, a survey was carried-out in Harare metropolitan province of Zimbabwe to determine prices, price components, pricing policies, source and availability of essential medicines (their innovator and/or generic equivalents) in both private and public retail sectors. Comparisons with 36 other low to middle-income countries in the rest of Africa, Americas, Eastern Mediterranean, Europe, Southeast Asia and Western Pacific were also conducted. A standardized methodology developed by World Health Organization and Health Action International (WHO/HAI) was used to survey a selected basket of 40 medicines. The selection was based on the WHO/HAI core medicines list and the latest version of the essential drug list of Zimbabwe. The survey was conducted in 110 private pharmacies, of which 55 were from the central business district, 33 from the high density and 22 from the low density suburbs. In both private and public sectors, availability of the selected essential medicines (low priced generics) was quite high (>80%). Fewer innovator brands were found for the selected medicines. Median price ratios (MPR) of the lowest priced generics revealed that many people still might be having their accesses to essential medicines compromised by high prices, particularly in the private sector (4.52). The public sector showed significant progress towards procurement efficiency (MPR of 1.5). More than 70% of the surveyed medicines were from manufacturers outside Zimbabwe with more than 60% being produced by Indian generic manufacturers. Zimbabwe still needs to do more on pricing, particularly in the private sector as well as promoting local production among other efforts in its quest to ensure all its people have access to quality, safe and effective medicines.