Research Articles (Pharmacology)

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Utility of multicellular spheroids for investigating mechanisms of chemoresistance in triple-negative breast cancer
(MDPI, 2025-08) Ncube, Keith Ntokozo; Van den Bout, Iman; Willers, Clarissa; Gouws, Chrisna; Cordier, Werner; werner.cordier@up.ac.za
Chemoresistance is a major challenge in the treatment of triple-negative breast cancer (TNBC). Multicellular spheroids are an attractive platform for investigating chemoresistance in TNBC, as they replicate the cues of the tumour microenvironment in vivo. We conducted a comprehensive literature search to summarise the multifactorial and interlinked mechanisms driving chemoresistance in TNBC spheroids. These mechanisms include spatial heterogeneity, hypoxia, extracellular matrix remodelling, tumour–stroma crosstalk, drug efflux, apoptotic resistance, and cancer stem cell signalling. Strategies for overcoming chemoresistance in TNBC spheroids include nanocarrier systems to overcome spatial diffusion limitations, pathway inhibition, and targeting tumour–microenvironment interactions. Despite their advantages, some spheroid models face challenges such as low reproducibility, a lack of heterogeneity, variability in size and shape, limited vascularisation, and constraints in long-term culture. Advanced culturing platforms such as clinostat bioreactors allow for extended culture periods, enabling mature spheroid drug testing. Furthermore, advanced analytical techniques provide spatially resolved spheroid data. These multifactorial and interlinked mechanisms reflect the tumour microenvironment in vivo that spheroids recapitulate, rendering them valuable models for studying chemoresistance. The incorporation of stromal components and advanced analytical workflows will enhance the utility and translational relevance of spheroids as reliable preclinical models for drug discovery in TNBC.
The global landscape of neuropsychiatric prescribing practices of nurses : a scoping review
(Wiley, 2025-07) Naidoo, M.; Filmalter, Cecilia Jacoba; Cordier, Werner; werner.cordier@up.ac.za
Mental healthcare service access in South Africa is currently strained due to, among others, shortages of specialised mental healthcare professionals. The National Strategic Plan for HIV, TB and STIs (2023-2028) recommends enabling nurses to diagnose, prescribe and dispense neuropsychiatric medication for promoting mental health services. The aim was to explore and describe the existing practices, strengths and challenges for nurses prescribing neuropsychiatric medication globally through a scoping and document review. A standardised search was conducted across PubMed, CINAHL and EBSCOHost electronic databases. An online Google search was conducted across governmental legislative and regulatory websites. The Joanna Briggs Institute scoping review framework was followed using relevant MeSH terms and free-text words. South African governmental and parastatal documentation relating to relevant regulatory frameworks affecting such prescribing authorisation in South Africa was analysed following Bowen (2009) guidelines. Of 817 citations identified, 20 reports were included. The included reports originated mostly from developed countries, with only one from South Africa. Patients and healthcare professionals were mostly positive towards including the prescription of neuropsychiatric medication in the nursing care model. Prescription of Schedule 5 and 6 controlled substances by nurses is already authorised in the USA and UK. In South Africa, nurses are not yet permitted and will require amendments to the legislative framework that guides nursing practice. Nurses can prescribe neuropsychiatric medications in certain developed countries; however, contextual research is necessary to ascertain whether South African stakeholders will support such an authorisation. Educational and interprofessional concerns will need to be thoroughly assessed to ensure that appropriate competencies are obtained, ensuring the boundaries of the scope of practice. Investigation of potential professional overlap of responsibilities and perceptional biases, as well as transformation of educational platforms, will be needed should such a recommendation come to pass. Furthermore, legislative changes will be required to authorise the prescription of neuropsychiatric medications.
WHO global research priorities for antimicrobial resistance in human health
(Elsevier, 2024-11) Bertagnolio, Silvia; Dobreva, Zlatina; Centner, Chad M.; Olaru, Ioana Diana; Donà, Daniele; Burzo, Stefano; Huttner, Benedikt D.; Chaillon, Antoine; Gebreselassie, Nebiat; Wi, Teodora; Hasso-Agopsowicz, Mateusz; Allegranzi, Benedetta; Sati, Hatim; IVanovska, Verica; Kothari, Kavita U.; Balkhy, Hanan H.; Cassini, Alessandro; Hamers, Raph L.; Van Weezenbeek, Kitty; Aanensen, David; Alanio, Alexandre; Alastruey-Izquierdo, Ana; Alemayehu, Tinsae; Al-Hasan, Majdi; Allegaert, Karel; Al-Maani, Amal Saif; Al-Salman, Jameela; Alshukairi, Abeer Nizar; Amir, Afreenish; Applegate, Tanya; Araj, George F.; Villalobos, Marlen Arce; Årdal, Christine; Ashiru-Oredope, Diane; Ashley, Elizabeth A.; Babin, François-Xavier; Bachmann, Laura H.; Bachmann, Till; Baker, Kate Susan; Balasegaram, Manica; Bamford, Colleen; Baquero, Fernando; Barcelona, Laura Isabel; Bassat, Quique; Bassetti, Matteo; Basu, Sulagna; Beardsley, Justin; Vásquez, Grey Benoit; Berkley, James A.; Bhatnagar, Anuj K.; Bielicki, Julia; Bines, Julie; Bongomin, Felix; Bonomo, Robert A.; Bradley, John S.; Bradshaw, Catriona; Brett, Ana; Brink, Adrian; Brown, Colin; Brown, Jeremy; Buising, Kirsty; Carson, Carolee; Carvalho, Anna Cristina; Castagnola, Elio; Cavaleri, Marco; Cecchini, Michele; Chabala, Chishala; Chaisson, Richard E.; Chakrabarti, Arunaloke; Chandler, Clare; Chandy, Sujith John; Charani, Esmita; Chen, Lisa; Chiara, Francesca; Chowdhary, Anuradha; Chua, Arlene; Chuki, Pem; Chun, Doo Ryeon; Churchyard, Gavin; Cirillo, Daniela; Clack, Lauren; Coffin, Susan E.; Cohn, Jennifer; Cole, Michelle; Conly, John; Cooper, Ben; Corso, Alejandra; Cosgrove, Sara E.; Cox, Helen; Daley, Charles L.; Darboe, Saffiatou; Darton, Tom; Davies, Gerry; De Egea, Viviana; Dedeić-Ljubović, Amela; Deeves, Miranda; Denkinger, Claudia; Dillon, Jo-Anne R.; Dramowski, Angela; Eley, Brian; Roberta Esposito, Susanna Maria; Essack, Sabiha Y.; Farida, Helmia; Farooqi, Joveria; Feasey, Nicholas; Ferreyra, Cecilia; Fifer, Helen; Finlayson, Heather; Frick, Mike; Gales, Ana Cristina; Galli, Luisa; Gandra, Sumanth; Gerber, Jeffrey S.; Giske, Christian; Gordon, Bruce; Govender, Nelesh; Guessennd, Nathalie; Guindo, Ibrehima; Gurbanova, Elmira; Gwee, Amanda; Hagen, Ferry; Harbarth, Stephan; Haze, John; Heim, Jutta; Hendriksen, Rene; Heyderman, Robert Simon; Holt, Kathryn Elizabeth; Hönigl, Martin; Hook, Edward W.; Hope, William; Hopkins, Heidi; Hughes, Gwenda; Ismail, Ghada; Issack, Mohammad Iqbal; Jacobs, Jan; Jasovský, Dušan; Jehan, Fyeza; Pearson, Antonieta Jimenez; Jones, Makoto; Joshi, Mohan P.; Kapil, Arti; Kariuki, Samuel; Karkey, Abhilasha; Kearns, Gregory L.; Keddy, Karen Helena; Khanna, Nina; Kitamura, Akiko; Kolho, Kaija-Leena; Kontoyiannis, Dimitrios P.; Kotwani, Anita; Kozlov, Roman S.; Kranzer, Katharina; Kularatne, Ranmini; Lahra, Monica M.; Langford, Bradley J.; Laniado-Laborin, Rafael; Larsson, Joakim; Lass-Flörl, Cornelia; Le Doare, Kirsty; Lee, Hyukmin; Lessa, Fernanda; Levin, Anna S.; Limmathurotsakul, Direk; Lincopan, Nilton; Lo Vecchio, Andrea; Lodha, Rakesh; Loeb, Mark; Longtin, Yves; Lye, David Chien; Mahmud, Asif Mujtaba; Manaia, Célia; Manderson, Lenore; Mareković, IVana; Marimuthu, Kalisvar; Martin, Irene; Mashe, Tapfumanei; Mei, Zeng; Meis, Jacques F.; Lyra Tavares De Melo, Flávio Augusto; Mendelson, Marc; Miranda, Angelica Espinosa; Moore, David; Morel, Chantal; Moremi, Nyambura; Moro, Maria Luisa; Moussy, Francis; Mshana, Stephen; Mueller, Arno; Ndow, Francis J.; Nicol, Mark; Nunn, Andrew; Obaro, Stephen; Obiero, Christina W.; Okeke, Iruka N.; Okomo, Uduak; Okwor, Tochi J.; Oladele, Rita; Omulo, Sylvia; Ondoa, Pascale; Ortellado de Canese, Juana Medarda; Ostrosky-Zeichner, Luis; Padoveze, Maria Clara; Pai, Madhukar; Park, Benjamin; Parkhill, Julian; Parry, Christopher M.; Peeling, Rosanna; Sobreira Vieira Peixe, Luísa Maria; Perovic, Olga; Pettigrew, Melinda M.; Principi, Nicola; Pulcini, Céline; Puspandari, Nelly; Rawson, Timothy; Reddy, Denasha LaVanya; Reddy, Kessendri; Redner, Paulo; Rodríguez Tudela, Juan Luis; Rodríguez-Baño, Jesús; Rogers Van Katwyk, Susan; Roilides, Emmanuel; Rollier, Christine; Rollock, Leslie; Ronat, Jean-Baptiste; Ruppe, Etienne; Sadarangani, Manish; Salisbury, David; Salou, Mounerou; Samison, Luc Hervé; Sanguinetti, Maurizio; Sartelli, Massimo; Schellack, Natalie; Schouten, Jeroen; Schwaber, Mitchell J.; Seni, Jeremiah; Senok, Abiola; Shafer, William M.; Shakoor, Sadia; Sheppard, Donald; Shin, Jong-Hee; Sia, Sonia; Sievert, Dawn; Singh, Ishwar; Singla, Rupak; Skov, Robert Leo; Soge, Olusegun O.; Sprute, Rosanne; Srinivasan, Arjun; Srinivasan, Subasree; Sundsfjord, Arnfinn; Tacconelli, Evelina; Tahseen, Sabira; Tangcharoensathien, Viroj; Tängdén, Thomas; Thursky, Karin; Thwaites, Guy; Tigulini de Souza Peral, Renata; Tong, Deborah; Tootla, Hafsah Deepa; Tsioutis, Constantinos; Turner, Katy M.; Turner, Paul; Omar, Shaheed Vally; Van de Sande, Wendy W.J.; Van den Hof, Susan; Van Doorn, Rogier; VeeraraghaVan, Balaji; Verweij, Paul; Wahyuningsih, Retno; Wang, Hui; Warris, Adilia; Weinstock, Hillard; Wesangula, Evelyn; Whiley, David; White, Peter J.; Williams, Phoebe; Xiao, Yonghong; Moscoso, Martin Yagui; Yang, Hsu Li; Yoshida, Sachiyo; Yu, Yunsong; Żabicka, Dorota; Zignol, Matteo
The WHO research agenda for antimicrobial resistance (AMR) in human health has identified 40 research priorities to be addressed by the year 2030. These priorities focus on bacterial and fungal pathogens of crucial importance in addressing AMR, including drug-resistant pathogens causing tuberculosis. These research priorities encompass the entire people-centred journey, covering prevention, diagnosis, and treatment of antimicrobial-resistant infections, in addition to addressing the overarching knowledge gaps in AMR epidemiology, burden and drivers, policies and regulations, and awareness and education. The research priorities were identified through a multistage process, starting with a comprehensive scoping review of knowledge gaps, with expert inputs gathered through a survey and open call. The priority setting involved a rigorous modified Child Health and Nutrition Research Initiative approach, ensuring global representation and applicability of the findings. The ultimate goal of this research agenda is to encourage research and investment in the generation of evidence to better understand AMR dynamics and facilitate policy translation for reducing the burden and consequences of AMR.
Antiretroviral-induced toxicity in umbilical cord blood-derived haematopoietic stem/progenitor cells
(Wiley, 2025-04) Hendricks, Candice Laverne; Ellero, Andrea Antonio; Mellet, Juanita; Stivaktas, Voula; Pepper, Michael Sean; michael.pepper@up.ac.za
Improvements in administration and efficacy of antiretroviral therapy (ART) have reduced rates of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) to < 2%. However, in utero exposure to antiretrovirals (ARVs) leads to abnormalities in HIV-exposed uninfected (HEU) infants. We determined the effect of five ARVs on human umbilical cord blood (UCB)-derived haematopoietic stem/progenitor cells (HSPC) with the aim of exploring a potential causal relationship with haematological abnormalities. Efavirenz (EFV) was cytotoxic to HSPCs alone and in combination with tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC). Dolutegravir (DTG) had a biphasic effect on HSPC expansion. Immunophenotypic analysis showed increased erythroid and granulocyte precursors after 7-day culture with these drugs. Finally, using colony forming unit (CFU) assays, we observed impairment in the formation of CFU-GEMM and CFU/Burst forming unit (BFU) erythroid (E) in the presence of DTG, lamivudine (3TC) and TDF, both visually and immunophenotypically. We conclude that multiple potential HSPC toxicities exist with ARVs commonly used in pregnancy, prompting the need for further research to confirm the safety of these drugs in this vulnerable group.
Combining an OSMAC approach and untargeted metabolomics to profile compounds exhibiting anti-HIV-1 activities in an endophytic fungus, Penicillium Rubens P03MB2
(Nature Research, 2025-07) Moloi, Neo; Khumalo, Mothusi C.; Nxumalo, Wonder Praise-God; Mtambo, Sphamandla E.; Mkhwanazi, Nompumelelo P.; Ndlovu, Sizwe I.
The persistent burden of HIV-1 in Sub-Saharan Africa underscores the need for innovative treatments, as current antiretroviral therapies cannot eliminate latent proviral reservoirs and face challenges from multidrug-resistant strains. This study investigates the potential of Penicillium rubens P03MB2, an endophytic fungus from the Albizia adianthifolia plant, as a source of novel anti-HIV-1 compounds. The fungus was cultivated in various media (malt extract broth, oats, and rice), with oat media yielding crude extracts exhibiting significant anti-HIV-1 activity. Active fractions were further analyzed using an untargeted metabolomics and molecular networking approach, revealing clusters of secondary metabolites, including coumarins and other anti-HIV-1-associated compounds. A virtual screening workflow was employed to assess the binding affinities of these metabolites against HIV-1 protease. Furthermore, molecular dynamics simulations were used to analyze ligand-protein complex stability. Binding free energy calculations highlighted diosgenin as a promising candidate, with a binding free energy of -34.59 kcal/mol, outperforming the co-crystallized ligand ORV. This research demonstrates the potential of secondary metabolites from Penicillium rubens as novel anti-HIV-1 agents, offering a foundation for further developing effective antiviral therapies.
Air travel and the risk of venous thromboembolism
(Medpharm Publications, 2025-04-01) Schellack, G.; Schellack, Natalie; Agyepong-Yeboah, Amma; natalie.schellack@up.ac.za
Passenger air travel is a convenient and frequently used mode of transportation across the globe. However, certain health risks are associated with commercial flights, many of which are inherent to this distinctive method of transportation. It has been shown that air travel innately carries an increased risk of the development of venous thromboembolism (VTE), and although small, this risk is significantly higher than in the general, healthy, non-flying population. Individual air travellers are strongly encouraged to consult a suitable healthcare professional for an individual risk assessment and guidance on suitable or required prophylactic measures prior to undertaking either frequent or long-distance travel via aeroplane.
Clearing the air : methods and challenges of smoking and vaping cessation
(Medpharm Publications, 2025-04-01) Van Nieuwenhuizen, T,J.; Schellack, Natalie; Bronkhorst, E.; Bronkhorst, E., Natalie; Savides, Isabella A.; natalie.schellack@up.ac.za
South Africa has a particularly high prevalence of smoking compared to the rest of the world. In spite of the fact that smoking rates in South Africa have been declining since the implementation of tobacco control measures in 1993, there are still an estimated eight million smokers in the country. Smoking has been associated with detrimental health risks and related complications for decades, and such health issues are further compounded by the high incidence of tuberculosis and human immunodeficiency virus/acquired immune deficiency syndrome in the population. Vaping has been offered as an alternative for smoking. This article aims to provide an overview of the importance of smoking cessation, and the nonpharmacological and pharmacological measures aimed at ensuring quitting. The vaping trend is fueled by the assumption that these products are safer and less harmful than traditional tobacco smoking. The rapid growth of the vaping industry has prompted debates on whether vaping functions as a smoking cessation aid or a gateway for new smokers. The evidence regarding vaping's efficacy in aiding smoking cessation is inconsistent, but there is compelling data suggesting a correlation between vaping and an increase in the number of smokers, particularly among the youth. Notwithstanding the well-established research on the greater harm of tobacco, early studies have already indicated the adverse effects of vaping. Despite the lack of comprehensive health studies, the expanding popularity of electronic cigarettes or electronic nicotine delivery systems such as vapes, especially among the younger demographic, has soared.
Beyond metformin : the expanding landscape of Type 2 diabetes treatment
(Medpharm Publications, 2025-03) Ncube, Keith Ntokozo; Malange, T.D.; keith.ncube@up.ac.za
Diabetes mellitus (DM) is a chronic, progressive metabolic disorder characterised by elevated and uncontrolled blood glucose levels and is a leading cause of morbidity and mortality worldwide. Type 2 DM accounts for over 90% of all diabetes cases and is primarily managed through lifestyle modification and pharmacological interventions. While metformin remains the first-line drug for the treatment of Type 2 DM, other adjunct therapies provide additional glycaemic control as well as cardiovascular and metabolic benefits. This review provides an overview of the pharmacological agents used in the management of Type 2 DM, and an insight into their mechanisms of action, therapeutic benefits, and side effects. Understanding these agents’ roles is crucial in optimising management and reducing possibly preventable and devastating sequalae of inadequately controlled diabetes
Management of erectile dysfunction
(Medpharm Publications, 2025-04-01) Schellack, Natalie; Schellack, G.; Nyane, Ntsoaki Annah; natalie.schellack@up.ac.za
Erectile dysfunction (ED), or impotence, significantly affects men from the age of 18 years but primarily those over 40 years of age. It is defined as the persistent inability to maintain penile erection sufficient for satisfactory sexual intercourse. EDis a multi-faceted condition that may involve any one (or more) of several different organic causes. Conversely, it may also be psychogenic in nature. This article provides an overview of the current classification, risk factors, impact of COVID-19 diagnosis and management of ED.
Mental health update - update on depression with a focus on vortioxetine
(Medpharm Publications, 2024) Jordaan, Beatrice
Depression, identified by the World Health Organization (WHO) in the International Classification of Diseases (ICD-11) as a complicated andmultifaceted condition, affects around 280 million people globally. In sub-Saharan Africa, mental health disorders, including depression,account for nearly 10% of the total disease burden, with depressive disorders being the most frequently diagnosed. Symptoms of depressioncan range from feelings of worthlessness and difficulty concentrating to sleep disruptions and suicidal ideation. Among the different typesof depression, major depressive disorder is the most prevalent. Extensive research has explored potential mechanisms contributing todepression, including genetic, neurochemical, and hormonal influences, such as those involving the hypothalamic-pituitary-adrenal axis.While both pharmacological and non-pharmacological treatments can effectively manage depression, antidepressants are typically the firstchoice. Vortioxetine, an antidepressant with multimodal activity, stands out due to its unique mechanism of action, combining serotonintransporter inhibition with direct modulation of 5-HT receptors. When left untreated, depression can result in serious physical, emotional andbehavioural health concerns. This review seeks to summarise current theories on the origins of depression and treatment strategies, with afocus on the therapeutic potential of vortioxetine.
Vaccines in the fight against antimicrobial resistance – perspectives from South Africa
(South African Medical Association, 2024-09) Brink, A.; Kagasi, A.; Musyoki, A.; Kagina, B.; Feldman, C.; Reddy, D..; Du Toit, E.; Kalanxhi, E.; Meyer, J.; Impalli, I.; Schonfeldt, M.; Sibanda, M.; Schellack, Natalie; Skosana, Phumzile; Essack, S.; Dlamini, S.; Ramsamy, Y.
Antimicrobial resistance (AMR), in which microbes adapt to and resist current therapies, is a well-recognised global problem that threatens to reverse gains made by modern medicine in the last decades. AMR is a complex issue; however, at its core, it is driven by the overuse and inappropriate use of antimicrobials. Socioeconomic factors have been identified as significant contributors to the emergence and exacerbation of AMR, especially in populations facing inadequate access to healthcare, poor sanitation services and high morbidity and mortality rates. Weak healthcare systems and water, sanitation and hygiene have been highlighted as fundamental risk factors for AMR emergence and transmission. Behavioural factors, such as purchasing antibiotics without a prescription from a registered healthcare professional, not completing the prescribed course or overly prolonged courses of antibiotics, using antibiotics to treat viral infections, lack of access to quality antibiotics, and the proliferation of substandard or falsified (SF) drugs, have also been identified as significant contributors to AMR. Low- and middle-income countries have a higher incidence of antibiotics being dispensed without a prescription than higher-income countries.
From economics to health outcomes : delving into the significance of reduced insulin prices
(South African Medical Association, 2024-08) Leuschner, Machel; Strydom, Morné; Steenkamp, Vanessa; machel.leuschner@up.ac.za
The recent substantial price reductions in insulin therapy by major manufacturers prompt an examination of their impact on South Africa (SA)’s healthcare. While Eli Lilly, Novo Nordisk, and Sanofi cut prices on long-acting basal insulin, among others, significantly, these insulins are not on SA’s Essential Medicines List (EML) for primary healthcare. With a high prevalence of diabetes, especially pre-diabetes, in the country, the EML’s neglect of newer long-acting insulin treatments hampers effective disease management. Despite efforts by the public and private sectors, insulin therapy initiation is delayed, impacting long-term outcomes. The introduction of smart insulin pens adds a technological dimension, but concerns persist about equitable access. Urging policy-makers to re-evaluate guidelines and decolonise the EML, the article emphasises enhancing patient quality of life and reducing the disease burden.
Patient knowledge, attitudes and behaviors related to antimicrobial use in South African primary healthcare settings : development and testing of the CAMUS and its implications
(Frontiers Media, 2025-05) Ramdas, Nishana; Biyela, Thobani; Thema, Mapula; Sibanda, Mncengeli; Sono, Tiyani Milta; Campbell, Stephen M.; Schellack, Natalie; Godman, Brian; Meyer, Johanna Catharina
BACKGROUND : Antimicrobial resistance (AMR) poses a global health threat, particularly in low- and middle-income countries (LMICs) including South Africa where limited resources and knowledge gaps exacerbate inappropriate antimicrobial use. To address this, the community antimicrobial use scale (CAMUS) was developed to assess patients’ knowledge, attitudes and behaviors regarding antimicrobial use in South African primary healthcare (PHC) settings, with the aim of informing antimicrobial stewardship (AMS) strategies. METHODS : Development of the CAMUS was informed by a scoping review and theoretical constructs from the Health Belief Model, Social Cognitive Theory, and Theory of Planned Behavior. A pilot study was subsequently conducted in two South African districts, an urban and a rural district, with 30 adult participants to provide insights into patients’ understanding of the items. Data collection involved administering CAMUS alongside a health literacy test followed by cognitive interviews to refine clarity and ensure understanding. A feasibility assessment was also conducted to evaluate the practical use of CAMUS in PHC settings. RESULTS : Participants demonstrated varied knowledge of antimicrobial use. While 60% correctly identified antibiotics as effective for bacterial infections, 93.33% incorrectly believed antibiotics could treat viral illnesses such as colds. Marginal health literacy was prevalent (86.67%). The CAMUS demonstrated feasibility, with an average completion time of 10 minutes. Questions were iteratively revised to improve future clarity and relevance based on the results of the cognitive interviews. Key findings highlighted misconceptions about antibiotics and the influence of social norms and systemic barriers on antimicrobial use behaviors. CONCLUSION : The CAMUS effectively captures the knowledge, attitudes and behaviors of antimicrobial use in South African PHC settings. Pilot testing demonstrated its feasibility to use it as a tool to assess patient knowledge, attitudes and behaviors related to antimicrobial use in a larger population, to subsequently guide AMS initiatives by addressing knowledge gaps and related barriers to improve future antimicrobial use. Future research will include development of a shorter version of the CAMUS, followed by validation in larger, more diverse populations and in local languages to enhance its usability when investigating antimicrobial use and AMR across LMICs.
Expert consensus on vitamin B6 therapeutic use for patients : guidance on safe dosage, duration and clinical management
(Dove Medical Press, 2025-04) Schellack, Natalie; Yotsombut, Kitiyot; Sabet, Arman; Nafach, Jalal; Hiew, Fu Liong; Kulkantrakorn, Kongkiat
PURPOSE : Vitamin B6 is a crucial water-soluble vitamin found in many foods and is involved in numerous physiological processes, including neurotransmitter synthesis and nervous system function. Although essential for overall health, both deficiency and excessive intake of vitamin B6 may lead to health complications, particularly peripheral neuropathy. This consensus statement aims to provide healthcare professionals with clear guidance on the safe and effective use of vitamin B6, focusing on its benefits, risks, recommended dosages, and treatment course. METHODS : This consensus statement was developed using a Delphi approach involving a panel of six experts from various medical specialties. This process includes a comprehensive literature review, two rounds of anonymous online surveys, and a virtual expert roundtable discussion. The GRADE approach was used to assess the quality of evidence for each recommendation. RESULTS : The expert panel reached consensus on five key statements. These key recommendations encompass the function of vitamin B6, complications due to vitamin B6 deficiency, dosage recommendations, adverse events, and monitoring guidance throughout the course of treatment. A washout period of 20– 40 days for the complete clearance of vitamin B6 was calculated based on pharmacokinetic parameters. A clinical pathway for managing patients who might benefit from vitamin B6 treatment was proposed. CONCLUSION : This consensus statement highlights the importance of recognizing the benefits and potential risks of vitamin B6. While the therapeutic dosage of vitamin B6 can be beneficial to treat deficiency, excessive intake can lead to adverse effects. This statement emphasizes the need for individualized patient care considering factors such as medical history, lifestyle, and potential drug interactions. Further research is needed to establish clearer dosage guidelines, understand the mechanisms of vitamin B6-induced neurological side effects, and optimize patient outcomes.
Update on the pharmacological management of neurodegenerative diseases : Alzheimer's disease
(Medpharm Publications, 2024) Flepisi, Brian Thabile; Hanser, S.; Balmith, Marissa; brian.flepisi@up.ac.za
Neurodegenerative diseases (NDDs) are the most common causes of morbidity and cognitive impairment, particularly among the elderly population worldwide. Due to increasing life expectancy, there has been an increase in the prevalence of NDDs. One of the most common NDDs is Alzheimer’s disease (AD), which is characterised by a complex, multifactorial irreversible aetiology, including the progressive loss of neurons. It is also the most common cause of dementia. Pathologically, AD is associated with the presence of amyloid plaques and intracellular neurofibrillary tangles. The management of AD focuses mainly on establishing an early, accurate clinical diagnosis, early drug administration, treatment of comorbidities and dementia-related complications, as well as treatment of behavioural and psychological symptoms. There is currently no cure for AD, and the currently United States Food and Drug Administration (US-FDA) approved drugs only offer symptomatic relief aiming to improve cognitive and behavioural symptoms; however, they do not target the underlying AD pathology or prevent neuronal degeneration. The current US-FDA approved drugs used for the management of AD include acetylcholinesterase inhibitors (donepezil, galantamine, and rivastigmine), N-methyl-D-aspartate (NMDA) receptor antagonist (memantine), and monoclonal antibody against Aβ (Lecanemab). It should be noted that all these approved drugs only assist in the management of symptoms; however, they do not prevent neuronal loss, brain atrophy, and progressive deterioration of cognition associated with AD. To curb the increasing prevalence of AD, new therapeutic strategies are required, including the development of gene therapy, drugs targeting Aβ, and drugs targeting neuronal hyperexcitability among others.
The misuse of analgesics and nonsteroidal anti-inflammatories in runners
(Medpharm Publications, 2024) Esterhuizen, C.; Cordier, Werner
Global participation in running has continued to grow over the last decade, with millions of people running weekly, regardless of distance. These events, particularly endurance running events, require months of progressive training and load adjustment, which, combined with other factors, increase the risk of developing running-related injuries. Inflammation is a natural biological response important for healing in musculoskeletal tissue; however, it may also contribute to the unpleasant experience of pain. Runners may suffer from exercise-induced pain and inflammation, necessitating using analgesics and nonsteroidal anti-inflammatories. Unfortunately, the inappropriate use of these drugs is frequently seen in athletes, which may impact their recovery after injury or general health status. This review presents in brief the current knowledge of running-related pathology and treatment thereof, including considerations of its misuse.
The impact of unprofessional behaviour on patient safety in South Africa : two cautionary tales
(Medpharm Publications, 2024) Schellack, Natalie; Maimin, J.; Kriel, M.; Moodley, S.; Padayachee, N.; natalie.schellack@up.ac.za
In terms of the Rules relating to the Code of Conduct, every pharmacist’s prime concern in the performance of his/her professional duties must be for the wellbeing of both the patient and other members of the public. A pharmacist must uphold the honour and dignity of the profession and may not engage in any activity which could bring the profession into disrepute.Pharmacists engaging in unprofessional conduct or conduct where their regard for their profession is disrespectful, may be involved in activities such as the selling of counterfeit medicines, dispensing medication without prescription, and selling excessive quantities of medicines liable for misuse or abuse, i.e. drug trafficking. These actions can be attributed to factors such as financial incentives, inadequate training, or personal challenges, none of which are acceptable. These pharmacists are viewed as rogue pharmacists with severe implications for patient safety and significant risk of bringing the profession into disrepute.There are also instances where pharmacists make dispensing errors, supplying incorrect medicines, incorrect strength of medicines or incorrect dosage instructions. These errors are generally inadvertent but can obviously have a negative impact on patient safety. As the custodian of medicine, it is crucial that the pharmacist makes every effort to prevent medication errors. Pharmacists must be aware of areas where the chances of dispensing errors are high, especially those caused by look-alike sound-alike (LASA) medications, as they can lead to adverse reactions or even death. Preventing LASA medication errors requires awareness, generic prescribing, pop-up alerts in computer systems, eye-catching labels and warnings, patient education, and the establishment of process and outcome measures. Pharmacists can also organise high-risk LASA drugs on separate shelves and implement double-checking systems for accuracy when dispensing medications.Dispensing errors can have severe consequences for the pharmacist, including monetary fines, registration suspension or removal, and public scrutiny. The misuse and abuse of codeine-containing medications pose significant health risks and pharmacists play a crucial role in harm reduction.Measures to address codeine overuse, misuse and abuse include enhanced regulatory measures, public health interventions, surveillance,training, and education. Without some form of centralised database, it is very challenging for a pharmacist to manage this problem as individuals utilise different pharmacies and their medication history is not linked. To address this problem, pharmacists can participate in initiatives such as the Codeine Care Initiative, a centralised data base of codeine-containing medicine use. This allows the monitoring of frequent purchasers of codeine and gives the pharmacist an opportunity to address codeine misuse at the point of dispensing.
Stepping up : a pharmacist’s role in managing diabetes and foot ulcers
(Medpharm Publications, 2024) Mlambo, Shamiso Shelter; Ncube, Keith Ntokozo; Parkar, Hafiza; shamiso.mlambo@up.ac.za
Diabetes mellitus (DM) is a significant global health problem, with over 537 million adults affected in 2021. A crucial complication of DM is diabetic foot ulcers (DFUs), which result from nerve damage and impaired circulation, leading to loss of function and high medical costs. The role of pharmacists in managing diabetes and DFUs has evolved from strictly dispensing medication to being healthcare providers that are actively involved in patient education on glycaemic control, wound care strategies, and promotion of medication adherence. Treatment of DFUs is mainly focused on maintaining a moist wound environment, preventing infection and pressure offloading. This article highlights the essential role of pharmacists in a multidisciplinary healthcare team to enhance patient outcomes by applying their expertise to reduce diabetes-related complications such as DFUs.
An overview of thyroid disorders and their management
(Medpharm Publications, 2024) Schellack, G.; Schellack, Natalie; De Moura-Cunningham, C.; natalie.schellack@up.ac.za
Disorders of the thyroid gland are frequently encountered in the clinical practice setting and typically fall into one of two categories, namelyhypothyroidism (i.e. deficient levels of circulating thyroid hormone), or hyperthyroidism (or thyrotoxicosis) that involves abnormally highlevels of thyroid hormone in the blood stream. This article provides a high-level overview of thyroid function, the two major pathophysiologicalabnormalities of the thyroid gland, as well as treatment modalities aimed at managing patients with thyroid pathology. In addition, a briefdescription of two major autoimmune conditions of the thyroid gland, namely Graves’ disease and Hashimoto’s thyroiditis, is also provided.
Evaluation of the labelling adherence of the food-associated effects of selected pharmacotherapy
(Medpharm Publications, 2024) Mbonani, N.; Olivier, Natascha; Cordier, Werner; werner.cordier@up.ac.za
BACKGROUND : Pharmacotherapy and dietary interventions often work together to enhance patient treatment and outcomes. Yet, food-associated effects, including food-drug interactions, remain a significant challenge, especially for oral pharmacotherapy. These interactions can undermine the safety and efficacy of medications and negatively impact patients’ nutritional status. Despite medicinal package inserts being the primary source of such information, studies from other countries highlight inconsistencies and inadequacies in the labelling of food-drug interactions. In South Africa, this critical issue remains largely unexplored, leaving potential risks unaddressed. The study aimed to evaluate the adherence of professional and patient information leaflets to labelling regulations concerning food-associated effects, providing some insight on a crucial yet often overlooked aspect of patient safety. METHODS : The South African Health Products Regulatory Authority (SAHPRA) labelling guidelines were used to evaluate the adherence to labelling of food-associated effects in the professional and patient information leaflets of warfarin, statins, fluoroquinolone and tetracycline antibiotics. RESULTS : The leaflets showed partial adherence to SAHPRA labelling guidelines. Food-drug interaction information was either lacking or inadequately described, particularly in relation to the mechanism of interaction, clinical outcomes, or recommendations. Although the information was mostly presented under appropriate headings, it was not always available under recommended sections and rarely cross-referenced. CONCLUSIONS : The labelling of food-associated effects in the evaluated professional and patient information leaflets was partially adherent to SAHPRA labelling guidelines, which may hinder effective guidance for healthcare professionals and patients. Although a small sample, non-adherence is evident and suggests bolstering is needed to mitigate potentially clinically significant interactions.

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