Research Articles (Pharmacology)

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    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.
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    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.
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    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
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    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.
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    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.
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    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.
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    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.
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    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.
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    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.
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    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.
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    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.
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    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.
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    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.
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    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.
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    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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    Less is more? A review of psilocybin microdosing
    (Sage, 2024-10) Savides, Isabella A.; Outhoff, Kim
    BACKGROUND : The applications of psilocybin, derived from 'magic mushrooms,' are vast, including a burgeoning practice known as microdosing, which refers to the administration of sub-hallucinogenic doses of psychedelic substances to obtain benefits without experiencing significant cognitive and perceptual distortion. However, current research is fairly new with several limitations and gaps that hinder adequate conclusions on its efficacy. AIMS : This semi-structured review aimed to identify and highlight research gaps in the field of psilocybin microdosing for future research. METHODS : A Preferred Reporting Items for Systematic Reviews and Meta-Analyses based strategy was employed, utilizing a chain of keywords and key phrases across multiple databases, augmented by a cross-sectional Google search for relevant grey literature in the form of the top 10 search results. A total of 40 studies and 8 unique websites were identified, summarized and tabulated into four distinct categories, namely non-clinical, clinical, observational and anecdotal evidence. RESULTS : The majority of available evidence originates from observational studies, while non-clinical and clinical study findings remain comparatively sparse and inconsistent. Web-based findings were consistent with current research findings. Key research gaps were highlighted: the imperative for more randomized placebo-controlled trials, exploration of dose-response ranges, psychological and personality testing of participants, utilization of active placebos, greater diversity in study populations, an increase in psilocybin-exclusive microdosing studies and the refinement of animal models. CONCLUSION : Definitive conclusions regarding the efficacy of psilocybin microdosing remain elusive, emphasizing the need for further study. Numerous research gaps necessitate consideration for future investigations.
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    Status and implications of the knowledge, attitudes and practices towards AWaRe antibiotic use, resistance and stewardship among low- and middle-income countries
    (Oxford University Press, 2025-04) Saleem, Zikria; Moore, Catrin E.; Kalungia, Aubrey C.; Schellack, Natalie; Ogunleye, Olayinka; Chigome, Audrey; Chowdhury, Kona; Kitutu, Freddy Eric; Massele, Amos; Ramdas, Nishana; Orubu, E. Sam; Cook, Aislinn; Khuluza, Felix; Zaranyika, Trust; Funiciello, Elisa; Lorenzetti, Giulia; Nantamu, Miriam; Parajuli, Ayuska; Kurdi, Amanj; Nabayiga, Hellen; Jairoun, Ammar Abdulrahman; Haque, Mainul; Campbell, Stephen M.; Van der Bergh, Dena; Godman, Brian; Sharland, Mike
    BACKGROUND : There are concerns globally with rising rates of antimicrobial resistance (AMR), particularly in low- and middle-income countries (LMICs). AMR is driven by high rates of inappropriate prescribing and dispensing of antibiotics, particularly Watch antibiotics. To develop future interventions, it is important to document current knowledge, attitudes and practices (KAP) among key stakeholder groups in LMICs. METHODS : We undertook a narrative review of published papers among four WHO Regions including African and Asian countries. Relevant papers were sourced from 2018 to 2024 and synthesized by key stakeholder group, country, WHO Region, income level and year. The findings were summarized to identify pertinent future activities for all key stakeholder groups. RESULTS : We sourced 459 papers, with a large number coming from Africa (42.7%). An appreciable number dealt with patients’ KAP (33.1%), reflecting their influence on the prescribing and dispensing of antibiotics. There was marked consistency of findings among key stakeholder groups across the four WHO Regions, all showing concerns with high rates of prescribing of antibiotics for viral infections despite professed knowledge of antibiotics and AMR. There were similar issues among dispensers. Patients’ beliefs regarding the effectiveness of antibiotics for self-limiting infectious diseases were a major challenge, although educational programmes did improve knowledge. The development of the AWaRe (Access, Watch and Reserve) system, including practical prescribing guidance, provides a future opportunity for the standardization of educational inputs. CONCLUSIONS : Similar KAP regarding the prescribing and dispensing of antibiotics across LMICs and stakeholder groups presents clear opportunities for standardization of educational input and practical training programmes based on the AWaRe system.
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    Defining and responding to the contextual drivers for implementation of antimicrobial stewardship in 14 neonatal units in South Africa
    (Oxford University Press, 2025-01) Van Den Bergh, Dena; Charani, Esmita; Dramowski, Angela; Annor, Ama Sakoa; Gijzelaar, Michelle; Messina, Angeliki; Van Jaarsveld, Andriette; Goff, Debra A.; Prusakov, Pavel; Balfour, Liezl; Bekker, Adrie; Cassim, Azraa; Govender, Nelesh P.; Holgate, Sandi L.; Kolman, Sonya; Tootla, Hafsah; Schellack, Natalie; Reddy, Kessendri; Fisher, Christine; Conradie, Lucinda; Van Niekerk, Anika; Laubscher, Anje; Alexander, Pearl; Naidoo, Thanusha; Dippenaar, Magdel; Bamford, Colleen; Brits, Sharnel; Chirwa, Pinky; Erasmus, Hannelie; Ekermans, Pieter; Rungen, Lerina; Kriel, Teresa; Mawela, Dini; Mjekula, Simthembile; Nchabeleng, Maphoshane; Nhari, Ronald; Janse van Rensburg, Marli; Sanchez, Pablo J.; Brink, Adrian; NeoAMS Study Team
    BACKGROUND : Research on the contextual drivers of antimicrobial stewardship (AMS) programme interventions in neonatal units is limited. METHODS : As part of a prospective mixed-methods multidisciplinary neonatal AMS (NeoAMS) interventional study in 14 South African hospitals, we applied a three-phased process to assess implementation barriers and contextual drivers experienced by participating health professionals. The study included: (Phase one; P1) a survey of pre-intervention barriers and enablers; (P2) written feedback during the study intervention phase; and (P3) semi-structured exit interviews. RESULTS : Respondents to the P1 survey (n = 100) identified 15 barriers, 9 in the domain of personnel resources, including staffing, time and workload constraints. Other barriers related to limited access to antimicrobial use and surveillance trends, complexity of neonatal care, absence of multidisciplinary team (MDT) AMS and change resistance. For P2, written feedback during implementation (n = 42) confirmed that the MDT approach facilitated systems changes, including policy adaptations, process improvements, strengthened infection control practices, and expansion of AMS MDT roles. MDT benefits were described as aligned team purpose, improved communication, and knowledge sharing. Reported challenges included time to meet and building trust. In P3 interviews (n = 42), improved interpersonal communication, trust, personal growth and confidence building were cited as highlights of working in multidisciplinary AMS teams. Extending the MDT approach to other hospitals, training more health professionals in AMS and increasing management involvement were identified as priorities going forward. CONCLUSIONS : Understanding the organizational and interprofessional context for NeoAMS implementation enabled an MDT approach to develop and optimize neonatal AMS with potential for adoption in similar resource-constrained settings.
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    Evaluating blood-brain barrier permeability, cytotoxicity, and activity of potential acetylcholinesterase inhibitors : in vitro and in silico study
    (Wiley, 2024-12) Maboko, Lerato Mamabote; Theron, A.; Panayides, J._L.; Cordier, Werner; Fisher, D.; Steenkamp, Vanessa
    Acetylcholinesterase inhibitors (AChEIs) remain the first-line treatment for Alzheimer's disease. However, these drugs are largely symptomatic and often associated with adverse effects. This study aimed to evaluate novel pharmacophores for their in vitro AChEI activity, blood–brain barrier (BBB) permeability, and cytotoxic potential, hypothesizing that a combination of AChEIs could enhance symptom management while minimizing toxicity. A library of 1453 synthetic pharmacophores was assessed using in vitro and in silico methods to determine their feasibility as an inhibitor of the AChE enzyme. An in-house miniaturized Ellman's assay determined acellular AChEI activities, while pharmacokinetic properties were evaluated using the SwissADME web tool. The combinational effects of in silico BBB-permeable pharmacophores and donepezil were examined using a checkerboard AChEI assay. Cytotoxicity of active compounds and their synergistic combinations was assessed in SH-SY5Y neuroblastoma and bEnd.5 cells using the sulforhodamine B assay. Cellular AChEI activity of active in silico BBB-permeable predicted compounds was determined using an SH-SY5Y AChE-based assay. An in vitro BBB model was used to assess the effect of compounds on the integrity of the bEnd.5 monolayer. Out of the screened compounds, 12 demonstrated 60% AChEI activity at 5 μM, with compound A51 showing the lowest IC50 (0.20 μM). Five compounds were identified as BBB-permeable, with the donepezil-C53 combination at ¼IC50 exhibiting the strongest synergy (CI = 0.82). Compounds A136 and C129, either alone or with donepezil, showed cytotoxicity. Notably, compound C53, both alone and in combination with donepezil, demonstrated high AChEI activity and promising BBB permeability, warranting further investigation.
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    Pilot study to evaluate patients' understanding of key terms and aspects of antimicrobial use in a rural province in South Africa : findings and implications
    (Wolters Kluwer Medknow Publications, 2025-01) Sono, Tiyani Milta; Mboweni, Veronica; Jelic, Ana Golic; Campbell, Stephen M.; Markovic-Pekovic, Vanda; Ramdas, Nishana; Schellack, Natalie; Kumar, Santosh; Godman, Brian; Meyer, Johanna Catharina
    INTRODUCTION : Antimicrobial resistance (AMR) is a global concern, necessitating the understanding of utilisation patterns and their rationale. Pilot studies have been conducted in a rural province in South Africa to determine the extent of self-purchasing of antibiotics by patients from independent and chain pharmacies. It is imperative to understand the extent of knowledge and concerns of patients regarding the key aspects of antibiotic use and AMR, and potential language barriers, when pharmacists and their assistants are discussing the key aspects with patients. Consequently, the aim was to pre-test a patient questionnaire translated in three native languages building on the findings from the English language pilot. MATERIALS AND METHODS : The English patient questionnaire (Parts 1 and 2) was translated to Sepedi, Tshivenda and Xitsonga. In total 30 patients were interviewed (5/language for Part 1 and Part 2 respectively) when leaving 10 chain and independent pharmacies. This was followed by interviews with patients to evaluate their understanding of questions and key concepts. RESULTS : Eleven of 15 patients interviewed for Part 1 received antibiotics, including 8 without a prescription. Only independent pharmacies (8/10) dispensed antibiotics without prescriptions. Interviews revealed concerns about antibiotic knowledge and AMR and that certain terms including ‘antibiotic’ and ‘AMR’ posed challenges with patient understanding of the purpose of antibiotics. For instance, one patient self-purchased antibiotics for ‘cleansing’ of sexually transmitted infections. The questionnaires in the native languages were subsequently revised so that explanations for terms, including ‘antibiotic’ and ‘AMR’ will be provided in the main study. CONCLUSION : Similar to the previous pilot studies, self-purchasing of antibiotics was observed among independent pharmacies, although at varying rates, with similar indications. Continued health literacy education for pharmacists and patients, especially with native language communication, are needed to address current challenges and will be explored in the main study.