Research Articles (Pharmacology)

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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.
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.
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.
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.
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 C.
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.
The role of patients with addressing inappropriate dispensing of antibiotics without a prescription especially in developing countries
(Wolters Kluwer Medknow Publications, 2025-01) Sono, Tiyani Milta; Schellack, Natalie; Godman, Brian
Antimicrobial resistance (AMR) is a growing global concern, significantly impacting on morbidity, mortality and healthcare costs, especially in low- and middle-income countries (LMICs).
Antimicrobial therapeutic drug monitoring in critically ill adult patients : an international perspective on access, utilisation, and barriers
(Elsevier, 2024-08) Williams, Paul G.; Cotta, Menino Osbert; Tabah, Alexis; Sandaradura, Indy; Kanji, Salmaan; Scheetz, Marc H.; Imani, Sahand; Elhadi, Muhammed; Pardos, Sònia L.; Schellack, Natalie; Sanches, Cristina; Timsit, Jean‑Francois; Xie, Jiao; Farkas, Andras; Wilks, Kathryn; Roberts, Jason A.
BACKGROUND: Therapeutic drug monitoring (TDM) is an effective method for individualising antimicrobial therapy in critically ill patients. The 2021 ADMIN-intensive care unit survey studied a wide range of intensive care unit clinicians worldwide to gain their perspectives on antimicrobial TDM. This article reports the responses from this survey relating to TDM access, utilisation, and barriers. METHODS: An online survey consisted of multiple-choice questions and 5-point Likert scales. The survey examined respondent’s access to minimum inhibitory concentration (MIC) results, drug assays, and dosing software, as well as barriers to TDM. RESULTS: The survey included 538 clinicians from 409 hospitals in 45 countries, with 71% physicians and 29% pharmacists. Despite most respondents having access to assays, 21% and 26% of respondents lacked access to vancomycin and aminoglycosides, respectively. In lower-income countries, almost 40% reported no access. Delayed drug assay turnaround time was the most significant barrier to TDM, particularly in lower-income countries. Routine access to MIC results was unavailable for 41% of respondents, with 25% of lower-income country respondents having no access to MIC or susceptibility reports. CONCLUSIONS: This global survey indicated that consistent TDM usage is hindered by assay access in some sites and the timeliness of assay results in others. Addressing barriers to TDM, particularly in low-income countries, should be a priority to ensure equitable access to affordable TDM.
Sodium, potassium-adenosine triphosphatase as a potential target of the anti-tuberculosis agents, clofazimine and bedaquiline
(MDPI, 2024-12-04) Mmakola, Khomotso Madimetsa Shelboy; Balmith, Marissa [; Steel, Helen C.; Said, Mohamed; Potjo, Moliehi; Van der Mescht, Mieke Adri; Hlatshwayo, Nomsa; Meyer, Pieter Willem Adriaan; Tintinger, Gregory Ronald; Anderson, Ronald; Cholo, Moloko C.
Multidrug-resistant tuberculosis (MDR-TB) patients are treated with a standardised, short World Health Organization (WHO) regimen which includes clofazimine (CFZ) and bedaquiline (BDQ) antibiotics. These two antibiotics lead to the development of QT prolongation in patients, inhibiting potassium (K+) uptake by targeting the voltage-gated K+ (Kv)11.1 (hERG) channel of the cardiomyocytes (CMs). However, the involvement of these antibiotics to regulate other K+ transporters of the CMs, as potential mechanisms of QT prolongation, has not been explored. This study determined the effects of CFZ and BDQ on sodium, potassium–adenosine triphosphatase (Na+,K+-ATPase) activity of CMs using rat cardiomyocytes (RCMs). These cells were treated with varying concentrations of CFZ and BDQ individually and in combination (1.25–5 mg/L). Thereafter, Na+,K+-ATPase activity was determined, followed by intracellular adenosine triphosphate (ATP) quantification and cellular viability determination. Furthermore, molecular docking of antibiotics with Na+,K+-ATPase was determined. Both antibiotics demonstrated dose–response inhibition of Na+,K+-ATPase activity of the RCMs. The greatest inhibition was demonstrated by combinations of CFZ and BDQ, followed by BDQ alone and, lastly, CFZ. Neither antibiotic, either individually or in combination, demonstrated cytotoxicity. Molecular docking revealed an interaction of both antibiotics with Na+,K+-ATPase, with BDQ showing higher protein-binding affinity than CFZ. The inhibitory effects of CFZ and BDQ, individually and in combination, on the activity of Na+,K+-ATPase pump of the RCMs highlight the existence of additional mechanisms of QT prolongation by these antibiotics.
South African dietitians' knowledge and perceptions of food-drug interactions and factors affecting it
(Wiley, 2025-02) Megaw, Christie; Olivier, Natascha; Cordier, Werner; werner.cordier@up.ac.za
BACKGROUND : Dietitians ensure that patients receive tailored medical nutrition therapy to integrate with pharmacotherapy safely. Dietitians require a pharmacological understanding to prevent detrimental food-drug interactions (FDIs). The study investigated dietitians' knowledge of FDIs and their information sourcing. METHODS : A cross-sectional online survey was conducted among registered South African dietitians to assess their knowledge of FDIs, the impact of food timing on drugs, and their sources of FDI information. The questionnaire included demographics, a 12-question knowledge assessment, and a qualitative section on information sourcing. Data from 70 valid responses, collected between 2 August and 19 September 2022, were analysed statistically using analysis of variance and chi-square tests to determine whether associations between knowledge scores and demographic factors were present. RESULTS AND DISCUSSION : Out of 70 responses, most participants were female (97.1%) and 47.1% had over 10 years of experience. The participants primarily worked in the areas of dietetics related to chronic and lifestyle-related disorders (75.7%) across various work settings, including in-patient care (32.8%), out-patient care (41.4%), and multi-disciplinary team environments (31.4%). Although not generalisable due to the low response rate (70 out of the 304 required responses for a 5% margin of error), knowledge deficiencies were observed. A cumulative mean knowledge score of 38.3% was observed, with gaps identified for fundamental FDIs. Drug package inserts (55.7%) and clinical websites (68.6%) were primarily used to source information regarding FDIs; however, the former did not always provide sufficient information. Participants proposed that knowledge deficiencies could be overcome with further education, and the development and/or use of mobile applications or summarisations that elaborate on FDIs. CONCLUSION : Knowledge gaps and uncertainties were identified regarding fundamental FDIs; however, further research is needed to pinpoint the specific sources of these deficiencies and the factors influencing them. To improve dietitians' knowledge of FDIs and ensure alignment with their scope and standard of practice, undergraduate curricula should be bolstered and benchmarked to national needs to facilitate graduate development, and additional learning opportunities provided, such as webinars and continuing professional development (CPD), to allow for continuous education for practicing dietitians. SUMMARY : The study provides insights into potential knowledge deficiencies about food-drug interactions in South African registered dietitians. Food-drug interaction information sources, both academic and nonacademic, need to be supplemented with continuous professional development. Package inserts are often not available or feasible as a source of information on food-drug interactions.
Glioblastoma cells alter brain endothelial cell homeostasis and tight junction protein expression in vitro
(Springer, 2025-01) Mokoena, Xolisile; Mabeta, Peaceful Lucy; Cordier, Werner; Flepisi, Brian Thabile
BACKGROUND : Glioblastoma (GBM) is an aggressive therapy-resistant brain tumour that may impacts the integrity of the blood–brain barrier (BBB). The BBB is a protective barrier of the central nervous system formed mainly by endothelial cells. This study aimed to investigate the in vitro effect of GBM cells on the BBB. METHODS : Brain endothelial (bEnd.3) cells were used as a model of the BBB. Glioblastoma-conditioned media (CM) was extracted at the 48-h (h) time-point from the U87 GBM cells and diluted to 40% with fresh media. The effect of the U87-CM collected at 48 h on bEnd.3 cell growth was evaluated following 48 and 72 h of treatment using the xCELLigence system. Additionally, bEnd.3 cell growth was also investigated in a U87 and bEnd.3 co-culture model continuously for 48 h using the xCELLigence system. The migration of bEnd.3 cells was assessed following 48 and 72 h using the migration scratch assay. The barrier integrity was evaluated continuously for 1 h using the transwell permeability, and the tight junction (TJ) protein expression was evaluated using Western blot assay following 48 and 72 h. RESULTS : There was a significant decrease in bEnd.3 cell growth following 32 h (p < 0.05), 40 h (p < 0.01), and 48 h (p < 0.001) of treatment with U87-CM, while co-culturing of bEnd.3 and U87 cells increased cell growth following 16 h (p < 0.05), 24 h (p < 0.001), 32 h (p < 0.01), 40 h (p < 0.001), and 48 h (p < 0.001). The migration of bEnd.3 cells significantly increased following both 24 (p < 0.05) and 48 h (p < 0.01) of treatment with U87-CM. The permeability of bEnd.3 cells co-cultured with U87 for 48 h was significantly increased (p < 0.05) at the 15- and 30-min time points. Furthermore, the expression of ZO-1 and occludin was significantly increased (p < 0.05) in both bEnd.3 cells treated with U87-CM as well as bEnd.3 cells co-cultured with U87 cells. CONCLUSION : The current findings suggest that U87 cells alter the integrity of bEnd.3 cells possibly through the secretomes in the CM and through cell–cell interactions in co-culture models. This may assist in the understanding of the mechanisms by which GBM affects the BBB, which may aid in the management thereof.
An ethnobotanical survey and pharmacological and toxicity review of medicinal plants used in the management of obesity in the North Central Zone of Nigeria
(Wiley, 2025-02) Anyanwu, Gabriel O.; Anzaku, Dorathy; Bulus, Yanga J.; Girgi, Jemimah N.; Donwell, Chinda C.; Ihuma, Jerome O.; Onyeneke, Eusebius C.; Bermano, Giovanna; Steenkamp, Vanessa
INTRODUCTION : Obesity is increasing worldwide. Due to the unavailability of affordable obesity drugs in most parts of Nigeria, many overweight and obese people rely on medicinal plants to manage obesity. Thus, the aim of this study is to document medicinal plants traditionally used in the treatment and management of obesity in the North Central Zone of Nigeria, determine the plants to which pharmacological assessment of their use in obesity management has not been reported, and assess their toxicity based on the literature. METHODS : Semistructured questionnaires and interviews were used to assess sociodemographic information of the 700 herb sellers/practitioners (100 for each state) who consented to participate in the study. Information gathered on plants that are traditionally used in the management of obesity included administration/dosage, method of preparation, plant part used, method of growth, and plant type. The field study was conducted over a one-year period, from March 2018 to March 2019. Reports of pharmacological activity pertaining to obesity as well as toxicity of the plants were obtained from the literature via scientific databases (Scopus, Web of Science, PubMed, Google Scholar, SciFinder, AJOL, PubChem, and other web sources) after the field survey. RESULTS : A total of 39 families and 70 plant species were used to treat or manage obesity. The majority of plant species used resulted in the family Leguminosae. The relative frequency of citation (RFC) and percentage values for the five most frequently used plants were as follows: Citrus aurantifolia (0.0500; 3.56%), Citrus limon (0.0457; 3.26%), Garcinia kola (0.0429; 3.05%), Zingiber officinale (0.0429; 3.05%), and Allium sativum (0.0414; 2.95%). The majority of the medications were prepared as decoctions (50.5%), and cultivated plants (62.86%) were in the majority of plants used. Results showed that 23 plants have no pharmacological report for antiobesity activities while among the five frequently used plants, only Garcinia kola was reported toxic in preclinical models. CONCLUSIONS : This paper provides a valuable compilation of the plants used in obesity treatment in the study area by indigenous healers, highlights plants with no reported pharmacological activity pertaining to obesity, and indicates the toxicity profile of used plants. However, further studies on the mechanism of action are warranted, especially where no reports were obtained.
Transitioning to quick response codes for patient information leaflet delivery
(Elsevier, 2025-03) Singh, Githa; Brand, S.J. (Sarel); Steenkamp, Vanessa; vanessa.steenkamp@up.ac.za
BACKGROUND : The inclusion of a patient information leaflet (PIL) in medicine packaging is a legal requirement in most countries. OBJECTIVE : To evaluate the feasibility of using quick response (QR) codes for electronic patient information leaflet (ePIL) delivery. METHOD : A mixed-method study based on surveys was conducted at the Tshwane District Hospital in South Africa. The demographics, ability and willingness of patients (330) and pharmacy staff (16) to scan a QR code for a commonly prescribed medicine was captured. A focus group study among 18 regulatory affairs pharmacists gauged their perception of ease of implementation of QR codes. RESULTS : Of the 330 patients, most were 26–55 years of age (67 %) and 70 % were female. Irrespective of patient age and gender, >80 % were willing/ able to scan the QR code and preferred the ePIL (35 %) or ePIL with a hardcopy (45 %). Patients (>96 %) found it easy to read the ePIL (C = 0.487, p < 0.001) and locate the information sought (C = 0.521, p < 0.001). This sentiment was shared by dispensing pharmacy staff: easier to read (C = 0.746, p < 0.05) and locate information (C = 0.630, p < 0.05), with 69 % preferring either the ePIL or ePIL with a hardcopy. All the regulatory affairs pharmacists preferred the ePIL and indicated that it was easy to create a QR code for ePILs. CONCLUSION : Patients, dispensing pharmacy staff, and regulatory affairs pharmacists are willing to transition to ePILs. This makes going green and updating information in real time possible.
Knowledge, attitudes, motivations and expectations regarding antimicrobial use among community members seeking care at the primary healthcare level : a scoping review protocol
(BMJ Publishing Group, 2025-02) Ramdas, Nishana; Meyer, Johanna C.; Schellack, Natalie; Godman, Brian; Turawa, Eunice Bolanle; Campbell, Stephen M.
INTRODUCTION : Inappropriate antibiotic use in (primary healthcare, PHC) settings fuels antimicrobial resistance (AMR), threatens patient safety and burdens healthcare systems. Patients’ knowledge, attitudes, motivations and expectations play a crucial role in antibiotic use behaviour, especially in low-income and middle-income countries including South Africa. There is a need to ensure measures of antibiotic use, interventions and future guidance reflect cultural, community and demographic issues associated with patient views to reduce inappropriate use of antibiotics and associated AMR. The objective of this scoping review is to identify key themes surrounding knowledge, attitudes, motivations and expectations among patients and community members regarding antimicrobial use in PHC settings especially in low-income and middle-income countries. METHODS AND ANALYSIS : This scoping review employs a comprehensive search strategy across multiple electronic databases, including OVID, Medline, PubMed and CINHAL, to identify studies addressing patients or community members seeking care at PHC facilities and exploring key drivers of antimicrobial use. The Covidence web-based platform will be used for literature screening and data extraction and the Critical Appraisal Skills Programme qualitative checklist will assess the quality of qualitative papers. Anticipated results will provide an overview of the current evidence base, enabling identification of knowledge gaps. A narrative synthesis of findings will summarise key themes and patterns in patients’ knowledge, attitudes, motivations and expectations related to antibiotic use across studies while considering methodological diversity and limitations. ETHICS AND DISSEMINATION : Ethics approval is not required for this scoping review. The findings of this scoping review will be disseminated through publication in a peer-reviewed journal, presentation at relevant conferences and workshops, and collaboration with policy-makers and healthcare stakeholders.
Knowledge, attitudes, motivations, expectations, and systemic factors regarding antimicrobial use amongst community members seeking care at the primary healthcare level: a scoping review
(MDPI, 2025-01) Ramdas, Nishana; Meyer, Johanna C.; Schellack, Natalie; Godman, Brian; Turawa, Eunice; Campbell, Stephen M.; natalie.schellack@up.ac.za
BACKGROUND/OBJECTIVES : Antimicrobial resistance (AMR) is a major global health challenge, particularly in low- and middle-income countries (LMICs). Understanding the knowledge, attitudes, motivations, and expectations of community members regarding antimicrobial use is essential for effective stewardship interventions. This scoping review aimed to identify key themes relating to the critical areas regarding antimicrobial use among community members in primary healthcare (PHC), with a particular focus on LMICs. METHODS : OVID Medline, PubMed, and CINAHL databases were searched using Boolean operators and Medical Subject Headings (MeSH) terms relevant to antimicrobial use and community behaviors. The Population, Intervention, Comparison, Outcome, and Study Design (PICOS) framework guided study selection, which focused on community members seeking care in PHC in LMICs. Data management and extraction were facilitated using the Covidence platform, with the Critical Appraisal Skills Programme (CASP) qualitative checklist applied for qualitative studies. A narrative synthesis identified and grouped key themes and sub-themes. Results: The search identified 497 sources, of which 59 met the inclusion criteria, with 75% of the studies conducted in outpatient primary care settings. Four key themes were identified: (1) the ’patient’ theme, highlighting beliefs, knowledge, and expectations, which was the most prominent (40.5%); (2) the ’provider’ theme, emphasizing challenges related to clinical decision-making, knowledge gaps, and adherence to guidelines; (3) the ’healthcare systems’ theme, highlighting resource limitations, lack of infrastructure, and policy constraints; and (4) the ‘intervention/uptake’ theme, emphasizing strategies to improve future antibiotic use and enhance access to and quality of healthcare. CONCLUSIONS : Stewardship programs in PHC settings in LMICs should be designed to be context-specific, community-engaged, and accessible to individuals with varying levels of understanding, involving the use of information and health literacy to effectively reduce AMR.
The malaria burden : a South African perspective
(Wiley, 2024-02-23) Balmith, Marissa; Basson, Charlize; Brand, Sarel Jacobus; marissa.balmith@up.ac.za
Malaria is a deadly disease caused by protozoan pathogens of the Plasmodium parasite. Transmission to humans occurs through the bite of an infected female Anopheles mosquito. According to the World Health Organization (WHO), an estimated 247 million cases of malaria were recorded worldwide in 2021, with approximately 619 000 malaria deaths. The initial signs of malaria can be mild and challenging to diagnose due to the signs and symptoms being similar to those of other illnesses. The malaria burden remains largely concentrated in the WHO sub-Saharan African region and has been recognised as a significant contributor to morbidity and mortality. This review aims to contribute to the existing knowledge on malaria in South Africa, a region within sub-Saharan Africa, focusing on the epidemiology and life cycle of the malaria parasite as well as diagnostic approaches for detecting malaria. In addition, nonpharmacological and pharmacological interventions for treating and preventing malaria infections will also be discussed herein. While there has been a significant reduction in the global burden of this disease, malaria remains a public health issue in South Africa. As such, the implementation of effective preventative measures and strategies, early diagnosis, and appropriate treatment regimens are crucial to reducing the malaria burden in South Africa.
Mapping evidence on the regulations affecting accessibility, availability and management of snake antivenom globally : a scoping review protocol
(BMJ Publishing Group, 2024-12) Majeed, Ramsha; Bester, Janette; Kgarosi, Kabelo; Strydom, Morné
INTRODUCTION: Snakebite envenomation has been declared a neglected tropical disease by the WHO since 2017. The disease is endemic in affected areas due to the lack of availability and access to antivenom, despite it being the standard treatment for snakebites. This challenge is perpetuated by the shortcomings of the regulatory systems and policies governing the management of antivenoms. This study aims to map the evidence about regulations of snake antivenom globally and identify gaps in the literature. This protocol provides an overview of the methodology and analysis which will be used to conduct the scoping review. METHOD AND ANALYSIS: The scoping review follows the guidelines from the Arksey and O’Malley framework for scoping reviews and will be reported using Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. A search strategy was developed with assistance from a health sciences librarian, and the search was done using six relevant databases. The databases used are PubMed, SCOPUS, ProQuest Central, Africa Wide Web, Academic Search Output and Web of Science. Articles in the English language and between 2009 and 2023 were included. The search results were collated, duplicates were removed and results were exported to Rayyan (https://www.rayyan.ai/) for screening. The initial screening for titles and abstracts is currently in progress, and thereafter the second round of screening will be done for full texts. Data extraction will be done using Google Forms. The results of the review will be synthesised using quantitative and qualitative tools. ETHICS AND DISSEMINATION: This review will provide guidance for studies investigating regulatory gaps globally and inform future policies governing antivenom management. Ethics approval for the complete postgraduate project was obtained from the University of Pretoria Research Ethics Committee. The review will be published in a scientific journal, and findings will also be disseminated using conference presentations. TRIAL REGISTRATION: This review has been registered on Open Science Framework (OSF): https://osf.io/54zja.
Use of osteogenic bone matrix in patients with traumatic long bone defects : an open label, single center study
(Elsevier, 2025-02) Murdoch, Marshall; Wittstock, Craig; Psaras, George; Widgerow, Alan; Lukhele, Mkhululi; Ramokgopa, Mmampapatla Thomas; Snyman, Jacques; Hutchings, Jane; Marcos, Elizabeth; Grisillo Biscardi, Anna; Cromarty, A.D.; Zheng, Xu; Duneas, Nicolaas; Govender, Shunmugam; duncan.cromarty@up.ac.za
BACKGROUND : Osteogenic Bone Matrix (Altis™ OBM) is a tissue-engineered, porcine-derived demineralized bone matrix prepared using a humanization processing technology that confers biocompatibility and improved osteoinductivity. The objective of this study was to determine the safety and efficacy of OBM in patients with traumatic long bone defects in an open-label, non-randomized single-center study. METHODS : Diagnosis and main criteria for inclusion were open long bone fractures graded as Gustilo-Anderson Grade II, IIIA or IIIB. 24 participants were enrolled from one center, of which 17 were assigned to the investigational group (OBM) and 7 to the standard of care (SOC) group. Participants were followed at intervals of one, two, six, and 13 weeks to undergo physical examinations and record adverse events, vital signs, electrocardiograms, hematology, blood biochemistry and circulating humoral antibodies against human and porcine Type I and II collagens. Efficacy of treatment over six months post-surgery was assessed by a panel of blinded radiologists to determine the proportion of subjects with radiographic bridging of fractures in both the OBM efficacy group and the SOC group. Limb function, weight-bearing, pain and mobility at the fracture site were assessed by the investigator. Patient satisfaction with the treatment and quality of life were assessed using the SF 36 quality of life questionnaire. RESULTS : 14 OBM patients and five SOC patients completed the first three months of the safety investigation. 10 OBM patients and four SOC patients completed the full six months of the efficacy investigation. Biochemical and hematological parameters were within normal ranges. The efficacy evaluation at six months indicated that 70 % of participants in the OBM group had bridging of the bone defect and 80 % were weight-bearing versus 50 % in the SOC group. The quality of life study demonstrated an increased level of satisfaction as compared with the baseline. Histological analysis of a single biopsy specimen at three months revealed bone regeneration activity within the implanted OBM. CONCLUSIONS : The study showed that treatment with OBM was well tolerated in participants and there was no evidence of clinically relevant toxicity or immunological, biochemical, hematological or adverse reaction due to the use of OBM. There was better bridging in the OBM group versus SOC. Pharmacoeconomic analysis showed OBM to be cost-effective versus standard of care.
Evaluation of Taraxacum officinale phytoconstituents as potential JNK1 inhibitors : perspectives from ADMET, molecular docking, molecular dynamics, and density functional theory
(Elsevier, 2024-12) Sosibo, Sphelele C.; Kruger, Hendrik G.; Nxumalo, Wonder Praise-God; Zondi, Zimbili
The impact of activated c-Jun N-terminal kinase isoform JNK1 chemical pathways in insulin biosynthesis poses a potential health risk of glucose intolerance. Blocking the activity of JNK1 is a promising route for the design of anti-diabetic drugs and associated metabolic syndromes. In this study, 17 extracts of Taraxacum officinale were chosen to bind JNK1 and ascertain their modulatory activity. We employed molecular dynamics, density functional theory and three docking approaches: standard precision, extra precision and quantum polarized ligand docking. The best binding free energy results were obtained from the quantum polarized ligand docking, with myricetin (1) showing a docking score of -10.464 kcal/mol, while quercetin (2) and daphnetin (3) displayed values of -9.769 and -7.136 kcal/mol respectively. Following this, 100 ns molecular dynamics simulations with Desmond showed stabilization average root mean square deviations of 2.34, 2.87, and 2.88 Å for myricetin, quercetin and daphnetin. Further, molecular dynamics revealed complexes of myricetin (ΔG = -38.81 kcal/mol) and quercetin (ΔG = -34.99 kcal/mol) as the most stable inside the JNK1 interface. The energy gaps for myricetin, quercetin and daphnetin were estimated to be 6.17, 6.00 and 6.53 eV employing the M06–2X functional in PCM solvation. Further, myricetin showed the strongest intramolecular hydrogen bonding with -13.06 kcal/mol. This study provides insights into possible anti-type-2 diabetes properties of Taraxacum officinale targeting JNK1.
Insomnia : what is currently available
(Medpharm Publications, 2023) Marais, Andre; Osuch, Elzbieta
Insomnia is an important public health burden and is the most ubiquitous sleep disorder in the general population, requiring accurate diagnosis and effective treatment. Sleep hygiene and cognitive behavioural therapy form the foundation of management. In addition, various pharmacological entities are at hand to augment insomnia disorder. Acute insomnia requires short-term management with appropriately indicated hypnotic agents, while chronic sleeping difficulties benefit more from antidepressants. This article informs the reader about the currently available sleeping agents in South Africa, and may not include more effective or potent agents used in other parts of the world that are not yet accessible for local prescription.
Prevalence of chronic kidney disease and associated risk factors among people living with HIV in a rural population of Limpopo province, South Africa
(Frontiers Media, 2024-07) Choshi, Joel; Flepisi, Brian Thabile; Mabhida, Sihle E.; Sekgala, Machoene Derrick; Mokoena, Haskly; Nkambule, Bongani B.; Ndwandwe, Duduzile; Mchiza, Zandile J.; Nqebelele, Unati; Kengne, Andre P.; Dludla, Phiwayinkosi V.; Hanser, Sidney
BACKGROUND: Limited evidence informs on the prevalence of chronic kidney disease (CKD) in people living with HIV (PLWH) in South Africa. Thus, this study aimed to determine the prevalence of CKD and its associated risk factors among PLWH within the rural province of Limpopo, South Africa. METHODS: We conducted a cross-sectional study of 143 participants, subdivided into groups of PLWH (n = 103) and individuals without HIV (n = 43). Structured questionnaires were used to collect and capture sociodemographic information including age, sex, alcohol intake, smoking status, and educational status. Basic measurements taken included levels of cluster of differentiation 4 (CD4+) count, body mass index (BMI), blood pressure, plasma cystatin C, and fasting serum glucose levels. Plasma cystatin C-based estimated glomerular filtration rate (eGFR) was calculated using the chronic kidney disease epidemiology collaboration (CKD-EPI) estimator to determine the prevalence of CKD. RESULTS: The prevalence of CKD was approximately 7% in PLWH. Multivariate logistic regression analysis showed that it was only diabetes mellitus (odds ratio of 5.795, 95% confidence interval, p = 0.034) and age (odds ratio of 1.078, 95% confidence interval, p = 0.039) that were significantly associated with CKD in PLWH. CONCLUSION: Chronic kidney disease was prevalent in PLWH, and it was further associated with cardiovascular risk factors, diabetes, and ageing. As PLWH age, the burden of CKD may be increased with the increase in cardiovascular-related comorbidities such as diabetes.

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