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OBJECTIVE: The irrational use of antibiotics is a leading contributor to antibiotic resistance. Antibiotic stewardship (AS) interventions predominantly focus on prescribers. This study investigated the influence and participation of inpatients in infection-related care, including antibiotic decision-making, within and across two tertiary hospitals in South Africa (Cape Town) and India (Kerala). METHODS: Through ethnographic enquiry of clinical practice in surgical pathways, including direct nonparticipant observation of clinical practices, healthcare worker (HCW), patient and carer interactions in surgical ward rounds and face-to-face interviews with participants (HCWs and patients), we sought to capture the implicit and explicit influence that patients and carers have in infection-related care. Field notes and interview transcripts were thematically coded, aided by NVivo 12® Pro software. RESULTS: Whilst observational data revealed the nuanced roles that patients/carers play in antibiotic decision-making, HCWs did not recognize these roles. Patients and carers, though invested in patient care, are not routinely involved, nor are they aware of the opportunities for engagement in infection-related decision-making. Patients associated clinical improvement with antibiotic use and did not consider hospitalization to be associated with infection acquisition or transmission, highlighting a lack of understanding of the threat of infection and antibiotic resistance. Patients' economic and cultural positionalities may influence their infection-related behaviours. In the study site in India, cultural norms mean that carers play widespread but unrecognized roles in inpatient care, participating in infection prevention activities. CONCLUSION: For patients to have a valuable role in AS and make informed decisions regarding their infection-related care, a mutual understanding of their role in this process among HCWs and patients is crucial. The observed differences between the two study sites indicate the critical need for understanding and addressing the contextual drivers that impact effective patient-centred healthcare delivery. PATIENT OR PUBLIC CONTRIBUTION: Ethnographic observations and interviews conducted in this study involved patients as participants. Patients were recruited for interviews after obtaining signed informed consent forms. Patients' identities were completely anonymized when presenting the study findings.
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Pessoal de Saúde , Pacientes Internados , Humanos , África do Sul , Antibacterianos , Centros de Atenção TerciáriaRESUMO
Antimicrobial resistance (AMR) is a critical health challenge in Nigeria as in many other countries in the sub-Saharan region of Africa. Our article describes how the challenges in the regulation and operations of Patent and Proprietary Medicine Vendors (PPMVs) in Nigeria provide a blind spot for the underuse of antimicrobials. This article also sheds light on how patients' antibiotic use and seeking behaviour facilitate this unwholesome practice. In addition, our article looks at the social determinants of this practice, such as poverty and poor education, and proffers solutions towards solving it. While previous research has investigated the knowledge, perceptions and attitudes of PPMVs towards antimicrobial use and AMR, our article is the first to critically raise concerns about the common practice of antimicrobial underdosing in Nigeria.
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Objective: To explore pharmacist roles in antimicrobial stewardship (AMS) in India, South Africa (SA), United Kingdom (UK) and the factors that contribute to their participation in the programme in these countries. Methods: Data were collected between April 2019 and March 2022 through semi-structured interviews with key AMS stakeholders from India (Kerala); SA (Western Cape province) and the UK (England). Interviews were conducted face to face or via Zoom and Skype platforms, audio recordings were transcribed verbatim and thematically analysed using a grounded theory approach aided by NVivo 12 software. Results: We interviewed 38 key AMS stakeholders (pharmacists and doctors). India and the UK have dedicated AMS pharmacists (Doctor of Pharmacy and Master of Pharmacy graduates with opportunities for additional post-graduate qualifications respectively). Pharmacists in the UK lead AMS programmes, while in India, predominantly in the private sector, pharmacists drive AMS in collaboration with clinicians. In SA, pharmacists (Bachelor of Pharmacy graduates) participate in AMS out of their own commitment in addition to their pharmacy responsibilities. Private sector pharmacists drive AMS while public sector pharmacists participate in clinician-led AMS programmes. Current pharmacy curricula do not provide adequate training in AMS, and this limitation shapes pharmacist roles and acceptance in AMS among clinicians in India and SA. Support of mentors (doctors/senior pharmacists) and self-motivated learning are key factors for effective pharmacist involvement in AMS. Conclusions: A contextually developed, standardized and accessible AMS training programme along with pharmacy curricula modification to include AMS, may facilitate prominent pharmacist roles in AMS.
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BACKGROUND: The link between healthcare worker (HCW) communication, teamwork and patient safety is well-established. Infection prevention and control (IPC) and antimicrobial stewardship (AMS) require multidisciplinary teamwork and communication. OBJECTIVES: We conducted a scoping review of published evidence on effective mechanisms of HCW team communication in hospitals with the intention of transferring and tailoring learning to IPC and AMS team communication. METHODS: PubMed, Scopus, Web of Science, and CINAHL were searched for studies that investigated HCW team communication across in-hospital patient pathways. Studies published between 2000 and 2021 that provided evidence on/or described the effect of communication on team and patient outcomes in hospital were included. Through a process of inductive qualitative content analysis, key themes in the included studies were identified. RESULTS: Of 537 studies identified, 53 (from high-income countries) were included in the data extraction. Fifty one percent (27/53) of studies were conducted in high acuity settings e.g., intensive care units. Standardizing or structuring the content and/or process of team communication was the most common goal of interventions (34/53, 64%). The key outcome measures were either team communication focused (25/34,74%) or patient and process outcome focused (8/34, 24%), such as reduced length of mechanical ventilation days, length of hospital stay, and shorter empiric antibiotic duration. Four studies (4/53, 8%) associated improved communication with positive IPC and AMS outcome measures. Mixed method intervention studies primarily facilitated collaborative input from HCWs and applied structures to standardize the content of patient care discussions, whereas observational studies describe component of team communication. CONCLUSIONS: A communication strategy that formalizes input from multidisciplinary team members can lead to optimized and consistent clinical discussion including in IPC and AMS-related care. Although we were unable to assess the effectiveness of interventions, the existing evidence suggests that optimizing team communication can have a positive effect on infection-related patient outcomes.
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Gestão de Antimicrobianos , Humanos , Controle de Infecções , Atenção à Saúde , Hospitais , ComunicaçãoRESUMO
Mentorship in global health remains an overlooked dimension of research partnerships. Commitment to effective mentorship models requires value-driven approaches. This includes having an understanding of (1) what mentorship means across different cultural and hierarchical boundaries in the health research environment, and (2) addressing entrenched power asymmetries across different aspects including funding, leadership, data and outputs, and capacity strengthening. Existing guidance towards equity and sustainability fails to inform how to navigate complex relationships which hinder effective mentorship models. We focus this perspective piece on human capacity strengthening in research partnerships through mentorship. Using a case study of a research partnership, we describe the lessons learnt and the challenges faced in the mentor mentee relationship while maintaining an effective and sustainable partnership. Human capacity strengthening must research projects and collaborations, and recognise local leadership and ownership. To be transformative and effective, practices need to be driven by common values across research teams.
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Saúde Global , Mentores , Humanos , Fortalecimento InstitucionalRESUMO
OBJECTIVES: Sub-Saharan African (SSA) countries are severely impacted by antimicrobial resistance (AMR). Due to gaps in access to diagnostics in SSA, the true extent of AMR remains unknown. This diagnostic gap affects patient management and leads to significant antimicrobial overuse. This review explores how point-of-care (POC) testing for pathogen identification and AMR may be used to close the diagnostic gap in SSA countries. METHODS: A narrative review exploring current clinical practice and novel developments in the field of POC testing for infectious diseases and AMR. RESULTS: POC assays for identification of various pathogens have been successfully rolled out in SSA countries. While implementation studies have mostly highlighted impressive test performance of POC assays, there is limited data on the impact of implementation on clinical outcomes and cost-effectiveness. We did not encounter local studies of host-directed POC assays relevant to AMR. Novel POC assays using real-time polymerase chain reaction, isothermal amplification, microfluidics, and other technologies are in various stages of development. CONCLUSIONS: Available literature shows that POC testing for AMR applications is implementable in SSA and holds the potential to reduce the diagnostic gap. Implementation will require effective regulatory pathways, incorporation of POC testing in clinical and laboratory guidelines, and adequate value capture in existing health financing models.
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Antibacterianos , Anti-Infecciosos , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Testes Imediatos , África Subsaariana , Sistemas Automatizados de Assistência Junto ao LeitoRESUMO
We report an empirical analysis of the use of imagery by the key actors in global health who set policy and strategy, and we provide a comprehensive overview, particularly related to images used in reports on vaccination and antimicrobial resistance. The narrative currently depicted in imagery is one of power imbalances, depicting women and children from low-income and middle-income countries (LMICs) with less dignity, respect, and power than those from high-income countries. The absence of any evidence of consent for using intrusive and out-of-context images, particularly of children in LMICs, is concerning. The framework we have developed provides a platform for global health actors to redefine their intentions and recommission appropriate images that are relevant to the topic, respect the integrity of all individuals depicted, are accompanied by evidence of consent, and are equitable in representation. Adhering to these standards will help to avoid inherent biases that lead to insensitive content and misrepresentation, stigmatisation, and racial stereotyping.
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Doenças Transmissíveis , Saúde Global , Criança , Feminino , Humanos , Países em Desenvolvimento , VacinaçãoRESUMO
Objective: To identify perceptions and awareness of changes in infection prevention and control (IPC) and antimicrobial stewardship (AMS) practices among healthcare workers (HCWs) during the COVID-19 pandemic in India and South Africa (SA). Method: A self-administered online survey which included participant demographics, knowledge and sources of COVID-19 infection, perceived risks and barriers, and self-efficacy. Data were analysed using descriptive statistics. Results: The study received 321 responses (response rate: 89.2%); 131/321 (40.8%) from India and 190/321 (59.2%) from SA; male to female response rate was 3:2, with majority of respondents aged 40-49 (89/321, 27.7%) and 30-39 (87/321, 27.1%) years. Doctors comprised 47.9% (57/119) of respondents in India and 74.6% (135/181) in SA. Majority of respondents in India (93/119, 78.2%) and SA (132/181, 72.9%) were from the private and public sectors, respectively, with more respondents in SA (123/174, 70.7%) than in India (38/104, 36.5%) involved in antimicrobial prescribing.Respondents reported increased IPC practices since the pandemic and noted a need for more training on case management, antibiotic and personal protective equipment (PPE) use. While they noted increased antibiotic prescribing since the pandemic, they did not generally associate their practice with such an increase. A willingness to be vaccinated, when vaccination becomes available, was expressed by 203/258 (78.7%) respondents. Conclusions: HCWs reported improved IPC practices and changes in antibiotic prescribing during the COVID-19 pandemic. Targeted education on correct use of PPE was an identified gap. Although HCWs expressed concerns about antimicrobial resistance, their self-perceived antibiotic prescribing practices seemed unchanged. Additional studies in other settings could explore how our findings fit other contexts.
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A cross-sectional survey among participants in India and South Africa to explore perceptions and awareness of SARS-CoV-2-related risks. Main outcome measures-proportion of participants aware of SARS-CoV-2, and their perception of infection risks as it related to their views and perceptions on vaccination, i.e., using COVID-19 vaccine uptake as proxy for awareness level. Self-administered questionnaires were used to collect data via web- and paper-based surveys over three months. Pearson's Chi-squared test assessed relationships between variables; a p-value less than 0.05 was considered significant. There were 844 respondents (India: n = 660, South Africa: n = 184; response rate 87.6%), with a 61.1% vs 38.3% female to male ratio. Post-high-school or university education was the lowest qualification reported by most respondents in India (77.3%) and South Africa (79.3%). Sources of pandemic information were usually media and journal publications (73.2%), social media (64.6%), family and friends (47.7%) and government websites (46.2%). Most respondents correctly identified infection prevention measures (such as physical distancing, mask use), with 90.0% reporting improved hand hygiene practices since the pandemic. Hesitancy or refusal to accept the SARS-CoV-2 vaccine was reported among 17.9% and 50.9% of respondents in India and South Africa, respectively; reasons cited included rushed vaccine development and the futility of vaccines for what respondents considered a self-limiting flu-like illness. In South Africa, vaccine acceptance was associated with improved hand hygiene practices since the pandemic and flu vaccination in the preceding year. No relationship was noted between awareness and practice of infection prevention measures (such as hand hygiene) and socio-demographic factors such as employment status or availability of amenities. Pandemic response and infection prevention and control measures through vaccination campaigns should consider robust public engagement and contextually-fit communication strategies with multimodal, participatory online and offline initiatives to address public concerns, specifically towards vaccines developed for this pandemic and general vaccine hesitancy.
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At the 2015 World Health Assembly, UN member states adopted a resolution that committed to the development of national action plans (NAPs) for antimicrobial resistance (AMR). The political determination to commit to NAPs and the availability of robust governance structures to assure sustainable translation of the identified NAP objectives from policy to practice remain major barriers to progress. Inter-country variability in economic and political resilience and resource constraints could be fundamental barriers to progressing AMR NAPs. Although there have been regional and global analyses of NAPs from a One Health and policy perspective, a global assessment of the NAP objectives targeting antimicrobial use in human populations is needed. In this Health Policy, we report a systematic evidence synthesis of existing NAPs that are aimed at tackling AMR in human populations. We find marked gaps and variability in maturity of NAP development and operationalisation across the domains of: (1) policy and strategic planning; (2) medicines management and prescribing systems; (3) technology for optimised antimicrobial prescribing; (4) context, culture, and behaviours; (5) operational delivery and monitoring; and (6) patient and public engagement and involvement. The gaps identified in these domains highlight opportunities to facilitate sustainable delivery and operationalisation of NAPs. The findings from this analysis can be used at country, regional, and global levels to identify AMR-related priorities that are relevant to infrastructure needs and contexts.
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Antibacterianos , Anti-Infecciosos , Humanos , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Política de Saúde , Saúde GlobalRESUMO
The SARS-CoV-2 infection, which causes the coronavirus disease (COVID-19), has affected lives, with very adverse outcomes in specific populations in the United States of America (USA), a high-income country, and two middle-income countries, Brazil and South Africa. This paper aims to discuss the relationship of race/ethnicity with COVID-19-associated factors in the three countries. The information is based on data collected from infectious disease/epidemiological centers in the USA, Brazil, and South Africa. Adverse COVID-19 outcomes have been associated with the burden of exposure and disease, linked to socioeconomic determinants, among specific ethnicities in all three countries. The prevalence of comorbidities before and the likelihood of work-related exposure in the context of COVID-19 infection puts ethnic minorities in the USA and some ethnic majorities and minorities in Brazil and South Africa at greater risk. We envisage that this work will contribute to ongoing discussions related to addressing socioeconomic determinants of health, and the need for stakeholders in various sectors to work on addressing observed health disparities for overall improvement in health and healthcare given the current pandemic.
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COVID-19 , Países em Desenvolvimento , Humanos , Grupos Minoritários , Pandemias , SARS-CoV-2 , Estados Unidos/epidemiologiaRESUMO
This article summarizes the consequences of the COVID-19 pandemic, on an international project to tackle antimicrobial resistance (AMR). The research leadership and process, the access to data, and stakeholders were deeply disrupted by the national and international response to the pandemic, including the interruption of healthcare delivery, lockdowns, and quarantines. The key principles to deliver the research through the pandemic were mainly the high degree of interdisciplinary engagement with integrated teams, and equitable partnership across sites with capacity building and leadership training. The level of preexisting collaboration and partnership were also keys to sustaining connections and involvements throughout the pandemic. The pandemic offered opportunities for realigning research priorities. Flexibility in funding timelines and projects inputs are required to accommodate variance introduced by external factors. The current models for research collaboration and funding need to be critically evaluated and redesigned to retain the innovation that was shown to be successful through this pandemic.
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COVID-19 , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Controle de Doenças Transmissíveis , Países em Desenvolvimento , Farmacorresistência Bacteriana , Humanos , Pandemias , PesquisaRESUMO
BACKGROUND: Whilst antimicrobial stewardship (AMS) is being implemented globally, contextual differences exist. We describe how the use of a massive open online course (MOOC) platform provided an opportunity to gather diverse narratives on AMS from around the world. METHODS: A free 3 week MOOC titled 'Tackling antimicrobial resistance: a social science approach' was launched in November 2019. Learners were asked specific questions about their experiences of AMS via 38 optional free-text prompts dispersed throughout the modules. Content analysis was used to identify key emerging themes from the learners' responses in the first three runs of the MOOC. RESULTS: Between November 2019 and July 2020, 1464 learners enrolled from 114 countries. Overall, 199 individual learners provided a total of 1097 responses to the prompts. The diverse perspectives describe unique challenges present in different contexts including ill-defined roles for pharmacists and nurses in AMS; inadequate governance and policy inconsistencies in surveillance for antibiotic consumption and antimicrobial resistance (AMR) in some countries; lack of ownership of antibiotic decision-making and buy-in from different clinical specialties; and human resource and technological constraints. Patients' knowledge, experiences and perspectives were recognized as a valuable source of information that should be incorporated in AMS initiatives to overcome cultural barriers to the judicious use of antibiotics. CONCLUSIONS: Analysis of learner comments and reflections identified a range of enablers and barriers to AMS implementation across different healthcare economies. Common challenges to AMS implementation included the role of non-physician healthcare workers, resource limitations, gaps in knowledge of AMR, and patient engagement and involvement in AMS.
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OBJECTIVE: To explore the existing evidence on patient understanding of and/or participation in infection-related care in surgical specialties. METHOD: A scoping review of the literature was conducted. PubMed, Web of Science, Scopus, and grey literature sources were searched using predefined search criteria for policies, guidelines, and studies in the English language. Data synthesis was done through content and thematic analysis to identify key themes in the included studies. RESULTS: The initial search identified 604 studies, of which 41 (36 from high-income and five from low- and middle-income countries) were included in the final review. Most of the included studies focused on measures to engage patients in infection prevention and control (IPC) activities, with few examples of antimicrobial stewardship (AMS) engagement strategies. While patient engagement interventions in infection-related care varied depending on study goals, surgical wound management was the most common intervention. AMS engagement was primarily limited to needs assessment, without follow-up to address such needs. CONCLUSION: Existing evidence highlights a gap in patient participation in infection-related care in the surgical pathway. Standardization of patient engagement strategies is challenging, particularly in the context of surgery, where several factors influence how the patient can engage and retain information. Infection-related patient engagement and participation strategies in surgery need to be inclusive and contextually fit.
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Gestão de Antimicrobianos , Humanos , Controle de Infecções , Avaliação das NecessidadesRESUMO
OBJECTIVES: To investigate the drivers for infection management and antimicrobial stewardship (AMS) across high-infection-risk surgical pathways. METHODS: A qualitative study-ethnographic observation of clinical practices, patient case studies, and face-to-face interviews with healthcare professionals (HCPs) and patients-was conducted across cardiovascular and thoracic and gastrointestinal surgical pathways in South Africa (SA) and India. Aided by Nvivo 11 software, data were coded and analysed until saturation was reached. The multiple modes of enquiry enabled cross-validation and triangulation of findings. RESULTS: Between July 2018 and August 2019, data were gathered from 190 hours of non-participant observations (138 India, 72 SA), interviews with HCPs (44 India, 61 SA), patients (six India, eight SA), and case studies (four India, two SA). Across the surgical pathway, multiple barriers impede effective infection management and AMS. The existing implicit roles of HCPs (including nurses and senior surgeons) are overlooked as interventions target junior doctors, bypassing the opportunity for integrating infection-related care across the surgical team. Critically, the ownership of decisions remains with the operating surgeons, and entrenched hierarchies restrict the inclusion of other HCPs in decision-making. The structural foundations to enable staff to change their behaviours and participate in infection-related surgical care are lacking. CONCLUSIONS: Identifying the implicit existing HCP roles in infection management is critical and will facilitate the development of effective and transparent processes across the surgical team for optimized care. Applying a framework approach that includes nurse leadership, empowering pharmacists and engaging surgical leads, is essential for integrated AMS and infection-related care.
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Gestão de Antimicrobianos , Procedimentos Cirúrgicos Cardiovasculares , Procedimentos Cirúrgicos do Sistema Digestório , Procedimentos Cirúrgicos Torácicos , Pessoal de Saúde , Humanos , Índia , Controle de Infecções , Pesquisa Qualitativa , África do Sul , CirurgiõesRESUMO
BACKGROUND: The effect of team dynamics on infection management and antimicrobial stewardship (AMS) behaviours is not well understood. Using innovative visual mapping, alongside traditional qualitative methods, we studied how surgical team dynamics and communication patterns influence infection-related decision making. MATERIALS/METHODS: Between May and November 2019, data were gathered through direct observations of ward rounds and face-to-face interviews with ward round participants in three high infection risk surgical specialties at a tertiary hospital in South Africa. Sociograms, a visual mapping method, mapped content and flow of communication and the social links between participants. Data were analysed using a grounded theory approach. RESULTS: Data were gathered from 70 hours of ward round observations, including 1024 individual patient discussions, 60 sociograms and face-to-face interviews with 61 healthcare professionals. AMS and infection-related discussions on ward rounds vary across specialties and are affected by the content and structure of the clinical update provided, consultant leadership styles and competing priorities at the bedside. Registrars and consultants dominate the discussions, limiting the input of other team members with recognised roles in AMS and infection management. Team hierarchies also manifest where staff position themselves, and this influences their contribution to active participation in patient care. Leadership styles affect ward-round dynamics, determining whether nurses and patients are actively engaged in discussions on infection management and antibiotic therapy and whether actions are assigned to identified persons. CONCLUSIONS: The surgical bedside ward round remains a medium of communication between registrars and consultants, with little interaction with the patient or other healthcare professionals. A team-focused and inclusive approach could result in more effective decision making about infection management and AMS.
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Gestão de Antimicrobianos , Visitas de Preceptoria , Antropologia Cultural , Comunicação , Hospitais , Humanos , Equipe de Assistência ao PacienteRESUMO
Addressing the silent pandemic of antimicrobial resistance (AMR) is a focus of the 2021 G7 meeting. A major driver of AMR and poor clinical outcomes is suboptimal antimicrobial use. Current research in AMR is inequitably focused on new drug development. To achieve antimicrobial security we need to balance AMR research efforts between development of new agents and strategies to preserve the efficacy and maximise effectiveness of existing agents. Combining a review of current evidence and multistage engagement with diverse international stakeholders (including those in healthcare, public health, research, patient advocacy and policy) we identified research priorities for optimising antimicrobial use in humans across four broad themes: policy and strategic planning; medicines management and prescribing systems; technology to optimise prescribing; and context, culture and behaviours. Sustainable progress depends on: developing economic and contextually appropriate interventions; facilitating better use of data and prescribing systems across healthcare settings; supporting appropriate and scalable technological innovation. Implementing this strategy for AMR research on the optimisation of antimicrobial use in humans could contribute to equitable global health security.
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Unlike the case of conventional drug formulations, dissolution tests have hitherto not been required for herbal medicinal products commercially available in South Africa. This study investigated dissolution of the South African Sutherlandia frutescens using selected flavonoid glycosides as marker compounds. Dissolution of markers was assessed in three dissolution media at pH 1.2, 4.5 and 6.8, and samples were analysed using a validated HPLC method. The dissolution profile of each marker varied for the different materials investigated. All three media utilised showed differences in flavonoid glycoside dissolution between the S. frutescens products evaluated, with f2 values < 50 for comparison of flavonoid dissolution from any two of the materials. Dissolution of S. frutescens materials could thus be characterised using the markers in all the media tested. This tool may be employed in the future for comparison of orally administered S. frutescens products, provided between- batch variability is evaluated and found less than between-sample variability.
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Fabaceae/química , Flavonoides/isolamento & purificação , Glicosídeos/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Concentração de Íons de Hidrogênio , Cinética , Fitoterapia , Folhas de Planta , Plantas Medicinais , SolubilidadeRESUMO
Economic challenges associated with noncommunicable diseases (NCDs) and the sociocultural outlook of many patients especially in Africa have increased dependence on traditional herbal medicines (THMs) for these diseases. A cross-sectional descriptive study designed to determine the prevalence of and reasons for THM use in the management of NCDs among South African adults was conducted in an urban, economically disadvantaged area of Cape Town, South Africa. In a cohort of 1030 participants recruited as part of the existing Prospective Urban and Rural Epidemiological (PURE) study, 456 individuals were identified. The overall prevalence of THM use was 27%, of which 61% was for NCDs. Participants used THM because of a family history (49%) and sociocultural beliefs (33%). Hypertensive medication was most commonly used concurrently with THM. Healthcare professionals need to be aware of the potential dualistic use of THM and conventional drugs by patients, as this could significantly influence health outcomes. Efforts should be made to educate patients on the potential for drug/herb interactions.