Prevalence, patterns and beliefs about the use of herbal medicinal products in Ghana: a multi-centre community-based cross-sectional study.

OBJECTIVE: Worldwide, herbal medicinal products (HMPs) play key roles in healthcare systems, especially in developing countries, yet there is inconsistent evidence about their prevalence and patterns of use in Ghana. This study therefore sought to determine the prevalence, patterns and beliefs about the use of HMPs in Ghana. METHODS: A descriptive community-based cross-sectional survey was conducted using a researcher-administered questionnaire on 1364 adults, selected from five communities for each of the ecological zones in Ghana using a multi-stage sampling procedure. The study was conducted between December 2019 and March 2020. RESULTS: The prevalence of ever use of HMPs was 76.5% with 73.0% of respondents using these products within the past year. Almost 60% of respondents reported using HMPs that were registered by the Ghana Food and Drugs Authority. About 56.7% used these products to cure diseases. All the sociodemographic characteristics (age, religion, marital status, educational level and employment status) except for sex were significantly associated with the use of HMPs (P < 0.001). For beliefs about HMPs, the proportion of respondents classified to be accepting, ambivalent, indifferent and sceptical was 14.3%, 25.2%, 47.5% and 13.07%, respectively. About 62.2% of study participants had plans to use HMPs in the future, and 69.1% were willing to encourage others to use such products. However, 51.6% of the participants did not perceive HMPs as more effective and safe compared with orthodox products. CONCLUSION: The prevalence of use of HMPs in Ghana is high, thus suggesting an appropriate public health policy to improve the regulation of these products and also provide basis for the integration of HMPs into the healthcare system in Ghana.

Education of pharmacists in Ghana: evolving curriculum, context and practice in the journey from dispensing certificate to doctor of pharmacy certificate.

BACKGROUND: Understanding the origin and evolution of education of pharmacists is important for practice and health system reforms. In Ghana, education of pharmacists started in the 1880s with the training of dispensers in a government hospital. Over the years, the curriculum and institutional arrangements changed and currently pharmacists are trained in universities. In this study we explored how and why education of pharmacists evolved in Ghana. METHODS: We used a case study design to systematically describe education of pharmacists reforms. Data was collected from October 2018 and December 2019 through document review and in-depth interviews. The data was analysed based on institutional arrangements and contextual factors influencing reforms from the 1880s through 2012, when the Doctor of pharmacy programme was initiated in Ghana. RESULTS: Reforms occurred around four main periods when institutional arrangements including the certificate awarded and expected roles were modified by educators and government. These are: (1) the Certificate of dispensing with dispenser-in-training and nurse-dispenser schemes (1880s to 1942), when dispensers were trained to assist doctors in dispensing or directly diagnosing and treating specific disease conditions. (2) the Diploma and Certificate of competency with the dispenser-in-training and pupil pharmacist schemes (1943 to 1960), where in addition to existing roles, pharmacists operated village dispensers. (3) the Bachelor of pharmacy degree (1961 to 2017), when pharmacists were trained mainly as medicines experts with a strong science base on all aspects of medicines from production, distribution and use; and over time with a gradual move to patient-oriented practice. (4) the Doctor of pharmacy degree (2012 to date), where in addition to existing roles, trainees are exposed to advance professional practice experiences. Important factors influencing the reforms included, health systems demands for village dispensaries and clinically oriented pharmacists, and harmonization with regional and international training and practice. CONCLUSION: Reasons influencing education of pharmacists reforms are context specific and are driven by historical experiences, national and international expectations as well as educators and regulators abilities to influence change. These reforms call for direct corresponding change in professional practice laws and regulation to enable pharmacists contribute fully to health care delivery in Ghana.

The Association between Diabetes-Related Distress and Medication Adherence in Adult Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a major public health problem associated with distress. T2DM can affect health outcomes and adherence to medications. Little is however known about the association between diabetes distress and medication adherence among patients with T2DM in Ghana. OBJECTIVE: The objective of the present study is twofold: to estimate distress associated with T2DM and to examine its association with medication adherence. METHODS: A hospital-based cross-sectional study was conducted among 188 patients with T2DM recruited from a diabetes specialist outpatient clinic at the Pantang Hospital in Accra, Ghana. Data were obtained using the Problem Areas In Diabetes (PAID) scale and the Medication Adherence Report Scale. RESULTS: The findings showed that about 44.7% of the patients showed high levels of diabetes-related distress. Poor adherence to medications was recorded in 66.5% of the patients. Patients who were highly distressed had 68% lower odds of adhering to their medications compared to those who were not (OR: 0.32, 95% CI: 0.15-0.65). A principal component analysis revealed four areas of T2DM distress which were conceptualized as negative emotions about diabetes, dietary concerns and diabetes care, dissatisfaction with external support, and diabetes management helplessness. CONCLUSION: Our findings suggest that diabetes distress is a significant determinant of medication adherence behaviour in patients with T2DM. Thus, incorporating routine screening for distress into the standard diabetes care within the Ghanaian health system and having health practitioners adopt holistic approaches to diabetes management will be important context-specific interventions to improve adherence and health outcomes of people living and coping with T2DM.

RND-type drug efflux pumps from Gram-negative bacteria: molecular mechanism and inhibition.

Drug efflux protein complexes confer multidrug resistance on bacteria by transporting a wide spectrum of structurally diverse antibiotics. Moreover, organisms can only acquire resistance in the presence of an active efflux pump. The substrate range of drug efflux pumps is not limited to antibiotics, but it also includes toxins, dyes, detergents, lipids, and molecules involved in quorum sensing; hence efflux pumps are also associated with virulence and biofilm formation. Inhibitors of efflux pumps are therefore attractive compounds to reverse multidrug resistance and to prevent the development of resistance in clinically relevant bacterial pathogens. Recent successes on the structure determination and functional analysis of the AcrB and MexB components of the AcrAB-TolC and MexAB-OprM drug efflux systems as well as the structure of the fully assembled, functional triparted AcrAB-TolC complex significantly contributed to our understanding of the mechanism of substrate transport and the options for inhibition of efflux. These data, combined with the well-developed methodologies for measuring efflux pump inhibition, could allow the rational design, and subsequent experimental verification of potential efflux pump inhibitors (EPIs). In this review we will explore how the available biochemical and structural information can be translated into the discovery and development of new compounds that could reverse drug resistance in Gram-negative pathogens. The current literature on EPIs will also be analyzed and the reasons why no compounds have yet progressed into clinical use will be explored.

Phytochemicals increase the antibacterial activity of antibiotics by acting on a drug efflux pump.

Drug efflux pumps confer resistance upon bacteria to a wide range of antibiotics from various classes. The expression of efflux pumps are also implicated in virulence and biofilm formation. Moreover, organisms can only acquire resistance in the presence of active drug efflux pumps. Therefore, efflux pump inhibitors (EPIs) are attractive compounds to reverse multidrug resistance and to prevent the development of resistance in clinically relevant bacterial pathogens. We investigated the potential of pure compounds isolated from plants to act as EPIs. In silico screening was used to predict the bioactivity of plant compounds and to compare that with the known EPI, phe-arg-ß-naphthylamide (PAßN). Subsequently, promising products have been tested for their ability to inhibit efflux. Plumbagin nordihydroguaretic acid (NDGA) and to a lesser degree shikonin, acted as sensitizers of drug-resistant bacteria to currently used antibiotics and were able to inhibit the efflux pump-mediated removal of substrate from cells. We demonstrated the feasibility of in silico screening to identify compounds that potentiate the action of antibiotics against drug-resistant strains and which might be potentially useful lead compounds for an EPI discovery program.

Structure of the AcrAB-TolC multidrug efflux pump.

The capacity of numerous bacterial species to tolerate antibiotics and other toxic compounds arises in part from the activity of energy-dependent transporters. In Gram-negative bacteria, many of these transporters form multicomponent 'pumps' that span both inner and outer membranes and are driven energetically by a primary or secondary transporter component. A model system for such a pump is the acridine resistance complex of Escherichia coli. This pump assembly comprises the outer-membrane channel TolC, the secondary transporter AcrB located in the inner membrane, and the periplasmic AcrA, which bridges these two integral membrane proteins. The AcrAB-TolC efflux pump is able to transport vectorially a diverse array of compounds with little chemical similarity, thus conferring resistance to a broad spectrum of antibiotics. Homologous complexes are found in many Gram-negative species, including in animal and plant pathogens. Crystal structures are available for the individual components of the pump and have provided insights into substrate recognition, energy coupling and the transduction of conformational changes associated with the transport process. However, how the subunits are organized in the pump, their stoichiometry and the details of their interactions are not known. Here we present the pseudo-atomic structure of a complete multidrug efflux pump in complex with a modulatory protein partner from E. coli. The model defines the quaternary organization of the pump, identifies key domain interactions, and suggests a cooperative process for channel assembly and opening. These findings illuminate the basis for drug resistance in numerous pathogenic bacterial species.

Mutations in MexB that affect the efflux of antibiotics with cytoplasmic targets.

Drug efflux pumps such as MexAB-OprM from Pseudomonas aeruginosa confer resistance to a wide range of chemically different compounds. Within the tripartite assembly, the inner membrane protein MexB is mainly responsible for substrate recognition. Recently, considerable advances have been made in elucidating the drug efflux pathway through the large periplasmic domains of resistance-nodulation-division (RND) transporters. However, little is known about the role of amino acids in other parts of the protein. We have investigated the role of two conserved phenylalanine residues that are aligned around the cytoplasmic side of the central cavity of MexB. The two conserved phenylalanine residues have been mutated to alanine residues (FAFA MexB). The interaction of the wild-type and mutant proteins with a variety of drugs from different classes was investigated by assays of cytotoxicity and drug transport. The FAFA mutation affected the efflux of compounds that have targets inside the cell, but antibiotics that act on cell wall synthesis and membrane probes were unaffected. Combined, our results indicate the presence of a hitherto unidentified cytoplasmic-binding site in RND drug transporters and enhance our understanding of the molecular mechanisms that govern drug resistance in Gram-negative pathogens.