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Ana Golić Jelić

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A. Jelić, V. Vučenović, Saša Vučenović, Vanda Marković-Peković, A. Kurdi, B. Godman, J. Meyer, R. Škrbić

Background Community pharmacies must balance public health obligations with economic sustainability. However, integrated methods that jointly manage medical and non-medical inventory in community pharmacies in LMICs are limited. Objective To develop and apply a dual-matrix model separating medical from non-medical products into operational control categories and introducing a High–Medium–Low profitability (HML-P) classification. Methods We conducted a retrospective, descriptive analysis of all items handled in six community pharmacies in the Republic of Srpska, Bosnia and Herzegovina, during the analyzed 2022 year (12-month period) (n = 10,541). Medical products were classified by Always Better Control (ABC) by purchase value and Fast-/Slow-/Non-moving (FSN) by dispensing frequency (predefined thresholds: >4/day = F, 1–4 = S, <1 = N) to form an ABC–FSN matrix. Non-medical products were classified by ABC and a new HML-P scheme (expert-defined Pareto cut-offs: 70%/20%/10% of cumulative gross profit) to form an ABC–HML-P matrix. Each matrix was consolidated into three control categories: I (strict), II (moderate) and III (minimal). Results Non-medical products constituted 76.4% of all items. The ABC–FSN matrix identified Im = 149 medical products for strict control, while the non-medical ABC–HML-P matrix identified Inm = 580 items for strict control and a large segment for minimal oversight (IIInm = 6218). A pronounced Pareto pattern was observed (≈10% of items accounted for 70% of spend and 70% of gross profit), alongside low daily movement (only 3.2% dispensed ≥1/day). Conclusions The proposed dual-matrix model provides a practical decision-support tool for community pharmacies. It helps prioritize availability of patient-critical medical products while supporting economic sustainability.

Tiyani Milta Maluleke, M. Maluleke, N. Ramdas, A. Jelić, A. Kurdi, Audrey K. Chigome, Stephen M Campbell, Vanda Marković-Peković, N. Schellack et al.

Background: Antimicrobial resistance (AMR) is now a critical issue in South Africa, enhanced by considerable inappropriate prescribing of antibiotics. There is currently variable dispensing of antibiotics without a prescription. Where this occurs, it is principally for urinary tract infections (UTIs) and sexually transmitted infections (STIs). Consequently, there is a need to comprehensively evaluate antibiotic dispensing patterns and factors influencing this to reduce AMR. Methods: A previously piloted questionnaire was administered to patients exiting three different categories of community pharmacies in a rural province. The questionnaire included data on the prevalence of antibiotics dispensed, whether without a prescription, and the rationale for this. Results: A total of 465 patients leaving community pharmacies with a medicine were interviewed. 54.4% of interviewed patients were dispensed at least one antibiotic, with 78.7% dispensed these without a prescription from either independent or franchise pharmacies. Metronidazole (36.1%) and azithromycin (32.7%) were the most dispensed antibiotics. STIs were the most common infectious disease for which an antibiotic was dispensed (60.1%), with 99.6% dispensed without a prescription. Upper respiratory tract infections (URTIs) were the most common infection where antibiotics were dispensed with a prescription (60.0%), with little dispensing without a prescription (7.1%). The most frequently cited reasons for obtaining antibiotics without a prescription were prior use (56.8%), long waiting times at PHC clinics (15.6%), and financial constraints (6.0%). Conclusions: There is an urgent need to review community pharmacists’ scope of practice, including allowing them to prescribe antibiotics for infectious diseases such as UTIs, similar to other countries. Concomitantly, utilise trained community pharmacists to engage with prescribers to improve future antibiotic use, especially for URTIs.

Tiyani Milta Maluleke, M. Maluleke, A. Jelić, Stephen M Campbell, Vanda Marković-Peković, N. Schellack, N. Ramdas, B. Godman, J. Meyer

Antimicrobial resistance (AMR) is an appreciable threat to public health, especially among low- and middle-income countries (LMICs), exacerbated by high levels of inappropriate prescribing and dispensing of antibiotics in these countries. There have been variable levels of dispensing of antibiotics without a prescription among community pharmacies in South Africa. Given the importance of community pharmacies, especially in rural South Africa, there is a need to assess their knowledge and attitudes towards antibiotics, AMR, and antibiotic stewardship. This was the aim of this study.A previously piloted questionnaire was administered to pharmacy personnel currently operating community pharmacies in a rural province in South Africa, where dispensing of antibiotics without a prescription is likely to be greatest. The questionnaire included key knowledge questions regarding antibiotics and AMR, as well as ways to reduce AMR. Community pharmacies were divided into three categories: Independent, chain, and franchise pharmacies.A total of 128 pharmacies participated (75.7%), with independent pharmacies representing the majority (60.9%). A total of 313 completed questionnaires were returned (78.3% response rate), including responses from 106 pharmacists (33.9%) and 207 pharmacist assistants (66.1%). Overall, there was very good knowledge among both community pharmacists and pharmacist assistants concerning antibiotics and AMR. However, there was a significant misconception regarding the potential role of antibiotics in relieving pain. Encouragingly, attitudes regarding the risks associated with obtaining antibiotics without a prescription among both community pharmacists and pharmacist assistants were high. There was also strong agreement among both community pharmacists and pharmacist assistants for potential solutions to AMR.Overall, the findings showed that most pharmacists and pharmacist assistants in this rural province demonstrated a strong understanding of the effectiveness of antibiotics in bacterial infections and their lack of effectiveness to treat viral infections. They also demonstrated considerable knowledge regarding the risks associated with the inappropriate dispensing of antibiotics without a prescription, as well as ways to address rising AMR rates.

Tiyani Milta Maluleke, M. Maluleke, A. Jelić, Stephen M Campbell, Vanda Marković-Peković, N. Schellack, Audrey K. Chigome, A. Cook, B. Godman et al.

Antimicrobial resistance is a considerable global health threat especially among low- and middle-income countries, exacerbated by considerable inappropriate dispensing of antibiotics. There have though been concerns with variable levels of dispensing of antibiotics without a prescription in South Africa. Consequently, a need to comprehensively estimate current levels of dispensing of antibiotics without a prescription, which was the aim of this study.Administer a previously piloted questionnaire to all currently operating community pharmacies in a rural province, where dispensing of antibiotics without a prescription is likely to be greatest. The questionnaire included data on the estimated prevalence of antibiotics dispensed, their class and indication, and whether dispensed without a prescription. Community pharmacies were categorized into three: Independent, Chain and Franchise.128/169 (75.7%) operational pharmacies participated, with independent pharmacies representing the majority (60.9%). There was a 78.3% response rate from 400 distributed questionnaires, including 106 pharmacists (33.9%) and 207 pharmacist assistants (66.1%) from 128 pharmacies. Antibiotics accounted for 47.9% (95% CI: 47.2%-48.6%) of all medicines dispensed. Penicillins were the most prevalent antibiotic dispensed (41.1%). Almost half (47.2%) of the antibiotics dispensed included macrolides, fluoroquinolones and cephalosporins, which are typically antibiotics from the Watch group. Sexually transmitted infections (33.5%) and upper respiratory tract infections (25.8%) were the most frequent indications for antibiotic dispensing. Overall, 69.3% of 128 participating pharmacies in this rural province in South Africa admitted to dispensing antibiotics without a prescription in the past 14 days, principally among independent pharmacies (98.7%). However, estimates suggest only 8.6% of the total volume of antibiotics being dispensed were dispensed without a prescription among the 88 community pharmacies admitting to this practice in the past 3 days. Encouragingly, 98.1% of community pharmacists and 97.6% of pharmacist assistants indicated they always or mostly offered symptomatic relief before dispensing antibiotics without a prescription to patients with self-limiting conditions.There were considerable concerns regarding the prescribing and dispensing of antibiotics in this rural province including Watch antibiotics. This included the number of community pharmacies, especially independent pharmacies, where patients could purchase antibiotics without a prescription. Multiple strategies involving all key stakeholder groups are need to improve future antibiotic use across South Africa and reduce AMR.

Z. Saleem, Biset Asrade Mekonnen, E. S. Orubu, Md Ariful Islam, Thuy Thi Phuong Nguyen, C. Ubaka, Deus Buma, Nga Bui Thi Thuy, Yashasvi Sant et al.

INTRODUCTION Antimicrobial resistance (AMR) poses a significant threat, particularly in low- and middle-income countries (LMICs), exacerbated by inappropriate antibiotic use, access to quality antibiotics and weak antimicrobial stewardship (AMS). There is a need to review current evidence on antibiotic use, access, and AMR, in primary care across key countries.Areas covered: This narrative review analyses publications from 2018 to 2024 regarding access, availability and use of appropriate antibiotics. EXPERT OPINION There were very few studies focussing on a lack of access to antibiotics in primary care. However, there was considerable evidence of high rates of inappropriate antibiotic use, including Watch antibiotics, typically for minor infections, across studied countries exacerbated by patient demand. The high costs of antibiotics in a number of LMICs impacts on their use resulting in short courses and sharing of antibiotics. This can contribute to AMR alongside the use of substandard and falsified antibiotics. Overall, limited implementation of national action plans, insufficient resources, and knowledge gaps, affects sustainable development goals to provide routine access to safe, effective and appropriate antibiotics. CONCLUSIONS There is a clear need to focus health policy on the optimal use of essential AWaRe antibiotics in primary care settings to reduce AMR in LMICs.

T. Sono, Veronica Mboweni, A. Jelić, Stephen M Campbell, Vanda Marković-Peković, N. Ramdas, N. Schellack, Santosh Kumar, B. Godman et al.

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. 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. 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. 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.

T. Sono, M. Maluleke, N. Ramdas, A. Jelić, Stephen M Campbell, Vanda Marković-Peković, N. Schellack, Santosh Kumar, B. Godman et al.

Introduction: There are concerns with rising rates of antimicrobial resistance (AMR) across countries with appreciable impact on morbidity, mortality and costs. Amongst low- and middle-income countries, a key driver of AMR is the excessive use of antibiotics in ambulatory care, with a critical area being the appreciable selling of antibiotics without a prescription often driven by patient demand and limited knowledge. There is currently conflicting evidence in South Africa regarding this practice. Consequently, there is a need to explore these critical issues amongst patients, especially in more rural areas of South Africa. A pilot study was undertaken to address this. Methods: A two-step descriptive approach was undertaken. This involved two questionnaires amongst patients exiting chain and independent community pharmacies followed by cognitive interviews. Results: Overall, 21 patients were approached for an interview, including 11 for Part 1 of the questionnaire with 3 declining, and 10 for Part 2, with 2 declining. Subsequently 8 patients completed each part of the questionnaire.. On average, it took 2 min 13 s to complete both parts. 3 of the 5 patients being dispensed an antibiotic were dispensed one without a prescription, with all 3 patients exiting from independent pharmacies. Key reasons for self-purchasing included money and convenience. There was mixed knowledge regarding antibiotics and AMR amongst the 8 patients interviewed with Part 2. Overall, there was a satisfactory understanding of the Part 1 questions, although some modifications were suggested. Some participants had difficulty with fully understanding the questions in Part 2, with a number of suggestions made to improve this for the main study. Conclusion: There were concerns with the extent of purchasing antibiotics without a prescription in this pilot study as well as the knowledge of patients regarding antibiotics and AMR. Both areas need addressing and will be explored further in the main study.

Martina Glavan, A. Jelić, Damien Levard, J. Frösen, S. Keränen, Bart A A Franx, Ana-Rita Bras, Estelle R. Louet, Á. Dénes et al.

Intracerebral aneurysms (IAs) are pathological dilatations of cerebral arteries whose rupture leads to subarachnoid hemorrhage, a significant cause of disability and death. Inflammation is recognized as a critical contributor to the formation, growth, and rupture of IAs; however, its precise actors have not yet been fully elucidated. Here, we report CNS-associated macrophages (CAMs), also known as border-associated macrophages, as one of the key players in IA pathogenesis, acting as critical mediators of inflammatory processes related to IA ruptures. Using a new mouse model of middle cerebral artery (MCA) aneurysms we show that CAMs accumulate in the IA walls. This finding was confirmed in a human MCA aneurysm obtained after surgical clipping, together with other pathological characteristics found in the experimental model including morphological changes and inflammatory cell infiltration. In addition, in vivo longitudinal molecular MRI studies revealed vascular inflammation strongly associated with the aneurysm area, i.e., high expression of VCAM-1 and P-selectin adhesion molecules, which precedes and predicts the bleeding extent in the case of IA rupture. Specific CAM depletion by intracerebroventricular injection of clodronate liposomes prior to IA induction reduced IA formation and rupture rate. Moreover, the absence of CAMs ameliorated the outcome severity of IA ruptures resulting in smaller hemorrhages, accompanied by reduced neutrophil infiltration. Our data shed light on the unexplored role of CAMs as main actors orchestrating the progression of IAs towards a rupture-prone state. Graphical abstract

T. Sono, M. Maluleke, A. Jelić, Stephen M Campbell, Vanda Marković-Peković, N. Schellack, Santosh Kumar, B. Godman, J. Meyer

Introduction: There is considerable concern with rising rates of antimicrobial resistance (AMR) with its subsequent impact on morbidity, mortality and costs. In low- and middle-income countries, a key driver of AMR is the appreciable misuse of antibiotics in ambulatory care, which can account for up to 95% of human utilisation. A principal area is the selling of antibiotics without a prescription. There is conflicting evidence in South Africa regarding this practice alongside rising AMR rates. Consequently, there is a need to explore this further, especially in more rural areas of South Africa. A pilot study was undertaken to address this. Materials and Methods: A two-step descriptive approach involving a self-administered questionnaire amongst pharmacists and their assistants followed by cognitive interviews with some of the participants. Results: Twenty-one responses were obtained from nine of the 11 community pharmacies invited to participate. Participating pharmacies were all independently owned. Ten of the 21 participants admitted dispensing antibiotics without a prescription, including both adults and children, representing five of the nine participating pharmacies. A minority dispensed antibiotics before recommending suitable over-the-counter medicines. These high rates were exacerbated by patient pressure. There were issues with the length of the questionnaire and some of the phraseology, which will be addressed in the main study. Conclusion: There were concerns with the extent of purchasing antibiotics without a prescription in this pilot in South Africa study. Key issues will be explored further in the main study.

T. Sono, E. Yeika, A. Cook, A. Kalungia, S. Opanga, J. Acolatse, I. Sefah, A. Jelić, Stephen M Campbell et al.

ABSTRACT Introduction Antimicrobial resistance (AMR) is a global concern. Currently, the greatest mortality due to AMR is in Africa. A key driver continues to be high levels of dispensing of antibiotics without a prescription. Areas covered A need to document current rates of dispensing, their rationale and potential ways forward including antimicrobial stewardship programmes (ASPs). A narrative review was undertaken. The highest rates of antibiotic purchasing were in Eritrea (up to 89.2% of antibiotics dispensed), Ethiopia (up to 87.9%), Nigeria (up to 86.5%), Tanzania (up to 92.3%) and Zambia (up to 100% of pharmacies dispensing antibiotics without a prescription). However, considerable variation was seen with no dispensing in a minority of countries and situations. Key drivers of self-purchasing included high co-payment levels for physician consultations and antibiotic costs, travel costs, convenience of pharmacies, patient requests, limited knowledge of antibiotics and AMR and weak enforcement. ASPs have been introduced in some African countries along with quality targets to reduce inappropriate dispensing, centering on educating pharmacists and patients. Expert Opinion ASP activities need accelerating among community pharmacies alongside quality targets, with greater monitoring of pharmacists’ activities to reduce inappropriate dispensing. Such activities, alongside educating patients and healthcare professionals, should enhance appropriate dispensing of antibiotics and reduce AMR.

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