Evaluation of Rational Medicines Use Based on World Health Organization Core Indicators: A Cross-Sectional Study in Five Health Districts in Mauritania.

Introduction: The rational use of medicines is essential for preventing adverse medicine reactions, achieving therapeutic outcomes, and optimizing treatment costs. While the irrational use of medicines is frequently reported in sub-Saharan Africa, to the best of our knowledge no formal studies have taken place in Mauritania thus far. The main objective of this study was therefore to analyze the rational use of medicines in public and private not-for-profit health facilities, in five health districts in Mauritania. Methods: We conducted a cross-sectional study to assess the rational use of medicines. We used the standard indicators derived from the methodologies of the World Health Organization (WHO) and International Network for Rational Use of Drugs (INRUD). Data were prospectively collected from 1050 prescriptions/patients, in thirty-one public and private not-for-profit health posts/centers in 5 health districts. The data were analyzed using the Statistical Package for the Social Sciences. P value less than 0.05 at 95% confidence interval considered for significance of relationships for associations in statistical test. Results: The average number of medicines per prescription was 2.21; 83.1% (1931/2325) of medicines were prescribed by generic name, but only 54% (1253/2325) were on the National Essential Medicine List (NEML). Antibiotics were prescribed in 62.4% (655/1050) of the consultations, and injectable medicines were prescribed in 15.6% (164/1050) of the consultations. The average consultation time was 16.32 minutes, and the average dispensing time was 97 seconds. Dispensed medicines were correctly labeled, and 83% (871/1050) of patients met the correct administration schedule. The NEML, and the "restricted NEML" for 76 commonly-used medicines, were available in all surveyed health facilities, but the National Therapeutic Guidelines were available in only 60.26% of them. Conclusion: Our findings indicate a possible excess of antibiotics prescriptions, and a likely lack of knowledge of the National Therapeutic Guidelines. There is a need to investigate in more detail the prescription patterns versus disease-specific therapeutic guidelines, and to qualitatively investigate the factors that contribute to the observed irrational prescribing. Moreover, training local staff in the rational use of medicines seems important.

Substandard and falsified medicines in African pharmaceutical markets: A case study from Ethiopia.

BACKGROUND: Substandard and falsified (SF) medicines are a global health problem. Their high prevalence is a threat to public health in low- and middle-income countries (LMICs). However, there are few street-level investigations of how this market works. This case study examines the supply and demand for SF medicines in Southern Ethiopia. METHODS: A cross sectional qualitative design, using semi-structured interviews supplemented by participant observation, was adopted. Study participants were selected using purposive, convenience, and snowball sampling techniques. They included pharmacists, physicians, wholesalers, pharmacy owners, regulatory staff, law enforcement agents and the local community. A total of 43 interviews were conducted. The study used Actor-Network Theory (ANT) as an analytic framework. RESULTS: The findings show that efforts to address the problem of SF medicines in Ethiopia struggle because of the lack of a clear framing of the issue and consensus on how it should be understood. The pharmaceutical market in Wolaita Zone, Southern Ethiopia is supplied with a wide variety of SF medicines from diverse sources. This complex supply chain emerges due to barriers to accessing essential medicines that are in demand. Control of SF medicines will require a range of interventions thoughtfully tailored to the local contexts and determinants of both supply and demand. CONCLUSION: The evidence of confusion, ambiguity, and uncertainty in defining the problem of SF medicines suggest that more research and policy work is required to refine understanding of the issue, and of the local market conditions that join demand and supply for different medicines in Southern Ethiopia. These are likely to apply more widely in comparable contexts throughout sub-Saharan Africa. The current global policy emphasis on stricter regulation and enforcement alone does not adequately address the social and economic factors that collectively create and shape user demand that is met by SF medicines.

The response to substandard and falsified medical products in francophone sub-Saharan African countries: weaknesses and opportunities.

Assuring the quality of medical products manufactured, imported or distributed in francophone sub-Saharan Africa remains a challenge, despite positive signals like the growing engagement in the benchmarking of regulatory authorities and -particularly- in the establishment of the African Medicines Agency. In this short report, we describe the existing activities to prevent, detect and respond to substandard and falsified products (SF) in this region, either through African multilateral organizations and initiatives led by the World Health Organization, or through the contribution of other stakeholders, such as local universities and procurement agencies. We underline that these emerging local stakeholders may play a pivotal role to guide and inform the national regulatory authorities about the prevalence and patterns of SF medical products, complementing the market surveillance and control, and building awareness of the importance of pharmaceutical quality assurance for public health.

Challenges of Antibiotic Formulations and Administration in the Treatment of Bloodstream Infections in Children Under Five Admitted to Kisantu Hospital, Democratic Republic of Congo.

Severe bacterial infections in children need prompt, appropriate antibiotic treatment. We report challenges observed within a prospective, cohort study on antibiotic efficacy in non-typhi Salmonella bloodstream infection (NCT04850677) in Kisantu district hospital (Democratic Republic of Congo). Children (aged > 28 days to < 5 years) admitted with suspected bloodstream infection (August 1, 2021 through July 31, 2022) were enrolled and followed until day 3 or discharge for non-typhi Salmonella patients. Antibiotics were administered to 98.4% (1,838/1,867) of children, accounting for 2,296 antibiotic regimens (95.7% intravenous, 4.3% oral). Only 78.3% and 61.8% of children were, respectively, prescribed and administered antibiotics on the admission day. At least one dose was not administered in 3.6% of children, mostly because of mismatch of the four times daily cefotaxime schedule with the twice-daily administration rounds. Inappropriate intravenous administration practices included multidose use, air-venting, and direct injection instead of perfusion. There was inaccurate aliquoting in 18.0% (32/178) of intravenous ciprofloxacin regimens, and thus administered doses were > 16% below the intended dose. Dosing accuracy of oral suspensions was impaired by lack of instructions for reconstitution, volume indicators, and/or dosing devices. Adult-dose tablets were split without/beyond scoring lines in 84.4% (27/32) of tablets. Poor availability and affordability of age-appropriate oral formulations contributed to low proportions of intravenous-to-oral switch (33.3% (79/237) of non-typhi Salmonella patients). Other quality issues included poor packaging, nonhomogeneous suspensions, and unsafe water for reconstitution. In conclusion, poor antibiotic products (no age-appropriate formulations, poor quality and access), processes (delayed prescription/administration, missed doses), and practices (inaccurate doses, [bio]safety risks) must be urgently addressed to improve pediatric antibiotic treatment.

Usefulness of medicine screening tools in the frame of pharmaceutical post-marketing surveillance.

The negative consequences of Substandard and falsified (SF) medicines are widely documented nowadays and there is still an urgent need to find them in more efficient ways. Several screening tools have been developed for this purpose recently. In this study, three screening tools were used on 292 samples of ciprofloxacin and metronidazole collected in Cameroon. Each sample was then analyzed by HPLC and disintegration tests. Seven additional samples from the nitro-imidazole (secnidazole, ornidazole, tinidazole) and the fluoroquinolone (levofloxacin, ofloxacin, norfloxacin, moxifloxacin) families were analyzed to mimic falsified medicines. Placebo samples that contained only inert excipients were also tested to mimic falsified samples without active pharmaceutical ingredient (API). The three screening tools implemented were: a simplified visual inspection checklist, a low-cost handheld near infrared (NIR) spectrophotometer and paper analytical devices (PADs). Overall, 61.1% of the samples that failed disintegration and assay tests also failed the visual inspection checklist test. For the handheld NIR, one-class classifier models were built to detect the presence of ciprofloxacin and metronidazole, respectively. The APIs were correctly identified in all the samples with sensitivities and specificities of 100%. However, the importance of a representative and up-to-date spectral database was underlined by comparing models built with different calibration set spanning different variability spaces. The PADs were used only on ciprofloxacin samples and detected the API in all samples in which the presence of ciprofloxacin was confirmed by HPLC. However, these PADs were not specific to ciprofloxacin since they reacted like ciprofloxacin to other fluoroquinolone compounds. The advantages and drawbacks of each screening tool were highlighted. They are promising means in the frame of early detection of SF medicines and they can increase the speed of decision about SF medicines in the context of pharmaceutical post-marketing surveillance.

Access to opioid analgesics for medical use at hospital level in the Democratic Republic of Congo: An exploratory mixed-method study.

OBJECTIVE: To investigate the availability of and access to opioid analgesics at hospital level in the Democratic Republic of Congo. METHODS: Exploratory mixed-method study combining a descriptive survey of the availability of opioid analgesics at hospital pharmacies with a qualitative survey that explored the experiences and perceptions of healthcare workers, managers, patients and caregivers, by means of a short questionnaire and of semi-structured interviews. The study was conducted in a convenience sample of 12 hospitals, located in five different provinces, in 2021. RESULTS: The quality and completeness of stock data for opioid analgesics were generally poor. Stock-outs were frequent. Only five hospital pharmacies had records on prescriptions of opioids in 2020. In-patients and caregivers indicated they generally must purchase opioids out-of-pocket, sometimes far from the place of residence. Doctors and nurses confirmed that prescribed opioids are often unavailable at the hospital pharmacy. Furthermore, they suggested an important need of training in pain management with opioids, and of effective regulation to ensure opioid availability. Pharmacists and managers recognised important weaknesses in the processes of needs quantification, stock management, planning and supply. CONCLUSIONS: Our exploratory study suggests the need of a complex set of coordinated actions to be undertaken by all relevant actors in DRC to correct the poor practices in opioids' management and to improve opioids' availability, affordability and adequate use. This will require a change of mindset to overcome the neglect of the health needs of persons with acute and chronic pain.

Boosting ethics review capacity in public health emergency situations: Co-creation of a training model for French-speaking research ethics committees.

BACKGROUND: Ethics review preparedness is a major foundation for national effective response to public health emergencies, because it promotes pertinent research and enhances the protection of research participants and communities. In low-income countries, it can also promote equitable research partnership. However, most relevant literature is in English and not easily accessible for the members of research ethics committees in French-speaking African countries. METHODS: A training module in French, addressing the issue of research ethics review during outbreaks and other public health emergencies, was designed based on a non-systematic literature review, and in order to be complementary to the Democratic Republic of Congo (DRC) national guidelines for ethics review. The module was administered to 42 members of the five ethics committees in DRC that expressed their interest for the training. RESULT: This training, co-designed with local stakeholders, in the local working language and taking into account local circumstances and regulation, provided participants with up-to-date insights of research ethics (and research ethics preparedness) in public health emergencies. It resulted in rich reflection and knowledge-sharing on good practices across the ethics committees. CONCLUSION: As most participating ethics committees do not have yet explicit standard operating procedures for expedited review of protocols submitted in emergency situations, this would be a next important step to facilitate emergency reviews in the most efficient way.

Age-modified factors associated with placental malaria in rural Burkina Faso.

BACKGROUND: Malaria in pregnancy can result in placental infection with fetal implications. This study aimed at assessing placental malaria (PM) prevalence and its associated factors in a cohort of pregnant women with peripheral malaria and their offspring. METHOD: The data were collected in the framework of a clinical trial on treatments for malaria in pregnant women . Placental malaria (PM) was diagnosed by histopathological detection of parasites and/or malaria pigment on placenta biopsies taken at delivery. Factors associated with PM were assessed using logistic regression. RESULTS: Out of 745 biopsies examined, PM was diagnosed in 86.8 % of women. Acute, chronic and past PM were retrieved in 11 (1.5 %), 170 (22.8 %), and 466 (62.6 %) women, respectively. A modifying effect was observed in the association of gravidity or anemia at the study start with pooled PM (presence of parasites and/or malaria pigment). In women under 30, gravidity ≤ 2 was associated with an increased prevalence of pooled PM but in women aged 30 years or more, gravidity was no more associated with pooled PM (OR 6.81, 95 % CI 3.18 - 14.60; and OR 0.52, 95 % CI 0.10 - 2.76, respectively). Anemia was associated with pooled PM in women under 30 (OR 1.96, 95 % CI 1.03 - 3.72) but not in women aged 30 years or more (OR 0.68, 95 % CI 0.31 - 1.49). Similarly, the association of gravidity with past-chronic PM depended also on age. A higher prevalence of active PM was observed in women under 30 presenting with symptomatic malaria (OR 3.79, 95 % CI 1.55 - 9.27), while there was no significant increase in the prevalence of active PM (presence of parasites only) in women with symptomatic malaria when aged 30 years or more (OR 0.42, 95 % CI 0.10 - 1.75). In women with chronic PM, the prevalence of low birth weight or prematurity was the highest (31.2 %) as compared with past PM or no PM. CONCLUSION: Despite the rapid diagnosis and efficacious treatment of peripheral infection, the prevalence of placental malaria remained high in women with P. falciparum peripheral infection in Nanoro, especially in younger women This underlines the importance of preventive measures in this specific group.

Out of the boxes, out of the silos: The need of interdisciplinary collaboration to reduce poor-quality medical products in the supply chain.

In this paper, we argue that understanding and addressing the problem of poor-quality medical products requires a more interdisciplinary approach than has been evident to date. While prospective studies based on rigorous standardized methodologies are the gold standard for measuring the prevalence of poor-quality medical products and understanding their distribution nationally and internationally, they should be complemented by social science research to unpack the complex set of social, economic, and governance factors that underlie these patterns. In the following sections, we discuss specific examples of prospective quality surveys and of social science studies, highlighting the value of cross-sector partnerships in driving high-quality, policy-relevant research in this area.

Study on identification, assay and organoleptic quality of veterinary medicines in Ethiopia.

BACKGROUND: Medicines of poor quality are currently prevailing problems undermining the quality of health care services in veterinary and human medicine. In this study, physico-chemical quality of veterinary medicines was evaluated. METHODS: A total of 959 veterinary medicines samples were collected during routine regulatory activities, i.e. pre-registration, re-registration, consignment checking and post-marketing surveillance, in Ethiopia. The samples were transported to Animal Products, Veterinary Drug and Feed Quality Assessment Centre (APVD-FQAC), which is the quality control laboratory of the Veterinary Drug and Feed Administration and Control Authority (VDFACA) and stored until analysis. The samples were subjected to visual inspection and chemical analysis following the United States, European or British Pharmacopoeias, or manufacturer's methods. RESULTS: The findings revealed that 12 (1.3%) of tested products showed defects in physical characteristics, packaging, or labelling information, while a total of 66 (6.9%) samples of the investigated products failed to comply with the Pharmacopoeias and supplier's specification limit set for assay. Of these, 60 samples did not comply with the minimum assay specification limit. CONCLUSION: Overall, 8.2% of the investigated veterinary medicine samples did not comply with the specification set for the investigated quality attributes and thus were categorized as of poor quality. This indicates the need for continued strengthening of regulatory functions.

Access to medicine among asylum seekers, refugees and undocumented migrants across the migratory cycle: a scoping review protocol.

INTRODUCTION: Migration creates new health vulnerabilities and exacerbates pre-existing medical conditions. Migrants often face legal, system-related, administrative, language and financial barriers to healthcare, but little is known about factors that specifically influence migrants' access to medicines and vaccines. This scoping review aims to map existing evidence on access to essential medicines and vaccines among asylum seekers, refugees and undocumented migrants who aim to reach Europe. We will consolidate existing information and analyse the barriers that limit access at the different stages of the migratory phases, as well as policies and practices undertaken to address them. METHODS: We follow the Arksey and O'Malley framework for knowledge synthesis of research, as updated by Levac et al. For reporting the results of our search and to synthetise evidence, we will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extended reporting guideline for scoping reviews. This scoping review consists of five iterative stages. Bibliographic databases (PubMed, CINAHL, Cochrane Database of Systematic Reviews and Scopus) and grey literature databases (Open Grey, Grey Literature Report and Google Scholar, Web of Science Conference Proceedings, non-governmental organisations and United Nations agency websites) will be searched for relevant studies. DISSEMINATION AND ETHICS: This review will be disseminated through a peer-reviewed article in a scientific open-access journal and conference presentations. Furthermore, findings will be shared at workshops of research and operational stakeholders for facilitating translation into research and operational practices. Since it consists of reviewing and collecting data from publicly available materials, this scoping review does not require ethics approval.

COVID-19 vaccine equity: a health systems and policy perspective.

INTRODUCTION: The global COVID-19 vaccine rollout has highlighted inequities in the accessibility of countries to COVID-19 vaccines. Populations in low- and middle-income countries have found it difficult to have access to COVID-19 vaccines. AREAS COVERED: This perspective provides analyses on historical and contemporary policy trends of vaccine development and immunization programs, including the current COVID-19 vaccination drive, and governance challenges. Moreover, we also provide a comparative health system analysis of the COVID-19 vaccine deployment in some countries from different continents. It recommends that the international Access to COVID-19 Tools Accelerator (ACT-A) partnership requires a strong governance mechanism and urgent financial investment. EXPERT OPINION: All WHO member states should agree on technology transfer and voluntary license-sharing via a commonly governed technology access pool and supported by a just Intellectual Property regime. Contextualized, dynamic understandings and country-specific versions of health systems strengthening are needed to improve vaccine equity in a sustainable matter.

Training on adequate use of opioid analgesics in West and Central Africa: a neglected step on the way to access to essential medicines?

Alleviating acute and chronic pain is a moral imperative for health professionals and health systems, and it requires adequate access to and use of essential opioid analgesics. However, this is still a neglected issue in global health, with striking inequalities in opioids availability between high and low- and middle-income countries. Countries most affected by lack of access are those with a fragile political situation and weak regulatory and healthcare systems. The main threats to accessibility, availability and affordability are situated at different levels: legislation and policy, financing, knowledge and cultural behavior, erroneous beliefs, and training and education. Among these threats, the lack of (adequate) training and education seems to be a cross-cutting issue. Exploring the current body of knowledge about training and educational activities related to use of opioid analgesics and palliative care, is helpful to understand gaps and to delineate priorities for setting up adequate interventions. When applied to West and Central Africa, this exercise reveals that there is little information (easily) available in the public domain. The African Palliative Care Association (APCA) appears to be the leading provider of capacity building activities in this region for key stakeholders, including national authorities, healthcare professionals and the general population; it is also very active in publishing and communicating about these issues. However, apart from APCA, there is little information on training programs' contents and long-term outcomes. Furthermore, trainings rarely target important stakeholders such as lawmakers, regulators, supply officers and the lay public (i.e., patients, caregivers, community leaders and members of the society as a whole). Hence, it is urgent to fill the existing gaps in training and educational activities to improve access to essential opioid analgesics in West and Central Africa, involving different stakeholders at the national and regional level. Furthermore, such experiences should be published and made publicly available to allow for mutual learning and further upscale.

Preprints in times of COVID19: the time is ripe for agreeing on terminology and good practices.

Over recent years, the research community has been increasingly using preprint servers to share manuscripts that are not yet peer-reviewed. Even if it enables quick dissemination of research findings, this practice raises several challenges in publication ethics and integrity. In particular, preprints have become an important source of information for stakeholders interested in COVID19 research developments, including traditional media, social media, and policy makers. Despite caveats about their nature, many users can still confuse pre-prints with peer-reviewed manuscripts. If unconfirmed but already widely shared first-draft results later prove wrong or misinterpreted, it can be very difficult to "unlearn" what we thought was true. Complexity further increases if unconfirmed findings have been used to inform guidelines. To help achieve a balance between early access to research findings and its negative consequences, we formulated five recommendations: (a) consensus should be sought on a term clearer than 'pre-print', such as 'Unrefereed manuscript', "Manuscript awaiting peer review" or ''Non-reviewed manuscript"; (b) Caveats about unrefereed manuscripts should be prominent on their first page, and each page should include a red watermark stating 'Caution-Not Peer Reviewed'; (c) pre-print authors should certify that their manuscript will be submitted to a peer-review journal, and should regularly update the manuscript status; (d) high level consultations should be convened, to formulate clear principles and policies for the publication and dissemination of non-peer reviewed research results; (e) in the longer term, an international initiative to certify servers that comply with good practices could be envisaged.