A cross-sector approach to explore socio-ecological associations with treatment engagement behaviours in Northern Ghana.

BACKGROUND: Cancer presents a growing global burden, not least in African countries such as Ghana where high cancer treatment dropouts has been identified due to numerous social, cultural and financial reasons. There is little understanding regarding patterns of treatment access behaviour, especially in Northern Ghana, which this study was designed to explore. METHODS: Through cross-sector collaboration, we extracted and clinically validated cancer patient records available in the Tamale Teaching Hospital. These were analysed descriptively and through multi-variate logistic regression. A treatment mapping process was also applied to highlight challenges in data collection. Multiple imputation with chained equations was conducted for high levels of missing data. Sensitivity analysis was applied to assess the impact of missing data. RESULTS: Treatment drop-out was high even when uncertainty due to missing data was accounted for, and only 27 % of patients completely engaged with treatment. High drop-out was found for all cancers including those covered by the Ghana National Health Insurance scheme. Multi-variate logistic regression revealed that social, health condition and systemic factors influence treatment engagement until completion. High missing data was observed for liver, ovarian, colorectal, gastric, bladder, oesophageal and head and neck and skin cancers, and soft tissue sarcomas, which limited model fitting. CONCLUSION: Treatment drop-out is a critical issue in Northern Ghana. There was high missing data due to the dynamic, complex and decentralised treatment pathway. Future studies are needed to understand the complex challenges in data recording. POLICY SUMMARY: Treatment drop out is a pertinent issue that policy makers should look to address. Further discussion with stakeholders involved in cancer treatment and data collection is required to better understand challenges to routine data collection in the local setting. This will allow policy to be designed to cater for the impact of multiple intersecting health and social factors on treatment completion.

Beliefs about antibiotics, perceptions of antimicrobial resistance, and antibiotic use: initial findings from a multi-country survey.

OBJECTIVES: To examine public beliefs about antibiotics, AMR, and knowledge of antibiotic use, and how these relate to self-reported antibiotic use. METHODS: Two hundred and fifty participants from 23 countries completed a cross-sectional, online survey assessing beliefs about antibiotics and AMR, knowledge of antibiotics, and antibiotic use. Descriptive statistics, Mann-Whitney U tests and Spearman's ρ correlations were used to understand relationships between outcomes. KEY FINDINGS: Respondents generally viewed antibiotics positively, with particularly strong beliefs regarding their benefit (M = 16.48 out of 20, SD = 2.62) and few concerns regarding their harm (M = 3.98 out of 10, SD = 1.82). Greater benefit beliefs about antibiotics were associated with fewer concerns about their overuse (P < .0001) and harm (P < .0001). Stronger perceived importance of AMR was associated with greater beliefs about the benefits of antibiotics (P = .006), greater concerns about their overuse (P = .009), and increased knowledge of appropriate use (P = .006). Those who reported inappropriately using their last antibiotics had greater concerns about overuse (P = .12) and less knowledge regarding appropriate use (P = .015), compared to those who did not. CONCLUSIONS: Generally, the public tends to view antibiotics as having strong benefits and have few concerns about their harm, which may have implications for inappropriate use. These initial findings highlight beliefs that could be targeted in messages to reduce inappropriate demand for antibiotics.

A critical review and analysis of the context, current burden, and application of policy to improve cancer equity in Ghana.

BACKGROUND: Cancer causes a major disease burden worldwide. This is increasingly being realised in low and middle-income countries, which account disproportionately for preventable cancer deaths. Despite the World Health Organization calling for governments to develop policies to address this and alleviate cancer inequality, numerous challenges in executing effective cancer policies remain, which require consideration of the country-specific context. As this has not yet been considered in Ghana, the aim of this review was to bring together and critique the social-environmental, health policy and system factors to identifying opportunities for future health policies to reduce cancer burden in the Ghanian context. A critical policy-focused review was conducted to bring together and critique the current health systems context relating to cancer in Ghana, considering the unmet policy need, health system and social factors contributing to the burden and policy advances related to cancer. CONCLUSION: The findings highlight the changing burden of cancer in Ghana and the contextual factors within the socio-ecosystem that contribute to this. Policies around expanding access to and coverage of services, as well as the harmonization with medical pluralism have potential to improve outcomes and increase equity but their implementation and robust data to monitor their impact pose significant barriers.

Tackling antimicrobial resistance: developing and implementing antimicrobial stewardship interventions in four African commonwealth countries through a health partnership model.

In recent years, health partnerships have shared infection prevention and control innovations between United Kingdom hospitals and Low-Middle-Income Countries. However, none had focused on antimicrobial stewardship (AMS), a core component of tackling antimicrobial resistance (AMR). This paper documents an effective approach to developing a program to increase AMS capacity in four African countries: Ghana, Tanzania, Uganda, and Zambia as part of the Commonwealth Partnerships for Antimicrobial Stewardship (CwPAMS) program. A systematic approach was applied to assess gaps in AMS interventions and inform the development of the CwPAMS program through deskbased assessments, including National Action Plans on AMR, online focus group meetings, and expert advisory group reviews. Twelve partnerships were selected for the CwPAMS program. AMS support tools were developed based on recommendations from the scoping, including an AMS checklist tool, a healthcare worker knowledge and attitudes questionnaire, and an antimicrobial prescribing app to support clinical decision-making. Training workshops on AMS were developed and delivered to volunteers in Africa and the UK using a train-the-trainer model. The tools and workshops facilitated capacity building for AMS through the generation and strengthening of knowledge, skills, commitment, structures, systems, and leadership among stakeholders in the UK and Africa. The overall average rating assigned to the program following independent evaluation using the Organisation for Economic Cooperation and Development Assistance Committee Evaluation Criteria was very good. The evaluation also highlighted that the majority of the HPs (75%) focused on AMS and/or improved prescribing practice; all HPs have developed and implemented AMS strategies, guidelines, and tools within their hospitals; and NHS staff were able to translate the knowledge and skills they had received early on in the program into clinical practice in response to COVID-19 challenges.

Medical pluralism, healthcare utilization and patient wellbeing: The case of Akan cancer patients in Ghana.

PURPOSE: As cancers increase in Ghana and in many low-and middle-income countries, healthcare utilization has become critical for disease management and patients' wellbeing. There is evidence that medical pluralism is common among cancer patients in Ghana and many other African countries, which results in lack of adherence to and absconding from hospital treatments. The objective of this study was to examine ways in which beliefs in disease causation influence medical pluralism among Akan cancer patients in Ghana. METHODS: A qualitative research approach was employed in this study. In-depth interviews were conducted for thirty (30) cancer patients who were purposively recruited from Komfo Anokye Teaching Hospital in Ghana. Thematic content analysis was used in analysing data. RESULTS: Our findings revealed that cancer patients ascribed both physical and spiritual causality to their illness. As such, they combined orthodox treatment with spiritual healing and herbal medicine. Regarding the order of therapeutic search, patients reported to herbal and spiritual centres before going to the hospital, a phenomenon which contributes to the late reporting and diagnosis as well as bad prognosis of cancers in Ghana. CONCLUSION: The findings of this research elucidate the relationship between culture and health care choices of cancer patients in Ghana. Increased awareness creation is crucial in eradicating myths surrounding cancers in Ghana.

What influences cancer treatment service access in Ghana? A critical interpretive synthesis.

OBJECTIVES: Multiple social-cultural and contextual factors influence access to and acceptance of cancer treatment in Ghana. The aim of this research was to assess existing literature on how these factors interplay and could be susceptible to local and national policy changes. DESIGN: This study uses a critical interpretive synthesis approach to review qualitative and quantitative evidence about access to adult cancer treatment services in Ghana, applying the socioecological model and candidacy framework. RESULTS: Our findings highlighted barriers to accessing cancer services within each level of the socioecological model (intrapersonal, interpersonal community, organisational and policy levels), which are dynamic and interacting, for example, community level factors influenced individual perceptions and how they managed financial barriers. Evidence was lacking in relation to determinants of treatment non-acceptance across all cancers and in the most vulnerable societal groups due to methodological limitations. CONCLUSIONS: Future policy should prioritise multilevel approaches, for example, improving the quality and affordability of medical care while also providing collaboration with traditional and complementary care systems to refer patients. Research should seek to overcome methodological limitations to understand the determinants of accessing treatment in the most vulnerable populations.

Scoping Review of National Antimicrobial Stewardship Activities in Eight African Countries and Adaptable Recommendations.

Antimicrobial resistance (AMR) is a global health problem threatening safe, effective healthcare delivery in all countries and settings. The ability of microorganisms to become resistant to the effects of antimicrobials is an inevitable evolutionary process. The misuse and overuse of antimicrobial agents have increased the importance of a global focus on antimicrobial stewardship (AMS). This review provides insight into the current AMS landscape and identifies contemporary actors and initiatives related to AMS projects in eight African countries (Ghana, Kenya, Malawi, Nigeria, Sierra Leone, Tanzania, Uganda, and Zambia), which form a network of countries participating in the Commonwealth Partnerships for Antimicrobial Stewardship (CwPAMS) programme. We focus on common themes across the eight countries, including the current status of AMR, infection prevention and control, AMR implementation strategies, AMS, antimicrobial surveillance, antimicrobial use, antimicrobial consumption surveillance, a one health approach, digital health, pre-service and in-service AMR and AMS training, access to and supply of medicines, and the impact of COVID-19. Recommendations suitable for adaptation are presented, including the development of a national AMS strategy and incorporation of AMS in pharmacists' and other healthcare professionals' curricula for pre-service and in-service training.

Development and Implementation of an Antimicrobial Stewardship Checklist in Sub-Saharan Africa: A Co-Creation Consensus Approach.

Antimicrobial stewardship (AMS) initiatives promote the responsible use of antimicrobials in healthcare settings as a key measure to curb the global threat of antimicrobial resistance (AMR). Defining the core elements of AMS is essential for developing and evaluating comprehensive AMS programmes. This project used co-creation and Delphi consensus procedures to adapt and extend the existing published international AMS checklist. The overall objective was to arrive at a contextualised checklist of core AMS elements and key behaviours for use within healthcare settings in Sub-Saharan Africa, as well as to implement the checklist in health institutions in four African countries. The AMS checklist tool was developed using a modified Delphi approach to achieve local expert consensus on the items to be included on the checklist. Fourteen healthcare/public health professionals from Tanzania, Zambia, Uganda, Ghana and the UK were invited to review, score and comment on items from a published global AMS checklist. Following their feedback, 8 items were rephrased, and 25 new items were added to the checklist. The final AMS checklist tool was deployed across 19 healthcare sites and used to assess AMS programmes before and after an AMS intervention in 14 of the 19 sites. The final tool comprised 54 items. Across the 14 sites, the completed checklists consistently showed improvements for all the AMS components following the intervention. The greatest improvements observed were the presence of formal multidisciplinary AMS structures (79%) and the execution of a point-prevalence survey (72%). The elements with the least improvement were access to laboratory/imaging services (7%) and the presence of adequate financial support for AMS (14%). In addition to capturing the quantitative and qualitative changes associated with the AMS intervention, project evaluation suggested that administering the AMS checklist made unique contributions to ongoing AMS activities. Furthermore, 29 additional AMS activities were reported as a direct result of the prompting checklist questions. Contextualised, co-created AMS tools are necessary for managing antimicrobial use across healthcare settings and increasing local AMS ownership and commitment. This study led to the development of a new AMS checklist, which proved successful in capturing AMS improvements in Tanzania, Zambia, Uganda, and Ghana. The tool also made unique contributions to furthering local AMS efforts. This study extends the existing AMS materials for low- and middle-income countries and provides empirical evidence for successful use in practice.

Pharmacist beliefs about antimicrobial resistance and impacts on antibiotic supply: a multinational survey.

Background: Pharmacists have important antimicrobial stewardship (AMS) roles yet limited literature exists on pharmacists' knowledge and beliefs about antimicrobial resistance (AMR) and antimicrobials and how these beliefs influence antimicrobial supply in different countries. Methods: A cross-sectional survey was disseminated to pharmacists around the world via the Commonwealth Pharmacists' Association and related networks. Data were collected on demographics, antibiotic supply practices, and knowledge and beliefs about AMR. Results: A total of 546 pharmacists responded from 59 countries, most commonly from Africa (41%) followed by Asia (26%) and Oceania (22%). Respondents supplied a mean of 46 ±â€Š81 antibiotic prescriptions/week, 73%±35% of which were given in response to a prescription. Overall, 60.2% dispensed antibiotics at least once without a prescription. Respondents had good knowledge (mean 9.6 ±â€Š1.3 (out of 12), and held positive beliefs about AMR [mean 3.9 ±â€Š0.6 (out of 5)]. Knowledge about antibiotics and beliefs about AMR were positively correlated. The odds of supplying antibiotics without a prescription were 7.4 times higher among respondents from lower income countries [adjusted odds ratio (AOR) = 7.42, 95% CI 4.16-13.24]. Conversely, more positive AMR beliefs were associated with a lower odds of supplying antibiotics without a prescription (AOR = 0.91, 95% CI 0.86-0.95). Conclusions: Most pharmacists had the good knowledge about antibiotics and positive beliefs about AMR. These beliefs were influenced by knowledge, work setting, and country income. A proportion of respondents provided antibiotics without a prescription; the likelihood of this occurring was higher in those who held more negative beliefs about AMR.

Improving Access to Antimicrobial Prescribing Guidelines in 4 African Countries: Development and Pilot Implementation of an App and Cross-Sectional Assessment of Attitudes and Behaviour Survey of Healthcare Workers and Patients.

Smartphone apps have proven to be an effective and acceptable resource for accessing information on antimicrobial prescribing. The purpose of the study is to highlight the development and implementation of a smartphone/mobile app (app) for antimicrobial prescribing guidelines (the Commonwealth Partnerships for Antimicrobial Stewardship-CwPAMS App) in Ghana, Tanzania, Uganda and Zambia and to evaluate patients' and healthcare providers' perspectives on the use of the App in one of the participating institutions. Two structured cross-sectional questionnaires containing Likert scale, multiple-choice, and open-ended questions were issued to patients and healthcare workers six months after the introduction of the app at one of the hospital sites. Metrics of the use of the app for a one-year period were also obtained. Download and use of the app peaked between September and November 2019 with pharmacists accounting for the profession that the most frequently accessed the app. More than half of the responding patients had a positive attitude to the use of the app by health professionals. Results also revealed that more than 80% of health care workers who had used the CwPAMS App were comfortable using a smartphone/mobile device on a ward round, considered the app very useful, and found it to improve their awareness of antimicrobial stewardship, including documentation of the indication and duration for antimicrobials on the drug chart. It also encouraged pharmacists and nurses to challenge inappropriate antimicrobial prescribing. Overall, our findings suggest that its use as a guide to antimicrobial prescribing sparked positive responses from patients and health professionals. Further studies will be useful in identifying the long-term consequences of the use of the CwPAMS App and scope to implement in other settings, in order to guide future innovations and wider use.

Together we unite: the role of the Commonwealth in achieving universal health coverage through pharmaceutical care amidst the COVID-19 pandemic.

The world currently faces unprecedented health challenges as COVID-19 poses a huge threat to health systems, economies and societies as we know it. The events of the current COVID-19 pandemic have further emphasised existing issues within our health systems. There is no better time than now to come together in global solidarity to tackle these evolving threats of COVID-19 pandemic. The Commonwealth is an ideally placed network to tackle these global health challenges, with its wide-reaching networks of governmental, non-governmental and civil society organisations across all continents. Although the biennial Commonwealth Heads of Government Meeting (CHOGM) originally scheduled to take place in Kigali in Rwanda 22-27 June 2020 has been postponed in view of COVID-19, Commonwealth country discussions are continuing, centred on the CHOGM key theme of 'Delivering a Common Future: Connecting, Innovating, Transforming', and five subthemes of Information and Communications Technology (ICT) and Innovation; Trade; Environment; Governance and the Rule of Law; and Youth. The planned CHOGM and Commonwealth itself provides all members a timely platform to consider innovative ways to connect, innovate and transform healthcare to meet the needs of their populations. This commentary considers these five CHOGM subthemes and how member nations can be supported to achieve universal health coverage through optimising medicines use and outcomes, in the midst of a global pandemic in line with the global health agenda.

Advancing health system strengthening through improving access to medicines: A review of local manufacturing policies in Ghana.

Providing access to quality-assured medicines is a fundamental component of strengthening health systems. Yet, the World Health Organization (WHO) estimates that 13.6% of all medicines in low- and middle-income countries (LMIC's) may be substandard or falsified (SF) impeding patient outcomes, imposing financial burden, and contributing to antimicrobial resistance. Circulation of SF medicines also undermines trust in the health system and legitimate health care professionals. It may erode trust in the manufacturers of genuine pharmaceutical products as well as health professionals who prescribe and dispense them. Failure to address challenges in medicines quality assurance and supply risks jeopardizing progress towards universal healthcare coverage. This editorial draws on perspectives from a Ghanaian context and highlights the importance of ensuring an adequate and stable medicine supply, specifically through mechanisms to foster local manufacturing. This will serve to address the problem of SF medicines, as well as providing opportunities for mutual benefit with multiple related sectors. The WHO's mechanism on substandard and falsified medical products 2020 highlights multiple sectors have a key role in combatting SF medicines. Although key considerations and initiatives in other sectors are beyond the scope of this article, local manufacturing should be viewed with WHO's a multilevel systemwide approach.

Editorial: Medicines pricing, access and safety in Morocco.

Unregulated supply of medicines compromises quality assurance and risks patient safety. The emergence of illegal medicines trafficking in Morocco presents a major health threat, which highlights the need for region-wide alignment in policies to drive stringent regulatory enforcement and robust health systems that ensure population- wide access to safe medicines. Herein, we draw on insights from a situational analysis in Morocco, as a lower- middle income setting, to present access to medicines through regulated supply procedures as a vital prerequisite for quality assurance and patient safety.

L'approvisionnement non réglementé en médicaments compromet l'assurance qualité et la sécurité des patients. L'émergence du trafic illégal de médicaments au Maroc constitue une menace majeure pour la santé, ce qui souligne la nécessité d'un alignement régional des politiques pour une application stricte de la réglementation et des systèmes de santé robustes garantissant l'accès de la population à des médicaments sûrs. Nous nous inspirons d'une analyse situationnelle menée au Maroc, en tant que pays à revenu moyen-inférieur, pour présenter l'accès aux médicaments par le biais de procédures d'approvisionnement réglementées, prérequis indispensable à l'assurance qualité et à la sécurité des patients.

Publisher Correction: A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage.

The original PDF version of this Article listed the authors as "Marcus J.G.W. Ladds," where it should have read "Marcus J. G. W. Ladds, Ingeborg M. M. van Leeuwen, Catherine J. Drummond et al.#".Also in the PDF version, it was incorrectly stated that "Correspondence and requests for materials should be addressed to S. Lín.", instead of the correct "Correspondence and requests for materials should be addressed to S. Laín."This has been corrected in the PDF version of the Article. The HTML version was correct from the time of publication.

Weaving the health and pharmaceutical care agenda through the themes of the commonwealth heads of government meeting (CHOGM), London 2018.

The biennial Commonwealth Heads of Government Meeting (CHOGM) this year is based around four key themes: prosperity, fairness, sustainability and security. This is an opportune time to consider the role of pharmacists in healthcare delivery, and particularly their contribution to achieving the United Nations Sustainable Development Goals (SDGs). As a member of the Commonwealth Health Professions Alliance (CHPA), the Commonwealth Pharmacists Association (CPA) has been working to ensure that pharmacy-related aspects of health are represented in the advocacy papers submitted by Civil Society. Echoing the CHPA's priorities around SDG 3 (health) and the attainment of sustainable universal health coverage (UHC), the CPA has been raising the profile of key priorities for our members, including: addressing the shortage of healthcare workers (with an emphasis on pharmacists); need for access to quality medicines and medicines information; tackling anti-microbial resistance and substandard/falsified medicines; and championing the role of digitalisation and partnerships. This editorial discusses how the work of the CPA links with the themes of CHOGM, the CPA's input into this meeting and the direction of travel 'Towards a Common Future' for health and pharmacy in the Commonwealth.

A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage.

The development of non-genotoxic therapies that activate wild-type p53 in tumors is of great interest since the discovery of p53 as a tumor suppressor. Here we report the identification of over 100 small-molecules activating p53 in cells. We elucidate the mechanism of action of a chiral tetrahydroindazole (HZ00), and through target deconvolution, we deduce that its active enantiomer (R)-HZ00, inhibits dihydroorotate dehydrogenase (DHODH). The chiral specificity of HZ05, a more potent analog, is revealed by the crystal structure of the (R)-HZ05/DHODH complex. Twelve other DHODH inhibitor chemotypes are detailed among the p53 activators, which identifies DHODH as a frequent target for structurally diverse compounds. We observe that HZ compounds accumulate cancer cells in S-phase, increase p53 synthesis, and synergize with an inhibitor of p53 degradation to reduce tumor growth in vivo. We, therefore, propose a strategy to promote cancer cell killing by p53 instead of its reversible cell cycle arresting effect.

Robust mitotic entry is ensured by a latching switch.

Cell cycle events are driven by Cyclin dependent kinases (CDKs) and by their counter-acting phosphatases. Activation of the Cdk1:Cyclin B complex during mitotic entry is controlled by the Wee1/Myt1 inhibitory kinases and by Cdc25 activatory phosphatase, which are themselves regulated by Cdk1:Cyclin B within two positive circuits. Impairing these two feedbacks with chemical inhibitors induces a transient entry into M phase referred to as mitotic collapse. The pathology of mitotic collapse reveals that the positive circuits play a significant role in maintaining the M phase state. To better understand the function of these feedback loops during G2/M transition, we propose a simple model for mitotic entry in mammalian cells including spatial control over Greatwall kinase phosphorylation. After parameter calibration, the model is able to recapture the complex and non-intuitive molecular dynamics reported by Potapova et al. (Potapova et al., 2011). Moreover, it predicts the temporal patterns of other mitotic regulators which have not yet been experimentally tested and suggests a general design principle of cell cycle control: latching switches buffer the cellular stresses which accompany cell cycle processes to ensure that the transitions are smooth and robust.