Conceptual framework for task shifting and task sharing: an international Delphi study.

BACKGROUND: Task shifting and sharing (TS/S) involves the redistribution of health tasks within workforces and communities. Conceptual frameworks lay out the key factors, constructs, and variables involved in a given phenomenon, as well as the relationships between those factors. Though TS/S is a leading strategy to address health worker shortages and improve access to services worldwide, a conceptual framework for this approach is lacking. METHODS: We used an online Delphi process to engage an international panel of scholars with experience in knowledge synthesis concerning TS/S and develop a conceptual framework for TS/S. We invited 55 prospective panelists to participate in a series of questionnaires exploring the purpose of TS/S and the characteristics of contexts amenable to TS/S programmes. Panelist responses were analysed and integrated through an iterative process to achieve consensus on the elements included in the conceptual framework. RESULTS: The panel achieved consensus concerning the included concepts after three Delphi rounds among 15 panelists. The COATS Framework (Concepts and Opportunities to Advance Task Shifting and Task Sharing) offers a refined definition of TS/S and a general purpose statement to guide TS/S programmes. COATS describes that opportunities for health system improvement arising from TS/S programmes depending on the implementation context, and enumerates eight necessary conditions and important considerations for implementing TS/S programmes. CONCLUSION: The COATS Framework offers a conceptual model for TS/S programmes. The COATS Framework is comprehensive and adaptable, and can guide refinements in policy, programme development, evaluation, and research to improve TS/S globally.

Molecules linked to Ras signaling as therapeutic targets in cardiac pathologies.

The Ras family of small Guanosine Triphosphate (GTP)-binding proteins (G proteins) represents one of the main components of intracellular signal transduction required for normal cardiac growth, but is also critically involved in the development of cardiac hypertrophy and heart failure. The present review provides an update on the role of the H-, K- and N-Ras genes and their related pathways in cardiac diseases. We focus on cardiac hypertrophy and heart failure, where Ras has been studied the most. We also review other cardiac diseases, like genetic disorders related to Ras. The scope of the review extends from fundamental concepts to therapeutic applications. Although the three Ras genes have a nearly identical primary structure, there are important functional differences between them: H-Ras mainly regulates cardiomyocyte size, whereas K-Ras regulates cardiomyocyte proliferation. N-Ras is the least studied in cardiac cells and is less associated to cardiac defects. Clinically, oncogenic H-Ras causes Costello syndrome and facio-cutaneous-skeletal syndromes with hypertrophic cardiomyopathy and arrhythmias. On the other hand, oncogenic K-Ras and alterations of other genes of the Ras-Mitogen-Activated Protein Kinase (MAPK) pathway, like Raf, cause Noonan syndrome and cardio-facio-cutaneous syndromes characterized by cardiac hypertrophy and septal defects. We further review the modulation by Ras of key signaling pathways in the cardiomyocyte, including: (i) the classical Ras-Raf-MAPK pathway, which leads to a more physiological form of cardiac hypertrophy; as well as other pathways associated with pathological cardiac hypertrophy, like (ii) The SAPK (stress activated protein kinase) pathways p38 and JNK; and (iii) The alternative pathway Raf-Calcineurin-Nuclear Factor of Activated T cells (NFAT). Genetic alterations of Ras isoforms or of genes in the Ras-MAPK pathway result in Ras-opathies, conditions frequently associated with cardiac hypertrophy or septal defects among other cardiac diseases. Several studies underline the potential role of H- and K-Ras as a hinge between physiological and pathological cardiac hypertrophy, and as potential therapeutic targets in cardiac hypertrophy and failure.

Research ethics review during the COVID-19 pandemic: An international study.

Research ethics review committees (ERCs) worldwide faced daunting challenges during the COVID-19 pandemic. There was a need to balance rapid turnaround with rigorous evaluation of high-risk research protocols in the context of considerable uncertainty. This study explored the experiences and performance of ERCs during the pandemic. We conducted an anonymous, cross-sectional, global online survey of chairs (or their delegates) of ERCs who were involved in the review of COVID-19-related research protocols after March 2020. The survey ran from October 2022 to February 2023 and consisted of 50 items, with opportunities for descriptive responses to open-ended questions. Two hundred and three participants [130 from high-income countries (HICs) and 73 from low- and middle-income countries (LMICs)] completed our survey. Respondents came from diverse entities and organizations from 48 countries (19 HICs and 29 LMICs) in all World Health Organization regions. Responses show little of the increased global funding for COVID-19 research was allotted to the operation of ERCs. Few ERCs had pre-existing internal policies to address operation during public health emergencies, but almost half used existing guidelines. Most ERCs modified existing procedures or designed and implemented new ones but had not evaluated the success of these changes. Participants overwhelmingly endorsed permanently implementing several of them. Few ERCs added new members but non-member experts were consulted; quorum was generally achieved. Collaboration among ERCs was infrequent, but reviews conducted by external ERCs were recognized and validated. Review volume increased during the pandemic, with COVID-19-related studies being prioritized. Most protocol reviews were reported as taking less than three weeks. One-third of respondents reported external pressure on their ERCs from different stakeholders to approve or reject specific COVID-19-related protocols. ERC members faced significant challenges to keep their committees functioning during the pandemic. Our findings can inform ERC approaches towards future public health emergencies. To our knowledge, this is the first international, COVID-19-related study of its kind.

Global inequity creates local insufficiency: A qualitative study of COVID-19 vaccine implementation challenges in low-and-middle-income countries.

INTRODUCTION: The COVID-19 pandemic has amplified pre-existing challenges to health promotion and care across the world, and particularly in low- and middle-income countries (LMICs). This qualitative study draws on data from a panel of immunisation experts and uses a novel framework of vaccine delivery domains to explore perspectives from those who live and work in these settings on the challenges to implementing COVID-19 vaccine programs in LMICs. METHODS: We conducted a thematic content analysis of 96 participant free text replies to questions from Round I of a three-round Delphi consensus study amongst global experts on COVID-19 vaccine implementation. RESULTS: Participant responses highlighted challenges to vaccine program implementation including issues related to equity; governance, decision-making, and financing; regulatory structures, planning, and coordination; prioritisation, demand generation, and communication; vaccine, cold chain, logistics, and infrastructure; service delivery, human resources, and supplies; and surveillance, monitoring, and evaluation. CONCLUSION: We reflect on our findings in light of global efforts to address vaccine inequity and emphasise three key areas salient to improving vaccination efforts during novel infectious disease outbreaks: 1) Ensuring safe and sustainable service delivery in communities and at points of care; 2) Strengthening systems for end-to-end delivery of vaccines, therapeutics, diagnostics, and essential supplies; 3) Transforming structural paradigms towards vaccine equity.

Evaluations of Continuing Health Provider Education Focused on Opioid Prescribing: A Scoping Review.

PURPOSE: Continuing health provider education (HPE) is an important intervention supported by health policy to counter the opioid epidemic; knowledge regarding appropriate program design and evaluation is lacking. The authors aim to provide a comprehensive understanding of evaluations of opioid-related continuing HPE programs and their appropriateness as interventions to improve population health. METHOD: In January 2020, the authors conducted a systematic search of 7 databases, seeking studies of HPE programs on opioid analgesic prescribing and overdose prevention. Reviewers independently screened the titles and abstracts of all studies and then assessed the full texts of all studies potentially eligible for inclusion. The authors extracted a range of data using categories for evaluating complex programs: the use of theory, program purpose, inputs, activities, outputs, outcomes, and industry involvement. Results were reported in a narrative synthesis. RESULTS: Thirty-nine reports on 32 distinct HPE programs met inclusion criteria. Of these 32, 31 (97%) were U.S./Canadian programs and 28 (88%) were reported after 2010. Measurements of changes in knowledge and confidence were common. Performance outcomes were less common and typically self-reported. Most studies (n = 27 [84%]) used concerns of opioid-related harms at the population health level to justify the educational intervention, but only 5 (16%) measured patient- or population-level outcomes directly related to the educational programs. Six programs (19%) had direct or indirect opioid manufacturer involvement. CONCLUSIONS: Continuing HPE has been promoted as an important means of addressing population-level opioid-related harms by policymakers and educators, yet published evaluations of HPE programs focusing on opioid analgesics inadequately evaluate patient- or population-level outcomes. Instead, they primarily focus on self-reported performance outcomes. Conceptual models are needed to guide the development and evaluation of continuing HPE programs intended to have population health benefits.

Identifying priority challenges and solutions for COVID-19 vaccine delivery in low- and middle-income countries: A modified Delphi study.

BACKGROUND: The rapid implementation of global COVID-19 vaccination programs has surfaced many challenges and inequities, particularly in low- and middle-income countries (LMICs). However, there continues to be a lack of consensus on which challenges are global priorities for action, and how to best respond to them. This study uses consensus-based methods to identify and rank the most important challenges and solutions for implementation of COVID-19 vaccination programs in LMICs. METHODS: We conducted a three-round modified Delphi study with a global panel of vaccine delivery experts. In Round I, panelists identified broad topical challenges and solutions. Responses were collated and coded into distinct items. Through two further rounds of structured, iterative surveys panelists reviewed and ranked the identified items. Responses were analyzed qualitatively and quantitatively to achieve consensus on the most important COVID-19 vaccine delivery challenges and solutions. RESULTS: Of the 426 invited panelists, 96 completed Round I, 56 completed Round II, and 39 completed Round III. Across all three rounds there was equal representation by gender, and panelists reported work experience in all World Bank regions and across a variety of content areas and organizations. Of the 64 initially identified items, the panel achieved consensus on three challenges and 10 solutions. Challenges fell under themes of structural factors and infrastructure and human and material resources, while solutions also included items within themes of communication, community engagement, and access and planning, processes, and operations. CONCLUSION: COVID-19 vaccine delivery is challenged by long-standing and structural inequities that disadvantage health service delivery in LMICs. These findings can, and should, be used by global health organizations to efficiently and optimally direct resources to respond to these key challenges and solutions.

Mal/adaptations: A qualitative evidence synthesis of opioid agonist therapy during major disruptions.

BACKGROUND: Opioid agonist therapy (OAT) has been severely disrupted by the COVID-19 pandemic. The risks of opioid withdrawal, overdose, and diversion have increased, so there is an urgent need to adapt OAT to best support people who use drugs (PWUD). This review examines the views and experiences of PWUD, health care providers, and health system administrators on OAT during major disruptions to medical care to inform appropriate health system responses during the current pandemic and beyond. METHODS: We conducted a systematic review and qualitative evidence synthesis. We searched three comprehensive datasets for qualitative and mixed-methods studies that examined OAT in the context of major disruptions such as natural disasters, and analyzed included studies using thematic analysis and the constant comparative method. We used conceptual frameworks of health systems resilience and adaptive systems to interpret our findings. RESULTS: We included 10 studies published between 2002 and 2020 that examined OAT in the context of hurricanes, earthquakes, and terrorist attacks. We organized our results into three themes: uncertainty, inconsistency, and vulnerability; regulatory inflexibility; and lack of coordination. The highly regulated but poorly coordinated systems of OAT provision lacked flexibility to adapt to major disruptions, thereby manufacturing vulnerability for both PWUD and health workers. CONCLUSIONS: OAT programs must be resilient and adaptable to face major disruptions while maintaining quality care. Our findings provide guidance to develop and implement innovative strategies that increase the adaptive potential of OAT programs while focusing on the needs of PWUD.

R&D during public health emergencies: the value(s) of trust, governance and collaboration.

In January 2021, Dr Tedros Adhanom Ghebreyesus, director-general of the WHO, warned that the world was 'on the brink of a catastrophic moral failure [that] will be paid with lives and livelihoods in the world's poorest countries'. We are now past the brink. Many high-income countries have vaccinated their populations (which, in some cases, includes third and even fourth doses) and are loosening public health and social measures, while low-income and middle-income countries are struggling to secure enough supply of vaccines to administer first doses. While injustices abound in the deployment and allocation of COVID-19 vaccines, therapies and diagnostics, an area that has hitherto received inadequate ethical scrutiny concerns the upstream structures and mechanisms that govern and facilitate the research and development (R&D) associated with these novel therapies, vaccines and diagnostics. Much can be learnt by looking to past experiences with the rapid deployment of R&D in the context of public health emergencies. Yet, much of the 'learning' from past epidemics and outbreaks has largely focused on technical or technological innovations and overlooked the essential role of important normative developments; namely, the importance of fostering multiple levels of trust, strong and fair governance, and broad research collaborations. In this paper, we argue that normative lessons pertaining to the conduct of R&D during the 2014-2016 Ebola epidemic in West Africa provide important insights for how R&D ought to proceed to combat the current COVID-19 pandemic and future infectious disease threats.

Beyond harm-producing versus harm-reducing: A qualitative meta-synthesis of people who use drugs' perspectives of and experiences with the extramedical use and diversion of buprenorphine.

INTRODUCTION: This review synthesizes the literature on the perspectives and experiences of people who use drugs to better understand motivations and behaviors related to the extramedical use and diversion of buprenorphine. Given the particular social construction of buprenorphine against methadone, and the centrality of concerns around extramedical use in delivering opioid agonist therapies, a focus on extramedical buprenorphine use can provide an important lens through which to analyze treatment for opioid use disorder. This review is framed within persistent tensions between potential harm-producing versus harm-reducing effects of extramedical use that have long been described for opioid agonist therapies. METHODS: The research team conducted a qualitative meta-synthesis based on a systematic search of eight databases as well as hand searching. The review includes all primary qualitative and mixed-methods studies related to the perspectives and experiences of people who use drugs on extramedical buprenorphine use. The study team carried out three rounds of qualitative coding using NVivo 12, and constructivist grounded theory and the constant comparative method informed the synthesis. RESULTS: The review includes twenty-one studies. Findings are organized into the following three themes: 1) the experiences of people who use drugs (PWUD) with extramedical use of buprenorphine and their motivations to engage in it (including the desire to self-medicate and achieve "stability", to manage ongoing use of other opioids, and to "get high"); 2) the relationship between extramedical use and formal medical opioid agonist therapy programs; and 3) the established drug economy of extramedical buprenorphine. CONCLUSIONS: The review identified varied and often divergent perspectives and experiences with extramedical buprenorphine use. An examination of the reported "normalizing" effects of extramedical buprenorphine suggests this practice as extending medicalized discipline beyond the clinical environment. Taken together, these findings identify a need to move beyond the tension of harm-reducing versus harm-producing effects toward forms of health care and promotion that focus on the needs, perspectives, and priorities of people who use drugs.

The ethical, social, and cultural dimensions of screening for mental health in children and adolescents of the developing world.

Despite their burden and high prevalence, mental health disorders of children and adolescents remain neglected in many parts of the world. In developing countries, where half of the population is younger than 18 years old, one of every five children and adolescents is estimated to suffer from a mental health disorder. It is then essential to detect these conditions through screening in a timely and accurate manner. But such screening is fraught with considerable ethical, social, and cultural challenges. This study systematically identifies, for the first time, these challenges, along with potential solutions to address them. We report on the results of an international multi- and inter-disciplinary three-round Delphi survey completed by 135 mental health experts from 37 countries. We asked these experts to identify and rank the main ethical, social, and cultural challenges of screening for child and adolescent mental health problems in developing nations, and to propose solutions for each challenge. Thirty-nine significant challenges emerged around eight themes, along with 32 potential solutions organized into seven themes. There was a high degree of consensus among the experts, but a few interesting disagreements arose between members of the panel from high-income countries and those from low- and middle-income nations. The panelists overwhelmingly supported mental health screening for children and adolescents. They recommended ensuring local acceptance and support for screening prior to program initiation, along with careful and comprehensive protection of human rights; integrating screening procedures into primary care; designing and implementing culturally appropriate screening tools, programs, and follow-up; securing long-term funding; expanding capacity building; and task-shifting screening to local non-specialists. These recommendations can serve as a guide for policy and decision-making, resource allocation, and international cooperation. They also offer a novel approach to reduce the burden of these disorders by encouraging their timely and context-sensitive prevention and management.

Ethical and scientific issues of nanotechnology in the workplace.

In the absence of scientific clarity about the potential health effects of occupational exposure to nanoparticles, a need exists for guidance in decisionmaking about hazards, risks, and controls. An identification of the ethical issues involved may be useful to decision makers, particularly employers, workers, investors, and health authorities. Because the goal of occupational safety and health is the prevention of disease in workers, the situations that have ethical implications that most affect workers have been identified. These situations include the a) identification and communication of hazards and risks by scientists, authorities, and employers; b) workers' acceptance of risk; c) selection and implementation of controls; d) establishment of medical screening programs; and e) investment in toxicologic and control research. The ethical issues involve the unbiased determination of hazards and risks, nonmaleficence (doing no harm), autonomy, justice, privacy, and promoting respect for persons. As the ethical issues are identified and explored, options for decision makers can be developed. Additionally, societal deliberations about workplace risks of nanotechnologies may be enhanced by special emphasis on small businesses and adoption of a global perspective.

Molecules linked to Ras signaling as therapeutic targets in cardiac pathologies

The Ras family of small Guanosine Triphosphate (GTP)-binding proteins (G proteins) represents one of the main components of intracellular signal transduction required for normal cardiac growth, but is also critically involved in the development of cardiac hypertrophy and heart failure. The present review provides an update on the role of the H-, K- and N-Ras genes and their related pathways in cardiac diseases. We focus on cardiac hypertrophy and heart failure, where Ras has been studied the most. We also review other cardiac diseases, like genetic disorders related to Ras. The scope of the review extends from fundamental concepts to therapeutic applications. Although the three Ras genes have a nearly identical primary structure, there are important functional differences between them: H-Ras mainly regulates cardiomyocyte size, whereas K-Ras regulates cardiomyocyte proliferation. N-Ras is the least studied in cardiac cells and is less associated to cardiac defects. Clinically, oncogenic H-Ras causes Costello syndrome and facio-cutaneous-skeletal syndromes with hypertrophic cardiomyopathy and arrhythmias. On the other hand, oncogenic K-Ras and alterations of other genes of the Ras-Mitogen-Activated Protein Kinase (MAPK) pathway, like Raf, cause Noonan syndrome and cardio-facio-cutaneous syndromes characterized by cardiac hypertrophy and septal defects. We further review the modulation by Ras of key signaling pathways in the cardiomyocyte, including: (i) the classical Ras-Raf-MAPK pathway, which leads to a more physiological form of cardiac hypertrophy; as well as other pathways associated with pathological cardiac hypertrophy, like (ii) The SAPK (stress activated protein kinase) pathways p38 and JNK; and (iii) The alternative pathway Raf-Calcineurin-Nuclear Factor of Activated T cells (NFAT). Genetic alterations of Ras isoforms or of genes in the Ras-MAPK pathway result in Ras-opathies, conditions frequently associated with cardiac hypertrophy or septal defects among other cardiac diseases. Several studies underline the potential role of H- and K-Ras as a hinge between physiological and pathological cardiac hypertrophy, and as potential therapeutic targets in cardiac hypertrophy and failure. Highlights - The Ras (Rat Sarcoma) gene family is a group of small G proteins - Ras is regulated by growth factors and neurohormones affecting cardiomyocyte growth and hypertrophy - Ras directly affects cardiomyocyte physiological and pathological hypertrophy - Genetic alterations of Ras and its pathways result in various cardiac phenotypes? - Ras and its pathway are differentially regulated in acquired heart disease - Ras modulation is a promising therapeutic target in various cardiac conditions.

Ethical and scientific issues of nanotechnology in the workplace.

In the absence of scientific clarity about the potential health effects of occupational exposure to nanoparticles, a need exists for guidance in decision making about hazards, risks, and controls. An identification of the ethical issues involved may be useful to decision makers, particularly employers, workers, investors, and health authorities. Because the goal of occupational safety and health is the prevention of disease in workers, the situations that have ethical implications that most affect workers have been identified. These situations include the a) identification and communication of hazards and risks by scientists, authorities, and employers; b) workers' acceptance of risk; c) selection and implementation of controls; d) establishment of medical screening programs; and e) investment in toxicologic and control research. The ethical issues involve the unbiased determination of hazards and risks, nonmaleficence (doing no harm), autonomy, justice, privacy, and promoting respect for persons. As the ethical issues are identified and explored, options for decision makers can be developed. Additionally, societal deliberations about workplace risks of nanotechnologies may be enhanced by special emphasis on small businesses and adoption of a global perspective.

Ethical and scientific issues of nanotechnology in the workplace

In the absence of scientific clarity about the potential health effects of occupational exposure to nanoparticles, a need exists for guidance in decisionmaking about hazards, risks, and controls. An identification of the ethical issues involved may be useful to decision makers, particularly employers, workers, investors, and health authorities. Because the goal of occupational safety and health is the prevention of disease in workers, the situations that have ethical implications that most affect workers have been identified. These situations include the a) identification and communication of hazards and risks by scientists, authorities, and employers; b) workers' acceptance of risk; c) selection and implementation of controls; d) establishment of medical screening programs; and e) investment in toxicologic and control research. The ethical issues involve the unbiased determination of hazards and risks, nonmaleficence (doing no harm), autonomy, justice, privacy, and promoting respect for persons. As the ethical issues are identified and explored, options for decision makers can be developed. Additionally, societal deliberations about workplace risks of nanotechnologies may be enhanced by special emphasis on small businesses and adoption of a global perspective.

Na ausência de evidência quanto a potenciais efeitos da exposição a nanopartículas sobre a saúde ocupacional, existe necessidade de orientação para os gestores a respeito dos riscos, perigos e dos possíveis controles. A identificação de questões éticas envolvidas é útil, particularmente para empregadores, empregados, investidores e autoridades de saúde, uma vez que o sentido e a meta da segurança ocupacional e de saúde é a prevenção de doenças para os trabalhadores. Essa situação inclui: (a) identificação e comunicação de riscos por cientistas, autoridades e empregadores; (b) aceitação dos riscos por parte dos trabalhadores; (c) seleção e implementação de controles; (d) estabelecimento de programas de detecção precoce; e (e) investimento em toxicologia e pesquisas de vigilância. A questão ética envolve determinação imparcial de riscos, não maleficência, autonomia, justiça, privacidade e promoção do respeito às pessoas. Identificadas e exploradas as questões éticas, várias opções se abrem ao gestor. Adicionalmente, deliberações societais acerca dos riscos no local de trabalho com nanotecnologia podem fundamentar a escolha por pequenos negócios dentro de uma perspectiva global.