Purely technical interventions aimed at enhancing evidence-informed decision-making (EIDM) have rarely translated into organizational institutionalization or systems change. A panel of four presentations at the Health Systems Global 2020 conference provides a basis for inference about contextual factors that influence the establishment and sustainability of institutional platforms to support EIDM. These cases include local structures such as citizen panels in Uganda, regional knowledge translation structures such as the West African Health Organization, global multilateral initiatives such as the “One Health” Quadrapartite and regional public health networks in South-East Asia. They point to the importance of political economy as well as technical capability determinants of evidence uptake and utilization at institutional, organizational and individual levels. The cases also lend support to evidence that third-party (broker and intermediary) supportive institutions can facilitate EIDM processes. The involvement of third-party supranational organizations, however, poses challenges in terms of legitimacy and accountability. The imperative to advance evidence-informed decision-making (EIDM) has never been greater . In an eIn this commentary, we aim to contribute to the debate on the role of institutions, organizational arrangements, and broader contexts in supporting EIDM in global health. Drawing on four cases derived from a panel discussion on this topic presented at the Sixth Global Symposium on Health Systems Research, we describe good practices and key challenges in EIDM as a basis for considering how institutional development can contribute to and inform more responsive global health policy and practice. The cases represent different contexts, and yet they all serve to illustrate the complexity of data sharing and evidence uptake, the importance of capabilities associated with the generation and use of evidence, and the role of other contextual determinants including political economy and the wider health sector infrastructure. We summarize the contextual characteristics, scope and key insights for each of the case studies in Table In the four sections that follow, we introduce and describe each of our cases—regional public health networks to facilitate data sharing in Southeast Asia, citizen panels to engage grassroots citizens in policy-making in Uganda, regional integration and capacity-building to support evidence-informed policy-making in West Africa, and multilateral collaboration for One Health in Africa. We close this commentary by weaving together the key insights, lessons and challenges that emerged from the four cases, and providing recommendations for improving EIDM in global health.www.gms-cdc.org). In addition, vertical programmes have been developed to strengthen regional response to specific diseases, including HIV [The Mekong subregion in Southeast Asia has historically been a hotspot for the emergence and transmission of infectious diseases. Over the past two decades, substantial progress has been made to strengthen disease prevention and control capacities. However, important regional challenges remain, including those associated with artemisinin-resistant malaria, avian influenza, tuberculosis and other endemic diseases that are less prominent on the global health agenda such as cholera and rabies . In recoding HIV , avian iding HIV  and malading HIV . While tOver time, these efforts have contributed to an unprecedented increase in the circulation of health data, information and expertise in the region, at times leading to joint outbreak investigations. However, a recent study of these networks also identified challenges to data sharing due to gaps between national information systems, different rules to govern the information flow inside and outside the countries and imbalances in technical capacities . As the In Southeast Asia, recent experiences in regional health cooperation illustrate significant involvement of third-party brokers such as the WHO regional offices, the ADB and the Association of Southeast Asian Nations (ASEAN). However, the institutional landscape is fragmented, with little coordination between overlapping initiatives funded by different donors . Today, This case describes the knowledge transfer work of the West African Health Organization (WAHO), which is a specialized health agency of the Economic Community of West African States (ECOWAS). During the past decade WAHO has become increasingly engaged in the promotion of evidence use for health policy-making at the national and regional levels, focusing particularly on strengthening the research use capacity of West Africa’s 15 national ministries of health –22. The Through the platform, WAHO’s research unit and the organization’s Member States work together to “coproduce” and implement tailored, context-sensitive intervention packages to address the specific knowledge transfer needs of individual countries. Interventions vary from in-depth capacity-building trainings on research communication and critical appraisal, and the establishment of networking fora to facilitate engagement and relationship-building between decision-makers, academics and other stakeholders, to the development of formal guidelines to support ministries of health in the complex process of accessing and (appropriately) applying evidence to decisions.However, while the importance of capacity strengthening, relationship-building and technical and procedural guidance should not be underestimated, a realist case study examining the development of WAHO’s KTP pointed to another factor of at least equal importance: institutions. WAHO’s research unit recognized that previous efforts to strengthen the use of evidence have often had disappointing results, and they argued that this was, at least in part, because of a failure to address issues at what is sometimes called the “institutional level” , 24. StuIn this spirit—and following much behind-the-scenes work by evidence champions within WAHO’s research unit—in 2017, the ECOWAS Assembly of Health Ministers unanimously approved a Resolution on the Use of Evidence, which acknowledged that “a significant amount of research is conducted and that very few findings are used in policy and practice” and called for the use of research evidence by Member States in “the development of health care policies, plans, standards and protocols” . Of courQuestions abound about appropriate approaches to engaging citizens and including their voices in policy-making, particularly in high-level policy processes. Citizens, unlike other stakeholders, may generally be less informed about a particular policy issue, or their voices may be unheard, especially with the use of approaches like citizen representatives, yet input from their lived experience is crucial to inform policy development and successful policy implementation and evaluation. In view of this, the Center for Rapid Evidence Synthesis (ACRES) at Makerere University, Uganda, piloted an experimental project involving citizen panels as a platform for empowering citizen to participate in high-level policy-making processes.ACRES was built with the aim of supporting policy- and decision-making with high-quality, relevant and timely evidence. It used citizen panels to provide an evidence-informed response to Uganda’s Education Service Commission in its consideration of policy reform options related to the teachers’ professional code of conduct . OrdinarBecause citizens may lack detailed information about the policy problem, the first panel allowed them to acquire and process knowledge that would permit meaningful contribution to the debate. This knowledge was applied in the second panel in which they engaged with the problem and contributed their views about potential policy solutions.Most participants were keen to be involved and contribute their views and experiences. There was a response rate of 89% (16 out of 18 invitees) for the first panel and 87.5% (14 of the 16 participants from the first panel) for the second panel. Citizens’ engagement increased in the second panel, as they reported feeling more at ease and more valued simply by being invited to the process a second time. Organizing a second panel, therefore, was crucial to enhance trust and build confidence in the participants. What emerged clearly was the importance of giving citizens adequate background information and time to understand the policy options and their wider implications. However, this experience also showed that spontaneous and unbiased feedback from participants must be encouraged throughout the process, with minimal external “control” and direction (including control from the panel moderators).In sum, this case highlights the value of citizen panels as an effective method to enable democratic participation in decision-making processes and therefore increase their legitimacy. Following this experience, further citizen panels were convened to inform other policy processes, including community management of the follow-up phase of multidrug-resistant tuberculosis (MDR-TB) in Uganda. Based on findings from a study designed to describe the adherence patterns of MDR-TB patients undergoing directly observed therapy (DOT) supervision at two health facility categories during an intensive phase of treatment , citizenDespite the great promise of these exercises, questions remain about their sustainability and institutionalization. Thus, ACRES and partners are involved in assessing this methodology further to determine contextual factors that affect its effectiveness, uptake and acceptance in different settings and contexts.Events ranging from the 2014–2016 Ebola virus disease outbreak in West Africa to the ongoing global novel coronavirus (COVID-19) pandemic underscore the importance of focusing on the intersection of animal, human and ecosystem health, or One Health. The One Health quadripartite, a collaboration between the Food and Agriculture Organization (FAO), Organization for Animal Health (OIE), the United Nations Environment Programme (UNEP) and WHO, provides Member States normative guidance for evidence-informed policy and programming with emphasis on sub-Saharan Africa since 2019, with the inclusion of UNEP in 2022 . DespiteAs part of the United Kingdom government’s support for strengthening pandemic preparedness and response, Tackling Deadly Diseases in Africa (TDDA) is a United Kingdom Foreign, Commonwealth & Development Office  and political economic analysis (PEA) in Cameroon, Chad, Côte d’Ivoire, Mali, Niger and Uganda to assess alignment of sectoral policies in each country as well as patterns across the six countries. A problem-driven PEA identified the major actors, incentives and interests in each country that shape space for change. These analyses informed mapping of the intra- and inter-sectoral challenges as a basis for identifying opportunities for bridging observed performance gaps.Findings from these analyses revealed a need for capacity-strengthening within and across sectors. Underinvestment in institutions and systems led to gaps in the structures supporting evidence-based policy and programme alignment . DivergeThese analyses also identified opportunities for subtle realignment of inter-sectoral engagement that could contribute significant impact. Shifts in country structures for coordination, for example, rotation among participating ministries, helped ensure more response programming and greater political buy-in . Fuller The case examples discussed in this paper are drawn from diverse geographical and cultural contexts—from West and Central Africa to Uganda to South-East Asia—and a variety of decision-making venues—from regional bureaucracies and national governments to local communities. Yet, some common threads run through these stories, providing lessons that can be used to inform the development of well-designed institutional platforms for linking knowledge and action for health.First, the cases highlight and contribute to the understanding that supply-side and demand-side factors have to be addressed in equal measure in evidence-informed health policy and practice. Early efforts to link evidence with policy tended to emphasize the supply side, with researchers being encouraged to gain skills to push their findings into decision-making . HoweverSecond, the cases also highlight the importance of institutional brokering structures that serve as intermediaries. These intermediaries are crucial in filling in knowledge, skill and resource gaps, for example, evidence synthesis skills and time, that the demand and supply sides may be missing to enable optimal engagement and exchange. This in turn highlights the need for both individual and institutional capacity-strengthening to provide sustained and sustainable structures and systems for data and other evidence sharing and synthesis, analysis and utilization.Third, the cases also provide a better understanding of the role of knowledge brokerage, especially as performed by institutions . While the traditional roles of knowledge generators (like academics and other researchers), and intended users (like policy-makers), have been well defined, the role of knowledge brokers, entrepreneurs and other intermediaries has been less clearly explored and understood , though While the case studies reflect a set of substantially different settings, a number of additional common themes are apparent. First, context is everything. While global norms and guidelines to facilitate the sharing and uptake of evidence in health policy and practice are increasingly available, recommendations and best practices are often decontextualized or depoliticized, with insufficient consideration of the underlying system of institutions, structures and norms which can direct and shape EIDM processes. This may be influenced by approaches to education and training that encourage simplistic and overly broad notions of research generalizability. However, as we have seen, a better understanding of context is not a secondary consideration, but is central to determining whether, how and what kind of evidence is useful for informing policy-making, and the institutional processes and structures most likely to facilitate its uptake.Second, political economy matters. The politics of evidence is well established , 44. Howmeans to the ends of improving the functioning, fairness and responsiveness of health systems and, ultimately, achieving the goal of longer and healthier lives. Evidence use in policy-making can take many forms and serve a number of functions, including instrumental problem-solving, learning and enlightenment, and providing ammunition for political debate and policy deliberation [Third, the imperative of achieving better health for all must stay at the centre of institutional knowledge transfer efforts. The targeted outcomes of these institutional measures—from increased evidence use by decision-makers, to improvements in data-sharing practices and greater citizen engagement in policy processes—are not just ends in themselves, but possible beration . Many—ifThe methods applied here also allow us to challenge some of the known and applauded approaches in EIDM or improve them. For example, the use of citizen panels challenges the use of citizen representatives—a widely used approach—where research has even found that it leaves those represented less informed and not much more empowered, may distort their input along the knowledge transfer continuum, and is affected by their relationship with leadership .Lastly, a focus on the importance of institutions should not obscure the fact that institutions are complex adaptive systems, and therefore unintended consequences are inevitable. Purposive intervention into the workings of complex social systems always produces unanticipated effects ; instituThese case examples spoke to a variety of institutional platforms—both organizational and regional—to enhance EIDM, and yet some important common lessons emerged, pointing to three significant tendencies in the uptake of evidence-informed policy. Although embedded in different contexts, these cases illustrate a continuum of key principles highlighting the complexity of data sharing and evidence use, the crucial role of capabilities associated with evidence generation and use, and other circumstantial determinants, including political economy, the wider health sector infrastructure, and the institutional context. Together, these observations highlight the importance of assessing other contextual domains of evidence—history, social and political change, and institutional alignment—in efforts to advance evidence-informed policy. They also point to the importance of brokers to marshal these allied domains and the limitations of a purely technical approach to EIDM. Most importantly, these stories reveal that capacity-building interventions and other technical solutions, while important, cannot be expected to generate sustainable improvements in EIDM in the absence of meaningful institutional change.


Clinical guideline development often involves a rigorous synthesis of evidence involving multidisciplinary stakeholders with different priorities and knowledge of evidence synthesis; this makes communicating findings complex. Summary formats are typically used to communicate the results of evidence syntheses; however, there is little consensus on which formats are most effective and acceptable for different stakeholders.This mixed-methods systematic review (MMSR) aimed to evaluate the effectiveness and acceptability (e.g. preferences and attitudes and preferences towards) of evidence synthesis summary formats for GDG members. We followed the PRISMA 2020 guideline and Joanna Briggs Institute Manual for Evidence Synthesis for MMSRs. We searched six databases  for randomised controlled trials (RCTs), RCTs with a qualitative component, and qualitative studies. Screening, data extraction, and quality appraisal were performed in duplicate. Qualitative findings were synthesised using meta-aggregation, and quantitative findings are described narratively.n = 64) and tailor content for different end users (n = 24).We identified 17,240 citations and screened 54 full-text articles, resulting in 22 eligible articles (20 unique studies): 4 articles reported the results of 5 RCTs, one of which also had a qualitative component. The other 18 articles discussed the results of 16 qualitative studies. Therefore, we had 5 trials and 17 qualitative studies to extract data from. Studies were geographically heterogeneous and included a variety of stakeholders and summary formats. All 5 RCTs assessed knowledge or understanding with 3 reporting improvement with newer formats. The qualitative analysis identified 6 categories of recommendations: ‘presenting information’, ‘tailoring information’ for end users, ‘trust in producers and summary’, ‘knowledge required’ to understand findings, ‘quality of evidence’, and properly ‘contextualising information’. Across these categories, the synthesis resulted in 126 recommendations for practice. Nine recommendations were supported by both quantitative and qualitative evidence and 116 by only qualitative. A majority focused on how to present information .The online version contains supplementary material available at 10.1186/s13012-022-01243-2. Contributions to the literatureSummaries are often used to communicate evidence synthesis findings; however, there is no consensus on the most effective way to communicate or what works for different audiences.This review explored the effectiveness and acceptability of different summary formats for different audiences.We identified recommendations to help evidence synthesis producers better communicate to different audiences. These include guidance on formatting, tailoring content for end users, instilling trust in the work, establishing and helping knowledge requirements, detailing the quality of included studies, and properly contextualising findings.Results can guide the creation of summary formats better tailored to end user’s needs).Clinical guidelines are an important tool for the practice of evidence-based medicine. Often involving rigorous syntheses of the best available evidence, clinical guidelines (CG) aim to improve healthcare in a cost-effective manner by assisting decision-making for clinicians and policymakers –3. GuideIn creating guidelines, GDGs need to consider evidentiary factors  alongside complex trade-offs between competing benefits and harms, side effects, and risks of various disease management options . The metEvidence synthesis summaries come in a variety of different formats such as one-page plain language reports, policy briefs, summary of findings tables, visual abstracts or infographics, and more. While summaries may be more easily understandable than complete systematic reviews , 13, revIt is critical to identify the best summary formats to ensure the best possible communication within multidisciplinary GDGs as they interpret evidence syntheses and develop clinical guidelines to support evidence-based decision-making . This stWe conducted a MMSR according to a preregistered and published protocol , 20, folEligible studies were included if they were randomised controlled trials (RCTs) comparing alternative summary formats for evidence syntheses, RCTs with a supplemental qualitative component, or qualitative studies such as focus groups, interviews, or open-ended surveys. Per our protocol, we restricted to these study designs as we chose to focus on the performance and impact of summary formats in optimal settings, and RCTs are the most appropriate design to evaluate effectiveness . We did Eligible participants were those who could be involved in clinical guideline development groups  and outcomes related to effectiveness, acceptability (e.g. views and preferences) of summary formats. We excluded studies involving students, journalists, or the general public as communication to these populations is more complex. Members of the general public were included if they were a patient representative involved in a guideline development group. Use of evidence synthesis summary formats to inform clinicians and patient’s decision-making regarding individual care was not the focus of this review .We searched six databases, Ovid MEDLINE, Embase MEDLINE , APA  PsycINFO, CINAHL , Web of Science, and Cochrane Library, from inception to April 20, 2021  on one article, required changes were discussed, and the final data extraction was performed using this form and the TiDiER checklist . Study qAs we did not have a sufficient number of quantitative studies included, we were unable to perform a meta-analysis, the Harboard test for publication bias , Egger’sQualitative findings were synthesised using the pragmatic meta-aggregation approach which allows a reviewer to present findings of included studies as originally intended by the original authors , 32. MetNVivo 12 was used to analyse results from primary qualitative studies and accompanying illustrations . One autTo synthesise findings from both qualitative and quantitative evidence, we followed the JBI guidance for MMSR and used a convergent segregated approach as we conducted separate quantitative and qualitative syntheses and then integrated the findings of each , 36. We n = 17,185). The yield rate is slightly lower than previous estimates likely due to the breadth of stakeholders, summary formats, and outcomes of interest . In two small RCTs, Rosenbaum et al. found that the inclusion of a SoF table in a review improved understanding and rapid retrieval of key findings compared to reviews with no SoF table   , while C= 0.001) . Opyio eto 0.99) . In two to 0.99) . The secCI: 28.0–36.0) vs. PLS: 22.5 (19.0–27.4); doctors median infographic score: 37.0 (26.8–41.3) vs. PLS: 24.0 (21.3–27.2)] [Two studies assessed satisfaction Table . Buljan 3–27.2)] . Carasco3–27.2)] .MD 2.8, SD 1.6) . Th. Th76]. Our results provide valuable information that can be used to improve existing formats and inform future research aimed at developing more effective evidence synthesis summary formats. The nine recommendations with mixed-methods support can be considered essential to consider for any summary format producer. The additional 20 items with 3 or more evidence streams supporting them can be considered as desirable, with further exploration needed into the full set of 126 items. Future research should further explore these proposed recommendations amongst the different guideline development group members to explore which items are particularly important for which stakeholder. Our research team plans to conduct a prioritisation exercise for these recommendations so we can use them as guidance for focus group workshops with GDG members. Furthermore, other mediums of summary formats not identified in this review could be explored further such as the use of podcasts or video abstracts or summaries.Additional file 1. PRISMA checklist.Additional file 2. Search strategy results.Additional file 3. Data extraction workbook.Additional file 4. Quantitative findings.Additional file 5. Qualitative synthesis recommendations.Additional file 6: Figures 6, 7, and 8. Recommendations for Practice.Additional file 7. Qualitative synthesis recommendations (with at least 3 supporting studies or mixed methods support).


Evaluating a learning health system (LHS) encourages continuous system improvement and collaboration within the healthcare system. Although LHS is a widely accepted concept, there is little knowledge about evaluating an LHS. To explore the outputs and outcomes of an LHS model, we evaluated the COVID‐19 Evidence Support Team (CEST) in Saskatchewan, Canada, an initiative to rapidly review scientific evidence about COVID‐19 for decision‐making. By evaluating this program during its formation, we explored how and to what extent the CEST initiative was used by stakeholders. An additional study aim was to understand how CEST could be applied as a functional LHS and the value of similar knowledge‐to‐action cycles.Using a formative evaluation design, we conducted qualitative interviews with key informants (KIs) who were involved with COVID‐19 response strategies in Saskatchewan. Transcripts were analyzed using reflexive thematic analysis to identify key themes. A program logic model was created to represent the inputs, activities, outputs, and outcomes of the CEST initiative.Interview data from 11 KIs were collated under three overarching categories: (1) outputs, (2) short‐term outcomes, and (3) long‐term outcomes from the CEST initiative. Overall, participants found the CEST initiative improved speed and access to reliable information, supported and influenced decision‐making and public health strategies, leveraged partnerships, increased confidence and reassurance, and challenged misinformation. Themes relating to the long‐term outcomes of the initiative included improving coordination, awareness, and using good judgment and planning to integrate CEST sustainably into the health system.This formative evaluation demonstrated that CEST was a valued program and a promising LHS model for Saskatchewan. The future direction involves addressing program recommendations to implement this model as a functional LHS in Saskatchewan. As a result, the CEST was established with an oversight committee consisting of members from the Emergency Operations Committee (EOC), USASK, and the Public Health Incident Command Center (PHICC). The EOC, Saskatchewan's COVID‐19 decision‐making body, used synthesized evidence from CEST to support decisions at the pandemic's onset where there was little or conflicting evidence.2.2A formative evaluation design was chosen to assess the experiences of Saskatchewan health system leaders who used CEST during the COVID‐19 pandemic. Used to understand and improve implementation during program development,2.3We invited 13 key informants (KIs) who were involved in various public health strategies for the Saskatchewan COVID‐19 response to be interviewed for the study. Participants were selected if they were primary users of CEST and had a role in decision‐making during the pandemic. Using a semi‐structured interview guide, a researcher (SW) asked the participants about the extent to which they used CEST in their work or practice, how CEST may have affected their decision‐making or provided value to their practice, whether CEST facilitated communication between health system partners, and what future application they envisioned. Prior to the interview, participants were briefed on the study objectives and written or verbal informed consent was obtained. Interviews were conducted between September and November 2021 via WebEx or Zoom and lasted an average of 15 min (7‐22 min). Following the interview, the recordings were transcribed verbatim by the same researcher and housed in NVivo (Version 12) for subsequent analysis. The protocols for this study were reviewed and approved for an Ethics Exemption by the USASK Behavioural Research Ethics Board for the purpose of program quality improvement (TCPS Article 2.2).2.4Guided by our three research aims, we conducted a reflective thematic analysis.3n = 5) and Saskatoon (n = 5), and an area in southern Saskatchewan (n = 1). Twelve themes were identified from the interviews: three associated with outputs, five associated with short‐term outcomes, and four associated with long‐term outcomes of the program. The long‐term outcomes are summarized using key informant recommendations for the future application of CEST.Of the 13 participants that were contacted, 11 (84.6%) agreed to be interviewed. The informants  included four medical health officers, three SHA directors, two physician leaders, an epidemiologist, and one chief nursing officer. Participants were from Saskatchewan's two largest cities, Regina (3.1Various participants discussed their experience with the CEST deliverables and how they were used in their practice. Three main output‐related themes were identified: 1) the production of evidence in a time of uncertainty, (2) the dissemination of evidence to stakeholders, and (3) the establishment of transparent knowledge‐sharing .The outputs of CEST were developed in response to this need and consisted of the rapid generation of COVID‐19 reviews, comprehensive summary reports, the delivery of reports to stakeholders, and the creation of an online dashboard.3.1.2The KIs emphasized the dissemination of evidence as a key deliverable from CEST and how it was used in practice. The team synthesized and condensed articles and documents from a variety of databases that were published by trusted organizations and institutions. Initially, CEST was only intended for internal use via the EOC and later became available to a wider audience within the SHA and MoH. As one participant described, “having the EOC as a vehicle to send out those requests in a written format, and the EOC receiving them, [evidence] got disseminated to a wider audience, and it did get that level of system‐learning and sharing.” (KI 9) Participants noted that as the pandemic progressed, the COVID‐19 rapid reviews were used for numerous public health strategies. CEST synthesized evidence around the impact of public health measures, best practices from other provinces, and vaccine roll‐out strategies. This included incentives for vaccine uptake and booster doses, inquiries for managing personal protective equipment (PPE), the recommended intervals between vaccine doses, breakthrough cases, sequencing, and information relating to vulnerable groups. Some participants also requested information about long COVID, the effectiveness of vaccines, and the epidemiology of variants, which became “evergreen” reviews that were regularly updated.3.1.3By building an online repository of completed COVID‐19 reviews, CEST provided a new infrastructure for knowledge to be shared across the provincial health authority. Several participants noted the utility of this resource and appreciated the convenience of returning to previous rapid review summaries. One KI described the value of a “synthesis of evidence … to present in a consumable fashion whereby decision‐makers could review it in a rapid fashion and come up with a decision.” (KI 1) Another KI emphasized how the dashboard added a layer of transparency by providing a central location for the reviews to be accessed any time.3.2Participants discussed several short‐term outcomes when asked about their experiences with CEST. Five themes were identified: (1) increased speed of rapid reviews, 2) increased access to reliable evidence, (3) influenced decision‐making, (4) increased confidence and reassurance, and (5) leveraged partnerships. Exemplar quotes are described in Table  increase3.2.1The urgency and rapid spread of COVID‐19 necessitated faster review and synthesis of the evidence compared to traditional research timelines. In doing so, it reduced the lag time between research synthesis and adoption into practice. One informant emphasized the speed of CEST, “The timelines for these evidence reviews, in retrospect, when I think back to it, we would ask for this information, and we'd give a 24‐to‐48‐h timeline for return. That's an incredible feat when you think about it… Quite clearly, the responsiveness of the Think Tank was excellent … the volume of review of evidence and the utility of that was equally amplified” (KI 1). Another had a similar observation, “One of the strengths of the team was the rapid response and the just‐in‐time information. I think it was very valuable to have that kind of rigor.” (KI 10) Other KIs mentioned a prompt turnaround time: “I can say that the rapidity with which evidence and opinion is now going from a clinical question or a pandemic‐related or COVID‐related question and becoming published is something I've never seen in my career as a physician or clinician.” (KI 1) Another emphasized, “[the CEST reviews] were really beyond our normal standard capacity, and we were looking for better ways.” (KI 9).3.2.2Early in the pandemic, KIs recalled the difficulty of navigating the amount of emerging information on COVID‐19. One KI described how CEST gave them access to the “right information … in the right [amount of] time.” (KI 10) Others described the efficiency of the central area for the evidence reviews, “having access to an informal way to get information that's relevant for the work that you do has been really valuable.” (KI 6). CEST was able “to synthesize the information out there and bring it to the organization in a way that can make it operational” (KI 11), providing access to a resource that was previously unavailable.Several participants mentioned how the rapid reviews provided credible evidence and were useful for communication purposes. One informant remarked, “how I use[d] the information in practice was to inform my communication with others to link it back to evidence” (KI 3). Participants emphasized that this was useful to challenge misinformation throughout the pandemic.3.2.3Before we had a provincial masking mandate, there was a lot of concern about: how would we determine mask exemptions? How would we manage those? Who should be mask exempt? And what is the evidence behind this? So, I turned to the Think Tank to ask them to do a rapid review on the efficacy of masking to decrease transmission of COVID‐19. We used that information directly to create guidelines for our clinicians. (KI 1).Overall, several informants said the CEST reviews played an important role in guiding leaders and influencing decision‐making. As one participant stated, “it did inform our decision‐making across the board.” (KI 1) CEST reviews provided evidence to the Clinical Expert Advisory group which informed the EOC and a COVID‐19 modeling team who were able to integrate the evidence with local and national data. One KI noted, “we used the information from the evidence reviews to determine the benefit on the model, and we adjusted it for Saskatchewan context.” (KI 8) A key informant (KI 4) mentioned how CEST reviews supplemented knowledge for Saskatchewan specific decisions. Another recalled how some decisions from an operational perspective in Saskatchewan had not yet been made at the national level (KI 6). Some informants also discussed how the evidence‐informed decisions by both formal and informal consultation with CEST. These methods included accessing the online repository, sharing reviews in EOC and Clinical Expert Advisory meetings, or by distributing reviews between colleagues through email. This information directly informed practice, as one KI stated:The KIs described how access to the CEST deliverables guided pandemic recommendations, the vaccine roll‐out campaign, guidance around PPE, vaccine hesitancy, and the implementation of public health programs. One key informant noted how the reviews guided proactive approaches to the vaccine booster rollout: “[CEST has] been really key in helping us get the international summary and international review of what people are seeing in other countries that's going to help us inform good decision‐making prior to national bodies making those decisions. We're rolling out the booster campaign now.” (KI 6) Another participant, who used the evidence reviews for the COVID‐19 vaccine implementation, commented on how it added value to their work, “[The Think Tank] always served the purpose of how we can use the data to make our strategy better.” (KI 5).3.2.4Having that background to know that there were evidence‐based recommendations gave me the confidence to be able to speak as a [leader], that we were following best evidence going forward and then I was able to communicate that to others. (KI 3)Some KIs expressed that evidence‐based reviews from CEST gave them a sense of reassurance and confidence to make decisions. Receiving relevant and timely information was valuable at decision‐making tables and in day‐to‐day practice. As one participant described:3.2.5Several participants commented on how the formation of CEST was a collaborative effort and leveraged partnerships with colleagues. The CEST initiative brought together librarians, clinician‐scientists, and academics who contributed their unique skills to support the response. Another KI said, “The Think Tank was quite helpful in providing the long COVID evidence review, but also in bringing together the right people to discuss long COVID and to try to position the SHA in an advantageous position when considering how to deal with long COVID” (KI 1), emphasizing that the Think Tank provided a foundation for a “best evidence approach” to healthcare needs. The research and clinical expertise of the team were useful to create comprehensive reports that were commonly shared among colleagues. A participant noted how CEST was circulated “with all [their] Medical Health Officer colleagues, [which] definitely stimulated conversation.” (KI 5).3.3All participants agreed that there could be a future application of the CEST initiative and suggested several recommendations. These were incorporated in four prominent themes, (1) strengthening collaboration to reduce duplication, (2) upgrading system components, 3) addressing limitations within research timelines, and (4) continuing to implement CEST as an LHS  Another reaffirmed this statement, “I think it was a real disconnect and a miss that our teams weren't more closely connected.” (KI 7) Strengthening the network between CEST and the data modeling team would help bolster the expertise of both.3.3.2To improve the awareness of CEST and the online dashboard, a participant recommended creating updates or an alert to notify when new evidence is available. Another KI suggested using infographics or tools to convey quick key messages and connect with the operational side of the health system (KI 7).3.3.3Research timelines don't necessarily line up with our operational timelines. As much as we like to, as a system, say that our decisions are evidence informed, often decisions are made without research, because it just takes so long to do research… the evidence reviews seem to be a bit delayed. And we also know, it's just the nature of research. (KI 7)Although CEST provided information relevant to pressing clinical and policy questions, two participants also noted that adjusting the rapid review evidence to a Saskatchewan context was challenging. Given that CEST only accessed published peer‐reviewed or grey literature, Saskatchewan‐specific data was not always contextualized with the review findings. Therefore, not all questions could be fully answered due to time constraints and the availability of evidence. One informant emphasized this outcome and how academia does not always meet desired timelines:3.3.4I could see a real close tie in terms of developing clinical standards going forward, not just related to COVID, it might not be on every clinical standard, but there is potential that a resource like the Think Tank could be reviewing upcoming questions of interest and help inform where we need to go with clinical standards, clinical appropriateness, that work, or there could be other linkages. (KI 3)Similarly, one participant mentioned that using CEST to gather information on relevant practices and models that can be applied in Saskatchewan was more important than simply generating more research. “We don't need a whole bunch more research. What we need is to be really well informed about the best practices that are out there and what has changed since they've been relevant … there is so much best practice in healthcare that's never implemented.” (KI 6) Another KI reiterated: “I do believe that it would be valuable to have that just‐in‐time information available for clinical decision‐making and administrative decision‐making as well…. There is value moving forward and hopefully the evidence from this discussion and others will help to point that it is a valuable and useful tool.” (KI 10).All participants agreed the program would be useful when asked about how CEST could be applied in the future, given that nothing currently exists to replace the role it can have in the health system: “I think it would be short sighted, and I think that we would not have a good foundation for new programs, or adjustment of programs that need to become better.” (KI 1) One participant (KI 10) recommended that implementing CEST sustainably into the health system would require good judgment and planning with research questions that are carefully considered. Likewise, some participants mentioned how health system leaders need to choose wisely in a system with limited resources and understand the coordination of the team to ensure it is a sustainable investment moving forward. Leveraging other skillsets within the health system where would also strengthen the capacity of the initiative. Another participant noted how health systems need “evidence‐based decisions about what we're investing in when it's one investment versus another.” (KI 3) Importantly, participants commented on how this initiative could support other health system needs beyond COVID‐19:4Despite a need for efficient and cost‐effective LHSs, there are only few high quality studies published about LHS implementation and evaluation.While all KIs agreed that the CEST could have future applications in the health system, several recommendations were made to help improve the initiative and achieve long‐term outcomes. To implement sustainably, factors such as limited funding and resources, coordination gaps, and optimizing applicability beyond COVID‐19 would need to be considered. This finding is important considering there has been wide support and encouragement to implement LHSs well before the COVID‐19 pandemic.4.1Our study has several limitations, including a small sample size of KIs who were the primary users of CEST. However, given the relatively small population of Saskatchewan (1.17 million), we were able to interview informants who had the most relevant experience using CEST during the pandemic response. Because the program was implemented and evaluated in a Saskatchewan‐specific context, our results may not be generalizable to other LHSs. Given the rapidly changing landscape, not all of the KIs were aware of the prioritization process that was used by the EOC. Considering the resources available at the time, CEST would have been quickly overwhelmed had the prioritization process been expanded. Gathering support from stakeholders5This formative evaluation explored user experiences with a COVID‐19 knowledge‐to‐practice initiative to assess its outputs and outcomes and describe how it might serve as a functional LHS in Saskatchewan. By conducting KI interviews, we found that implementing an LHS was valued as a sustainable initiative at a provincial level in Saskatchewan. Through the evaluation of an LHS initiative, users and collaborators can understand whether a program has the desired outcomes or not. Therefore, this formative evaluation provided an opportunity to improve the implementation of an LHS initiative.This study was funded by the College of Medicine Research Award (CoMRAD), University of Saskatchewan. Grant/Award number: 353905.The authors declare that there is no conflict of interest.


Macrophage activation syndrome (MAS) is a severe life-threatening hyperinflammatory state with uncontrolled activation and proliferation of macrophages and T-lymphocytes. MAS has variable causes and risk factors. Early diagnosis and optimum management could be lifesaving.Our aim was to develop a consensus, evidence-based recommendations for the diagnosis, evaluation, and treat-to-target management of pediatric MAS.This study was carried out to achieve an Egyptian expert consensus on a treat-to-target management strategy for MAS using the Delphi technique. The multistep process strategy was used in developing a consensus, evidence-based treatment guidelines for MAS, started by developing 7 key clinical questions by a scientific committee according to the Patient/Population, Intervention, Comparison, and Outcomes (PICO) approach. The core leadership team identified pediatric rheumatology clinicians and researchers throughout Egypt. To generate evidence for MAS management, an evidence-based, systematic literature review was done. To obtain a consensus, the Delphi procedure (3 rounds) was used.Twenty-three expert panel participated in the 3 rounds with a response rate of 100%. A total of 19 recommendations, categorized into 2 sections (11 in the diagnosis section and 8 in management), were obtained. The agreement with the recommendations (ranks 7–9) ranged from 86.9 to 95.7%. The consensus was reached  on all the clinical standards. Algorithms for management have been also developed.This was an expert, consensus recommendation for the diagnosis and treat to target of MAS, based on the best available evidence and expert opinion. The guidelines fill a gap in the literature as it presents a T2T approach for MAS. Macrophage activation syndrome (MAS) is also considered a type of secondary hemophagocytic lymphohistiocytosis (sHLH) associated with rheumatological diseases . MAS is Similar to its pathogenesis, treatment of MAS has been a matter of controversy. Parenteral treatment of high doses of corticosteroids has typically been used to treat MAS; nonetheless, occasional fatalities have been seen even among patients receiving high doses of corticosteroids. High-dose intravenous immunoglobulins, cyclophosphamide, plasma exchange, and etoposide have all been used with conflicting results –8.Despite the fact that early diagnosis is associated with better outcomes, early detection of MAS remains a challenge. This has been attributed to the lack of a single pathognomonic trait or even a set of universal diagnostic criteria for MAS. Similarly, early management is a true life-saving competition . There aThe study design was developed using scientific evidence and consensus, which was based on both existing scientific evidence and clinical experience. The purpose of this multistep method was to develop a clinical gold standard for MAS treat-to-target management in children using the “Clinical, Evidence-based, Guidelines” (CEG) initiative protocol . The evidence-based component of the manuscript adhered to the preferred reporting items for systematic reviews and meta-analyses criteria for systematic review publication . The EgyIt is made up of four professionals with backgrounds in pediatric rheumatology, inflammatory arthritis, and macrophage activation syndrome. The core team was involved in managing and coordinated the work of the team; assisted in the development of the project’s scope and initial Patient/Population, Intervention, Comparison, and Outcomes (PICO) clinical questions; came to an agreement on the key questions to be included in the guidelines; nominated the expert panel; and drafted the manuscript.The target population, categorization criteria, the intervention, diagnostic test, or exposure under investigation, the comparison(s), and the outcomes used to quantify efficacy, effectiveness, or risk were all defined by a set of structured key questions. The following methods were used to collect evidence to answer the clinical questions: formulation of clinical questions, structure of questions, search for evidence, critical evaluation and selection of evidence, presentation of results, and recommendations. The systematic literature search and, as a result, clinical care standards are based on these questions, as indicated in Table The literature review was carried out with the help of a methodology expert, under the supervision of an experienced literature review consultant, and was based on specific research topics relating to the diagnosis and treatment of MAS. The team finished the literature search , data abstraction, and evidence quality evaluation . FollowiThe PICO questions Table  were useRelevant studies were chosen using inclusion and exclusion criteria applied to the literature found using the search methodology.Articles included were systematic reviews, randomized controlled trials (RCTs), uncontrolled trials, and observational studies including cohort, case-control, and cross-sectional studies.Conference abstracts, commentaries, editorials, and non-evidence-based personal/narrative reviews were excluded.The core leadership team nominated 23 participants. The criteria for their selection included practice in the Egyptian Health System, professional knowledge, and experience in the field of pediatric rheumatology (minimum 8 years) especially including management of inflammatory arthritis and macrophage activation syndrome. The expert panel contributed in creating the scope of the project, refining the PICO questions, and voting on the recommendations by actively participating in scientific research on pediatric rheumatic disorders.To aid in the standardized identification of the guideline components, a structured template was created based on the answers to the structured key questions and the literature research. For each guideline component, the format in which the recommendations/information will be presented and extracted has been determined.The Delphi method is a structured method for gathering vital information about a certain issue that is extensively used. It is predicated on the notion that group projections are more accurate than individual forecasts. The Delphi method’s goal is to build consensus forecasts from a group of experts in a structured iterative manner. Its methodology is based on a succession of “rounds” of questionnaires sent to experts. The Delphi method generally involves the following stages: (1) A group of experts is gathered together. (2) Forecasting tasks/challenges are assigned to professionals and distributed. (3) Experts provide preliminary forecasts and justifications. In order to provide feedback, these are collated and summarized. (4) The experts receive comments, which they consider when revising their forecasts. This process can be repeated until there is a reasonable level of consensus. (5) The final forecasts are created by combining the forecasts of the experts. The key features of this method are the anonymity of participants and the controlled feedback –15.To reach a consensus on the T2T (treat to target) strategy in MAS, three Delphi rounds were conducted. After the major features of the approach were determined, a discussion group worked with the scientific committee to specify the aspects that would be included in the questionnaire. The structured Delphi approach ensures that all participants’ perspectives are taken into account equally, and it is especially effective for geographically diverse cities like Egypt. Online surveys were used to conduct the Delphi procedure. The Internet questionnaire’s first round featured 20 issues related to MAS’s T2T strategy.Three rounds of live online voting were held, each with a strict time limit. All members of the task force were invited to participate, and the start and end times of each round of voting were announced ahead of time. Anonymous votes were gathered and evaluated, and we handed out the unique access links. At the same time as the voting procedure, comments on rephrasing, potential ambiguity, and unidentified overlaps were received for each statement. The task force members were the only ones who could vote on the statements.Each statement was rated between 1 and 9 with 1 being “complete disagreement” and 9 being “complete agreement.” Generally, 1–3, 4–6, and 7–9 represent disagreement, uncertainty, and agreement, respectively. It is not necessary for members to vote on all statements, and they are invited to abstain if they believe a statement is outside their area of competence. As a result, a vote of “uncertainty” indicates “inconvenience about the accuracy of the recommendation.” All statements allow for the submission of comments, which the scientific committee reviews after each round of voting. Members were also encouraged to make remarks wherever they voted a disagreement in all of the voting rounds. This will allow the panel to spot a case of statement misinterpretation and nullify the vote on that statement.Prior to data analysis, a definition of consensus was defined. It was concluded that if at least 75% of the participants agreed (scoring 7–9) or disagreed (scores 1–3), consensus would be attained –14. If aThe first round took place between 12 and 15 May 2021 (4 days). The aspects about which respondents did not reach consensus in this first round were revised in view of the comments and included in the second round. The second round took place (1 week after the first round) and remained for 4 days, between 22 and 25 May 2021 (4 days). The third round took place (2 weeks after the second round) and remained for 4 days between 11 and 14 June 2021 (4 days).This study was performed in accordance with the Helsinki Declaration. The “Clinical, Evidence-based, Guidelines” (CEG) initiative protocol was approved by the local ethical committee: ethical approval code: 34842/8/21, ethical board Tanta University. According to national standards, written ethics approval from the experts involved in this project was not required. In accordance with data protection standards, all participants were kept anonymous.In the study selection process, we found 443 potentially relevant studies by search strategy. In total, 410 were excluded by screening of title and abstracts . Therefore, relevant 33 studies were included for full article review. Twenty studies were excluded as citations did not provide evidence matching a PICO. Therefore, we included 13 studies in this work , who participated in the three rounds. Respondents were drawn from different governorates and health centers across Egypt: Cairo University (26.1%), Ain Shams University (13.05%), Tanta University (8.7%), Benha University (4.35%), Alexandria University (4.35%), Suez Canal University (8.7%), Zagazig University (8.7%), Minia University (4.35%), Mansoura University (4.35%), Fayoum University (4.35%), Assiut University (4.35%), Menofeya University (4.35%), and Sohag University (4.35%).The Delphi form was sent to the expert panel . Consensus was reached on the inclusion of clinical standards on 90% of the items . There were comments raised regarding the wording of some of the recommendations. MAS presentations with various disorders, as well as MAS and COVID-19, received more comments (excluding minor editing suggestions). The number of statements which were added after round 1 was 1 in the diagnostic criteria section, 2 in the management section, and 2 statements in the MAS and COVID-19 section.The response rate for round 2 was 100% (23/23). Consensus was reached on the inclusion of clinical standards on 89.6% of the items . There were comments raised regarding the wording of some of the recommendations. Comments (excluding minor editing suggestions) were more frequent for MAS presentations with different diseases, differential diagnosis, monitoring and follow-up, and management of resistant and severe cases section. Diversity of opinion was greatest for the item “management of resistant and severe cases.” The number of statements which were added after round 2 was one statement in the differential diagnosis section, three statements were added to the monitoring and follow-up section, and two statements were added to the MAS and COVID-19 section. Several statements were revised after round 2; most edited statements were in the management of resistant and severe cases section (5 statements), one statement was amended in each of key point, early diagnostic tools, treat-to-target strategy, and MAS and COVID-19 sections.The response rate for round 3 was 100% 23/23). The frequency of high rank recommendation (ranks 7–9) ranged between 86.9 and 95.7%. One statement was retired for similarity with another statement. Consensus was reached  on all the clinical standards. Table 3/23. TheAt the end of Delphi round 3, a total of nineteen recommendation items were concluded. These were categorized into 2 sections: 11 recommendations under the diagnosis and 8 under management. Table There was a high level of agreement 8.26 + 1.7 (agreement percentage: 95.65%) on the criteria for early diagnosis of MAS (level of evidence (LE) 3, strength of recommendation (SoR) B, level of agreement H). These tools are summarized in Table As MAS could complicate many disorders, MAS presentations with different diseases have been assessed and presented in Table Table Macrophage activation syndrome is a life-threatening condition in childhood, which is seen most commonly in sJIA, jSLE, Kawasaki disease, and infectious diseases. It is characterized by persistent unremitting fever, hepatosplenomegaly, lymphadenopathy, marked depression of all 3 blood cell components, intravascular coagulation, impaired liver function, and central nervous system dysfunction . In a poThe 2020 Egypt census revealed that the number of population is 104,124,440, of them 33.62% are children in the age range of 0–14 years old and 18.01% in the range of 15–24 years of age [Because MAS is a potentially fulminant disorder that can evolve into a life-threatening consequence of inflammatory rheumatic disease , it is cExpert consensus recommendations for the diagnosis and treatment of MAS are expected to play an essential role, given the absence of high-level evidence for diagnosis and management of MAS. The Delphi technique has shown to be a reliable tool for achieving such consensus and selecting future research directions . The DelWhen using the Delphi process, consensus is reached when the percentage of people who agree or disagree is between 50 and 80% –23. WhenAt least one clinical criterion and at least two laboratory criteria must be present simultaneously for MAS to be diagnosed. Bone marrow aspiration is performed to search for evidence of macrophage hemophagocytosis, and it may be necessary only in doubtful cases . These cTreat to target has established itself as a guiding strategy for the treatment of inflammatory arthritic conditions, and it is based on several principles: identifying a target and a tool to measure it, evaluating the target at a pre-determined time point, a commitment to change the therapy if the target is not met, and shared decision-making. Previous research has advocated either an evidence-based treatment method  or a theBeyond the use of steroids which was highlighted in previous works , 8, 21, Given the current circumstances of the COVID-19 pandemic and possible serious conditions that appear to be linked to coronavirus disease 2019 in children , this guThis was an expert, consensus recommendation for the diagnosis and treatment of MAS, based on the best available evidence and expert opinion. The guidelines fill a gap in the literature as it presents a T2T approach for MAS. These suggestions should make it easier to find the best ways for diagnosing and management of this illness, as well as improve practice consistency, and promote the highest standards of care.


The world is facing an unprecedented systemic shock to population health, the economy and society due to the devastating impact of the COVID-19 pandemic. As with most economic shocks, this is expected to disproportionately impact vulnerable groups in society such as those in poverty and those in precarious employment as well as marginalised groups such as women, the elderly, Black, Asian and Minority Ethnic (BAME) groups and those with health conditions. The current literature is rich in normative recommendations on plural ownership as a key building block of an inclusive economy rooted in communities and their needs. There is, however, a need for a rigorous synthesis of the available evidence on what impact (if any) plural ownership may potentially have on the inclusivity of the economy. This review seeks to synthesise and compare the available evidence across the three economic sectors .We will search eight bibliographic databases , ProQuest Public Health, Web of Science, Research Papers in Economics (Repec) – EconPapers) from the earliest data available in each database until January 2021. Grey literature will be identified from Google (advanced), Google Scholar and 37 organisational websites identified as relevant to the research question. We will include comparative studies of plural ownership from high-income countries that report outcomes on access to opportunities, distribution of benefits, poverty, and discrimination. A bespoke search strategy will be used for each website to account for the heterogeneity in content and search capabilities and will be fully documented. A standardised data extraction template based on the Population-Intervention-Context-Outcome (PICO) template will be developed. We will assess the strength of evidence for different forms of economic ownership identified in relation to the impact of each on the four economic outcomes of interest, paying particular attention to the role of wider contextual factors as they emerge through the evidence.The findings of this review are intended to inform policymaking at local, national and international level that prioritises and supports the development of different economic and business models.Open Science Framework registration DOI: 10.17605/OSF.IO/BYH5AThe online version contains supplementary material available at 10.1186/s13643-022-01955-y. The world is facing an unprecedented systemic shock to population health, the economy, and society due to the devastating impact of the COVID-19 pandemic. The magnitude of the impact on the economy globally and in Scotland is not yet fully understood but is likely to be far-reaching with a ripple-effect that will be felt for years to come. As well as the large national deficit, the country is likely to face a sharp recession. As with most economic shocks this is expected to disproportionately impact vulnerable groups in society such as those in poverty and precarious employment [Many will be aiming to “bounce back” to the economy pre-crisis as soon as possible. However, the economic and social challenges we face, as well as the continued threat of the resurgence of COVID-19 infections means that now more than ever we need to learn and adapt to be better able to manage the challenges ahead. There is much we can draw on from the work pre-crisis on designing a more resilient, inclusive economy for the future; one that embeds the economy back into society and protects those who are most vulnerable .To achieve a Scotland where the population and the economy thrives, structural changes are needed. The Scottish National Performance Framework (SNPF)  already “broadening of the different types of enterprises that serve our local economies, so that there are more community-embedded forms of business ownership which are more likely to generate wealth for local residents and communities.”  Plural ownership has been identified as a key building block towards a more inclusive economy, potentially delivering a more equitable distribution of income, wealth and power. It refers to a broadening of the models of ownership of the production and sales of goods and services to distribute ownership and control among a greater range of stakeholders, such as employees, customers, producers or the community. It has been described as a:Evidence suggests that plural ownership can deliver a number of benefits. These include wage growth, job growth and security, increased employee control, increased accessibility to the job market for marginalised populations, community cohesion and resilience, increased business survival, and retained wealth within the community. Reflecting the potential for plural ownership of the economy to deliver such benefits, it is included as one of the five pillars of community wealth building .One way of representing the economy is using Pearce’s model Fig. . This ilThe current literature is rich in normative recommendations for plural ownership as a means of fostering a more inclusive economy through a focus on communities and their needs. There is however a need for a rigorous synthesis of the available evidence on what impact (if any) plural ownership may potentially have on community wealth and the drive towards a more inclusive economy. This review seeks to synthesise the available evidence across the three sectors  and what is known about the impact of different forms of ownership in each sector on the development of a more inclusive economy.The research question was formed using a combination of the SPICE  and PICO  approaches.The following research question will form the basis for this systematic evidence review: What is the evidence from comparative studies that plural forms of economic ownership, without restrictions in time, person or place, have differential impacts on a broad range of inclusive economic outcomes, and thereby might support change towards a more inclusive economy?We developed this protocol in accordance with PRISMA-P 2015. See Additional file The inclusion and exclusion criteria for screening of studies were informed by the PICOS framework and are shown in Table According to Lampel  ; ProQuest Public Health; Web of Science; Research Papers in Economics (Repec)–EconPapers; Fraser of Allander Institute; Joseph Rowntree Foundation; Centre for Local Economic Strategies (CLES); Scottish Government; Democracy Collaborative; NCEO-National Center for Employee Ownership; The Next System Project; Power to Change; United Nations (UN); Organisation for Economic Cooperation and Development (OECD); OECD library; World Bank; International Monetary Fund (IMF); International Labor Organization; Trade Unions Congress (TUC); European Commission; New Economics Foundation; Business in the Community; Carnegie UK Trust; Economic and Social Research Council (ESRC); Employee Ownership Association; Co-operatives UK; London School of Economics; Nesta; Forum for the Future; World Health Organization (WHO); Esmée Fairbairn Foundation; Centre for Thriving Places; Scottish Community Development Centre; Social Enterprise Scotland; Social Enterprise UK; Social Finance; World Cooperative Monitor; UWS-Oxfam Partnership; International Finance Corporation; Business for Inclusive Growth; WISE Campaign.We built up the key search terms for the bibliographic database searches using the PICO framework Table . IncludeThe key terms used to search for grey literature using Google and Google Scholar are shown in Table When searching each website for grey literature a flexible approach using multiple search pathways was used due to the heterogeneous nature of website content, design and variations in search functionality. This ensured that each website was interrogated effectively. The search pathways used for each website will be clearly documented as part of the systematic review.The Refworks  referencGoogle and Google ScholarThe first 100 PDF results returned for each search on Google and Google Scholar (excluding minutes and book reviews) will be imported to Sciwheel and will go through blind dual title and abstract screening.WebsitesDue to the heterogeneous nature of the websites potentially relevant to this review and inherent difficulties in dual-screening, we will single-screen websites for relevant content from title/abstract or summary equivalent, documenting all approaches used to interrogate each website separately and recording each search for transparency. Grey literature selected in this way at the ‘title/abstract’ stage will then be imported to Covidence systematic review management software to the full-text screening stage. All imported grey literature will then be dual-screened at the full-text screening stage.All peer-reviewed studies will go through a blind dual-screening process of both the title and abstract and then full-text of all remaining eligible studies. Disagreements will be resolved by consensus, and if necessary arbitration of a third person. Papers excluded at the full-text screening stage will be detailed in an A standardised data extraction template will be piloted and refined in Covidence. For the pilot, ten studies will be chosen randomly for data extraction by two reviewers. Both reviewers of each paper will independently extract key information from each paper deemed eligible from the full-text screening stage. Where any key information is missing from a paper, we will attempt to contact the author(s) for clarification.Administrative data , date of study, funding source)° Type of study (drop down list)° Population/setting for study° Intervention(s)° Comparator(s)° Outcome(s)▪ If yes, which study was retained for the review and why?° Is study reported more than once?Study characteristicsMethodsKey resultsKey conclusionsQuality of underlying evidence Contextual factors The key data points to be extracted from each paper are shown below.Access to opportunitiesi.Education, training, employmentii.Owning and running businessesiii.Owning and managing community assetsiv.Finance (to facilitate the above)These include:Access to opportunities will also depend on removal/lack of barriers to opportunities, such as social or cultural barriers.i.Resources, such as good quality jobs, wealth, assets and living standardsii.Distribution of power including: economic power, power related to the generation and communication of knowledge, including the media, power around shaping cultural and beliefs systems, power around shaping institutional cultures (related to item 1) collective power and positional power.iii.The presence or absence of exploitative practices in relation to plural ownership.Distribution of the benefits of the economyi.Data on levels of poverty in society.Povertyi.Impact of plural ownership (if any) on both active and passive discriminatory practices.DiscriminationThis review will focus on four key economic outcomes from our working inclusive economy definition necessary (though not sufficient) to help support a more inclusive economy  tool  will be For systematic reviews, we will use ‘A MeaSurement Tool to Assess systematic Reviews 2’ (AMSTAR2)  criteriaWe will assess the strength of evidence for different forms of economic ownership identified from the literature in relation to the impact of each on the four economic outcomes of interest, paying particular attention to the role of wider contextual factors as they emerge through the evidence, e.g. the balance between economic systems, regulation, financial support, and labour. We will aim to distinguish between the evidence of impact for different discrete models where there are data available but this will be non-systematic.Due to the anticipated heterogeneity of interventions, outcomes, comparators and contextual factors across studies, it will not be feasible to undertake a meta-analysis of results. Instead, we will carry out a narrative synthesis of the evidence and will report this in accordance with the Synthesis WIthout Meta-analysis (SWiM) guidelines. Pearce’s three economic systems model will be used as an economic framework  to help guide the synthesis.Grading of Recommendations Assessment, Development and Evaluation  approacWe will disseminate our findings through peer-reviewed publication as well as an accessible publication, through discussions with interested partners, and via our expert advisory group.North Ayrshire Council, other local authorities, Scottish Government, national and international policy makers and practitioners, academics, third sector bodies.The development of the systematic review protocol and the systematic review will be guided by the internal project management team  and the expert advisory group.An initial scoping exercise  was carried out to identify studies which had sought to review or generate evidence on different forms of economic ownership and their inclusive economic impact. From this, we identified gaps in evidence which we used to formulate the research question for our proposed systematic review.We carried out a pilot search for peer-reviewed literature using search terms collated from literature identified from the scoping search and feedback from the expert advisory group.Both sensitive and specific versions of the searches were then run on all eight databases identified as potentially relevant to the research question and key search terms were further refined i.e. ambiguous terms were either removed or revised to keep the study focussed on the research question. The sensitivity of the search was tested by looking for the inclusion of key papers  in the results. The search strategy used for the EBSCO Econlit database, as an example, is shown in Additional file Additional file 1. PRISMA-P-checklist.Additional file 2. Econlit (EBSCOhost)s–Search strategy.


Biogenic amines (BAs) are a family of nitrogen-bearing natural organic molecules with at least one primary amine, which play an important role in living organisms. Elevated concentration of BAs may cause neuron disorder, Parkinson's disease and many other diseases. Therefore, it is essential to monitor BAs in living organisms. Herein, we reported a resorufin-based fluorescence probe for sensing of various BAs. Upon nucleophilic substitution reaction with BAs, the probe released resorufin, affording to strong fluorescence emission at 592 nm with rapid response (<8 min), good selectivity and a low detection limit (LOD = 0.47 μM). The probe has low cytotoxicity and good membrane permeability, and has been successfully used to visualize BAs in living cells and zebrafish with good performance. A resorufin-based pre-fluorophore can achieve high contrast ratio imaging of biogenic amines in cells and zebrafish without washing steps. A certain amount of monoamines have diastolic and contractile effects on blood vessels and muscles,1,2 and have important regulatory effects on mental activities and cerebral cortex.3 Spermine and spermidine are the major components of polyamines, which can promote the synthesis of DNA, RNA and protein during the growth of organisms.3 BAs are indispensable components in living organisms and have important physiological functions in live cells.4 However, when the human body ingests excessive amounts of BAs, it can cause allergic reactions such as headache, nausea, palpitations,5 changes in blood pressure,6 as well as respiratory disturbances.7 Besides, BAs are also associated with various diseases, such as uterine cancer,8 lupus erythematosus,9 and liver disease.10 Therefore, the detection and identification of BAs are important issues for human health.Biogenic amines (BAs) are a family of nitrogen-bearing natural organic molecules with at least one primary amine group, which contain monoamines and polyamines. Monoamines mainly include tyramine, histamine, putrescine, cadaverine, phenylethylamine, tryptamine, 11–17Fluorescence probe has evolved into an important tool to track biomolecules by imaging microscopy due to its advantages of simple operation, fast response, high selectivity, high sensitivity, and excellent spatial–temporal resolution.18–20 ester21 and cyano group.22,23 However, these probes usually have strong background fluorescence interference, which cannot achieve high contrast ratio imaging of biogenic amines. Another approach is covalent coupling of amines with reactive fluorophores such as isothiocyanate,24N-hydroxysuccinimidyl (NHS) esters,25 and sulfonyl chloride groups.26 Nonetheless, these approaches are not ideal for the detection of amines due to the strong background fluorescence of fluorophores, which require washing steps to remove the excessive reactive fluorophore that did not react with amine. To eliminate the background fluorescence signals and avoid washing or distaining steps, an in situ activated fluorescent probe is preferable.27,28 In particular, it is highly desirable to create high brightness fluorophore with narrow absorption and emission bands within visible to near infrared (NIR) light region, since it could minimize parasitic signals from Rayleigh scattering (or auto-fluorescence) and reduce fluorescent resonance energy transfer (FRET)-based quenching under high concentration of local dyes.21,29 Moreover, pre-fluorophore approach, namely converting a non-fluorescent precursor to fluorophore through specific chemical reaction, might serve as a fast and selective sensing method to detect BAs in situ.A couple of BAs-specific fluorescent probes have been developed on the basis of BAs-mediated nucleophilic reaction with aldehyde,30–33 which enable it to be an efficient building block for creating fluorescent probes. By the virtue of these advantages, herein, we utilized resorufin as a starting material to prepare a fluorescent probe RHC for visualizing BAs. The caproyl group was attached to the hydroxyl group of resorufin to form caproyl ester group, which made the probe non-fluorescent and colourless. After reaction with BAs, the caproyl ester group of RHC was facilely removed through nucleophilic substitution reaction and thus released strong fluorescent resorufin dye . High-resolution mass spectra (HRMS) were determined on a HP-1100 LC-MS Spectrometer. UV-vis absorption spectra were performed on a SHIMADZU UV-800 spectrophotometer. Fluorescence spectra were measured on a Hitachi F-900 fluorescence spectrophotometer.Resorufin and hexanoyl chloride were bought from Sigma Aldrich and utilized without further purification. Cadaverine (Cad), putrescine, glutathione (GSH), cysteine (Cys), glucose, NaH2.22Cl2 was added dropwise to resorufin  and K2CO3  at ice-water bath under N2 atmosphere for 2 h. After quenching with saturated brine, the reaction solution was extracted with CH2Cl2. The crude product was purified by flash column chromatography  to give RHC  as a yellow powder. 1H NMR  δ ppm, 7.82 , 7.46 , 7.17 , 7.14 , 6.89 , 6.36 , 2.63 , 2.37 , 1.80 , 1.35 , 0.97 . 13C NMR  δ/ppm 186.4, 171.4, 153.7, 149.4, 148.2, 144.4, 135.14, 134.8, 131.2, 125.0, 119.3, 109.7, 107.2, 34.3, 31.2, 29.7, 22.3, 13.9. HR-MS (ESI): calculated for [C18H17NO4 + H]+ 312.1236, found 312.1238.Hexanoyl chloride  in 20 mL of anhydrous CH2.34 cells per well and incubated for 24 h. Then, RHC solution (10 μM) was added and incubated at 37 °C for 30 min. Afterward, the cells were washed twice with PBS, and various amounts of cadaverine were added and incubated for 15 min. Finally, fluorescence images were recorded on a Nikon A1 laser-scanning confocal microscope.L929 cells were seeded in confocal plates with the density of 2 × 102.44 day old zebrafish were cultured in an E3 embryo medium containing RHC (10 μM) at 28 °C for 30 min. Then, the zebrafish were washed with E3 embryo medium for three times, and incubated with various amounts of cadaverine for 15 min. Finally, the fluorescence images were recorded on a Nikon A1 laser-scanning confocal microscope.33.11H NMR, 13C NMR and HR-MS  contain at least one primary amine in their molecular structure, which has high nucleophilic activity to take aminolysis reaction with ester group. To develop a fluorescent probe for BAs, we used resorufin to prepare probe RHC, in which caproyl ester group acted as reactive recognition site for BAs. On the other hand, the caproyl ester group was attached to the oxygen atom of resorufin dye to mask the fluorescence of resorufin. In this case, the probe RHC was non-fluorescent and colourless. BAs would take nucleophilic substitution with the caproyl ester group to remove it. Consequently, the resorufin was released, affording strong red fluorescence. RHC was easily synthesized by routine method, and its structure was characterized by 3.2Cadaverine is one of typical BAs produced by enzyme-catalyzed decarboxylation of natural lysine in living organisms. Herein we chose cadaverine as a representative BAs to investigate the sensing performance of RHC. First, we examined the UV-vis absorption spectra and fluorescence responses of RHC towards cadaverine. RHC was pale yellow in PBS containing 10% DMSO. Upon the addition of cadaverine (0–100 μM), an obvious absorption peak appeared at 578 nm . This abΦf < 0.002) in DMSO/PBS buffer (v/v = 1/9) due to the caproyl ester group, which masked the fluorescence of resorufin by protection of the phenol –OH. Upon the addition of cadaverine, a fluorescence band emerged at 592 nm. The fluorescence intensity became much stronger as the concentrations of cadaverine increased. Moreover, a good linear correlation was observed between the emission intensity  and cadaverine concentrations (0–100 μM), and the detection limit (LOD) for cadaverine was 0.47 μM based on 3σ/k. By examining the absorption and emission spectra, we found that the absorption and fluorescence spectra of RHC after reaction with cadaverine were almost identical to resorufin,30–33 suggesting that resorufin was generated after the probe RHC reacted with cadaverine. The 1H NMR spectra of the product also supported our hypothesis. As shown in Fig. S4 , and other common biomolecules GSH, H2PO4−, HPO42−, HCO3−, HS−, NO3−, glucose. As shown in −, Na+, K+, Cys, GSH, HPO42−, HCO3−, HS−, NO3−. Besides, ordinary organic amines such as N,N-diisopropyl ethylamine, triethylamine, 4-methylpiperidine, diethylamine, and ethylamine only induced much weaker fluorescence enhancement, which might be attributed to the stronger nucleophilicity of diamino-containing biogenic amines. These results indicated that RHC has good selectivity for cadaverine and putrescine over other amines and anions. Therefore, the probe RHC was favourable for imaging BAs in living cells and zebrafish.To examine the selectivity of RHC for BAs, we measured the fluorescence response of RHC to various biological substances that generally exist in the living organisms, including biogenic amines (cadaverine and putrescine), organic amines . Moreover, low cytotoxicity and good membrane permeability of probe RHC enable it serve as a good indicator for imaging biogenic amines both Fluorescence imaging in zebrafish were performed at the Department of Experimental Research from Guangxi Medical University Cancer Hospital. All zebrafish procedures were performed in accordance with the Guidelines for Care and Use of Laboratory Animals of Guangxi Medical University Cancer Hospital and approved by the Animal Ethics Committee of Guangxi Medical University Cancer Hospital.Sheng-Lin Pei: investigation, methodology, formal analysis, writing – original draft. Jin Zhang: investigation, formal analysis. Wanyun Ge: investigation, methodology. Chao Liu: investigation of sensing mechanism. Ruilong Sheng: conception, writing – review & editing. Lintao Zeng: methodology, formal analysis, writing – original draft. Ling-Hui Pan: conception, supervision, writing – review & editing.There are no conflicts to declare.RA-012-D2RA06482K-s001


Postpartum depression (PPD) is an important cause of discomfort and dysfunction that impair the quality of life and the daily functionality not only of the patient but also of her child and her family, in its entirety. New treatment options have been made available for this pathology, but their use is restricted by methodological aspects, like the difficulty of administration, lack of enough data regarding their long-term efficacy, and costs.To conduct a literature review in order to find the most evidence-based pharmacological interventions for PPD.A literature review was performed through the main electronic databases  using the search paradigm “postpartum depression” AND “treatment” OR “pharmacological agents”. All papers published between January 2000 and August 2021 were included.Among the most evidence-based agents for PPD treatment are serotonin selective reuptake inhibitors (SSRIs). As individual agents, sertraline seems to be the most supported antidepressant by evidence from clinical trials, followed by escitalopram/citalopram, and fluoxetine. Other antidepressants supported by clinical data were venlafaxine, desvenlafaxine, nortriptyline, and bupropion. A 6-12 months maintenance treatment is considered optimal after remission, in women with a low risk of recurrence. Brexanolone, zuranolone, and ganaxolone are members of a new class of drugs studied for postpartum depression, but currently, only the first agent is FDA-approved for this indication.SSRIs are the most supported by evidence treatments for PPD, and brexanolone is a drug with a new mechanism, dedicated to this pathology that provides new hope for recovery.No significant relationships.


Emulsion explosives (EE) have been commercially available in various forms for over 50 years. Over this period, the popularity and production technology of this class of energetic materials have been developing constantly. Despite this rapid rise to prominence and, in some applications, prevalence over traditional energetic materials, remarkably little information is available on the physicochemical and energetic properties of these materials and factors affecting those properties. This work is dedicated to presenting the fundamental information relevant to the features, properties and applications of EEs, while highlighting the most significant recent progress pertaining to those materials. Particular emphasis has been given to providing information about the types, composition, modifications and detonation parameters of EEs, as well as to highlighting the less obvious, emerging applications of EEs. Emulsion explosives (EE) are one of the most recently developed classes of energetic materials ,2,3,4,5 The unique feature of EE matrices is that they are insensitive to initiation and cannot sustain detonation without being sensitised. This feature resulted in them being classed as oxidising agents, specifically with no. UN 3375, being assigned to class 5.1 as per ADR/RID regulations . Al. Al32]. 2) are also highly toxic and corrosive gases [In order to provide context for the above, it should be noted that exposure to 50 ppm of CO for approximately 30 min is considered non-threatening, whereas exposure to 200 ppm of CO concentration induces the first symptoms of carbon monoxide poisoning . Althougve gases .Predicting the properties of energetic materials based on their composition is an extremely difficult but worthwhile task, as it helps to minimise the exposure of personnel to those materials by reducing the number of experiments required to determine and fine-tune the properties of energetic materials being developed. Recently, a model for predicting the amount of post-detonation gases produced upon the detonation of ANFO- and EE-type energetic materials has been proposed . DespiteEEs are commonly utilised in civilian blasting operations, particularly in mining. In this application, the use of bulk EEs is continuously increasing its market share  due to tThe use of EEs in blasting operations associated with mining often encounters practical issues arising from the conditions existing in boreholes, both natural  and produced during the drilling of boreholes . In this regard, both the loading of boreholes and the reliability of detonation taking place across the entire length of the borehole are significant and common issues. The issue of loading boreholes is largely technical and requires careful control over the pressure and flow rate of the loaded EE.Conversely, the reliability of detonation may easily be compromised, particularly in deep boreholes, due to the hydrostatic pressure exerted by the pillar of the EE. Depending on borehole depth, this pressure can be large enough to induce gas bubble compression in the bottom section of the borehole. This can be avoided by limiting borehole depth or resolved to some extent, by utilising a higher initiating stimulus. Another phenomenon that needs to be taken into account in regards to the reliability of detonation is the timing of detonations in neighbouring boreholes. When the blast wave caused by nearby detonation travels through a borehole containing EE, momentary compression of the gas bubbles present in the EE takes place, causing it to temporarily lose sensitivity to initiation. If this issue is not taken into account during the planning of blasting operations, it can even lead to misfires.The use of EEs for testing the mechanical properties of construction materials is a non-obvious application that is of particular importance, both due to the relevance of data that can be acquired and due to the ever-present threat of bomb terrorism. In a recent work, the experimental testing of reinforced concrete was combined with a theoretical work-up, in order to yield a methodology for testing and modelling the fracture and resistance of brittle materials to blast loads . In the Another non-straightforward application of EEs is in explosive welding. Compared to traditional welding methods, explosive welding allows a broader range of metals and alloys to be combined. In this approach, the use of EEs instead of traditional, high-performance energetic materials was found to allow welding even highly dissimilar materials , due to The issue of water bodies, through which marine transport takes place, being covered with ice is important from an economical standpoint, particularly so in sub-polar and polar locations. One of the methods of removing such ice coverage is to employ energetic materials, due to their significant brisance. In the reported case, EEs were used for this purpose and a model of the behaviour of ice under blast loading was developed, potentially opening up a new avenue of application for these energetic materials .Powder metallurgy is a relatively young field, dealing with the processing of metals from powders. In this field, energetic materials are frequently used as sources of mechanical work for compressing the processed powders into solid elements. The use of EEs for this purpose has been recently reported and even though metal powder solidification was readily achieved, the amount of used EE is relatively large, in the range of 500–1000 g for compressing approx. 60 g batches of iron powder . Even thAn important risk associated with conducting blasting operations is the occurrence of ground vibrations, often referred to as para-seismic oscillations. Such vibrations can propagate over long distances, damage and even topple buildings. Recently, a dynamic finite element model has been utilised to model these vibrations . Althoug2+ ions have been found to lower the thermal decomposition temperature of EEs from approximately 280 °C to approximately 271 °C and to promote crystallisation in EE matrices [An important consideration in terms of EE safety is their possible contamination. Among commonly encountered contaminants, Fematrices .Despite high entry requirements into the subject of EEs, the development of this class of energetic materials continues and appears to be attracting increasing research interest over recent years. This is due to both the significant improvements to the performance and the safety features of these materials, making them an increasingly more favourable alternative for traditional energetic materials in general and for nitroester-based energetic materials in particular.The issues of the rheology and stability of both the EE matrices and the sensitised EEs have been a particular focus among recent works due to the practical considerations associated with the instruments and processes of sensitising and loading the EEs into boreholes. This aspect of EE development is also more readily available, as testing the rheology of even sensitised EEs does not necessitate conducting blasting operations and can be safely conducted in a specialised laboratory setting.It should be noted, however, that the rheology of EEs ties in with the issue of the population and size distribution of pores in the sensitised EE. Despite multiple studies, the subject remains controversial and requires further experimental exploration. A particularly important question in this regard is that of the nature of the impact of the porosity parameters on the energetic performance and sensitivity of the EEs.In contrast, the works dedicated to improving the energetic performance of EEs are significantly fewer, due to the extremely significant need to perform blasting repeatedly in a variety of experimental configurations, while ensuring the safety of both personnel and the utilised instruments. Even so, such works are highly valuable, both scientifically—pushing forward our understanding of the processes occurring in those energetic materials and the myriad factors influencing these processes—as well as economically, due to the fact that even a minute improvement in the performance of EEs translates into more efficient blasting operations, allowing more rock to be mined with a lesser total amount of energetic material utilised.Among the above, particular attention should be paid to emerging additives to EE formulations, as the inclusion of even relatively common substances as additives was proven to significantly improve various properties of the EEs. This trend is expected to bring even further improvements to the properties and performance of EEs in the future, helping promote new, higher standards in the development and use of energetic materials.The implementation of increasing standards for EEs inevitably involves discussion of the personnel health and environmental impacts of such materials. In this regard, the composition and amount of gases produced during the energetic decomposition of EEs is an essential, but under-explored issue. Although some strides have been made in limiting the emissions for EEs, the subject remains a significant issue, as current EE formulations produce carbon monoxide and nitrogen oxides in the post-detonation gases. Reducing these emissions remains an important, unresolved issue that needs to be overcome, in order to achieve “green” EEs.