Background: The purpose of this review was to analyze and correlate the findings for zirconia implants in clinical, preclinical and in vitro cell studies in relation to surface structure. Methods: Electronic searches were conducted to identify clinical, preclinical and in vitro cell studies on zirconia implant surfaces. The primary outcomes were mean bone loss (MBL) for clinical studies, bone-to-implant contact (BIC) and removal torque (RT) for preclinical studies and cell spreading, cell proliferation and gene expression for cell studies. The secondary outcomes included comparisons of data found for those surfaces that were investigated in all three study types. Results: From 986 screened titles, 40 studies were included for data extraction. In clinical studies, only micro-structured surfaces were investigated. The lowest MBL was reported for sandblasted and subsequently etched surfaces, followed by a sinter and slurry treatment and sandblasted surfaces. For BIC, no clear preference of one surface structure was observable, while RT was slightly higher for micro-structured than smooth surfaces. All cell studies showed that cell spreading and cytoskeletal formation were enhanced on smooth compared with micro-structured surfaces. Conclusions: No correlation was observed for the effect of surface structure of zirconia implants within the results of clinical, preclinical and in vitro cell studies, underlining the need for standardized procedures for human, animal and in vitro studies. Two-piece titanium dental implants with a roughened endosseous surface are frequently used to achieve fast and stable osseointegration ,2,3,4. THence, when zirconia implants were introduced, the endosseous surface was also structured in accordance with the consensus for titanium implants. Currently available zirconia implants are either made of 3 mol% yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) or alumina-toughened zirconia (ATZ). The first zirconia implants on the market were sandblasted to create a rough surface. Currently available implants display moderately rough to rough features with smoothened edges created via sandblasting followed by acid etching, via laser ablation, additive sintering of small zirconia particles or injection molding ,13,14,15Clinical medium-term data are available for moderately rough zirconia implants ,17,18,19Preclinical studies with zirconia implants have been conducted to compare mainly the bone-to-implant contact (BIC) or removal torque (RT) of zirconia with titanium implants . The choNo review analyzed if the findings from in vitro cell studies are consistent with preclinical data and are consequently relevant for conducting clinical studies for the respective surface structures of zirconia. Hence, the purpose of this review was to analyze and correlate the findings for zirconia implants in clinical with preclinical and in vitro cell studies to evaluate the influence of the surface structure on the outcome.This systematic review was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P ) statemeFor the present review, the focused (PICO) question to be addressed was as follows: “In clinical, preclinical and in vitro studies, what are the outcomes , removal torque (RT), cell behavior) of zirconia dental implant surfaces with regard to the surface structure?”A systematic electronic search of Medline via Pubmed and Embase was performed between June and August 2021. Articles in English and German were considered. The following terms and combinations were applied: ) OR “zirconia implant” OR “ceramic implant”) AND  OR  OR (“osteoblasts” OR “cell proliferation” OR “cell spreading” OR “gene expression”)). Additionally, recent systematic reviews ,26,27 weHuman trials, preclinical and in vitro osteoblastic cell studies investigating zirconia implant surfaces that were published between January 2000 and December 2021;Randomized clinical trials or cohort studies with at least 10 patients included ;Details on the surface structure of zirconia and implant manufacturer are given;Reported details of marginal bone loss of clinical trials, BIC or RT of preclinical studies, osteoblastic cell behavior  for in vitro studies comparing two different zirconia surfaces.The inclusion criteria were defined as follows: Studies that did not meet the inclusion criteria were excluded from this work. Data from multiple publications on the same patient population were summarized, and the last published work was cited.After elimination of duplicates, the reviewers  independently screened titles, abstracts and full texts meeting the selection criteria. Disagreements regarding the inclusion and exclusion of studies were resolved by discussion between the reviewers.Data extraction into Excel tables was independently performed for all included studies . From the included full-text articles, the following data were extracted: author(s), year of publication, number of included patients and implants, implant material (yttria-stabilized zirconia (Y-TZP)/alumina-toughened zirconia (ATZ), controls, implant design (1-piece/2-piece), specimen dimension, implant manufacturer, implant surface treatment, surface roughness, time period between implant placement and prosthetic treatment, type of restoration (single crown (SC)/fixed dental prostheses (FDP)), number of implant failures, observation period (months), implant survival (%), mean bone loss , bone-to-implant contact , removal torque , animal, cell line, cell spreading, cell proliferation and gene expression.Primary outcomes were MBL for clinical studies, BIC and RT for preclinical studies, and cell spreading, cell proliferation and gene expression for cell studies. Secondary outcomes included comparisons of data found for those surfaces that were investigated in all three study types.The mean MBL values from clinical studies of the same study population were collected for each follow-up. Data of studies using the same implant type were then pooled when data were extracted at the same follow-up. Further, data of implants with similar surface treatments were pooled at each follow-up. The BIC values and RT values of the included preclinical studies were listed for each intervention point. Values were further pooled by surface treatment and animal model for each intervention point. Minipig and pig were considered as species pig. Findings for cell spreading, cell proliferation and gene expression of in vitro cell studies were analyzed descriptively by comparing the results of the investigated surfaces within each study.The electronic data base search and the respective results are displayed in Details on clinical studies are given in An overview of the animal studies is given in The BIC at the respective intervention time for each study is displayed in Cell studies with osteoblastic cells comparing two differing zirconia implant surfaces are presented descriptively in The purpose of this review was to analyze and correlate the findings for zirconia implants in clinical with preclinical and in vitro cell studies to evaluate the influence of the surface structure on the outcome. As only sandblasted, sinter and slurry-modified, as well as sandblasted and subsequently etched surfaces were investigated in the included clinical trials, only those findings could be compared with preclinical and in vitro cell studies. The best performance with the highest survival rates and the lowest MBL in the clinic were observed for sandblasted and subsequently etched surfaces, followed by sinter and slurry-modified and sandblasted surfaces. In preclinical studies, the BIC values reported for sandblasted and subsequently etched and sinter and slurry-modified surfaces seemed similar, deviating slightly at each intervention point. Osseointegration of sandblasted surfaces progressed slower; however, data were only available for two intervention time points. Unfortunately, none of these surfaces were compared with each other regarding the RT and in cell studies with osteoblasts.The zirconia implants currently on the market with clinical studies included in this review are either one-piece Y-TZP implants that are sandblasted by Bredent ,30, sandOverall, the clinical outcome of zirconia implants irrespective of the surface can be considered promising confirming previous reviews ,25,26,27In preclinical studies, no clear preference of one surface structure could be identified. Surprisingly, surfaces with lower surface roughness that were machined or injection-molded provided comparable BIC to modified surfaces. When smooth surfaces were directly compared with rougher surfaces within the same set-up, even higher , similarThe RT values were lower for machined compared with rougher surfaces ,61,67; hAs previously observed, BIC and RT were highly affected by the selected animal model . OsseoinCell studies should be a prerequisite for conducting animal studies. Only one group considered comparing the outcome of their cell study with a preclinical model with rats using the same surfaces . MachineUnfortunately, no clinical study with machined zirconia implants exists to further investigate the potential of this surface structuring method. Only the fact that radiological long-term data from a clinical study prove a tight contact between the polished zirconia transmucosal part and bone  supportsAlthough a great effort is made to conduct in vitro, preclinical and clinical studies, no correlation can be observed within the respective results, underlining the need for standardized procedures for animal and human studies, especially concerning ethics. Additional attention should be focused on choosing an appropriate control group for animal and human research having only one varying parameter from the test group. The tested materials and surfaces are to be properly characterized using scanning electron microscopy and more parameters of surface roughness than the arithmetical mean. In vitro cell and preclinical studies using the same implant surfaces should be mandatory prior to a clinical trial to validate the study designs. In addition, there is a strong need for guidelines for conducting clinical trials with implants and for the parameters to be obtained and reported.In clinical studies, the lowest MBL was reported for sandblasted and subsequently etched surfaces, followed by a sinter and slurry treatment and sandblasted surfaces;In preclinical studies analyzing BIC, no clear preference of one surface structure was observable. The RT was slightly higher for micro-structured than smooth surfaces. The BIC and RT values were highly influenced by the chosen animal model;All cell studies showed that cell spreading and cytoskeletal formation were enhanced on machined compared with micro-structured surfaces;No correlation was observed between the outcomes, underlining the need for standardized procedures for animal and human studies.The conclusion must be interpreted with care as the study designs of the included clinical, preclinical and cell studies are highly heterogenous and vary regarding the follow-up time and implant design. Within the limitations of this review that investigated the impact of surface structure of zirconia implants it can be concluded that:


WHO publishes public health and clinical guidelines to guide Member States in achieving better health outcomes. Furthermore, WHO’s Thirteenth General Programme of Work for 2019–2023 prioritizes strengthening its normative functional role and uptake of normative and standard-setting products, including guidelines at the country level. Therefore, understanding WHO guideline uptake by the Member States, particularly the low- and middle-income countries (LMICs), is of utmost importance for the organization and scholarship.We conducted a scoping review using a comprehensive search strategy to include published literature in English between 2007 and 2020. The review was conducted between May and June 2021. We searched five electronic databases including CINAHL, the Cochrane Library, PubMed, Embase and Scopus. We also searched Google Scholar as a supplementary source. The review adhered to the PRISMA-ScR (PRISMA extension for scoping reviews) guidelines for reporting the searches, screening and identification of evaluation studies from the literature. A narrative synthesis of the evidence around key barriers and challenges for WHO guideline uptake in LMICs is thematically presented.The scoping review included 48 studies, and the findings were categorized into four themes: (1) lack of national legislation, regulations and policy coherence, (2) inadequate experience, expertise and training of healthcare providers for guideline uptake, (3) funding limitations for guideline uptake and use, and (4) inadequate healthcare infrastructure for guideline compliance. These challenges were situated in the Member States’ health systems. The findings suggest that governance was often weak within the existing health systems amongst most of the LMICs studied, as was the guidance provided by WHO’s guidelines on governance requirements. This challenge was further exacerbated by a lack of accountability and transparency mechanisms for uptake and implementation of guidelines. In addition, the WHO guidelines themselves were either unclear and were technically challenging for some health conditions; however, WHO guidelines were primarily used as a reference by Member States when they developed their national guidelines.The challenges identified reflect the national health systems’ (in)ability to allocate, implement and monitor the guidelines. Historically this is beyond the remit of WHO, but Member States could benefit from WHO implementation guidance on requirements and needs for successful uptake and use of WHO guidelines.The online version contains supplementary material available at 10.1186/s12961-022-00899-y. Member States’ health systems determine WHO guideline uptake; weaker health systems continue to have low uptake and use of WHO guidelines.The challenges for WHO guideline uptake reflect the health systems’ (in)ability to allocate, implement and monitor adherence to the guidelines. Historically this is beyond the remit of WHO, but Member States could benefit from WHO implementation guidance on requirements and needs for successful deployment of normative and standard-setting products.Robust feedback mechanisms between WHO and Member States help to optimize WHO guideline uptake in Member States and contribute to the guideline development process.end-users regarding what can or should be done in specific situations to achieve the best health outcomes possible. Guidelines are the fundamental means by which the organization fulfils its technical leadership role in health  actions to improve health at three levels: the advancement of knowledge and skills among practitioners; the expansion of support and infrastructure for health promotion in organizations; and, the development of cohesiveness and partnerships for health in communities” [Healthcare providers play an invaluable role in healthcare delivery. Hence, the capacity-building of healthcare providers is essential in a health system. Advancement of knowledge and skills among practitioners is an important aspect of capacity-building . WHO defunities” .For communicable diseases, studies found that the strength of recommendation and evidence quality determined national policy adoption of WHO HIV guidelines in LMICs in South-East Asia and Africa . In contFor MNCH, in 2018, WHO called for global action towards the elimination of cervical cancer, with a key strategy, among others, to screen 70% of women between the ages of 35 and 45 years. A study suggests well-organized screening programmes in high-income countries, but due to the lack of extensively experienced clinicians, LMICs did not achieve similar progress . A revieThough providers perceive PPH guidelines as useful, lack of guideline awareness, poor access to guidelines, prioritizing experience over evidence and incorrect clinical practice were key barriers to PPH guideline implementation in Kosovo . In anotWHO recommends antenatal care (ANC) for a positive pregnancy experience for women, regardless of the income status of the country. However, lack of access to external training programmes was reported as a key barrier to compliance with ANC and PPH guidelines in LMICs –51. In 2ten essential public health operations” emphasized in WHO’s essential public health services framework [Adequate funding is essential for fulfilling the “ramework . HoweverFor communicable diseases, indoor residual spraying (IRS) is a proven effective malaria vector intervention if correctly implemented using WHO-recommended insecticides. Implementation of IRS programmes in malaria-endemic countries has often been constrained by funding limitations. For example, IRS programme implementation in Malawi was found to be uncertain due to limited funding, cost of alternative insecticides and technical resource challenges experienced in the country .The 2013 WHO guidelines for antiretroviral therapy (ART) recommend expanding eligibility to include several new groups of people living with HIV, notably all HIV-infected adults with CD4þ T-cell counts between 350 and 500 cells/ml, all pregnant women and serodiscordant couples regardless of CD4þ T-cell count, and all HIV-positive children up to the age of 5 years. These guidelines were expected to double the number of people living with HIV/AIDS (PLHIV) on treatment, but several challenges limited its uptake in many countries , 53, 56.In 2015, WHO provided guidelines recommending that any person at substantial risk of HIV be offered oral pre-exposure prophylaxis (PrEP) containing tenofovir disoproxil fumarate (TDF) as an additional prevention choice. Further, in 2017, PrEP medicines were listed in WHO’s EML, including TDF/emtricitabine (FTC) and TDF in combination with lamivudine (3TC). By the end of 2018, at least 40 countries (20.6%) were anticipated to have adopted WHO’s oral PrEP recommendation. However, policy uptake and programmatic coverage of PrEP services were constrained by the underlying cost of PrEP services in LMICs . Since 2For NCDs, WHO recommends virtually eliminating trans fat from the global food supply. LMICs such as India face several challenges, requiring a multisectoral food chain approach to remove trans fats from the food supply. Empirical evidence suggests that economic incentives for manufacturing foods using healthier oils are imperative in India and elsewhere . In 2012For MNCH, in 2007, the 60th WHA passed a resolution entitled “Better medicines for children”. Subsequently, WHO recommended the inclusion of child-appropriate dosage formulations in the EMLs of Member States. However, LMICs have either delayed or not included these recommendations in their national EML. The key barriers included a lack of resources that hindered the formal transfer of the policy from the global to the local level . A qualiPublic health infrastructure provides the necessary foundation for undertaking the basic responsibilities of public health, which have been defined as the 10 essential public health operations . Every pFor communicable diseases, the LMICs, especially sub-Saharan African countries, had suboptimal uptake of WHO ART guidelines due to inadequate health systems in those countries. The barriers reported included no operating budget to support scale-up, difficulty transporting samples, delays in commodity procurement and distribution, inadequate laboratory information systems, insufficient trained human resources dedicated for viral load testing, equipment breakdown, delay in equipment repair, inadequate laboratory and storage space to accommodate sample volume, and insufficient viral load testing results management  , 65.For TB prevention, improved access to rapid diagnostics for TB drug resistance and second-line TB treatment was recommended . Based oFor MNCH, in the vast majority of countries, ANC is provided free of charge. Accessibility and availability of local transport , indirect costs associated with transport to and from the clinic in resource-poor settings and the purchase of additional medicines were reported as barriers to ANC engagement in several LMICs . The lacPublic health in LMICs is complex; implementing and taking up broad-sweeping guidelines is even more complex. Our findings reveal that guideline uptake in any one WHO Member State is influenced by a multifactorial interplay of factors such as awareness of guidelines, funding, infrastructure, legislation and regulations. While most of the identified barriers can be directly attributed to challenges within the national health systems context, some barriers are associated with the WHO guidelines themselves.Health systems are expected to fulfil three main functions—healthcare delivery, fair treatment to all and meeting health expectations of the population, for which governance is vital. Health system governance is “an aggregation of normative values such as equity and transparency within the political system in which a health system functions” . It invoHealth infrastructure challenges encompassing management and operations issues, systems and technical needs, to community resources were evident in guideline uptake for the health conditions selected in the study. For example, the review findings suggest that lack of infrastructure is a critical barrier for guideline uptake and use in ANC in LMICs . These fThe resource constraints were evident in the evaluation studies undertaken in LMICs, particularly the clinical practice guidelines. For example, with regard to WHO ART guidelines uptake, most of the LMICs did not have a health system in place for guideline uptake and use, requiring domestic, bilateral and multilateral funding to support guideline implementation. In addition, human resources capacity gaps such as poor-quality training, lack of opportunities for skill enhancement and lack of accountability for adherence to guidelines, lack of communication/interprofessional collaboration, and ethnic/cultural differences were cited as barriers to WHO guideline uptake and use in healthcare settings . These cWeak health systems hinder the implementation of effective interventions . Poor upNotwithstanding health systems challenges, the review findings suggest that the WHO guidelines themselves were either unclear or weak and were technically challenging. Evidence from implementation research has shown that detailed implementation plans are often necessary for local policy-makers to use WHO guidelines. Studies have also found that end-users’ adherence to and uptake of guidelines are negatively affected by guidelines without adequate implementation plans , 88, 89.Further, implementation advice was often not provided, especially in terms of sustained capacity-building, which limited stakeholder engagement , and guiOur findings also suggest that WHO guidelines were being used as a reference by Member States when developing their national guidelines. However, guideline dissemination and the monitoring and evaluation of guideline uptake were not well documented by WHO or the Member States for optimizing guideline uptake. A WHO-commissioned assessment of the contribution of WHO guidelines to improving reproductive, maternal and newborn health in the South-East Asia Region found that WHO engaged its intended audience by deploying various dissemination means . However, the process was not well monitored or documented regarding the distribution of emails, downloads from websites and distribution of printed copies . SimilarThe WHO GPW13 focuses on Triple Billion targets to achieve measurable impacts on population health at the country level. The Triple Billion targets include one billion more people benefiting from universal health coverage, one billion more people better protected from health emergencies, and one billion more people enjoying better health and well-being. WHO’s guidance is vital in achieving the Triple Billion targets and measurable impacts on population health for the Member States. As the review findings determine the direct correlation between guideline uptake and health systems, the organization, while producing evidence-based guidelines for better health outcomes in Member States, should continue to encourage the building of stronger health systems to optimize the WHO guidelines in the Member States. Additionally, WHO should monitor and evaluate the uptake of its guidelines with either existing or new monitoring, evaluation and learning frameworks and feedback loops between WHO and Member States for optimizing WHO guideline uptake in Member States. WHO SMART  guidelines are a comprehensive set of reusable digital health components as a way forward for optimizing guideline uptake .Guideline developers should work collaboratively with guideline implementors and researchers to design and conduct evaluations of guideline implementation, especially in the LMICs, to identify additional contextually sensitive barriers and facilitators. Targeted implementation strategies could then be developed and tested in the local settings. Also, the funding organizations should focus on and encourage these evaluation and monitoring studies. As for addressing the barriers related to the WHO guidelines, researchers should focus on the impact of different formats and reporting characteristics of the guideline recommendations, and engage with guideline implementors and developers to identify the optimal formats that they could accept.WHO maintains the Global Index Medicus (GIM) data, which provides worldwide access to biomedical and public health literature produced by and within LMICs. By not including GIM in our search strategy, the review may have missed some critical articles from the LMICs. Also, our screening criteria included literature in English only, restricting the review to articles published in the English language.The challenges for WHO guideline uptake reflect the health systems’ ability to allocate, implement and monitor the guidelines. Historically this is beyond the remit of WHO, but Member States could benefit from WHO implementation guidance on requirements and needs for successful deployment of WHO’s NSPs, including the guidelines. The impact on health outcomes is derived primarily from guideline implementation; however, the extent to which guidelines are implemented in countries, and the quality of that implementation, largely remains unknown. WHO guidelines are referenced and adapted to a large extent at the country level into national policies, strategies, plans and clinical guidelines.Additional file 1. Search strategy.


Many commercial actors use a range of coordinated and sophisticated strategies to protect business interests at the expense of public health, for example: attacking and undermining legitimate science, intimidating and vilifying critics, and framing and reframing discussion and debate. These strategies can be thought of as a ‘Corporate Playbook’ that spans numerous health and planet-harming industries. To counter this Corporate Playbook and advance health and wellbeing, public health actors need to develop, refine, and modernize their own Public Health Playbook.This paper seeks to consolidate thinking around how public health can counter and proactively minimize powerful commercial influences. It draws on previous attempts to develop approaches to counter commercial influence for public health, sustainability, human rights and democracy, and develops eight thematically grouped strategies.We propose an initial eight strategies: 1) Expand the public health workforce and coalitions; 2) Increase public sector resources; 3) Link with and learn from social movements to foster collective solidarity; 4) Protect public health advocates from industry threats; 5) Develop and implement rigorous conflict of interest safeguards; 6) Monitor and expose corporate activities; 7) Debunk corporate arguments; and 8) Leverage diverse commercial interests.This set of strategies seeks to amplify inherent assets of the public health community and create opportunities to explicitly counter the Corporate Playbook. These strategies are not exhaustive, and our aim is to provoke further discussion and exploration on this topic. Moving forward, there is a need for further work to develop a rigorously researched and tested Public Health Playbook.


Access to affordable inhaled medicines for chronic respiratory diseases (CRDs) is severely limited in low- and middle-income countries (LMICs), causing avoidable morbidity and mortality. The International Union Against Tuberculosis and Lung Disease convened a stakeholder meeting on this topic in February 2022.Focused group discussions were informed by literature and presentations summarising experiences of obtaining inhaled medicines in LMICs. The virtual meeting was moderated using a topic guide around barriers and solutions to improve access. The thematic framework approach was used for analysis.A total of 58 key stakeholders, including patients, healthcare practitioners, members of national and international organisations, industry and WHO representatives attended the meeting. There were 20 pre-meeting material submissions. The main barriers identified were 1) low awareness of CRDs; 2) limited data on CRD burden and treatments in LMICs; 3) ineffective procurement and distribution networks; and 4) poor communication of the needs of people with CRDs. Solutions discussed were 1) generation of data to inform policy and practice; 2) capacity building; 3) improved procurement mechanisms; 4) strengthened advocacy practices; and 5) a World Health Assembly Resolution.There are opportunities to achieve improved access to affordable, quality-assured inhaled medicines in LMICs through coordinated, multi-stakeholder, collaborative efforts. The rising burden of non-communicable diseases (NCDs) represents a substantial threat to health and development worldwide; 41 million people each year die of an NCD, and the burden of NCDs affects the poorer segments of society the most; 77% of all NCD deaths occur in low- and middle-income countries (LMICs).8Previous efforts by the International Union Against Tuberculosis and Lung Diseases (The Union) to facilitate procurement of quality-assured, essential, affordable asthma medications for LMICs, the Asthma Drug Facility Programme, were discontinued in 2013 due to factors, including lack of political commitment and limited local disease management strategies.The initiative was led by GM and KM , who identified key stakeholders drawing on The Union’s extensive networks. Efforts were made to be inclusive of a broad range of stakeholders to obtain viewpoints from various backgrounds.These key stakeholders were engaged in procurement, treatment and policy-making decisions relating to the use of inhaled medicines in LMICs. They included patients, academics, representatives of international multilateral organisations, pharmaceutical companies and clinicians, and are included as authors of this paper. They were individually approached from July 2021 and invited to participate in the virtual group discussion. All contributors provided consent. No formal ethics approval was required. The preparation of, and the meeting itself, was undertaken during the COVID-19 pandemic which affected the ability of some to participate and necessitated a virtual conversation. In preparation for the meeting, contributors submitted audio-recorded presentations on barriers, potential solutions and pathways to the solutions from their perspective. These, and two recently published articles, were available to all contributors in advance to inform the discussions.12The 2-hour virtual meeting was hosted, recorded and transcribed on Zoom (zoom.us) on 4 February 2022. During the discussions, participants were able to post comments and questions on the chat facility. The focus group discussions involved structured conversations moderated by facilitators , who used a topic guide designed around “barriers to access”, “solutions” and “pathway to solutions” . The fac13The transcript of the meeting, the chat and the visual imageries were analysed using the thematic framework approach with NVivo v12 . This is a qualitative approach involving the analysis of key patterns in meaning and the identification of broad themes from qualitative data.https://prezi.com/view/eOuY7719eZlGKvrgf1Vj/). The following themes emerged.Twenty stakeholders provided presentations that were available pre-meeting and 58 people attended the meeting  Resolution for Diabetes, which were strongly supported by patient representation.Ultimately, political commitments by individual countries for funding, policies and investment are needed. A WHA Resolution on care for all children, adolescents and adults with CRDs would help focus attention and resources on implementing the solutions needed. Close collaboration between the WHO, clinicians, ministries of health, respiratory advocates, communities and patients will be needed to achieve such a resolution and implement its recommendations .Several barriers to accessible, affordable and quality-assured inhaled medicines in LMICs were identified, including limited awareness, paucity of data, ineffective procurement and poor communication . Many obThe use of standardised tools, such as an updated WHO PEN guideline, the WHO/Health Action International  or MedMon methodologies, allow reliable data collection and benchmarking among countries.27The strengths of our approach included the participation of a wide range of relevant stakeholders, including patients, patient advocacy organisations, national and international respiratory societies, global organisations that develop CRD management strategies, pharmaceutical companies, the Global Alliance Against CRDs (GARD) and the WHO. The structured approach to the organisation and implementation of the meeting, drawing on qualitative research methodology, allowed us to take a robust approach to the analysis and synthesis of the discussions. Limitations included there being other stakeholders, outside of The Union’s networks, who were not contributors and could have brought valuable perspectives. Challenges included conducting a virtual meeting, the large number of participants and limited time for discussion.To our knowledge, this is the first time an international meeting has been convened to tackle this topic since the World Asthma Meeting in 1998.In conclusion, we suggest that with sufficient targeted resources, collaborative multi-stakeholder action could overcome the barriers in access to affordable, quality-assured, essential inhaled therapies for people with CRDs in LMICs. Given the expertise and experience within this group of stakeholders, we suggest the following areas for collaborative action: 1) work together with people living with asthma and COPD to understand their needs and co-create solutions; 2) raise awareness and reduce stigma among local communities using multimedia information campaigns; 3) develop clinical guidance and implementation tools that address the needs of healthcare providers in LMICs; 4) ensure that the WHO Essential Medicines List is aligned with current evidence and existing WHO guidance; 5) explore targeted solutions to challenges across the inhaled medicines supply chain continuum, particularly to streamline procurement processes and to guarantee the quality of products; 6) develop strategies to address challenges around the affordability of inhaled medicines; 7) collect and share CRD-related data  to inform policy and practice; 8) develop and deliver targeted messages to local and national governments to drive evidence-based policy and mobilise resources for CRDs; 9) work with national governments and the WHO to build the case for a WHA Resolution on improving access to effective asthma and COPD care for all; and 10) share examples of good practice, lessons learnt and resources for advocacy or education to maximise impact .Click here for additional data file.


Malaria in pregnancy (MIP) increases the risk of poor maternal and infant outcomes. To reduce these risks, WHO recommends insecticide-treated net (ITN) use, intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP), and prompt case management. However, uptake of these interventions remains sub-optimal in Madagascar. A scoping review was conducted to determine the breadth and depth of information available during 2010–2021 about Madagascar’s MIP activities and to identify barriers and facilitators to MIP interventions uptake.PubMed, Google Scholar, and USAID’s files  were searched using the terms “Madagascar AND pregnancy AND malaria,” and reports and materials from stakeholders were collected. Documents in English and French from 2010 to 2021 with data regarding MIP were included. Documents were systematically reviewed and summarized; results were captured in an Excel database.Of 91 project reports, surveys and published articles, 23 (25%) fell within the stated time period and contained relevant data on MIP activities in Madagascar and were categorized accordingly: eight (35%) quality of care, including health facility readiness, provider knowledge and commodity availability; nine (39%) care-seeking behaviour; and, six (26%) prevention of MIP. Key barriers were identified: nine articles mentioned SP stockouts; seven found limitations of provider knowledge, attitudes, and behaviours (KAB) regarding MIP treatment and prevention; and, one reported limited supervision. MIP care seeking and prevention barriers and facilitators included women’s KAB regarding MIP treatment and prevention, distance, wait times, poor service quality, cost, and/or unwelcoming providers. A 2015 survey of 52 health facilities revealed limited client access to antenatal care due to financial and geographic barriers; two 2018 surveys revealed similar findings. Self-treatment and care-seeking delays were reported even when distance was not a barrier.Among the studies and reports on MIP in Madagascar, the scoping review frequently noted barriers that could be mitigated by reducing stockouts, improving provider knowledge and attitudes, refining MIP communication, and improving service access. There is a need for coordinated efforts to address the identified barriers is the key implication of the findings. Malaria in pregnancy (MIP) is a serious condition for both mother and fetus that can lead to anaemia, low birthweight, stillbirth, and maternal death . To reduThe entire population of Madagascar is at risk of malaria, and the reported incidence ranged from < 1 to 100 cases per 1,000 population across the island nation in 2021 . MadagasFor IPTp, SP is administered as directly observed therapy (DOT) every four weeks starting at 13 weeks of gestational age. IPTp is delivered during ANC visits in health facilities by a health care worker ((HCW), nurse, midwife, or physician). In three pilot districts, Madagascar is testing IPTp delivered at the community level by trained community health volunteers (CHVs). This pilot, Transforming Intermittent Preventive Treatment for Optimal Pregnancy (TIPTOP), is designed to investigate the impact of community-IPTp on improving access and uptake . In addiData to determine MIP burden is limited in Madagascar. The Madagascar National Malaria Control Programme (NMCP) in collaboration with other Ministry of Health departments, sets targets for ANC attendance, IPTp uptake, and ITN coverage and use, and monitors progress toward achieving these targets. IPTp indicators include the proportion of recently pregnant women who initiated IPTp (IPTp1) and the number who completed three courses (IPTp3) used to estimate IPTp coverage. Population-based household surveys, such as the Malaria Indicator Survey (MIS), include self-reports of ITN and IPTp use, and indicate low uptake of both interventions. The most recent Madagascar MIS, conducted in 2016, revealed that 69% of pregnant women reported sleeping under an ITN the previous night, and 10% of women who had given birth in the previous two years reported taking a minimum of three doses of IPTp . More reAs a first step toward improving MIP services in Madagascar, the NMCP, US President’s Malaria Initiative (PMI), and the Institut Pasteur de Madagascar (IPM) conducted a scoping review to determine what available information existed regarding MIP activities in Madagascar and to identify barriers and facilitators of ANC attendance and IPTp uptake. A scoping review was selected as the most appropriate methodology due to the limited number of articles in the published literature, and the potentially substantial information in unpublished project reports and surveys.This work was guided by the methodological framework for scoping reviews developed by Arksey and O’Malley , and refThe purpose of this review was to determine the breadth and depth of available information on MIP activities in Madagascar and to describe the status of MIP prevention and treatment activities, including ANC attendance, IPTp uptake, ITN use and prompt care seeking among pregnant women.Studies and reports on maternal health care in Madagascar were collected by searching databases and inquiries regarding non-published articles to key informants, which included members of the NMCP and partner organizations. For published articles, PubMed and Google Scholar were searched using the terms “malaria AND pregnancy AND Madagascar” for the years 2010–2021. The same terms and time frame were used to search for reports in the US Agency for International Development (USAID)’s database: the Development Clearing House (DEC). References in these documents were reviewed for additional relevant materials. Key informants were contacted via email regarding relevant reports, surveys and studies that may not have been in searchable databases. Titles and abstracts of materials identified during the search were compiled in an Excel database and screened by two reviewers. Only titles and abstracts with information on MIP in Madagascar were included for further review. If publications or final reports were available, interim reports of the same project were excluded. Only materials available in English or French were reviewed; if both English and French versions of a document were available, only the English version was included.Documents were reviewed for relevant content and grouped as: care seeking; MIP prevention; and, quality of care, including health facility/health care worker capacity for providing MIP services. Documents that did not include information on any components of MIP prevention or treatment specifically in Madagascar were excluded. A data extraction tool based on PRISMA  extension guidelines for scoping reviews was designed to capture and summarize relevant findings . For eacA total of 91 documents were found for the period 2010–2021; these included articles published in peer reviewed journals, PowerPoint presentations, infographics, and reports from USAID-funded projects. Dissertations from Madagascar universities were not searchable, and a review of article citations did not produce any additional materials. Public documents and poster presentations were shared through key informant consultations. Of the 91 documents, 23 (25%) met the inclusion criteria. Of the included documents, six (26%) were peer-reviewed publications, 16 (70%) were partner reports, and one was an infographic (4%)  varied greatly among the included documents; nine documents reported data on two IPTp doses (IPTp2); while only eight documents contained information about three or more doses (IPTp3 or IPTp3 +). Coverage of IPTp3 and IPTp3 + among women who had given birth in the previous 12 months ranged from 8.4% in a 2012–2013 nationwide evaluation [Factors associated with IPTp2 uptake in one analysis conducted in 2014 among mothers of a child under the age of two included years of education, IPTp/ANC ideation, and exposure to malaria messaging . HoweverAmong pregnant women who reported having an ITN in their home in one survey, 98% reported sleeping under an ITN the previous night and understanding the benefits of ITNs for malaria prevention . In thisThe reviewed documents contained data about care seeking  collected through cross-sectional surveys or from ANC registers.In a 2017 survey, 89% of women reported attending at least one ANC visit during their most recent pregnancy . This isWomen reported different facilitators of and barriers to seeking care. Eight documents confirmed that barriers to care seeking and ANC attendance included distance from facilities; cost; negative perceptions of health facilities, including unwelcoming providers; a preference for traditional healers; a lack of personnel and supplies at health facilities; and/or concerns about personal security , 21–25. Tazomoka, which translates to ‘mosquito fever’, whereas community members referred to it as tazo, which translates to ‘fever’; thus, the study concluded that health communication campaigns could be misunderstood [A 2016 study found that the language used to describe malaria differed between providers and clients. For example, providers referred to malaria as derstood .Facilitators to care seeking were also reported, albeit less frequently. Some women mentioned being motivated to seek care because of the perceived high quality of care provided at facilities. In one study, most women of reproductive age (86.5%) felt confident in their ability to seek appropriate care . A modelEight documents reported on efforts to improve components of quality of care  , 26–29. A 2017 health facility assessment in Manajary District found providers possessed a high level of knowledge about malaria prevention and control; 100% cited ITN use and 94% cited SP as a means of preventing malaria. However, only two-thirds (64%) were comfortable assessing gestational age, a necessary action to early provision of IPTp. Only 11% cited malaria detection and treatment as a means of prevention and control .Stockouts of SP were a major issue impacting quality of care in multiple documents. A 2015 report found that SP was available at 75% of university hospitals, 10% of regional referral and district hospitals, and 27% of health centres . The docNone of the documents reviewed in the scoping exercise contained information about the treatment of malaria in pregnancy nor coordination needed between the NMCP and the MCH programmes or other relevant MOH divisions.This scoping review highlights several common themes regarding prevention of malaria among pregnant women in Madagascar. Critical barriers to prevention activities and knowledge gaps were identified or confirmed by this review, and prevention measures with high reported uptake were noted across the studies, surveys and reports. The review confirmed the existence of few published studies on MIP in Madagascar and most available information was found in donor-funded project implementation reports (16 of the 23 documents). While many of the documents contained information on multiple elements considered essential for MIP programmes, none of the reviewed documents systematically reported on all the essential elements required for a comprehensive MIP programme; in particular, all were missing information about effective diagnosis and case management of MIP, as well as the collaboration needed between NMCP and MCH programmes. Collaboration with MCH is important because MIP activities are implemented on the ANC platform. Although the quality varied greatly, the studies and reports contained rich information to inform future intervention and research approaches.The most common barriers to MIP prevention included distance from health facilities , unwelcoThis review revealed that ITN use among pregnant women was consistently high, as was women’s knowledge of the importance of sleeping under an ITN. This is similar to findings from other malaria-endemic countries: a systematic review of 98 studies on IPTp and ITN use found that ITN delivery through ANC had fewer obstacles than IPTp uptake . For IPTThis review identified health system weaknesses contributing to the quality of care such as commodity stockouts, the lack of data on supportive supervision of HCWs providing MIP services, and HCW knowledge gaps. Documents examining providers’ knowledge of MIP guidelines reported low competency in MIP interventions, and several partner reports planned for interventions to improve provider knowledge , 28, 29.Several gaps in reporting and implementation of activities to address barriers were identified. There is a dearth of high-quality, disaggregated data on malaria morbidity and mortality among pregnant women, with very little information on clinical management of pregnant women experiencing febrile illness. There is also a lack of information on potential solutions to increase IPTp uptake in Madagascar, such as utilizing traditional healers to provide targeted messages on MIP prevention or providing pregnant women with SP tablets at their first ANC visit to take at home each month instead of requiring directly observed therapy.Relevant information in doctoral theses and reports from non-governmental organizations (NGOs) may have been missed in this review because they were not in searchable databases. However, informal consultations with key stakeholders were conducted to help mitigate this limitation. Databases from World Bank, Global Fund, UNICEF, and other partners were not searched, so it is likely that relevant documents were not reviewed for inclusion. Also, the quality of documents in the review varied; key variables were missing definitions, and statistical information for interpreting results or making comparisons was unavailable.This scoping review identified individual- and system-level deficiencies impacting the quality of MIP services in Madagascar. It identified available information and gaps ; which gaps require more investigation  and current interventions needing updates . The lack of information about diagnosis and treatment of malaria among pregnant women and the coordination between NMCP and MCH are important programming considerations as well. Finally, the review identified noteworthy strategies requiring additional information, such as women’s perceptions of their access to IPTp or engaging traditional healers in delivering effective prevention messages. These findings can assist Ministries of Health and partners in strengthening comprehensive MIP programming efforts.


Exploring the coupling coordination mechanism between higher education and environmental governance is conducive to understanding the mutual interactions between them and thus enhancing mutual development. This study constructs the coupling coordination mechanism and the aggregated evaluation index system to measure the mutual coordination relations between them, assesses the performances and the coupling coordination degrees between them in the case of western provincial regions in China, and proposes countermeasures based on the prediction results. It is found that the performances of higher education are relatively more stable than those of environmental governance, and the distributions of the average performance grades exist noticeable geographical differences. Besides, the coupling coordination degrees increase with mild fluctuations with relatively small spatial variations, demonstrating the balanced and similar coordinated development status among regions; furthermore, in the future, the gaps in the coordination status among regions will gradually decline. This study highlights the mutual coordination mechanism between the two subsystems, compares the coupling coordination status among regions both temporally and spatially, and proposes specific, generalizable development suggestions that contribute to the academic sector, policymakers, ecology, and sustainability. Higher education and environmental governance are two critical factors in accelerating social development. The relationship between higher education and environmental governance is complicated ; howeverIn order to explore the coupling coordination development between the two, this article firstly constructs the coupling coordination mechanism between them and sets up the aggregated evaluation index system; secondly assesses the performances and the coupling coordination degree between them with an improved information entropy weight method and coupling coordination model with the case of western provincial regions in China; thirdly predicts the coordination tendencies by using gray prediction model, and proposes suggestions for future coordinated growth.The contributions are as follows: theoretically, the study constructs the coupling coordination mechanism and the evaluation index system accordingly; practically, differentiated countermeasures are provided based on the temporal-spatial comparisons of the coupling coordination status, which are helpful references to places with similar conditions; sustainably, the study confirms our determination to achieve sustainable development of both society and environment at the same time.This study defines higher education as the condition and the level where the local post-secondary education sector is qualified and competitive , 10. HigHigher education impacts environmental governance positively. Firstly, higher education sectors provide increasing skillful graduates and professional engineers to solve environmental governance problems and enhance environmental governance performance , 14. BesHigher education also influences environmental governance negatively. The teaching schemes, curriculums, and textbooks accompanied by higher education development are usually relatively lagging compared with the social reality, which to some degree impede the current requirement and the actual performances of environmental governance , 26. BesEnvironmental governance positively impacts higher education. Firstly, benign environmental governance results provide better environmental resources such as good lands, clear water, and fresh air, which are competitive factors to attract more talented teachers and students and thus enhance the local higher education quality . MeanwhiEnvironmental governance also affects higher education negatively. First, environmental governance occupies much public funding; when the local budgets or funds are constant, environmental governance means more funding will be allocated, and less money will be given to the local higher education sector, which limits the development of the local higher education sector . BesidesPrevious studies have proved that higher education and environmental governance interact complicatedly; therefore, it is needed to explore their interaction mechanism so that mutual positive interactions and balanced growth can be achieved. Coupling coordination, which describes the interaction status between systems, can evaluate the complicated interactions between higher education and environmental governance. The coupling coordination model, which reflects the interactions from disharmony to harmony between systems, has proved valuable and appropriate for analyzing systems’ mutual effects via interactions , 47. PreIt is necessary to analyze the coupling coordination status between higher education and environmental governance, and deepen the understanding of such interactions. It benefits more effective evaluation of higher education and environmental governance and helps propose more suitable suggestions for coordinated growth between them. Nevertheless, empirical research on the coupling coordination between them is not easy because there are no precise coupling coordination mechanisms and no widely accepted theoretical frameworks or indicators to measure them. Additionally, though conducive to this study, former studies regarding the relations of higher education and environmental governance usually ignore spatial-temporal comparisons of multiple places, which is essential to understand the coordination relations between them comprehensively. Therefore, in this study, it is necessary to conduct the coupling coordination research between higher education and environmental governance by comparing multiple places from both temporal and spatial perspectives.This study selects the 12 western provincial regions of the West China Development Strategy, including Shaanxi, Inner Mongolia, Ningxia, Gansu, Qinghai, Xinjiang, Tibet, Chongqing, Sichuan, Guizhou, Yunnan, and Guangxi . We seleThere are bilateral coupling coordination interactions between higher education and environmental governance; therefore, it is possible to construct a coupling coordination mechanism to illustrate such complicated coordination relations .In this mechanism, the higher education subsystem and the environmental governance subsystem follow the “input-output” framework and “pressure-state-response” frameworks, respectively , 50, 52.For the higher education subsystem: (1) higher education input  positively or negatively affect the three dimensions of environmental governance. For instance, more input to teaching leads to better performances of students and higher awareness to participate in the environmental governance activities; the more input to research in environmental governance, the higher the possibility of applying the more advanced technologies to reduce environmental pollution and achieve better environmental governance performances. On the contrary, more resources or funding allocated to the teaching and research of the local higher education sector may occupy the resources or funding of environmental governance, which to a certain degree restricts the effectiveness of the responsive actions of environmental governance. (2) Higher education output  impacts environmental governance positively and negatively. Specifically, more high-qualified personnel output provides academic support to reduce environmental waste, enhance environmental governance states, process environmental impact assessment, and take responsive actions to treat environmental governance issues. The high-quality academic or research outputs provide theoretical foundations or guidelines to enhance the environmental governance status and offer resources, benefits, policies, and countermeasures to decrease environmental governance pressure. On the contrary, the research output of higher education  directly pollutes the environment, decreases the environment quality, and increases the burden of environmental governance response; some controversial or even unethical academic output is likely to decrease the state of the environment and hinder the quality of environmental governance responsive actions , 45, 53.For the environmental governance subsystem: (1) environmental governance pressure  affects the input and output of higher education in positive and negative directions. In detail, increasing environmental pollution leads to increased research funding to study environmental governance. As a result, the research output in this field will increase accordingly. On the contrary, severe environmental governance problems such as pollution are detrimental to the persons in the higher education sector, who affect the input and output quality of higher education; also, the increasing pressure of environmental governance decreases the attractiveness and competitiveness of the local higher education and thus hinders the personnel input and output quality of higher education. (2) Environmental governance states  can promote or impede the input and output of higher education. For example, improved environmental governance states enhance the quality of higher education input: improved environment quality provides significant references for researchers exploring environmental-related issues such as sustainability and carbon neutralization and provides proper cases for teachers to discuss environmental governance. Besides, the enhanced environmental status improves higher education output: benign environment status enhances the satisfaction and performances of participants in higher education. On the contrary, deteriorating environmental quality sometimes restricts higher education: capital investments in higher education are more likely to escape from places with poor environmental quality; thus, both the input and output of higher education will be impeded. (3) Environmental governance response  supports and restricts higher education. In detail, more fiscal devotions of environmental governance treatment facilities encourage higher education personnel to focus on this field and pay more attention to developing related facilities, which in turn facilitates the growth of personnel and their high-qualified performances in academics and research. Besides, laws and regulations aiming to enhance environmental governance encourage professionals in the higher education sector to devote more resources to study and propose corresponding countermeasures. On the contrary, as the total amount is limited, investments in environmental governance practices occupy the input to higher education, which hinders the high-quality growth of higher education , 54–58.This article constructs an aggregated evaluation index system based on the coupling coordination mechanism to empirically assess higher education and environmental governance’s performances and coupling coordination degrees. The index should meet the following principles: (1) the index should cover the primary contents and main dimensions of higher education and environmental governance; (2) the index should be accepted and applied in previous research and have been proved scientifically; (3) the index can measure and reflect the mutual relationship between these two subsystems; (4) the data should be temporally and spatially available; (5) the index should be easy to understand , 56. AftIn the evaluation index system, the subsystem of higher education is sub-divided into two dimensions with eight aggregated indices, which are based on the input-output framework , 53. TheThe subsystem of environmental governance is sub-divided into three dimensions with 13 indices based on the Pressure-State-Response framework , 66. EnvWhen assessing the performances and coupling coordination degrees, weights of indices will be first determined. Several methods calculate the weights of indices and the systems’ performances. One valuable method is the improved information entropy weight method, which combines the traditional information entropy weight method and the technique for order preference by similarity to an ideal solution method (TOPSIS). There are several advantages of the improved information entropy weight method, including (1) easy to calculate, (2) getting weight objectively without factitious manipulations, (3) exhibiting relatively importance of different indices and making relative variations much clearer, and (4) covering deficiencies of using one method solely such as critical components missing , 67. ThiThe data collection process is mainly from the China Statistical Yearbook on Environment, China Statistical Yearbook on Education, Compilation of Statistics on Science and Technology of Higher Education Institution, and China Statistical Yearbook (2005–2020). These references are from national authorities and guarantee the objectivity and correctness of the research results.X. For the original matrix X, i and j are the option and index, respectively. This article selects the data of 12 western provincial regions enjoying the West China Development Strategy for 16 years; thus, there are 12×16 = 192 options in total for every index. According to i = 1, 2, …, m; j = 1, 2, …, n. In order to avoid value insignificance, values of 0 in the original matrix are replaced as 0.01, which is common in the standardization process T and Y = T; then calculate 0(t), and 0(t). If EP is no less than 0.6, the sequence is applicable for predictions [than 0.5 . Besidesdictions .Figs The performances of the higher education subsystem were relatively more stable than those of the environmental governance subsystem. In detail, most regions fluctuated within the same grades or two adjacent grades. For instance, Shaanxi fluctuated within the grade Good (0.6000–0.7999), and Xinjiang fluctuated within the grade Ordinary (0.2000–0.3999); Chongqing and Sichuan fluctuated between Fair (0.4000–0.5999) and Good (0.6000–0.7999), Guangxi, Yunnan, Inner Mongolia, and Qinghai fluctuated between Ordinary (0.2000–0.3999) and Fair and Tibet fluctuated between Poor (0.0000–0.1999) and Ordinary. The relatively stable performances of higher education were mainly because of the annual continuous and stable investments in higher education from the local authorities. However, there were some fluctuations in specific years for some regions, which was mainly because of the hysteresis effect of the higher education outputs such as academic papers and publications, which led to imbalanced performances between the dimensions of higher education input and higher education output, and which led to fluctuating performances of higher education among years. The relatively mild fluctuations of higher education are also proved by other cases or regions in other literature ; such siThe performances of the subsystem of environmental governance were relatively more fluctuating; in other words, many regions fluctuated among the three grades. In specific, within the five grades, namely Grade Poor (0.0000–0.1999), Ordinary (0.2000–0.3999), Fair (0.4000–0.5999), Good (0.6000–0.7999), and Excellent (0.8000–1.0000), Guangxi, Sichuan, Guizhou, and Ningxia (one-third of the regions) fluctuated among grades Ordinary, Fair and Good. Besides, the other two-thirds of the regions fluctuated between two grades, and no one fluctuated within the exact grade, just like the performances of the higher education subsystem. Moreover, there were relatively more obvious upgrading tendencies for the performances. In detail, from 2004 to 2019, 9 of the 12 regions witnessed increases in performance values, among which five regions  had upgradations to higher grades, which was more than the higher education subsystem (7 regions had increase and four regions had upgradations). The more apparent fluctuations of the environmental governance performances were mainly because of the imbalanced investment differences in waste treatments per capita among different years, which indirectly proves the significant effects of fiscal investments from local authorities on effective environmental governance. A former study also proves the annual variations of performances in environmental governance , demonstThe spatial distributions of the average performance grades of the two subsystems are similar in that the West regions had weaker performances than other regions. Xinjiang, Tibet, and Qinghai had lower grades than others in the higher education and environmental governance subsystem, demonstrating higher education’s relative input and output, and the relative pressure, status, and response to environmental governance were less satisfying. Former studies evaluated the actual performances of these three regions’ higher education and environmental governance and showed similar results , 58, 65,The spatial distributions of each subsystem exhibited a noticeable difference: there were relatively significant regional differences in the average performances for the higher education subsystem, whereas the spatial differences of the environmental governance subsystem were slight. In detail, for the higher education subsystem, there were also two regions falling in the Ordinary grade in the north and south respectively (Inner Mongolia and Guizhou) except for the three western regions mentioned before; besides, there were three regions  in the Good grade, which further expanded the spatial imbalances and differences. Such variations demonstrated that the traditional advanced regions in higher education  still maintained relatively high competitiveness and benign performances. On the contrary, for the environmental governance subsystem, except for the three western regions, all the other regions were in the same Fair grade; the minor spatial differences demonstrated that the environmental governance performances among regions were similar. Comparing the two subsystems, we could interpret that the regions with relatively low performances in higher education can achieve relatively high environmental governance (Inner Mongolia and Guizhou). Such results are somehow inconsistent with the former studies, which believe that regions in western China are almost weak in higher education, and the environmental governance among regions is not much balanced , 73. SucWe can find that most regions witnessed mild fluctuations of COU. In detail, some regions had apparent fluctuations; for instance, Gansu in 2013 had an apparent increase, and Tibet in 2015 and 2017 faced an evident decline; such noticeable fluctuations were mainly because of the apparent changes in specific subsystems: Gansu in 2013 had an apparent increase in environmental governance performance, whereas Tibet in 2015 and 2017 had apparent declines in higher education performances. Such fluctuations illustrate that specific subsystems would promote or impede the coupling coordination relations in the coupling coordination mechanism. This finding tells policymakers that they should make specific policies and take specific actions to decrease the impeding subsystems’ effects and gradually achieve more benign coordination between subsystems. The fluctuations are common in the coupling coordination relations, which are also seen in previous studies, such as between tourism and air environment governance ; thus, wAnother finding is that almost all regions fluctuated between the approaching and moderate coordination grades within the years. The regions fluctuated among the three grades, illustrating that the differences in COU were relatively small, and regions had relatively balanced and similar coordinated development statuses. Such relatively few differences demonstrate that all regions achieve similar efficient coordination growth, which proves that it is possible to reduce the statistical bias caused by demographical and geographical differences and to depict more accurate results when we compare regions from the perspectives of "per capita" or "proportion" rather than the "absolute quantity." Such results also prove the success of the high-quality development strategy in China, which aims to narrow the gaps among regions and achieve more benign and coordinated growth in every aspect. Certain studies use the "absolute quantity" indicators to evaluate the coupling coordination development of other systems  and obtained similar mild fluctuations and few differences. That is mainly because the regional differences are not so apparent (the absolute quantity differences are less obvious and are similar to "per capita" numbers) , 63. TheThe spatial variations of the coupling coordination relations between higher education and environmental governance are in Generally, the grades of COU were upgrading in the observed years. For instance, Ningxia and Guizhou upgraded their grades from approaching coordination in 2004 to slight coordination in 2019; Guangxi and Chongqing upgraded from slight coordination in 2004 to moderate and favorable coordination in 2019, respectively. The upgrades prove that these regions can attain a more benign coordination status between higher education and environmental governance when enjoying preferential policies such as the high-quality and develop-the-west strategies. In other studies, we can also find that taking China as an example, the coupling coordination status of other systems, such as finance and air environment, is upgrading , illustrThe gaps of COU between the regions in the west and others were gradually declining. In detail, in 2005, the three regions in the west  were in the approaching coordination and approaching incoordination grades, whereas, since 2017, these regions had reached the higher grade of slight coordination, which gradually declined their gaps with other regions. Such decline in gaps was mainly because of the tremendous inputs and investments in higher education and environmental governance in these three regions from the national and local authorities. The three regions enjoyed tremendous benefits from policies such as the West China Development Strategy, the West Special Program of National Social Science Foundations of China, the Plan of Pair Support for Higher Education Institutions in the Western Regions, the River Manager System, the Policy of Constructing Modern Environmental Governance System, and Liangshan Development (achieve harmonious and coordinated development between economy and environment protection). Therefore, more benign coordinated development between higher education and environmental governance is possible if sufficient funding and support from the authorities are devoted. Former studies also prove that when fundings and policies are fully and reasonably applied, the coupling coordination development of regions will be achieved .The predictions of the spatial variations of COU are in There are different performances of higher education and environmental governance from both temporal and spatial perspectives for different regions, and some regions witness the potential decline of the coupling coordination degrees; therefore, policymakers should propose specific while differentiated countermeasures to enhance the performances and the coupling coordination status between higher education and environmental governance. These countermeasures are also favorable references to other regions encountering similar situations.For the western regions with relatively low performances and coupling coordination degrees of higher education and environmental governance (such as Xinjiang) and the regions with declining tendencies of the coordination status (such as Yunnan and Gansu), policymakers need to eliminate the obstructive factors and to prevent the decline of the coupling coordination degrees. There are several specific countermeasures.The local policymakers should devote more budgets to the local higher education development and environmental governance; the money can be used in the teaching and research of the local higher education sector and waste treatment expenditures. Such accurate fiscal devotion will eliminate the obstacles of higher education input and environmental governance response actions and gradually prevent further decline.Introduce special incentive policies to encourage better output of higher education and more peaceful state or responsive actions of environmental governance. The authorities can offer cash prizes, honors, and awards for extraordinary research projects, highly-recognized academic papers and publications, and those who actively protect the environment and participate in environmental impact assessment issues. The incentive policies will encourage as many people as possible to enhance their performances and the coordination between higher education and environmental governance with precise actions and results.For regions with increasing performances and coupling coordination degrees (such as Tibet), it is essential to grasp the cherished opportunities to maintain such increasing tendencies and achieve better grades; policymakers can determine the critical competitive advantages or strengths and make the most of them. There are several suggestions to realize more harmonious coordination growth.Make proper strategies and policies according to local conditions. Before deciding on the development pathways, policymakers should conduct an in-depth analysis of local core opportunities and strengths and invite third-party experts to optimize the pathways based on the local competitiveness. Adjusting measures to local conditions will enable the policymakers to develop the coupling coordination between subsystems efficiently on the right track.Initiate cooperation programs with other regions or countries to explore new differentiated development approaches and to achieve better coupling coordination development. Regions are enabled to exchange resources they did not have; with the newly obtained resources, policymakers can propose new differentiated pathways to achieve better performances and a more benign coordination status. This policy will be beneficial for the regions to discover new opportunities and other key competitiveness so that the increased tendencies can be maintained.For regions with relatively high performances and coupling coordination relations , policymakers can develop more and better methods to coordinate better higher education and environmental governance. There are some countermeasures.Categorize different indicators and take differentiated approaches to enhance the values of indicators. It is better to maintain the status quo for the indicators that are difficult to further optimize in a short time (such as forest cover rate). It is better to take various actions for the indicators that can be further improved immediately . Differentiated treatment of different indicators helps policymakers enhance performance and coordination statuses efficiently.Summarize the existing advanced experiences into theories and better apply these theories to explore new and innovative approaches in future development practices. Professionals are encouraged to participate in the whole process; the sublimation of practice into theory is helpful for policymakers to carry out practical innovation and enhance the coordination with new approaches.Generally speaking, some effective countermeasures for national authorities can enhance the coordinated development in the country.Initiate national strategies and laws to promote the coordinated development of higher education and environmental governance. The national strategies should be directive so local authorities can identify specific details suitable for local conditions, and the national laws should clarify the positive and negative lists. These will affect the local policymakers that their legal actions to enhance the local coordination performances will be supported and protected by the state power, and their illegal countermeasures will be strictly forbidden.When evaluating the actual performances of each region, the national authority should consider the demographical differences; when allocating resources, the authority should consider proportions or “per capita” more than the absolute quantity. These will give policymakers more accurate insights into the coordination development between higher education and environmental governance.This article selects the 12 western provincial regions as the case, explores their performances in higher education and environmental governance, assesses and predicts the coupling coordination degrees between higher education and environmental governance, and proposes countermeasures that are valuable references to other places with similar situations. Key findings are summarized below.For the performances of both subsystems, the higher education subsystem is relatively more stable temporally; spatially, the distributions of the average performance grades of the two subsystems exist with apparent geographical differences.For the coupling coordination degree, the degrees increase with mild fluctuations temporally; spatially, the grades of the coupling coordination degrees are upgrading, and the gaps among regions are gradually declining.For the future tendencies of the coupling coordination status, temporally, the coupling coordination degrees of the following years will remain stable with slight increases in most regions; spatially, the gaps among regions will gradually decline.There are several contributions to this study.Academically, this study constructs a coupling coordination mechanism between higher education and environmental governance, establishes the aggregated evaluation index system to depict the coordination interaction modes, and proposes differentiated countermeasures. These enrich the theories of coupling coordination, higher education, and environmental governance and provide practical academic support for the western regions to achieve more peaceful higher education development and environmental governance.Practically, this study provides applicable differentiated countermeasures based on the theoretical analysis and temporal-spatial comparisons; these measures are practical, feasible, and targeted and can provide significant support for policymakers to formulate follow-up policies and blueprints. These make the policy decision procedures more scientific, practical, and convincing.Sustainably, this study explores the coupling coordination relations between higher education and environmental governance and obtains encouraging results that these two subsystems can achieve benign coordination interactions. It signals that social development and the environment can coexist harmoniously and promote each other; therefore, we can promote social growth without sacrificing the environment and promote environmental governance without giving up better social development. This insight further strengthens our determination to achieve sustainable development and environmental protection.The limitations and future research agenda are as follows.2.5" are neglected because the data are too challenging to obtain, though we admit they are essential actually; indices "number of students" and "total investment of waste treatments" are neglected because they focus on the absolute quantity rather than the proportion. The future research agenda would endeavor to collect more data to include those critical indices, carefully select some representative "absolute quantity" indices, and construct a comprehensive evaluation index system.Some indices are excluded. For instance, indices "satisfaction with higher education" and "average concentrations of PMThe study precision is limited. We only select annual data rather than quarterly or monthly data; besides, we only select the data of the provincial regions rather than the cities in these provincial regions. We admit that quarterly or monthly data of cities will significantly enhance the study precision and lead to a more detailed understanding of the coupling coordination status. The future research agenda would collect more detailed data (quarterly data of cities) to observe detailed temporal and spatial changes in the coupling coordination status.S1 Table Performance of the higher education subsystem.(ZIP)Click here for additional data file.S2 Table Performance of the environmental governance subsystem.(ZIP)Click here for additional data file.S3 Table COU.(ZIP)Click here for additional data file.S4 Table(DOCX)Click here for additional data file.


The identification of current gaps in high-impact medical research in Saudi Arabia has international significance due to the trend of collaborative research in the field of health and medicine and the focus on knowledge-sharing. The purpose of this study is to assess the current focus, gaps, and priorities in health research in Saudi Arabia.We employed a mixed-method research approach to achieve research objectives. (1) a systematic review of scientific research studies that are published between January 2020 to January 2022 in the top fifty Q1 medical science journals (2) a cross-sectional survey collected data from professionals employed in various organizations including the Ministry of Health (MoH), Ministry of Education (MoE), health organizations and universities, and the health industry. The close-ended survey questions inquired about the broad and specific areas of ongoing health research projects by these researchers and organizations in Saudi Arabia.n = 741), Pub Med (n = 244) and Google Scholar . After screening, (n = 26) original studies were selected for detailed evaluation and synthesis. Among these (n = 7) studied infectious diseases, (n = 7) cancer, and cardiac disease (n = 5). These studies focused on the etiology, treatment management and therapy outcomes of these health conditions. The survey was completed by (n = 384) respondents from these organizations. Most of the ongoing research projects focus on clinical sciences (27%) followed by basic sciences (24%) and public health research (24%) and a limited number of researchers were involved in healthcare management (2%) and informatics (2%). Most research focused on kidney and liver disorders (80%), obesity (74%), diabetes (74%), hormonal diseases (64%), and infectious disease (66%); it is equally important to design and fund research in some of the neglected areas including reproductive health (3%), physical and mental disabilities (1%).The literature search on databases identified Science Direct (Findings suggest that current gaps in original research from Saudi Arabia are in healthcare service quality, reproductive health, physical and mental disabilities and health informatics. Researchers and funding agencies and international collaborative projects should prioritize these areas. The World Health Organization (WHO) urges global, regional, and local research to improve access and delivery of healthcare services to all sections of the population in accordance with their regional and national circumstances . The WHOResearch studies in the field of health sciences assess health problems, understand their causes, utilize the research findings to formulate policies, practices, and products; and evaluate the effectiveness of health interventions. Saudi 2030 vision also aims to devise efficient healthcare systems by expanding and improving the quality of healthcare services as well as financing health services to achieve universal health coverage. The Saudi government allocated both financial and human resources in scientific research to strengthen the procedures for data sharing and access to updated information and supported institutions and health organizations to conduct research, which is helpful in assessing their progress toward the Saudi 2030 vision. In 2015, more than 3.2 billion Saudi Riyal were invested in science and technology projects, out of which ~23% of the total funding went to medical and health research projects. In addition, the Ministry of Education (MoE) has taken nearly 24 initiatives to support research and development activities including research capital funding, university-industry partnership programs, international collaborations, research training, and knowledge-sharing platforms  research articles were published in PubMed indexed journals from Saudi Arabia during this period. Out of total research that was contributed by countries from Arab sphere during this period, around 27% was by Saudi Arabia.A bibliometric analysis of research papers that were published between 1980 and 2014, demonstrated that (33%) of research articles published during this period were focused in area of clinical and health research . A totalThe current reliable estimates of high-impact research productivity in Saudi Arabia are limited to scholarly research published until 2017 , 11. TheThe current study adopts a mixed-method approach to gain deeper insight that will be useful for setting appropriate courses of action to achieve the research and development goals. The identification of current gaps in high-impact medical research in Saudi Arabia has international significance due to the trend of collaborative research in the field of health and medicine and focus on knowledge-sharing. According to recent estimates, 65% of Saudi Arabia's scientific output between in the past two decades involved international collaborations . InternaThe specific objectives of this study are as follows:- To assess the current trends and existing gap in health science research in Saudi Arabia.- To determine future priorities for scientific research in health science.- To make suggestions for the re-formulation of health research strategies and international collaboration in specific area to enhance high-impact research productivity in Saudi Arabia.The study employed a mixed-method research approach that included (1) a systematic review of high-impact scientific research studies published between January 2020 and January 2022 in the top fifty Q1 journals and (2) a cross-sectional survey of key stakeholders comprising researchers, administrators and key informants in organizations that fund clinical and public health research in Saudi Arabia conducted in March and April 2022.The systematic review was completed using the PSALSAR framework which has six steps. The details of each step followed to complete this systematic review are presented in n = 384) professionals who were in any of the three given roles, namely a researcher, an administrator, or a representative of the funding organization/s, completed the survey forms.Data on the online survey form were collected from key informants and researchers working in various organizations in Saudi Arabia during the study period. These included administrators from the Ministry of Health (MoH) and the Ministry of Education (MoE), researchers and faculty from higher educational institutions/universities, governmental and non-governmental healthcare organizations, research funders, independent researchers in health organizations and universities, research consultants, staff in health industry involved in research and development projects. A total of  studies from Saudi Arabia were published in these journals during this period. Out of (n = 26) original studies, (n = 7) focused on infectious diseases, cancer (n = 7) cardiac disease (n = 5) particularly the etiology, treatment management, and therapy outcomes of these diseases. Other published studies focused on diabetes (n = 1), dental problems (n = 1), maternal health (n = 1), child obesity (n = 1), inherited disease condition (n = 1), emergency healthcare services (n = 1), and treatment protocol for amiodarone therapy (n = 1). Most of the published studies were funded by key organizations supporting scientific research in Saudi Arabia including the King Abdullah International Medical Research Center, King Abdullah bin Abdul-Aziz University, and some in collaboration with international funding agencies. Pharmaceutical research was funded by pharmaceutical companies such as Pfizer, AstraZeneca and, Genomic Health.The information extracted from the articles published in the top 50 Q1 medicine journals between January 2020 and January 2022 is shown in Among the respondents, 61% identified as researchers, whereas 21% were associated with organizations that fund the health research projects. Participants were involved with various organizations directly and indirectly implicated in research work, and the majority were affiliated with the MoH (47%). Among the researchers, 28% were working as principal investigators and co-investigators .The analysis of ongoing projects of respondents revealed that almost one-third of the current research focuses on clinical sciences; almost one-quarter of the research is focused on basic sciences (24%), and an equal proportion is on pharmaceutical sciences (24%), and basic sciences (21%). The analysis revealed that around 2% of current research focuses on the quality of healthcare and (2%) on medical informatics .The findings  demonstrAmong the specific areas of health research, 80% of current research projects are drug trials; over 50% of the ongoing research focuses on disease pathology (54%); nearly one-third of the studies focus on radiology and informatics (29%); and less than one-quarter focus on surgery (17%). Finally, few current research studies (2%) focus on intensive care and life support .The current study aimed to inspect the current focus, trends, and gaps in population health research in Saudi Arabia based on data obtained from a systematic review of high-impact journal publications in the past 2 years and a survey of research leaders to collect information about their ongoing research projects. The current study is significant because the Saudi government is moving toward a knowledge-based economy and has taken several initiatives over the past decade, such as research funding and collaborations with international research organizations for higher education, research and innovation . It alsoOur findings show that a smaller number of ongoing research projects have focused on maternal health, reproductive health, and developmental disabilities. This finding aligns with the previous literature , 38; whiFinally, the findings from the survey also demonstrated that a limited number of current projects study issues related to healthcare management and medical informatics. Since Saudi Arabia has adopted several health reforms and automation of healthcare systems, it is important to allocate more resources to study how this automation is increasing the efficiency of healthcare systems, as well as the challenges faced by the healthcare force and patients.This study adopted a mixed-method approach to conduct a comprehensive analysis of the current focus of scientific research on population health in Saudi Arabia. A systematic review of studies published in high-impact journals and a cross-sectional survey of key players in the field was an effective research methodology to accomplish the research objectives and provide useful insights. The current study's findings are helpful in identifying existing gaps in health research and making recommendations for future research priorities. The findings demonstrate some of the positive outcomes of initiatives taken by the Saudi MoH and MoE to promote scientific research in Saudi Arabia in the past decade, as a result, few important original studies were published in the top high-impact medical journals. Original scientific studies in the field of medicine require labs, technological equipment, and appropriate research training, along with the enhancement of critical thinking and creative abilities, to develop leaders in scientific research in Saudi Arabia. Therefore, the study findings underline the need to invest in these areas, and such measures will be effective in enhancing the outcomes of existing research initiatives and smooth progress to achieve the Saudi 2030 vision. Among the study limitations, the current systematic review limited the analysis to the specific period of the last 4 years and the top 50 high-impact journals. In addition, the cross-sectional survey comprised of close-ended questions and thus a detailed assessment of underlying reasons for the lack of research on certain topics were not conducted. Qualitative studies are needed to identify obstacles and issues that must be addressed to prioritize research areas. Qualitative studies are recommended in the future to obtain the opinions of leaders in scientific research, which will be useful in formulating strategic plans and addressing the existing gaps in health research. Understanding the needs and roles of stakeholders will provide more insight to overcome barriers and appropriate actions to achieve research and development goals, the ensure the availability of adequate resources at an institutional level to conduct such studies. Globally, research is being conducted at a fast pace, and it is necessary to design research that identifies, the specific reasons restricting the production and publication of high-impact health research in Saudi Arabia. Some of the priorities for future research funding in the health sciences in Saudi Arabia should focus on health issues such as physical and mental disabilities, reproductive health, maternal health and dental disorders. In additions, original studies should be funded to assess progress and development on health informatics and the quality of healthcare services in Saudi Arabia.In conclusion, some of the important studies that have been conducted in the last decade on MERS-CoV, cancer and cardiac diseases in Saudi Arabia were published in few top high-impact science journals. This number must be increased further, and future research should focus on identifying the key reasons to address this gap. It is a positive development that most of the ongoing research projects focus on major health problems in the Saudi population such as kidney and liver diseases, obesity, diabetes and hormonal diseases. However, there are some existing gaps in research in some specific areas such as physical and mental disabilities, dental diseases and reproductive health problems should also be considered in future research. The impact of major developments in the healthcare industry, such as the expansion of health informatics systems and the delivery of healthcare services should also be investigated to devise appropriate healthcare policies and procedures.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The studies involving human participants were reviewed and approved by Ethical Review Committee University of Ha'il. The patients/participants provided their written informed consent to participate in this study.Conceptualization, systematic review, data analysis, write-up, and review and revision: AA-S. Systematic review, data analysis, write up, and review and revision: SH. Data collection, data extraction, and review and revision: FA. Systematic review, data extraction, review and revision, and references: MA. All authors contributed to the article and approved the submitted version.