This study explores the association between childhood immunization and gender inequality at the national level. Data for the study include annual country-level estimates of immunization among children aged 12–23 months, indicators of gender inequality, and associated factors for up to 165 countries from 2010–2019. The study examined the association between gender inequality, as measured by the gender development index and the gender inequality index, and two key outcomes: prevalence of children who received no doses of the DTP vaccine (zero-dose children) and children who received the third dose of the DTP vaccine (DTP3 coverage). Unadjusted and adjusted fractional logit regression models were used to identify the association between immunization and gender inequality. Gender inequality, as measured by the Gender Development Index, was positively and significantly associated with the proportion of zero-dose children . Consistently, full DTP3 immunization was negatively and significantly associated with gender inequality . These associations were robust to the use of an alternative gender inequality measure  and were consistent across a range of model specifications controlling for demographic, economic, education, and health-related factors. Gender inequality at the national level is predictive of childhood immunization coverage, highlighting that addressing gender barriers is imperative to achieve universal coverage in immunization and to ensure that no child is left behind in routine vaccination. Gender equality is not only an important standalone goal, but also a key contributor to and indicator of health of populations more broadly . Gender In addition to gender inequality in specific health outcomes or determinants, aggregate measures of gender inequality more broadly can be informative indicators that influence population health. Two widely-used measures of gender inequality at the population level are the Gender Development Index (GDI)  and the To examine the relationship between gender inequality indices and childhood immunization across countries, we utilize two outcomes related to the combined diphtheria, tetanus and pertussis vaccine (DTP): zero-dose children, or zero-dose DTP, a proxy for children who have missed immunization services entirely, and DTP3 immunization coverage (DTP3), a proxy for children who have accessed the full series of basic immunizations. These outcomes together represent both extremes of the immunization cascade . The DTPIn this study, we assess whether gender inequality is related to immunization at the national level. We expand upon previous work in this area  using reThe data used in this study include annual national estimates of childhood immunization, indicators of gender inequality and other demographic, economic and social characteristics. Data were available for up to 165 countries per indicator per year, spanning from 2010 through 2019.The associations between childhood immunization and gender inequality were assessed for two primary outcomes based on national coverage of the DTP vaccine among children under one. The first outcome was the prevalence of zero-dose children, or zero-dose DTP, defined as the percentage of surviving one-year old children who have not received the first dose of the DTP vaccine series. The second outcome was the prevalence of DTP3 immunization (DTP3), that is, the percentage of one-year old children who have received three doses of the DTP vaccine.We examined factors selected a priori to account for demographic, geographic, and other human development characteristics that have been shown in the literature to be associated with national childhood immunization levels . These iTo capture human development, we first utilized the human development index (HDI), which is a summary measure of achievements in three key dimensions of human development: a long and healthy life, access to knowledge, and a decent standard of living. HDI is computed as the geometric mean of normalized indices for each of the three dimensions . We analGender inequality was measured using two metrics: the gender development index (GDI) and the gender inequality index (GII). Gender inequality is a complex construct to capture quantitatively; we chose, therefore, to examine two measures to ensure robustness of findings.GDI measures gender inequalities in achievement in the three basic dimensions of human development captured by the HDI: health, education, and control over economic resources. To calculate the GDI, the HDI is calculated separately for men and women in a country, and the GDI is the ratio of HDI value among women to HDI value among men. Additional detail on GDI construction has been published elsewhere .(1)GDI=GDI values below 1 indicate higher human development among men than women, a value equal to 1 indicates equality, and values above 1 indicate higher development among women than men. We created a binary analysis variable for GDI based on quintiles of its sample distribution , dichotomized to high gender inequality favoring men (Q1) vs. medium/low/negligible gender inequality (Q2–Q5). We analyzed GDI as this binary measure in regression analyses.GII measures gender-based disadvantage in three dimensions: reproductive health , empowerment , and the labor market (measured by labor force participation). It shows the loss in potential human development due to inequality between women’s and men’s achievements in these dimensions. It is scaled from 0 to 1, with 0 reflecting a situation where women and men fare equally, and 1 reflecting a situation where one gender fares as poorly as possible in all measured dimensions . We analGDI and GII were selected as they are two widely-used gender inequality indicators which are publicly available at the national level across countries and across years.We first produced basic descriptive statistics and cross tabulations of immunization outcomes and gender inequality indices, as well as unadjusted outcome distributions by levels of gender inequality, for the most recent year of data available (2019). We then conducted a series of regression analyses to examine the association between childhood immunization and the level of gender inequality using a pooled 10-year dataset. All country-years for which data were available were included in analyses. As the outcomes are transformed to proportions with values between 0 and 1, all models were estimated using fractional logit models  ,42.The outcome indicator, Y (zero-dose DTP or DTP3 coverage), was estimated as a function of an indicator of gender inequality and other covariates. The estimated fractional logit model has the form:Models that used GDI were estimated with a binary variable equal to 1 if countries were in the high gender inequality category (Q1), and 0 if countries were in any of the four medium/low/negligible inequality categories (Q2 to Q5). Models that used GII were estimated including the index as a continuous variable measured between 0 and 1. Summary immunization coverage levels are presented by binary  levels of both indicators.Model (1) estimates the unadjusted association between the outcome and gender inequality (GDI or GII), without controlling for any other factors;Model (2) includes controls for annual population growth and age structure (measured as the percentage of the population under 15 years of age), percentage of urban population, and the three individual dimensional indices of the HDI ;Model (3) includes the same controls as Model (2), but the level of human development is measured through the overall HDI, instead of the three dimension-specific indices;Model (4) includes the same controls as Model (2), but the level of human development is measured through three specific economic, education, and health indicators, namely: natural log of GDP per capita PPP, mean years of schooling for the population 25 or older, and the log of current per capita health expenditure PPP.For each immunization outcome and measure of gender inequality, four models were estimated:All four models also accounted for non-parametric time trends via year fixed effects.All model results are presented in tables; for simplicity, we present in text and figures only results from the model with the largest likelihood and best fit, Model 2.p < 0.05 for all comparisons including adjusted odds ratios (AORs); 95% confidence intervals (CIs) are reported throughout. All analyses were conducted using STATA 16.1 [All regressions were estimated with standard errors clustered at the country level. Statistical significance was set at ATA 16.1 .Data were available for at least one year in the range 2010 to 2019 for 165 countries for GDI and for 162 countries for GII . In the In 2019, the most recent year of available data, higher gender inequality was associated with higher prevalence of zero-dose DTP and lower DTP3 immunization coverage in unadjusted cross tabulations . CountriThe results of the fractional logit regressions are presented by the measure of gender inequality used. The model with the largest likelihood and best fit (Model 2) was the preferred model to describe main results in text and figures. Full regression output for all models can be found in The first set of models are estimated using the GDI indicator, dichotomized as high gender inequality (favoring men) or not.GDI was significantly associated with both zero-dose prevalence and DTP3 coverage in regression analyses . In counEstimated coefficients can also be interpreted as average partial effects; that is, the percentage point change in the outcome variable (zero-dose DTP or DTP3 coverage) for a change in the category of gender inequality See . CountriThe association between gender inequality and childhood immunization was further examined using the GII as an alternative measure of gender inequality. The GII was analyzed as a continuous variable ranging from 0 to 1, with 0 representing total gender equality and 1 representing total gender inequality favoring men. We replicated the same four models as used to analyze GDI.Estimated marginal effects of GII on immunization outcomes, as reported in Results from these analyses indicate that the level of gender inequality in a country was significantly associated with national childhood immunization rates during the time period 2010–2019, with greater gender equality associated with improved immunization coverage. These findings were consistent across both examined outcomes of childhood immunization, reflecting the two extremes of the DTP immunization cascade (zero-dose DTP and DTP3), and across both examined measures of gender inequality, GDI and GII. Greater gender equality was associated with markedly better immunization coverage in unadjusted bivariate comparisons in 2019, whereby coverage of DTP3 was more than 10% higher and zero-dose prevalence was 7% lower in countries with lower gender inequality compared to countries with high gender inequality. These findings were consistent in direction and significance of effects in multi-year, multivariate regression analyses. Though precise model estimates differed, these findings were not sensitive to the choice of additional demographic and human development indicators included in regression models. In total, these findings suggest that gender inequality is a meaningful and statistically significant predictor of childhood immunization at the national level, even when accounting for other known correlates of immunization coverage including demographic, geographic, and human development indicators capturing wealth, education, and health, as well as year fixed effects which capture non-parametric time trends in both immunization and gender development.These findings confirm calls for the reduction of gender barriers to improve immunization access, and add to the evidence that gender equality is tantamount to ensure universal coverage and equity in childhood immunization ,10,11. RWhy Gender Matters: Immunization Agenda 2030 [Findings from this study suggest that policies and interventions which directly address gender inequality are needed to ensure high and equitable immunization coverage. Gender responsive measures in policy and practice can address some of the immediate challenges faced by caregivers in accessing immunization services for their children. Practical examples of such measures include establishing the location and timing of vaccine clinics based on mothers’ work schedules and time availability, holding vaccination clinics in locations that are easily accessible for mothers, or having female vaccinators in communities where it is not socially acceptable for men and women to interact. These measures can improve coverage services for a short period; however, approaches that have sustained impact will be those that address deeper inequalities, including those factors captured by the GDI and GII such as education and control of resources. Maternal education, and, by proxy, gender inequality in education, has in particular been extensively studied and shown to be a determinant of child immunization ,48,49,50nda 2030 . Often tnda 2030 , multi-snda 2030 . Howevernda 2030 ,27.Findings from this study should be considered in light of several limitations. First, these analyses involved a cross-sectional ecological analysis, and therefore cannot demonstrate causality. However, plausible theoretical pathways between gender equality and childhood immunization outcomes, as well as prior literature with similar findings using individual-level and qualitative analyses, support the importance of the observed associations. Second, these are national-level analyses which may conceal within-country differences in association; observed associations likely underestimate the associations between gender inequality and immunization coverage among the most marginalized populations. Future work is planned to examine the relationships between measures of gender inequality and immunization coverage at the subnational level. Third, the measures of gender inequality examined here (GDI and GII) have several limitations, including capturing only some elements of the broader construct of gender inequality, and sensitivity to indicators and variable definition ,55. DespThis study also has several strengths. It uses 10 years of data from up to 165 countries, presenting a more complete global analysis than any previously published work. Findings were robust to the choice of gender inequality measure (GDI and GII) and to the choice of immunization indicator (DTP3 and zero-dose DTP), as well as to model specifications, strengthening the conclusion of significant and meaningful associations between gender inequality and coverage. Though the ecological nature of these analyses preclude any conclusions on causality, the alignment of findings with previous published work using individual-level , countryOur study found a significant negative relationship between national gender inequality and immunization coverage, using recent data from 165 countries and an ecological analysis approach. The results produced in this study strengthen the evidence base emphasizing the negative impact of gender inequality and gender related barriers in childhood immunization coverage, and bolster calls for gender-transformative policies and practices to ensure universal childhood immunization coverage and equity in immunization services.


TSC1, located on chromosome 9q34 and encoding hamartin, orTSC2, located on chromosome 16p13.3 and encoding tuberin. Hamartin and tuberin form a heterodimer that suppresses the mTOR pathway, which coordinates various aspects of cell functioning, including cell growth, differentiation, metabolism and proliferation.Tuberous sclerosis complex (TSC) is a genetic disorder with an incidence of 1:6000 live births. TSC affects multiple organ systems in widely variable presentations and is characterized by high rates of neurological and neuropsychiatric comorbidities. The genetic diagnosis is possible by identification of pathogenic mutations in eitherThe natural history of TSC indicated that symptoms might present differently between pediatric and adult individuals, reinforcing the importance of keeping independent clinical and genetic criteria. According to the International Consensus published in 2021, all individuals suspected of having TSC, regardless of age, should undergo MRI of the brain to assess for the presence of (sub-)cortical tubers and for other neuronal migration defects, subependymal nodules, and subependymal giant cell astrocytomas (SEGAs).Systemic manifestations of the disease, such as cardiac rhabdomyomas, can be detected on routine prenatal ultrasound, and brain involvement can be assessed in prenatal MRI by identification of features described above, allowing definite prenatal diagnosis.Epilepsy is highly prevalent and one of the major risk factors of developmental disorders associated with TSC, such as intellectual disability, autism and TSC-associated neuropsychiatric disorders (TAND). Because the first seizures usually appear during the first year of life, this offers a potential window for pre-symptomatic intervention. Studies have shown that abnormal electroencephalography (EEG) frequently precedes the onset of clinical seizures by several weeks to months. Thus, spikes on routine surveillance EEG are thus a reliable biomarker in TSC for impending onset of epilepsy. The International Consensus recommends routine EEG in asymptomatic infants with TSC every 6 weeks up to age 12 months and every 3 months up to age 24 months. Different types of seizures may coexist in the course of TSC. The most destructive are infantile spasms, which occur in approximately 30–60% of patients.Recent studies have shown a potential beneficial role of preventative antiepileptic treatment in TSC patients, with the possibility of improved outcomes in epilepsy and in cognition. For example, the EPISTOP trial demonstrated a potential neuroprotective effect from pre-symptomatic treatment, but the study was limited by its open label design and small enrollment numbers. The PREVeNT trial is formally studying the preventative use of vigabatrin in a double-blind, placebo controlled multicenter design, and will evaluate both 3-year epilepsy and neurodevelopmental outcomes. Another early intervention is epilepsy surgery, which are performed at an increasingly young age, aiming to prevent developmental fallout from recurrent seizures and medication exposure.The rapid development of precision medicine has led to novel needs in terms of evidence generation. Studies describing the natural history of TSC, along with reliable biomarkers and better understanding of the disease pathway, will allow the development of appropriate treatments. For instance, the mTOR inhibitor everolimus has been evaluated in randomized controlled clinical trials specifically to treat seizures in TSC, and was found to be an effective therapeutic option.Arquivos de Neuro-Psiquiatriareflects a single tertiary center experience embedded in the Brazilian healthcare system. However, their report demonstrates care that is current and up to date with other major centers across the world. I encourage the interested reader to keep a close eye on TSC, as it is serving as a model disease for rapid advances and even paradigm shifts in the field of pediatric epilepsy.The study published by Pereira et al.


Sub-Saharan Africa (SSA) has a significant proportion of populations living in urban slum conditions, where exposure to multiple environmental stressors and social inequalities is ubiquitous. This commentary synthesizes commonalities in recent environmental health studies from urban cities in East and West Africa, presented during a symposium sponsored by the Africa Chapter of the International Society of Environmental Epidemiology (ISEE) in August 2020. A key takeaway from this symposium is the need for harmonization of epidemiologic and exposure data collection in three domains tailored to the SSA context: (1) improvements in socioeconomic status (SES) measurement through harmonization in the conceptualization and operationalization of SES indicators; (2) improvements in air pollution exposure assessment in resource-constrained contexts by better integration, validation, and harmonization of exposure data of air pollution and mitigating factors; and (3) harmonization in the assessment of health outcomes and biomonitoring of contaminants. Focusing on these three domains would galvanize environmental epidemiologists in SSA around shared data collection instruments and shared data platforms and facilitate the pooling of data across the continent. Fostering this collaborative research will enable researchers and decision-makers to glean new insights and develop robust environmental health interventions and policies for SSA urban slums and for improved population health. Rapid urbanization without adequate planning or infrastructure capacity has contributed to the development of informal settlements or slums in low- and middle-income countries. Major cities in Sub-Saharan Africa (SSA) are home to some of the world’s largest slum settlements. The Kibera slum in Nairobi is the largest urban slum in Africa Amegah, 2021) [021 [2]. These environmental exposures in slum settlements undoubtedly contribute to the high burden of disease and ill-health, including cholera, gastroenteritis, respiratory illnesses, adverse pregnancy outcomes and cardiovascular diseases ,7,8,9. SThe social determinants of health were recognized early on in Europe, with the publication of Rudolf Virchow’s “Report on the Typhus Epidemic in Upper Silesia” and Friedrich Engels’ “Condition of the Working Class in England” 1844) ,12. Henc44 ,12. HThe two studies from Nigeria and Uganda urban cities showed the clear links between various measures of SES, such as level of education and household income, household assets, and housing material, with household cooking and lighting fuel usage. Socio-economic status was also shown to influence the ability of households to engage in activities that can mitigate exposure to cooking fuel emissions. While these realizations are not new, the level of similarities regarding the types of fuels being used and what these fuels were used for among Africa’s urban poor was conspicuous. As just one example, Kerosene is commonly used for both household cooking and for lighting indoors in the urban context of SSA economically deprived populations. There are clear linkages between SES, household air pollution sources and exposure mitigating factors, and the common burdens in different regions of urban SSA. However, there remain limited, focused efforts to validate and harmonize measures of SES in the conduct of environmental epidemiological research in SSA that involve populations from urban slum environments, using tools and methods that demonstrates validity and reliability of the SES indicators. Being able to conceptualize and operationalize a harmonized measure of SES in urban SSA is vital not only for designing research studies but also for interpreting its results in defining the extent of exposure disease association and, more importantly, determining the size of health benefit achievable through feasible exposure reductions.Significant disparities and limitations of air pollution exposure assessment approaches currently being implemented in different urban regions of Africa were highlighted at the symposium. The major disparity discussed is the lack of consistent access to air monitoring instruments in SSA countries to facilitate exposure assessment studies. Air monitors are typically obtained from international collaborators in the Global North and in most cases, borrowed for intermittent sampling periods, to support short-term research studies, and eventually returned at the conclusion of sampling campaigns. Such air pollution exposure assessments are thus heavily reliant on external partners—collaborations which may be fleeting due to funding constraints and funding imbalances globally. Short-term air sampling campaigns further limit the ability to accurately estimate chronic or acute exposures in a consistent and representative manner. While these disparities and limitations can partially be due to resource constraints, we note that many of these constraints are shared regionally and perceived as barriers to conducting high-quality exposure assessment for air pollution. These shared resource constraints can become an opportunity for enhanced collaboration and harmonization of data collection methods on the continent. Despite the relative lack of data on the diversified sources of household and ambient air pollution in SSA’s urban slum neighborhoods, these sources are likely to overlap across the region. It follows that the ways to mitigate household and ambient exposures will coincide as well, albeit with some inherent variability based on cultural differences, differences in the level economic development between regions, and differences in non-modifiable factors such as meteorology and geography. However, the shared characteristics can be harnessed to develop both survey-based and monitoring-based air pollution exposure assessment strategies that are standardized for SSA’s urban context. In addition, various low-cost air sensors and information and communication technologies (ICT) have emerged recently that can foster more data harmonization and data sharing. Freely available satellite remote sensing data can be fused with ground-level air monitoring for improvements in air pollution exposure assessment in SSA. Available satellite data products are varied and include (but not limited to) aerosol optical depth (AOD) available from Moderate Resolution Imaging Spectroradiometer (MODIS) and Visible Infrared Imaging Radiometer Suite (VIIRS) or precursor measurements of PM available from the TROPOspheric Monitoring Instrument (TROPOMI) and the Geostationary Operational Environmental Satellite Forward Processing (GEOS-FP). Such data products are able to provide high spatiotemporal resolution of pollutant measurements to help augment sparse air monitoring in SSA and support modeling efforts in the region ,21,22,23Global burden of disease estimates indicates that SSA suffers disproportionately from environmental pollution. However, the underlying data to support these estimates are not as reliable as data from higher-income countries . There iThe benefits of cooperation and pooling of cohort data have already been enumerated by others . These iThe Demographic and Health Surveys (DHS) Program has a measure of household air pollution (HAP) and water, sanitation, and hygiene (WASH) , which iFuture research priorities in line with this commentary’s observations should focus on robust measurement of SES, the socioeconomic differentials in environmental pollution and human exposures in SSA regions to help understand how socioeconomic disadvantage can trigger environmental pollution as well as predisposes individuals to exposure. Such research is urgently needed to trigger sustained action for addressing socioeconomic inequalities in African countries.In conclusion, we make a strong and compelling case for conceptualizing and harmonizing a measure of SES and environmental pollution in African countries to enable comparison of environmental epidemiological data across countries for the needed policy impact.


Integrated delivery of primary health care (PHC) services is a health reform recommended for achieving ambitious targets of the Sustainable Development Goals and Universal Health Coverage, responding to growing challenges of managing non-communicable and multimorbidity. However, more evidence is needed on effective implementation of PHC integration in different country settings.This rapid review synthesized qualitative evidence on implementation factors affecting integration of non-communicable disease (NCD) into PHC, from the perspective of implementers. The review contributes evidence to inform the World Health Organizations’ guidance on integration of NCD control and prevention to strengthen health systems.The review was guided by standard methods for conducting rapid systematic reviews. Data analysis was guided by the SURE and WHO health system building blocks frameworks. We used Confidence in the Evidence of Reviews of Qualitative Research  to assess the confidence of the main findings.The review identified 81 records eligible for inclusion, from 595 records screened. We sampled 20 studies for analysis (including 3 from expert recommendations). Studies covered a wide range of countries (27 countries from 6 continents), the majority from low-and middle-income countries (LMICs), with a diverse set of NCD-related PHC integration combinations and implementation strategies. The main findings were categorised into three overarching themes and several sub-themes. These are, A: Policy alignment and governance, B: Health systems readiness, intervention compatibility and leadership, and C: Human resource management, development, and support. The three overarching findings were assessed as each having a moderate level of confidence.The review findings present insights on how health workers responses may be shaped by the complex interaction of individual, social, and organizational factors that may be specific to the context of the intervention, the importance of cross-cutting influences such as policy alignment, supportive leadership and health systems constraints, knowledge that can inform the development of future implementation strategies and implementation research.The online version contains supplementary material available at 10.1186/s12913-023-09151-x. The global burden of non-communicable disease (NCD) is growing and becoming the leading cause of preventable mortality –3. NCDs,Primary health care (PHC) is defined by WHO as: “A whole-of-society approach to health intended to maximize the level and distribution of health and well-being through three components: (a) primary care and essential public health functions as the core of integrated health services; (b) multisectoral policy and action; and (c) empowered people and communities.” . PHC theIntegration of health service delivery is a health reform recommended for achieving ambitious targets set for controlling the rising burden of NCDs , and comorbidity of other disease in people living with long-term communicable disease, like HIV and TB , 11–14. Integration requires various organizational changes in health systems to ensure connectivity, linkage, alignment, and collaboration in the delivery of various service, with view to ensure more efficient, effective, equitable health care for the complex burden of diseases , 15, 16.While the aim is for integrated services to create synergistic use of the available resources and reducing duplication, reconfiguration or reform of health services may face barriers , 15, 16.. Questions remain on how best to provide integrated PHC services, and more evidence is needed on feasibility, acceptability, and effectiveness of PHC integration types in various settings, including what are health worker perspectives of implementation considerations … and showing impact on population health.” (p20).Given the complexity of change required for integrated delivery of services, an organizational culture that is “outward looking” or open to innovation is essential . In an i“I think there will always be tensions between the people who are in commissioning and managing roles who want to manage the process to get the results delivered as quickly as you can, and the people who are clinicians who are delivering it trying to get the balance, realistic time scale and not letting the thing wallow and not deliver. But I think it is a constructive tension. (p135).Transformational leadership allows for balancing a centralized, structured and directive leadership approach at the macro level (country and systems) and meso level (across institutions), with allowing staff to exercise more flexibility at the microlevel of clinical leadership and frontline service delivery , 42, 43.Transformative leadership is supported when there is shared leadership that is aligned across levels, and where there is strategic planning and knowledge of change management at all the management levels , 43. ChaFurther, transformative leadership can provide clarity on team and individual staff roles and responsibilities, build meaningful and sustained partnership across organizations, and develop inter-disciplinary teams and collaborative care practices  The roleHuman resource management, development and support are major considerations for implementing integration of services; with the need for strategic realignment of financial, management, human resource systems to support the integration reform objectives. This involves human resource availability, appropriate skills and staff training, as well as supportive management and supervision , 47–50.“… managing stock-out, staffing distribution, rotation of staff and the way external support is provided  affect ability to provide integrated care.” (p13).Integration reforms require availability of appropriate human resources, both in terms of adequacy of numbers, but also in terms of configurations of leadership and of co-ordination, staff skills mix and staff distribution , 47–49. Organization of staffing, such as changing employees’ roles and responsibilities to facilitate integration, requires careful management, as it is associated not only with the skills of providers but also their attitudes to their changing roles and functions , 47, 49.The individual and organizational characteristics of service providers may determine their ability to provide integrated care . ProvideGood quality training and capacity development of staff are important considerations for supporting integration initiatives, as noted earlier. Good quality training has been characterized as needing to be comprehensive, tailored, flexible and interactive , 45. It “Involvement of content-experts (familiar with NCD prevention and management in low-resources settings) helps strengthen and accelerate consensus development and adoption of evidence-based standards of care and best practices.” (p7).Good-quality, diverse training by content experts was considered a good motivator for staff in supporting their implementation of integrated services , 41, 45:However, a shortage of specialists to train others in a multidisciplinary team can limit the development and thus the support of front-line staff , 36. For“The success of integration efforts is strongly associated with the quality of interpersonal and inter-institutional relations, including a commitment and willingness to change; a sense of belonging and appreciation; trust and communication; and credibility.” (p6-7).Successful and sustainable integration requires careful engagement with stakeholders throughout integration reform process; it depends on personal, social, and organizational factors, including the quality of interpersonal and inter-institutional relationships –44, 46. Supportive supervision and mentoring are considered key elements for engaging and motivating providers. It was noted that supervision that take only a technicist ‘tick-box’ approach , will have limited results. It is recommended that supervision should rather be aimed at developing staff skills and experience to enable them to make good decisions about patient care . This is" In other words, the systems software (people) can affect how effectively the systems hardware is utilized to deliver integrated services.” (p12).Effective provider engagement and support for implementing integration would require support for both structural (‘hardware’) resources as well as organisational culture and relational resources ‘(software’) , 36, 42."In our study, the relationship of trust between colleagues appears to be at least as important as that between frontline workers and managers.” (p13).The common “software” elements that were found in better-performing facilities include strong, supportive supervision, regular rotation of staff among services and motivated, confident staff who can work in teams . Comment“Teamwork is not easy: we need to find a trade-off between hierarchy and teamwork.” (p12).Integrated service delivery often require collaboration between teams from different disease programmes or working across disciplinary areas care , 44, 46.Managing professional tension requires focused investment in team building for inter-professional practice and developing a shared vision , 46. It The aim of this rapid review was to synthesize qualitative evidence on implementation considerations integration of NCD-related services into primary health care services, from the perspective of health workers, managers, and policy makers. The evidence covered a wide range of countries, from both high and low and middle-income settings, and from a variety of disease programmes and implementation strategies for integration.The findings highlight the important role of and enabling policy environment where governance mechanisms and policy are in support of the integration reform. Policy alignment with health system support services such as financial, supply chain and health information systems provide further support for the operational elements of implementation. The importance of health system readiness for implementing a new and complex intervention was highlighted, including how the baseline functional level of the health system can determine the capacity and success of implementation. A related factor is the compatibility of the new integration reform with the existing health service organisation, and the need for a ‘good fit’ with routine health service delivery. Transformative leadership is highlighted as important for leading, co-ordinating, and supporting implementation, and for change management, including managing both the technical (hardware), and the relational aspects (software resources) required for effective implementation. Finally, the review highlights the crucial role of effective managing, development, and support of human resources. This includes not only adequate staff availability and appropriate staff skill mix, but also development of staff knowledge and skills to ensure capacity, confidence, and motivation for integration, and the need for supportive supervision. Studies acknowledged the importance of community and patient involvement in planning, implementing, and monitoring integration, though interventions did not include such patient involvement.When considering the applicability of the findings to LMICs in particular, key considerations are high-level political and leadership commitment, policy alignment with resources, harmonization of government and donor funding to prevent further fragmentation, and alignment with national plans , and information and monitoring systems. A review of primary care models for NCD interventions in Sub-Saharan Africa largely concurs with our review findings, especially regarding the importance of training, multidisciplinary teams, and supportive supervision , but it Our main themes were roughly clustered according to the WHO health system building blocks  , and covThe findings in our review are also in alignment with findings from several reviews on different aspects of integration interventions –57. In aIntegration is a complex health reform, and the experience of stakeholders is important for understanding the barriers and facilitators. We observed a wide variety of integration interventions in terms of different configurations of disease programmes , as well the intervention implementation strategies . This heterogeneity of integration interventions has been found in other reviews of PHC integration models , 52, 58.The number of eligible studies identified for this review indicates that the evidence base is growing. While cross-sectional stand-alone qualitative studies of provider experience provide an important perspective, given the complexity and long-term nature of integration reform, we need more innovative, in-depth, longitudinal studies, using for example, ethnographic method and theoretical frameworks. More detailed descriptions of the intervention components and the local health care context is required (perhaps drawing on a taxonomy of implementation strategies), to allow for appraisal of the applicability of findings to similar settings. In a recent effectiveness review of integrated services for diabetes and hypertension in LMICs the authors noted the challenge of heterogeneity of interventions and called for more rigorous evaluations that include implementation research, economic evaluation and qualitative research on barriers and facilitators . FinallyN = 51), which was a sub-sample of the total number of eligible studies (N = 81), and the sample size was small which are further limitations. Drawing on additional WHO expert resources is not standards and could have skewed the sample. Finally, while our findings are based on wide scope of integration studies, we were not able to update our search to account for studies related to integration of services that may have been implemented address health service related to the COVID-19 pandemic. There are likely important recent findings with COVID pandemic-specific implications that are no captured in this search, and this calls for a further review of Covid-related service integration.Rapid reviews are valued for providing health decision-makers with timely access to evidence, though streamlining systematic review methods make it susceptible to bias . Our revNevertheless, the studies identified covered a large, diverse geographical spread, income settings, different configurations of disease programmes being integrated and a variety of integration implementation strategies and appear to reflect both the homogeneity and similar implementation considerations noted in other reviews , 54–56. The rapid review produced qualitative evidence on factors influencing implementation of NCD-related integration into PHC, across diverse country settings and integration intervention types. The review findings presents insights on how health workers responses may be shaped by the complex interaction of individual, social, and organizational factors that may be specific to the context of the intervention and show the importance of cross-cutting issues such as policy alignment, supportive leadership and health system constraints. This knowledge on the dynamics influencing health worker responses can inform the development of future implementation strategies and implementation research.Additional file 1: Supplementary file 1. NCD-related PHC Integration review: PRISMA Checklist.Additional file 2: A: Medline search strategy used for the Cochrane (parent) review on Health care worker perceptions and experiences of PHC integration [15]Additional file 3: Criteria for inclusion and exclusion of studies for screening.Additional file 4: Additional file 4. Characteristics of papers included in the sampling frame.Additional file 5: Table:CERQual assessments for seven main findings of the PHC Integration rapid review.


Ageism, winter, technology and safety were barriers identified by both groups. Outdoor spaces and infrastructure, transportation, community facilities, and Covid-19 pandemic were identified as barriers and/or facilitators. Older adults identified the ageing process as a barrier and diversity of the city, health and mobility and technology as facilitators. For stakeholders, barriers were deprivation and poverty, gender differences, and ethnicity, whereas age-inclusive activities were a facilitator. Organic and active opportunities for older adults and stakeholders to connect, co-produce knowledge on urban environments and share resources presented foundations of solution-building and future collaboration. CSS effectively facilitated a range of stakeholders across local urban spaces to collaborate and co-produce ideas and solutions for enhancing local urban environments to promote active and healthy ageing.Urban age-friendly initiatives strive to promote active and healthy ageing by addressing urban influences that impact individuals as they age. Collaborative community partnerships with multi-level stakeholders are crucial for fostering age-friendly initiatives that can transform urban community health. Employing a citizen social science (CSS) approach, this study aimed to engage older adults and stakeholders in Birmingham, UK, to (i) identify key urban barriers and facilitators to active and healthy ageing, and (ii) facilitate collaboration and knowledge production to lay the groundwork for a citizen science project. Older adults ( The idea of age-friendly cities has become a global movement that considers the role urban environments present for age-related challenges . ConsideEmploying a bottom-up participatory approach, the age-friendly agenda brings together the interests from older adults and urban planners to collaborate, co-produce knowledge and foster age-friendly spaces. Yet developing and actualizing inclusive and supportive age-friendly environments is argued to present a key gap for governance and public policy . A lack and inform policy  identify key urban barriers and facilitators to active and healthy ageing in local urban areas of Birmingham, UK; and (ii) to build on CSS to facilitate collaboration and knowledge production in order to form the foundations of a network that can further purpose collective policy recommendations to promote an age-friendly society.Our Voice CS for health equity approach  employ the A qualitative CSS approach was employed to actively engage older adults and community stakeholders to identify local urban barriers and facilitators and build the foundations of a network that can reflect on social concerns influencing the wider ageing urban community. The approach was deemed suitable as it employs a co-production level of CS, where individuals engage throughout all stages of a project, which can facilitate the generation of new knowledge from the individual and a collective group of individuals engaged  or community stakeholders only (n = 2 discussion groups) and were audio recorded by GW. One older adult discussion group included a community stakeholder from the same local area. The format of the groups included a study introduction and the use of three open-ended questions to facilitate discussions. These were shared at the start of the discussion, a strategy that has shown to facilitate stakeholder engagement and partnerships in the age-friendly agenda  and 11 community stakeholders  took part in 6 online discussion groups (60–90 minutes) exploring key urban barriers and facilitators to active and healthy ageing. The online discussion groups, which were held via Zoom Video Communications (5.8.4 (2421)), were separate for older adults only . GW completed an inductive analysis  using a GW transcribed each audio transcript to become familiar with the data. GW generated raw codes by identifying and coding all segments of a transcript to identify barriers or facilitator codes present. Both latent and semantic coding were completed based on the explicit content of what an individual said whilst applying an interpretative view to capture the meaning .GW examined each code to combine or collapse them together to produce more meaningful codes. Themes were then developed based on the combined codes that underpin each theme present for barriers or facilitators.Codes and themes were initially shared with AS and JP to be examined and discussed. This discussion guided a further stage of coding completed by GW, which involved collapsing codes further to produce more meaningful themes. The second set of themes was re-shared with AS and JP to discuss and produce a final set of themes.The audio transcript and the final set of themes were shared with older adults and community stakeholders for transcript verification  and membThe majority of older adults were White British (62%), married (68%), educated to university degree level or above (75%), and lived in Birmingham for a minimum of 30 years (68%). The residences of the older adults covered 11 of the 69 wards in Birmingham. The 11 wards represented the more deprived (9%), mid ranking (18%), least deprived (55%) and affluent areas (18%) across Birmingham. Ethnic groups across the wards included White British or White other (54.7%–87.8%), Asian (3.8%–30.9%), Black (1.2%–13.2%) and other ethnicities (1%–3.2%). Two of the 11 wards (18.9%) represented similar ethnic groups to Birmingham as a city, with 1 ward (9.1%) having higher Asian ethnicities and 8 wards (72%) having higher white ethnicities . The majA total of 13 barrier themes and 8 facilitator themes were identified across the older adult and community stakeholder groups. Out of these themes, 10 barrier themes and 7 facilitator themes were identified by older adults, and 12 barrier themes and 5 facilitator themes were identified by community stakeholders . Overallhealth and mobility, ageism, crime and safety), environmental , socio-cultural , economic  and political  domains of urban environments in Birmingham. Themes also overlapped across multiple urban domains, with the transportation theme representing movement across local urban areas , high costs of public transportation (economic), and the need for policy and local regulations to make public transportation more frequent and affordable . Similarly, technology was identified to facilitate online social activities and connections , present high costs as technology advances (economic), and a need for digital exclusion strategies and policies to be put in place . Covid-19 and winter were also themes highlighted by both groups. Covid-19 included barriers such as closed or lack of facilities for activities, decreased group activities, health concerns, and facilitators including increased outdoor activity and connecting through digital technology. Winter highlighted barriers such as darker evenings, reduced activity and fear of slipping due to bad weather.Nine matching barriers and four matching facilitators highlighted a range of interconnected and multi-level themes present across local urban spaces in Birmingham. The matching themes covered elements of personal : “I wanted a self-help group which everything was prepared, and ladies were willing to come, ladies and gents both. But I could not find, there’s no community centre or anything like that…I could not get a place”.P1 : “I’m wondering whether one of the partners in the organisation I am part of is somewhere near her, there might be an opportunity …the church has a charity which would allow yoga so if I send you the information, it might be that there is somewhere near P3 that would be interested in what she’s got to offer”Collaboration between community stakeholders led to the sharing of information and resources for local programmes, groups and schemes being run. Information about local park initiatives and organizations undertaking work in green spaces was shared between one group, whilst another group invited each other to local meetings happening. One group connected over their similar goals for local urban programmes, identifying ways to adapt current work in green spaces to be applicable across all community spaces. Stakeholders also shared ways to enhance each other’s schemes by sharing local research and identifying the need to put healthy ageing into an all-ages context:P3 : “I think putting it in sometimes into an all-ages context might actually be more helpful in terms of moving this forward”.P2 : “On that point, have you heard of the 8 to 80 cities which is research looking at how if you make it good for eight year olds, you also make it good for a two year olds, or vice versa”.P1 : “No, I haven’t but that’s exactly the point.”Employing a CSS approach, this study generated new knowledge about urban spaces in the context of social science. This knowledge was based on both the individual and collective voices of older adults and community stakeholders, alongside facilitating connections and resource sharing between these social actors. The main findings of this study demonstrate (i) the identification of urban barriers and facilitators to active and healthy ageing specific to the local-evel context of Birmingham; and (ii) the suitability of CSS for enabling knowledge production and collaboration at a preliminary stage.Cities encompass distinct concerns at the city, community and street levels which require suitable age-friendly approaches that can address these differing needs . The disCovid-19 which encompassed a range of context-specific influences identified by both groups. The closing of churches and lesbian, gay, bisexual and transgender facilities was seen to have reduced social contact, whilst perceived increase in crime and limited capacity on buses due to health risks decreased outdoor activity. However, local WhatsApp groups increased neighbourhood connections, and socially distanced changes to cafés and shops were viewed to make spaces comfortable. Whilst it is clear that older adults have been greatly impacted across their local communities and care settings by Covid-19 (Considering the local context of barriers and facilitators highlights the issues and needs of older adults at the local level and can develop urban indicators that facilitate age-friendly processes in local urban environments (The presence of community facilities, support and activities are specific local facilitators to Birmingham. All groups mentioned the importance of urban allotments and open garden events for facilitating walking, gardening activities and opportunities to socialzse with other residents. Public health research evidence supports the importance of allotments for older adults, which are associated with reduced stress and better perceived social cohesion and health (Employing a CSS approach at this stage facilitated discussions between older adults and stakeholders to co-produce a set of urban barriers and facilitators, which were grounded in real-world experiences and knowledge. Having a common framing of these urban influences engaged groups further to share ideas and co-produce actions in the facilitator themes. Age-inclusive sports such as cricket and engaging further with technology to address the divide between older adults and younger age groups were collectively discussed as facilitators by both groups. This indicates a sense of value in this exploratory phase in which CSS facilitated a collaborative generation of knowledge about urban spaces that surpassed consultation. Both older adults and stakeholders were able to discuss and identify collective initiatives and actions based on social concerns and embodied experiences present across urban spaces (CSS provided active opportunities to operationalize the joining of community-based knowledge and resources among older adults, stakeholders and also with the researcher. This facilitated co-production of relevant local knowledge on urban environments, rather than being solely directed by scientific practices, supporting the potential for legitimacy between these individuals for further collective and agreed-upon actions in urban spaces . CollaboA key strength of this study is the collaboration and shared knowledge resource facilitated by CSS. Older adults and a wide range of stakeholders collaborated to identify and discuss urban influences across Birmingham. This enabled a knowledge resource of ageing-well and urban planning processes to be shared, a collective identification of contextual and meaningful urban influences, and the foundations of a network to be formed.A priority area for attention in future studies is the representation of voices and experiences of ethnically and gender-diverse groups of older adults. This study utilized a qualitative and highly involved approach which encompassed the voices of a small group of older adults and aimed to build a community of interest around age-friendly urban change. Participants in our study were predominantly female and White English. Females are shown to have different mobility and travel needs  and pursOur Voice CS for health equity framework (CSS facilitated togetherness, networking and connection between older adults and between stakeholders to present a set of matching concerns and a sense of common purpose for urban spaces in Birmingham. These are elements that can inform decision-makers about the views of older adult residents (This study effectively engaged older adults and a range of stakeholders through a CSS approach to collaborate, share concerns and co-produce ideas for enhancing local urban environments across Birmingham. A set of urban barriers and facilitators were identified by both groups, presenting a range of matching features across personal, environmental, socio-cultural, economic and policy domains. Older adults and stakeholders collaborated during discussions to generate actions and solutions to further promote active and healthy ageing, including providing a range of age-inclusive activities. The emerging connections and resources shared between older adults and between stakeholders, alongside the alignment of matching urban barriers and facilitators, indicate the potential foundation for a collaborative network that can continue to be engaged further. Employing CSS shifted the focus of urban health promotion from targeting the individual to instead considering collaboration between individuals to identify community needs within urban environments, further supporting the increasing evidence base of the importance of place-based health promotion initiatives.daac126_suppl_Supplementary_Material_1Click here for additional data file.daac126_suppl_Supplementary_Material_2Click here for additional data file.


Depression is one of the leading causes of psychiatric disability across the globe because of its high prevalence and chronic, treatment resistant and recurrent nature. Erythropoietin (EPO), well known for its effects on blood cells, has also a key role in neuroprotection and cognitive function.The authors aim to explore the potential of EPO to treat depressive disorders (DD) and related cognitive dysfunction.A literature research was conducted on PubMed starting from the MeSH terms: “Erythropoietin” and “Depressive Disorders”. The results selected for our analysis corresponded to investigations using EPO based on an adult population with DD.The research provided 14 results, of which 9 met the defined criteria. Different types of studies with variable samples were considered, including randomized clinical trials (RCTs) and a systematic review. Overall, despite records of reduction in depression symptomatology and increased quality of life, evidence does not demonstrate statistically significant reductions in depression severity through the use of EPO in the treatment of DD. However, several RCTs examined its effect on cognitive performance, founding effective improvements in memory, verbal recall and recognition. The underlying potential mechanisms and the current limitations in the use of EPO, and of the available studies are analysed and discussed.Although EPO does not appear to be effective treating depression, it may play a role in improvement of deficits in memory and executive function. Larger RCTs evaluating its potential use are needed, in order to move towards better clinical practice, quality of life and functional reintegration of these patients.No significant relationships.


With the increasing exchange of domestic and international personnel, local infections of tropical infectious diseases are continuing in tropics and imported infections are emerging in non-tropics, some of which are accompanied by oral manifestations. Therefore, it is essential for dental professionals to identify the related oral manifestations, who are working for domestic medical service, international medical assistance, peace-keeping medical service or medical support of international joint military exercises. This study aims to investigate the attitude and knowledge of Chinese dental professionals on tropical infectious diseases and oral health, and to explore the difference between different genders, education backgrounds, professional identities, professional titles and tropics working experience.Network questionnaire was used to evaluate the knowledge and attitude of 236 Chinese dental professionals towards tropical infectious diseases and oral health.The scores of the participants on tropical infectious diseases and oral health were quite low. Although working experience in the tropics partially affected the understanding, there was no difference between different genders, education backgrounds, professional identities and professional titles.The understanding of dental professionals on tropical infectious diseases and oral health was insufficient. It is necessary to improve the clinical education and management specified with tropical infectious diseases and oral health.The online version contains supplementary material available at 10.1186/s12903-022-02250-x. Nowadays, personnel exchange has been largely increased because of increasingly open domestic and international cooperation, such as tourism, business, international assistance, peace-keeping action and international joint military exercises. As a result, sporadic and local epidemics of imported infectious diseases, being prevalent in tropics, have been reported in non-tropics –5. FurthOral-maxillofacial system has been reported to be affected by such infectious diseases, such as parasitic diseases , 7, viraTherefore, the aim of current study is to uncover the attitude and knowledge of dental professionals on tropical infectious diseases and oral health, and to explore the difference between different genders, education backgrounds, professional identities, professional titles and tropics working experience. We expect that these findings will alert tropical doctors to improve clinical education and management of tropical medicine and oral health.The network questionnaire (The Tencent Technology (Shenzhen) Co. Ltd, China), having been validated by a pilot study, was designed by three experts majoring in stomatology, infectious diseases and tropical medicine, respectively. Some changes were made based on the feedbacks of the pilot participants , including linguistic errors and improper statements. The reliability and validity of the questionnaire were evaluated by Cronbach’s α Coefficient (0.92) and Goodness of Fit Index (0.83). The final questionnaire consisted of 56 questions, concerning general information (6 items), attitude towards tropical infectious diseases and oral health (5 items), understanding of tropical infectious diseases (24 items), tropical infectious diseases related oral health (17 items) and management of tropical infectious diseases in dental clinic (4 items).By 2021, there were 278,000 registered dental professionals in China . AccordiThe data were divided into two parts: attitude and knowledge on tropical infectious diseases and oral health. The data were statistically analyzed between different genders, education backgrounds, professional identities, professional titles and tropics working experience. The score of each part of knowledge was normalized to 10, thus the total score was 80.p < 0.05.Descriptive statistics (number and percentage) was used to analyze general information of samples and attitude of the dental professionals towards tropical infectious diseases and oral health. Chi-square test or continuity correction was used to analyze the difference of ratio in different groups. Student’s t test and One-way ANOVA were used to analyze the Mean between different groups. The statistical significance was A total of 241 dental professionals from 25 provincial regions of China were recruited as participants. However, 236 participants completed the questionnaires (97.9%). There were 121 males and 115 females; 174 postgraduates, 54 graduates and 8 junior college graduates; 211 doctors and 25 nurses; 26 participants with senior titles, 126 participants with intermediate titles, and 84 participants with junior titles; 24 participants with tropics working experience, 212 participants without such experience. The average age was 35.7 years old (23–59 years old).  and systematical study experience 41.7% vs 21.7%) of the dental professionals on tropical infectious diseases and oral health  some infected patients or patients with drug-induced adverse events, need to be identified, may firstly visit the dentists for their accompanied oral discomfort –8, 13–16The network questionnaire was formulated to evaluate the understanding of the dental professionals on tropical infectious diseases and oral health: (1) The attention and study experience of the dental professionals on tropical infectious diseases was insufficient. Tropics working experience positively improved the attention and study experience of the dental professionals on this topic, whereas gender, education backgrounds, professional identities and professional titles did not affect it. It is indicated that the participants with tropics working experience might have seen some suspected cases during their clinical practice to improve the attention and study experience. (2) Most dental professionals realized the importance of study on tropical infectious diseases and oral health. Additionally, most dental professionals realized that it was helpful for the management of tropical infectious diseases through oral manifestation identification. All these suggest that the dental professionals’ attitude was positive on this topic. (3) The low score of the tropical infectious diseases and oral health suggested that mastery of the knowledge was poor among the dental professionals. In addition, gender, education backgrounds, professional identities, professional titles and tropics working experience could not ameliorate the understanding of knowledge, suggesting that (1) academic education, continuing education and clinical education are not satisfied on this topic; (2) some suspected cases might be misdiagnosed by some dental professionals; (3) learning and mastery of the knowledge was insufficient among the participants with tropics working experiences, although they have seen some suspected cases and realized the importance of tropical infectious diseases and oral health.With regard to the tropical infectious diseases and oral health, there were three types of surveys exploring knowledge mastery of medical and dental providers. Firstly, most research reported the knowledge and attitude of medical or dental professionals towards infectious diseases, such as AIDS , 24, hepLack of the knowledge and understanding of this topic might bring certain risks for the management of infectious diseases in dental clinics, such as misdiagnosis, missed diagnosis, delayed diagnosis and even leading to spread of infectious diseases. Therefore, it is urgent to develop an educational and training system for tropical infectious diseases and oral health: (1) Compile textbooks on tropical infectious diseases and oral health, including the knowledge about tropical infectious diseases; associated oral manifestations; oral adverse events of commonly used drugs for infectious diseases; clinical management; emergency treatment and follow-up treatment instructions, and so forth. (2) Offer public course of this topic in academic education, continuing education and clinical education. (3) Offer targeted guidance and training for the dental professionals who will be working in tropics, such as international medical assistance, peace-keeping medical service and medical support of international joint military exercises. (4) Establish a public communication platform to share popular scientific information, case report and discussion of this topic. We hope to raise concerns of this topic and improve the role of the dental professionals in the management of tropical infectious diseases through aforementioned measures.Tropical infectious diseases are highly related to oral health, neglect of which might trigger the spread of infectious diseases. We first investigated the understanding of tropical infectious diseases and oral health among dental professionals, which was neglected by most medical professionals and researchers. The data of the investigation showed that the dental professionals were lacking in understanding on tropical infectious diseases and oral health, which might bring hidden danger to oral and public health. It is necessary to improve dental education and management specified with infectious diseases and oral health.Additional file 1: Sample characteristics of the study.


Although artificial turf fields are utilized widely around the world, sufficient research has not yet been conducted to assess the potential human and environmental health risks posed by the chemicals contained in the fields’ fibers, backing, and often-used crumb rubber infill. Consequently, there is wide variation in governmental policies.Review the notable policies concerning artificial turf and crumb rubber infill in the European Union, United Kingdom, United States of America, Canada, China, Qatar, and the Global Stockholm Convention of the United Nations.Information was collected that included published papers, technical and policy reports, and grey literature. These were then analyzed by a collaborative group familiar with the environmental policies in their respective countries to extract the pertinent legislative or regulatory information. The group members were primarily identified through their involvement in publications pertinent to artificial turf and crumb rubber infill health research and included environmental health professors, active researchers, and governmental agency officials. Most information on direct policies was taken directly from reports provided to the public by various governmental agencies responsible for their countries’ regulations, often available within the respective agency’s online archives.There are significant differences in the regulatory approaches adopted by the investigated countries with regards to artificial turf and its crumb rubber infill. Some regions, such as the European Union, have taken substantial steps to limit the fields’ chemical components to which the public and environment are exposed. Other regions and countries have done far less to address the issue. Most policies relate directly to (i) the fields themselves, (ii) the microplastic components of crumb rubber infill, or (iii) the concentrations of harmful polycyclic aromatic hydrocarbons (PAHs), perfluoroalkyl and polyfluoroalkyl substances (PFAS), and heavy metals.While nearly every country acknowledges the potential health risks posed by heavy metals, microplastics, PAHs, and PFAS chemicals, very few have actually implemented artificial turf and crumb rubber infill regulations and/or established adequate surveillance measures to protect those regularly exposed to the fields. The European Chemicals Agency (ECHA) reported that in 2012 the European Union (EU) was home to at least 13,000 full-sized artificial turf fields and at least 45,000 smaller fields . It is fThere is currently much debate over the human and environmental health risks posed by the use of these artificial fields due to evidence of harmful chemicals contained in the artificial turf fibers and in the crumb rubber infill. A recent study from Yale University concluded that there are at least 306 different chemical agents in the crumb rubber infill, with as many as 197 exhibiting carcinogenic characteristics . It was This paper aims to review the international policies surrounding artificial turf and its crumb rubber infill. Regulations from the regions of the EU, United Kingdom (UK), USA, Canada, China, Qatar, and the Global Stockholm Convention are discussed.The countries and regions included in this study were selected to provide a partial representation of the current regulatory status in Asia, Europe, the Middle East, North America, and any globally-impacting agreements.Information was collected from published papers, technical and policy reports, and the grey literature. These were then analyzed by a collaborative group familiar with the environmental policies in their respective countries in order to extract the pertinent information  from often long, detailed reports. These individuals were primarily identified through their involvement in publications pertinent to artificial turf and crumb rubber infill health research, indicating a familiarity with the chemicals of concern and capability of understanding the existing regulations around these chemicals. They included environmental health professors, active researchers, and governmental agency officials. Much information on policies was taken directly from reports provided to the public by various governmental agencies responsible for their countries’ regulations, such as the ECHA for the EU and the US EPA for the USA; these were commonly available on the respective agency’s website or online archives. The search for pertinent policies was undertaken between May 2021 and January 2022. The analyzed documents and reports were primarily published in English, with some having been translated from their original language. Some documents, such as policies from China, were received in their original language and analyzed by the members of the collaborative group able to report the findings in English. Limitations of this study include the difficulty in locating and accessing governmental policies and regulations, particularly if the primary language of the country was not English. This meant that the policy collection may not be completely exhaustive in its entirety, and some pertinent policies may exist that are not considered herein.To understand the progression of the EU’s artificial turf regulations, a brief summary of organizational hierarchy is required. The Registration, Evaluation, Authorization, and Restriction of Chemicals (REACH) was an EU law created in 2006 that requires the registration of chemicals synthesized in or imported into the EU and established the European Chemicals Agency (ECHA) . The governing bodies in the EU can use REACH to restrict the permitted amounts of certain hazardous chemicals or to ban them outright, if necessary. REACH sets ‘minimum’ standards that member states and manufacturers may choose to further restrict, if they are so inclined. The ECHA applies approved chemical legislations and contains the Committee for Risk Assessment (RAC) and the Committee for Socio-Economic Analysis (SEAC). The RAC and SEAC advise the European Commission on potential policies concerning the posed substance risk to human and environmental health and the socio-economic implications of such policies, respectively. When chemical regulatory legislation is proposed by the European Commission, ratified by the EU member states represented in the REACH Committee, and approved by the European Parliament and the Council of the European Union, it is then in effect for all 27 member countries of the EU.The EU’s efforts have been the most ambitious in mitigating the potential human and environmental health effects posed by artificial turf. The two primary target areas for such efforts have focused on the PAH and microplastic content. With regard to PAHs, in March 2018, the ECHA published a record specifying the EU regulation of eight PAHs of concern: benzo[a]pyrene (BaP), dibenzoanthracene (DBahA), benzo[a]anthracene (BaA), chrysene (CHR), benzo[j]fluoranthene (BjFA), benzo[b]fluoranthene (BbFA), benzo[k]fluoranthene (BkFA), and benzo[e]pyrene (BeP) . The lim2 (50kg/full sized field), although it stated a clear preference for the complete ban on the use of microplastics in turf infill . In June 2020, the RAC issued an opinion supporting this restriction and recommended a ban on all microplastics utilized in infill for artificial turf fields after a transition period of six years . As anotf infill . The SEAf infill . At the f infill . While nf infill . Despiteμg/m2 in textiles and coated materials and to 10 mg/kg in substances . As of July 2020, perfluorooctanoic acid (PFOA) has been banned by the same EU POP regulation . After the restriction on PFOA was passed into EU law, concern was soon raised over the use of another PFAS subclass, perfluorohexane-1-sulphonic acid (PFHxS), as a subsequent alternative. Both the SEAC and the RAC issued opinions in 2020 supporting limitation of PFHxS use in the EU, meaning that the onus is on the European Commission to draft an official policy proposal for review . In January 2020, perfluorobutane-1-sulphonic acid (PFBS) was placed on the REACH chemical list of substances of very high concern . This means that the chemical is considered worthy of equal caution as shown to carcinogens, reprotoxicants, and mutagens. Concern has also been raised over the problem of substituting a banned PFAS chemical with another harmful PFAS chemical in the market, just as with the case of replacing PFOA with PFHxS. Due to this issue and the enormous number of substances in the PFAS family, the Netherlands is heading an EU proposal with Belgium, Denmark, Germany, Norway, and Sweden to implement a complete ban on the entire group of PFAS chemicals . The EU’s existing Persistent Organic Pollutants (POPs) regulation was expanded in 2009 to restrict the use of perfluorooctane sulfonic acid (PFOS) to 1 hemicals . The proThe withdrawal of the UK from the EU (Brexit) in December 2020 caused many operational and policy complications, including how the UK environmental regulation system would operate. Instead of complying with EU REACH chemical regulations, the new UK REACH now acts to set and enforce such limits . While the EU and UK REACH operate independently of each other, the UK REACH was, in principle, founded to maintain the key principles of its EU counterpart. Although the UK is free to maintain current EU standards and follow future EU regulations, the EU-UK Trade and Cooperation Agreement (TCA) (established in December 2020) allows the UK to establish its own regulations . The TCAAt the time of writing, the UK REACH limitations relating to artificial turf PAH regulations only include the same EU limits on extender oils used in tire manufacturing and the same 1 mg/kg PAH limit on products supplied to the general public that come into direct or prolonged contact with the human skin or oral cavity . There is no active legislation on the limitation of microplastics in artificial turf, even though the Environment Agency  published a quality protocol in 2009 stating that no routes should exist for crumb rubber water runoff from the artificial turf fields . The proIn 2018, the UK Government approved a ban on all microplastics used in the composition of cosmetic and personal care products . While tThe UK appears to have the same regulatory stance on PFAS chemicals as that of the EU before Brexit in 2020.Adding to the already-complicated UK regulatory network, individual countries within the UK are free to establish their own environmental regulations, provided that they at least meet the minimum UK REACH requirements. To provide an example of this, one could consider Scotland’s stance relative to that of the UK. The government of Scotland has previously indicated that it plans on upholding EU environmental standards after leaving the EU, and aims to use the UK Withdrawal from the European Union (Continuity) (Scotland) Act 2021 to follow EU regulations when they see fit . This The Health and Safety Executive (HSE) monitors Great Britain  for worker health and safely in a variety of spaces, including local authority premises, sports grounds, and school playing fields . It alsoEnvironmental regulations in the USA can be implemented at the federal, state, and local levels. The regulatory network of the federal government concerning artificial turf and its crumb rubber infill is virtually nonexistent, as is regulation of the notable chemicals contained therein. The gap between the USA and the EU is best demonstrated in the regulations (or lack thereof) concerning the PAH chemicals from which crumb rubber infill is composed. PAH content is regulated in the US by many agencies including the American Conference of Governmental Industrial Hygienists, the National Institute for Occupational Safety and Health (NIOSH), the Occupational Safety and Health Administration (OSHA), and most notably the US Environmental Protection Agency (US EPA) . While sThe USA similarly has no direct regulations in place for concentrations of heavy metals in crumb rubber infill. Concerns about the levels of zinc in the artificial turf infill have been raised in recent years, with one study detecting an upper value of 14,150 ± 1344 mg/kg in the crumb rubber . These fThe USA has paid considerable attention to PFAS chemicals that pose a potential threat to human and environmental health. The EPA uses the Toxic Substances Control Act (TSCA) to analyze and control harmful PFAS chemicals . A largeIn 2020, the Massachusetts Toxics Use Reduction Institute (TURI) published a PFAS background report that included two studies showing the presence of numerous PFAS chemicals of concern  in artificial turf fibers and backing . Both stIn December 2021, the EPA issued a public health advisory for both PFOA and PFOS . HoweverIn 2015, the US Government passed the Microbead-Free Waters Act, which banned the use of cosmetic products containing microplastics . In thisIn terms of direct policy, the majority of the USA  has no existing regulations concerning artificial turf and crumb rubber. Nevertheless, the issue has been gaining attention, and dispersed throughout the country are areas that have implemented policies favoring fields with sustainable alternatives to crumb rubber infill. Leading the way in 2009, the Los Angeles Unified School District placed a ban on synthetic turf fields containing crumb rubber infill, and required all newly installed turf fields to utilize alternative infill materials . In 2015In summary, although the USA recognizes microplastics and the PAH and PFAS chemicals contained in artificial turf fibers and crumb rubber infill to be harmful to human and environmental health, no federal policies have been developed and implemented that directly regulate the installation or chemical composition of artificial turf fields. Similarly, the vast majority of state and local governments have established no regulations. The lack of legislative action likely stems from the absence of conclusive studies demonstrating that average use of the artificial turf fields leads to adverse human health effects. With the conduct of more comprehensive and focused investigations, it is anticipated that part 2 of the Federal Research Action Plan on Recycled Tire Crumb Used on Playing Fields and Playgrounds will shed more light on the health risks of artificial turf fields and provide a foundation for the development of additional policies.The Canadian government has not established any standards that directly regulate artificial turf fields or crumb rubber infill. The Canadian Environmental Protection Act (CEPA) (1999) defined a toxic substance as one that enters or may enter the environment under concentrations or conditions that may have an immediate or long-term harmful effect on the environment, may constitute a danger to the environment on which life depends, or may constitute a danger in Canada to human life or health . When a 3 has been placed, along with limits on air emissions, drinking water and food contamination, and (in British Columbia only) on soil standards  . A totaltandards . BecauseIn June 2017, Canada released the Microbeads in Toiletries Regulations, placing a near-identical ban on the sale, manufacture, and import of cosmetic microplastics as that of the USA and the UK . As was the case for the other two regions, no limits have been placed on microplastics released into the environment from artificial turf fields.Canada does not manufacture PFAS chemicals. However, they may be imported into the country . Canada 2•h), respectively  . In 2020At the time of writing, it would appear that no standards have been established by the Chinese Government concerning the concentration of PFAS chemicals in artificial turf and crumb rubber infill. Similarly, no policies appear to have been created to address the issue of microplastics in these products.There appears to be no regulatory network of the Qatar Government surrounding artificial turf fields and crumb rubber infill. In April 2021, Qatar released the Ashghal Recycling Manual, which was created, in part, to detail the specifications and specific criteria for generation of crumb rubber from recycled tires. This document outlined thorough and extensive standards for the structure, coating, performance, and quality of the crumb rubber granules, but it did not provide limitations for any chemicals of concern  . Our sea3 . ROPME was formed, in part, to enforce the Kuwait Regional Convention for Cooperation on the Protection of the Marine Environment from Pollution, which was also signed by Qatar in 1979 . This Re3 . While sQatar is recently of particular note regarding athletics safety because it is serving as host of the upcoming 2022 FIFA World Cup.The Stockholm Convention is an agreement created by the United Nations (UN) in 2004 and signed by over 152 countries to control the release of persistent organic pollutants . GermaneA summary of the main relevant regulations for countries discussed in this review is provided in The regulations listed are only those pertinent to the topic of artificial turf fields and crumb rubber infill. These regulations are not exhaustive, but are a collection of notable policies relevant to the topic. A label of “none” indicates that our search failed to locate any policies pertinent to the regulatory area. Abbreviations: polycyclic aromatic hydrocarbons (PAHs); perfluoroalkyl and polyfluoroalkyl substances (PFAS); benzo[a]pyrene (BaP); dibenzoanthracene (DBahA); benzo[a]anthracene (BaA); chrysene (CHR); benzo[j]fluoranthene (BjFA); benzo[b]fluoranthene (BbFA); benzo[k]fluoranthene (BkFA); benzo[e]pyrene (BeP); perfluorooctane sulfonic acid (PFOS); perfluorooctanoic acid (PFOA); perfluorobutane-1-sulphonic acid (PFBS); The Registration, Evaluation, Authorization, and Restriction of Chemicals (REACH); perfluorohexane-1-sulphonic acid (PFHxS); European Union (EU); Environmental Protection Agency (EPA); perfluorocarboxylic acids (PFCA).The chemicals listed are only those contained in regulations pertinent to the topic of artificial turf fields and crumb rubber infill. Abbreviations: polycyclic aromatic hydrocarbons (PAH); benzo[a]pyrene (BaP); dibenzoanthracene (DBahA); benzo[a]anthracene (BaA); chrysene (CHR); benzo[j]fluoranthene (BjFA); benzo[b]fluoranthene (BbFA); benzo[k]fluoranthene (BkFA); benzo[e]pyrene (BeP); perfluoroalkyl and polyfluoroalkyl substances (PFAS); perfluorooctane sulfonic acid (PFOS); perfluorooctanoic acid (PFOA); perfluorobutane-1-sulphonic acid (PFBS); long-chain perfluorocarboxylic acids (PFCA); perfluorohexane-1-sulphonic acid (PFHxS); antimony (Sb); arsenic (As); barium (Ba); cadmium (Cd); chromium (Cr); lead (Pb); mercury (Hg); selenium (Se); zinc (Zn); volatile organic compounds (VOC); polybrominated biphenyls (PBB); polybrominated diphenyl ethers (PBDE).Artificial turf and crumb rubber infill contain and elaborate a wide range of substances  that can pose a threat to human health and the environment. Given their potential for adverse impacts, one might expect that countries would have established policies that regulate their use and/or limit the extent to which humans or the environment are exposed to them. After a review of the governmental policies relating to artificial turf, crumb rubber infill, and the substances associated with them, it is clear that there is great variability between countries regarding (i) whether the various chemicals are subject to regulation , and (ii) whether artificial turf and crumb rubber infill are directly considered for regulation. For example, the EU has the most comprehensive regulations regarding PAHs, microplastics, and PFAS, and includes direct consideration of artificial turf and crumb rubber infill for PAHs and microplastics. Others, like the USA and Canada, have regulations on the substances but have not established exposure limits for artificial turf and crumb rubber infill.Of the substances subject to governmental regulation, the PAHs have been subjected to the most scrutiny, likely because many of these chemicals are known carcinogens and may elicit serious adverse health effects through exposure . Given that artificial turf infill is most commonly created from shredding used tires that contain PAHs, one might expect that the regulations surrounding these chemicals would apply to the infill. This was the case for China, the EU, and the UK. Canada and the USA enacted regulations that established PAH levels for other exposure sources , but not for artificial turf or crumb rubber infill.Compounds closely related to PAHs have also been detected in crumb rubber in the Netherlands, although most have not been regulated in any country . These iMicroplastics have been identified as products of concern because they are not biodegradable and can thus create bioaccumulation problems in the outside environment (Accessed 7 July 2021). This affects general ecological health and contamination levels of food and drinking water (Accessed 7 July 2021). The ECHA estimates that around 42,000 tons of microplastics pollute the environment annually; escaped artificial turf crumb rubber infill is the largest individual contributor, being responsible for as much as 16,000 tons (Accessed 7 July 2021). For those countries regulating microplastics, the majority  only regulate levels in cosmetics and personal products, and do not address crumb rubber infill.Cadmium, lead, and zinc are present in crumb rubber infill. While such metals can exert negative effects on the environment and human health , most WeThe PFAS family of compounds is of notable concern. Often referred to as “forever chemicals,” PFAS are known for their resistance to degradation in both the environment and biological systems (including the human body), and, relatedly, their persistence and accumulation over exceptionally long periods of time  are becoming increasingly prevalent as a low maintenance, consistent surface alternative to grass fields. The routine use of these fields by sportspeople and children makes these populations vulnerable to exposure to the chemicals contained in (or emitted from) the artificial turf and associated infill. This consideration would certainly apply to occupational exposure, such as with workers involved in artificial turf installation and maintenance. Globally, few to no direct policies currently exist that would serve to protect any of these people from artificial turf chemicals. This may relate, at least in part, to insufficient or unreliable information about the health effects of artificial turf (and associated crumb rubber infill) substances. Legislative decision-making in this area is further hindered by a lack of knowledge about adverse human health effects of other crumb rubber substances  . Clearly