This review aimed at evaluating the possible benefits that caloric restriction (CR) may provide to periodontal disease progression and response to treatment.Electronic search on Medline, Embase and Cochrane, and manual search were performed to identify pre-clinical and on human studies reporting the consequences of CR on clinical and inflammatory parameters related to periodontitis. Newcastle Ottawa System and SYRCLE scale were used to assess the risk of bias.Four thousand nine hundred eighty articles were initially screened, and a total of 6 articles were finally included, consisting of 4 animal studies and 2 studies in humans. Due to the limited number of studies and heterogeneity of the data, results were presented in descriptive analyses. All studies showed that, compared to the normal (ad libitum) diet, CR might have the potential to reduce the local and systemic hyper-inflammatory state as well as disease progression in periodontal patients.Within the existing limitations, this review highlights that CR showed some improvements in the periodontal condition by reducing the local and systemic inflammation related to the periodontitis and by improving clinical parameters. However, the results should be interpreted with caution since robust research such as randomized clinical trials is still missing.This review shows that some dietary/caloric restrictions approaches may have the potential to improve periodontal conditions and, in addition, highlights a need for human studies with a robust methodology in order to draw stronger evidence-based conclusions.The online version contains supplementary material available at 10.1007/s00784-023-05052-9. Periodontitis is a microbially driven host-mediated disease that leads to loss of periodontal attachment and bone . At firsNutrition is intended as the process of taking in food and its use for growth, metabolism and repair . While nThe effects of nutrition in maintaining health and in the predisposition to periodontal disease has been gradually emerging in several studies that reported effects such as gingival bleeding reduction , reducedSeveral human and animal investigations have also been published concerning the possible effects of nutrition on management of periodontal disease.A recent systematic review of animal models concluded that macronutrients that have any effect on oxidative stress or immune system  seem to be important for the prevention or treatment of periodontal disease . A GermaFurthermore, different approaches including fasting diets have been used over the years with promising results in terms of longevity and health span . Two typUp to date, only few studies investigated the possible effect of a caloric restriction regimen on periodontal disease, and the results were controversial in terms of systemic outcomes (i.e. inflammation) and clinical parameters , 16.However, to our knowledge, no systematic reviews have been published to date which summarize the evidence about the potential effect of caloric restriction on periodontal disease. Therefore, the aims of the present systematic review were to (i) assess if restriction of caloric intake may have an effect on periodontal disease and response to treatment and (ii) summarize the quality of the existing evidence of caloric restriction and periodontitis.The present review was registered in PROSPERO .This systematic analysis was performed according to the Preferred Reporting Items for Systematic Review and Meta‐Analyses (PRISMA) statement , 18.Does a restriction of caloric intake have an effect on periodontal disease and treatment response ?Population: patients with measures of periodontal diseaseExposure/intervention: diets with caloric restrictionControl: patients continuing their regular diet or a diet with no caloric restrictionOutcomes: inflammatory markers, clinical variables  and patient-reported outcome measurements (PROMs)Study design: randomized controlled trials, cross-sectional studies, case-control studies, longitudinal cohort studies (retrospective or prospective), and animal studies reporting data on (i) periodontal disease diagnosis (at baseline and if applicable post-intervention) and comparison between two groups, including one with caloric restriction and one with normal diet , were included.Reviews, case reports and studies which included less than 10 participants were excluded.Electronic literature searches were conducted independently by two authors (GM and PS) through Medline, Embase and Cochrane Library Database, including studies published up to November 15, 2022.The following research strategy was used:  OR caloric restriction (MeSH terms) OR nutrition (keywords) OR diet (MeSH terms) OR fasting (MeSH terms)) OR dietary intervention (keywords) AND ((periodontitis (MeSH terms) OR periodontal diseases (MeSH terms) OR gingivitis (MeSH terms) OR periodontal patients (keywords) OR periodontal inflammation (keywords) OR gingival (keywords)).Journal of Dental Research, Journal of Clinical Periodontology, Journal of Periodontology and Journal of Periodontal Research (from 2000).The search was complemented by an Open Grey search and by conducting a manual search  in the following stages:Any papers that did not meet the inclusion criteria were excluded. After the full text screening (steps 1 and 2), the two reviewers compared the studies included by at least one of them and joined them all into a final database.Study designNumber of patients includedPopulation demographic Setting Definition and diagnosis of periodontal disease/health and of periodontal progressionDefinition of dietary interventionControl groupPeriodontal intervention (if any)Which variables were measured before and after intervention/controlOutcomes of the interventionFundingConflict of interestData were independently extracted by two independent reviewers (GM and PS). A data extraction form was used for each study in order to extract relevant data (mentioned below) to be included in this review:In studies published after 2017, classification of periodontitis according to the “2017 World Workshop” including Staging and Grading  or previCaloric restriction is ideally defined as a reduction of average daily caloric intake, between 10 and 40%, without malnutrition and without affecting the intake of essential nutrients like vitamins and minerals . Howeverhttp://www.ohri.ca/programs/clinical_epidemiology/oxford.htm) was followed for assessing the risk of bias in human studies, whereas, for animal studies, the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) tool24 [The Newcastle Ottawa System (NOS) protocol  tool24  was usedData were presented descriptively. Two separate data syntheses were provided for animal and human studies, respectively. Each outcome of the included studies was showed in summary tables.The study selection process is described in Fig. The main characteristics of included animal model studies are summarized in Table A further study  with theA more recent mice model study  used twoThe main findings of human studies included are summarized in Table A cohort study conducted in a periodontally healthy Korean population  adopted Another cohort study , carriedAccording to the SYRCLE scale for animal studies, all studies presented an unclear risk of bias . Newcastle Ottawa System revealed that the two cohort studies , 16 had This systematic review assessed the evidence for the potential effect of different dietary restrictions on the periodontium. The analysed studies collectively showed that certain dietary restrictions might have the potential to reduce the local and systemic hyper-inflammatory state in periodontal patients. Besides, promising results demonstrated that dietary restriction may also impede periodontal disease progression. However, the evidence so far is very limited.The last decades have brought a clearer understanding about the effect of diet on a whole series of human diseases and conditions. Several studies on the association of dietary intervention and periodontitis have also been published –13.Very interestingly, caloric restriction and prolonged fasting are considered as a robust physiologic stimulus which causes a mild-to-moderate biological stress that, in turn, leads to numerous endocrine and neurobiological responses from systemic levels up to molecular signalling pathways . As summEven though fasting has been used by several populations since ancient times, the modern approaches involving fasting regimens have been developed following the principles of a periodic fasting, that is a diet that aims at simulating a real fasting and that hence is called “fasting mimicking diet” (FMD), which is applied for 4–7 days once every 15–30 days or less. The FMD consists of 30–50% of the normal caloric intake and a composition which mimics the effects of water only fasting on a number of markers, consumed for 4–7 consecutive days, followed by one transitioning day before returning to the ad libitum feeding , 31. ThiA pre-clinical study included in this review reported that, after inducing the periodontitis, caloric restriction might dampen the periodontitis inflammatory response in monkeys . SeveralIntriguingly, the existing human evidence partially confirm these pre-clinical findings. In fact, Pappe et al. adopted a fasting approach in MetS subjects with advanced periodontal disease and highlighted that, without providing any periodontal treatment, a short-term reduction in BoP and GCF volume occurred , albeit While at present the evidence is lacking, should an effect of dietary restriction on periodontal outcomes be proven, dietary regimes could be associated to mechanical periodontal therapy in order to improve clinical outcomes and potentially reduce systemic inflammation. In the clinical reality, complete fasting may be difficult to achieve. Therefore, an interesting solution to improve compliance might be to adopt a fasting mimicking diet approach  . NotablySeveral limitations are present in the present review. First, the limited amount of the studies that was included. Second, the majority of them were animal studies, and three out of four were conducted by the same research group –25. FurtIn conclusion, to the best of our knowledge, this is the first systematic review that assesses the possible effect of dietary restrictions on periodontal disease. Overall, despite the paucity of the existing studies and some controversial but promising results, the present review concludes that some dietary/caloric restriction approaches may have the potential to affect periodontal conditions by reducing the local and systemic inflammation and by improving clinical parameters. In the search for adjunctive tools to improve periodontal outcomes and based on the promising evidence so far, there is an urgent need of methodologically robust studies that could evaluate dietary restrictions as an adjunctive therapy in patients with periodontal disease, assessing its potential effects on clinical and local/systemic outcomes and patient-reported outcome measurements, in the short- and long-term period.Supplementary file1 (PDF 45 KB)Below is the link to the electronic supplementary material.


It is an important objective of ecological restoration to select suitable plant species in order to construct plant communities and achieve certain soil and water conservation capacities. Using species functional traits to construct a response-and-effect framework is a promising method for determining how species in changing environments will influence ecosystem functions. Here, we investigated plant functional traits, soil properties, and ecohydrological functions for the most common vegetation restoration types in mid-Yunnan, China, and used seven plant functional traits to identify seven plant functional effect types in relation to soil and water conservation capacity, and two plant functional response types to soil physicochemical properties. The results indicated that specific leaf area was the key trait not only for functional effect types, but also for functional response types. In addition, eight overlapping species between plant functional response types and functional effect types were selected as the key restoration species. These results provide a methodological guide for species selection for recovery, as well as a species inventory for the restoration of degraded ecosystems in this region.Great efforts have been made to improve the soil and water conservation capacity by restoring plant communities in different climatic and land-use types. However, how to select suitable species from local species pools that not only adapt to different site environments, but also achieve certain soil and water conservation capacities is a great challenge in vegetation restoration for practitioners and scientists. So far, little attention has been paid to plant functional response and effect traits related to environment resource and ecosystem functions. In this study, together with soil properties and ecohydrological functions, we measured the seven plant functional traits for the most common species in different restoration communities in a subtropical mountain ecosystem. Multivariate optimization analyses were performed to identify the functional effect types and functional response types based on specific plant traits. We found that the community-weighted means of traits differed significantly among the four community types, and the plant functional traits were strongly linked with soil physicochemical properties and ecohydrological functions. Based on three optimal effect traits  and two response traits (specific leaf area and leaf nitrogen concentration), seven functional effect types in relation to the soil and water conservation capacity  and two plant functional response types to soil physicochemical properties were identified. The redundancy analysis showed that the sum of all canonical eigenvalues only accounted for 21.6% of the variation in functional response types, which suggests that community effects on soil and water conservation cannot explain the overall structure of community responses related to soil resources. The eight overlapping species between the plant functional response types and functional effect types were ultimately selected as the key species for vegetation restoration. Based on the above results, we offer an ecological basis for choosing the appropriate species based on functional traits, which may be very helpful for practitioners involved in ecological restoration and management. Soil and water conservation is one of the most important ecological functions and services. Because of their influence on soil erosion, ecohydrology, and water quality, changes in land use or management have imposed great pressure on watershed ecological restoration and management ,2. The mreTs) and plant functional effect types (PFefTs). This provides an effective way to select suitable species that can not only cope with specific environmental conditions, but also improve ecosystem functions.Trait-based approaches are increasingly used to explore the responses to environmental changes and ecological effects on ecosystem processes and functions ,8. RecenreTs and PFefTs has been suggested in the literature [reT is a group of plants with similar responses to a given environmental factor and that PFefT is a group of plants with a similar effect on certain ecosystem variables [reTs and PFefTs are similar or closely correlated, the effects of environmental change on the community functional structure may potentially spread to the ecosystem functions. Conversely, if PFreTs and PFefTs are distinct, communities may be able to withstand the effects of environmental changes while still maintaining ecosystem functions, despite changes in community functional structure. Lavorel and Garnier demonstrated that traits related to nutrient gradients and those affecting ecosystem functions overlapped highly [reTs and PFefTs appears to be useful for identifying key restoration species and exploring the relationships between the response of community to environmental disturbance and the effect on ecological functions [The differentiation between PFterature ,18. It id highly . Therefounctions . HoweverreF to site resources and PFefF in relation to the soil and water conservation capacity for the common species of the Central Yunnan Plateau. The main aims in this context are (i) to compare the differences in plant traits, soil properties, and ecohydrological functions across different vegetation restoration types; (ii) to examine the relationships between functional traits and environmental factors and ecohydrological functions; and (iii) to identify functional traits for choosing species of PFreTs and PFefTs for revegetation of soil erosion area and control of water and soil loss.The Central Yunnan Plateau is a crucial region for soil and water conservation in the Yangtze River Basin. Previous research has shown that plant attributes  are close to ecohydrological functions , which sPinus yunnanensis after deforestation. Other remnant coppices and pastures were abandoned and formed different secondary stands. This area currently includes secondary shrubland (SL), Pinus yunnanensis coniferous forest (CF), mixed needle–broad-leaved forest (MF), and natural secondary forest (NSF). These four main vegetation restoration types were selected to investigate the species traits, soil properties, and ecohydrological functions.Field work was done in Mouding County , which is about 200 km west of Kunming, Yunnan Province, China. The region has a warm temperate zone (Köppen–Geiger climate classification), with an average annual rainfall of 846 mm. The rainy season runs from May to October. The soil of the area is Cambisols (FAO/UNESCO classifications). A subtropical evergreen broad-leaved forest served as the area’s primary vegetation, but it has now been nearly entirely destroyed. Since the 1980s, some of the area has been replanted with fast-growing Five non-contiguous duplicate plots were randomly assigned for each plant community type. All 20 plots had similar climatic conditions, soil types, and slope gradients. All of the woody species (height > 30 cm) were identified and counted. The species relative abundance was calculated based on the diameters at the breast height or basal area.Seven representative plant functional traits were evaluated for the identification of the plant functional types, which are related to the plant structure, nutrients, and growth. The functional traits include the specific root length (SRL), leaf area (LA), leaf nitrogen concentration (LNC), leaf dry matter content (LDMC), specific leaf area (SLA), tree height (H), and plant growth type (GT). LNC, SLA, SRL, and LDMC were selected as the response traits relative to water and nutrients , and GT,n = P − Tf, where In is the sum of canopy interception (Ic) and stemflow (Sf), and P and Tf represent precipitation and throughfall, respectively. The difference between the mass of dry material and wet material was used to calculate the maximal water-retaining capacity of litter (MWClitter). The formula used to determine the soil maximum water-retaining capacity (MWCsoil): MWCsoil = 10,000 Pt h, where Pt is total porosity of soil and h is soil depth. We installed an automatic flow gauge to measure the amount of soil surface runoff along the lower edge of each plot. After each runoff occurrence, 500 mL of soil surface runoff was sampled and the soil erosion was measured by drying three replicates of 50 mL runoff at 105 °C. To create a new average volume, the soil surface runoff and soil erosion data from the previous four years were averaged. Three random plots from among the five plots were chosen to monitor the ecohydrological processes and functions. Two automatic rain gauges and two normal rain gauges were placed in an open area of the experimental station to monitor precipitation. Moreover, plastic collectors were put in place under the canopy of 10 sample trees to catch the throughfall. Because of the extremely low percentage of stemflow, we combined canopy interception and stemflow in this study and used the following formula: Iipa represents the relative abundance of species i in plot p, it represents the mean trait value of species i. Soil physicochemical properties, CWMs, and water and soil conservation parameters under different vegetation types were compared using one-way analysis of variance (ANOVA) and the Fisher’s least significant difference (LSD) test. In addition, we analyzed the correlations between the plant traits and soil properties and water and soil conservation parameters using Spearman’s correlation. As the plant community’s functional diversity index, the mean species trait values and the species relative abundance were used to compute the CWMs for each trait and plot as follows ,23: CWMiefTs and PFreTs across all of the communities. The performances of PFefTs and PFreTs in each quadrat were taken as explanatory variables and response variables, respectively. Moreover, the overlapping species between PFefTs and PFreTs were identified as the key restoration species for the construction of soil and water conservation forests.PFTs were defined using the optimization algorithm and were implemented with SYNCSA software . The algDifferent functional traits showed trait-specific responses to the community restoration types. SL and CF had a higher CWM for SLA, LNC, and SRL. MF and NSF had a higher CWM for LDMC, LA, and H . For then. Variations in the CWMs for SLA and SRL were significantly associated with soil TP, soil surface runoff, and soil erosion. Moreover, there were close negative relationships between soil erosion and CWMs for LA and H  , a subgroup of two traits (SLA and LNC) defined two plant functional response types (PFreTs) . SpeciesefTs) defined by three optimal traits  were found with a large congruence ρ of 0.40. Grouped in PFefT-1 were those species with a higher SLA and SRL, despite the lowest LA. The most representative species was Keteleeria evelyniana. Grouped in PFefT-2 were species with a lower SLA, SRL, and LA, such as Cyclobalanopsis glaucoides and Pinus yunnanensis. Plant type PFefT-3 included those species with the lowest SLA and LS and the lowest SRL . PFefT-4 was the species with the highest SRL and the lowest LS, similar to Myrsine africana. The first four PFefTs had higher presence values, and the average performance of PFefT-2 (Avg. Perf. = 15.5) was the highest among the seven functional types  only explained 21.6% of the variation in the response matrix (PFreTs). Meanwhile, the values of all canonical eigenvalues were smaller than the first non-canonical eigenvalues  and five shrub species   . These oefTs and PFreTs. Functional traits optimally defining PFefTs were SLA, SRL, and LA. SLA and LA had significant effects on the water holding capacity of leaves and the rainfall interception capacity of forest canopies [reTs, SLA and LNC were the better traits for optimally defining PFreTs. It has been confirmed that SLA and LNC are better response traits in many studies [reTs, which suggests that representative data on LNC, SLA, SRL, and LDMC are not sufficient for the identification of PFreTs and that more response traits should be selected for defining PFreTs.Our results have shown that SLA is the better trait for optimally defining PFcanopies , and SRLcanopies ,26. In t studies ,19,27,28efTs) defined by three optimal traits  were found with a maximum congruence. The results showed that the first three PFefTs had lower leaf areas, which was not consistent with the fact that the larger the leaf area was, the higher the rainfall interception of the leaf and canopy and the lower the water and soil loss. These results may suggest that leaf area was not the main factor controlling soil and water loss. Canopy, litter layer, and root-bearing soil were found to have important roles in water and soil conservation. SLA was an effective indicator of rainfall interception by the canopy. At the same time, SLA was also an indicator of litter decomposition. Leaves with higher SLA always had faster decomposition rates, resulting in lower litter mass accumulation and soil and water conservation capacities. Species with higher SRL would be important for increasing the maximum water-retaining capacity of soil and reducing the soil surface runoff and soil erosion by root nets [efTs in the first three PFefTs with medium SLA and SRL may be explained by the patterns of trade-off between the growth rate and cumulative biomass because plants with a higher SLA and SRL always have a higher growth rate, but have lower cumulative biomass. Grouped in PFefT-3 were the understory shrub species with the lowest SLA and lower SRL. Shrub species affected rainfall interception and soil erosion by the shrub canopy layer and surface root-bearing soil.Seven plant functional effect types , such as a lower LNC and high N resorption efficiency from senescing leaves [In the identification of plant PFg leaves ,20.Achieving efficient soil and water conservation in the Central Yunnan Plateau is the key concern for forest managers and ecologists ,29. MainreTs and PFefTs and to identify key species in the subtropic mountain ecosystem. However, the limitations of this method should be considered by forest managers and ecologists. For example, interspecific relationships among the selected species were not considered in this method, considering that interspecific competition may affect the community functional structure or ecosystem functions. Further research into traits and interspecific relationships and tradeoffs would improve the accuracy of this method. Nevertheless, this research suggests that a trait-based method may help guide forest restoration and management to maintain ecosystem services.We used the response-and-effect trait framework to assess the overlap between PFIn the present study, we demonstrated that plant functional traits can be used to construct a response-and-effect framework for determining how species in changing environments will influence ecosystem functions. Our results showed that different functional traits displayed trait-specific responses to community restoration types. Analyses of the correlations and optimization algorithm suggested that SLA was the key response and effect trait, and it could not only effectively respond to soil resources, but it also strongly affected soil ecohydrological functions. Based on three optimal effect traits  and two response traits (SLA and LNC), seven functional effect types in relation to soil and water conservation capacity  and two plant functional response types to soil physicochemical properties were identified. Moreover, eight overlapping species between plant functional response types and functional effect types were selected as the key restoration species. These results provide a methodological guide for species selection for recovery, as well as a species inventory for the restoration of degraded ecosystems in this region.


In order to reignite gains and accelerate progress toward improved malaria control and elimination, policy, strategy, and operational decisions should be derived from high-quality evidence. The U.S. President’s Malaria Initiative (PMI) Insights project together with the Université Cheikh Anta Diop of Dakar, Senegal, conducted a broad stakeholder consultation process to identify pressing evidence gaps in malaria control and elimination across sub-Saharan Africa (SSA), and developed a priority list of country-driven malaria operational research (OR) and programme evaluation (PE) topics to address these gaps.Five key stakeholder groups were engaged in the process: national malaria programmes (NMPs), research institutions in SSA, World Health Organization (WHO) representatives in SSA, international funding agencies, and global technical partners who support malaria programme implementation and research. Stakeholders were engaged through individual or small group interviews and an online survey, and asked about key operational challenges faced by NMPs, pressing evidence gaps in current strategy and implementation guidance, and priority OR and PE questions to address the challenges and gaps.Altogether, 47 interviews were conducted with 82 individuals, and through the online survey, input was provided by 46 global technical partners. A total of 33 emergent OR and PE topics were identified through the consultation process and were subsequently evaluated and prioritized by an external evaluation committee of experts from NMPs, research institutions, and the WHO. The resulting prioritized OR and PE topics predominantly focused on generating evidence needed to close gaps in intervention coverage, address persistent challenges faced by NMPs in the implementation of core strategic interventions, and inform the effective deployment of new tools.The prioritized research list is intended to serve as a key resource for informing OR and PE investments, thereby ensuring future investments focus on generating the evidence needed to strengthen national strategies and programme implementation and facilitating a more coordinated and impactful approach to malaria operational research.The online version contains supplementary material available at 10.1186/s12936-023-04654-8. Despite significant progress over the past two decades in reducing malaria-related morbidity and mortality, malaria remains an important public health threat, especially in sub-Saharan Africa (SSA) . In 2021Research prioritization efforts for malaria to date have often been ad hoc. Some countries have processes to define national research priorities for malaria control and elimination, but often the resulting research agenda is not updated regularly, shared broadly, or tracked for progress , 10. FurCurrent donor and government investments in malaria control and elimination are predominantly focused on delivery of interventions . OperatiUCAD and PMI Insights facilitated a broad stakeholder consultation process to identify pressing operational challenges and critical evidence gaps in malaria control and elimination policy, strategy, and guidelines, and to define a priority list of OR and PE topics to address these challenges and gaps. The overarching objective of this effort was to foster improved alignment of country research priorities with those of key funding agencies to better coordinate and align future malaria OR and PE efforts.The research prioritization process consisted of four main stages that were carried out between February 2021 through February 2022: (1) design of the process (Feb–Jun 2021); (2) synthesis of existing information (Mar–Jun 2021); (3) gathering of stakeholder input on priority research topics (Jul–Oct 2021); and (4) evaluation and ranking of the identified research priorities against a set of defined evaluation criteria (Dec 2021–Feb 2022).An overarching framework was first developed to guide the implementation of the process . The fraA document review was conducted to capture information on: (1) malaria operational challenges and bottlenecks faced by NMPs within SSA in the implementation of their programmes; (2) evidence gaps in national or global malaria policy, strategy, and implementation guidance; and (3) outputs from recent national, regional (within SSA), and/or global level research prioritization processes. To focus on gathering more current and relevant operational challenges, evidence gaps, and research prioritization outputs, the scope of the review was limited to documents, reports, and literature from 2015 through 2021. The review included current or most recent National Malaria Strategic Plans from PMI focus countries, PMI Malaria Operational Plans from 2019 and 2020, recent WHO Malaria Programme Review and Mid-term Review reports from countries within SSA, WHO Evidence Review Group meeting reports, WHO Global Malaria Programme guideline development group meeting reports, WHO Malaria Policy and Advisory Group meeting reports, Roll Back Malaria Working Group meeting reports, Cochrane reviews of specific malaria interventions, and reports or publications on country, regional, and global-level malaria research prioritization research outputs.All documents were reviewed, coded, and analysed in the online qualitative software programme Dedoose using the defined thematic areas Fig. . FurtherTo gather stakeholder input, a mixed-methods approach was used that entailed key informant interviews (KIIs), focus group discussions (FGDs), and an online survey with individuals from five target stakeholder groups: NMPs in PMI focal countries within SSA; academic/research institutions from malaria-affected countries in SSA; WHO country and Africa Regional Office representatives; technical partners working in or providing support to malaria research or programming; and funding agency representatives from PMI, the Global Fund, and Bill & Melinda Gates Foundation. A stakeholder mapping was conducted to identify potential participants from these five key stakeholder groups. Partners engaged in the prioritization process, including PMI Insights consortium partners, UCAD, PMI, BMGF, and GFATM, were asked to provide recommendations for individuals to consult. RBM working group member lists and malaria organization and project websites were also reviewed to identify potential participants.KIIs and FGDs were conducted with all target stakeholder groups, except for technical partners. Participants for KIIs and FGDs were selected purposively based on their role within their organization and experience in malaria control and elimination research and/or programming. Participant sampling was conducted in a way to ensure a diverse group of participants based on experience working in different transmission settings; geographic representation was taken into account for stakeholders based within SSA. Selected participants were invited to participate in an interview via email. For the NMPs and research institutions, the participants contacted were encouraged to invite other representatives from their institution to participate. Representatives from each of the stakeholder groups were selected to participate in either a KII or FGD based on participant availability. For the FGDs, there was no mixing of participants across institutions. Altogether, 15 NMPs, 18 research institutions, and representatives from WHO, PMI, GFATM, and BMGF were targeted for KIIs and FGDs. KIIs and FGDs were conducted using a semi-structured interview guide, and were carried out in English, French, and Portuguese as appropriate. Participants verbally consented to participate prior to the interviews. Interviews were conducted using Microsoft Teams or Zoom virtual platforms.An online survey was used to gather inputs from technical partners identified through the stakeholder mapping. All identified participants from the stakeholder mapping  were sent the online survey using the SurveyMonkey platform. The survey was shared in English and French, and participants were asked for written consent for their participation. The online survey was available for six weeks, with up to 3 reminders sent to the participants.The three main themes explored in the KIIs, FGDs, and online survey were similar to those investigated in the document review: (1) key operational challenges and bottlenecks experienced by NMPs in the implementation of their programmes; (2) evidence gaps in national and global malaria policy, strategy, and implementation guidance; and (3) priority OR and PE questions that could help to address the key challenges and identified evidence gaps. Data from the KIIs, FGDs, online survey, and the document review were analysed and organized by the key thematic areas in the prioritization framework, the three key topic areas explored , and across the different stakeholder groups. To identify which OR and PE topics would be selected for the evaluation process (Stage 4), only topics that were identified by at least three stakeholder groups and/or through the document review (at least three different sources) or by at least three NMPs or research institutions, were prioritized for evaluation and ranking.An independent evaluation committee was formed to conduct the evaluation of the OR and PE priority topics identified during Stage 3. The committee comprised 17 representatives from NMPs , research institutions within malaria-affected countries (n = 9), and WHO (n = 2). Committee members were selected to ensure diverse representation across geographic areas with SSA, malaria area(s) of technical expertise, gender, and type of institution.The evaluation process and scoring methodology used was adapted from the Child Health and Nutrition Research Initiative (CHNRI) research priority setting methodology , 23. TheFor each OR/PE topic, a research priority score (RPS) and average expert agreement (AEA) score was calculated. The RPS score was calculated by taking the average score across all criteria, for each OR/PE topic. The AEA was calculated as the percent of evaluators who chose the mode for each evaluation criteria question, averaged across the ten evaluation questions . The AEA ranged from a low of 40.3 to a high of 67.6 (out of 100). Table The top three ranked OR and PE priorities were in the areas of prevention and chemoprevention, with the highest ranked topic focusing on testing and evaluating different delivery mechanisms to reach and sustain high coverage of insecticide-treated nets (ITNs) among hard-to-reach and highest risk populations. The second and third ranked topics related to generating evidence on the effectiveness and cost-effectiveness of different combinations of prevention and chemoprevention interventions, including addressing the combination of the new RTS, S/AS01 malaria vaccine with chemoprevention.Several prevention topics addressed indoor residual spraying (IRS), including testing and evaluating approaches for maximizing IRS impact (topic #9), assessing the impact of IRS and focal/reactive IRS (topic #10), assessing approaches for reducing the cost/improving the efficiency of IRS (topic #14), and evaluating different strategies or packages of interventions to prevent the resurgence of malaria cases following the withdrawal of IRS (topic #28). Topics related to ITNs included evaluating approaches to improve routine/continuous distribution channels (topic #10) and evaluating the effectiveness of social and behaviour change (SBC) approaches/interventions to improve ITN use in settings where access to ITNs is high (topic #31). A crosscutting prevention topic on evaluating different insecticide management or rotation strategies on insecticide prevalence and intensity ranked fifth.Of the topics on chemoprevention, three addressed seasonal malaria chemoprevention (SMC)—evaluating the impact and cost-effectiveness of expanding the age range, geographical coverage, and rounds of treatment of SMC (topic #6); evaluating strategies for achieving high SMC coverage and adherence (topic #8); and testing of approaches to improve cost and resource efficiency in the delivery of SMC (topic #28). The two topics on intermittent preventive treatment in pregnancy (IPTp) had similar focuses—evaluating strategies to improve IPTp coverage (topic #23) and efficiency of the delivery of IPTp (topic #25). The last topic addressed assessing the most effective delivery platform for perennial malaria chemoprevention (PMC) in infants (topic #18).Seven topics addressed the area of case management, which encompassed case management in public and private sectors, as well as at community level. The highest ranked topic in case management was on testing and evaluating approaches or interventions to reduce the frequency of stockouts of key commodities for malaria case management, with a focus on community-level stockouts (topic #3). Other case management topics addressed community health workers’ motivation and retention (topic #7), delayed care-seeking (topic #15), and improving health care provider adherence to malaria case management and integrated management of childhood illness guidelines . The lowest ranked case management topic was on testing different approaches for working with or incentivizing the participation of the private sector in the referral, diagnosis, treatment, and reporting of malaria cases (topic #32).The top ranked topics in surveillance, monitoring, and evaluation (SME) included assessing approaches for improving analytic and data use capacity, and data use culture (topic #10), evaluating the current performance of surveillance systems (topic #17), and assessing the feasibility and benefit of different digital tools/systems for use at the community level for data capture, reporting, and transmission to HMIS/DHIS2 (topic #19).In terms of cross-cutting topics, two of the prioritized topics related to SBC/community engagement (CE) focused on generating evidence on the effectiveness and cost-effectiveness of different SBC/CE approaches or interventions on healthcare seeking, adherence to treatment and uptake of key prevention interventions (topic #13), and assessing the long-term effectiveness and duration of impact of different SBC approaches for malaria treatment and prevention behaviours (topic #22). The last crosscutting topic (topic #33) focused on assessing the impact of cross-border movement of people on the malaria burden and evaluating the effectiveness of different strategies to reduce malaria transmission across international borders.The findings from the research prioritization process highlighted the most pressing challenges and critical evidence gaps facing NMPs in SSA and identified a set of OR and PE priorities that are directly linked to finding solutions and filling the gaps for many of them. The 33 priority topics identified in this process all received a relatively high RPS (above 70), demonstrating that the evaluation committee generally felt all topics were important to address. The lower and more wide-ranging AEA scores across the topics (ranging from 40 to 68) were likely a reflection of the diverse composition of the evaluation committee members across different geographies and transmission settings within SSA. Committee members remarked on these differences during the meetings convened to discuss the evaluation scores and rankings, reflecting that members perspectives of priority topics are in large part based on their background and country experience.Several key themes emerged from this process. First, NMPs continue to face a multitude of challenges in the implementation of core malaria prevention and control interventions. The challenges identified by stakeholders are not new, but rather reflect persistent and intractable issues faced by NMPs and more broadly, ministries of health. Many of the challenges emphasized by stakeholders relate to broader health system issues—insufficient human and financial resources, inadequately trained workforce, supply chain failures leading to commodity stockouts, poorly integrated and inadequate data systems, and lack of high-quality data for decision-making—that act as barriers to NMPs in achieving their national malaria strategic plan goals and coverage targets. These challenges have been previously documented and recognized as critical to enhance progress in malaria control and elimination , 25. It Another emergent theme was that NMPs feel that there is a lack of evidence on the effectiveness and cost-effectiveness of specific interventions and intervention packages to inform programmatic decision-making, especially with respect to sub-national tailoring and targeting of interventions. As new tools become available and are introduced at country level, this evidence will become even more critical given stagnant budgets. The perceived lack of sufficient evidence may be in part driven by the inadequate dissemination of research findings and translation of the evidence for policy and programmatic use, a challenge previously highlighted in many middle- and low-income countries –28. ThisLastly, the findings reiterated the challenges that NMPs face in achieving the core intervention coverage targets outlined in their national malaria strategic plans. The prioritized OR and PE topics highlight the importance of identifying solutions to overcome the challenges of achieving and maintaining high coverage of core interventions, as well as improving the effectiveness of their delivery. While substantial progress has been made in the scale-up of interventions over the past two decades, gaps in coverage targets persist . OR and A key objective for developing this prioritized list of OR and PE topics is to support and guide more coordinated investments in the research priorities by funding agencies. These agencies were actively engaged in the process from inception to garner their buy-in and help drive their use of the outputs to inform future investment decisions. It should be noted that the 33 research priorities identified in this process represent common themes and priorities rather than specific research questions. Funders can use this list as a starting point, and work with NMPs and their research partners to define contextually specific and relevant research questions. The outputs may also serve as a resource for NMPs and researchers from malaria-affected countries to advocate and position for funding on topics that align with their country research priorities. The list can also complement and supplement other processes undertaken at the country level to identify priority research questions. Additionally, as progress is made against these priorities, new research questions will inevitably emerge, highlighting the importance of regularly updating the priority list.The process used for this research prioritization effort aimed to build upon other recent malaria research prioritization efforts. The desk review revealed a few country- and regional-level malaria research agendas that included some similarly themed operational research questions –32. HoweA strength of this process was that we adapted the CHNRI method , which pThis prioritization process had a few limitations. Although the process included input from a broad group of stakeholders within SSA, there was limited participation from stakeholders in lower transmission and elimination settings. As a result, the identified OR and PE priorities largely reflect issues in high and moderate malaria transmission settings. The robustness of the process was also impacted both by the timeframe for gathering stakeholder inputs and non-response among several invited stakeholders to provide inputs. It will be useful to explore other platforms or approaches to improve stakeholder participation for future iterations of the process and consider developing separate research agendas for high/moderate transmission settings and lower transmission and elimination settings within SSA.The research prioritization process was a valuable exercise to identify key operational challenges faced by NMPs, pressing evidence gaps, and a set of priority OR and PE topics for the SSA region. The prioritized list of topics can serve as an important resource to support funding agency alignment with country priorities and for furthering partnerships with national stakeholders toward formulating specific and relevant research questions for their country context. Ensuring sufficient investment to address the prioritized topics will be a critical step to addressing the persistent challenges and coverage gaps, and helping to reignite progress in malaria control and elimination. It will be important to track progress and regularly update this list to ensure its continued relevance.Additional file 1: Table S1. Evaluation criteria definitions. Table S2. Evaluation criteria scores for OR and PE topics by evaluation criteria question and overall research priority score. Table S3. Average expert agreement scores for OR and PE topics by criteria question and overall.


Fifteen million babies are born preterm globally each year, with 81% occurring in low- and middle-income countries (LMICs). Preterm birth complications are the leading cause of newborn deaths and significantly impact health, quality of life, and costs of health services. Improving outcomes for newborns and their families requires prioritising research for developing practical, scalable solutions, especially in low-resource settings such as Bangladesh. We aimed to identify research priorities related to preventing and managing preterm birth in LMICs for 2021-2030, with a special focus on Bangladesh.We adopted the Child Health and Nutrition Research Initiative (CHNRI) method to set research priorities for preventing and managing preterm birth. Seventy-six experts submitted 490 research questions online, which we collated into 95 unique questions and sent for scoring to all experts. A hundred and nine experts scored the questions using five pre-selected criteria: answerability, effectiveness, deliverability, maximum potential for burden reduction, and effect on equity. We calculated weighted and unweighted research priority scores and average expert agreement to generate a list of top-ranked research questions for LMICs and Bangladesh.Health systems and policy research dominated the top 20 identified priorities for LMICs, such as understanding and improving uptake of the facility and community-based Kangaroo Mother Care (KMC), promoting breastfeeding, improving referral and transport networks, evaluating the impact of the use of skilled attendants, quality improvement activities, and exploring barriers to antenatal steroid use. Several of the top 20 questions also focused on screening high-risk women or the general population of women, understanding the causes of preterm birth, or managing preterm babies with illnesses . There was a high overlap between research priorities in LMICs and Bangladesh.This exercise, aimed at identifying priorities for preterm birth prevention and management research in LMICs, especially in Bangladesh, found research on improving the care of preterm babies to be more important in reducing the burden of preterm birth and accelerating the attainment of Sustainable Development Goal 3 target of newborn deaths, by 2030. An estimated 11% of live births or 14.8 million babies are born preterm globally every year -4. AdditAlthough high- and lower-resource countries do not differ drastically in rates of preterm birth, they do not share the resulting burden equally due to a large survival gap in preterm newborns between them and a substantially higher impact of preterm birth low- and middle-income countries (LMICs) ,2,6. LMIBangladesh, a LMIC in South Asia, witnessed high neonatal and child mortality declines during a two-decade period starting in the early 1990s. However, this progress has stalled since 2010, requiring a re-evaluation of the current strategic focus and interventions to avert deaths due to preventable causes such as birth asphyxia, pneumonia, and prematurity . BangladAdvancing a research agenda for the prevention and management of preterm neonates across the continuum of care is critical to addressing the burden of preterm births in LMICs, and specifically, in Bangladesh ,24. ReseGiven that preterm birth complications will continue to be the leading cause of newborn and child mortality, stagnation in efforts to address this issue may hinder progress towards achieving the SDG-3 targets in Bangladesh and many low-resource settings. The NIHR Global Health Research Group on Preterm Birth Prevention and Management (PRIME), therefore, undertook a research priority-setting exercise using the Child Health and Nutrition Research Initiative (CHNRI) method . Since tWe adopted the CHNRI method  to set rWe identified and established a process management team of 17 members from the PRIME collaborating institutions in Bangladesh, South Africa and the UK, entrusting them to coordinate the research priority-setting exercise. All team members were experienced in conducting maternal and newborn health research and included biomedical and laboratory scientists, health systems and public health researchers, clinicians, and social scientists. The team conducted planning workshops in Bangladesh and South Africa to define the scope and scoring criteria for the priority-setting exercise. Online workshops were later held to iteratively review and consolidate research questions and discuss the research prioritisation activity results.The process management team discussed and specified the context of this research priority exercise in terms of space, population, and time; disease, disability, and death burden; and research domains. The goal of this phase was to identify research questions that have the potential to reduce the burden of premature birth and accelerate the progress towards achieving SDG Target 3 in LMICs, with a particular focus on Bangladesh as a high-burden country  technical experts in the field of preterm birth research − Keynote speakers in Preterm Birth Dialogues Conference (South Africa)− Author list of articles published on preterm birth published in the last 10 years found in Web of Science Core Collection database− Personal Communication− SnowballingAn online platform was developed and email invitations were sent to over 500 global technical experts to participate in the research priority-setting exercise. In the first online survey, we asked the technical experts to systematically list research questions on preventing and managing preterm birth across the four research domains according to the predefined context. The exercise was open to all research methodologies and study designs . Participants could submit up to 10 priority research questions for each research domain based on their knowledge and expertise. Seventy-six technical experts  submitted 490 research questions (an average of 6.4 research questions per person) between July and December 2019. Around two-thirds of the experts were public health and health systems researchers, while a half were involved in clinical services. Around 90% of the technical experts were experienced in working in LMICs  (step four), which we then used to calculate weighted research priority scores. Seventy-six experts ranked the criteria; those for effectiveness (3.25) and potential for burden reduction (3.25) received the highest ranks, followed by answerability (3.02), deliverability (2.79), and equity (2.70).We used a password-protected Microsoft Structured Query Language (SQL) Server 2008 R2 as the central database for maintaining the quality and safety of data. We set up validation rules  to prevent inconsistencies and other errors during data entry.We calculated intermediate, unweighted, and weighted research priority scores (RPS) for each of the five scoring criteria used to discriminate the 95 research questions for this exercise . For eacIn the next step, we calculated weights by dividing the observed average rank for each criterion by the expected average rank where all five criteria are equally important (which should be 3.00) . In our We also calculated the average expert agreement (AEA) for each of the 95 research questions using the formula below . The AEAWe obtained ethical approval for the study from the research and ethics review committees of International Centre for Diarrhoeal Disease Research Bangladesh  (PR-18055). Experts provided informed consent during the start of both online surveys, and participants were aware that they could exit the surveys at any time without any penalty. We maintained the participants’ privacy and confidentiality during data collection, management, and analysis, and used contact information only to send survey invitations and reminders. We removed personal identifiers (i.e. names) before analysis and kept the data in secure and password-protected devices.The overall weighted RPS for the 95 research questions ranged from 0.903 (highest) to 0.638 (lowest). The AEA ranged from 0.85 to 0.66, and we observed a positive association between AEA and RPS . Among the top 20 research priorities for LMICs (Eleven (55%) of the top 20 research priorities were categorised as health systems and policy research, four as research to develop existing interventions (20%), three as epidemiological research, and two as the development of new interventions.(Table S2 in the ). For the criteria reduction of the burden, the other two leading research questions that experts agreed on were determining the impact of skilled birth and neonatal care attendants on survival outcomes for babies and improving transport and referral systems for preterm, LBW, or small for gestational age (SGA) infants in LMICs. There was also high agreement that improving or strengthening referral and transport systems for women and newborns, followed by assessing the impact of the presence of skilled birth and neonatal care attendants on survival outcomes for babies, would improve equity  ; 14 of the top 20 questions prioritised by researchers in HICs and 16 prioritised by those in LMICs appeared in the overall LMIC list .We also observed a high overlap (16 questions) between the top 20 questions identified by LMIC and international experts We also attempted to classify research priorities by the expertise of scorers listed in Many children are still being born preterm and are suffering from short- and long-term consequences of preterm-related complications. With only a decade left to reach the SDGs, many countries will fail to achieve the targets related to child mortality and newborn mortality unless the challenges in the prevention and management of preterm birth are addressed urgently ,4,5. As Of the top 20 research questions in LMICs or Bangladesh, six were related to identifying gaps or challenges or improving the implementation of either facility-based or community-based KMC. Although KMC has been identified and epitomised as a critical intervention in reducing mortality and morbidity in preterm infants (including ENAP), as recommended by the World Health Organization (WHO), its application and scale-up, especially in LMIC settings, have been challenging due to health systems bottlenecks and demand side barriers such as poor quality, lack of awareness, acceptability, and access -40. For Despite increases in access to institutional care, about one-third of women in LMICs still deliver at home without adequately skilled staff or cannot timely access care due to poor referral and transport mechanisms linking women and newborns to care ,50,51. SThis priority-setting exercise has also highlighted several epidemiological studies, mainly from experts from Bangladesh, szch as determining the prevalence and cause of sepsis in preterm newborns, understanding the effect of antepartum complications, nutritional status or nutritional interventions ECD interventions on birth outcomes or preterm babies. This indicates that, despite evidence from many HICs, there is still a lack of evidence regarding epidemiological studies from many LMICs including Bangladesh .Although most participating experts had experience conducting research in LMICs, we attempted to stratify our analysis based on their geographical location and by expertise of scorers. While our findings indicate a high overlap in the top 20 research priorities, there is a 10%-30% divergence between groups. For example, while international experts have prioritised research related to the implementation of antenatal corticosteroids, determining the effectiveness and cost-effectiveness of various strategies  for treating preterm infants, the effect of ECD interventions on preterm newborns, epidemiology of nosocomial infections in newborn nurseries or SCANU, experts from Bangladesh ranked them as #36, #49, #48, and #52, respectively; they also focused on questions related to improving care for newborns at the community level in the top 20, which were given lower scored by international participants. Similarly, differences were observed by scorer’s expertise, especially those with expertise in LSR, possibly due to the low response in this category (n = 8). Previous exercises have highlighted similar discordance between regional, international, or high and LMIC contexts or by expertise ,69. DespAnalysis of research questions by criterion revealed how the criteria could be used to determine the strengths and weaknesses of specific research questions . For exaOne of this exercise's main strengths is adapting the CHNRI methodology. Apart from being transparent, structured, and flexible, other practical benefits are its low cost and the ease of conducting it online. However, we also faced some challenges. Our survey response rates were low during the elicitation of research questions and the scoring process. This is not uncommon with this method ,70 and mThe list of research questions to be scored was also long and time-consuming to collect, resulting in scorer fatigue. For the set of 95 research questions, each respondent had to provide a total of 1425 (95 × 15) scores, which took over an hour to complete. About 61% of the scorers had completed the scoring process in full, and about 69% scored at least half of the questions. To reduce preferential bias due to scoring fatigue, we randomly presented research questions to each scorer, ensuring that all questions had an equal chance of being scored ,72 and aOther potential biases inherent in this methodology include the possibility of excluding valuable research ideas during the research question elicitation phase or consolidation phase . While tEngaging a diverse group of stakeholders has improved the legitimacy, credibility, inclusiveness, contextual relevance, and ownership of the prioritised research, leading to greater investment opportunities ,73-75. HThis exercise, drew on the expertise of a diverse group of participants who contributed to and scored questions to develop a set of research priorities that reflect the needs in Bangladesh and other LMICs on prevention and management of preterm birth going forward. The findings provide guidance to national level and LMICs stakeholders on future research investments in the area. Prior reviews of research priority setting exercises have continually stressed the importance of having a dissemination strategy with key stakeholders for optimal uptake of the identified priorities . As suchPreterm birth is the leading cause of newborn deaths in LMICs. Achieving the highly ambitious SDG target of reducing neonatal mortality rate (NMR) to ≤12 per 1000 live births will require accelerated efforts to prevent and manage preterm birth and its complications. The findings from this study offer a set of prioritised research questions related to improving the prevention of preterm birth and care and management of the preterm baby, which, we hope, will help bring further attention and more secure funding from donors, researchers and policymakers globally, in LMICs and Bangladesh.


Dengue, a mosquitoborne flavivirus infection, is increasingly a disease of older adults who are more likely to have chronic diseases that confer risk for severe outcomes of dengue infection. In a population-based study in Taiwan, adjusted risks for dengue-related hospitalization, intensive care unit admission, and death increased progressively with age. Aedes aegypti mosquito–borne flavivirus infection; a secular trend for dengue is a shift in the age of case-patients and deaths from children to adults and older adults  (Age-specific attack rates during the outbreak were similar across age groups  Figure, The epidemiologic shift of dengue to adults and older adults has increased recognition that advanced age is a risk factor for severe and fatal outcome after dengue infection (,Adults and older adults comprise an increasing proportion of dengue cases in many countries, even as those populations reach ages where the prevalence of chronic diseases increases (>65 years of age. Projections suggest that 10% of the total global population by 2060 will be persons >65 years of age living in Asia (Since 1990, dengue cases and deaths have increased disproportionately among adults >50 years of age compared with children <15 years of age, in whom the number and proportion of cases and, especially, deaths, have declined (Additional information about increased risk for severe outcomes of dengue infection, Taiwan, 2014–2015.


Socioeconomic status has long been associated with population health and health outcomes. While ameliorating social determinants of health may improve health, identifying and targeting areas where feasible interventions are most needed would help improve health equity. We sought to identify inequities in health and social determinants of health (SDOH) associated with local economic distress at the county-level.For 3,131 counties in the 50 US states and Washington, DC , we conducted a retrospective analysis of county-level data collected from County Health Rankings in two periods (centering around 2015 and 2019). We used ANOVA to compare thirty-three measures across five health and SDOH domains  that were available in both periods, changes in measures between periods, and ratios of measures for the least to most prosperous counties across county-level prosperity quintiles, based on the Economic Innovation Group’s 2015–2019 Distressed Community Index Scores.With seven exceptions, in both periods, we found a worsening of values with each progression from more to less prosperous counties, with least prosperous counties having the worst values . Between 2015 and 2019, all except six measures progressively worsened when comparing higher to lower prosperity quintiles, and gaps between the least and most prosperous counties generally widened.In the late 2010s, the least prosperous US counties overwhelmingly had worse values in measures of Health Outcomes, Clinical Care, Health Behaviors, the Physical Environment, and Social and Economic Factors than more prosperous counties. Between 2015 and 2019, for most measures, inequities between the least and most prosperous counties widened. Our findings suggest that local economic prosperity may serve as a proxy for health and SDOH status of the community. Policymakers and leaders in public and private sectors might use long-term, targeted economic stimuli in low prosperity counties to generate local, community health benefits for vulnerable populations. Doing so could sustainably improve health; not doing so will continue to generate poor health outcomes and ever-widening economic disparities. Since local economic distress is associated with worse health outcomes, policymakers should consider returns to health as a motivator for improving economic distress.The potential magnitude of the impact of reducing economic disparities on clinical quality, outcomes, and health behaviors should be considered when investing to improve local economic conditions.Targeted economic stimuli to generate local, community health benefits for vulnerable populations living in the least prosperous areas may be an effective way to improve population health. Socioeconomic status has long been associated with population health and health outcomes in industrial countries. –3 In theThe distribution of economic prosperity among US communities has undergone significant changes in recent decades, resulting in heightened inequality in local economic prosperity.  This hasTo identify characteristics associated with such areas, we sought to identify cross-sectional and longitudinal inequities in health, clinical care, health behaviors, and SDOH associated with local economic distress at the county level, using 2015 and 2019 data from County Health Rankings.For 3,131 counties in the 50 US states and Washington, DC , we obtained Distressed Communities Index (DCI) scores from the Economic Innovation Group.  ConstrucIn both years, we compared the health and SDOH measures across prosperity quintiles, defined by county-level DCI scores  using Analysis of Variance (ANOVA). We calculated the ratio of values for the least to the most prosperous county quintiles. Further, for each prosperity quintile, we calculated the change in values for each prosperity quintile between 2015 and 2019. Finally, we calculated the ratio of values for the least to the most prosperous counties between the first and second period and provided an indication of whether the gap between the least and most prosperous counties was widening, narrowing, or staying the same. We used SPSS v 28  for all analyses.In 2019, we found a progressive worsening of values with movement to a less prosperous quintile for all except five measures  Table . All HeaIdentical patterns were found when examining earlier data Table , with thWhen comparing ratios of values in the least to the most prosperous counties in 2015 and 2019, 20 measures demonstrated a widening of the gap between the least and most prosperous counties, 10 demonstrated a narrowing, and 3 remained the same Table .In the late 2010s in the US, less prosperous counties had worse values than more prosperous ones in 29 of 33 measures of Health Outcomes, Clinical Care, Health Behaviors, the Physical Environment, and Social and Economic Factors; for 26 of those measures, during a time of economic growth across the US, there was a progressive worsening of measure values with each move from a higher to a lower prosperity county. Further, with four exceptions, measures in the least prosperous counties worsened more than those in the most prosperous counties between approximately 2015 and 2019, suggesting that inequities in health and SDOH measures associated with economic prosperity increased during that period.The general stepwise nature of the relationship between increasing economic distress and the measures we studied suggests a structural relationship that has led to a systemic and sequential worsening of health as one descends the economic prosperity ladder. Our findings support that local economic prosperity is associated with health status, health outcomes, and health care quality in Medicare fee-for-service patients ,6 and otNot all measures demonstrated a stepwise worsening with increasing local economic distress. Physical Environment and Social and Economic Factors measures showed distinct patterns, both cross-sectionally and over time. Nonetheless, measures in the Physical Environment were invariably worse in the least prosperous counties.It is worth noting that we found an inverse relationship between reporting of excessive drinking and local economic prosperity, though binge drinking increased across all prosperity quintiles between 2015 and 2019. Indeed, binge drinking is more common in members of higher household incomes and those with greater educational attainment. [Our study has several limitations. First, our results are derived from data in two relatively close time periods in a relatively stable financial time; studies of different time periods may have different results. Importantly, we evaluated periods before the COVID-19 pandemic and reports suggest that economic and health inequities have increased since COVID-19 began;  thereforDespite these limitations, our findings suggest that investment in low prosperity qualified ‘economic opportunity zones’ might not only improve local economic conditions, but also improve community health,  thereby Our findings suggest that local economic prosperity may serve as a proxy for the health and SDOH status of the community. Communities operate within the context of federal and state policies that shape local economic conditions including the allocation of resources and strategic priorities.  Together


Research on occupational causes of cancer has identified 47 known Group 1) agents associated with 23 types of cancer through 2017, an increase from 28 agents in 2004 ( agents aDespite achievements in identifying occupational causes of cancer, a range of research needs remain, including identifying additional cancer sites for Group 1 agents and more definitive studies for exposures where the evidence among humans remains limited or inadequate –7. ThereResearch recommendations to address classification uncertainties for 20 priority occupational agents have been detailed . They inThere have been calls to update existing cohorts when valuable follow-up time has accrued allowing investigation of the full potential impact of exposures on health . There iIn parallel, epidemiological research has innovated over time to comprise increasingly larger-scale prospective cohort studies and consortia, use of electronic data linkage, causal inference methods and triangulation of evidence, reinforcing the ongoing utility of observational research methods . The recEfforts to stimulate future research and investment in occupation and cancer may benefit from the use of new rapidly evolving research methods, closer alignment with global public health priorities, and strengthening of international partnerships supporting excellence and inclusiveness in research. For example, a range of methodological advancements have emerged from application of exposome concepts in epidemiology. In Europe, birth cohort consortia seeking to characterize the early-life exposome, as well as other efforts, have driven much innovation , 26. TheA range of statistical methods for analysis of multiple correlated exposures have advanced . ExtendeHowever, there is an ongoing need for continued efforts to better characterize the occupational and corresponding non-occupational exposome over the lifecourse. Research priorities include establishing new cohort studies with appropriate biosample collection, improved questionnaire and personal monitoring data, increasing multidisciplinary collaboration to utilize innovative data and methods, and integrating genetic data in exposome studies for causal inference -40. At tResearch on occupation and cancer may benefit from closer alignment with recent high-profile initiatives on related topics as well as with global public health priorities. The United Nations Sustainable Development Goals note the need for decent work . The EU Rapidly changing work conditions were exemplified during the COVID-19 pandemic, with potential direct or indirect effects on health and cancer. Shifts in overall global cancer research focus were also described . IncreasPublic health efforts directed at catching-up in cancer screening and on improving health systems and public health literacy following the COVID-19 pandemic may offer opportunities to advance cancer control and improved health literacy at work , 56. FurThe potential importance of climate change in cancer, including occupation and cancer, may also not be fully understood , 63. CliLastly, strengthened international partnerships are critical for future advances in occupational cancer research. Efforts in coordination of European birth cohort studies, and later occupational cohort studies, have led to major advancements in research and inclusiveness , 70, 71.The need for occupational epidemiological and exposure monitoring studies in low- and middle-income countries has long been recognized. Priorities for cancer research in low- and middle-income countries have recently been described as separate to those of high-income countries, and highlighted the need to reduce the burden of patients presenting with advanced-stage disease, primary prevention and early detection, and innovative and affordable technology in cancer control . DocumenThe occupational epidemiology community has a great opportunity to promote new efforts in occupation and cancer while at the same time reducing inequalities in health and research.