Aside from specific environmental conditions, poor agricultural practices contribute to mold and thus the mycotoxin contamination of crops. This study investigated Bangladeshi farming households’ (i) awareness of and experience with mold contamination of food crops; (ii) knowledge and awareness of the timing, causes, and consequences of mold and mycotoxin contamination; and (iii) knowledge of the recommended agricultural practices for controlling and preventing mold contamination of food crops. A survey was conducted with 1280 households in rural areas of Habiganj district, Bangladesh. Basic descriptive statistics were calculated, and mixed-effects linear regression analyses were performed to examine associations between household characteristics and overall knowledge scores. The awareness of mold contamination of food crops was very high  and a shared experience among households . Yet, the majority  demonstrated a low level of knowledge of the timing, causes, and preventive practices regarding mold contamination of crops. Knowledge scores were similar over demographic groups and better for households with more arable land. The findings suggest a generally insufficient knowledge of the conditions that favor mold contamination and the measures for preventing mold contamination of food crops. These findings underline the need for tailored interventions to promote good agricultural practices and reduce mold contamination of food crops. Mold contamination of food crops is widespread and constitutes a leading global food safety concern . The groMycotoxin occurrence at levels above European Union and Codex limits is estimated to affect around 20% of food crops globally, while the occurrence above detectable levels ranges between 60% and 80% . MycotoxIn general, the mold contamination of food crops and subsequent mycotoxin production depends on several factors, including the plant species; environmental conditions, such as moisture and temperature; and the presence of other fungi, microbes, and insect pests ,16,17. BIn Bangladesh, for instance, several biomarker surveys ,26,27,28Therefore, this study aimed to investigate farming households’ (i) level of awareness and experience with mold contamination of food crops; (ii) knowledge and awareness about the timing, causes, and consequences of mold and mycotoxin contamination; and (iii) knowledge of the recommended agricultural practices for controlling and preventing mold contamination of food crops.Food and Agricultural Approaches to Reducing Malnutrition (FAARM) cluster-randomized controlled trial in two sub-districts of Habiganj district in Bangladesh’s Sylhet Division . FAARM included 2700 young married women in 96 settlements (geographic clusters) who were interested in gardening and had access to at least 40 m2 of land. Settlements were randomized into 48 intervention and 48 control clusters. The FAARM trial evaluated the impact of a homestead food production program, implemented by the international non-governmental organization Helen Keller International, on undernutrition in young children. Alongside nutrition and hygiene education, the FAARM project promoted homestead production of nutritious foods through home gardening and poultry rearing among intervention households to improve garden productivity and dietary diversity and to eventually reduce child stunting. Further information on the FAARM trial is available in the study protocol [Maternal Exposure to Mycotoxins and Adverse Pregnancy Outcomes (MEMAPO) prospective cohort study is an add-on study to the FAARM trial that collected data on a subsample of 447 pregnant FAARM women to investigate the role of mycotoxins in the development of specific adverse pregnancy outcomes.This study was conducted within the protocol . The MatA structured questionnaire was developed collaboratively with local experts and farmers, adapting recommended guidelines for preventing mold contamination of cereals  to the lA cross-sectional study was conducted among a sample of FAARM participants during the FAARM endline household survey from November 2019 to April 2020. As awareness of mold appeared high among FAARM respondents during the first two weeks of data collection, instead of asking all households, a sub-sample was targeted to enable faster data collection while maintaining sufficient power. We examine data collected from all FAARM households visited during the first 16 days of data collection, FAARM households containing pregnant women who had been recruited in the MEMAPO study, and an additional random 25% of the remaining FAARM households. The sub-sample was drawn from all FAARM settlements. Overall, a total of 1371 households were targeted for inclusion in this study.To characterize the recruited households, data on the following variables were extracted from the FAARM endline survey and illustrated in The survey instrument collected the following specific knowledge information: (i) awareness of mold contamination of food crops; (ii) the stages of crop production where mold contamination can occur; (iii) conditions and practices that promote mold contamination during growing, harvesting, and storage; (iv) the consequences of mold contamination of crops; (v) awareness of mycotoxin production; (vi) stability of mycotoxins to cooking and food/feed preparation, (vii) harmful effects of mycotoxin exposure in farm animals; (viii) harmful effects of mycotoxin exposure in humans; and (ix) recommended measures for preventing mold contamination at all stages of crop production . This inAs the terms “mold” and “mycotoxin” are technical, respondents were first screened for their awareness and understanding of identified local terms for mold and mycotoxins . To those who were unsure or gave an inaccurate definition, these terms’ proper meanings were explained in the local language with the help of the visual aid. Thereafter, only those who indicated that they knew about mold were further interviewed on their level of awareness, experience, and knowledge regarding mold contamination of food crops. Where respondents did not know the answer to a primary question, related sub-questions were assumed to be also unknown and thus skipped. Trained data collection officers administered the questionnaires through face-to-face interviews with respondents without reading out answer options but by selecting mentioned options and entering any other answers provided. After 25 March 2020, the last few interviews with 31 households were conducted by phone due to the COVID-19 pandemic. All data were collected and entered electronically using Open Data Kit on tablets  as outlip < 0.15), adjusting a priori for household wealth and the household head’s educational level. For ease of interpretation, household size and size of the homestead and agricultural land were categorized as illustrated in Descriptive statistics  were calculated using sampling probability weights to reflect the unequal probabilities in selecting study participants due to the study’s sampling design and controlling for clustering, i.e., similarity of participants at the settlement level. Wald tests were used to examine differences in the response proportions and average knowledge scores between FAARM intervention and control households. Linear regression models with both fixed and random effects (mixed-effects linear regression), applying sampling probability weights, and controlling for settlement-level clustering, were used to examine associations between household socio-demographic characteristics and mold mycotoxin knowledge score. Subsequently, a multivariable mixed-effect model was built with those socio-demographic variables associated in the crude analysis . About half of respondents knew that drought conditions could favor mold proliferation before harvest, whereas about one-fifth mentioned high temperatures and overgrown weeds as causes of mold proliferation. Among the respondents who were aware of mold contamination during harvesting, heavy rain during harvesting was the predominantly known condition for mold proliferation (79%). Around half of the respondents correctly mentioned the use of moist containers as a risk factor for mold during harvesting, while around a quarter mentioned leaving soil on pods. Among respondents aware of mold contamination during the post-harvest and storage stage, heaping wet, freshly harvested crops was the predominantly cited condition for mold proliferation (84%). Limited air circulation in the storage area was mentioned by 38%. Around one-quarter were aware that storage in a damp environment, e.g., in wet bags, and poultry or rodents in the storage area were risk factors for mold contamination. The knowledge of favorable conditions for mold contamination was generally higher among households belonging to the FAARM intervention group than among controls.The study population had a fair level of knowledge of the harmful effects of mold and mycotoxin contamination. Most respondents reported the adverse effects of mold contamination of food crops, such as a change in color (71%), change in taste (67%), change in smell (52%), and reduced harvest quantities (51%). Most respondents (71%) also recognized that moldy feeds were harmful to farm animals, predominantly mentioning diarrhea (92%) as a consequence, as well as less frequently reduced weight gain and growth (10%) or reduced production of milk and eggs (6%). Over 80% of respondents knew that mold that contaminated food crops might produce toxins, and of these, over 80% knew that these toxins might remain in food even after processing or cooking. Nearly all respondents (97%) were aware that toxins produced by mold were harmful to humans. As examples, many mentioned non-specific gastrointestinal disorders, including nausea, vomiting, and stomach ache (74%). Awareness of severe long-term effects in humans was much lower, with only a third mentioning chronic liver disease and less than 10% mentioning cancer and reduced growth in children.p = 0.004). Based on the scoring criteria, 85% of households were classified as having a low knowledge level (<30% of maximum achievable score) regarding the timing and conditions for mold contamination of crops. In comparison, 14% had a fair level of knowledge, and only 1% had good knowledge (achieving at least 60% of the maximum score). The vast majority of households (86%) were judged to have a low level of knowledge of recommended preventive practices, while 14% had a fair knowledge level. In contrast, the knowledge of the harmful effects of mold and mycotoxin contamination of crops was much higher, with 77% of households having a fair level of knowledge, an additional 4% a good level of knowledge, and only 19% having low knowledge, in this regard. Combining all the knowledge domains, 80% of households had a low overall knowledge of mold and mycotoxin contamination and prevention. The remaining fifth had a fair level of knowledge, and less than 1% had good knowledge.The overall mold and mycotoxin knowledge score was associated with various socio-demographic characteristics in bivariable analyses .In multivariable regression analyses , belongiIn most low-income settings where mycotoxin exposure is prevalent, the knowledge, awareness, and practice of rural subsistence farmers’ regarding mold contamination of food crops remains poorly studied. This survey was thus conducted among rural Bangladeshi farming households to (i) determine their level of awareness and experience with mold contamination of food crops (ii) and to assess their knowledge of the contamination conditions and harmful effects of mold contamination, as well as (iii) their knowledge of the recommended agricultural practices for controlling and preventing mold contamination of food crops.As far as the authors are aware, this is the first KAP study on mold and mycotoxin contamination of food crops in Bangladesh and its neighboring countries. So far, a limited number of studies worldwide have been conducted on this topic. The high general awareness of and experience with mold in this study agrees with the findings of the limited, available studies on this topic, conducted mainly in eastern and southern African countries ,36,37,38The almost universal level of awareness of mold in general, and of mold contamination of food crops amongst respondents provides a true reflection of the ubiquitous presence of mold in the environment. The identified local terms for “mold’: “Chhatrak”, “Chita”,” Maista”, “Maiska”, and “Kalo Dag”, were spontaneously known and understood by the majority of respondents (60%). This makes these terms useful and applicable in subsequent mold and mycotoxin research in the country. Aside from the research, these local terms may also help agricultural and health officers improve information, education, and communication interventions regarding mold and mycotoxin, as they avoid the difficulties with using the technical terms. For example, in a similar study conducted in Malawi , only 11fusarium species, and storage mold, mainly the Aspergillus and Penicillium species, and their respective mycotoxins [The predominant experience of mold contamination during the field and post-harvest stages of crop production in this community indicates a possible widespread exposure to both field mold, mainly the cotoxins . The reccotoxins ,26,27,28Understandably, the respondents’ knowledge of the timing of mold contamination appears to be in keeping with their personal experience with mold contamination, mainly during the pre-harvest stage. Their responses, however, demonstrate a lack of awareness of the possibility of mold contamination during the harvesting and post-harvest storage stages of crop production. The respondents’ knowledge of favorable contamination conditions during the pre-harvest, harvesting, and storage stages of crop production appears limited. However, what they know about contamination conditions seems to be in keeping with their knowledge of the recommended agricultural practices to prevent mold contamination at the different crop production stages ,29,40. TIn the present study, the respondents’ knowledge was relatively better regarding the observable changes in mold-contaminated crops, the awareness of subsequent mycotoxin production, and the persistence of these toxins even after processing and cooking. Similarly, the majority of the respondents recognized that mold was dangerous to both humans and livestock. Considering that these households were commonly involved in subsistence farming, these results were not surprising. They were likely to be borne from their personal experiences. Unfortunately, in low-resource settings, an awareness of the harmful effects of mycotoxins does not necessarily translate into the avoidance of moldy foodstuffs. For example, in a similar survey in Malawi, although most respondents (88%) knew that mycotoxins were harmful to human health, about half of them still consumed these contaminated foods due to a food shortage .In the multivariable analysis, having the highest level of arable land was associated with a better knowledge score . BesidesHowever, the study population’s overall low average knowledge score (19.4 out of 81) underpins an urgent need for tailored information, as well as educational and communicational intervention in this setting. To the best of our knowledge, there have been no recent interventions in farming households in the study area to raise awareness of mold contamination of farm crops and inform on the relevant preventive agricultural practices. In this study, the households who are less informed regarding mold contamination of food crops also had smaller farms and are most likely not targeted by agricultural extension officers. Nevertheless, since most households are involved in subsistence farming and food storage, at least at some point in the year, mold awareness campaigns should not ignore households less involved with farming.This study’s unique strengths include using the appropriate local terms for mold and mycotoxins during data collection, using a probabilistic sampling approach with adequate sample size, and ensuring a high response rate to minimize bias and maximize the validity of study results. Furthermore, the design of the knowledge score was based on current evidence-based recommendations and accounted for the relative importance of different knowledge categories. The comprehensive data collected also allowed for the evaluation of the relationship between mold and mycotoxin knowledge and several household socio-demographic characteristics. Despite these strengths, one needs to take into consideration the following inherent limitations when interpreting the results. Firstly, as with most KAP studies, this study’s findings relate to reported rather than observed practices. Thus, it is assumed that the inability to provide correct answers reflects a real lack of knowledge and not a misunderstanding of the questions. Nevertheless, careful planning, pre-testing, and proper training of local data collectors were carried out to minimize any cultural or technical gaps and resolve any unclear issues.It is also worth considering that, as many attributes are compared simultaneously between the FAARM intervention and control groups, it becomes more likely that the groups will differ on at least one attribute due to chance alone. Consequently, one needs to interpret some of the observed differences in the comparative analyses with caution. Finally, as the study was conducted in rural households in Habiganj district, who also participated in the FAARM trial, the findings cannot necessarily be generalized to other areas. However, the FAARM study population is typical for rural settings in Bangladesh and so findings may also apply to similar settings. Moreover, it may also be worthwhile collecting data on people living in Bangladesh’s urban areas to obtain a general idea about mold and mycotoxins knowledge among non-farming households. Nevertheless, the study provides valuable insights into the levels of awareness and experience, as well as the knowledge of rural farming households in Bangladesh regarding mold and mycotoxin contamination of food crops. Thus, the study provides a primary point of reference that will help the relevant public health and agricultural officers set priorities, develop practical information, educational and communicational interventions, and measure the changes from their interventions.This study’s findings demonstrate that, in low-income settings with a high mycotoxin occurrence, rural farming households, who may be aware of mold contamination of food crops in general, may still have substantial knowledge gaps regarding the prevention and control of mold contamination and exposure to mycotoxins. Providing rural farming households with better information about mold control and prevention in food crops could improve their knowledge and limit exposure to mycotoxins in the community. Even though this knowledge does not necessarily lead to a change in behavior, the identified gaps in the population’s knowledge of mold contamination conditions, and the consequences of the mold contamination of crops, should form the basis for developing tailored interventions to prevent and manage mold mycotoxin contamination at different stages of crop production.


The use of artificial intelligence (AI) and robotics in endovascular neurosurgery promises to transform neurovascular care. We present a review of the recently published neurosurgical literature on artificial intelligence and robotics in endovascular neurosurgery to provide insights into the current advances and applications of this technology.The PubMed database was searched for "neurosurgery" OR "endovascular" OR "interventional" AND "robotics" OR "artificial intelligence" between January 2016 and August 2021. A total of 1296 articles were identified, and after applying the inclusion and exclusion criteria, 38 manuscripts were selected for review and analysis. These manuscripts were divided into four categories: 1) robotics and AI for the diagnosis of cerebrovascular pathology, 2) robotics and AI for the treatment of cerebrovascular pathology, 3) robotics and AI for training in neuroendovascular procedures, and 4) robotics and AI for clinical outcome optimization.The 38 articles presented include 23 articles on AI-based diagnosis of cerebrovascular disease, 10 articles on AI-based treatment of cerebrovascular disease, two articles on AI-based training techniques for neuroendovascular procedures, and three articles reporting AI prediction models of clinical outcomes in vascular disorders of the brain. Innovation with robotics and AI focus on diagnostic efficiency, optimizing treatment and interventional procedures, improving physician procedural performance, and predicting clinical outcomes with the use of artificial intelligence and robotics. Experimental studies with robotic systems have demonstrated safety and efficacy in treating cerebrovascular disorders, and novel microcatheterization techniques may permit access to deeper brain regions. Other studies show that pre-procedural simulations increase overall physician performance. Artificial intelligence also shows superiority over existing statistical tools in predicting clinical outcomes.The recent advances and current usage of robotics and AI in the endovascular neurosurgery field suggest that the collaboration between physicians and machines has a bright future for the improvement of patient care. The aim of this work is to equip the medical readership, in particular the neurosurgical specialty, with tools to better understand and apply findings from research on artificial intelligence and robotics in endovascular neurosurgery. Artificial intelligence (AI) is generally defined as the ability of a machine to analyze data and use it to learn and model human behavior. The general subtypes of AI technology that are currently being used and studied in healthcare are machine learning (ML), which identifies and analyzes patterns to detect associations in a dataset; deep learning (DL), which allows machines to make decisions through the use of neural network (NN) models; natural language processing, which allows machines to analyze human language; computer vision, through which computers can learn by analyzing images and videos; and physical robotics used for surgical procedures ,2. In thBy comparison, robotic systems in surgery are generally divided into three categories: 1) active systems, which work autonomously; 2) semi-active systems, in which the surgeon complements the preprogrammed component of the robot; and 3) surgeon-driven systems . The curUnderstanding the impact and advances that robotics and AI have in the overall management of cerebrovascular disease will fundamentally and permanently enhance endovascular neurosurgery. Artificial intelligence has shown promise in both diagnostic and treatment settings. Deep learning algorithms have been effective in image recognition and may be instrumental in the improvement of decision-making in the clinical setting ,9. For eWhile the use of robotics in neurovascular intervention is in its infancy, promising steps have been made to incorporate this technology into clinical practice. Interventionalists have employed AI and robotics to enhance medical treatment, yet most advances have been implemented in interventional cardiology; for instance, the CorPath GRX robotic system  has been utilized for coronary interventions since 2012 and was approved for peripheral vascular procedures in 2018 . The CorWithin this work, we review the recent literature on the role of AI and robotics in endovascular neurosurgery to summarize significant findings from a series of reports and experimental studies in order to inform neurosurgeons and physicians in any medical specialty who wish to better understand emerging technology and its influence on clinical practice. Specifically, we survey the literature from January 2016 to August 2021 to understand how AI and robotics impact the diagnosis of cerebrovascular disorders, the treatment of cerebrovascular disorders, the training of endovascular neurosurgeons, and the outcome optimization in the management of neurovascular disease.MethodsIn order to perform an analysis of the existing literature on robotics and artificial intelligence in endovascular neurosurgery, the PubMed database was searched for articles between January 2016 and August 20, 2021. We selected this time window to focus on the examination of the most recent literature. The search terms utilized were "neurosurgery" OR "endovascular" OR "interventional" AND "robotics" OR "artificial intelligence." Initially, 1296 articles were identified.Articles were included in this study if they presented primary data related to AI or robotics in the context of endovascular neurosurgery , arteriovenous fistulas, intracranial hemorrhage, and strokes), as well as optimization of catheterization procedures. To focus on novel primary data, literature reviews were excluded. To focus further on endovascular neurosurgery, articles were excluded if their focus was on non-neurovascular pathology .A careful reading of the above articles revealed four general classes of AI and robotics research: 1) robotics and AI for diagnosis in endovascular pathology, 2) robotics and AI for the treatment of endovascular pathology, 3) robotics and AI for training in neuroendovascular procedures, and 4) robotics and AI for clinical outcome optimization. Articles under the diagnosis category were further classified into intracerebral hemorrhage (ICH) and Moyamoya disease detection, vascular visualization and diagnosis of vascular pathology , and diagnosis of large vessel occlusion (LVO) and stroke. This subclassification is intended to help the reader map the many uses of AI as they pertain to different cerebrovascular pathologies.ResultsA total of 1296 articles were initially identified from the PubMed database. After applying the inclusion and exclusion criteria, 38 papers were selected for review and analysis: 23 articles on AI-based diagnosis of cerebrovascular disease, 10 articles on AI-based treatment of cerebrovascular disease, two articles on AI-based training techniques for neuroendovascular procedures, and three articles reporting AI prediction models of clinical outcomes in vascular disorders of the brain. Figure AI-Based Diagnosis of Cerebrovascular DisordersTwenty-three articles describing AI-based diagnostics in endovascular neurosurgery were included. A complete description of the results from these studies can be found in Table We identified seven articles that demonstrated the potential clinical utility and time-effectiveness that DL algorithms offer in the setting of stroke and LVO -25. MoreSeven of the identified studies focused on intracranial aneurysm detection and surveillance and reported successful results using AI-assisted diagnosis -32. SilvFour studies were related to AI-based ICH diagnosis or classification -40, and AI-Based Treatment of Cerebrovascular DisordersTen articles describe the role of AI/robotics-based treatment of neurovascular disorders -18,43-47AI/Robotics in Neuroendovascular TrainingTwo studies looking at AI/robotics-based training and simulation of neurovascular procedures were included ,49. A fuAI/Robotics in Clinical Outcome Optimization for Neurovascular DiseaseThree articles described the use of AI in outcome prediction and optimization in the setting of neurovascular disease and treatment. Two retrospective studies and one prospective study were included -52. TablDiscussionArtificial Intelligence and robotic systems have transformed the practice of medicine, allowing for time-effective diagnosis, efficient patient categorization and treatment, improved diagnostic accuracy, and precise and safe surgical interventions. We describe the spectrum of various AI algorithms and robotic systems in endovascular neurosurgery and give readers an opportunity to understand the current impact that this technology may have on neurovascular practice and patient care. In particular, ML and DL algorithms may facilitate the detection of life-threatening conditions such as stroke and LVO, ICH, and ruptured aneurysm, while other algorithms can assist with surveillance such as ensuring that unruptured aneurysms have not grown or changed in morphology. For ischemic stroke, Morey et al. used the Viz LVO algorithm in a real-world experiment, and it resulted in decreased door-to-neurovascular team notification times, which in turn resulted in faster reperfusion and augmented clinical outcomes . EvolvinRobotic systems in interventional procedures also have the potential for more practical interventions and improved outcomes. Although robotic systems are generally thought to decrease procedural times, Cheung et al. and Weinberg et al. have demonstrated that this is not always true, primarily owing to increased robotic cannulation times and a lack of operator familiarity with the robotic system ,54. HoweRobotics naturally may make surgery safer for providers as well. The Percutaneous Robotically Enhanced Coronary Intervention (PRECISE) study found that by using robotic aids, the median radiation exposure to operators was reduced by 95.2%  . The useAlthough robotic systems in endovascular procedures have limitations such as a lack of haptic feedback, the literature in this review suggests that the incorporation of this technology is forthcoming and will continue to improve. In this landscape of rapid change and innovation, limitations to AI and robotics must be further explored and studied through rigorous testing. Although this poses a challenge for the development of a larger number of clinically safe algorithms, AI technology may pave the way for the future in clinical practice and augment practicing physicians’ capabilities to efficiently recognize life-threatening conditions.As the incorporation of AI and robotics continue, this new technology will fundamentally have an impact on healthcare costs to the individual and society. Approximately $3.3 trillion is spent by the United States on healthcare ,58, and Our review indicates that AI and robotics in endovascular neurosurgery have an extremely promising future, albeit with an unknown impact on interventional costs. Becoming familiar with this technology and understanding its intricacies and clinical applications can be beneficial for neurosurgeons and neurointerventionalists alike, as AI research and its clinical applications continue to grow and evolve. We hope to encourage not only neurosurgeons but also other physician specialties to become acquainted with these advances since they may become the standard for improved patient care in the future.


Implementation researchers are increasingly using economic evaluation to explore the benefits produced by implementing evidence-based practices (EBPs) in healthcare settings. However, the findings of typical economic evaluations  are rarely sufficient to inform decisions about how health service organizations and policymakers should finance investments in EBPs. This paper describes how economic evaluations can be translated into policy and practice through complementary research on financing strategies that support EBP implementation and sustainment.We provide an overview of EBP implementation financing, which outlines key financing and health service delivery system stakeholders and their points of decision-making. We then illustrate how economic evaluations have informed decisions about EBP implementation and sustainment with three case examples: (1) use of Pay-for-Success financing to implement multisystemic therapy in underserved areas of Colorado, USA, based in part on the strength of evidence from economic evaluations; (2) an alternative payment model to sustain evidence-based oncology care, developed by the US Centers for Medicare and Medicaid Services through simulations of economic impact; and (3) use of a recently developed fiscal mapping process to collaboratively match financing strategies and needs during a pragmatic clinical trial for a newly adapted family support intervention for opioid use disorder.EBP financing strategies can help overcome cost-related barriers to implementing and sustaining EBPs by translating economic evaluation results into policy and practice. We present a research agenda to advance understanding of financing strategies in five key areas raised by our case examples: (1) maximize the relevance of economic evaluations for real-world EBP implementation; (2) study ongoing changes in financing systems as part of economic evaluations; (3) identify the conditions under which a given financing strategy is most beneficial; (4) explore the use and impacts of financing strategies across pre-implementation, active implementation, and sustainment phases; and (5) advance research efforts through strong partnerships with stakeholder groups while attending to issues of power imbalance and transparency. Attention to these research areas will develop a robust body of scholarship around EBP financing strategies and, ultimately, enable greater public health impacts of EBPs. Contributions to the literatureWe describe the need for implementation research to inform financing strategies, which secure and direct funds to support EBP adoption and continued use.We articulate an important gap between economic evaluation findings from research and the development of financing strategies in practice and policy.Our overview of EBP financing identifies the roles and relevant decisions for key health service system stakeholders.Our case examples highlight how different EBP financing strategies have been used to translate data on economic impact into practice and policy.We propose a research agenda for advancing the complementary impact of economic evaluations and financing strategies.Implementation research often presupposes that increased use of evidence-based practices (EBPs) will produce improved health and associated benefits for patients, health systems, and society. Researchers are increasingly using economic evaluations to empirically compare costs and outcomes between discrete clinical scenarios—including use of EBPs and associated implementation strategies –3. Yet tSuch translation is important, given that the added costs of implementing and sustaining EBPs are a barrier to their use in healthcare settings –6. Balanhow to finance EBPs and implementation strategies. Research from varied global contexts consistently shows that economic evaluations are one of many important factors in decision-making about EBP use [Much as efficacy findings about EBPs rarely change clinical practice without concerted implementation efforts, economic evaluation findings alone are unlikely to change large-scale patterns of investment in EBPs. A major remaining challenge—and the focus of this paper—is determining  EBP use –18. Fina EBP use . In what EBP use , the soc EBP use , 22, the EBP use )—e.g., tMaximizing the public health impact of EBPs requires strategies that align service delivery and financing to effectively support and sustain implementation . Such stThe present paper describes how economic evaluations and financing strategies can together inform EBP implementation within healthcare policy and practice. We begin with an overview of financing for EBP implementation, highlighting key decisions involved for stakeholders. We then present three case examples depicting how the results of economic evaluation can inform those decisions—and the limitations encountered. We conclude by articulating a research agenda in which investigations of economic impact and financing strategies can mutually advance large-scale investment in EBPs.service delivery system involves direct provision of health services (including EBPs) and includes health service provider organizations  and the patients they serve. Also within this system, health service organizations may receive non-monetary support and guidance in using EBPs from purveyor/intermediary organizations  [financing system is made up of various agencies that provide funding to health service organizations in exchange for delivering care. Examples of funders include government agencies  that support services directly or through related research, non-profit foundations, donors, and insurance plans . Each funder may provide financing to health service organizations and/or engage in complex interactions with other funders . Altogether, payments to providers and provider organizations from funding agencies account for most healthcare expenditures  . (2) The the USA , 22); thFigure The financing of EBP implementation—and the role of economic evaluation therein—is highly complex, as shown in Fig. The first case is a Pay-for-Success financing initiative  designed to address youth detention and incarceration through improved behavioral health services in Colorado. Detention and incarceration remain common, albeit largely ineffective, responses to serious youth behavioral problems in the USA , 30 and In 2018, the Colorado Office of State Planning and Budgeting, in coordination with other state agencies and outside experts, chose to implement a behavioral health EBP called multisystemic therapy (MST ) as one Complex economic considerations limit availability of MST, despite strong evidence of its economic benefits from reduced recidivism and out-of-home placements . For exaThe Pay-for-Success financing strategy followed several key steps. First, the government prioritized a social problem and determined a solution to implement; the State of Colorado sought to decrease youth detention, incarceration, and recidivism by implementing MST in regions underserved for youth behavioral health. Second, private investors interested in achieving social impact provided the upfront capital for implementation. One bank (Northern Trust Corporation) and two foundations  were the investors for MST. The Center for Effective Interventions at the University of Denver was chosen as the intermediary organization for MST to provide implementation support to the community-based behavioral health agencies delivering the intervention. The investors, together with the Colorado State Office of Children Youth and Families and the Center for Effective Interventions, were appointed voting members of the Governance Committee overseeing the project. The Committee developed plans for an independent evaluator  to measure outcomes across 3 years of active MST implementation plus 1 year of follow-up evaluation. Finally, the Committee developed plans for the state government to repay the investors through “success payments” if the project meets key implementation outcomes  and youThe substantial cost-benefit tradeoffs of MST were integral to supporting the financing arrangements for this project. Based on published evidence of >$3 for each dollar spent , 37 and Over 1.6 million people are diagnosed with cancer annually in the USA, and almost 600,000 die from it, making it the second greatest cause of death . The cosThe oncology care EBPs required by the OCM were selected based on extensive clinical and economic evidence; for example, patient navigation services and expanded access to clinician experts have been shown to decrease the utilization of low value and avoidable acute care . The goaTo address the financing barriers to oncology EBP use, the OCM builds on fee-for-service payments with two additional payment mechanisms , 44: (1)After stakeholder input but before the structure and amounts of the proposed case management and incentive payments were finalized, Centers for Medicare and Medicaid Services conducted a simulation budget impact analysis of OCM for Medicare and oncology practices . To deveAs of February 2020, the OCM included 139 participating practices, over 6000 practitioners, approximately 25% of Medicare fee-for-service chemotherapy-related cancer care , and 10 non-Medicare payors . As oncoThis last case highlights how selection of financing strategies is also an important consideration during intervention development. The US opioid use disorder (OUD) epidemic has resulted in widespread impairment, death, and economic impacts . MedicatConducted an assessment of resources needed to sustain INSPIRE Specified funding objectives  and related determinants for each resource Identified candidate financing strategies  for each funding objectiveDespite its strong foundation, INSPIRE could prove challenging to implement even if it improves MOUD retention. Family treatments for substance use disorders have low uptake in service systems, due to financing barriers for interventions that focus on people other than the identified patient  and the These activities have identified Medicaid billing options that could most sustainably finance INSPIRE groups and a need for private funding to purchase technology that support persons can use to participate. The remaining steps are to (4) work with health system partners  and funding agency partners to track INSPIRE implementation costs and help them select financing strategies (from step 3) that sustainably cover those costs; then, (5) monitor and evaluate financial viability over time. The result will be a comprehensive fiscal map outlining how INSPIRE can be financially sustained in primary care systems—should the pragmatic trial show it produced significant clinical benefits for its costs.Fiscal mapping offers a unique approach to financing decisions for new interventions like INSPIRE. Typically, health service providers offer services for which funding agencies are willing to offer payment  see als. InterveA major challenge to implementing and sustaining EBPs is covering associated costs with the limited, fragmented funding available , 23, 24.First, as articulated elsewhere , maximizSecond, changes in real-world financing systems can inform future economic evaluations. Health systems are being transformed by the needs of chronic disease management, health promotion, management of health risks at a population level, and paying for outcomes (vs. fee-for-service) . As payoThird, it will be challenging to evaluate which financing strategies are most effective and economically beneficial under a given set of conditions. It remains unclear what level of evidence  justifies a given level of financial risk and who should bear that risk. Many financing strategies involve coordinating funds across multiple levels of the service system ecology  and/or across multiple service systems . Designing these strategies is technically complex and requires expertise from finance, accounting/billing, and economics professionals. For example, cost-sharing among the parties involved is a challenging aspect of financing strategy design; healthcare reforms increasingly shift costs onto providers, who risk lower reimbursements or even penalties for not achieving quality standards or desired outcomes . It willFourth, the impact of financing strategies should be investigated across pre-implementation, active implementation, and sustainment phases . Almost Finally, researchers need to navigate relationships among health service organizations and their funding sources see Fig.  when stuIt is important to note several limitations of our analysis. We presented case examples related to EBP treatment models, but it will also be important to explore the challenges of financing of EBPs that are preventive interventions, screening/assessment tools, or policy solutions—where returns on investment tend to be diffuse and unfold slowly over time . FurtherIn conclusion, EBP financing strategies offer promising solutions for translating economic evaluation results into policy and practice, but raise numerous questions. Those questions illustrate the various dimensions of interventions, systems, and broader contexts that will be important to consider as researchers and stakeholders develop a robust field of scholarship around EBP financing strategies.


Suicide and suicide attempts have become more prevalent in recent years, with notable increases in the US in all age groups and geographic locations. Risk of suicide is particularly high among patients diagnosed with bipolar disorder or severe depression, especially when associated with mixed features or agitation, or with co-occurring substance abuse. Factors contributing to such risk include relative social and geographic isolation and low access to sources of support or clinical care. In addition, unemployment, poverty, demoralisation and opioid abuse have been identified as important risk factors. Notably, overall longevity rates in the US, though rising for many decades, have recently been declining, in part owing to suicide and substance overdoses. A particular circumstance associated with strikingly high rates of suicides and attempts is the days and weeks following discharge from psychiatric hospitalisation. Although the incidence of such events is low, there is a need for more secure aftercare planning and implementation. Research on therapeutics aimed at reducing suicidal risk and all-cause mortality among psychiatric patients remains severely under-developed. Suicide is strongly associated with mood disorders, especially bipolar disorders and severe or melancholic major depression, and is particularly likely among adolescents and young adults, and with co-occurring substance abuse  in 2003 to nearly 13.4/100k PEY in 2016, overall, and rates of fatal drug overdoses in the country increased by more than 4.4-fold from 1999 to 2015  can serve as an et al., et al., et al., We also evaluated risk factors associated with suicidal behaviour among patients with specific major mood disorders diagnosed by modern DSM-5 criteria (Baldessarini et al., et al., et al., et al., An especially dangerous time for suicidal risk is immediately following discharge from psychiatric hospitalisation (Chung et al., These findings indicate high risks of suicides and attempts soon after hospital discharge, with one-third of the one-year risk occurring within the initial two weeks. They strongly encourage more secure aftercare planning and immediate implementation following hospitalisation, particularly among patients with a severe mood, psychotic or substance abuse disorder, and those whose hospitalisation was indicated by emerging suicidal risk. A challenge to this recommendation of high vigilance and vigorous protection is that suicidal events, though much more prevalent following hospital discharge compared to other times in the course of mental illnesses, are still infrequent. We estimated that over 400 discharges would occur in order to encounter a single suicidal act within four weeks of hospital discharge (Forte The findings briefly reviewed here, arising largely from our recent research, indicate that suicide rates are increasing markedly, at least in the US. We are now able to state with greater confidence the association of suicidal behaviour with particular types of psychiatric illness based on current diagnostic criteria, to clarify risk factors for particular mood disorders, and to identify conditions associated with particularly high risk.et al., et al., et al., Proposed explanations for the observed recent, adverse, epidemiological trends summarised here remain impressionistic and incomplete. Moreover, means of effectively decreasing suicidal risk and of all-purpose mortality associated with major psychiatric illnesses remain unsatisfactory. Of particular concern, studies of therapeutic interventions specifically aimed at reducing suicidal risk are rare and extremely challenging to carry out in an ethical and scientifically credible manner. Indeed, only clozapine for schizophrenia has been recognised by the US FDA as having significant potential to reduce suicidal risk (Meltzer


Adolescent girls and young women account for a disproportionate fraction of new HIV infections in Africa and are a priority population for HIV prevention, including provision of pre-exposure prophylaxis (PrEP). Anchoring PrEP delivery to care settings like family planning (FP) services that women already access routinely may offer an efficient platform to reach HIV at-risk women. However, context-specific implementation science evaluation is needed.The Family Planning Plus Project is a prospective, pragmatic implementation evaluation, designed as a stepped wedge, cluster randomized trial, at 12 clinics in Kenya. In collaboration with the Kenya Ministry of Health and Kisumu County Department of Health, we will introduce integration of HIV risk screening and PrEP delivery in public health FP clinics. The core multifaceted implementation strategies to integrate PrEP in FP clinics will include: (1) PrEP delivery by existing FP clinic staff, (2) health provider training, (3) PrEP technical assistance to coach and mentor providers, (4) joint supervision with Kisumu County health officials, and (5) stakeholder engagement. All core components of PrEP delivery—including screening for HIV risk, HIV testing, dispensing, adherence and risk reduction counseling, assessment of side effects, and provision of refills, or safety assessment—will be conducted by existing FP clinic staff as part of a standard care service package. The goal is to catalyze sustainable scale-up within existing infrastructures beyond the project. We will rigorously evaluate implementation outcomes and impact, using the RE-AIM  framework, and we will use Organizational Readiness for Implementing Change (ORIC) and the Consolidated Framework for Implementation Science Research (CFIR) to assess readiness to implement and contextual enablers and barriers of implementation, including how clinics innovate efficient delivery systems.Anchoring PrEP delivery to existing FP systems and staffing has tremendous potential to address barriers that women face in accessing HIV prevention and PrEP care, including lack of time, cost, and stigma of visiting a facility solely for HIV prevention. The FP Plus Project will initiate preparation for full-scale and sustainable model of integration of comprehensive HIV prevention services, including PrEP implementation, in public health FP clinics in low-income settings.Trial registrationClinicalTrials.gov on December 14, 2020: NCT04666792Registered with  Contributions to the literatureYoung African women are a priority for HIV prevention including PrEP provision because they account for a disproportionate percentage of new HIV infections.Routine family planning clinics are attractive settings for PrEP implementation due to broad coverage for sexually active women. However, there is limited real-world evidence on effective strategies for integrated family planning and PrEP delivery in African settings.Rigorous implementation science evaluations from this work will provide important information on how to effectively and sustainably reach at-risk women for PrEP in resource-limited settings. The findings will also be valuable in translating emerging HIV prevention modalities into real-world implementation.Women account for a disproportionate percentage of individuals with new HIV infections in Africa and are a priority population for HIV prevention , includiIn the recently completed PrEP Implementation in Young Women and Adolescent (PrIYA) program , we pioneered PrEP provision in FP clinics and demonstrated feasibility of integrating PrEP provision in FP systems using project-dedicated staff embedded in FP clinics . Over 12The overall goal of the FP Plus Project is to catalyze integration of comprehensive screening for HIV risk and PrEP delivery in public health FP clinics in Kenya. The specific aims are:1) Facilitate integration of comprehensive screening for HIV risk behaviors and delivery of PrEP in public FP clinics and evaluate program impact.2) Assess clinic readiness to implement PrEP, fidelity to PrEP service delivery, impact on current services, and facilitators and barriers to integrating PrEP delivery in FP clinics3) Assess incremental costs, budget impact, and affordability of integrating PrEP delivery in FP clinics4) Refine and optimize simple data systems that will expand and support delivery of integrated FP and HIV prevention services at scale.The population includes sexually active HIV-uninfected women of reproductive years accessing FP services in the Kisumu area of Kenya, given it is a high HIV burden area . The proEligibility to participate in the program will reflect the real-world implementation nature of this work. Thus, the program will be set up for all women of reproductive age ( ≥15 years), HIV uninfected or of unknown HIV status receiving routine FP services. The broad eligibility criteria is designed to align with the public health nature of this work; to operate effectively, efficiently, and ethically in community settings, PrEP will need to be broadly accessible to all at-risk adolescent girls and young women who shoulder the biggest burden of HIV infections in this setting. Determination of eligibility for PrEP will be conducted according to the Kenya national PrEP guidelines. All women determined to be at risk for HIV, or expressing interest in PrEP, will have access to PrEP medication free of charge as part of the Kenya national PrEP scale-up program.The FP Plus Project is a prospective, pragmatic stepped wedge cluster randomized trial (SWCRT). In collaboration with the Kenya MOH and Kisumu County department of health, systematic screening for HIV risk and counseling for and provision of PrEP will be introduced and actively promoted in FP clinics in three staged successive waves (steps), occurring approximately every three months with an average of 60 HIV-uninfected women accessing services per clinic per step, and four clinics initiating implementation per step Fig. . We willRandomization was carried out at the beginning i.e., a single point in time , randomizing the order with which the clinics (clusters) cross over from usual care to implementation of the intervention package. Randomization was conducted without restriction and implemented in two-stages using an online wheel-of- fortune. First, clinics were assigned to three groups of four clinics each and second, the groups were then assigned to the order  to which they would start implementation Fig. .For this implementation project, the intervention to integrate PrEP in Kenyan FP clinics is a multifaceted implementation strategy with the following core components: 1) promotion of comprehensive screening for HIV risk and PrEP eligibility by existing FP staff ; 2) Training of existing health care providers; 3) PrEP technical assistance to coach and mentor health providers; and 4) Joint supervision with Kisumu County health officials. At all implementing clinics, we will conduct a pre-implementation needs assessment to understand and document current processes on HIV risk screening and testing, existing PrEP screening and provision , STI screening, testing and treatment, and male partner testing. Prior to initiating implementation at each clinic, we will conduct clinic-wide training for health care providers, and we will engage existing FP providers in ongoing continuous quality improvement to optimize PrEP delivery. Clinics will start implementation after two weeks of intensive training. Each clinic will have at least 12 months of intensive implementation of the intervention package followed by at least 12 months of maintenance phase  using the approved case-based interactive Kenya MOH/NASCOP PrEP training curriculum . ContentWe will conduct ongoing technical assistance to clinics using trained experienced program nurses to coach, mentor, and guide FP clinics to troubleshoot emerging challenges with integrating new services. Technical advisors (TAs) will be project nurses with training in PrEP delivery. TAs will conduct structured periodic visits to each clinic to engage with the health care providers and observe and document PrEP implementation processes, with a specific focus on delivery modifications over time to understand integration optimization within and between facilities. Using rapid-cycle analysis approaches, TAs will make summary reports at the end of each clinic visit highlighting what changed, why it changed, who initiated the changes, and outcome of any changes instituted. Best practices will be shared across all clinics (cross-clinic pollination) for possible adoption. The project will work with the County Health team and implementing clinics to optimize simple data systems that include indicators for screening HIV risk and PrEP provision.At each clinic, the TAs will visit the clinic weekly for first three months, and then complete monthly visits through the 12-month intensive implementation phase. During the maintenance phase, TAs will complete quarterly visits or as requested by the implementing clinics focused on understating institutionalization of integration. Every three months throughout the first 18 months of intervention implementation , the TAs will be accompanied to the facility visits by County health and or Kenya MOH/NASCOP supervisors to audit for process and integration indictors for FP services, HIV prevention services, and PrEP and progress.The co-primary outcomes will be the proportion of women screened for HIV risk and PrEP eligibility and the number and proportion of women eligible women who initiate PrEP. The study has been powered for the PrEP eligibility screening outcome. The denominator will consist of all HIV uninfected women accessing services at the implementing FP clinic during each step (time period). Although screening for HIV risk behaviors is an expected service in FP clinics, it is not routinely done or documented in most FP settings. After the intervention, we expect to see screening for HIV risk and PrEP among general population women to increase from ~5% to 25% (mean ~20%). We used an intracluster correlation coefficient value of 0.15, which is generally considered conservative in this context, and we conservatively allowed the proportion of HIV-uninfected women counseled on HIV risk and PrEP to be 6% in the absence of intervention at the end of the study . Given these parameters, if we enroll 56 HIV-uninfected women in each of the 12 clinics during each of the first four steps (including the baseline step), where four clinics initiate the intervention in each of first three post-baseline steps , we would have 80% power. Note that these calculations provide the number of HIV-uninfected women required; the number of women needing to be screened would be higher (and would depend on the HIV positivity rate). To fully understand how clinics build new efficient systems for delivery of integrated FP and HIV prevention services, we will study data on a total of at least 5000 women accessing routine services across the 12 FP clinics. This sample size will permit a full-scale test of the system, since implementation outcomes and the efficiency in delivery are to a greater part at the system level, above and beyond the individual client encounter.We will use multiple data sources Table  to robusClinical records in FP clincs are documented on standardized MOH FP register which collects program data on age, contraception method use, women HIV status, and cervical counseling. In collaboration with the Kisumu county health team, new indicators on screening for HIV risk and PrEP eligibility as part of our goal to streamiline simple but scalable HIV porevention program indicators. For persons who initiate PrEP, Kenya MOH clinical encounter form (PrEP Card) is used for clinical monitoring and program evaluation. Dedicated project staff will weekly abstract program data  and individual clinical records from these standard MOH tools. Individual data will be used to characterize PrEP screening, PrEP eligibility and initiation, HIV risk profiles of PrEP initiators, self-reported adherence, retention, HIV infection, and side effects.We will conduct rigorous mixed-methods evaluation using the RE-AIM framework to gain a comprehensive understanding of how effectively PrEP implementation is integrated in FP systems and program impact Table . The RE-At each clinic prior to implementation, we will administer a validated organizational readiness for change ORIC psychometric tool  to cliniWe will conduct workflow mapping at all sites to identify potential bottlenecks, differences and commonalities among sites at baseline and annually. We will solicit provider engagement in defining new flow maps to accommodate new tasks and patient flows. Current and future flow maps will be created for each site to demonstrate new pathways.We will prospectively conduct qualitative interviews to rigorously understand key influences on integration of HIV prevention and PrEP in FP clinics, at the level of individual women (clients), healthcare providers, the organization , and the health system (policy key-informants). Interviews will use the Consolidated Framework for Implementation Science Research (CFIR)  to guideQualitative interviews with women will assess women’s experiences accessing and using (or not using) HIV prevention services, including PrEP in FP clinics, confidence in the health system, decision-making processes, partnership dynamics, and stigma and community norms around HIV and FP. Because our overarching goal is development of a sustainable HIV prevention program broadly, not specific to PrEP, stratified purposive sampling will be used to ensure that the overall sample represents relevant sub-populations of women including , 25: 1) Qualitative interviews with healthcare providers at FP clinics  and policy key informants  will be conducted during baseline, early implementation and maintenance phases to understand contextual enablers and barriers of implementation acceptability, feasibility, and fidelity. We will specifically evaluate knowledge and confidence delivering PrEP, perception of the impact of PrEP delivery on current FP service provision, and suggestions for efficient integration approaches in the context of FP clinics. Analysis of personal experiences with integrated FP and PrEP delivery will be used to identify determinants of successful implementation and innovative strategies that can be harnessed for future scale-up.We will use quantitative tools including cross-sectional exit surveys among women to complement qualitative interviews. Surveys will focus on understanding HIV risk perceptions, services offered or expected to be offered, quality of care and women satisfaction with services received, and women’s experiences with the health systems. Cross-sectional surveys will be conducted during baseline period and at least annually by project dedicated staff, as clients exit the facility. These surveys will help obtain important data that cannot be obtained from program tools. We will also use a quantitative tool for CFIR inner settings  with cliWe will prospectively document the extent to which the core components of the PrEP implementation are implemented as planned. We will examine fidelity across dimensions of adherence, exposure, quality of delivery, provider responsiveness, and program differentiation. We will assess and document factors that affect fidelity, including characteristics of providers, clinics, women, the FP or community context, and program support systems . Specifically, we will use unannounced standardized patient actors to measure fidelity of the implementation of comprehensive HIV prevention services, including PrEP delivery . Patient actors will visit a subset of clinics for two consecutive visits, once to screen for HIV risk and PrEP, and a second time to refill PrEP. At the end of each unannounced visit, the standardized patient will complete a checklist to document offered services, quality of services received, provider attitudes, and visit duration.Among women who initiate PrEP, adherence will be objectively evaluated by tenofovir levels measured from dried blood spots collected at a subset of randomly selected visits (~10-20%). Adherence will also be measured using pharmacy refill records , and self-report .Within the programmatic setup, we will establish an open cohort of HIV-uninfected women to measure individual-level outcomes on incident HIV and STIs, HIV prevention behavior, PrEP use, and adherence. The cohort will enroll up to 900 women, including women who do and do not choose to initiate PrEP. Eligible women must be HIV negative, sexually active, age 15 years and older, and have at least one behavioral factor defined by the Kenya PrEP guidelines to indicate a substantial ongoing risk of acquiring HIV (as described in the Subsection on Screening for HIV risk and PrEP). Informed consent will be obtained for all research procedures not related to routine care. Cohort participants will complete visits at one month and then quarterly after enrollment for up to 24 months with HIV testing and a brief questionnaire on sexual behaviors, FP and prevention methods use, HIV and STI risk, partner relationship, stigma, mental health, and for women initiated on PrEP, dried blood spots will be collected for objective assessment of adherence. All cohort activities will be conducted by project-dedicated staff. In addition to promotion of standard screening and treatment for STIs across all clinics, we will perform baseline etiological testing for curable STIs (Chlamydia trachomatis and Neisseria gonorrhea) to document the burden for women enrolled in the cohort. Urine from cohort follow-up visits will be archived for future STI testing.We will conduct activity-based costing, staff interviews, and time and motion studies to estimate the cost and model the budget impact of integrating PrEP provision in FP clinics on annual basis, over a 5-year horizon. Using data on the incremental cost estimated during the implementation phase, we will assess the budget impact on the Kenya MOH and Kisumu County budgets for integrating the interventions incorporating the eligible population size, and current MOH and Kisumu budget expenditures, and evaluate for scenarios with current and future HIV prevention methods mix. We will consider direct program costs to ensure that measurements of MOH costs reflect the opportunity cost of the resources used in delivering services. Program costs will also be collected from the project budget, public health clinic budgets, government reports, and the health economics literature, as we have done in previous work –30. The All abstracted health and patient data are kept secure and confidential through adherence to institutional policies and procedures for securely storing, maintaining, and updating health record information. All health record and patient data are securely stored on password protected and encrypted servers and these data will not be released externally except under specific data sharing agreements. All study results will be presented in aggregate, and no individual patient or provider will be identifiable.The primary analysis will use individual-level data from the SWCRT , individual-level data from the blood sample cohort (PrEP adherence), individual-level data from the longitudinal research cohort, and clinic-level data from the SWCRT (HIV diagnosis). Descriptive statistics of the outcomes will be summarized by study step  and clinic within each step, as well as overall.The co-primary outcome to evaluate the intervention effect will be: 1) proportion of women screened for on HIV risk and PrEP; and 2) PrEP uptake. Analyses of the remaining outcomes  will be descriptive and will only involve individuals enrolled  and data collected (for clinic-level outcomes) after the intervention was initiated. The relative risk (RR) for the effect of the intervention on each outcome will be estimated from the individual-level data (based on baseline and steps one to three) using a generalized estimating equations (GEE) approach , 32. Spe. In addition, we will use a combination of conventional and directed content analysis approaches [Qualitative data  will be used to interpret and explain contextual influences on individual RE-AIM dimensions or patterns of results across implementation phases and/or clinics. We will use rapid qualitative analysis approaches to obtain real-time information –37 that proaches  to identClinicalTrials.gov on December 14, 2020 (NCT04666792). Amendments to the study protocol will require approval from the Ethics Review Committee of the Kenyatta National Referral Hospital- University of Nairobi and the Human Subjects Division of the University of Washington. Any amendments will be communicated via trial registration updates and reported in any published manuscripts associated with the study as necessary.This protocol  was registered with The study team for this award is committed to public dissemination of results of the project to local stakeholders in Kenya, the global scientific community, and global policymakers. Dissemination of study results will follow principles of good participatory practice. Results will be published in conference abstracts and peer-reviewed journals. Study results will be disseminated through presentations to global and local stakeholders and policymakers in Kenya, including working in close collaboration with the Kenyan Ministry of Health to help foster immediate translational impact. Authorship eligibility will be determined according to the International Committee of Medical Journal Editors recommendations.The project activated in March 2021 and implementation is currently ongoing and expected to end in 2024.As PrEP implementation gradually expands in Africa, initial delivery points have centered in HIV care centers focused on serodiscordant couples, “drop-in” centers, and youth-friendly “safe spaces,” for key populations. For women, access has been limited mostly through a few demonstration projects in FP and antenatal clinics.The FP Plus project offers a timely opportunity to move from small-scale PrEP demonstration projects to full-scale service delivery for women in Africa. Since the 2015 WHO global recommendation for PrEP was released, understanding how to rapidly and efficiently translate this effective prevention intervention into real-world settings has been the priority, but most work in Africa remains focused on controlled demonstration projects, mostly in research clinics. We have pushed beyond this boundary with the PrIYA project, a demonstration pilot project that has shown that it may be feasible to integrate PrEP in FP systems. In this study we move to the next phase and evaluate whether fully integrating PrEP provision in FP clinics as a one-stop location for women-centered health care services can be done successfully at scale with implementation science evaluations. Our study leverages existing infrastructure and expertise of FP providers in counseling for sexual history and program delivery on a variety of contraception methods, to embed clinical assessment and PrEP provision in combination HIV prevention package. Using current health system, staffing and supply chain and has tremendous potential to address barriers that women face for PrEP access, including lack of time, cost, and stigma of visiting a facility solely for HIV prevention. With more efficient PrEP integration, there is opportunity to improve FP care and optimize women-centered care with a one-stop approach to clinic. The implementation methods and lessons learned through our novel FP-based PrEP care pathway will provide information on sustainable integrated service delivery that can be translated to other African settings. Importantly, the application of rigorous implementation science approaches to understand implementation will be valuable for advancing other emerging novel HIV prevention modalities into real-world delivery.In Kenya’s devolved government structure, the MOH sets and guides national policy, but implementation of policy and public health services is under the county governments. Our proposed work aligns with the Kenya MOH and Kisumu County priority goals, which makes the probability of impact high. In 2016, Kenya MOH developed a national PrEP implementation framework , and nat


Flaviviridae have a wide global and economic impact due to high morbidity and mortality. Flaviviridae infection usually leads to severe, acute or chronic diseases, such as liver injury and liver cancer resulting from hepatitis C virus (HCV) infection, dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS) caused by dengue virus (DENV). Given the highly complex pathogenesis of Flaviviridae infections, they are still not fully understood at present. Accumulating evidence suggests that host autophagy is disrupted to regulate the life cycle of Flaviviridae. Organelle-specific autophagy is able to selectively target different organelles for quality control, which is essential for regulating cellular homeostasis. As an important sub process of autophagy, lipophagy regulates lipid metabolism by targeting lipid droplets (LDs) and is also closely related to the infection of a variety of pathogenic microorganisms. In this review, we briefly understand the LDs interaction relationship with Flaviviridae infection, outline the molecular events of how lipophagy occurs and the related research progress on the regulatory mechanisms of lipophagy in Flaviviridae infection. Exploring the crosstalk between viral infection and lipophagy induced molecular events may provide new avenues for antiviral therapy.Diseases caused by  Flaviviridae consists of a group of enveloped viruses with positive single strand RNA genomes, including hepatitis C virus (HCV) of the genus Hepacivirus, dengue virus (DENV) and Zika virus (ZIKV) of the genus Flavivirus, bovine viral diarrhea virus (BVDV) and classical swine fever virus (CSFV) of the genus Pestivirus  disease, placing nearly 3.9 billion people, mainly in poor countries, at constant risk of infection due to the lack of completely effective vaccines and antivirals against DENV. Recently, an increasing number of studies have shown that Flaviviridae extensively regulate host lipid metabolism, underscoring the importance of LDs in viral infection , as an intracellular degradation system that maintains cellular metabolic homeostasis and cell survival when cells face various stresses such as nutrient deprivation and accumulation of damaged organelles, is an essential defensive cellular program. Autophagy for the degradation of various organelles has been well-known in the last century, but its function in the degradation of LDs has been intensively studied only in recent years  catalyze the last step in the TG biosynthesis pathway, while acyl-CoA cholesterol acyltransferases 1 and 2 (ACAT1 and ACAT2) determine CE synthesis   for subsequent delivery to the autolysosome in which the LDs are degraded, the molecular basis of which is the attachment of tagged cargo to the autophagosome via adaptor proteins  can exploit host resources, evade host immunity mechanisms and hijack autophagy to facilitate its own replication, which may also be a potential mechanism by which they utilize LDs   was reduced and inversely correlated with lipophagy induction in DENV infected-cells. Although AMPK normally stimulates tuberous sclerosis complex 2 (TSC2)-dependent inactivation of mTORC1 signaling , and recently it was found to play a relevant role in lipophagy induced by DENV and other flaviviruses , decreased the number of LDs per cell indicating a link between lipid metabolism and virus replication  RNA viruses  has the potential to be new observational approach of metabolic disorders as well as infectious diseases.Over the past decade, our knowledge of the importance of viral remodeling of cellular metabolism has increased dramatically. Although many examples have been well-documented, there is still relatively little understanding of the detailed mechanisms of how these metabolic alterations are promoted. LDs are the crux of replication assembly of flavivirus control  and Forkhead box protein O1 (FoxO1), calcium signaling transduction, small molecules including ethanol, etc. How these cues relate to each other, and what are the triggering molecular mechanisms specific to lipophagy are unclear. To this end, the dynamic relationship of lipophagy and viral infection remains to be further explored.KW: writing—original draft preparation. SF, LZ, and FZ: writing—review and editing. MZ, HY, and JC: conceptualization, supervision, and project administration. All authors contributed to the conception and design of the work. All authors have read and agreed to the published version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Social programs are services provided by governments, nonprofits, and other organizations to help improve the health and well-being of individuals, families, and communities. Social programs aim to deliver services effectively and efficiently, but they are challenged by information silos, limited resources, and the need to deliver frequently changing mandated benefits.We aim to explore how an information system designed for social programs helps deliver services effectively and efficiently across diverse programs.This viewpoint describes the configurable and modular architecture of Social Program Management (SPM), a system to support efficient and effective delivery of services through a wide range of social programs and lessons learned from implementing SPM across diverse settings. We explored usage data to inform the engagement and impact of SPM on the efficient and effective delivery of services.The features and functionalities of SPM seem to support the goals of social programs. We found that SPM provides fundamental management processes and configurable program-specific components to support social program administration; has been used by more than 280,000 caseworkers serving more than 30 million people in 13 countries; contains features designed to meet specific user requirements; supports secure information sharing and collaboration through data standardization and aggregation; and offers configurability and flexibility, which are important for digital transformation and organizational change.SPM is a user-centered, configurable, and flexible system for managing social program workflows. Government and community-based organizations are responsible for delivering social services to clients through social programs provided at the national, state, county, and city levels. Social programs are critical to the health and welfare of many citizens, as they provide a wide range of benefits , such asIn contrast to commercial entities, government agencies administering social programs face unique challenges regarding service delivery and their operational processes, including (1) information silos that limit decision-making abilities, (2) requirements to balance privacy with data sharing and transparent use of public funds, 3) reduced financial resources but growing demand for services, 4) legislative and organizational influences on eligibility and entitlement, and 5) the need to document the delivery of mandated services for beneficiaries across multiple categorical programs ..13].The features and functionalities described in The SPM modules presented in The latest version of SPM has been used by more than 50 programs in 13 countries  and 13 lEligibility and entitlement determination are often complex, time-consuming, and one of the most frustrating aspects of social program service delivery for administrators and clients. A large US city department of human resources used SPM’s universal access module to redesign their Supplemental Nutrition Assistance Program (SNAP)  to digitIn April 2018, the city implemented a citizen-facing portal, available in 7 languages, to deliver the SNAP and other benefits via clients’ own desktop and mobile phones. The design of the portal was informed by 30 shadowing sessions, 10 interviews, and 20 scenario testing sessions. Iterative prototyping and co-design workshops were also conducted to refine the portal design.A retrospective pre-post comparison of SPM metrics  was conducted using monthly data collected in April 2018 and April 2019 . The medIn the assessed periods, application rejections because of failure to provide documentation were reduced by 20% from 2674 in April 2018 to 2139 in April 2019 and center visits were reduced by 37% from 71,116 in April 2018 to 44,803 in April 2019. Of the 30,000 SNAP applications submitted in August 2019, 80% were submitted on the web through client-mobile devices via SPM’s universal access module. Client experience satisfaction was also measured with a web-based 5-star rating survey emailed to participants after they completed the application process. Responses  were collected with an average rating of 4.31 out of 5  for the SNAP application and 4.44 out of 5 for the SNAP recertification.A US state’s health and human services department designed a program to improve the way state county departments provided services to families and allow caseworkers to spend less time on administrative tasks and more time helping individuals and families. Specifically, the state wanted real-time data sharing and aggregation across different health and human services divisions. At the time, most families were served through multiple categorical programs. Concurrently, the state wanted to limit the amount of system customization for each county yet be flexible enough to allow each to use legacy systems in a consolidated system managing all benefits and services until legacy systems could be sunset.SPM was implemented in 2012, and information technology systems were modernized in more than 100 counties for 8 years. Deployments of SPM were designed to be interoperable with legacy systems so that incremental rollout could occur . SPM hasIn a large city in Germany, 7 local districts and 40 regional agencies are responsible for protecting children from abuse. Two special government organization units support these districts and agencies in defining and monitoring policies and providing financial and technical resources. In an effort to provide better outcomes and serve clients more efficiently, the government sought to use SPM to improve processes for client intake, case management, and communication between agencies. Specific needs included improving upon reports of abuse, traditionally done through telephone and fax machines, and better data sharing and collaboration. The government leveraged the SPM platform to address these needs, including applications for verification of evidence and provider management for managing interactions between the government and local agencies, such as foster care. Implementation-specific modules included the social enterprise collaboration for supporting multidisciplinary teams and the child welfare module for managing child abuse cases. The solution was implemented in stages where standards for social services relevant to child abuse cases, such as foster care, were defined; an interface among SPM, legacy systems, and systems of local agencies was then deployed. In the second stage, modules for managing clients were implemented. These modules provided local agencies and the government with case management capabilities for documenting and sharing information related to interactions with children and families, services, contacts, worker visits, and judicial processes.SPM allows caseworkers to view and manage a wide range of information in one place, from the initial receipt of an allegation through the final case outcome. This information enables bidirectional information sharing among local agencies and can then be used to document outcomes digitally. For example, when an allegation is made, supporting information such as police reports is automatically imported into SPM. As of June 2019, SPM in this city had 1300 users, 370,000 clients, and more than 200,000 cases and processed approximately 50,000 transactions per month since its implementation in 2014. This represents an average increase of 60% in the number of cases processed per year compared with the legacy system.We presented a configurable and modular system that delivers integrated cross-program and cross-agency solutions for needs-based and contribution-based social service programs ,17-21. AThe flexibility of SPM provides advantages in implementation and change management for the digital transformation of social programs. Most legacy social program systems have automated key program processes. Usually developed ad hoc, these older systems are complex, heterogeneous, and high maintenance. At the same time, these organizations tend to be risk-averse and often dependent on specific products or platforms . Rather Finally, data aggregation and sharing are important for improving outcomes and tracking program success by reducing information gaps and providing a holistic view of clients. Previous research has demonstrated that integrated case management with a multidisciplinary approach may improve positive outcomes for clients . SPM supThis system description is limited in that the implementations described are on-premise solutions currently. Data quality and silos can limit the extent of insights and analytics, and how these data are presented influences decision-making. Improving program performance and achieving better health outcomes requires bringing together and presenting data visually to enhance decision-making abilities. These are common challenges for any enterprise-wide solution. We have made the platform more flexible and portable by moving more core processes of SPM to the cloud. We have released SPM to work on an open-source container application platform so that users can secure and use their data across multiple environments, including public and private clouds. We are also providing analytic capabilities across social programs and in a visual format at the point of decision-making to better assess the impact of social programs on health outcomes.This viewpoint highlights the features of SPM with use cases selected to illustrate its generalizable features, such as benefits management, health and human services administration, and case coordination. These case studies were limited by organizations that were willing to share data and participate in the research. We were not able to design metric collection a priori, so the data for each use case are based on what could be provided by participating organizations.SPM is a user-centered, configurable, and flexible system designed to manage social program workflows. Its features and functionalities support the goals of social programs through improved service delivery to beneficiaries with functionalities and features for complex eligibility and entitlement, convenient access to services, complex case management, organizational and policy change management, and program transparency. More than 50 government organizations, 280,000 caseworkers, and 30 million beneficiaries are served through SPM, demonstrating the flexibility and scalability across social program types and settings in designing administrative systems that support a streamlined workflow.


The COVID-19 pandemic and associated public health measures to prevent its spread have important implications for the health and wellbeing of older Veterans. Prior to the pandemic, social isolation was already recognized as a risk for older adults, contributing to increased risk of depression, physical inactivity, and mortality. Stay-at-home orders, social distancing, and transitions to new ways of delivering care have meant that many of the ways in which older Veterans connect with VA and others have changed. Older Veterans and Veterans with serious mental illness (SMI) are especially vulnerable to experience negative impacts from social isolation and loneliness. This symposium will present on four novel and adapted strategies for engaging with older Veterans during the COVID-19 pandemic and beyond: 1) VA Connection Plans, a whole health intervention to promote social connections for older Veterans with and without SMI (Peeples); 2) telehealth adaptations to PEER, an in-person, peer-delivered exercise intervention for older Veterans with SMI ; 3) VA Compassionate Contact Corps, a VA Voluntary Service program to connect older Veterans with friendly volunteers via telephone (Sullivan); and 4) group telehealth interventions to foster social connection among older Veterans and their families (Weiskittle). Kim Van Orden, geropsychologist and director of the Hope Lab (Helping Older People Engage) at the University of Rochester Medical Center, will serve as discussant.