Ecological niche models are widely used in ecology and biogeography. Maxent is one of the most frequently used niche modeling tools, and many studies have aimed to optimize its performance. However, scholars have conflicting views on the treatment of predictor collinearity in Maxent modeling. Despite this lack of consensus, quantitative examinations of the effects of collinearity on Maxent modeling, especially in model transfer scenarios, are lacking. To address this knowledge gap, here we quantify the effects of collinearity under different scenarios of Maxent model training and projection. We separately examine the effects of predictor collinearity, collinearity shifts between training and testing data, and environmental novelty on model performance. We demonstrate that excluding highly correlated predictor variables does not significantly influence model performance. However, we find that collinearity shift and environmental novelty have significant negative effects on the performance of model transfer. We thus conclude that (a) Maxent is robust to predictor collinearity in model training; (b) the strategy of excluding highly correlated variables has little impact because Maxent accounts for redundant variables; and (c) collinearity shift and environmental novelty can negatively affect Maxent model transferability. We therefore recommend to quantify and report collinearity shift and environmental novelty to better infer model accuracy when models are spatially and/or temporally transferred. Excluding highly correlated variables does not affect Maxent model performance. Model transfer may lead to novel environment and collinearity shift, while both can negatively affect model performance. The relationship between a species' distribution and environmental conditions is known as species' ecological niche  should be treated in Maxent modeling. Indeed, we examined recent papers citing the major Maxent references . Howeven et al. . Others n et al. . Though The influence of collinearity on regression‐type models can be twofold: (a) the effect on model training caused by the degree of predictor collinearity and (b) the effect on model transfer caused by differences in the correlation structure of predictor variables between training and testing (or projecting) regions . Thus, the issue of collinearity in Maxent must be considered from the perspective of model transfer, that is, transferring a model across space and/or time to different environmental conditions  determine whether the performance of Maxent models declines in model transfer scenario compared with nontransfer scenario and determine whether the commonly adopted variable selection strategy  is effective in improving Maxent model performance, (b) assess the effect of variable selection strategy in controlling the degree of predictor collinearity and assess the effect of model transfer on environmental novelty and collinearity shift, and (c) determine the effect of environmental novelty, degree of predictor collinearity, and collinearity shift on model transfer performance. To achieve our objectives, we simulated scenarios of model transfer and nontransfer, selected predictors with and without considering collinearity, and quantified model performance, degree of predictor collinearity in the training region, and environmental novelty and collinearity shift between training and testing regions.2To address our first objective, determining whether model transfer and variable selection strategy influence Maxent performance, we compared model performance between model transfer and nontransfer scenarios and between two variable selection strategies that either included or excluded highly correlated predictors Figure . To addr2.1http://www.iucnredlist.org/) of all North American carnivore mammals listed in Kays and Wilson  and only retained records associated with verifiable sources , to limit the inclusion of erroneous records. To avoid any marginal occurrences that may bias models  around each species occurrence point and used them as training regions  and random selection of less correlated variables (VRandomLowCor). For VRandom, we randomly selected a subset of predictors from a pool of environmental variables; VRandom serves as the control group for VRandomLowCor, as well as to represent studies that do not account for collinearity. For VRandomLowCor, we randomly selected a subset of predictors that are less correlated (based on random background points) using the 0.7 threshold for correlation coefficient , and thus, we only present presented results associated with the latter. Our method of quantifying environmental novelty is comparable to the method of calculating environmental similarity in mobility‐oriented parity  on model performance , using model performance as the dependent variable, transfer scenario and variable selection scheme as fixed effects, and continent and species as nested random effects  for the 22 North America species and from 21 to 191  for the nine Australian species included in this study Table . The perWe found that transferring models led to significantly lower model performance, indicated by lower AUC, TSS, and sensitivity values compared with the nontransfer scenario Table . Model tThe linear mixed models showed that both degree of collinearity shift and environmental novelty had a negative effect on model performance, while predictor collinearity was not correlated with model performance Table .4Despite frequent mentions in the literature, the effects of predictor collinearity on Maxent models have not been well understood; thus, approaches toward documenting and dealing with collinearity have been arbitrary. Our study clarifies whether, when, and how collinearity affects model performance in Maxent. First, we show decreased model performance in model transfer scenarios, a well‐known phenomenon observed in many studies ; thus, the results have broad implications for Maxent applications. Also, our study was conducted across two continents with varied climatic regimes. The use of real landscapes makes our study more likely to capture the complexities that are commonplace in empirical studies. It is worth reflecting on how frequently collinearity shift and novel environments are coupled or decoupled. In our study, the scenario of model transfer was the major driver of collinearity shift and novel environments, suggesting that the presence of collinearity shift and novel environments could be commonly coupled during the model transfer Figure . This isIn contrast with using data from real world, there is an increasing trend of using virtual species and even virtual landscapes in methodological explorations in ENM  Maxent is capable of regulating contributions from redundant variables, rendering its robustness to degree of predictor collinearity in model training; (b) Maxent is not immune to environmental novelty and collinearity shifts, and we thus recommend estimation of these factors to better infer uncertainties when models are spatially and/or temporally transferred; and (c) the strategy of removing highly correlated variables has little impact in Maxent model performance because of the way Maxent deals with redundant variables and the independence between degree of predictor collinearity and collinearity shift.None declared.All authors conceived the study; X.F. and R.P. prepared the data; X.F. conducted the analyses with help from D.S.P. and Y.L.; X.F. drafted the manuscript; and all authors interpreted the results and contributed to the revision of the manuscript. Click here for additional data file.


The World Health Organization (WHO), World Organisation for Animal Health (OIE), Food and Agricultural Organization of the United Nations (FAO), and Global Alliance for Rabies Control (GARC) have established a global goal for the elimination of dog-mediated human rabies deaths by 2030 ,2. A sigGovernment’s commitment to disease interventions begins with a multisectoral, One Health understanding of the disease burden and agreement that a given disease is a national priority. To facilitate prioritization of a county’s top endemic and emerging zoonotic diseases, the Centers for Disease Control and Prevention (CDC) has developed a One Health Zoonotic Disease Prioritization tool (OHZDP) , offeredhttp://www.who.int/rabies/news/RUA-Rabies-launch-plan-achieve-zero-rabies-human-deaths-2030/en/). In some countries intragovernmental support has been fostered through rabies champions—persons who undertake advocacy and awareness roles to motivate communities and governments to action. To support development of rabies champions, the GARC provides annual awards for community leaders [For countries that have not prioritized control of rabies or committed to rabies elimination as a national priority, advocacy and increased recognition of the rabies burden may help foster intragovernment support. Several tools for rabies advocacy have been developed in recent years. In 2017, United Against Rabies (UAR), a collaboration of four partners—WHO, the FAO, the OIE and the GARC—was created to advocate for rabies control. UAR fosters a multistakeholder platform to engage countries and experts to advance towards zero dog-mediated human rabies deaths by 2030   [In the early stages of rabies control advocacy there are often limited data on the burden of the disease, and data that are available are based on rudimentary surveillance systems that capture only a fraction of human rabies cases . Several/aracon) . Two int/aracon) . The sec/aracon) .Once countries have committed to rabies control as a priority, it is important to evaluate the current capacity and gaps in logistical capacity, personnel, and financial support. To evaluate a country’s rabies program, the GARC, the FAO, the OIE, and WHO developed the Stepwise Approach towards Rabies Elimination (SARE) tool . During https://garc.shinyapps.io/gdrep/) [The Global Dog Rabies Elimination Pathway (GDREP) tool was developed to help estimate the financial and human capital required to achieve canine rabies elimination . This to/gdrep/) ,30.These resources provide practical guidance for developing rabies control programs, detailed protocols to conduct field operations, and estimates of the cost, time, and personnel to achieve the goal of rabies elimination. Lacking from these available resources is guidance for how governments and their external partners can foster host government leadership of these rabies control activities.A proposed strategic approach for coordinating rabies engagement and elimination collaborations  was devePrioritization of diseases has been performed in a multitude of ways ,9,47–49 Once the efforts to garner the commitment of the country to prioritize rabies control or elimination are successful, conducting a SARE evaluation is a strategic next step to identify critical gaps that may be hindering rabies control progress. The host government and partners should determine the most impactful activities that pertain to short-term rabies control success by considering the outcome of the SARE report . FurtherApproaches to generating comprehensive rabies control strategies were separated into three broad categories based on host government priorities, funding availability, and logistical capacity. Countries with limited logistical capacity and funding for rabies control should consider investing in programs that improve human rabies case detection, in an effort to bolster support for rabies control activities. Countries with moderate logistical and funding capacity should focus on activities that can quickly reduce human rabies deaths. Such activities include improving access to rabies post-exposure prophylaxis (PEP) and improved rabies surveillance systems. Countries with high levels of logistical and fiscal capacity should consider supporting activities that will permanently eliminate canine rabies . Given the One Health approach required to control rabies, activities will often overlap, and the order in which activities are implemented is flexible and based upon country-specific context.Sustained commitment to rabies control often requires recognition of the disease burden. Burden is best characterized through routine public health surveillance activities to characterize the number of human and animal cases . LaboratCountries that lack a dedicated rabies surveillance system may consider integrating human rabies surveillance into an existing program that detects common clinical signs of rabies such as fever or encephalitis. Acute neurologic  or acute febrile illness (AFI) syndromic surveillance programs may provide such a platform for improved case detection ,53. UtilIf the country does not currently have surveillance capacity, community surveys or health center trace-back surveys to elucidate rates of dog bites, human rabies deaths, and health-seeking behaviors can produce valuable information for conducting country-specific burden estimations .Human rabies deaths can be drastically reduced through improved access to vaccines for persons with suspected rabies exposures . ProvisiFor various reasons, countries often opt to initiate IBCM through pilot projects . Pilot pCountries that currently have the desire and resources to eliminate canine rabies and have implemented programs to increase access to vaccines for persons with rabies exposures should focus efforts on mass dog vaccination. These activities should include enumeration of the dog population, evaluation of an array of vaccination strategies, and development of a vaccination program with a goal of ≥70% coverage in endemic areas. Organizations such as World Animal Protection and OIE have developed resources to help planning and evaluation of dog vaccination campaigns, as well as management of stray dog populations; these resources can be found on the rabies control blueprint, section “Case Studies and Documents”.The strategic approach considers changing capacity and priorities of the host government to control rabies. The activities proposed by this approach can serve as a general guide rather than a fixed path towards rabies elimination. For example, a country may choose to conduct dog vaccination programs, an activity in Activity IIIc, while building a pilot IBCM project, an activity in Activity IIIb. The approach incorporates frequent reevaluation of country progress and priorities by repeating the SARE evaluation every two years. The government and their external partners can also reevaluate their progress and priorities by frequent measurement of program impacts and progress of activities. Results and lessons learned should be shared with all partners to improve program advocacy.Much of Kenya’s progress in rabies elimination has been noted by the activities conducted between 2000 and 2015, including their initial efforts to describe the epidemiology of rabies and assess the most effective vaccination strategy for rabies elimination through empirical data and mathematical modeling ,58. In 2The establishment of the ZDU has been a catalyst for the rabies control program in Kenya and the region. Between 2012 and 2014, the ZDU organized multistakeholder forums for rabies experts in the country to develop a rabies elimination plan. The plan gained further support and was strengthened in 2015, when the country conducted a SARE workshop. The GDREP was conducted in 2017 (Activity II). This elimination plan has attracted donor support for canine rabies vaccination and surveillance campaigns in two pilot counties, which will inform implementation in other regions (Activities IIIb and IIIc) . In addiAt the time of initial engagement in 2011, Haiti’s surveillance system detected, on average, 10 annual human rabies deaths, while the international community and RabiesEcon modelling estimated more than 100 deaths ,25,32. TIn 2013, Haiti’s national rabies laboratory was established, and a passive animal rabies surveillance system was implemented with combined inputs from the agriculture and public health sectors. This activity served to increase the awareness of rabies (an 18-fold increase in detection of rabid dogs was demonstrated within the first 6 months of operation), and it functions as a platform for human and animal health workers to collaboratively investigate human and animal rabies cases (Activities IIIa and IIIb) .Engagement between Haitian government and several external partner agencies grew between 2014 and 2017. A formal SARE workshop was conducted in 2015 and GDREP in 2016 (Activity II), and the national rabies control plan was updated to reflect priority activities. Several educational trainings were supported by the CDC and the GARC, which included a workshop in which over 40 Haitians were awarded the Rabies Educator Certificate (Activity I) [At the onset of this collaboration in 2011, the Haitian government and their external partners had conflicting opinions as to the priority of rabies control among the numerous public health issues impacting Haiti. Therefore, initial efforts were directed towards obtaining government commitment and support by demonstrating the disease burden ,56. HaitRabies elimination requires a One Health approach with long-term and large-scale commitments, both from international entities as well as host governments. In many situations, external partners of the governments of rabies-endemic countries will likely be needed to provide technical expertise or to supplement fiscal and logistical gaps. However, sustainable rabies elimination programs are based on host government leadership ,3. Disea


Universal health care (UHC) is garnering growing support throughout the world, a reflection of social and economic progress and of the recognition that population health is both an indicator and an instrument of national development. Substantial human and financial resources will be required to achieve UHC in any of the various ways it has been conceived and defined. Progress toward achieving UHC will be aided by new technologies, a willingness to shift medical tasks from highly trained to appropriately well-trained personnel, a judicious balance between the quantity and quality of health care services, and resource allocation decisions that acknowledge the important role of public health interventions and nonmedical influences on population health.The September 1978 Alma- Ata Declaration is a landmark event in the history of global health. The declaration raised awareness of “health for all” as a universal human right,whose fulfillment reduces human misery and suffering, advances equality, and safeguards human dignity. It also recognized economic and social development and international security as not only causes, but also consequences, of better health. In addition, it highlighted the power of primary health care and international cooperation to advance the protection and promotion of health in resource-constrained settings.Building on the achievement of Alma-Ata and gaining further traction from the Millenium Development Goals and the Sustainable Development Goals set by the United Nations, universal health care (UHC) has emerged in recent years as a central imperative of the World Health Organization (WHO), the United Nations and most of its member states, and much of civil society. UHC characterizes national health systems in which all individuals can access quality health services without individual or familial financial hardship. More broadly, UHC covers social systems that provide medical and nonmedical services and infrastructure that are vital to promoting public health.Although there are numerous articulations of the UHC agenda, the WHO and World Bank offer a relatively simple UHC service-coverage index that is useful for intercountry comparison. This index focuses on four categories of health indicators: reproductive, maternal, and child health; infectious disease control; noncommunicable diseases; and service capacity and access. Comparison of UHC index values for 129 countries reveals that country index scores are positively correlated with income per capita, though there is considerable variation in scores among countries with similar incomes. These variations presumably reflect differentials in income inequality, commitment to public health infrastructure, and the quality and reach of human resources for health. The WHO and World Bank also offer multiple measures of health spending–related financial hardship in assessing UHC, which do not increase monotonically with increasing income, health spending per capita, or coverage of health services. Rather, catastrophic health expenditures tend to be lower in countries that channel health spending through public social security or insurance programs, rather than private insurance schemes.The financial cost of massively expanding access to health care globally is a formidable barrier to achieving UHC. For example, the Disease Control Priorities Network estimates that low- and lower-middle-income countries would, on average, need to raise their respective annual per capita health expenditures by U.S.$53 and U.S.$61 per person to achieve coveragewith the essential UHC package of 218 core interventions, a sizable burden in relation to average expenditure increases in recent years. Wealthy industrial countries are much further along the path to achieving UHC, though they also face challenges involving rising costs of new health care technologies and the growing share of their populations at the older  ages.Technically and economically efficient approaches to the achievement of UHC may include the use of electronic medical records, telemedicine systems, digital monitors for drug adherence, and clinical decision–support applications; expansion of the quantity and quality of human resources for health at the physician, nurse, and community health worker levels; improvements in inventory systems and supply chains for the delivery of vaccines, drugs, diagnostics, and medical devices; screening for risk factors and early signs of disease; and focusing on the often neglected domains of surgical care, reproductive health, and mental health. Also key will be efforts to ensure universal access to proven public health interventions that address social and environmental determinants of health, such as health education campaigns; access to safe water; regulation of excessive sugar and salt in the food supply; control of tobacco and the unsafe consumption of alcohol; road traffic safety; walkable city designs; expanding enrollment in high-quality primary and secondary schools; and more equitable distributions of income and wealth.Achieving UHC is an ambitious aspiration and a powerful indicator of human progress. Fortunately, it may be expected to deliver myriad health, economic, and social welfare benefits along the way, helping to mobilize the substantial political and financial resources needed for its continued future expansion. Universal health care (UHC) characterizes national health systems wherein all individuals can access quality health services without individual or familial financial hard ship. More broadly, UHC covers social systems that provide medical and nonmedical services and infrastructure that are vital to promoting public health.ThenotionofUHCdates toOtto vonBismarck, who established the world’s first national social health insurance system in Germany in 1883 , which is useful for intercountry comparisons. They define this index in terms of 16 indicators, grouped into four categories: reproductive, maternal, newborn, and child health; infectious-disease control; noncommunicable diseases; and service capacity and access  Network has compiled 218 distinct cost-effective interventions, which they argue should form a standard of essential services for LMICs because they address a substantial burden of disease. Unlike the indicators in the WHO– World Bank index, more than one-third of the DCP Network’s essential interventions—including tobacco taxes, air pollution reduction, and road safety improvements—focus on broader social or environmental determinants and would require non–health care sector involvement. . Sub-SahAlso notable are the instances of similar income countries having highly disparate index scores. For example, Nigeria and Vietnam both have per capita GDPs around U.S.$2200, but Vietnam’s UHC index score is 34 points higher than Nigeria’s. This reflects the fact that Vietnam outperforms Nigeria on several indicators, including reported rates of three-dose diphtheriatetanus- pertussis infant vaccination coverage (94 versus 42%), births attended by skilled professionals (94 versus 35%), and households with access to basic sanitation (78 versus 32%). Dissimilar income distributions in the two countries offer a plausible partial explanation for the coverage discrepancies. An estimated 78% of Nigeria’s population lives on less than U.S.$3.20 per day in 2017 dollars, compared with only 32% of Vietnam’s population , HIV/AIDS, and malaria. For these diseases, early treatment of affected individuals can terminate the chain of transmission, thereby reducing disease incidence. For example, over a 7-year time period, HIV-uninfected individuals living in areas with high antiretroviral therapy coverage in Kwa Zulu Natal, South Africa, were 38% less likely to acquire HIV than those in areas with low coverage  could undermine the benefits of expanded service coverage. Even though existing UHC frameworks allude to this problem, quality-related indicators can be hard to measure, and achieving high quality of care will be especially challenging with large-scale expansion of coverage . SiAs these examples suggest, poorly functioning health systems are a central challenge to realizing the benefits of UHC. Health systems in LMICs commonly suffer from a variety of weaknesses, including absenteeism and insufficient training among health care workers, mistreatment of patients by health care workers, corruption, poorly functioning inventory systems and supply chains, electricity cuts and outages, and lack of clean water. These shortcomings in health care delivery often reflect higher-level problems in governance and market failures. Achieving UHC will therefore require innovations in the structure and operation of health systems to ensure that rapid expansion in coverage is not undermined by shortcomings in delivery and quality of care.With regard to the scope of UHC, it is entirely appropriate for countries to prioritize different health interventions in their UHC agendas to address local needs and constraints. It is also reasonable to expect the number of health services considered essential in each setting to undergo progressive expansion over time to reflect changing resource availability and to address new or emerging health concerns. For example, the WHO–World Bank index—perhaps the most prominent articulation of the UHC agenda— mostly focuses on health service coverage for conditions that have been long-standing global health priorities, such as maternal health, HIV, and TB. The index does not emphasize measurement of service coverage for other conditions that contribute substantially to the global burden of disability or death, such as depression and anxiety  and conditions that require basic surgical care (inaccessible to about 5 billion people) ; achieving coverage with the essential UHC package (218 core interventions) would require an annual spending increase of U.S.$53 and U.S.$61 per person on average  offer another, more widely accepted, strategy for expanding the health care workforce and increasing the coverage and effectiveness of primary health care. Growing evidence suggests that these programs can contribute to improved outcomes in child nutrition, maternal health, HIV, and TB . MoreoveIntegrating innovative technologies into health systems—including electronic medical records, clinical decision–support applications, telemedicine, digital medication-adherence technologies, and point-of-care diagnostic tests—could also facilitate UHC by improving the reach, timeliness, efficiency, and quality of clinical care and public health monitoring. These technologies could improve the quality and coverage of longitudinal clinical records, facilitate health care providers’ use of evidence-based clinical care algorithms, extend access to specialized medical knowledge to rural communities, reduce time delays for diagnosis and treatment, and enable real-time monitoring of medication adherence. Artificial intelligence and machine learning have the potential to perform some tasks—such as interpreting x-rays, electrocardiograms, and electroencephalograms— that currently require highly trained and specialized health care workers.Technological innovations will not obviate the need to dramatically increase the health care workforce in LMICs, but they could still prove to be game changers as the global community tries to rapidly scale up health service delivery to achieve UHC. The ambitious scope of the UHC agendamay provoke physicians and public health experts to reimagine how to deliver health services. New frontline health care personnel  and innovative technologies could help to move care provision into nontraditional spaces, such as homes or workplaces, extending the existing health system’s effective reach.Four decades after the Alma-Ata Declaration articulated primary care for all as being a most important worldwide social goal, the global community is striving to achieve UHC with renewed interest and ambition. A central motivation of the UHC agenda is the belief that access to health care—with the goals of extending longevity, minimizing disability, and diminishing suffering—is a fundamental human right that advances equality and safeguards human dignity. Achieving UHC would represent one of the most ambitious ventures in the area of human rights, even if UHC were defined narrowly as universal delivery of essential health services. In addition, evidence suggests that well-implemented universal coverage of essential health services could improve welfare more broadly, by reducing economic inequalities, promoting economic well-being, and, perhaps, improving social and political stability.A broader UHC conception that aims to also address the nonmedical determinants that most strongly shape human health would have even greater implications for society and would require broader social transformations. Addressing cross-cutting social and environmental determinants that contribute to ill health—such as wealth inequality; race, gender, and caste discrimination; air pollution; and lack of water and sanitation facilities—could lead the UHC agenda to intersect more closely with the human rights, One Health, and Planetary Health agendas in the coming decades.Numerous potential pitfalls could impede UHC expansion or undermine its positive impact on health and well-being. Most challenging, perhaps, is the need to increase health financing rapidly enough to facilitate universal coverage of essential health services among LMIC populations that are simultaneously growing in size and aging. For example, for the world’s less-developed regions, an increase of roughly 1 billion people isprojected from 2018 through 2030, with the percentage aged 60 years or older projected to increase from 10.6 to 14.2%(Ultimately, the path to UHC and the interventions prioritized in this process will be unique to each country pursuing universal coverage. Although achieving full UHC is a daunting task, incremental steps toward fulfilling this goal also offer myriad health, economic, and social welfare benefits. cognizing these benefits should help mobilize the resources needed for continued future expansion of UHC.


Transporting nursing home Veterans to hospitals for outpatient care can present many challenges, including lengthy time in transit, coordination difficulties between the hospital and nursing home, and travel burden on Veterans. In June 2017, the VetConnect program began offering Veterans in Colorado residing in Department of Veterans Affairs (VA) contracted Community Nursing Homes (CNHs) and State Veteran Nursing Homes (SVHs) telehealth appointments in Geriatrics, Mental Health, Palliative Care, and Psychiatry via clinicians at the Rocky Mountain Regional VA Medical Center (VAMC). Then in June 2018, VetConnect expanded to offer Virtual Tours for Veterans transitioning out of inpatient care to CNHs the opportunity to virtually tour the CNH, connecting with CNH staff through video for a more stress-free and informed transition from hospital to CNH. In winter 2018, VetConnect expanded once more to include Dementia Educational Outreach Series for CNH and SVH staff, allowing them to connect virtually to VA staff with expertise in dementia care and other Veteran-specific topics such as treating post-traumatic stress disorder (PTSD). To date, VetConnect has provided 502 telehealth visits, 18 Virtual Tours, and 4 dementia ECHO trainings (with 58 nursing home staff participants). Evaluation measures to be presented include collection and analysis of telehealth nurse field notes , creation of process maps, conducting key stakeholder interviews, and identification of potential impacts the VetConnect program has had on VA to CNH and SVH relationships and Veteran health.


The growing healthcare industry is generating a large volume of useful data on patient demographics, treatment plans, payment, and insurance coverage—attracting the attention of clinicians and scientists alike. In recent years, a number of peer-reviewed articles have addressed different dimensions of data mining application in healthcare. However, the lack of a comprehensive and systematic narrative motivated us to construct a literature review on this topic. In this paper, we present a review of the literature on healthcare analytics using data mining and big data. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a database search between 2005 and 2016. Critical elements of the selected studies—healthcare sub-areas, data mining techniques, types of analytics, data, and data sources—were extracted to provide a systematic view of development in this field and possible future directions. We found that the existing literature mostly examines analytics in clinical and administrative decision-making. Use of human-generated data is predominant considering the wide adoption of Electronic Medical Record in clinical care. However, analytics based on website and social media data has been increasing in recent years. Lack of prescriptive analytics in practice and integration of domain expert knowledge in the decision-making process emphasizes the necessity of future research. Healthcare is a booming sector of the economy in many countries . With itAnalytics is the way of developing insights through the efficient use of data and application of quantitative and qualitative analysis . It can In this review, we systematically organize and summarize the published peer-reviewed literature related to the applied and theoretical perspectives of data mining. We classify the literature by types of analytics , healthcare application areas , and data mining techniques ; and we report the data source used in each review paper which, to our best knowledge, has never done before.There is a large body of recently published review/conceptual studies on healthcare and data mining. We outline the characteristics of these studies—e.g., scope/healthcare sub-area, timeframe, and number of papers reviewed—in There is no comprehensive review available which presents the complete picture of data mining application in the healthcare industry. The existing reviews (16 out of 21) are either focused on a specific area of healthcare, such as clinical medicine (three reviews) ,19, adveBeyond condensing the applied literature, our review also adds to the body of theoretical reviews in the analytics literature. Current theoretical reviews are limited to methodological challenges and techniques to overcome those challenges ,16,27 anThe methodology of our review followed the checklist proposed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) . We assediscussing the application of data mining and big data in the healthcare decision-making process were retained for full-text review. To make the screening process efficient, duplicate articles were removed at the eligibility phase instead of screening phase of the PRISMA review process . Finally, 117 articles were retained for the review. Exclusion criteria: This included articles reporting on results of: Selected literature and their selection process for the review are described in this section. Initially a two phase advance keyword search was conducted on the database Web of Science and one phase (Phase 2) search in PubMed and Google Scholar with time filter 1 January 2005 to 31 December 2016 in “All Fields”. Journal articles written in English was added as additional filters. Keywords listed in The full text of each of the 117 articles was reviewed separately by two researchers to eliminate bias . To asseTo summarize the body of knowledge, we adopted the three-step processing methodology outlined by Levy and Ellis  and WebsThe network diagram of selected articles and the keywords listed by authors in Out of 117 papers included in this review, 92 applied analytics and 25 were qualitative/conceptual. The methodological quality of the analytical studies (92 out of 117) were evaluated by a modified version of 8 yes/no questions suggested in JBI Critical Appraisal Checklist for Analytical Cross Sectional Studies . Each quWe applied the Critical Appraisal Skills Programme (CASP) qualitative research checklist  to evaluThe distribution of articles published related to data mining and big data analytics in healthcare across the timeline of the study (2005–2016) is presented in Expert System with Application was the dominant source of literature on data mining application in healthcare with 7 of the 117 articles. Journals were interdisciplinary in nature and spanned computational journals like IEEE Transection on Information Technology in Biomedicine to policy focused journal like Health Affairs. Articles published in Expert System with Application, Journal of Medical Systems, Journal of the American Medical Informatics Association, Healthcare Informatics Research were mostly related to analytics applied in clinical decision-making and healthcare administration. On the other hand, articles published in Health Affairs were predominantly conceptual in nature addressing policy issues, challenges, and potential of this field.Articles published in 74 different journals were included in this study. Out of 117 articles, 92 applied analytics for decision-making in healthcare. We discuss the types of analytics, the application area, the data, and the data mining techniques used in these articles and summarize them in We identified three types of analytics in the literature: descriptive , predictive  and prescriptive . Five of the 92 studies employed both descriptive and predictive analytics. In To identify types of data, we adopted the classification scheme identified by Raghupathi and Raghupathi  which taData mining techniques used in the articles reviewed include classification, clustering, association, anomaly detection, sequential pattern mining, regression, and data warehousing. While elaborate description of each technique and available algorithms is out of scope of this review, we report the frequency of each technique and its sector wise distribution in A high proportion (8 out of 9) of pharmacovigilance papers used association. Use of classification was dominant in every sector except pharmacovigilance b. Data wWe delved deeper into classification as it was utilized in the majority (57 out of 92) of the papers. There are a number of algorithms used for classification, which we present in a word cloud in Clinical decision support consists of descriptive and/or predictive analysis mostly related to cardiovascular disease (CVD), cancer, diabetes, and emergency/critical care unit patients. Some studies developed novel data mining algorithms which we review. CVD is one of the most common causes of death globally ,77. Its Risk factors related to Coronary Heart Disease (CHD) were distilled into a decision tree based classification system by researchers . The autData mining has also been applied to diagnose Coronary Artery Disease (CAD) . ResearcTraditional data mining and machine learning algorithms  may not be advanced enough to handle the data used for CVD diagnosis, which is often uncertain and highly dimensional in nature. To tackle this issue, researchers  proposedElectrocardiography (ECG)—non-invasive measurement of the electrical activity of the heartbeat—is the most commonly used medical studies in the assessment of CVD. Machine learning offers potential optimization of traditional ECG assessment which requires decompressing before making any diagnosis. This process takes time and large space in computers. In one study, researchers  developeData analytics have also been applied to more rare CVDs. One study  developeThe disease burden related to diabetes is high and rising in every country. According to the World Health Organization’s (WHO) prediction, it will become the seventh leading cause of death by 2030 . Data miResearchers extracted knowledge about diabetes treatment pathways and identified rare forms and complications of diabetes using a three level clustering framework from examination history of diabetic patients . In thisData analytics have also been applied to identify patients with type 2 diabetes. In one study , using fDifferent statistical and machine learning algorithms are available for classification purposes. Researchers  comparedCancer is another major threat to public health . MachineDespite many advances in treatment, accurate prediction of survival in patients with cancer remains challenging considering the heterogeneity of cancer complexity, treatment options, and patient population. Survival of prostate cancer patients has been predicted using a classification model . The modIn addition to predicting survival, machine learning techniques have also been used to identify patients with cancer. Among patients with breast cancer, researchers  have proMachine learning has also been used to identify the nature of cancer  and to understand demographics related to cancer. Among patients with breast cancer, researchers  applied The Emergency department (ED) is the primary route to hospital admission . In 2011Chest pain admissions to the ED have also been examined using decision-making framework. Researchers  proposedIntensive care units cater to patients with severe and life-threatening illness and injury which require constant, close monitoring and support to ensure normal bodily function. Death is a much more common event in an ICU compared to a general medical unit—one study showed that 22.4% of total death in hospitals occurred in the ICU . SurvivaIn addition to CVD, diabetes, cancer, emergency care, and ICU care, data mining has been applied to various clinical decision-making problems like pressure ulcer risk prediction, general problem lists, and personalized medical care. To predict pressure ulcer formation , researchers  developeFor data mining algorithms, which often show poor performance with imbalanced  data, researchers  developeThe patient problem list is a vital component of clinical medicine. It enables decision support and quality measurement. But, it is often incomplete. Researchers have  suggestePersonalized medicine—tailored treatment based on a patient’s predicted response or risk of disease—is another venue for data mining algorithms. One group of researchers  used a bAmong patients with asthma, researchers  used envAmong patients with Parkinson’s disease, researchers  introducAmong patients with kidney disease, researchers  developeAmong patients over 50 years of age, researchers  developeAnother group of researchers  addresseResearchers have also used data mining to optimize the glaucoma diagnosis process . TraditiData mining has also been applied to  compare Data mining has been used in 38 studies of clinical decision-making CVD (7 articles), diabetes (seven articles), cancer (five articles), emergency care (two articles), intensive care (two articles), and other applications (16 articles). Most of the studies developed predictive models to facilitate decision-making and some developed decision support system or tools. Authors often tested their models with multiple algorithms; SVM was at the top of that list and often outperformed other algorithms. However, 15 ,73,74,76Data mining was applied to administrative purposes in healthcare in 32% (29 articles) of the articles reviewed. Researchers have applied data mining to: data warehousing and cloud computing; quality improvement; cost reduction; resource utilization; patient management; and other areas. Data warehousing  and clouApart from clinical purposes, data warehouses can be used for research, training, education, and quality control purposes. Such a data repository was created using the basic idea of Google search engine . Users cTen articles applied data mining to cost reduction, quality improvement and resource utilization issues. One group of researchers predicted healthcare costs using an algorithmic approach . They usA sizable amount ($37.6 billion) of healthcare costs is attributable to medical errors, 45% of which stems from preventable errors . To aid Length of Stay (LOS) is another important indicator of cost and quality of care. Accurate prediction of LOS can lead to efficient management of hospital beds and resources. To predict LOS for CAD patients, researchers  comparedTo predict healthcare quality, researchers  used senIdentification of influential factors in insurance coverage using data mining can aid insurance providers and regulators to design targeted service, additional service or proper allocation of resources to increase coverage rates. To develop a classification model to identify health insurance coverage, researchers  used datAmong patients with lung cancer, researchers  investigOveruse of screening and tests by physicians also contributes to inefficiencies and excess costs . CurrentPatient management involves activities related to efficient scheduling and providing care to patients during their stay in a healthcare institute. Researchers  developeImproving publicly reported patient safety outcomes is also critical to healthcare institutions. Falls are one such outcome and are the most common and costly source of injury during hospitalization . ResearcData mining has beed applied  to invesData mining has also been applied  to analyThe relationship between epidemiological and genetic evidence and post market medical device performance has been evaluated using HCUPNet data . This feHealth data privacy and medical fraud are issues of prominent importance . We reviThe challenges of privacy protection have been addressed by a group of researchers  who propDetection of fraud and abuse  uses big data analytics. Using gynecological hospital data, researchers  developeIn summary, patient data privacy and fraud detection are of major concern given increasing use of social media and people’s tendency to put personal information on social media. Existing data anonymization or de-identification techniques can become less effective if they are not designed considering the fact that a large portion of our personal information is now available on social media.Mental illness is a global and national concern . AccordiTo classify developmental delays of children based on illness, researchers  examinedTo predict early diagnosis for mental disorders , researchers developed a model detecting abnormal physical activity recorded by a wearable device . They peTo classify schizophrenia, another study  used freUse of data analytics in diagnosing, analyzing, or treating mental health patients is quite different than applying analytics to predict cancer or diabetes. Context of data  seemed more important than volume in this case , howeverSeven articles addressed issues that were not limited to any specific disease or a demographic group, which we classified as public health problems. To make data mining accessible to non-expert users, specifically public health decision makers who manage public cancer treatment programs in Brazil, researchers  developeAnalysis of disease outbreaks has also applied data analytics. ,133 InflTo store and integrate multidimensional and heterogeneous data  applied to diabetes management, but generalizable to other diseases researchers  proposedA real-time medical emergency response system using the Internet of Things (networking of devices to facilitate data flow) based body area networks (BANs)—a wireless network of wearable computing devices was proposed by researchers . The sysDecision support tools for regional health institutes in Slovenia  have beeTo build better customer relations management at an Iranian hospital, researchers  applied The application of data mining to public health decision-making has become increasingly common. Researchers utilized data mining to design healthcare programs and emergency response, to identify resource utilization, patient satisfaction as well as to develop automated analytics tool for non-expert users. Continuation of this effort could lead to a patient-centered, robust healthcare system.Pharmacovigilance involves post-marketing monitoring and detection of adverse drug reactions (ADRs) to ensure patient safety . The estResearchers considered muscular and renal AEs caused by pravastatin, simvastatin, atorvastatin, and rosuvastatin by applying data mining techniques to the FDA’s Adverse Event Reporting System (FAERS) database reports from 2004 to 2009 . They foThree more studies used the FDA’s AERS report database. In an examination of ADR “hypersensitivity” to six anticancer agents  data minFurthermore, dose-dependent ADRs have been identified by researchers using models developed from structured and unstructured EHR data . Among tWe identified one study that used data outside of adverse event reports or HER data. For early detection of ADR, one group of researchers used online forums . They idTwenty-five of the articles we reviewed focus on the theoretical aspects of the application of data mining in healthcare including designing the database framework, data collection, and management to algorithmic development. These intellectual contributions extend beyond the analytical perspective of data—descriptive, predictive or prescriptive analytics—to the sectors and problems highlighted in The existing theoretical literature on disease control highlighted the current state of epidemics, cancer and mental health. To help physicians make real-time decisions about patient care, one group of researchers  proposedAnother group of researchers  data quaThree papers ,156,157 Three papers ,159,160 Theoretical research on personalized-health care services—treatment plans designed for someone based on the susceptibility of his/her genomic structure to a disease—also emerged from the literature review. One study  highlighA myriad of extant theoretical points has also been identified in the literature. These topics range from exploiting big data to: study the paradigm shift in healthcare policy and management from prioritizing volume to value ,167; aidData mining has been applied in many fields including finance, marketing, and manufacturing . Its appPersonalized careThe EMR is increasingly used to document demographic and clinician patient information . EMR datLoss of information in pre-processingPre-processing of data, including handling missing data, is the most time-consuming and costly part of data mining. The most common method used in the papers reviewed was deletion or elimination of missing data. In one study, approximately 46.5% of the data and 363 of 410 features were eliminated due to missing values . In anotSimilar to missing data, deletion or elimination is a common way to handle outliers . HoweverCollecting healthcare data for research purposeTraditionally, the primary objective of data collection in healthcare is documentation of patient condition and care planning . IncludiAutomation of data mining process for non-expert usersThe end users of data mining in healthcare are doctors, nurses, and healthcare professionals with limited training in analytics. One solution for this problem is to develop an automated  system for the end users . A cloudInterdisciplinary nature of study and domain expert knowledgeHealthcare analytics is an interdisciplinary research field . As a foIntegration in healthcare systemVery few articles reviewed made an effort to integrate the data mining process into the actual decision-making framework. The impact of knowledge discovery through data mining on healthcare professional’s workload and time is unclear. Future studies should consider the integration of the developed system and explore the effect on work environments.Prediction error and “The Black Swan” effectIn healthcare, it is better not to predict than making an erroneous prediction . A littlMoreover, prediction models may be better at predicting commonplace events than rare ones . ResearcThe development of an informed decision-making framework stems from the growing concern of ensuring a high value and patient-focused health care system. Concurrently, the availability of big data has created a promising research avenue for academicians and practitioners. As highlighted in our review, the increased number of publications in recent years corroborates the importance of health care analytics to build improved health care systems world-wide. The ultimate goal is to facilitate coordinated and well-informed health care systems capable of ensuring maximum patient satisfaction.This paper adds to the literature on healthcare and data mining  as it isWe also shed light on some promising recommendations for future areas of research including integration of domain-expert knowledge, approaches to decrease prediction error, and integration of predictive models in actual work environments. Future research should recommend ways so that the analytic decision can effectively adapt with the predictive model subject to errors and unpredictable incidents. Regardless of these insightful outcomes, we are not constrained to mention some limitations of our proposed review approach. The sole consideration of academic journals and exclusion of conference papers, which may have some good coverage in this sector is the prime limitation of this review. In addition to this, the search span was narrowed to three databases for 12 years which may have ignored some prior works in this area, albeit the increasing trend since 2005 and less number of publications before 2008 can minimize this limitation. The omission of articles published in languages other than English can also restrict the scope of this review as related papers written in other languages might be evident in the literature. Moreover, we did not conduct forward (reviewing the papers which cited the selected paper) and backward (reviewing the references in the selected paper and authors’ prior works) search as suggested by Levy and Ellis .Despite these limitations, the systematic methodology followed in this review can be used in the universe of healthcare areas.


California’s Mental Health Services Act has infused funding for workforce education and training into the public mental health system. However, funding has not kept pace with an existing behavioral health workforce shortage crisis, the rapid growth of an aging population, and the historical lack of geriatric training in higher education for the helping professions. This study draws on findings from a recent evaluation of how older adults are served by California’s public mental health delivery system, and a review of state planning documents and academic literature, to describe gaps and deficiencies in the workforce that serves older adults. While California has more than 80,000 licensed behavioral health professionals in a variety of disciplines, very few have specialized training in geriatrics. Across the U.S., there are fewer than 1,800 geriatric psychiatrists and only about 3% of medical students take any geriatrics electives during their training. Very few nurses (1%), psychologists (4%), or social workers (4%) have training in and/or specialize in geriatrics. Of additional concern in California is the lack of representation of ethnic and racial minorities, and rural/urban geographic disparities in the distribution of the behavioral health workforce. Recommendations for advancing policy change to improve the preparation and distribution of the geriatric behavioral workforce are presented to three distinct audiences: state policymakers and administrators; educational institutions, accrediting bodies, and licensing boards; and county mental health/behavioral health departments and their contracted providers.


Increased demand for healthcare services in countries experiencing high HIV disease burden and often coupled with a shortage of health workers, has necessitated task shifting from professional health workers to Lay Health Workers (LHWs) in order to improve healthcare delivery. Maternal and Child Health (MCH) services particularly benefit from task-shifting to LHWs or similar cadres. However, evidence on the roles and usefulness of LHWs in MCH service delivery in Sub-Saharan Africa (SSA) is not fully known.To examine evidence of the roles and impact of lay health worker programmes focusing on Women Living with HIV (WLH) and their HIV-exposed infants (HEIs).A scoping review approach based on Arksey and O’Malley’s guiding principles was used to retrieve, review and analyse existing literature. We searched for articles published between January 2008 and July 2018 in seven (7) databases, including: MEDLINE, Embase, PsycINFO, Joanna Briggs, The Cochrane Library, EBM reviews and Web of Science. The critical constructs used for the literature search were “lay health worker”, “community health worker”, “peer mentor”, “mentor mother,” “Maternal and Child health worker”, “HIV positive mothers”, “HIV exposed infants” and PMTCT.Thirty-three (33) full-text articles meeting the eligibility criteria were identified and included in the final analysis. Most  of the included studies were conducted in South Africa and used a cluster RCT design . The most commonly performed roles of LHWs in HIV specific MCH programmes included: community engagement and sensitisation, psychosocial support, linkage to care, encouraging women to bring their infants back for HIV testing and supporting default tracing. Community awareness on Mother to Child Transmission of HIV (MTCT), proper and consistent use of condoms, clinic attendance and timely HIV testing of HEIs, as well as retention in care for infected persons, have all improved because of LHW programmes.LHWs play significant roles in the management of WLH and their HEIs, improving MCH outcomes in the process. LHW interventions are beneficial in increasing access to PMTCT services and reducing MTCT of HIV, though their impact on improving adherence to ART remains scanty. Further research is needed to evaluate ART adherence in LHW interventions targeted at WLH. LHW programmes can be enhanced by increasing supportive supervision and remuneration of LHWs. In countries severely affected by HIV and AIDS, shortages of health workers present a significant obstacle to scaling up quality HIV services. The increased demand for services in high HIV burdened countries on the understaffed healthcare system has resulted in task shifting to Lay Health Workers (LHWs) in order to mitigate shortage of staff and improve service delivery –3. In 20LHWs are individuals who have not had formal tertiary or professional healthcare training and certification but have received some basic training for healthcare duties that they are required to perform within a particular intervention . Given tThe roles of LHWs are diverse, transcending from dealing with clients on a one-to-one basis at health facilities and in communities, interacting with the client’s family, to being involved in undertaking sensitization campaigns on HIV testing, feeding practices around HEIs, importance of male partner testing and championing implementation of health policies , 6. As pAlthough there is evidence to support the effectiveness of utilising LHWs to improve certain MCH indices such as promotion of breastfeeding, and increased uptake of childhood immunisation and cervical cancer screening, evidence remains scanty on the role of LHWs in several other specific MCH interventions such as those for HIV positive mother-HEI pairs . As Sub-The review aims to identify the roles played by LHWs in HIV related MCH health interventions, as well as the impact on the health outcomes of WLH and their HIV-exposed children in high HIV burden African countries.This scoping review presents work commissioned by mothers2mothers (m2m) that aimed to identify and synthesise research findings on current evidence of the role of LHWs in improving MCH in SSA by utilising literature from quantitative, qualitative and implementation science research. Sub-analysis of LHW’s role in HIV-specific MCH interventions was conducted to benchmark current evidence with m2m action plans.We conducted a scoping review in accordance with Arksey and O’Malley’s guiding framework for scoping reviews  and furtOur key research question was, “What are the roles played by LHWs in HIV related MCH interventions as well as the impact on the health outcomes of WLH and their HIV-exposed children in high HIV burden African countries?” From this, a team of three researchers identified the major constructs that included: a) Lay Health Worker b) Maternal and Child health c) HIV-exposed infants. We refined our search terms as our familiarity with literature increased as recommended by Daudt and colleagues  to increUsing the PICO framework, studies were included if they met the following criteria: i) HIV positive mothers alone or with their exposed baby pairs were targeted by the intervention, ii) interventions implemented in Africa for which LHWs were utilised in implementing the intervention, iii) papers with or without a comparator, iv), MCH outcomes including HIV testing, early infant diagnosis of HIV, ART adherence, viral suppression, utilisation of PMTCT services, retention in care, and knowledge of PMTCT. Additional outcomes explored include maternal depression, exclusive breastfeeding, infant growth and facility delivery rates, iv) studies published in English Language between 2008 and 2018, which coincides with the period in which WHO recommended task shifting of HIV and AIDS services, allowing lower health cadres to assume greater responsibility in HIV care delivery[We included any study design, both quantitative and qualitative studies, mixed methods studies and previously published systematic reviews, to answer our research question. Systematic reviews were identified for the purpose of reviewing their included studies for potentially relevant studies. We did not conduct risk of bias as per the Joanna Briggs Institute Scoping Review Methods Manual and scoping reviews on health-related topics.Duplicate screening of studies was done on the basis of title and abstract, and the full text. Potentially relevant studies were first identified by title by two independent reviewers. When the title proved to be inconclusive for assessing potential relevance, abstracts were read to decide whether a specific study should be included. All the identified studies were collated into EndNote for easy management of our references. Duplicates were removed from EndNote and the remaining studies were exported to Covidence software for screening. The screening process was conducted by two independent reviewers and was guided by the inclusion and exclusion criteria. Discrepancies during the screening process were resolved through discussions among the team.a priori and pilot tested on a sample of five included papers. Two reviewers carried out data abstraction, and two other reviewers checked quality for consistency and accuracy.We abstracted data on article characteristics: country where research was conducted; LHW programme characteristics and contextual factors, such as type of intervention, role of LHWs in intervention, frequency and intensity of engagement; barriers and facilitators to programme implementation. In addition, results of any formal assessment or evaluation of HIV specific MCH outcomes, such as MTCT rate, HIV testing, ART initiation among HIV positive pregnant and/or breastfeeding women and their infants, adherence to ART, uptake of EID of HIV and infant HIV status. Data abstraction was conducted using a standardised data extraction form that was developed Our initial database search identified 431 relevant studies. After screening of titles and abstracts, 72 papers were retained. Of those, we excluded 39 articles after full-text review. Finally, 33 primary studies were identified for inclusion .Most studies were designed as cluster randomized controlled trials n = 13, 39.4%), or cohort study design n = 9, 27.3%). Other study designs in identified studies were, quasi-experimental , cross sectional n = 3, 6.1%), qualitative  and RCTs . Standard of care was often used as the comparative reference, in 23 of the studies. The studies originated from LHW interventions across eight countries in SSA. The highest number of studies originated from interventions in South Africa (13 studies) followed by Zimbabwe (6 studies) and Malawi with five studies, and Nigeria (3 studies), and Uganda, Tanzania, Kenya and Ethiopia each with one study. The nomenclature used to refer to LHWs was mentor mother in eight studies .1%, qual–17 follo3, 39.4%,7.3%. OthThe most commonly performed roles by LHWs in MCH programmes included: health education, psychosocial support, linkage to care and defaulter tracing. In performing these roles, LHWs carry out several activities such as encouraging women to bring their babies back for HIV testing post-delivery, assisting mothers living with HIV (MLH) to access vital documentation and social grants, 26, 27.LHWs were reported to play a crucial role in patient education, 19 of the 33 identified articles stated that education was a key component of the intervention delivered by LHWs , 28–30. LHW’s formalised links to health facilities improved their ability to influence and inform the community about where to access health services , 32 and For mother-infants pairs initiated into care, the LHW role is mainly centred on counselling and psychological support to promote positive living and self-efficacy in HIV management . LHWs prData on retention in care and utilisation of PMTCT services by mother-child pairs was reported in 14 studies. For instance, the Mamekhaya Project which provided cognitive behavioural interventions using the m2m model found that involving mentor mothers in education and support for HIV positive women increased HIV and PMTCT knowledge scores, particularly about understanding the meaning and importance of viral load, CD4 results and the efficacy of ART . SimilarLHW interventions in South Africa have been shown to increase ANC attendance, improve linkage to HIV care and administration of ART to infants , 21, 29.ART initiation was explored in ten studies. Follow-up visits of pregnant women by CHWs in their homes in Malawi from the time of HIV diagnosis at ANC to post-delivery resulted in improved initiation of mothers and infants on ART from baseline levels of 8.8% to 87.7% . It alsoThree studies reported on rate of facility delivery outcome. In Kenya, CHWs encouraged pregnant WLH to go to ANC and deliver their babies at the clinic. This led to a significant increase in the number of WLH delivering at health facilities from an average of 6.5 to 14 . In NigeFive studies explored the behavioural outcome of partner testing and disclosure. The Mamekhaya intervention reported no significant intervention effect on partner testing as 50% of WLH in the intervention and 45.2% of WLH in the control had a partner tested for HIV. WLH attAdherence and viral suppression were explored in 14 studies. The impact of LHWs on adherence to ART and by extension elimination of MTCT is not well elucidated. Some studies have reported benefits in favour of LHW interventions , while oIn contrast, the PURE study in Malawi reported non-significant differences in viral suppression between HIV positive pregnant and breastfeeding mothers receiving peer support with those receiving routine PMTCT services only, HIV virological suppression was 84% which is below the UNAIDS 90% suppression desirable target in all treatment support arms . These rEID was reported in seven studies. Exposure to LHW interventions increased timely presentation to clinics for EID of HIV , measureNine studies reported on the exclusive breastfeeding outcome, infant nutrition options and the implications on infant growth. LHW programs have increased rates of early and exclusive breastfeeding . A volunFamily planning was explored in five studies. Mentor mothers facilitated the empowerment of WLH to better negotiate for condom use and to agree to family planning with partners . CommuniThe impact of psychosocial support on positive coping and depressive symptoms was explored in seven studies. LHW initiatives have been shown to improve mental health and ability to cope with HIV stigma, and to reduce the prevalence of depressive symptoms among WLH by helping them identify and establish social support networks . Mentor In as much as LHW programmes have shown a positive impact on HIV-specific MCH outcomes of WLH and their exposed children, their implementation faces numerous challenges. Mentor mothers found it difficult to document and complete patients’ outcome on clinical forms because they were not trained to do so . In SoutIf LHW programmes are initiated when there is no national policy to support it, its implementation can be affected as reported by Tomlinson and colleagues where the Good Start CHW intervention was implemented at a time when national policy did not support exclusive breastfeeding for HIV-infected women in South Africa . CharginA comparative synthesis of three implementation studies in Nigeria (MoMent), Malawi (PURE) and Zimbabwe (EPAZ) reported that common challenges to LHW programmes included involvement of male partners and concerns over confidentiality and privacy . In someThe scoping review aimed to examine the roles and impact of lay health worker programmes targeting MCH outcomes of WLH and their HIV exposed children. We found that LHWs play crucial roles in the education of mothers, linkage to care, providing psychosocial support to MLH and their HEIs, tracing defaulters, promoting exclusive breastfeeding and presentation of mothers with theirs babies to the clinic for EID of HIV. As highlighted in a previous systematic review investigating the roles of CHWs in HIV care in SSA, LHWs were reported to enhance the reach, uptake and quality of HIV services, as well as the dignity, quality of life and retention in care of people living with HIV .The majority of the studies we found were conducted in South Africa. HIV and AIDS research is arguably a dynamic area of research in South Africa given the burden of HIV and AIDS in the country , more deThe findings show that delegating of specific tasks to cadres of LHWs can increase access to HIV services and can improve the quality of care for HIV. The roles of LHWs have expanded to accommodate the growing needs of WLH and their HEIs, and providing a holistic coverage of care including clinical, educational and psychosocial support to prevent attrition and to keep mother-child pairs in HIV care. Well-functioning and sustainable service delivery heavily relies on support and training, resources at LHW’s disposal and the quality of implementation.We found that uptake of PMTCT services and psychosocial support were the main target of the identified interventions, followed by interventions to increase ART initiation and EID. Importantly, WLH require knowledge on PMTCT, how to care for their exposed infants and how to live healthy , 46, 47.Other clinical conditions such as maternal depression and infections were subject to study to a lesser degree in our review. We suggest that future studies should better reflect the mental wellbeing and coping efficacy of HIV positive mothers, as the prevalence of maternal depression especially among postpartum women can exceed 35% .Many studies described LHW interventions but most lacked clear information about details of their tasks or the methods used to interact with mother-child pairs, and frequency of contact with clients. In addition, a few explained why the standard of care intervention alone was inadequate. To enhance our understanding and eventually replicate the interventions in other settings, we recommend clarity regarding intervention adequacy and more detailed descriptions of the development of the intervention including fidelity, dosage and challenges encountered . For insOur findings highlight that while LHWs encouraged adherence to ART, there was an insignificant impact on most LHW programmes with suboptimal adherence levels reported , 33, 37.There is paucity of data on the role of social and cultural context on the uptake of interventions within African communities. Moreover, some researchers argue that using a multifaceted approach that considers contextual settings, leadership involvement and shared learning fora will more likely yield better results. This gives credence to the argument that a “no one size fits all” approach is better suited to closing the implementation gap for priority prevention programs such as PMTCT of HIV . LHW proOur review has its strengths and limitations. The extent of our search was broad, as we aimed to give a holistic view of the studies in the field. Our scoping review is however limited as we did not look into grey and unpublished literature. In addition, we did not screen for quality of studies, and thus studies included vary widely regarding methods and sample sizes. Also, the exclusion of non-English publications in our search could have omitted studies published in journals in non-English speaking countries. The majority of studies did not exclusively examine LHW interventions targeted at mothers living with HIV and their HEIs. Finally, the success of LHW programmes is often dependent on implementation fidelity, the scope of training provided to LHWs, and adequacy of resources. We were not able to differentiate between projects on the basis of these implementation issues.The most commonly reported roles of LHWs include health education, psychosocial support, linkage to care and defaulter tracing. Findings of this scoping review show that delegation of tasks to cadres of LHWs can increase access to care among WLH and their baby pairs, retention in care, exclusive breastfeeding, presentation of HEIs at clinics for EID for HIV, use of effective family planning methods and negotiating for safe sex. There is, however, no effect on adherence to ART, and mixed findings for impact on viral suppression, male partner testing and increasing facility delivery rates. Program quality and fidelity can be enhanced by motivating LHWs through provision of adequate remuneration, integration of LHW programs into the public health system and supportive supervision to sustain the success of interventions.S1 File(DOC)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.


Digital strategies have been formally recognized as a critical health systems strengthening strategy to help meet the Sustainable Development Goals and universal health coverage targets. This landscaping collection reviews multiple possible approaches across health system pillars, from digital referrals to decision support systems, identifying key knowledge gaps across these domains and recognizing the growth needed in the field to realize its full potential. Digital strategies have been formally recognized as a critical health systems strengthening strategy to help meet the Sustainable Development Goals and universal health coverage targets. This landscaping collection reviews multiple possible approaches across health system pillars, from digital referrals to decision support systems, identifying key knowledge gaps across these domains and recognizing the growth needed in the field to realize its full potential. Over a decade ago, the emergence of mobile phone networks across the globe presented a novel opportunity for rapid improvement in global health. Although health system challenges were not important drivers of this global mobile network proliferation, the public health and clinical community rapidly recognized the potential of mobile phones to tackle many immense challenges experienced by health systems, including early diagnosis, access to care, and equitable provision of services.Initially a wide field of discordant experimentation, in the past 5 years digital health has seen an unprecedented convergence on a shared vocabulary,As we noted previously,In May 2018, at the 71st World Health Assembly, WHO member states unanimously endorsed a resolution on digital healthIn May 2018, WHO member states unanimously endorsed a resolution for governments to recognize the importance of digital systems for facilitating health systems strengthening and achieving universal health coverage.The landmark June 2018 WHO digital health guidelines development meeting and soon-to-be-published guidelines on digital interventions for health systems strengtheningGlobal Health: Science and Practice, we present 6 articles that explore the ever-growing overlap between health systems and digital health, with each paper led by experts in these 2 domains. Supported by the Aetna Foundation, teams of researchers and practitioners in these often-intersecting domains were asked to use their respective lenses and knowledge of the literature to explore and present an overview of state-of-the-art evidence that illustrates how digital health is being leveraged to address health system constraints across each of the WHO health system building blocks.In this special issue of Labrique et al.MeessenA scoping review of digital technologies that focus on the health workforce, led by Long, Pariyo, and Källander,Finally, 2 articles take on the dual aspects of health service delivery—separately tackling digital innovations that target the providers of care (supply-side focus) and the receipt of care . Together with digital health colleagues at WHO, Gibson et al.As described earlier, digital strategies have been formally recognized as a critical strategy to help meet the Sustainable Development Goals and universal health coverage targets. As such, this landscaping collection reviews multiple possible approaches, from digital referrals to decision support systems, identifying key knowledge gaps across these domains and recognizing the growth needed in the field to realize its full potential. Strengthening the digital strategy evidence base is crucial, as it provides the necessary support to convince investors and risk-averse governments to invest in this solution space. Across all 6 articles in this supplement, key areas for research, investment, and evidence generation are highlighted, providing a road map for resource allocation in digital health moving forward. An important objective of this series was to identify the ‘big unanswered questions’ that may further the interdisciplinary meeting of health systems strengthening and digital health. The entropy and chaos of the early days of digital health is rapidly decreasing, guided by strong leadership, clear visions, and key investments in ‘global goods.’Strengthening the digital strategy evidence base is crucial, as it provides the necessary support to convince investors and risk-averse governments to invest in this solution space.


In 2007, the United States successfully eliminated canine rabies virus variant. Globally, however, dogs remain the principal source of human rabies infections. Since 2007, three cases of canine rabies virus variant were reported in dogs imported into the United States, one each from India (2007), Iraq (2008), and Egypt (2015) ( On December 20, 2017, a shipment of four rescue dogs arrived at JFK from Cairo, Egypt. Two transporters and one owner retrieved the dogs, with planned distribution to foster homes and permanent owners in Connecticut, Maryland, and Virginia. A fifth dog on the flight, traveling with a separate flight parent and not part of this shipment, shared the cargo hold and was temporarily housed in New Jersey and West Virginia before reaching its Washington destination. One of the four dogs, a male Chihuahua mix aged 6 months (dog A), was noticeably agitated and bit the flight parent before boarding the plane in Egypt. Dog A was imported with tooth fractures and exposed maxillary bone, reportedly from being struck by a car in autumn 2017.On assessment at a Connecticut veterinary clinic on December 21, dog A exhibited hyperesthesia (increased sensitivity to stimuli) and paresis. The dog bit a veterinary technician during a blood draw procedure and died shortly thereafter. The clinic submitted brain tissue for rabies testing to CDPHL. On December 26, CDPHL confirmed rabies virus infection by direct fluorescent antibody testing and informed CDC. On December 28, CDC confirmed the direct fluorescent antibody results and determined the variant was consistent with Africa 4 subspecies canine rabies virus circulating in Egypt .After CDPHL’s notification of confirmed rabies, CDC’s New York Quarantine Station initiated a contact investigation to identify animals or persons potentially exposed to dog A during its infectious period (10 days before symptom onset until death [December 9–21]). CDC contacted health departments in the chain of distribution of all five dogs in the cargo hold to initiate rabies exposure assessments; these health departments included the Maryland Department of Health, Virginia Department of Health, New York City Department of Health and Mental Hygiene, New York State Department of Health and Mental Hygiene, and Washington State Department of Health. The investigation also included U.S. Customs and Border Protection (CBP), the U.S. Department of Agriculture’s Animal and Plant Health Inspection Service, the airline that transported the animals, and the domestic cargo offloading company at JFK.State health department staff members interviewed dog A’s caretakers, volunteers, and employees associated with the involved rescue groups and veterinary hospital staff members for potential exposure. Public health investigators for Maryland, New Jersey, New York, Washington, and West Virginia determined that the animal transporters and foster home volunteers had no direct contact with dog A; therefore, no postexposure prophylaxis (PEP) was recommended for those persons. Connecticut public health officials, in accordance with national guidelines  were individually crated within the airplane cargo hold. A fifth dog , that was not part of the rescue organization shipment, shared the same cargo hold space. The animals were never removed from the crates during shipment, so they could not have had direct contact with dog A. Therefore, dogs B, C, D, and E were not considered exposed to dog A during transport. Dog A had no contact with any dogs after exiting the airport and was placed in isolation at the veterinary clinic. All five dogs had certificates indicating rabies vaccination both at ≥3 months and ≥30 days before arrival at a U.S. port of entry , as requElimination of the canine rabies virus variant from the United States required approximately 5 decades and hundreds of millions of dollars. Imported cases present an ongoing opportunity for reestablishment of the variant and require lengthy and costly investigations to prevent additional cases in both humans and animals.This report describes the sixth importation of a rabid dog into the United States in the past 15 years and the third from the Middle East; all six were rescued dogs  also are common in stressed dogs during long-distance travel, and, unless the animal is near death, ill dogs could be overlooked. Increased education of rescue organizations both domestically and internationally and enhanced focus on dogs from countries where canine rabies virus variant is circulating could help increase awareness of the significance of rabies control in dog importations and reduce the potential for importation of cases.Public health challenges associated with the global movement of animals include importation of canine rabies virus variant into the United States from countries where the virus is enzootic.A rabid dog imported into the United States from Egypt, with documentation of rabies vaccination but no medical history, resulted in a six-state investigation and administration of rabies postexposure prophylaxis to multiple persons.Use of flight parents who have no medical history for the dog they are transporting poses a potential human and animal health threat. To prevent reintroduction of the canine rabies virus variant, the United States needs to continue vigilance at ports of entry, domestic surveillance infrastructure, and high dog vaccination coverage.


Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that are key players in synaptic transmission and plasticity. They are composed of four subunits, each containing four functional domains, the quaternary packing and collective structural dynamics of which are important determinants of their molecular mechanism of function. With the explosion of structural studies on different members of the family, including the structures of activated open channels, the mechanisms of action of these central signaling machines are now being elucidated. We review the current state of computational studies on two major members of the family, AMPA and NMDA receptors, with focus on molecular simulations and elastic network model analyses that have provided insights into the coupled movements of extracellular and transmembrane domains. We describe the newly emerging mechanisms of activation, allosteric signaling and desensitization, as mainly a selective triggering of pre-existing soft motions, as deduced from computational models and analyses that leverage structural data on intact AMPA and NMDA receptors in different states. These processes can only be understood in depth through a study of the molecular events involved in synaptic communication . One keymulation . AMPARs mulation . The twoA vast number of functional and structural studies have helped elucidate the molecular origin of channel responses observed in experiments, such as agonist-dependent channel opening to multiple conductance states and a process called desensitization where the channel closes with ligand still bound ,10. StruThe dimeric arrangement of the LBDs within a receptor, with two clamshells facing away from each other, gave rise to an initial model where cleft closure could either drive channel opening by pulling apart the lower lobes B, left oIn recent years, a number of agonist-bound crystal structures of whole AMPARs revealed some conformational changes without channel opening  and a crStructural data alone are not sufficient to make inferences on the mechanisms of function. Yet, the multitude of structures in different states have helped elucidate the conformational landscape accessible to these receptors. These, along with single-molecule experiments such as fluorescence resonance energy transfer (FRET) and related methods, nuclear magnetic resonance (NMR) spectroscopy, and double electron–electron resonance (DEER) spectroscopy have been applied to the study of iGluR dynamics . Structu2Molecular dynamics (MD) simulations use a detailed force field to describe all the covalent and non-covalent interactions between all atoms in the system including the protein as well as surrounding water and ions A. This mH of the second derivatives of the potential with respect to deformations. The decomposition of H yields a spectrum of normal modes of motions. The lowest frequency modes among them describe the most accessible collective motions that are usually functional, and occur at biologically relevant (microsecond to millisecond) timescales [An alternative and complementary approach is to use a coarse-grained model, such as elastic network models (ENMs), which enables one to efficiently visualize the large collective modes of motions of the system at the expense of atomic details . The adomescales . ENMs camescales ,73 and tmescales .3The arrival of the first LBD structures from AMPAR subunit GluA2 in 1998  and 2000Since then, studies have increasingly accessed longer timescales and carried out more detailed characterizations of conformational changes. This phase started around 2006 with simulations of the GluA2 LBD  and the Recent increases in computing power have further enabled the simulations of larger systems such as LBD dimers, which provided insights into rearrangements linked to desensitization ,92, and Once whole receptor structures became available, simulations were carried out on tetramers including both the LBD and TMD for the GluA2 AMPAR  and the Most recently, a set of MD simulations each on the order of five microseconds carried out with the Anton supercomputer for AMPAR LBD monomers and dimers revealed the detailed mechanism, energetics and kinetics of glutamate binding to individual LBD clamshells .4Elastic network model NMA has been applied much more extensively to large assemblies than all-atom MD simulations where the system size becomes an issue. Large conformational changes such as the splaying apart of the NTD dimers of iGluRs observed in low resolution electron microscopy studies ,33 are bANM analysis was initially applied to NTD monomers and dimers where clamshell closure and inter-subunit rearrangements were linked to allosteric signaling ,94,100, ANM studies of whole receptors provided a first glimpse of the dynamic coupling between the NTD, LBD and TMD layers ,99,102. A recent study by Popescu and coworkers used ENMs for flexible fitting of electron microscopy data and transition pathway modelling, yielding insights into NMDAR activation . In addi5selective excitation of pre-existing motions i.e. glutamate binding to the LBD selectively triggers cooperative motions from amongst those soft modes already encoded by the receptor structure. Such intrinsic modes of motion of whole receptors and isolated domains have been visualized using MD simulations [iGluRs have a large extracellular region that facilitates an extensive spectrum of dynamic rearrangements, which are being extensively explored in structural and computational studies. All these observations translate into a ulations ,87,93,98ulations ,99,104, ulations ,99,102 rbottom diagrams and Movie 1), which vary from an O-shape organization in the compact state (panel A) through the classical N-shape in the starting structure (panel C) to a splayed apart, stretched shape at the other end of the mode (panel D).Mode 4 of the AMPAR A resemblThe rearrangement of the NTDs in the compact AMPAR (panel A) approximates that of the inhibited NMDAR (panel B). The compact, inhibited-like state exhibits a close packing at the LBD-TMD interface where closure of the LBD clamshells could have less influence through the coiled LBD-TMD linkers not receiving as much tension. The release transition along this AMPAR ANM mode C–D showsThe second global mode, mode 6 of the AMPAR, involves a set of cooperative dynamics, which is likely important for activation  modes of motion that often agree with and build upon experimental data from structural studies, albeit at low resolution. In particular, these intrinsically accessible and energetically favorable modes of motion, analyzed in the context of existing experimental  data and atomic-simulations performed for substructures, reveal well-defined couplings between the motions of AMPAR domains, and provide better glimpses of channel activation, desensitization and inhibition mechanisms than static structures alone. An emerging picture is an allosteric communication between the NTD, LBD and TMD modulated by glutamate binding to the LBD, which selectively triggers pre-existing robust modes uniquely encoded by the overall tetrameric architecture.None.


Dengue was first reported in Puerto Rico in 1899 and sporadically thereafter. Following outbreaks in 1963 and 1969, the Centers for Disease Control and Prevention has worked closely with the Puerto Rico Department of Health to monitor and reduce the public health burden of dengue. During that time, evolving epidemiologic scenarios have provided opportunities to establish, improve, and expand disease surveillance and interventional research projects. These initiatives have enriched the tools available to the global public health community to understand and combat dengue, including diagnostic tests, methods for disease and vector surveillance, and vector control techniques. Our review serves as a guide to organizations seeking to establish dengue surveillance and research programs by highlighting accomplishments, challenges, and lessons learned during more than a century of dengue surveillance and research conducted in Puerto Rico. Aedes mosquitoes. In addition, dengue cases frequently appeared in the same household ≈2 weeks after the first household member fell ill, which suggested to King that infections might occur around the household. These observations collectively led King to suspect that dengue already was endemic in Puerto Rico by 1915.In 1916, Walter W. King , a surgeMany of King’s prescient observations remain true. Yet, despite extensive resources expended to understand and combat dengue, rates of illness and death caused by dengue continue to increase worldwide . Through observation of 2,777 persons during the 1963 outbreak, dengue was described as an acute febrile illness lasting 4–7 days with infrequent minor hemorrhagic manifestations  was established in 1969 to collect basic demographic and clinical data from patients with suspected dengue. By 1970, PDSS enabled detection of dengue cases in southwestern Puerto Rico during the dry season, providing further evidence that dengue was endemic  was insufficient to monitor dengue because clinicians were often unable to distinguish dengue from influenza, leptospirosis, rubella, and other common causes of acute febrile illness .In 1982, a new surveillance system that included active surveillance sites to augment passive reporting was implemented; this system emphasized monitoring virus transmission in 31 sites across the island  in Southeast Asia during the 1970s, increased effort was dedicated to monitoring the clinical severity of dengue in Puerto Rico. The first DHF cases were retrospectively detected from 1975 .During a large epidemic in 2010, the Puerto Rico Secretary of Health redirected public health resources from vector control campaigns, which had repeatedly been shown to be ineffective, and instead used them to conduct islandwide clinical trainings. To ensure participation, the Secretary made it mandatory for most practicing physicians to complete the course or face a penalty of losing their medical license (Aedes or Toxorhynchites mosquitoes followed by immunofluorescent detection of DENV antigen (The first laboratory diagnostic tool used to detect increased antibody titers in serum specimens collected from persons enrolled in the serosurvey during the 1963 outbreak was hemagglutination inhibition (HI), confirmed with complement fixation (CF) . CF alsoHI and virus isolation were the most common diagnostic techniques used in the early 1980s to mid-1980s. Use of cultured mosquito cells to isolate virus and immunofluorescence with monoclonal antibodies to identify viruses enabled observation of dissemination of DENV-1 and DENV-4 across Puerto Rico during the 1981–82 epidemic  protocol to detect DENV nucleic acid in serum specimens , biocontrol , and source reduction to control larvae; and studies of vector competence and transmission dynamics. The efficacy of ultralow volume space spraying with malathion and pyrethroids was evaluated in 1987, as was aerial application of naled using C-130 aircraft. Unfortunately, such efforts had no effect on epidemic trends and variable levels of success in reducing DENV transmission (Extensive research was conducted during the 1980s on use of insecticides to control adult Ae. aegypti eradication program during the 1960s (54 in 55 in After having been standardized as a vector surveillance tool during the 0s 54 in . Around 56 in 57 in Ae. aegypti mosquitoes and risk for DENV infection (reference 58 in 59 in 60 in Ae. aegypti mosquitoes (reference 61 in After observations that adult mosquito populations do not correlate well with larval densities, in the early 2000s pupal populations were reported to have a nonlinear relationship with density of adults (reference 62,63 in Dengue remains a major public health concern throughout the tropics and subtropics. In Puerto Rico, close alliance of CDC with PRDH has proven to be integral not only in detecting and responding to epidemics but also in furthering the collective understanding of the molecular, diagnostic, epidemiologic, and entomologic characteristics of dengue. Dengue surveillance and research have therefore demonstrated a mutually beneficial and interdependent relationship to combat dengue. Dengue surveillance also has promoted the recognition and study of nondengue acute febrile illnesses, an attribute further shown during the recent emergence in Puerto Rico of chikungunya virus in 2014 and Zika virus in 2015 (references 64 in The demonstrated limitations in chemical approaches to dengue control have inspired several alternative interventions (reference Additional references for lessons learned from dengue surveillance and research, Puerto Rico, 1899–2013.