Charting significant growth in science production over the 20th century in four European Union member states, this neo-institutional analysis describes the development and current state of universities and research institutes that bolster Europe’s position as a key region in global science. On-going internationalization and Europeanization of higher education and science has been accompanied by increasing competition as well as collaboration. Despite the policy goals to foster innovation and further expand research capacity, in cross-national and historical comparison neither the level of R&D investments nor country size accounts completely for the differential growth of scientific productivity. Based on a comprehensive historical database from 1900 to 2010, this analysis uncovers both stable and dynamic patterns of production and productivity in Germany, France, Belgium, and Luxembourg. Measured in peer-reviewed research articles collected in Thomson Reuters’ Science Citation Index Expanded, which includes journals in the fields of Science, Technology, Engineering, Mathematics, and Health, we show the varying contributions of different organizational forms, especially research universities and research institutes. Comparing the institutionalization pathways that created the conditions necessary for continuous and strong growth in scientific productivity in the European center of global science emphasizes that the research university is the key organizational form across countries. Charting huge growth in science production over the 20th century in four EU member countries, we analyze the development and contemporary state of universities and research institutes that bolster Europe’s position as a key region in global science. On-going internationalization (and Europeanization) of higher education and science challenges traditional nation-based studies. In response, neo-institutional analyses have explored the powerful diffusion of worldwide ideas and norms in science  and in the contemporary Bologna process. They are connected in multilevel governance and participate in myriad joint education and research programs, such as Erasmus. At the intersection of the Germanophone and Francophone worlds, these countries differ in languages and cultures, in demographics and geography, and in resources devoted to education and science, yet not necessarily consistently. In an era of internationalization, massive growth in the scientific output of these four countries simultaneously reflects competition and collaboration. Our comparison uncovers contrasting investments in research and development (R&D) and variable institutionalization of higher education and science systems.Measured in papers published in leading peer-reviewed journals of the Science Citation Index Expanded (SCIE), the volume of scientific output differs, sometimes unexpectedly, according to institutionalized structures of higher education and research. For example, the relative importance of universities, research institutes, and firms differs across cases, even as the research university’s contribution rises. The overall scientific output in science and technology disciplines increased dramatically over the 20th century, with Europe losing, but regaining its position as the global “center of gravity”  or a set of strong research universities in different regions . The two larger countries  maintain differentiated systems of universities (of varying size and prestige) and extra-university research institutes (connected in large umbrella associations or coordinated by government agencies). This requires considerable state investment: “The most consequential scientific revolutions of our time could not have happened in universities without massive government and/or corporate support” Kennedy : 314. AlComparing the level of gross domestic expenditures on R&D (GERD) as a proportion of GDP—“research intensity”—in the four countries shows considerable variance. To estimate the impact of investments in science, a time lag should be recognized. Here, we select GERD two years before the last publications gathered in our database were published to indicate the relevant investments (2008). The OECD mean was 2.29% while the EU-15 mean was 1.91%. Germany had increased its R&D investments to 2.60%. France has been relatively stable above 2% since 2000 (2.06% in 2008). Belgium invested 1.92%; just below France, but far lower than Germany. Luxembourg had a mean of 1.64%, lower than its three neighboring countries. None have reached the EU target of 3% to be invested in “innovation.” Thus, these countries’ investments vary by a factor of two . Our selection of countries reflects higher education and science systems with different institutional structures to examine and compare which institutional setting(s) provide the best conditions for scientific production and productivity.The institutional settings and organizational forms in which research is conducted affect overall capacity and scientific productivity. Establishing new organizations involves high costs and myriad challenges, especially for small states due to limited native highly qualified human capital and lack of economies of scale  and in such increasingly influential government initiatives  and organizations (European Research Council) that fund European science on the frontier Flink . FocusinWe measure science production on the basis of a dataset from Thomson Reuters (Web of Science) of published papers in selected science and technology disciplines, including health. The increasing role of conference proceedings and other publication formats in STEM disciplines with high growth rates  are only partially reflected in the SCIE database. Nevertheless, peer-reviewed journal articles are the most important and traditional type of publications in these fields, next to patents—and the growth rate of scientific publications is still increasing overall, with disciplinary differences  or Germany’s Max Planck Society—though founded in the 20th century, are similarly well-established. The countries differ in the time elapsed since establishment and in the differentiation of these organizational forms and fields. Comparing the four research university sectors, Germany and Belgium are more highly institutionalized than France and Luxembourg. By contrast, in research institutes, France and Germany have large, differentiated non-university research sectors.According to the volume of produced STEM papers and to historical reach, we sketch the development of universities and research institutes in Germany and France, then in Belgium and Luxembourg, showing how capacity for producing scientific papers has grown over time. To understand the level and extent of institutionalization of universities and research institutes in each country, we display these systems depending on the development of the (non)university sectors Fig. . Europe We begin with process-tracing in each country, based on synthesis of the research literature in multiple languages and emphasizing the founding dates of organizations and system institutionalization. Process-tracing helps us to understand sequential  events and allows us to explore developmental processes in specific cases Mahoney : 88f. WeGermany is home to the undisputed model of the research university and significant extra-university research institutes. Yet universities have been underfunded for decades  is the main promoter of science. Furthermore, the European Commission and more than 16,000 foundations offer innumerable possibilities to apply for financial support for education and research  after massification of tertiary education. Since the 1960s, this new organizational form provides a more applied and praxis-oriented focus. Investments in  research are less significant; however, increasingly their faculty members do conduct research, often collaborating with industry. They have become more like research universities, even if the monopoly on granting doctoral degrees remains in universities  challenged the German higher education system as the dominant locale for fundamental research. In this sector, research was institutionally separated from teaching. Today, 83 Max Planck institutes are located in Germany and 5 institutes abroad; the newest—the Max Planck Institute for International, European, and Regulatory Procedural Law—opened in Luxembourg in 2012. After WWII, further competitors entered the growing organizational field of extra-university research: The Fraunhofer Society was established in 1949 to focus on applied sciences and industrial contract research (today: 67 institutes). The Leibniz Association was established in 1997, but had existed since 1977 known as the “blue list” (Blaue Liste), a collection of diverse research institutes with regional or national significance and varying emphases on fundamental or applied research (today: 89 institutes). The Helmholtz Association of German Research Centers (2001), dealing with research related to infrastructure (Vorsorgeforschung) comprises 18 very large research institutions (Großforschungseinrichtungen) and around 40 federal research institutions in a range of fields related to national interests   Hohn . Germany50) Hohn .Fig. 3Scwww.mpg.de/de/imprs). Because only research universities in Germany have granted doctoral degrees, others depend on close collaboration or “strategic partnerships.” Furthermore, this concept has been affected by three developments: massification, segregation of research and teaching, and growing third-party funded research.With the emergence of newer path-breaking hybrid types of research (and teaching) as well as universities of applied science demanding the right to confer doctoral degrees, the German higher education system confronts a new situation. The structural duality of the German system no longer seems unassailable or as sustainable. Examples of newer boundary-spanning organizations include the Karlsruhe Institute of Technology (KIT), an amalgam of the Karlsruhe Research Center (Helmholtz) and the Technical University of Karlsruhe, as well as the International Max Planck Research Schools (IMPRS) as examples for inter-institutional, international, and interdisciplinary collaboration  is dominant, though many of its researchers establish or work in research laboratories (research groups) physically located within universities. France finances and maintains prestigious extra-university research units and institutes, many, but not all, under the CNRS umbrella. With 79 universities, 205 grandes écoles,Ecole Normale Supérieure, six research organizations, ten engineering and business schools, and two educational clusters that host 10,000 researchers and 300 laboratories.France’s differentiated higher education system consists of a range of universities, some very strong in research and others more focused on teaching and applied fields. Universities are challenged by the elite higher professional schools, the grandes écoles/university divide and the split between selective and non-selective segments as well as distinctions between CNRS researchers and academy members at the top and regular university faculty members below. While the key organizational form for research may be—increasingly—the university, CNRS laboratories and institutes play a key role within them and more generally in producing science. The grandes écoles constitute a diverse group of highly selective and prestigious institutions that train future elites: higher-level civil servants, professors and researchers, engineers, and company managers  bill, passed in August 2007, grants significant power to university presidents. The proclaimed aim: to meet the demands of the “knowledge economy” and to bring French universities to the level of excellence of major international competitors. The French “excellence initiative,” designed to strengthen research collaborations and consortia of researchers within a differentiated higher education system, cannot eliminate decades of specialization and uneven development. Ironically, the German Excellence Initiative aimed to do the opposite, creating more differentiation in a less stratified, less differentiated higher education system , while em Münch .grands établissements was established to support and develop training and research, including the École pratique des hautes études (1868) and the Institut Pasteur (1887), which has grown in capacity and influence  joint laboratories with universities and industry. CNRS is significant for France’s scientific development and international standing in a wide range of fields. Organized in associations, university faculty members may apply to establish collaborations with one of the national research institutes, or associated laboratories receive funding, and sometimes CNRS staff, while autonomous research units—called Other publically-funded extra-university research institutions conduct strategic research related to national needs, from infrastructure and energy to agriculture and health, all part of a powerful centralized state Clark . The funTurning now to output, we examine France’s overall scientific productivity in STEM, and find continuously rising output and strengthened university-based research. The non-university/university sectoral divide has been narrowed see Fig. . These sThus, in both France and Germany, extra-university research institutes play an important role in research, as do the associations that directly fund research by selecting the best scientists and providing them with research-conducive conditions. Despite the dual structure that places emphasis and concentrates resources in the research institutes, with varying degrees of independence and collaborations across the institutional divide, both enjoy significant capacity and output.Turning now from two very strong mid-sized science-producing countries to two smaller countries, Belgium and Luxembourg have undergone significant transformations in higher education and research through European and within-nation policy interventions. Belgium exhibits considerable endogenous dynamics given the internal cleavages that exist, from language and religion to geography. Despite hosting the key European capital city, Belgium faces political challenges in maintaining a functioning nation-state. Next to Belgium, Luxembourg shows considerable diversity in languages as does its Flemish- and French-speaking neighbor. Over centuries, stemming from its modest size, the Grand Duchy has been majorly influenced and affected by the countries with which it shares roots and borders. Socially and demographically, the small state Luxembourg is hyper-diverse and growing rapidly, reflected in science as well Meyer . These cDue to its cultural and political history, the Belgian education landscape is divided into language communities also responsible for higher education and research policies. The two largest communities are Flemish-speaking Flanders and French-speaking Wallonia. A small group of German-speaking Belgians live mainly in Eupen. Brussels, the cosmopolitan European capital, provides a central meeting place for these communities (Dassen and Luijten-Lub Université Libre de Bruxelles and Vrije Universiteit Brussel). In 2003, two public institutions, the University Institute Antwerp (UIA) and the State University Centre Antwerp (RUCA) and the private University Faculty Saint Ignatius Antwerp (UFSIA) were merged to form the University of Antwerp. Students in Flanders can also study at the Dutch Open University in the Netherlands or the Transnational University of Limburg, a cross-border university merger of the University of Hasselt and the Netherlands’ University of Maastricht (van Petegem and Imbrecht Belgium has six state-funded older major universities (University of Liège and Ghent University), Catholic (Catholic University Leuven and Catholic University Louvain) or free .Since 1874, fundamental scientific research has been an exclusive part of universities in Belgium.Regardless of the different structures in parts of Belgium, the majority of Belgium’s scientific output results from centuries-old and newer strong research universities.Situated in the heart of Western Europe, Luxembourg long relied on other countries to provide most higher education and advanced research. While Luxembourg’s capacity in higher education and research has risen rapidly, it remains limited in comparison to the other countries. Luxembourg, like Belgium and France, hosts one of the three European Union capital cities, and thus symbolizes European and global goals. Decision-makers rhetorically support investments in higher education and science, yet national policymakers have recently limited the planned growth of R&D, favoring consolidation. The Bologna process considerably intensified the on-going standardization in European higher education, with Luxembourg signing the declaration years before the University of Luxembourg (UL) was founded (2003)—built upon several organizations that provided teacher training, conducted research, and served national priorities. Scientifically, strategic investments in promising research areas of national priority are meant to compensate being a new, small university Meyer . TransfoLuxembourg’s small, but diverse higher education system is matched by a number of research institutes and medical facilities active in various scientific fields. Consolidation in the publically-funded research sector aims to achieve (even) better results, although given the investment timeframe and the quick rise in productivity, it is too early to conclusively measure the effects of capacity-building efforts. In January 2015, two Public Research Centres—Henri Tudor and Gabriel Lippmann—merged to form the Luxembourg Institute of Science and Technology (LIST), designed to achieve critical mass internally and strong visibility externally. Several years ago, a new contract stipulated that the UL should collaborate with the country’s public research institutes in research areas thought to develop and diversify the economy. The 3LIU consortium includes the University, LIST, Luxembourg Institute of Health (LIH)—a hybrid of the CRP Health and the Integrated Biobank of Luxembourg—and the Luxembourg Institute of Socio-Economic Research (LISER). The research university is the centerpiece of the science system, with strong ties to all the other research institutes and funding bodies, now mainly sharing Campus Belval.The organizational field of research in Luxembourg has grown substantially over time Meyer . Yet theUniversité de la Grande Region) and globally, a key advantage.Although Luxembourg’s policymakers attempt to diversify the economy beyond financial services and to improve R&D infrastructure and bolster conditions for innovation, some question whether the country has sufficiently endowed its university and strengthened its research institutes given European and global competition in tertiary education and science Meyer . The GraWhile the national university is the leading single organization in scientific output in natural sciences, the research institutes and hospitals together produced more articles. Given this duality in terms of research output, Luxembourg’s state-funded science output derives from both pillars, as in Germany and France. We now turn to explicitly compare scientific productivity in the four countries.The over-time and cross-national comparisons emphasize that Germany, France, Belgium, and Luxembourg, as larger and smaller neighboring countries embedded in the EU, have contrasting policies in R&D and varying investments and proportions of scientists of all employees. Their higher education and research systems reflect different institutionalization pathways and combinations of universities and institutes, each organizational form contributing more or less to scientific productivity. In each country, research universities and research institutes (often gathered in umbrella associations) contribute different proportions to overall scientific output, but in all four countries the research universities represent the key organizational form.The total number of SCIE publications for the four countries over the 20th century shows massive increases, especially since the 1970s and again over the past decade. With major differences in scale, Germany and France have increased their output dramatically over the past four decades. Belgium’s production has grown strongly as well, but more evenly. Luxembourg, given its small size and later investments in R&D, must identify particularly promising areas if it hopes to enhance its more qualitative than quantitative contribution to global science. As absolute numbers are difficult to interpret across cases of different size and science capacity, we calculated the scientific output per one million inhabitants see Fig. . This enComparing the absolute production levels of countries historically manifests the dramatic rise of science. The four countries examined here have, since the 1980s, witnessed a veritable boom in the publication of scientific articles in STEM disciplines as well as health. Comparing cases of very different size, we must, of course, acknowledge issues of scale and scope. When analyzing the number of these publications per 1,000,000 inhabitants, we find an even more dramatic rise, especially over the past decade. This productivity measure provides more comparable indicators and also reorders the countries. In contrast to the investments, viewed in “research intensity” Fig. .Our study investigated the contributions of different research organizational forms to scientific productivity. We compared the production of STEM research in four larger and smaller countries in Europe. As presented earlier Fig. , these cOur key finding is that the institutionalization of the research university sector and reliance on it supports high productivity see Fig. . In factExamining four contributors to the European center of science productivity, we found remarkable sustained growth, building on the evolving institutionalization of research universities and institutes and embeddedness in worldwide scientific networks. The elaboration of scientific communication through a world of scientific journals built upon peer-review and rising (inter)national competition and collaboration in STEM fields spur global growth—with Europe still central to global science.lingua franca of English in which research must be reported in leading SCIE journals affect scientific output as well as the attention paid to particular research or the measurement of productivity. More generally, the conditions of the research enterprise and the publication strategies of individual researchers have shifted, with these factors requiring further fine-grained analysis.A surprising result is that the most established and high-volume absolute producers, Germany and France, have been outpaced by Belgium, with small state Luxembourg catching up in scientific productivity per capita (on a much lower level of absolute production). More investment in R&D does not necessarily yield more STEM research in international, English language journals indexed by Thomson Reuters’ Web of Science database, although its coverage is steadily growing. Technological change that facilitates communication and collaboration, internationalization, and the global In investigating what makes these European countries successful in science, we identified the long-term development yet differential elaboration of research universities and research institutes. Turning to these diverse organizational forms, we unsurprisingly find dual pillars of strength in science—research institutes and research universities—in France and Germany, but the dominance of research universities in all four countries. Regarding the unique contribution of universities, this organizational form, despite its relatively modest proportion of funding, remains the key contributor of STEM publications. In contrast to the resource-dependency argument that systems with strong research institutes without teaching obligations and funds primarily devoted to research should be more productive, we show that it is those systems relying on strong university sectors that are relatively more productive.In cross-national and historical comparison, neither solely size of country nor level of R&D investments account completely for the growth of scientific productivity. While newer entrants to the world of science can quickly increase their capacity and productivity by investing heavily in research infrastructure and recruiting talent worldwide, especially the older established universities and associations of research institutes have successfully driven the considerable increase in science production over the last several decades.The exploratory historical and comparative research reported here uncovered not only huge growth historically, but also relatively stable patterns of productivity of the universities within countries, albeit with growth in France and even more in Luxembourg. Next steps in understanding better the publication patterns—not only in the fields of science, technology, engineering, mathematics, and health—include analysis of the size and international networks of communities of researchers, the contributions of various organizational forms in the diverse non-university sector, including firms, and organization-level studies of those most productive organizational forms—most centrally the research university.


Care coordination is a challenge for patients with kidney disease, who often see multiple providers to manage their associated complex chronic conditions. Much of the focus has been on primary care physician (PCP) and nephrologist collaboration in the early stages of chronic kidney disease, but less is known about the co-management of the patients in the end-stage of renal disease. We conducted a systematic review and synthesis of empirical studies on primary care services for dialysis patients.Systematic literature search of MEDLINE/PubMED, CINAHL, and EmBase databases for studies, published until August 2015. Inclusion criteria included publications in English, empirical studies involving human subjects , conducted in US and Canadian study settings that evaluated primary care services in the dialysis patient population.Fourteen articles examined three major themes of primary care services for dialysis patients: perceived roles of providers, estimated time in providing primary care, and the extent of dialysis patients’ use of primary care services. There was general agreement among providers that PCPs should be involved but time, appropriate roles, and miscommunication are potential barriers to good primary care for dialysis patients. Although many dialysis patients report having a PCP, the majority rely on primary care from their nephrologists. Studies using administrative data found lower rates of preventive care services than found in studies relying on provider or patient self-report.The extant literature revealed gaps and opportunities to optimize primary care services for dialysis patients, foreshadowing the challenges and promise of Accountable Care / End-Stage Seamless Care Organizations and care coordination programs currently underway in the United States to improve clinical and logistical complexities of care for this commonly overlooked population. Studies linking the relationship between providers and patients’ receipt of primary care to outcomes will serve as important comparisons to the nascent care models for ESRD patients, whose value is yet to be determined. Overall and disease-specific management and care coordination is a challenge for patients with complex and multiple chronic conditions (MCC), who typically see multiple providers to manage one or more co-morbid conditions. This problem is amplified for patients with kidney disease, whose condition is associated and co-morbid with highly prevalent conditions such as hypertension, diabetes, and heart disease. Much of the literature and intervention efforts have focused on primary care and nephrology physician collaborative care in the early stages of chronic kidney disease (CKD), with an emphasis on primary care physician (PCP) intervention to prevent, detect, treat, and slow the progression of kidney disease. Studies have generally found lack of clarity on the roles and responsibilities of clinical management among providers , poor coHowever, less is known about primary care physician (PCP) and nephrologist co-management of patients in the end-stage of renal disease. Specifically, most patients with advanced kidney failure undergo chronic dialysis treatments and are clinically managed by clinical staff at dialysis facilities on a frequent basis . Due in part to the rigidity of the dialysis treatment schedule, management of co-morbid illness and their complications by providers outside of the dialysis unit is challenging. Patients commonly receive supervision of non-renal health needs during their dialysis treatment visits due to convenience and familiarity. As a result, primary care management may default to renal providers. Compared to early-stage CKD care, this observed focus – of nephrologist involvement in treating primary care needs of patients with end-stage renal disease (ESRD) – raises important questions about the role of the PCP, traditionally considered the patient’s medical home for continuous comprehensive care and the “quarterback” responsible for assessing, balancing, and coordinating the care of patients’ multiple competing conditions , 6. Who Understanding the provision of primary care among nephrologists and PCPs, fragmentation of care, and outcomes in dialysis patients is an emerging and important concern . The antThis literature review is guided by conceptual frameworks for care provided to individuals with MCC  and intedialysis patients as those with ESRD and undergoing chronic dialysis treatment . Primary care is more loosely defined. We adopted the Institute of Medicine’s definition of primary care’s scope of services [providers of primary care services include physicians represented in internal medicine, family medicine, geriatric medicine, general medicine, and nephrology, as well as non-physician providers such as physician assistant, nurse practitioner, and registered nurse. Last, we considered several settings where provision of primary care services take place, including physician offices and clinics of internal, family, and geriatric medicine, nephrology clinics, and dialysis centers.In this review, variables of interest pertain to the provision of primary care services among patients undergoing chronic dialysis treatment. For the purpose of this structured literature review, we conducted a broad search of the two main terms of ‘dialysis’ and’ primary care’, due to the anticipated paucity of published studies in this area. We defined services , which iFrom the published literature, we applied several eligibility criteria for inclusion in critical synthesis of the literature. Publications in English, empirical studies involving human subjects , conducted in US and Canadian study settings and published until August 2015 were included for review. Editorials, letters, and literature review articles, and duplicate citations and publications that did not evaluate primary care services in the dialysis patient population were excluded.Literature included for synthesis were identified using 3 search strategies. The primary approach involved searching MEDLINE/PubMED, CINAHL, and Embase electronic databases for articles related to primary care services for dialysis patients. This search strategy employed numerous Medical Subject Headings (MeSH) and keywords related to primary care and dialysis patients Fig. . EligibiKey information in each article was extracted by 2 reviewers . Data included overall study design, study setting and participants, and key measures. Key variables of interest included the types of providers, primary care services, and outcomes that were assessed or reported and authors’ results.Keyword searches in electronic databases resulted in 13,841 citation hits, of which 10 met inclusion criteria. The large number of excluded citations and papers were largely due to the broad search terminology regarding primary care and prevention. Another 4 relevant articles were identified through backward search methods, resulting in a total of 14 articles regarding primary care services for dialysis patients Fig. .Fig. 2Idn = 13, 93%) and one study was conducted in Canada. Of the 14 articles, there were 9 (64%) studies that conducted cross-sectional surveys or qualitative interviews with providers or patients, 4 retrospective cohort studies, and 2 quasi-experimental interventions . The cross-sectional surveys collected responses from a roughly equal share of nephrologists [n = 3), or data obtained from medical chart review (n = 1) [Characteristics of the studies addressing primary care services for dialysis patients are described in Table ologists , non-nepologists –17 and pologists . Four st (n = 1) –24. No sn = 11 studies), followed by nephrologists (n = 4), and PCPs (n = 3). Interestingly, however, there was less variation among the types of outcomes assessed from the patient perspective, compared to the wider array of provider-oriented outcomes examined. Key measures about or reported by patients included whether patients had or used a PCP [should provide primary care services [Across studies included in this review, the dialysis patient was the most common unit of observation .Among the findings in this literature, we found overall general agreement among providers that PCPs should be involved in primary care of dialysis patients. Despite this agreement, a potential barrier to realizing this may be the adequacy of time for PCPs to provide good primary care to dialysis patients and subsequent incongruent expectation and coordination between provider specialties. At the same time, the logistical barriers to accessing care and time burden of dialysis care for patients are a significant factor, which may also attribute to the majority of dialysis patients relying on primary care services from their nephrologists, despite their report of greater confidence in primary care delivered by non-nephrologist PCPs. These findings generally apply to all dialysis patients, as found in the few studies that explicitly assessed differences between in-center hemodialysis and home-based peritoneal dialysis patients. Although more PD than HD patients report having family practitioner , PD patiAcross studies reported from a variety of patient and provider perspectives, we found varying degrees of consistencies of primary care service delivery and use with important implications on patient outcomes. On one hand, consistent reporting of delivery and receipt of primary care services may reflect accurate reporting across survey respondent types. On the other hand, high provision of care reported by nephrologists and PCPs may also suggest duplicative care. The pooled findings related to overall delivery and receipt of preventive care suggest potential gaps in care, where studies of administrative data found lower rates of preventive care services than found in studies relying on provider or patient self-report. The mechanisms underlying these inconsistent findings is unclear: this may be due to recall bias in self-reported data and potentially incomplete documentation of care in administrative data, but may also highlight discordant expectations and communication between patients, nephrologists, and PCPs that lead to gaps in care. The difficulty in communication between providers  is also Although providers generally agreed that PCPs should be involved in primary care of dialysis patients, the optimal extent of this involvement is unclear. For example, many patients report having a non-nephrologist PCP, but simultaneously report reliance on nephrologists for referrals, counseling, preventive care, symptom and disease management; services that traditionally fall under the expertise of a PCP in the non-dialysis setting. There are no formal guidelines on the provision of primary care for individuals with ESRD, and the clinical benefit and cost-effectiveness of traditional health maintenance in this high-risk population remains controversial , 29. WhiAltogether, these findings highlight opportunities for improvement and have important implications on the amount and quality of primary care that dialysis patients receive and on healthcare policy, as depicted in Fig. While this is an emerging area of concern, it is useful to consider its importance and the findings from the extant literature in the context of changes in the healthcare delivery system for ESRD patients. Aided by improving survival rates, the US is experiencing growing ESRD prevalence and a shrinking nephrology and primary care workforce. Recent system-level interventions, such as Medicare’s managed care program demonstration for ESRD patients and the Comprehensive ESRD Care model aim to reorganize ESRD patient care through the collaboration of dialysis clinics, nephrologists and other US providers. This latter effort has resulted in Medicare-funded ESRD Seamless Care Organizations (ESCO) to improve care coordination and outcomes for Medicare beneficiaries. Thus, the research synthesized here foreshadows the challenges and opportunities for ESCOs to retool structures and processes of care across provider types to improve clinical and logistical complexity of care for patients on chronic dialysis.Future research will want to examine the extent to which singular care is coordinated and communicated across patients, nephrologists and PCPs, as well as ways to optimize such multidisciplinary care for dialysis patients and improve outcomes. The extant literature presented here reveal gaps and opportunities for future research to augment and improve the evidence base. First, there is a paucity of claims-based research. The differential findings of studies based on administrative data versus individual self-reported observational studies, suggest that the truth is probably somewhere in between. Well-designed mixed methods research can examine the impacts of structures and processes of care coordination in a more nuanced way than quantitatively or qualitatively-based studies alone. Second, the studies examined in this review examined a limited set of outcomes in dialysis patients’ primary care. More studies linking the relationship between providers and patients’ use and receipt of primary care to outcomes  will serve as important comparisons to the nascent ESCOs, whose value is yet to be determined.


Laboratory systems worldwide are challenged not only by the need to compete for scarce resources with other sections of national health care programmes, but also with the lack of understanding of the critical role that laboratories play in the accurate diagnosis and monitoring of patients suffering from high-burdens of disease. An effective approach to establishing cost-effective laboratory systems that provide rapid and accurate test results for optimal impact on patient care is to move away from disease-specific programmes and establish integrated laboratory services. An integrated laboratory network provides all primary diagnostic services needed for care and treatment without requiring patients to go to different laboratory facilities for specific tests. Such a network focuses on providing quality-assured basic laboratory testing through the use of common specimen collection, reporting and diagnostic platforms that can be used across diseases. An integrated laboratory system also provides specimen transport to specialised laboratories and an environment conducive to the introduction and use of new and more complex technologies that would benefit the patient population and public health systems as a whole. As such, this article described various strategies for, and practical examples of, the successful integration of laboratory services. This has led to wasted resources because of duplications of equipment and training and inefficient use of human capacity. During this time of increased awareness and programmatic scale-up, it is imperative to establish integrated national laboratory systems to optimise quality, efficient and cost-effective testing.Human immunodeficiency virus (HIV) and/or AIDS, tuberculosis (TB) and malaria remain major threats that undermine the health of global populations and account for approximately five million deaths every year.The demand for laboratory services to meet the diagnostic and treatment needs for HIV has helped drive investment in new and renovated laboratories to provide comprehensive laboratory diagnostic services for monitoring patients on anti-retroviral therapy with CD4, chemistry, haematology, molecular tests such as measuring plasma Ribonucleic acid (RNA) levels, testing of HIV-1 drug resistance mutations and testing for opportunistic infections. However, this expansion and investment in laboratory capacity should be optimised to serve the needs of other diseases of public health importance, provide general diagnostic services to support clinical care and support other public health priorities such as re-emerging infectious diseases and chronic diseases.An integrated laboratory network can be defined as one that has the ability to provide all primary diagnostic services needed for the care and treatment of patients without requiring them to go to different laboratories for specific tests. To meet these requirements the network should, (1) be focused on providing quality-assured basic laboratory testing, (2) use common specimen collection, timely reporting and diagnostic platforms that can be used across diseases within the same facility and (3) increase capacity for introducing and using new and more complex technologies.Integrated systems have several advantages. Firstly, and most importantly, they can support timely and comprehensive care and treatment without the costs and delays associated with referral to specialised facilities for particular diagnostic exams. An integrated system can benefit patients and clinical staff at hospitals located in urban centres, as well as patients served at the community level in remote areas. Secondly, new diagnostic platforms, such as microscopes with dual light and fluorescent capacity and molecular diagnostic equipment, have the potential to perform assays for more than one disease. An integrated laboratory approach will ensure that these tools can be used optimally by cross-trained technical staff. Thirdly, integrating diagnostic services for different diseases within the same facility helps avoid duplication of investments in infrastructure and laboratory supporting systems, such as specimen transport, supply chain management and information systems. Lastly, an integrated approach to training can help ensure standardisation of core laboratory issues, such as quality assurance and standard operating procedures, as well as ensure the more efficient delivery of training. The examples below show how these approaches are both practical and successful.Laboratory systems in resource-poor countries are challenged by, (1) dilapidated infrastructures, (2) lack of funding for developing and implementing national policies, strategic planning, and quality management systems, (3) unlinked referral and reporting services and (4) inadequate human resources, including lack of organised in-service training and long-term career pathways. The difficulty of dealing with all these challenges separately by each programme should provide sufficient reason to encourage integration of services. However, overcoming the traditional vertical approach in which higher level public health laboratories have been established to provide support for disease-specific ministerial directorates and programmes has proven difficult. Furthermore, an unintentional negative effect of the disease-specific approach to laboratory strengthening has been the neglect of the core public health laboratory functions. Most often, integrated laboratory services are usually found only at the district, sub-district and primary health centre levels. However, establishment of parallel laboratories within a national health care system is neither cost-effective nor conducive to efficient and coordinated patient care.Integration of laboratory systems and services at different levels of the health system will ensure optimisation of the investments in laboratory-system strengthening by Ministries of Health, as well as those of international donors, such as the Global Fund to Fight AIDS, TB, and malaria, the World Bank, the US President’s Emergency Plan for AIDS Relief (PEPFAR), and others. In the past, donor funding mechanisms have contributed to the fragmentation of laboratory capacities because they usually have been earmarked for disease specific efforts; although, recently, there is a trend towards greater flexibility. Various strategies for integration are outlined in the subsections below.8National laboratory systems  must be capable of providing accurate, timely and cost-effective testing that is in line with each country’s programmatic goals and available clinical interventions. It is necessary to define at which level of a national laboratory network certain services or diagnostic platforms should be performed. These decisions should be based on testing complexity, throughput, specimen referral requirements and the needs of the public health programme and patient population being served. Laboratories are complex systems that include components such as personnel, equipment, supplies and infrastructure, as well as support systems for information management, purchasing and inventory, and systems for evaluation and continuous improvement, such as internal and external quality assessment and occurrence management. Developing and implementing a national laboratory policy and strategic plan that ensures integrated capacity at each level of the network can enable countries to work with partners and donors in defining specific objectives, setting standards and allocating appropriate funding and personnel for sustainable laboratory services.9 This approach requires strong leadership and coordination by the local ministries, along with partner and donor compliance, and includes many benefits, such as reduced procurement costs for commodities, easier implementation of quality assurance programmes and integration of multi-focused testing that uses shared equipment. For example, partners could work together in developing specialised facilities that would accommodate instruments for molecular diagnostics of TB, HIV and other diseases, rather than building separate labs dedicated to only one disease. Training, equipment maintenance and quality management systems could be standardised to allow technicians to work using similar techniques across diseases. Joint coordination amongst partners at the onset of a laboratory-related project could enable each partner to play a preferred role in areas where they have a relative advantage or expertise.Laboratory infrastructure, test menus, technology, platforms and commodities should be standardised in each country to avoid duplication, as agreed upon by programme and laboratory representatives from 13 resource-poor countries in the Maputo Declaration of 2008.10Strengthening of national laboratory systems depends on close partnerships – beyond the laboratory facility itself – with technical and clinical professionals, healthcare managers at the community, regional and national levels, and public health programmes. Clinicians should support, facilitate and demand high-quality and responsive laboratory support for appropriate patient care. Clinicians should also be involved in ensuring that testing algorithms are cost-effective, are based on sound evidence and have a relevant impact on clinical decision-making and patient-important outcomes.There are two basic aspects to implementing integrated services within laboratories. The first is focused on provision of adequate services for patients presenting with particular clinical symptoms indicative of major infectious diseases. For example, an integrated laboratory should have the capacity to adequately monitor HIV-positive individuals for TB, malaria, or other opportunistic infections, or to provide rapid molecular testing for multi-drugresistant TB (MDR TB) in HIV and TB co-infected patients in order to improve infection control and treatment outcomes . ConversThe second aspect focuses on the establishment of integrated diagnostic platforms or instruments that can be used for a variety of tests. The simplest example can be an integrated system for collecting and transporting specimens for TB and HIV testing or monitoring. A further step can be the integration of microscopy testing for TB, malaria and other parasitic pathogens. The most promising approach for cross-cutting disease testing is offered by the molecular platform. Polymerase chain reaction (PCR) molecular testing can be used to detect rapidly and identify a wide range of viral and bacterial pathogens, including those that cause endemic diseases such as HIV, TB and malaria, and emerging infectious diseases such as new strains of influenza.In 2006, a state of the art bio-safety level (BSL)-2 central laboratory was established at the Ethiopian Health and Nutrition Research Institute (EHNRI) in Addis Ababa through PEPFAR funding to support the laboratory diagnosis of HIV patients. Since then, technical support has been provided by international partners to help establish testing and training capacity for HIV serology and external quality assessment (EQA), HIV incidence, CD4 counts, biochemistry, haematology and molecular testing for viral load and early infant diagnosis (EID). Beginning in 2008, support was provided through the Foundation for Innovative New Diagnostics (FIND) to create two BSL-3 TB testing laboratories in Addis Ababa: the first at the HIV laboratory at EHNRI, to host the National Reference Laboratory for Tuberculosis (NRLT), and the second at St. Peter’s Hospital, a central hospital responsible for the care of TB and HIV co-infected patients experiencing TB treatment failure or relapse. The testing capacity of the two laboratories now includes liquid and solid growth detection and drug susceptibility testing for TB, lateral-flow immuno-assay for identification of TB and rapid detection of MDR TB by the molecular line probe assay (LPA). The newly renovated molecular unit at St. Peter’s will also be used to restart HIV viral load testing at the hospital, a function that had been stopped in the past because of problems related to inadequate infrastructure for molecular testing. In addition, molecular LPA testing for MDR TB will soon be introduced in four Ethiopian regional laboratories that are currently performing HIV DNA PCR for EID.11 Services provided by the laboratory network include HIV rapid tests, adult CD4 counts, paediatric CD4 percentages, haematology, blood chemistries, syphilis serology, cryptococcal antigen test, TB smear microscopy, culture, drug susceptibility testing (DST), and molecular LPA. Use of appropriate technology at all service levels and a robust quality assurance programme provide high quality integrated laboratory services.In Nigeria, a multifaceted, integrated, tiered laboratory programme has been established by the Institute of Human Virology at the University of Maryland to support a PEPFAR-funded scale-up of AIDS care and treatment in 26 states.12 Then TB LPA and HIV DNA PCR were implemented in an adjacent, newly constructed clean-room facility, resulting in the establishment of integrated TB and HIV testing in a single facility. By using an integrated approach, implementation of novel molecular TB diagnostics paved the way to introduce HIV molecular testing capacity in the country.The National TB Reference Laboratory (NTRL) located at the Queen Elizabeth II Hospital in Maseru, Lesotho, was renovated by FIND and other partners to provide capacity for TB culture and molecular diagnostics. Following strengthening of TB smear microscopy testing through training and the establishment of a quality assurance programme, the NTRL was first renovated to create a BSL-3 facility to implement TB culture, DST and rapid immunoassay-based identification of TB, with EQA provided from South Africa.13 Planning is ongoing for the provision of support for localised outbreaks of H1N1 (swine) influenza.Molecular HIV laboratories in Africa have been called on to respond rapidly to laboratory surveillance for outbreaks of avian influenza. During the 2005 outbreak of avian influenza, the PEPFAR-supported Global AIDS Program laboratory in Entebbe, Uganda, provided training for about 60 laboratory experts on the use of PCR diagnosis for avian influenza. Also in 2006, the PEPFAR-supported laboratory at Asokoro Hospital in Abuja, Nigeria, was instrumental in providing diagnostic support for an investigation of an avian influenza outbreak in Nigeria.The African Centre for Integrated Laboratory Training (ACILT) was established in 2008 to develop and offer hands-on training courses for front-line laboratory staff. ACILT’s vision is to provide for a healthier Africa through quality laboratory practices to combat major infectious diseases. Hosted by the South African National Institute for Communicable Diseases and the National Health Laboratory Service, ACILT has a governance board consisting of experts from collaborating international institutions.Before establishing ACILT, needs assessments were performed in 10 resource-poor African countries to determine which topics would be most important for building capacity amongst laboratory personnel. Courses were then developed collaboratively by ACILT and international partners including the US Centers for Disease Control and Prevention (CDC), FIND and the World Health Organization to ensure standardisation. As of early August 2011, 720 participants from 29 countries had participated in more than 20 hands-on training courses covering: HIV DNA PCR for EID, HIV incidence assay, TB culture and identification, EQA for HIV rapid testing, national laboratory strategic planning, biosafety, laboratory management, and laboratory accreditation.ACILT satellite courses are offered at sites outside of South Africa. A two-week course on TB culture and drug susceptibility testing was recently offered to South-East Asian participants in Bangkok and one-week courses on the molecular LPA testing for MDR TB have been hosted by the new laboratory facility at EHNRI, at the National TB Reference Laboratory of Lesotho, and at the Institut Pasteur in Abidjan, Côte d’Ivoire. ACILT TB culture and molecular LPA course materials have also been translated into French and Portuguese through a partnership with the American Society for Microbiology.An integrated network of laboratories is indispensable for providing national support for global health initiatives for HIV, TB, malaria and other public health priorities. However, an integrated national laboratory network should be able to provide all needed primary diagnostic services for patients at each level of service without requiring patients to go to different facilities for specific tests. Such laboratory services might be delivered either directly at defined levels of the network or indirectly by using an integrated specimen collection, referral and reporting system. The extent of integration at different levels of the laboratory system should always be based on the complexity, throughput and specimen referral requirements of the particular diagnostic platforms. Last but not least, an integrated system allows increased capacity and preparedness for implementation of new technologies to improve the quality of current diagnostics and to address newly emerging public health concerns. This article has presented examples to demonstrate how some resource-limited countries have benefited from an integrated approach for clinical laboratory strengthening. These strategies could be replicated more broadly.


Low-dose, high-frequency (LDHF) training is a new approach best practices to improve clinical knowledge, build and retain competency, and transfer skills into practice after training. LDHF training in Ghana is an opportunity to build health workforce capacity in critical areas of maternal and newborn health and translate improved capacity into better health outcomes.This study examined the costs of an LDHF training approach for basic emergency obstetric and newborn care and calculates the incremental cost-effectiveness of the LDHF training program for health outcomes of newborn survival, compared to the status quo alternative of no training. The costs of LDHF were compared to costs of traditional workshop-based training per provider trained. Retrospective program cost analysis with activity-based costing was used to measure all resources of the LDHF training program over a 3-year analytic time horizon. Economic costs were estimated from financial records, informant interviews, and regional market prices. Health effects from the program’s impact evaluation were used to model lives saved and disability-adjusted life years (DALYs) averted. Uncertainty analysis included one-way and probabilistic sensitivity analysis to explore incremental cost-effectiveness results when fluctuating key parameters.For the 40 health facilities included in the evaluation, the total LDHF training cost was $823,134. During the follow-up period after the first LDHF training—1 year at each participating facility—approximately 544 lives were saved. With deterministic calculation, these findings translate to $1497.77 per life saved or $53.07 per DALY averted. Probabilistic sensitivity analysis, with mean incremental cost-effectiveness ratio of $54.79 per DALY averted ($24.42–$107.01), suggests the LDHF training program as compared to no training has 100% probability of being cost-effective above a willingness to pay threshold of $1480, Ghana’s gross national income per capita in 2015.This study provides insight into the investment of LDHF training and value for money of this approach to training in-service providers on basic emergency obstetric and newborn care. The LDHF training approach should be considered for expansion in Ghana and integrated into existing in-service training programs and health system organizational structures for lower cost and more efficiency at scale. In the last 2 decades, under-5 mortality rates have declined by nearly 50% and the rate of decline has increased over the last decade, largely due to increases in coverage and access to essential reproductive, maternal, newborn, and child health (RMNCH) services . DespiteGhana has sought to increase access to and affordability of key RMNCH services by expanding national health insurance and providing free maternal care . DespiteClinical care quality is strengthened by increased knowledge, acquired skills, and peer consultation; training in many forms has long been utilized to improve clinical performance and, consequently, RMNCH outcomes . The besLow-dose, high-frequency (LDHF) is an approach to improve the in-service training model to better enhance the health workforce capacity, sustain health provider gains in knowledge and skills, and help learners translate clinical lessons into practice . The conThis study examines programmatic costs and health effects, calculated by DALYs averted, of LDHF training on institutional stillbirth rates and on newborn survival outcomes of 40 facilities included in the impact evaluation in three regions of Ghana from 2014 to 2017 and compares the incremental cost-effectiveness of LDHF training with the alternative of no training (the status quo).Of the 24.7 million people that live in Ghana, 21.4% are in the Central, Western, and Upper West regions where the LDHF training program was jointly planned with the Ghana Health Service and Ministry of Health and coordinated so as not to overlap with existing programs . In 2011The LDHF training program was adapted from a 2-week classroom-based basic emergency obstetric and newborn care (BEmONC) package to two 4-day low-dose onsite trainings. The LDHF trainings incorporated high-quality onsite instruction with a whole-team perspective, clinical simulation-based practice with models, mentorship and coaching, and a daily lunch. Following the LDHF trainings, content is reinforced through high-frequency mentorship: individual phone calls between regional GHS master mentors (MMs) and trainees, peer practice with medical models in the facility, and text message reminders and quizzes. Nongovernmental organization (NGO) staff contacted the trained MMs, peer practice coordinators, and providers to ensure mentoring and practice were continuing after the LDHF onsite training and also monitored the mobile messaging system to make sure text messages sending appropriately. In contrast to traditional training models, which train a small subpopulation of health workers outside of the clinical setting, in the LDHF model all midwives and nurses providing labor, delivery, and immediate postpartum care at a participating facility have the opportunity to receive the same training.Program activities are understood through three phases: Development—adaptation of the curriculum from workshop to LDHF training approach; Startup—planning and conducting MM trainings, health information officer trainings, and regional health team meetings; and, finally, Implementation—organizing and conducting LDHF trainings in two main sessions (LDHF1 to cover basic care and LDHF2 for complications) with provider knowledge and skills assessments, and initiating mobile mentoring (mMentoring) and peer practice. Additional details on the program and health effects measurement are found in the Accelerating Newborn Survival project impact evaluation . A full Assuming a 3-year analytic time horizon corresponding to the program’s length, data on economic costs were collected for all program activities based on a review of program financial records, including purchase orders, original receipts kept on record in the finance department, and recurring overhead allocation reports. Cost details were confirmed and supported by interviews with the LDHF implementation team, especially important because many program costs were summarized and reported at the regional rather than the activity level. Personnel salaries were increased per fiscal year based on informant interviews and human resources records, and applied monthly to appropriate phases during which staff were supporting the program. Market prices or regional price averages were used to value the furniture, equipment, and other resources used by LDHF program staff. Operating costs were included for each phase, by time period and value of personnel effort, building space, maintenance and utilities, and furniture and equipment used by the LDHF training program.Development costs included costs associated with adapting the BEmONC curriculum, including personnel time and editing services to develop the learning resource package of materials: facilitator and learner manuals, slides for instruction, and standardized assessments. Startup costs included all inputs related to regional health team meetings and trainings for health information officers and MMs. The main inputs were transportation, program staff per diem and resource personnel fees, and food and lodging costs associated with the necessary travel. Implementation costs included all inputs related to the LDHF trainings and mMentoring follow-up. These similarly included transportation, personnel, and accommodations costs but also trainee-associated costs of lunch and training materials as well as equipment and expendables costs for simulation-based trainings, including practice models of MamaNatalie™ and NeoNatalie™, medical equipment, examination gloves, face masks, and cleaning supplies.Key cost model assumptions are as follows: 1) once averaged from multiple data sources or direct from one single and validated source, a cost is stable and representative of further repeated activities at the facility or regional level, 2) key development and startup costs such as curriculum development were allocated across all facilities that received LDHF training, 3) personnel time and salary cost were measured monthly and then averaged based on the corresponding timeline of each LDHF program phase so as to have one personnel cost for each staff member during each phase, 4) expendable training items are costed based on either facilities or region depending on rate of use and reusability as informed by the LDHF clinical training team. The program costs collected represent Jhpiego’s LDHF training program reach to three regions, 40 facilities, and 428 health workers receiving training.The impact evaluation of the LDHF training intervention on newborn survival measured health effects by tracking institutional newborn mortality within 24 h of birth or until discharge and institutional intrapartum stillbirths; indicators were tracked at the facility with supplemental registers in 1-month increments and pooled as 6-month average rates . Each trDisability-adjusted life years (DALYs) were calculated in this analysis using estimated lives saved, average life expectancy in Ghana, no age weighting, omitting years lived with disability (YLD), and discounting at 3% so as to discount health effects at the same rate as costs . Unlike The cost and health effect data were collected from existing records from the implementation of the LDHF training and from the impact evaluation; the cost-effectiveness analysis using this data was determined nonhuman subjects research by the Johns Hopkins Bloomberg School of Public Health Institutional Review Board.The analysis of cost data was conducted in Excel. All costs are presented in 2015 US dollars. All capital costs are discounted at 3% and one-time development and startup activities annualized for the analytic time horizon of 3 years, matching the actual program timeframe . The actTo determine the incremental cost-effectiveness of program activities, a simple decision tree was created using TreeAge Pro 2017 software comparing incremental cost and effects of LDHF training to no training . Base caAs part of sensitivity analysis, we tested model variations and developed a major set of modifications through discussion with the LDHF program team to explore sustainability and changes in the LDHF program activities if continued or implemented within the Ghana health system. Assumptions were tested together to assess the cost of the essential activities of the LDHF training program implementation in a sustainable scenario that maximizes efficiencies. This Essential LDHF Program scenario was then compared to a traditional BEmONC workshop training hosted by the Ghana College of Nurses and Midwives (GCNM). The GCNM conducted three workshops on BEmONC targeting educational institution tutors and their teaching facility lead clinical preceptors. Two-week-long workshops were conducted in Accra and Kumasi: one week of classroom-based learning and a second week of field site coaching and hands-on experience, both facilitated by GCNM staff and guest trainers. Follow-up was conducted mainly via phone calls to all trained providers; however, one onsite follow-up visit was conducted to create a case study of how the training had influenced the participating providers. Costs were collected for the traditional workshop with the same methods used to collect the LDHF training costs.The full cost of the LDHF training program for all 40 facilities over the 3-year analytic time horizon in three regions was $823,134. The mean total cost per facility was $20,578 including $114 for development , $695 for startup , and $19,769 for implementation . As an average of 11 health care providers participated at each facility, the total program mean cost per provider trained is $1974.Personnel  and the LDHF trainings held as two separate facility-based visits were the major drivers of the program costs: 20% of overall cost for LDHF1 and 14% for LDHF2 . This enhances the base capacity of many providers and the facility as a whole, rather than sole reliance on a single trained colleague who may or may not be present when needed.The LDHF program and lessons learned directly support Strategy 6, “Improving the capacity of facility-level health workers to address newborn care,” as set forth in the National Newborn Health Strategy and Action Plan 2014–2018 by the Ministry of Health, Ghana . ThroughHow do we judge the value for money of this new approach? The impact evaluation of the LDHF training showed that this approach led to increased competency, retained knowledge and competency at 1 year, and associated health effects of decreased newborn deaths and stillbirths at the facility . These eWe tested the model with univariate, multivariate, and probabilistic sensitivity analyses to better understand how our results would change in relation to changes in key parameters. The cost-effectiveness results were mainly affected by changes in effectiveness of the LDHF training program in improving newborn health outcomes, changes to personnel structures or salaries, or changes to LDHF training costs. In the multivariate deterministic calculation of best case and worst case, the cost per DALY averted ranged from $19.09 to $149.08; in the probabilistic sensitivity analysis, the mean cost per DALY was very similar to the base case but the range was slightly smaller, $24.42–$107.01. All scenarios simulated to test incremental cost-effectiveness of LDHF training compared to no training were highly cost-effective when assessed with the threshold of GNI per capita, $1480 in Ghana in 2015 .Lancet priority-setting article of 2006, low-cost opportunities for sub-Saharan Africa in MNH care interventions—such as increasing primary care coverage, care quality, and targeted neonatal packages—range from $82 to $409 per DALY averted [In a  averted . The LDH averted , 42. Gha averted , 44. As  averted , 46. We The most common alternative training is an offsite BEmONC classroom-based workshop; we conducted a cost analysis of such workshop trainings led by the GCNM in Accra and in Kumasi. The GCNM workshops targeted midwifery tutors from pre-service educational institutions across Ghana whereas Jhpiego’s LDHF program targeted midwives practicing in hospitals. For this reason, as well as other confounding variables relative to the assessments and aspects of the respective institutions, health effects of the traditional BEmONC training were not evaluated or pursued for inclusion in the cost-effectiveness analysis. Comparing program costs alone still contributes by clarifying differences in key program activities and the associated costs as well as measuring efficiency when considering total cost per trainee between the workshop and LDHF training. One of the major distinctions between LDHF and workshop-based approaches is that many staff present at the facility can be trained in LDHF whereas one or two representatives from a facility are typically trained in a workshop-based training.Other new training methods for maternal, newborn, and child health care improvement have been studied, though few connect this training with associated health outcomes. One such program implemented in seven states of South Sudan had several critical components in common with Jhpiego’s LDHF training in Ghana: an 8-day training course for local trainers, a shorter course for trainees, use of mannequins for training, and reusable medical equipment left for newborn resuscitation and care. Over 2 years, this program trained 708 frontline health workers with a sustained improvement of 40.4% in maternal objective structured clinical examination (OSCE) scores and 3.1% in newborn OSCE scores at the time of 2-month follow-up and resulting increased referral rates . Though The major limitation was a lack of a comparison group of facilities trained with the alternate approach, a BEmONC traditional workshop, in the same time period, for which the same health outcomes could be measured. Although a GCNM BEmONC workshop covered the same training content as the LDHF program during the same time period, the fundamental differences in facility and trainee characteristics rendered any comparison of facility health outcomes invalid. Jhpiego and the Ghana Health Service coordinated to minimize any MNH trainings that could be potential confounding factors to the impact of the LDHF approach; although a few sporadic trainings may have taken place, no trainings with hands-on practice, follow up, and mentoring were recorded during the timeframe . Future The LDHF approach to training presents a unique opportunity to build lasting capacity for cadres of frontline health workers that currently receive only basic training. These are the same health providers who may not usually be selected for workshop training programs due to lack of experience or seniority in the facility; arguably, these frontline health workers have the most need to engage with trainers and are most likely to provide care to patients regularly. LDHF responds to this need and—quite literally—meets providers where they are in order and helps them achieve outstanding gains in knowledge and competency, retain that capacity, and use their skills and expertise in effectively improving MNH outcomes.At $53.07 per DALY averted, this intervention is highly cost-effective when considered with several critical cost-effectiveness thresholds and represents good value for money in Ghana. To accelerate progress toward SDG 3, LDHF training for basic emergency newborn and obstetric care should be considered for adoption and scale-up by the GHS and other implementing partners. Additional modifications building on lessons learned from cost modeling have potential to make the LDHF training program more efficient in future implementations.


Mobile health  is the use of mobile communication technologies to promote health by supporting health care practices . mHealth technologies (such as mobile phones) can be used effectively by health care practitioners in the distribution of health information and have the potential to improve access to and quality of health care, as well as reduce the cost of health services. Current literature shows limited scientific evidence related to the benefits of mHealth interventions for breast cancer, which is the leading cause of cancer deaths in women worldwide and contributes a large proportion of all cancer deaths, especially in developing countries. Women, especially in low- and middle-income countries (LMICs), are faced with low odds of surviving breast cancer. This finding is likely due to multiple factors related to health systems: low priority of women’s health and cancer on national health agendas; lack of awareness that breast cancer can be effectively treated if detected early; and societal, cultural, and religious factors that are prevalent in LMICs. The proposed systematic review will examine the impact of mHealth interventions on breast cancer awareness and screening among women aged 18 years and older.The objectives of this study are to identify and describe the various mHealth intervention strategies that are used for breast cancer, and assess the impact of mHealth strategies on breast cancer awareness and screening.Literature from various databases such as MEDLINE, EMBASE, PsycINFO, CINAHL, and Cochrane Central Register of Controlled Trials will be examined. Trial registers, reports, and unpublished theses will also be included. All mobile technologies such as cell phones, personal digital assistants, and tablets that have short message service, multimedia message service, video, and audio capabilities will be included. mHealth is the primary intervention. The search strategy will include keywords such as “mHealth,” “breast cancer,” “awareness,” and “screening,” among other medical subject heading terms. Articles published from January 1, 1964 to December 31, 2016 will be eligible for inclusion. Two authors will independently screen and select studies, extract data, and assess the risk of bias, with discrepancies resolved by dialogue involving a third author. We will assess statistical heterogeneity by examining the types of participants, interventions, study designs, and outcomes in each study, and pool studies judged to be statistically homogeneous. In the assessment of heterogeneity, a sensitivity analysis will be considered to explore statistical heterogeneity. Statistical heterogeneity will be investigated using the Chi-square test of homogeneity on Cochrane's Q statistic and quantified using the I-squared statistic.The search strategy will be refined with the assistance of an information specialist from November 1, 2017 to January 31, 2018. Literature searches will take place from February 2018 to April 2018. Data extraction and capturing in Review Manager  will take place from May 1, 2018 to July 31, 2018. The final stages will include analyses and writing, which is anticipated occur between August 2018 and October 2018.The knowledge derived from this study will inform health care stakeholders, including researchers, policy makers, investors, health professionals, technologists, and engineers, on the impact of mHealth interventions on breast cancer screening and awareness.Prospero registration number CRD42016050202 Mobile health  is a component of electronic health  and involves the use of mobile communication technologies to promote health by supporting health care practices  . mHealthThe mobile devices or technologies applied to health include mobile phones as well as smartphones, tablets, portable media players, and their mHealth apps . The groWE-CARE, which is an intelligent telecardiology system using mobile 7-lead electrocardiogram devices [PIERS on the Move is a low-cost, easy-to-use application for accurately predicting the risk of adverse outcomes associated with preeclampsia in pregnant women [MEDITECH allows access to clinical data including lab results, vital signs, intake and output, allergies, active medications, and documents (reports and notes) on a smartphone [Wireless System for Emergency Responders is an application for emergency medical service specialists that identifies chemical and biological hazards on the basis of symptoms and signs by providing access to the National Library of Medicine (NLM) Hazardous Substances Data Bank radiological and biological substance report [mHealth applications also contribute to improvements in health care through diagnoses, monitoring, and/or treatment. One application developed for use in treatment is  devices . Anothernt women . MEDITECartphone . Wirelese report .Breast cancer is the most common cancer in women worldwide, with an estimated 1.67 million new cases diagnosed in 2012 . Most woEvidence has shown that intervention by health care practitioners can be effective in improving awareness, knowledge, attitudes, and screening practices for early detection of breast cancer among women . CurrentSeveral mHealth intervention strategies have been implemented to address breast cancer. One example is an investigation of the effect of mHealth with pedometer use on function and quality of life (QOL) among breast cancer patients . The resCurrent evidence supports the use of mHealth for addressing cancer broadly. Our intention is to systematically review the literature to aid us in assessing the impact of mHealth on breast cancer screening and awareness. The study examines the impact of mHealth technology as an intervention on breast cancer awareness and screening attendance of women, compared to conventional interventions that promote awareness and screening.This manuscript adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Protocols (PRISMA-P) 2015 checklist as a condition of submission for systematic review protocols . This prThe study design for this review will include randomized and nonrandomized studies. Nonrandomized studies will include case-control, cohort, and cross-sectional studies in which mHealth was the primary intervention used for breast cancer awareness and screening.Study participants will be women aged 18 years and older. All races, ethnicities, employment statuses, occupations, and roles of women in the reviewed studies will be eligible for inclusion.The relevant mHealth interventions to be included in the study should focus primarily on positively impacting breast cancer awareness and screening. mHealth interventions for health care consumers (women >18 years of age) have been designed to increase healthy behaviors  or increase hospital attendance  . The intThe technology used for mHealth includes mobile devices that have cellular communication capabilities that allow for wireless and/or 3G/4G capabilities. These devices include: mobile phones , PDAs and PDA phones, tablets, mobile/smart phone apps, ultra-portable computers, and smart books ,26.The mHealth functions that will be considered comprise voice over Internet protocol (VOIP), SMS, text messaging, MMS, email, social media, and Internet . Some mHThe impact of mHealth interventions on breast cancer awareness and screening will be assessed by reviewing: (1) increased attendance at breast cancer clinics; (2) the stage of breast cancer when diagnosed, as this would assist in determining whether mHealth has promoted early detection and screening; and (3) increased breast cancer enquiries via call centers, online forums, and social media.User acceptability will not be assessed as an outcome. Breast cancer awareness in this study is described as the ability to be fully informed and knowledgeable of the breast cancer disease . In addiThe setting of the study will not be limited by geographic location. All continents, countries, and health facilities where mHealth research on breast cancer was conducted will be included. This approach allows for all relevant information sources to be captured.The following study types will be excluded from the review: (1) all studies on male breast cancer, due to the rarity of this disease in men; (2) breast cancer detection and treatment studies; (3) studies not performed on human subjects; (4) studies reported before January 1, 1964 and after December 31, 2016; (5) letters, reviews, commentaries, and editorials; (6) studies lacking primary data and/or explicit method description; (7) non-English studies and publications; and (8) duplicate studies that are published in more than one report (the most comprehensive and up-to-date version will be used).While the earliest keyword “mobile health” was identified in the literature in 1991 by Casson and Leder , relevanOther databases to be considered within the study scope and objectives will include trial registers, SpringerLink, Wiley InterScience, Institute of Electrical and Electronics Engineers, Association for Computing Machinery Digital Library; and CiteSeer . For triThe search strategy will include key terms, as detailed in Manual searches of reference lists of primary studies included in the review, and the reference lists of relevant and previously published reviews, will be undertaken. Full text articles of the studies extracted from the reference lists will be reviewed. Unpublished studies will be identified from universities and other databases, and the same eligibility criteria will be applied.The first author will retrieve all the relevant articles from the various databases, based on the finalized search strategy. All of the literature obtained will be saved using reference management software. Two contributing authors will independently screen the titles and abstracts of retrieved studies for eligibility. These authors will make a final assessment for inclusion using the full text article, and discrepancies and disagreements will be resolved by the third author.A data extraction form will be used for the extraction of key information, including: (1) country of study setting; (2) type of participant/study population/demographic characteristics ; (3) type of mHealth device used ; (4) method of communication ; (5) nature of the mHealth intervention; (6) type of study ; (7) type of outcomes measured; and (8) findings/results.If discrepancies are identified when extracting data, these will be discussed by the first two authors. If no consensus is reached, the third author will mediate. Missing data will be requested from study authors via email . If we rTwo authors will use the recommendations by the International Cochrane Collaboration  to indepA descriptive synthesis will be undertaken in accordance with the Centre for Reviews and Dissemination . The chaMean differences and standard deviations will be calculated for continuous outcomes. Ratios and their corresponding 95% confidence intervals will be determined for dichotomous outcomes. Participants, interventions, and outcomes of each study will be examined to ascertain heterogeneity. Data will be pooled; if the collected data is sufficiently similar, a meta-analysis will be conducted. However, if the variability between studies is high the results will not be pooled and a narrative synthesis will take place.2) test which quantifies heterogeneity; this test will allow for the quality of the evidence to be validated [The statistical software Review Manager  will be utilized to capture the data and perform the meta-analysis. The statistical test for heterogeneity includes the I-squared  to investigate possible sources of heterogeneity. The second analysis will determine how excluded studies could have influenced the overall result. The third analysis will be to determine how the result would differ should only high-quality studies be included .The sourcing of literature in accordance with the inclusion and exclusion criteria of the study is underway. All data extracted are grouped under the various headings as specified in the data extraction form . It is anticipated that the review will be completed in mid-2018.This review will identify and describe the impact of mHealth interventions for breast cancer awareness and screening on women of aged 18 years and older. The findings of the systematic review will inform the design of mHealth interventions for breast cancer. Furthermore, the study will highlight which mHealth technology modalities  are appropriate for the target audience when creating awareness of breast cancer.The datasets used and/or analyzed during the current study will be available from the corresponding author upon reasonable request.