Background: Despite the importance of inclusive employment, described in Goal 8 of the Sustainable Development Goals (SDGs), employment of persons with psychiatric disabilities in Africa is lower than among the general population.Objective: The aim of this scoping review is to explore evidence related to the barriers to and facilitators of employment of persons with psychiatric disabilities in Africa.Methods: A literature search was conducted using six relevant electronic databases of articles published between 1990 and 2017.Results: Eight studies were identified and analysed regarding barriers and facilitators of employment of persons with psychiatric disabilities. The dynamic adaptation of the bio-psycho-social model was used as an analytical framework. Identified barriers include ill health, (anticipated) psychiatric illness, social stigma and discrimination, negative attitudes among employers and the lack of social support and government welfare. Facilitators of employment include stability of mental illness, heightened self-esteem, a personal decision to work despite stigma, competitive and supported employment, reduction in social barriers/stigma and workplace accommodations.Conclusion: Employment of persons with psychiatric disabilities is essential, yet there is dearth of scientific evidence to identify contextual models that might be useful in African countries and other low-and middle countries (LMICs). This gap in information would benefit from further research to improve the employment rates of persons with psychiatric disabilities in Africa. Worldwide, employment rates among people with psychiatric disability are significantly lower than those of general population and even of individuals with other types of disabilities ,2. AccorSuch an employment gap between people with a mental disability and the general population can only partially be explained by the disorder; true employment rates may be masked by stigma and discrimination that are closely associated with mental health issues . These oWhen discussing mental health-related disabilities, it is important to highlight the lack of consensus on what constitutes mental disability. Severe mental illnesses such as schizophrenia, bipolar disorder and schizoaffective disorders are major causes of mental disability . Also, gIn order to be able to influence the employment rates of people with mental health disabilities, it is important to have an overview of existing barriers and known facilitators. Among the known barriers are: illness-specific factors, discriminatory attitudes among employers, lack of education and skills, and the failure to implement government provisions and recommendations for employment of persons with disabilities . To overAlthough there are evidence-based studies on barriers to and facilitators of employment of persons with a mental disability in HICs ,12,14, fThe issue of employment of individuals with a psychiatric disability can be influenced by a wide range of factors, of which some are linked to the individual in question, namely sex , age, spBeyond the original three elements – biological , psychological  and interpersonal  – the model adds the contextual aspects  and specifically focuses on the way the four groups influence each other and the person’s health. Moreover, it takes a developmental perspective on the elements, taking into account that they change over time, and hence are referred to as ‘dynamics’.The review was conducted using the Joanna Briggs Institute (JBI) Methodology for Scoping Reviews . The objA systematic search was undertaken across six relevant databases  on 9 March 2017. An updated search was conducted in September 2017. The search terms were based on the synonyms of: mental/psychiatric disabilities; employment; and a list of all African countries. Boolean operators AND; OR and NOT were used to construct the syntax see . All relThe initial search yielded 3771 papers and this was reduced to 2890 after eliminating 911 duplicates. Title and abstract screening was conducted using the predefined eligibility criteria  by IDE aTo synthesize the collected evidence, an extraction table was created. The following items were included: author, year of publication, study setting (including country), study design, study population, sample description and setting, main findings and limitations. The extraction was conducted by IDE and reviewed together with EVS BJR and JFGB. A summary of the data extraction is presented in Once data extraction had been completed, a narrative synthesis  was undeEight studies were included in the analysis. We observed a dearth of studies on the barriers to and facilitators of employments of persons with psychiatric disabilities in African countries. The identified studies had a varied, yet relatively limited, geographical range: three each were from Nigeria –31 and SMethodologically, six of the studies were quantitative: five had a cross-sectional design –31,35,36Five of the studies focused on experiences of individuals diagnosed with psychiatric disorders ,32–34,36Two of the studies of persons with psychiatric disabilities were in settings offering vocational rehabilitation services ,36, one Identified barriers and facilitators will be discussed separately in accordance with the dynamic representation of bio-psycho-social model by Lehman et al. .Our choice to contextualize the results using the bio-psychosocial model was to ensure a systematic presentation of all the different factors at play. Although, it would have been useful to present the results according to the different actors relevant to employability, the available data made this impossible. For instance, the studies on employers or individuals involved in employment decisions focused on the attitude of employers and not their perceptions on barriers and on how to improve employment for person with mental disabilities.Our analysis identified five major clusters of barriers to employment: presence and severity of illness, underlying psychological load (including fear of relapse), social stigma, discrimination and negative attitudes by others, lack of skills/education and absence of policy support.One of the most frequently named barriers to successful employment for people with mental health disabilities was ill health. Some papers talked about the effects of the more physical symptoms . From thNiekerk and colleagues showed that apart from the presence of the mental health disorder itself, anticipation and fear of a relapse in symptoms was associated with a reduced desire to seek or retain employment in persons with psychiatric disorders .The interpersonal factors that influence the ability and motivation to find employment can broadly be described as prevalence of negative and stigmatizing attitudes and beliefs. Social stigma and discrimination were reported as a barrier to employment for people with psychiatric disabilities in six of the eight studies included in the study –33,35. SIn a cross-sectional survey in Nigeria, Eaton  reportedSeveral of the identified papers discussed the employers’ and their representatives’ beliefs and attitudes as employment barriers. A survey of human resource personnel in Nigeria revealed that 72.2% of respondents would rather work with people with physical than mental illness and 73.3% would not want to share an office with someone with a mental illness . WorkplaNegative attitudes among employers observed in a survey of senior federal civil servants in Nigeria found that 72% of the respondents indicated their unwillingness to work with people with mental illness and 77% had never done so . In the Among the identified contextual factors were lack of tools for work and relative absence of government policy support.The study by Eaton  showed tLinked to that, several studies discussed a more structural, higher-level barrier: lack of institutionalized policy protection for people with mental illnesses. In the study by Oyefeso et al.  it was rWe found five clusters of facilitators of employment for person with psychiatric disabilities, namely stability or reduced severity of mental illness, resolution of psychological conflicts, workplace accommodations, reduction in social barriers/stigma and governmental support.Stability of mental illness and utilization of mental health services were reported as facilitators of employment and job retention ,36. Job A further trend was that participants who were more at ease with the effects of psychiatric impairment on their identity and functioning seemed better able to maintain their roles….. participants who resumed work despite the occurrence/continuation of mild symptoms were more successful in maintaining such participation .Resolution of a personal psychological conflict, heightened self-esteem and a personal decision by an individual with a psychiatric disability to work in spite of stigma are reported as major determinants of employment and work –34. In tAmong the interpersonal factors facilitating employment are the ones linked to the direct working environment of individuals with mental disabilities.In her study, Niekerk  identifiReduction in social stigma and improved social welfare were also reported facilitators of employment for people with psychiatric disabilities ,31–34. TDespite the fact that in this study we identified certain biological, psychological, interpersonal and contextual factors that are shown to influence the employment of our study group, it is also important to bear in mind the interconnectedness and mutual influence of these factors as presented by Lehman et al. . All theEmployment models such as sheltered or supported employment are used in HICs to facilitate the employment of persons with a disability –39. WherSecond, cooperative income-generation groups of persons with psychiatric disabilities was reported as a useful model of employment and a pathway towards competitive employment and resolution of work identity crisis . CooperaThird, SE services which assist persons with psychiatric disabilities to engage in competitive employment were identified as a useful option for the return to work of people with psychiatric disabilities in resource-poor settings . Where tOur study observed a striking lack of evidence regarding the employment of people with psychiatric disability throughout Africa. Despite using broad selection criteria, we were able to identify just eight papers discussing the issue. There may be several explanations. In African countries, there is associated stigma and lack of interest in mental illness; a situation that is worsened by lack of human resources for mental health care ,40. The In this article, we presented an overview of the barriers to and facilitators of employment for people with psychiatric disabilities in Africa. The analysis was performed using the expansion of the bio-psycho-social model . In the The biological factors influencing work participation are linked to the physical or mental health of the individual in question. Several studies have noted that fluctuation in mental illness led to disruption of work and inability to continue in a job ,32,33,36The biological barriers to employment seem to be closely linked to the psychological ones. It was shown that the anticipation of psychiatric illness affects work ability, because the individual feared that the illness may recur and lead to interrupted employment . These fIn order to foster these coping strategies, it is also important to address stigma and negative beliefs about the psychiatric disabilities, which several studies find constitutes a considerable interpersonal barrier to employment of our target group . PervasiThe identified contextual factors influencing the employment of people with psychiatric disabilities in Africa were connected both to more practical aspects (absence of necessary tools), and also highlighted a more structural problem – the absence of government policy support.Limited access to the necessary tools and equipment for work was described as an underlying factor that could explain reduced work participation . This fiLast, but not the least, the need for government support for the issue of employment of people with psychiatric disabilities was highlighted in several papers ,35 . TheHowever, when reviewing the results of this study one should be aware that the barriers and facilitators identified do not exist in isolation, but rather mutually influence each other. This presents both a challenge and an opportunity for potential interventions in the field. And we advocate more research about this interconnectedness.This study also recorded three models or sources of employment for people with psychiatric disabilities, namely self-employment , cooperaThe results of this study need to be interpreted with caution, taking the methodological and contextual factors into account. First, the studies included in this study represent a very broad spectrum, while being quite limited in number. In addition to the specific limitations of the individual studies, the inclusion of studies from diverse populations presents particular challenges for interpretation of the findings. Also, our study criteria excluded grey literature which may have covered issues relating to employment that is often not considered in health care research.There was also diversity in the terms used to describe psychiatric disability. The use of the terms like ex-mental patient  and ex-rIt is pertinent once again to underline the paucity of original studies that explore barriers to and facilitators of employment for individuals with severe mental illness in Africa. The few studies drawn upon in this review demonstrate an urgent need for focused research in this area. Perhaps the stigma associated with mental illness extends to research in mental illness. This may be true in Africa, where stigma of mental illness is rife and extended to mental health care providers.The employment of people with psychiatric disabilities is essential and has both human rights justifications and socioeconomic benefits for those affected, society and governments. The dearth of context-relevant scientific evidence in Africa is of concern. There is a lack of evidence and the existing evidence is highly fragmented and outdated. This gap in information would benefit from further research on how to improve the employment rates among persons with psychiatric disabilities in Africa and the achievement of Goal 8 of the SDGs.


Medical practice variation refers to differences in health service utilization among regions in the same country. It is used as a tool for studying health inequities.In 2011, the OECD launched a Medical Practice Variation Project which examines regional differences within countries and explores the sources of the inter-regional differences. The aim of this study is to examine the patterns and trends in geographic variation for selected health services in Israel.The analysis is based on data from the National Hospital Discharges Database (NHDD) of the Israeli Ministry of Health. The eight procedures and services studied were: medical admissions ; hip fractures; caesarian sections; diagnostic cardiac catheterization; cardiac angioplasty (PTCA); cardiac bypass surgery (CABG); hysterectomy; and knee replacement surgery. The data are presented for the 7 districts in Israel, determined by address of residence.The procedures and services with the lowest variation across the seven districts were medical admissions (RR between regions-maximum/minimum 1.3) and hip fractures (RR 1.44), while the one with the highest variation was CABG (RR 1.98). The Israeli periphery, and the northern district in particular, had higher rates of medical admissions, knee replacement and cardiac procedures. When studying the trend over time, we found a decrease in use rates for most procedures, such as coronary bypass (R. 04) and CABG (R 0.8). Medical admissions decreased by 8%, with the highest decline (16%) observed in the central districts.This study provides Israeli policy makers with information which is vital for the strategic planning of service development, such as strengthening preventive medical services in the community, reducing cardiovascular risk factors in the periphery and expanding the national publication of clinical quality scores.The online version of this article (doi:10.1186/s13584-016-0127-y) contains supplementary material, which is available to authorized users. In recent years, much effort has been expended by the Israeli government to reduce the gaps between the country’s periphery and center in the health sector. Internationally, one of the first and most prominent tools in this area that compares variations in health services between different areas is called Medical Practice Variations. The first research group in this field published its work in what later developed to be known as “medical practice variation studies” or “small area analysis”Typically, in countries with low inter-regional variation, services are considered to be optimized. However, achieving low medical variation doesn’t represent always good medical services . It is easier to achieve low medical variation in medical conditions with a simple diagnosis or treatment, such as treatments of fractures, as opposed to conditions requiring awareness and/or targeted testing, such as the treatment of colorectal cancer –5.Large variations are often characterized by differences in socioeconomically status, and differences in the health condition of the population. In these cases there is a direct correlation between the use of health services and several influential factors such as resource allocation, medical staff employment, expertise, training and more –8.In September 2014 the OECD published a report that examined the extent of inter-regional variation within 13 countries)Australia, Belgium, Canada, the Czech Republic, Finland, France, Germany, Italy, Portugal, Spain, Switzerland, England and Israel), for a variety medical service . This arThe aim of this study is to examine trends over the last decade in the use of selected hospital services by the population residing in Israel and to compare usage rates and trends across regions.The data presented in this study are based on the National Hospital Discharges Database (NHDD) maintained by the Health Information Division in Israel’s Ministry of Health. The database is continually updated, with hospitals providing information electronically on a quarterly basis. The database includes all acute care hospitals as well as some of the psychiatric and long-term care facilities. Only acute care hospitals were included in this study. The database contains records of each individual admission. Patients’ identity numbers are encrypted to allow follow-up studies, while preventing identification of individuals to protect patient privacy. The database includes demographic and hospitalization data. The demographic data include age, gender and residence (village/town/city code), as well as the patient’s health fund provider. The hospitalization data include general information such as admission type (planned or via the emergency room), discharge type , detailed information at the departmental level such as date of admission and discharge from each department, diagnoses listed and procedures performed in each admission, which are coded according to the ICD-9-CM classification.Eight categories of hospital care were examined, after being selected by an OECD expert: medical admissions  plummeted by more than half, from 122 per 100,000 in 2002 to 52 in 2012. In most districts the rate decreased by two-thirds, while in the Northern and Haifa districts it decreased by 45%. In 2012, the highest rates of CABG were recorded in the Northern, Southern and Haifa districts.The rate of cardiac catheterization (diagnostic) has decreased over the past decade. The national rate fell by 23% in 2002–2012, from 489 per 100,000 inhabitants to 380. The downward trend was recorded in most regions, with the largest decline (33%) in the Tel Aviv district, while in the Southern district the rate inclined in about 8% stable in the last decadeThe rate of therapeutic catheterization (PTCA) Fig.  has decrFor most of the health care services and procedures studied within the Geographic Variations in Health Care OECD report, the general trends in health care activities and procedure rates at the national level in Israel, over the past ten years, have been similar to those observed in many other OECD countries . HoweveThis study analyzed both 2012 rates and 2002–2012 trends, for Israel as a whole and for its seven districts. For all of the services examined in this study, the 2012 rates were significantly different between the districts. The smallest differences between districts in 2012 were recorded for hysterectomies, with a rate ratio of 1.3, and the highest rate ratio was for CABG, with a rate ratio of 2.0.1 This paper focuses on geographic variations in Israel so to learn and improve policy making. Usually, these unwarranted variations in the practice of medicine and the use of medical resources are being analyzed through several main general causes, among them: disease patterns among districts, degree of agreement between providers and supply-side factors, underuse of effective care, misuse of preference-sensitive care and overuse of supply-sensitive care. In order to provide a systemic approach for the policy makers in Israel, this paper will analyze the results via some of these methods.Geographic variation in medical practice styles reflect not only differences in patient needs but might be due variations in practice of medicine, in resource allocation and in equal access to services. These unwarranted variations need to be addressed by countries who wish to improve healthcare performances. As the Darmoth project stats unwarranted variation in the practice of medicine and the use of medical resources are the inappropriate use of medical resources are the basis of ineffective care and must be addressed.With regard to the trends over time, at the national level, the study found a significant increase in knee replacement surgery, and significant declines in hip fracture repair surgery and hysterectomy. A decline in medical admissions was observed as well among all the seven regional trends. However, despite this decline there is still a consistent and clear gap between central and peripheral regions, reflecting the highest medical admission rate in the periphery and the lowest in the center of country.In this section, we first consider possible explanations for the 2012 inter-regional differences and then consider possible explanations for the difference in trends across regions and services. We also discuss the extent to which the Israeli patterns and trends are similar to those found in other countries.Some of the inter-regional differences in 2012 rates may be related to uneven access to care as well as differences in socioeconomic and health status between the regions. Although these differences had never been published through geographical areas, they were studied and published by the Ministry Of Health report on 2013 through socioeconomic perspectives.A) The disease patterns among districts B) The degree of agreement between providers C) The supply-side factors.In addition, we shall discuss, when it is relevant, the results from additional perspectives: failure to provide effective care, failure to provide preference sensitive care, and overuse of supply sensitive care.PTCA: The procedure which holds the highest variation with rate ratios of 1.98, in 2012, between the highest and lowest regional rate, is highest in the periphery (the northern and southern districts). Regarding the disease patterns, there is a direct correlation between ischemic heart diseases and the cardiovascular risk factors that are the highest in low socioeconomic status as mentioned earlier. Therefore, these differences are expected and will not change dramatically until there will be a reduction in smoking and obesity rates in the periphery. However, the high rates of CABG in the periphery could not be explained through the arguments of “degree of agreement” and “supply-side factors. This assumption derives from the fact that, the northern district, doesn”t hold a cardiac surgery unit, and the southern district holds only one.This major variation correlates also to the underuse of effective care, as preventive medicine and glycemic control and also correlates to the Misuse of preference-sensitive care, in this case, cardiac catheterization .Knee replacements, a procedure which holds the second highest variation with rate ratios of 1.78, in 2012, between the highest and lowest regional rate, is highest in the periphery. Regarding the disease patterns, this can be attributed to both the high rate of obesity and the lack of proper prevention in the periphery, which can be reduced by good obesity control and osteoarthritis treatment. Regarding the argument of “degree of agreement” there isn’t a clear indication for knee replacement, which can imply for an over use to this surgery in the periphery. Regarding “supply-side factors”, it is unreasonable that this is one of the reasons since most of the hospitals in the center of Israel hold several advances units, which specialized in knee replacement, where these units in the periphery are less developed.This variation correlates also to the misuse of preference-sensitive care, in this case, conservative therapy such as physical therapy and weight loss.The third procedure with the highest variation is cesarean section with rate ratios of 1.68, in 2012, between the highest (The city of Haifa) and lowest regional rate . This low rate in Jerusalem can be attributed to demographical and cultural reasons: In Jerusalem, which holds the lowest rates, the population is religious and therefore avoid Cesarean Section in order to reach high number of labors. In Chifa, which holds the highest rates, the population is secular with low rates of labors per capita.This variation correlates also to the misuse of preference-sensitive care, in this case, a regular labor, and also overuse of supply sensitive care, since cesarean section is considered to be a convenient solution in difficult labors.Hysterectomy, this procedure holds the lowest variation with rate ratios of 1.31, in 2012, between the highest and lowest regional rate.Regarding the disease patterns, there are not preventable risk factors for the clinical statues that cause the need for this procedure. This fact minimizes the gaps between the periphery and the center of Israel in the usage of this procedure and implies on the importance of gaining equality, not only in treatment, but also in preventive medicine. Regarding the arguments of “degree of agreement”, there is not always clear indication for this procedure but there are still several common well established indications for the procedure. As for “supply-side factors”, there isn’t any specific uniqueness regarding the tariff or pricing method of this procedure. Therefore, the fact that the risk factors are uniform nationally could be a proper explanation to the low variation.The second procedure with a relatively low variation is surgery after hip fracture, with rate ratios of 1.44, in 2012, between the highest (The city of Tel-Aviv) and lowest regional rate (The city of Chifa). This fracture is common especially in old people and females. Regarding the disease patterns, there are clear preventable risk factors for a hip fracture, among them preventing and treating osteoporosis. However, after stratifying the population to age and gender, there is no clear correlation in this aspect, since the highest rates are not in the periphery. Regarding the argument of “degree of agreement” there is a clear indication for surgery after hip fracture5, which can well explain the low rate of variation. As for “supply-side factors”, this relatively low variation could be explained by close control of the ministry of health on hospital. This control aims to measure the delivery of this surgery in 48 h for patients who were admitted to hospital with a hip fracture. The outcomes of this control are reflected both on a national publication of the results and also in a differential Tariff for hospitals which operating this patients in less than 48 h after admission. It is suggested that this policy, had led all hospitals to acquire similar guide lines and protocols for treating patients with this diagnosis.Following these results and analysis, it is clear that the appropriate community medicine, before reaching hospital, is crucial for reducing variations between different regions, especially between the periphery and the center. Hence, it is not surprising that a 2010 study had revealed significant gaps in the availability of secondary community-based medical services, with relative shortages in the periphery for internal medicine, surgery and various sub-specialties .Generally speaking, the trends in health care activities and procedure rates at the national level in Israel over the past ten years have been similar to those observed in many other OECD countries.Comparing trends in procedures and hospitalizations over the years 2001–2012 reveals that Israel has in most cases the same trends as the other countries that were measured in this study . There hThe only procedure for which Israel  doesn’t converge to the general international trend is PTCA . This phThe trends regarding cardiac care procedures are mixed and difficult to interpret. On the one hand, as in many other OECD countries, there has been a sharp decline in CABG rates in Israel, as a higher share of people with ischemic heart disease were treated with less invasive procedures. These interventions where based on cardiac catheterization and aggressive preventive treatments which included both secondary prevention and primary, both in hyperlipidemia, pre-diabetes and diabetes, and after first coronary event.On the other hand, the national standardized rate of coronary angioplasty (PTCA) also decreased between 2000 and 2011, which is not consistent with the trend observed in most other OECD countries.As national trends, the Israeli patterns of cross-regional variation are similar to those found in other countries. Knee replacement rates display high levels of variations, which can vary by more than fourfold across countries. Cardiac procedures rates show the highest level of geographic variations; they vary by more than three-fold across countries and also have the highest level of within-country variation for more than half of the countries.However, analyzing Israel’s PTCA trends, which are not congruent with international trends of PTCA , raises On the one hand, as in most of the OECD countries, a sharp drop in the performance of coronary artery bypass surgery was seen in recent years. This decline is attributed to the diversion of some surgical activities into catheterization procedures. On the other hand, and unlike other OECD countries, a decline in the performance of invasive cardiac catheterization (PTCA) was observed. However, this downward trend was not uniform to all of the districts. While in the peripheral areas (the Northern and Southern districts), there was a sharp rise in the performance since 2002 to 2005 and from then some moderate changes, in other districts a decline was observed throughout the decade. These opposite trends, which can be seen in Fig. A thorough report published by the Ministry of Health in 2012 set a quantitative target of narrowing by 15% the disparities in mortality from cardiovascular conditions before age 75 between low-income persons and the population-wide average 14 the The Ministry of Health, as part of a broader governmental policy, is continuing to strengthen the periphery by adding hospital beds and qualified personnel , improving infrastructure and by adding quality measurements.In the years ahead, the Ministry of Health will further investigate these trends in geographic variations in the use of hospital services across Israel and try to determine the factors that may explain these differences.Steps should be taken to preserve the trend of reduced hospitalization rate by strengthening both community and preventive medicine services. These steps should be taken especially in the periphery, were the admission rates are still relatively high.As the trend in PCI rates differs between the central of Israel and its periphery, and this is at variance with the situation in other countries, the Ministry of Health should carry out research which will examine these differences and their practical and clinical motives and implications.As for the relatively high rates of the PCI procedure in Israel, the Ministry of Health should examine its high tariff.Following the negative trend and low variation in hysterectomy rates, that are being attributed to the usage of clinical guide lines and to the fact that socioeconomic status doesn’t affect the risk factors that are leading to this procedure, the Ministry of Health should focus on reducing risk factors which derives from inequality in health and should consider expending the usage of clinical guidelines to other clinical fields .Following the low variation in surgery after hip fracture, that are being attributed partially both to the national publication of the results and to the allocation of a differential tariff for hospitals which operating this patients in less than 48 h after admission, the Ministry of Health should consider expending the usage of these methods, not only for improving clinical outcomes, but also for reducing geographical variations in health services.The Ministry of Health should measure and publish extensive data regarding the correlation between geographical erase and risk factors for cardiovascular disease and other disease.The Ministry of Health should measure and publish extensive data regarding the distribution of medical practices by districts in order to explain the observed usage patterns or referral patterns.The main policy implications of the findings of this study are as follow:This study provides, for the first time, a broad comparison of health service utilization among areas in Israel, which can be divided into the center of the country and its periphery. The findings of this paper can help policy makers assess, plan and initiate strategies in service supply which will strengthen preventive medical services in the community, reduce cardiovascular risk factors in the periphery and expand the national publication of clinical quality scores.


Yolk accumulation and its regulated degradation are therefore crucial for successful development, however, most of the molecular mechanisms involved in the biogenesis, sorting and degradation of targeted yolk organelles are still poorly understood. ATG6 is part of two PI3P-kinase complexes that can regulate the recruitment of the endocytic or the autophagy machineries. Here, we investigate the role of RpATG6 in the endocytosis of the yolk macromolecules and in the biogenesis of the yolk organelles in the insect vector Rhodnius prolixus. We found that vitellogenic females express high levels of RpATG6 in the ovaries, when compared to the levels detected in the midgut and fat body. RNAi silencing of RpATG6 resulted in yolk proteins accumulated in the vitellogenic hemolymph, as a consequence of poor uptake by the oocytes. Accordingly, the silenced oocytes are unviable, white (contrasting to the control pink oocytes), smaller (62% of the control oocyte volume) and accumulate only 40% of the yolk proteins, 80% of the TAG and 50% of the polymer polyphosphate quantified in control oocytes. The cortex of silenced oocytes present atypical smaller vesicles indicating that the yolk organelles were not properly formed and/or sorted, which was supported by the lack of endocytic vesicles near the plasma membrane of silenced oocytes as seen by TEM. Altogether, we found that RpATG6 is central for the mechanisms of yolk accumulation, emerging as an important target for further investigations on oogenesis and, therefore, reproduction of this vector.In oviparous animals, the egg yolk is synthesized by the mother in a major metabolic challenge, where the different yolk components are secreted to the hemolymph and delivered to the oocytes mostly by endocytosis. The yolk macromolecules are then stored in a wide range of endocytic-originated vesicles which are collectively referred to as yolk organelles and occupy most of the mature oocytes cytoplasm. After fertilization, the contents of these organelles are degraded in a regulated manner to supply the embryo cells with fundamental molecules for  R. prolixus. Insects silenced for this gene generate oocytes lacking most of their yolk components, and, as a consequence, their F1 embryos are not viable. Thus, these findings are important in the context of vector population control and can help us to further understand the molecular mechanisms of yolk uptake and oocyte formation in these animals.In oviparous animals all the nutrients and energy needed for the embryo cells are previously stored in the eggs, in the form of what we call yolk. The yolk is the food of the embryo, and, like our food, it needs to be broken down into nutrients and energy to supply the embryo cells rapid growth and division. The yolk-macromolecules are maternally synthesized, accumulated in the oocytes into specific organelles and, after fertilization, they are degraded in a regulated manner throughout early embryogenesis. The cellular and molecular mechanisms that govern these components accumulation and degradation are still mostly unknown. This is our interest in this work. We found that one specific gene (RpATG6) is crucial for the endocytosis of the yolk components by the oocytes in the insect vector of Chagas disease  Oocytes are remarkable cells in the matter of accumulating macronutrients. Oviparous animals have evolved to produce germline cells that not only enter meiosis to generate a gamete, but also differentiate into a giant cell designed to support embryo growth. Once fertilized, the egg is able to fulfill embryo development away from the maternal body. To accomplish that, an oocyte typically grows up to 5,000x its original size by accumulating macromolecules in a highly specialized cytoplasm with maternal mRNAs, proteins, ribosomes, mitochondria and so on. That stock of macronutrients is referred to as yolk. The yolk components are entirely made by the mother in a major metabolic challenge where proteins, lipids and carbohydrates are synthesized and delivered to the oocytes mostly by endocytosis. The yolk macromolecules are stored in a wide range of endocytic-originated vesicles which are collectively referred to as yolk organelles and occupy more than 99% of the mature oocytes cytoplasm –3. AfterA. thaliana, D. melanogaster, C. elegans and mice  Lp was not accumulated inside the oocytes [R. prolixus . Thus, we cannot rule out the possibility that maybe a small fraction of the lipids in the oocytes of R. prolixus is delivered through Lp endocytosis.Apart from the main yolk proteins vitellin and RHBP, we also observed a decrease in the storage of TAG and PolyP, both major non-protein yolk components of the oocytes. 30–40% of the dry weight of the full grown oocyte is comprised by lipids, mostly fatty acid, cholesterol, phospholipids and triacylglycerol (TAG) . Among t oocytes  and 2) i oocytes . However oocytes . Also, aR. prolixus [As for PolyP, it is possible that it is also linked to vitellin, but it has never been properly tested. Further experiments testing the synthesis and delivery mechanism of PolyP to the oocytes are necessary to understand their fate in the oocytes. Glycogen also comprises the yolk, but while extra ovarian organs produce proteins and lipids, glycogen is synthesized in the ovary itself . The accprolixus . AccordiCarausius morosus, differential acidification of the yolk organelles was already described and correlated with proteolytic activity [Periplaneta americana and R. prolixus, some small yolk organelles were described as acidocalcisome-like organelles, and they can be fractioned by differential centrifugation [Boophilus microplus the proteolytic activity has also been correlated with differential acidification of yolk granules and with vesicles in the cortex of the fertilized egg [Our findings that the microvilli and endocytic vesicles are not properly formed in the silenced oocytes, and that part of the yolk organelles in the oocyte cortex have abnormal morphology further support the assumption that endocytosis was compromised. It is generally acknowledged that the mature oocyte comprises different types of what we collectively call yolk organelles, and that this is the result of distinct packaging routes during oogenesis where the size and localization of the yolk vesicles within the oocyte is maternally-determined. Several groups have described that the yolk organelles population is not homogeneous in the fertilized egg. The vesicles can vary in its macromolecule contents, density and size, and for several models it is possible to fractionate the yolk organelles in accordance with their difference of size and density –56. In tactivity . In Perifugation , 59. Forized egg . At earlR. prolixus. Since the yolk storage and degradation are crucial events for proper oocyte formation and embryo development, understanding the role of RpATG6 could contribute to the elaboration of vector control strategies. This is especially important in the context of Chagas Disease, in which, to this day, the main forms of control and prevention in endemic areas are vector-avoiding tactics, as the use of insecticide sprays and bednets (www.who.int/chagas/en/). Such approaches are virtually the same ones that have been done in the past decades, so it becomes evident how little accomplishments we have made in our efforts to manage this insect population and dispersion. Certainly, that lack of progress is at least partially due to our scattered knowledge regarding the insect reproduction biology from a molecular point of view. In this context, we think that contributions to this field are of key importance and may help us to further understand vectors biology and to elaborate new tactics for population control and the prevention of vector-borne NTDs such as Chagas Disease.Altogether, we found that RpATG6 has a key role in the uptake of the main yolk proteins and in the biogenesis of the yolk organelles in S1 FigA. Multiple sequence alignment of conserved domains Coiled Coil Domains (CCD), Nuclear Export Signal (NES), Becl2-homology-3 motif (BH3) and Evolutionarily Conserved Domain (ECD) in Rhodnius prolixus, Drosophila melanogaster and Homo sapiens. The structure of the different domains of ATG6/Beclin1 was previously described in Homo sapiens [B. Matrix of similarity and identity of Atg6/Beclin1 protein sequence in different species (SIAS Server). Reference sequence Rp–Rhodnius prolixus. Dm–Drosophila melanogaster; Hs–Homo sapiens; Mm–Mus musculus; At–Arabidopsis thaliana; Sc—Saccharomyces cerevisiae; Bm–Bombyx mori; Am–Apis mellifera. sapiens  (*) corr(TIF)Click here for additional data file.


Singapore is a hotspot for emerging infectious diseases and faces a constant risk of pandemic outbreaks as a major travel and health hub for Southeast Asia. With an increasing penetration of smart phone usage in this region, Singapore’s pandemic preparedness framework can be strengthened by applying a mobile-based approach to health surveillance and control, and improving upon existing ideas by addressing gaps, such as a lack of health communication. FluMob is a digitally integrated syndromic surveillance system designed to assist health authorities in obtaining real-time epidemiological and surveillance data from health-care workers (HCWs) within Singapore, by allowing them to report influenza incidence using smartphones. The system, integrating a fully responsive web-based interface and a mobile interface, is made available to HCW using various types of mobile devices and web browsers. Real-time data generated from FluMob will be complementary to current health-care- and laboratory-based systems. This paper describes the development of FluMob, as well as challenges faced in the creation of the system. Seasonal influenza affects nearly 20–25% of the Singapore population . The allEconomic modeling has recently demonstrated that the treatment-only strategy for influenza resulted in a mean number of 690 simulated deaths, 13,950 hospital days, an equivalent of 2.5 million workdays lost, and a mean economic cost of USD$469.8 million per year . ExistinGiven the absence of an efficient surveillance system that addresses challenges within hospitals in Singapore, this paper reports the design and development of a prototype integrated mobile-health participatory influenza surveillance system entitled FluMob. Following a review of literature on information and communication technology (ICT) approaches to addressing influenza tracking and surveillance, we describe FluMob’s architecture, followed briefly by the methodologies used to recruit and retain users. Finally, we present the challenges the research team faced in the various phases of the implementation of the intervention, and lessons learnt, which will be useful to public health researchers and practitioners involved in similar initiatives or interventions in the future.Participatory epidemiology (PE) is a concept that has increasingly been used in health surveillance in recent years. It uses community involvement to improve the understanding and control of diseases and was most prominently brought to attention by work conducted in Africa investigating animal health from information gathered by local farmers .Outbreaks Near Me” and “Ushahidi” have been effective in optimizing the collaboration between ICT and health surveillance  on a weekly basis. The near real-time data generated from the system will be complementary to current health-care- and laboratory-based systems in assisting with streamlining hospital outbreak response among HCWs and informing vaccine policy. Figure The FluMob application consists of mobile operating systems (Android and iOS) and a responsive web portal. These applications are integrated into a central database using common web services. Central servers hold the business logics related to the FluMob application and the report analysis module. Once users are registered in the system, they have to log in with user identifications and passwords. There are no identified constraints in the application, and it is a simple, user-friendly process. All required data will be stored in an encrypted manner for security and confidentiality purposes.software environment (SE) and hardware environment (HE).The operating environment of FluMob can be divided into two components: The SE is the collection of software required to operate the application, and those used in the FluMob application are Windows server 2008 R2, Apache/2.4.17, PHP Version 5.5.30, MySQL 5.6, Android studio, and xCode for iOS development.The HE refers to the set of hardware required to deploy the application. The FluMob central server is configured with Core2 Intel Xeon Processor with four cores, 8 GB of random-access memory, and 500 GB of storage space. The main server supports any number of web clients. Based on the initial system prototype, more than 100 clients are expected, and the system was tested with 500 dummy clients. The system supported 100 concurrent users without any technical malfunctions. The maximum number of sever connections was restricted to 100 connections, which proved to be sufficient, as database servers will be configured to allow connection pooling. There are no specific security mechanisms added to the client application, but predefined private keys to communicate with central servers have been implemented.Figure via mass emails. Upon responding, users are given a link to the relevant software app store to download the free app. Once the app is loaded on the mobile phone, each user is first asked to register by filling a form capturing demographic, lifestyle details, and medical history. Figure The FluMob system is being tested and used by consenting participants from Tan Tock Seng Hospital (TTSH) and KK Women’s and Children’s Hospital (KKH). TTSH has a Communicable Disease Centre and is the designated hospital to handle and manage outbreaks of novel diseases. KKH is a women’s and children’s hospital, with a large inpatient and outpatient pediatric patient workload. The research is being conducted using standard research practice and ethics guidelines. An optimal sample size of 278 was calculated for the study’s statistical validation representing the health-care workforce using G*Power analysis . HoweverClinical and social scientists from collaborating institutions developed and collated a range of questions to capture data relating to HCW demographics, lifestyle, influenza virus symptoms, and prevention. FluMob registration requires participants to fill in a form capturing demographic details , workplace information , information about family , lifestyle behaviors , medical history , as well as technology use and acceptance . The questions serve as a baseline for researchers to understand the lifestyle patterns and technology consumption among local HCWs. Descriptive analyses could potentially assist in the development of policies for disease monitoring and preventive measures. The data collected at registration can also be used for analytics at a later stage to identify any potential relationship between demographics, lifestyle behaviors, medical history, and vulnerability to influenza.Health-care workers are prompted to submit weekly health reports on whether they have ILI symptoms, a dichotomous “yes-or-no” question is first presented to the users to capture the presence of ILI symptoms after they have chosen their ward/location of duty. If users answer “no,” they will then receive a “thank you” note for submission and can immediately resume their daily work tasks or activities. Conversely, when users have declared having ILI symptoms, they will be asked to specify their symptoms from a list, which includes fever, cough, muscle/joint pain, vomiting, diarrhea, and others. After which, users will then need to provide further information regarding the illness, such as the date of onset and end of symptoms, body temperature, whether they have fever, medical services visited, medication taken as well as some medical leave-related questions. Finally, they will be asked to rate their health status on the day itself on a scale of 0–100.This component was designed to enhance surveillance efforts with real-time information about ILI episodes among the clinical and non-clinical staff in both hospitals. The reports are submitted on mobile phones or web browsers to assist the research team in detecting potential influenza outbreaks within the hospital. Users are provided with incentives after submitting a certain amount of reports. As soon as a user has submitted the report, the information is stored in a data repository, which allows clinicians and researchers to gather real-time crowd-sourced information for clinical analytics so as to inform strategies for disease surveillance, prevention, and management.The Android version of the application was introduced to the health workers at TTSH and KKH in May 2016, and saw over 50 HCWs from TTSH signing up for the study within the first week. The iOS version was launched later in June 2016, and there are currently more than 200 iOS users who have installed the FluMob application. At this stage, the team has steadily recruited almost 700 participants. Of these, approximately 50% are regularly submitting weekly reports.A number of challenges were faced in the development and implementation of the system. This section will look at the challenges faced, and how they were addressed and resolved by the team. The first trial was encountered during the development phase of the application. The most recent data available  show thaTherefore, the technical expertise of the research team focused only on the development of Android-based applications and outsourced the development of the iOS version to an external development specialist. Due to the demands of the project and other unforeseen circumstances, the study was first launched only with the Android application, and interested IOS individuals had to be put on waiting list for more than a month. When the IOS version was finally released and individuals on the wait list were re-contacted, a lot of the initial interests had waned leading to only 75% of them being successfully recruited into the study.To prevent the coding and programming issues described earlier, a platform where both Android and iOS mobile phone applications can be developed simultaneously can be considered in the future. A software called Appcelerator Titanium  can be uThe second challenge pertained to the type and number of survey questions that were to be included in both the registration and the weekly reports sections of the FluMob application. The researchers were faced with the arduous task of filtering through numerous survey questions that effectively measured demographic variables  and overall health of the participant . Sifting through previously published peer-reviewed literature took time, and numerous meetings were required to settle on the questions which were to be included.N = 10) of participants from TTSH. This allowed for feedback to be collected and amendments made prior to the large-scale implementation of the application.This issue was resolved by meeting frequently, and by using scales that have been previously tested and established in their efficacy at measuring ILI symptoms. The team also resolved differences in opinion in an objective, evidence-based manner, which allowed for more empirical formulation of survey questions. The question list was pilot tested on a small sample (The final challenge arose in the form of inter-organizational and transdisciplinary research. The research team comprises of clinician scientists, social scientists, and research engineers, hailing from several different institutions; Nanyang Technological University, KKH, TTSH, National University of Singapore, and National Public Health Laboratory. Figure In Figure The research team resolved the issue of constant iterations of the survey by completing full scale testing within 1 week and freezing any changes that could be made to the application a week prior to launch. The final version of the survey was fully agreed upon by both clinical and social scientists and allowed for a measurement of the full spectrum of variables that permitted all the research hypotheses to be tested effectively. The nature of having experts of varied specializations gave project a larger research scope, limited to not just social science or clinical science. This is an example of how transdisciplinary research can be both an advantage and a disadvantage to the implementation of such a research project.The completion of the study period will see detailed data analysis, which includes an analysis of the weekly reports and cases identified for follow-up. The registration questions will serve as a baseline for researchers to understand the lifestyle patterns and technology consumption among local HCWs. Descriptive analyses will also yield valuable data and could potentially assist in the development of policies for disease monitoring and preventive measures. The data collected at registration can also be used for analytics at a later stage to identify any potential relationship between demographics, lifestyle behaviors, medical history, and vulnerability to influenza.At the next stage, our plan is to incorporate health education messaging and communication. The present system allows for users to select the option to enable or disable notifications and avoids broadcasting of messages, instead electing to personalize reminder messages for each user. The research team wants to build on this and is considering including, in a subsequent version of FluMob, a health education messaging service that will send out health educational messages to users when they report having flu-like symptoms. For example, if a user were to report fever as a symptom, a notification would be sent to the user to encourage them to wear a mask, avoid contact with others, or to see a doctor. Two areas of academic inquiry are being considered by the research team; the first tests the efficacy of more tailored messages, and the second studies the effects of various modalities of communicating health messages.The FluMob study is currently under deployment with participants in both hospitals where data are being collated, the results of which will be analyzed in the near term future. At of the time of writing, recruitment numbers are still increasing, and weekly influenza reports from HCWs are being steadily submitted. The research team is presently building upon the knowledge gained to create a novel integrated syndromic surveillance system for general public use, which they hope will further address the gaps in disease prevention on a wider national and regional scale, and streamline influenza surveillance to reduce the burden of emerging infectious diseases.This study was carried out in accordance with the recommendations of DSRB, National University of Singapore with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the National University of Singapore.ML, BA, CFY, PY, and SF were involved in the conceptualization of the paper and the overall editing. KJ, AS, and KS wrote the main sections of the paper. HX and CJ were involved in data collection in their respective hospitals. UJ, AK, and KS were involved in the technical development of the application. SC was the overall coordinator for the project.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


A free maternal health policy was implemented under Ghana’s National Health Insurance Scheme to promote the use of maternal health services. Under the policy, women are entitled to free services throughout pregnancy and at childbirth. A mixed methods study involving women, providers and insurance managers was carried out in the Kassena-Nankana municipality of Ghana. It explored the affordability, availability, acceptability and quality of services. In this manuscript, we present synthesised results categorised as facilitators and barriers to access as well as lessons learnt (implications).Reasonable waiting times, cleanliness of facilities as well as good interpersonal relationships with providers were the facilitators to access. Barriers included out of pocket payments, lack of, or inadequate supply of drugs and commodities, equipment, water, electricity and emergency transport. Four lessons (implications) were identified. Firstly, out of pocket payments persisted. Secondly, the health system was not strengthened before implementing the free maternal health policy. Thirdly, lower level facilities were poorly resourced. Finally, the lack of essential inputs and infrastructure affected quality of care and therefore, access to care. It is suggested that the Government of Ghana, the Health Insurance Scheme and other stakeholders improve the provision of resources to facilities. A free maternal health policy was implemented in Ghana in July 2008 under the National Health Insurance Scheme (NHIS). The policy allows all pregnant women to have free registration with the NHIS after which they would be entitled to free services throughout pregnancy, childbirth and 3 months postpartum. The policy was one of Ghana’s key strategies for the achievement of the Millennium Development Goals (MDGs) and now, the Sustainable Development Goals (SDGs), specifically the reduction of maternal and child deaths and the achievement of universal health coverage (UHC).It is unclear whether the policy has achieved its desired outcomes in all parts of Ghana. In other resource constrained settings, it has been shown that there are gaps in similar policy implementation, as these are often implemented without careful planning and inadequate infrastructure as well as resources in terms of workforce and funding –3. ImpleAccess to services is complex and multidimensional  and is dThe study was cross-sectional, combining quantitative and qualitative studies using the convergent parallel mixed methods design. The study area was the Kassena-Nankana municipality in rural Northern Ghana. Quantitative data were collected from women (n = 406) who gave birth in facilities and at home. In-depth interviews were conducted among providers and insurance managers n = 28), while focus group discussions were held with the same category of women (n = 10) who participated in the quantitative study. Details of the design, study area, sampling, data collection and analysis are published in , 8., while fThe results have been synthesised and categorised as facilitators and barriers to access in terms of; affordability, availability, acceptability and quality of care. Figure The benefits of the free maternal health policy was widely acknowledged as it promoted the use of services. Other reviews in low- and middle-income settings have reported a significant positive relationship between health insurance including fee exemptions and the use of services , 10. IntEqually, we found that the facilities were reported to be clean and providers to be respectful and friendly. The environment of facilities as well as the attitudes of providers are important predictors of service usage. A review on the determinants of women’s satisfaction with services in low- and middle-income countries has shown that the interpersonal relationships of providers dominated factors influencing women’s use of services . It is eWomen interviewed indicated that they were very satisfied or satisfied with quality of care. This result is in line with studies conducted in India and Bangladesh where women were reportedly satisfied with services provided under the Chiranjeevi and the Maternal Health Voucher Schemes respectively , 16. HowOur study demonstrated that, despite the policy, women still made out of pocket (OOP) payments for drugs, supplies, laboratory services including ultrasound scans and transport as well as the purchase of other items for childbirth. The results corroborate findings from similar settings. For instance, despite a policy in Ethiopia to provide free services for women, 65% of facilities required women to make payments for some services  and in SDistance and time taken to reach the nearest facility were perceived in our study to be impediments to care seeking. The result is not isolated. In South Africa and Zambia, women revealed long distances to facilities which hindered access , 25. LikWhile women reported being satisfied with care, this was not the case for the providers. Providers recognised that the situation meant that the care they were providing was sub-standard. Providers often know what ‘good’ care should be even if their clients are willing to accept less than ‘good’. Other studies have highlighted similar issues, for example, in Bangladesh; while women reported satisfaction with services, providers were unhappy with care provision due to staff and logistics challenges, the lack of laboratory services and insufficient supervision .Although the Government of Ghana has prioritised maternal health by implementing the policy a decade ago, the results of our study raise critical questions about the ability of the policy to meet its goals. Our study highlighted four useful lessons for policy makers and other stakeholders in Ghana. These lessons are relevant to other countries who have implemented or are planning to implement fee free policies.OOP payments were common. The cost of transport, laboratory services, drugs and supplies made service utilisation difficult especially for poor women. The lack of funds in facilities was a result of the delay in payments by the NHIS, partly caused by the claims process and to some extent the lack of adequate funds for the scheme. The establishment of the electronic claims submission system by the NHIS is a step in the right direction as this will reduce fraud and abuse, help contain costs and promote the financial sustainability of the NHIS , 28. TheSustainable sources of funding to ensure funds are available for claims payment within the stipulated time (1 month following submission to the NHIS). Currently, the NHIS relies on a 2.5% value added tax  on some categories of goods and services as one of its main sources of funding . An addiThe inadequacy or unavailability of drugs and supplies, equipment, transport and infrastructure meant the health system was unable to support the successful implementation of the policy. This is synonymous with settings in low- and middle-income countries, where the outbreak of epidemics and other emergencies, for example, the outbreak of the Ebola Virus in West Africa, exposed the vulnerability and weaknesses of the health system , 31. StrLower level facilities (CHPS compounds) in the study are poorly resourced for the provision of services to people living in distant and remote communities. Nevertheless, these play a crucial role, acting as gatekeepers to the health system and as the first point of care for women, including the poor. These facilities also provide basic preventive and curative services. Thus, strengthening peripheral health systems is key to the achievement of good health outcomes as well as the attainment of UHC. Our study highlights the need for an expansion in the infrastructure of the CHPS compounds, including the provision of emergency transport at the community level, as well as the provision of water and electricity in the facilities.Water and electricity are crucial for the effective operation of facilities. Water helps maintain hygiene and sanitation in facilities, while electricity facilitates the sterilisation of equipment as well as storage of drugs, vaccines and associated adjuvants , 38. TheQuality of care is compromised by the lack of essential inputs and infrastructure in facilities. Poor quality of care not only discourages women from service usage, but does not permit the achievement of good health outcomes. For instance, implementing fee free policies may lead to an increase in the use of services but maternal deaths may not reduce proportionately if the quality of care is poor . All preIn conclusion, lessons from our study included the persistence of OOP payments, a vulnerable health system, poorly resourced lower level facilities and low quality of care due to the lack of essential inputs and infrastructure. These negatively affect the drive towards reducing maternal and child deaths and the attainment of UHC. It is suggested that the Government of Ghana, the NHIS and other stakeholders improve the provision of resources to facilities, especially lower level ones.The study has its limitations. Firstly, the estimated levels of OOP payments might be underestimated, as productivity losses for women and their caregivers were not determined. Secondly, recall bias on the part of the women cannot be ruled out since the interviews and discussions were held after women had given birth.


The 2030 Sustainable Development Agenda emphasizes the importance of quality of care in the drive to achieve universal health coverage. Despite recent progress, challenges in service delivery, efficiency and resource utilization in the health sector remain.The Ministry of Health Department of Standards and Regulations sought to operationalize the Kenya Quality Assurance Model for Health. To this end, the European Practice Assessment (EPA) was adapted to the area of Reproductive and Maternal and Neonatal Health.The adaptation process made use of a ten step-modified RAND Corporation/University of California Los Angeles (UCLA) Appropriateness Method. The steps included a scoping workshop, definition of five critical domains of quality in the Kenyan context , a review of policy documents, management and clinical guidelines, grey and scientific literature to identify indicators in use in the Kenyan health system and an expert panel process to rate their feasibility and validity.The resulting 278 indicators, clustered across the five domains, were broken-down into 29 dimensions and assigned measure specifications. A set of data collection tools were developed to furnish the indicators and piloted at two health facilities. They were subsequently finalized for use in 30 health facilities in 3 counties.The integrative and indicator-based aspects of the EPA process could be readily adapted to facilitate the operationalization of a practical quality assurance approach in Kenya. Concerns about the quality of health care have risen high on the international agenda in recent years, as countries strive to strengthen their health systems and deliver universal health coverage. Evidence suggests that even where health care utilization rates increase in many low and middle income countries (LMIC) , 2, thisDespite notable efforts on the part of Government, development partners and other actors, the health sector in Kenya continued to be plagued by challenges in service delivery, efficiency and resource utilization. Beyond the problems of lacking infrastructure and shortages of equipment, drugs and staff, there are also known deficiencies in the quality of care. These are especially pronounced in the areas of Maternal and Neonatal Care, family planning and in the provision of services for the survivors of Sexual and Gender-based violence .As a result, the maternal mortality rate remains unacceptably high at 360 per 100 000 live births . Even thIn 2009, the Kenya Quality Assurance Model for Health (KQMH) was established. A 2011 review of the KQMH found it to be suitably comprehensive in its scope but noted that only a minority of facilities had received any orientation on how it should be used and even in facilities where such training had taken place little implementation had been achieved . With thWith support of the Deutsche Gesellschaft für internationale Zusammenarbeit (GIZ), the European Practice Assessment (EPA) was adapted to fill this implementation gap in Kenya. EPA is implemented in >2000 health facilities in Germany since 2003 as well as in six other European countries –14 with In collaboration with the Ministry of Health and DRSR a ten step-modified RAND Corporation/University of California Los Angeles (UCLA) Appropriateness Method process was used to develop the quality measures and adapt the EPA. The process is laid out in Table via outpatients [At the scoping workshop it was agreed that the Kenyan version of EPA, the Integrated Quality Management System (IQMS) would focus on the following five domains: ‘People (staff and patients), Management, Clinical Care, Quality & Safety and the Interface between inpatients and outpatients care’. Including the interface was considered crucial as most of the previous quality improvement efforts in the country had focused upon inpatients care, whilst in Kenya it is known that the majority of patient contacts occur patients . Moreovepatients  as well The search comprised two steps. Firstly, health sector strategy, policy and planning documents, management and clinical guidelines, Standard Operating Procedures, and relevant grey literature were collated. Secondly, searches of the Pubmed and Direct Science databases were run using the terms ‘Quality of care’ and ‘Kenya’, with first abstracts and then full texts consulted. The resulting yield of documents were all reviewed for indicators already existing in areas related to the main domains; reproductive care, maternal and neonatal care, referral between facilities, services for survivors of gender-based violence, the interaction between facilities and communities, and general quality management strengthening. Relevant indicators were found in 40 of the documents as explained in . At thisA paired review of the indicators showed that there were often duplications or strong similarities between indicators. At this stage, duplicate indicators were deleted (57), and similar indicators from different sources combined, resulting in the removal of (34) indicators. In addition, indicators that facilities could not influence themselves, or were difficult to measure, for example not being suitable for repeated measurement overtime but rather one off recording were removed (45). The indicators were assigned to the five proposed domains, and clustered into possible dimensions so that these could also be reviewed by the expert panel. Only very few indicators for patient and staff satisfaction were identified from documents available within the Kenyan health system or scientific literature relating to Kenya. Internationally validated indicators were therefore referred to for these areas, and 22 indicators for patient satisfaction , the source document and possible questions or measurement prescriptions (items) that could be used to acquire the data needed for each indicator were prepared. An example of the items developed for one indicator is provided in Fig. A multidisciplinary panel of fifteen experts was invited to rate the indicators. Applicants were selected according to pre-defined criteria covering the clinical areas of interest at different levels of the health system, as well as from a policy and research perspective. The final selection included gynaecologists from district hospitals, nurses/midwives experienced in the provision of maternal, neonatal and child health services, as well as in caring for survivors of gender-based violence, a health-facility in-charge, a hospital manager, an academic familiar with Quality Management, representatives from the Division of Reproductive Health from province and district level, from the DSRS and the faith-based sector.At the first workshop, the panel members reviewed the indicators, identified those of greatest relevance and assessed them according to the Specific, Measurable, Achievable, Relevant and Time-bound (SMART) criteria. In the case of the patient and staff indicators, the panel's function was to review and endorse their applicability in the Kenyan context.Preference was given to indicators for which data were already being collected, e.g. in family planning, antenatal care and delivery registers and on post rape care forms to avoid generating additional workload at facility level, and to make the process of routine data collection more meaningful for the quality improvement effort. Upon the panel's advice, further expert opinion was sought to develop additional indicators on drug and laboratory services as this was found to be a gap and led to the development of 25 and 23 new indicators, which were added to the register in advance of the rating. After these steps were completed, there was an updated register of 310 indicators.In a next step, all the indicators in the updated register were reviewed to ensure they could be precisely measured as this reduces the risk of bias related to variation of results . For exaThe 310 indicators in the revised register underwent a rating process at the rating workshop. Analyses were based on the RAND/UCLA Appropriateness Method . IndicatThe experts then checked the weighting of the rate indicators between the five proposed domains. It was confirmed that all the twelve focus areas of KQMH were addressed by the five domains and twenty-nine dimensions of IQMS  to 5 (excellent), with an additional non-applicable/not relevant box. It required patients to confirm that they have used the facility at least twice before the current visit and to indicate the kind of services used at the current visit. The survey included questions on staff attitudes, how far patients felt listened to, received rapid relief of symptoms, encountered availability of drugs, clarification of instructions and privacy/confidentiality. Yes or no questions on whether fee schedules were prominently displayed, fees were paid, receipts issued or exemptions observed as applicable were also included.The ‘staff survey’ also made use of a five-point likert scale, with an additional non-applicable/not relevant box. Staff were asked to agree or disagree with statements on whether supervision was provided in a supportive manner, team responsibilities were well defined, there is a good working atmosphere in the team, staff can voice their opinions without fear of reprisals, there was clear communication from management, equipment is available in working order, etc. Moreover, respondents are asked to express satisfaction with the working conditions , as well as with relations with the community. Yes or no questions on whether the staff member had a signed contract, written job description and had undergone an annual appraisal in the last 12 months were also included. Some aspects of the staff survey were already published .The ‘facility self-assessment’ comprised the auto-evaluative element of the IQMS. In advance of the assessment by the external facilitator, this is sent to the facility manager for completion. It draws heavily on readily available registers including the ANC register, family planning register, stock cards, maternity register, HMIS and laboratory records and focuses on acquiring quantitative data to furnish the indicators, e.g. total number of patients for different services and the proportion of them receiving various aspects of ANC, delivery and postnatal care. It also explored support provided to staff, staff appraisal processes, infection control, supply chain issues and aspects of financial management.The ‘facilitator assessment’ maps closely to the self-assessment but also picks up aspects raised in the patient and staff surveys for triangulation purposes. As the facilitator already has the results of those two surveys when they visit the facility for the first time the assessment provides them with the opportunity to explore aspects that these may have raised. This assessment also has an element of verification, for example, requiring the assessor to look at random records to see how well they have been kept, and to establish stock levels and availability of functioning equipment on the actual day of the assessment.Finally, the facilitator conducts an ‘interview with the facility manager’ using a pre-defined interview guide. This is designed to explore the synergies between the different areas, and to gain a deeper understanding of processes like efforts to motivate staff, or how to learn from critical incidents—where the discussion covered who does the analysis of such incidents, if there is formal structure for doing so, and an examination of some examples in the last quarter and what action was subsequently taken.During the development of the tools, care was taken to make use of triangulation and to gather data for the sub-questions for each indicator from a variety of sources.Table Once the data collection tools had been developed, they were field tested at two facilities between January and February 2013. Staff were encouraged to fill out the staff survey whilst the project coordinator was still at the facility. For staff that were absent a collection box was left and arrangements made for collection at an agreed date. The patient survey was carried out orally in local languages. At least 100 responses per facility were sought from patients attending Antenatal Care, Postnatal, Family Planning and Maternity services. Once this number had been obtained, the process was considered complete. These surveys were complemented with the information received from the facility managers via their self-assessment.A trained EPA facilitator with previous experience of working in sub-Saharan Africa supported the new quality facilitators to review the analysis of the data that had been collected from each facility in advance of the facility visits. This enabled them to start to generate a picture of the facility and where problems in need of greater examination might lie.The process of the facility visits took 3 days and included a visit of the target departments/services  for the facilitator assessment. The facilitators were accompanied by the head nurse of each facility and the respective responsible person of the service. Next, the interview with the Hospital  Management Team was carried out using the interview guide. Facilitators then prepared the results and fed them back firstly to management and secondly to the rest of the team. Directly after the feedback sessions, the staff were supported to prepare a list of goals and priority areas and a plan of action for improvement including quick wins.A feedback workshop involving managers and staff was arranged for the two initial pilot facilities. The self-evaluative nature of the approach was well received. In particular, the process was praised for making the importance of data for planning and prioritization more clearly apparent. As the approach rests strongly on the use of national indicators, this meant that the results could easily be fitted into national planning and monitoring and evaluation processes.The approach was found to be highly practical and appreciated for enabling facilities to set realistic priorities and commence the improvement process quickly without any additional significant resources. Both facilities were already able to present concrete steps they had already taken to improve quality since the field testing with the facility assessment took place. One facility received poor feedback about the attitude of their staff from the patient survey and had since arranged a focus group with women attending ANC to explore and address this.After the field testing process, the tools were finalized. This did not involve any changes to the indicators, but at the level of the items/sub-questions some refinement were made and some additional items added to make the measurement clearer. In addition, the sequencing was adjusted, for example to enable the facilitator to deal with all issues on a certain topic, or gather all information from a single registry before moving to the next aspect. IQMS is currently used in 30 health facilities in 3 counties.The EPA approach is highly integrative and takes pre-existing indicators from national systems as well as available QI initiatives as it starting point. With the exception of the 44 international indicators that were retained through the review and rating process, 234 of the 278 indicators used in the ISQM had previously existed in the Kenyan health system.In addition to exploring clinical areas, the approach offers the possibility to illuminate health system bottlenecks like drug distribution systems and facility accounting issues. The data collected via the various tools are transferred into indicators and visually displayed for feedback to the facility team as an integral part of the facility visit process. This breathes life into the process of collecting data for indicators. Based upon the objective and precise measurement and presentation of detailed results, facility teams can be supported to set their own quality targets making best use of existing resources according to the principle of Pareto. Moreover, the approach offers the possibility for facilities to compare baseline results with those of subsequent assessment so they can chart their progress. It also allows for the results of a facility assessment to be benchmarked against the average result of all the participating facilities.Adapting the EPA in Kenya did support the operationalization of the KQAM, in particular because it provided facility level health managers with a practical tool for responding to patient demands and optimizing quality in small, effective ways without having to first wait to mobilize extensive resources.