Change agency in its various forms is one intervention aimed at improving the effectiveness of the uptake of evidence. Facilitators, knowledge brokers and opinion leaders are examples of change agency strategies used to promote knowledge utilization. This review adopts a realist approach and addresses the following question: What change agency characteristics work, for whom do they work, in what circumstances and why?The literature reviewed spanned the period 1997-2007. Change agency was operationalized as roles that are aimed at effecting successful change in individuals and organizations. A theoretical framework, developed through stakeholder consultation formed the basis for a search for relevant literature. Team members, working in sub groups, independently themed the data and developed chains of inference to form a series of hypotheses regarding change agency and the role of change agency in knowledge use.24, 478 electronic references were initially returned from search strategies. Preliminary screening of the article titles reduced the list of potentially relevant papers to 196. A review of full document versions of potentially relevant papers resulted in a final list of 52 papers. The findings add to the knowledge of change agency as they raise issues pertaining to how change agents’ function, how individual change agent characteristics effect evidence-informed health care, the influence of interaction between the change agent and the setting and the overall effect of change agency on knowledge utilization. Particular issues are raised such as how accessibility of the change agent, their cultural compatibility and their attitude mediate overall effectiveness. Findings also indicate the importance of promoting reflection on practice and role modeling. The findings of this study are limited by the complexity and diversity of the change agency literature, poor indexing of literature and a lack of theory-driven approaches.This is the first realist review of change agency. Though effectiveness evidence is weak, change agent roles are evolving, as is the literature, which requires more detailed description of interventions, outcomes measures, the context, intensity, and levels at which interventions are implemented in order to understand how change agent interventions effect evidence-informed health care. The field of evidence-informed healthcare is broad and encompasses a variety of theories, methodologies, methods and tools. A decision maker needs to negotiate a range of interrelated cognitive, social and creative processes of evidence selection and construction, and a range of contextual factors and behavioral changes in order to make effective health care decisions ,2. This et al.  perform), for whom does it work , in what circumstances (different characteristics), and why ’ The overarching question in this study, therefore, was: What change agency characteristics work, for whom do they work, in what circumstances, and why? To answer this overarching question, we devised three specific questions:The purpose of this realist review was to determine how change agency ‘interventions’ may operate in different contexts and with what effects. This realist review is set within the standard realist evaluation or review question; 1. How do the characteristics of the change agent affect knowledge utilization?2. How does the interaction between the change agent and the setting affect knowledge utilization?3. What is the overall effect of the change agent on knowledge utilization?Realist synthesis  focuses e.g., individual, team, organization (level), and evidence of particular contextual issues shaping the intervention   successful in these roles . Given tThis knowledge and skill set assists change agents in addressing the variety of contextual issues that need to be addressed in bringing about change. In addition, these contextual issues can interact with personal characteristics and may impact the relative importance of particular characteristics and skills. The change agent role does not seem to require a formal position or formal authority, with social influence and social interaction being key components of the role. However, this is in contrast with the need for formal recognition of the role, and the potential for formality to facilitate influence over knowledge and information flow, an important part of change agency.The limitations of this study relate to the review period, the quality of included papers, the sensitivity of the search strategy, as well as issues related to the lack of theory in published papers.This realist review was undertaken in 2007 and included literature between the period of 1997 to 2007. This 10-year timespan includes a period of time when a large quantity of evidence-informed practice, knowledge translation and research utilization papers were published, and indeed represents the period when implementation science research began to emerge. However, we are conscious that in the six years since the review has been conducted, many more papers have been published that will add further to this review. While we are aware that our review adopted a focus on change agency as an intervention, we are confident that the literature included is representative of the research in this field at that time and that this realist review provides a platform for further development and expansion. We are not aware of any other review that has focused on ‘change agency’ as a concept or term in and of itself to date.Included papers ranged from less-detailed accounts of ‘success stories’  to thoseUse of well-established theories was not uniformly evident across included papers. In fact, absence of theory was almost as frequent as use of a theoretical framework; and reference to individual concepts, such as research utilization , facilitFinally, while we have attempted to make our search strategy as sensitive as possible (and erred on the side of sensitivity as opposed to specificity), we are conscious that Knowledge Utilization continues to be a poorly indexed area of literature, and so it is difficult to design a perfect search strategy. In order to compensate for this limitation, we involved the entire group in overseeing and reviewing search strategies and search results in order to ensure we were being as comprehensive as possible.As the first realist review of change agency research, a comprehensive, inclusive review of the published evidence has been produced, summarizing what the literature demonstrates about the personal characteristics and context within which change agency functions as well as the effectiveness of change agents. The review highlights significant gaps and provides direction for future development of change agency for evidence-informed healthcare. Change agency strategies currently used to foster knowledge utilization include opinion leaders, facilitators , practice developers, education outreach, academic detailing, and the use of multiple change agents. While evidence of effectiveness is weak, in some cases in terms of outcomes data, there is evidence that supports the importance of opinion leader and facilitator roles. The literature would benefit from better descriptions of interventions and determination of outcomes, as well as more detail on the context, intensity and levels at which interventions are implemented. If a focus on measurement of appropriate outcomes and detailed reporting can be realized, the field can learn more from the implementation of change agency roles across different contexts. At this time, there does not seem to be adequate evidence to assess whether particular roles and associated mechanisms are more effective in particular contexts, or to make generalizations about which change agent(s) work best for which professional groups or settings. However, there is emerging evidence to suggest that ‘fit’ might be an important mechanism, such that if there is compatibility between a change agent’s characteristics, approach, relationship with individuals and teams, and the contextual conditions in which they are working, their chances of being more successful in change agency might be enhanced. This review contributes to what we know about contexts in which the effect of change agency can occur, mechanisms through which change agency functions, and outcomes addressed in the literature within the scope of this review. It is expected that additional work to test hypotheses generated could further contribute to what is known about the contexts, mechanisms, and outcomes related to change agency effectiveness.Alison Hutchinson is a member of the International Editorial Board of Implementation Science. Bridie Kent is an Associate Editor for Implementation Science; other editors made all decisions on this manuscript.BM and JRM led the project. All authors participated in defining the scope of the review. KD and ESC executed the search. All authors undertook the appraisal of evidence and data extraction. All authors were involved in the analysis process. AMH led the documentation of the study process. KD led the development of the narrative. BM wrote the first draft of the paper; JRM, AH, and KD commented on it. All authors provided feedback on various drafts, and read and approved the final manuscript.Search strategies and databases.Click here for fileseven‒step approach to data analysis and synthesis.Click here for file


Parents of children with intellectual disabilities and/or physical disabilities are supposed to have an increased risk for parenting stress and psychological distress. We as professional caregivers sometimes experience difficulties in keeping good relations or communicating with the parents. Professional workers in 460 institutions and consultation centers throughout Japan answered a questionnaire on their clinical experiences. About 90% of the facilities experienced “distressed parents,” and the parents' condition such as mental health seemed to influence this. Signs of a depressive state were the most common psychiatric disturbances detected, and it was notable in the pervasive developmental disorder group. More welfare support, presence of support groups, support from other family members, and medical treatment of the parents' problems were considered to be helpful and thus requested to be improved. Training more professionals who can properly deal with the parents' mental health needs is an urgent matter that must be tackled. Many previous studies have revealed that parents, especially mothers, of children with developmental disabilities such as intellectual disabilities (IDs), developmental delay, and physical and sensory handicaps are more likely to show signs of psychological distress or depressive symptoms and to exhibit lower well-being than parents of typically developing children –5. It isRecently, the mental health needs of adults with ID have also been taken up for discussion. Studies have revealed that psychiatric disorders are more prevalent in people with ID compared within the general population . In factIn Japan, high-quality psychiatric services for the parents of children with ID are assumed to be not well established. So far, the major portion of resources has been directed to the treatment of and services connected with the children, and not enough attention has been paid to the actual mental condition and needs of the parents. To our knowledge, there have been no reports on a nationwide scale on the mental health and distress of parents having children with developmental disabilities in Japan. Since the understanding of the parents' mental health may be essential for providing more appropriate support, we aimed to obtain a clear perspective on the situation facing the parents through this facility-based nationwide study.The current survey included 1,102 institutions and consultation centers for children with developmental disabilities distributing in all prefectures in Japan, which were listed in the national register of agencies, organizations, and institutions related to intellectual disabilities  and the The questionnaire was written in Japanese and was divided into two sections with a total of 47 multiple choice questions. There was space to fill out for 5 of the questions. The first section sought information about the characteristics of the facility, such as staff adequacy, the scale of the facility, the health promotion services provided, the ages of their clients, and the clients' main disabilities, namely, ID, pervasive developmental disorder (PDD), profound intellectual and multiple disabilities (PIMD), physical disabilities, and others. The second section sought information about the clients' parents, such as signs of mental health distress and their needs, from the professional caregivers' point of view. Also measures taken by the professional caregivers when encountering distressed parents were asked in detail.Questionnaires were mailed in October 2008, with an explanatory letter to the person in charge of each institution or consultation center. When agreement was met to participate in this study, one or more service providers in each facility completed the questionnaire based on all sources of information available. The questionnaire was to be returned unsigned, using the stamped, self-addressed envelope enclosed. For ethical considerations, the information disclosed in the questionnaire was in a form which made it impossible to identify the facility and clients. This study was approved and carried out under the supervision of the Japan League on Developmental Disabilities (JIDD).P value of 0.05 or less was considered to be statistically significant. Answers to open-ended questions were analyzed thematically by coding them into separate categories.The statistical analysis including the chi-squared test was performed with the aid of the Statistical Package for the Social Sciences 15.0 . A two-sided A total of 460 out of 1,102 facilities replied within four weeks, the response rate being 41.7%. According to the clients' main disabilities, each facility was classified into the following categories: ID, PDD, PIMD, physical disability group, and others . The lasThe service providers who actually replied to the questionnaire were well trained and experienced. Many were working for over 20 years. Their average age (SD) was 44.7 (9.5) years old for the ID group, 53.0 (7.6) for the PDD group, 48.3 (8.4) for the PIMD group, and 55.3 (4.9) for the physical disability group. Their professions were diverse. Among the responders, there were 176 (38.3%) physicians, nurses, or psychologists. Many certified child care workers also responded.373 out of the 415 facilities (about 90%) experienced cases with difficulties when communicating with the clients' parents. The percentage was high regardless of the children's disabilities, being concretely highest in the PDD group (96.9%) and lowest in the physical disability group (86.7%). The service providers noticed that the difficulties seemed to be increasing. The proportion of such parents, out of the total, was reported to be “almost none” (5% or less) or “few” (less than one fourth of the clients) in most of the facilities . It shouχ2(df = 9) = 41.9, P < 0.001]. In the PIMD and physical disability groups, the parent's poor socio-economic status and heavy care-giving burden, reflecting the child's level of disability, were considered to be major factors in approximately one-third of the cases.The primary reason for these difficulties was thought to be the parent's personal condition, such as poor mental health . This waχ2(df = 12) = 65.1, P < 0.001]. Well-treated cases were only 5% out of the total; thus, most of these conditions were considered to be not medically well treated.Signs of depression or a depressive state were the most common psychiatric disturbances seen in the parents. Among the four groups, the PDD group most commonly experienced cases which showed signs of depression or a depressive state in parents. The proportion of such parents was approximately 70% of the total .When a parent suffered from signs of psychiatric disturbances, more than half of the children experienced maltreatment. The details of inappropriate treatment were analyzed . PhysicaVarious measures were taken to deal with these difficult cases . The leaMany factors were reported to affect the mental health of parents. The presence or absence of support from other family members  and the existence (or not) of a medical condition in the parent were major factors . PracticTo fulfill the demanded future role of their facility, respondents expressed the importance of more collaboration with other institutions and consultation centers and the necessity for more special training courses targeting support professionals and recognized the urgent demand for more specialists especially psychologists who can support the mental health needs of both the children and their parents.In the present study, we surveyed institutions and consultation centers for children with developmental disabilities in Japan, which play a central role in the social support networks. This facility-based nationwide survey revealed the situation facing the parents of children with ID and other developmental disabilities from the professional caregivers' point of view. Almost all of the facilities experienced difficulties in keeping good relations with the clients' parents, regardless of the children's disabilities, and the majority of service providers noted that the proportion of such parents, out of the total, was roughly between 5 and 25%, and still increasing. The primary reason for these difficulties was thought to be the parent's condition, such as their mental health and background. Also, signs of depression or a depressive state were assumed to be the most common psychiatric disturbance seen. These results suggested that thorough consideration of the parents' mental health needs, especially prevention of depressive conditions and support for parents suffering from them, is urgent-demanded task for facilities.ID, attention-deficit/hyperactivity disorder (AD/HD), and PDD are common developmental disorders, and the latter two are noted to have substantial genetic components . It has The findings of the present survey must be interpreted allowing for the limitations of the use of unconfirmed data reported by professional caregivers' who come into contact with children as their clients, and their parents on a day-to-day basis. Evidently, the service providers' perspective on parental mental health was consistent with previous reports from Western countries on major mood disorders and PDD. In other words, facilities where the clients were diagnosed as having PDD experienced significantly more cases of parents with signs of a depressive state compared to other facilities, and the onset of depression was considered to be prior to the birth of the child in many of the cases.Although these professional caregivers were well trained and well experienced, only, one-third were physicians, nurses or psychologists. On account of the limitations of these data, we emphasize confirming the diagnoses of psychiatric disturbances through direct contact with the parents by specialists such as psychiatrists is necessary in future studies, for accurate understanding of the overall problem. In Japan, there is no official system to check and document the parents' condition including their mental health status. Parents are not accustomed to being asked about their own mental health, so there is a tendency to avoid discussion on matters concerning themselves. This was the major reason why we asked the professional caregivers about the parents' condition, not the parents directly, in this study. But still we judged it to be worthwhile at this moment to summarize the professional caregivers' impression on this issue, since the case in Japan has never been described in detail despite of its importance.Because the majority of burden for daily care of handicapped children is typically carried by mothers, particular concern is raised for their adaptation. In the past studies, the psychosocial outcomes in mothers were said to be better predicted by psychosocial factors such as more active social life and family resources . Recent Since the burden for daily care is mainly carried by the mother, similarly in Japan, service providers tend to be in contact with the mother more frequently than other family members . This maPractical use of social support networks such as participation in face-to-face family support groups, more financial support for the household, more direct welfare support for the child, and medical treatment of the parent's psychiatric disturbance were reported to be helpful and thus requested to be improved, in order to meet the mental health needs of the parent. We would like to emphasize the fact that although the importance of medical treatment for the parents' psychiatric disturbances was pointed out, it was also realized that these conditions were presently not being medically well treated. This shows that current psychiatric services in Japan are not adequate to meet the complex mental health needs of the parents appropriately. To resolve this challenging issue, more intensive collaboration between other child-care facilities and organizations, aiming at the mental health needs of the parents, is demanded. The paucity of trained psychiatrists and other allied professionals also needs to be addressed, and in order to fulfill this, sufficient discussion and research on the establishment of an effective training system for specialists is warranted.Providing direct advice for the parents on the utilization of social support networks is a reliable measure that can be immediately taken. Training more professionals who can properly deal with the parents' mental health needs is an urgent matter that must be tackled. More direct welfare support for the children is naturally helpful. Overall, the present study is the first nationwide survey that examined the professional caregivers' perspective on the mental health of parents of children with developmental disabilities, and it underscores the importance of understanding and supporting the parents' mental health needs, which leads to more appropriate support for children with developmental disabilities.


The Netherlands Society of Cardiology (NVvC) and the European Society of Cardiology have assumed responsibility for the quality of care in the Netherlands and in Europe. To this end, the societies organise congresses and publish journals to promote exchange of information on research and developments in cardiology. The societies develop guidelines for prevention, diagnosis and management of cardiovascular disease and they promote education programmes. Surveys and registries provide information on the actual practice of cardiology, to assess whether the guidelines are followed in clinical practice, to identify areas where improvements can be made and to verify whether the guidelines, and the clinical trials on which these are often based, really address the patients which we see in our practices Fig. . UnfortuThe report by Soedamah-Muthu and others from the Alpha-Omega trial  is a gooThe Alpha-Omega trial enrolled 4835 patients with a history of myocardial infarction from 32 hospitals between 2002 and 2006. Their mean age was 69 years and 78% were men. Overall the patients were treated intensively: in 2006, 98% received antithrombotic drugs, 87% a statin (and 3% or more other lipid-modifying drugs), 75% a beta blocker, and 59% an ACE inhibitor or angiotensin II receptor blocker. Lipid levels and blood pressure were reasonably controlled, but no information was provided on the level of control of diabetes in the 22% of patients with this disease. As in other surveys conducted in the same period  may plan to discuss the guidelines and the underlying clinical trials again at a next congress and education programme. We may question the use of other, non-statin, lipid-modifying drugs in at least 3% of the patients since these drugs may reduce the LDL-cholesterol level, but there are no consistent data that these drugs have a favourable impact on survival or reduction of cardiovascular events. The outcomes of the ongoing IMPROVE-IT trial to assess the value of ezetimibe in secondary prevention are eagerly awaited. Indeed, we might sit back and be reassured that in our practice we need just a bit more attention to further improve our secondary prevention measures.However, to my regret, no data on the 32 individual practices are presented in the report. To assess the quality of our practices we cannot hide behind overall data from our country, even if one third of the hospitals in the Netherlands have provided these data. We need to compare the actual data from our own practice, from our own hospital, with others to identify areas for our own improvement. We need actual data from 2011 and 2012 and should not be satisfied with a review of data collected several years ago because practices change, as illustrated again in Fig. A registry of all procedures, outcome and complications is a requirement for licences for interventional cardiology and other procedures. The National Cardiovascular Data Registry (NCDR) has been created for this purpose. Registries for pacemaker and ICD implantation, for percutaneous coronary interventions and for percutaneous aortic valve implantation have been developed, but I understand that data collection is slow, that existing registries in different hospitals are not fully consistent and that no agreement has been reached on the type of reports which professionals and the public may expect. Yet, agreement on the content of many registries was reached at the European level several years ago  and a fiProf. dr. Maarten L. SimoonsThoraxcentrum, Erasmus MC, Rotterdam, the Netherlands


There are strong and direct relationships between undernutrition and the disease caused by infectious organisms, including the diverse pathogens labeled as neglected tropical diseases (NTDs). Undernutrition increases the risk of infection, the severity of disease and the risk that children will die, while the physical damage, loss of appetite, and host responses during chronic infection can contribute substantially to undernutrition. These relationships are often synergistic. This opinion article examines the role of nutrition in controlling NTDs and makes the point that mass drug treatment - the major strategy currently proposed to control several diseases - is crucial to controlling disease and transmission, but is only the start of the process of physical recovery. Without adequate energy and nutrients to repair damaged tissues or recover lost growth and development, the benefits of treatment may not be evident quickly; the effects of control programs may be not appreciated by beneficiaries; while vulnerability to reinfection and disease may not be reduced. There is substantial potential for nutritional interventions to be added to large-scale programs to deliver drug treatments and thereby contribute, within a broad strategy of public health interventions and behavior change activities, to controlling and preventing NTDs in populations, and to restoring their health. The fundamental basis of the relationship between an infectious organism and its host is nutritional because the host is the source of all nutrients needed by the organism for maintenance, growth, and reproduction . But theThe relatively new classification by the World Health Organization (WHO) of 17 diseases as 'NTDs' includes eight that are caused by at least 23 species of parasitic worms or helminths . The hopThe NTDs listed in Table Although parasites are dependent on their hosts for their nutritional needs, nutrition is only the first of four inter-related factors that influence the outcome of infection. The second is the virulence of the pathogen, which is often related to the multiplication of microparasites such as bacteria and protozoa, or to the numbers of macroparasites such as helminths acquired, and to where and how they live within the host and cause disease. The third factor is the innate susceptibility of the host to infection, which may be related to the presence of specific receptors on body surfaces or to non-specific defenses against infection such as gastric acidity. The fourth factor is acquired resistance to infection, mediated by cellular and humoral immune responses, both of which are influenced by nutritional status .Although both virulence and susceptibility are largely genetically mediated, the occurrence or outcome of disease can be influenced by the nutritional status of the host. This is illustrated in Figure Parasitic organisms and nutrition have separate and combined effects on their host: nutritional status can affect the disease caused by parasitic organisms, parasitic organisms can impair nutritional status, and the two may interact so that their combined effects are synergistic or antagonistic.Chlamydia trachomatis has also been shown to be related to the severity of trachoma [A first point to make is that for many NTDs there is a difference between being infected and being diseased. The number of organisms greatly affects the severity of disease and any nutritional effects, particularly for helminths, although the ocular bacterial load of trachoma , so the trachoma , althougvice versa, is hard to obtain. A few longitudinal studies of children have clearly shown that repeated episodes of respiratory and intestinal infections, including worms, are associated with undernutrition and growth failure [The evidence for the effect of nutrition on infection and  failure ,16. But C. trachomatis was lower in vitro when grown in a medium containing an iron chelating compound than without, suggesting that iron is required for infection to occur [To help understand how undernutrition may influence the processes of infection and disease, Figure to occur .There is considerable evidence that acquired immune responses (Arrow B), which may be full or partial, are impaired by specific micronutrient deficiencies especially of vitamin A, zinc, and iron ,20. PartThere is sparse evidence that undernourished hosts may become diseased because of a burden of parasites that a well-nourished host would tolerate (Arrow C), but there is evidence for some species that good nutrition can diminish the effects of parasites that might otherwise cause disease. For example a well-nourished host could replace small to moderate blood losses caused by hookworms or schistosomes, so that anemia may not occur ,23.Litomosoides carinii showed a greater death rate among protein-deficient animals given the same infectious dose as well-nourished rats [There is strong evidence that undernourished hosts are in general at greater risk of dying of infectious diseases than well-nourished hosts (Arrow D), mostly based on analyses of the relationship between underweight and the risk of dying ,25. Examhed rats .Schistosoma spp [There is a little evidence, also from studies of animals, that drugs may be less effective in undernourished hosts (Arrow E), particularly animals infected with soma spp ,28, perhThe effects of undernutrition and infection outlined in Figure The diseases listed in Table Loss of appetite may make an important contribution to the development of undernutrition and may be exacerbated if the caregiver's response is to withhold food or, for reasons of culture or poverty, give a nutritionally poor diet . AlthougTrichuris trichiura reported effects of anthelmintic treatment on tests of cognition [Stunted growth and underweight in children are probably among the most important consequences of NTDs, particularly due to intestinal nematode worms . There iognition , but morA. duodenale [N. americanus [T. trichiura [S. mansoni and S. haematobium cannot be related to the number of worms but have been shown to be as much as 126.0 mL/day [The loss of blood caused by worms has been estimated to be 0.14-0.26 mL/worm/day for uodenale , 0.02-0.ericanus , and 0.0richiura . The dai0 mL/day ,42. Ther0 mL/day , but bloThere is no constant linear relationship between worm load and the hemoglobin concentration as the amount of iron in the diet and its absorption efficiency, which typically ranges from 5% to 25% depending on its dietary quality , can serThe main method used to assess whether NTDs have an effect on human health or growth is to undertake randomized trials of treatment, although having untreated controls is now hard to justify. The effects of treatment on most nutritional outcomes is difficult to assess, mainly because drugs kill only worms, they do not provide the nutrients needed for catch-up growth, or for any other consequent deficit for that matter. For example, if hemoglobin is being lost because of hookworms or urinary schistosomiasis then stopping that loss with an anthelmintic drug does not have an effect on the manufacture of hemoglobin in the bone marrow, that rate is mainly dependent on the quality and quantity of the diet to provide nutrients for hemopoiesis. A relative deficiency of even one micronutrient may be rate-limiting, which might explain why some studies of giving iron supplements alone to anemic people after deworming have found no effect on their hemoglobin concentration ,46. It aTrichuris dysentery syndrome found that they grew on average 10.9 cm/year after treatment, more than two standard deviations above the rate expected of children of the same height-for-age [As recovery occurs only slowly for chronically undernourished individuals if their diet is not improved, supplementary food or micronutrients are usually required. For example, a study of schoolchildren in Tanzania reported an increase in hemoglobin concentration of 3.6 g/L three months after children were treated with albendazole and praziquantel alone, but the children given supplements of iron and vitamin A in addition showed an increase of 22.1 g/L over the same period . It may -for-age . If no nAlthough supplementary feeding programs are relatively expensive, there is potential to deliver low-cost micronutrient supplements at the same time that people are treated for NTDs, especially to school children . Table 2As with most treatments, the major financial and economic costs arise from delivering treatments to target populations such as schoolchildren. These costs are hard to standardize or compare for a number of reasons: because methods of costing differ and may not include the costs incurred by schools ; becauseBut drugs alone are not necessarily 'rapid impact interventions' ; they maBut most of the pathogens that are the focus of major NTD control efforts do not have specific and identifiable symptoms until disease is severe, while much of the damage to the eyes, skin, lymph ducts, liver, and kidneys is irreversible. If the effects of treating NTDs are to be quickly apparent, particularly to the mothers of children, then supplementary nutrients may be one of the simplest and least expensive interventions that there is to promote recovery after treatment and contribute to NTD control.Although we are making a case for the value of nutritional supplements after treating NTDs, we recognize that a truly integrated control program needs more than pills. For example, it is possible to treat several NTDs at once where they co-occur ; other dFigure Figure NTD: neglected tropical disease.The authors declare that they have no competing interests.AH was commissioned by Helen Keller International (HKI) to write a review that led to this paper. AH drafted the paper to which all authors contributed and approved the final version.AH is a nutritionist and parasitologist who is Visiting Reader in Public Health Nutrition at the University of Westminster, UK. YZ is a physician, parasitologist, and Africa Regional Coordinator for NTD Control for HKI. CM is Director of NTD Control for HKI, based in the USA. SB is a Vice-President of HKI and Regional Director for Africa.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1741-7015/10/41/prepub


This paper provides an overview of the historical development and current status of the Lives Saved Tool (LiST). The paper provides a general explanation of the modeling approach used in the model with links to web sites and other articles with more details. It also details the development process in developing both the model structure as well as the assumptions used in the model. The paper provides information about how LiST has been and is currently being used by various organizations and within national health programs. We also provide a review of the work that has been done to try to validate the outputs of the model. Lives Saved Tool (LiST) is modelling software that has been in use the past 10 years. The initial version of the software was created as part of the work for the Child Survival Series published in The Lancet in 2003 [Lancet Nutrition Series in 2008 [The  in 2003 . The mod in 2008 . During LiST was shifted into the public domain by making the program freely available as part of the Spectrum Policy Modeling System software package (Spectrum). This arrangement not only offered users the advantages of the DemProj module to make demographic projections, it also incorporated the AIDS Impact Module (AIM) to estimate the impact of interventions affecting HIV/AIDS [LiST has been expanded further to estimate the impact of interventions on birth outcomes and stillbirths [At this point, HIV/AIDS . In morellbirths , maternallbirths , in addiLiST was initially conceived and has been extensively used to estimate the impact of scaling up interventions on mortality as a way to quantify the potential effectiveness of an intervention, to stress the need for refocusing priorities, or to set targets at a global level [al level -6. TheseLiST in developing countries to guide the strategic planning process is another valuable way in which the modeling tool is being used [LiST to develop multiple scale-up scenarios in order to compare the impact on mortality due to various combinations of proven interventions. For example, if a country has decided to roll out community health workers who will provide broader access to treatment for malaria, pneumonia and diarrhea, one can use LiST to estimate the change in coverage of these interventions over time and then estimate their combined impact on mortality. Alternatively, one can develop a second scenario where these workers are also trained to provide education about breastfeeding to young mothers. These estimates of impact of various packages of grouped interventions can then be evaluated in conjunction with cost and feasibility considerations to decide which strategy should be implemented.Use of ing used . PolicymLiST has been used is to evaluate the impact of large-scale programs that aim to scale up health services for mothers and children. In this type of analysis, LiST can be used to translate measured coverage changes into anticipated or projected estimates of mortality reduction [LiST to understand and help attribute the causes of measured or observed declines in mortality to specific activities. In a recent case study in Niger, LiST was applied to assess the contribution of different interventions to observed reductions in child mortality [A third way that eduction . Retrosportality .LiST has been characterized as a linear, mathematical model that is deterministic [LiST, the primary inputs are coverage of interventions and the outputs include changes in population-level risk factors  or cause-specific mortality , maternal mortality and stillbirths). The relationship between changes in inputs (intervention coverage) and one or more outputs is specified in terms of the effectiveness of the intervention for reducing the probability of that outcome. Outcomes of interest include either cause-specific mortality or a risk factor for mortality . The overarching assumption in LiST is that mortality rates and the cause of death structure will not change dynamically, and that any differences will be solely in response to changes in intervention coverage. The model assumes that changes in distal variables such as increases in per capita income or higher levels of maternal education will affect mortality by increasing coverage of interventions or reducing risk factors.ministic . It descLiST. These evidence-based interventions have been demonstrated to reduce stillbirths, neonatal deaths, deaths among children aged 1-59 months, maternal mortality or risk factors. Interventions can be linked to multiple outcomes, with some interventions linked to multiple causes of death and risk factors. The key feature of LiST is that it allows one to look at the impact of scaling up coverage of multiple interventions simultaneously, and does not assess only a single intervention or single cause as is the case for many natural history models.Currently, there are approximately 70 separate maternal and child health interventions within LiST, the efficacy of an intervention is defined in terms of the reduction of a cause of death or risk factor. The calculation of impact is simple when considering only a single intervention, because the change in coverage times the efficacy of the intervention is applied to the level of cause-specific mortality. For example, there may be 10,000 diarrhea deaths in children aged 1-59 months, and the proposed intervention is the introduction of a new vaccine that would be 50% effective in reducing diarrhea mortality. If coverage reaches 50%, diarrhea mortality among children would be reduced to 7,500 ). If a second or a third intervention is added, the same approach is followed, although the impact of the additional diarrhea intervention(s) would be applied to the residual diarrhea deaths. Following the previous example, if the second new diarrhea intervention is also 50% effective and coverage reaches 50%, diarrhea mortality would fall to 5,625 . By using cause-specific efficacy and applying each intervention to the residual deaths remaining after the previous intervention, LiST ensures that double counting is avoided and the potential impact of multiple interventions is not erroneously inflated.The model has several structural features that must be considered in order to appropriately estimate how scaling up coverage of multiple interventions and changing risk factors will impact mortality. First, the effectiveness or efficacy of an intervention must be described in terms of reductions in cause-specific mortality rather than overall mortality. With cause-specific estimates of efficacy, the combined impact of interventions can be computed. Within LiST has a fairly simple age structure that serves as a theoretical cohort. The age periods used in LiST include pregnancy (among women aged 15-49), 0-1, 1-5, 6-11, 12-23 and 24-59 months for children. Within the model, impact in one age period has a cascading effect on what happens in the next period. For example, if interventions that have an impact on neonatal mortality are scaled up, more children would be expected to survive that period and will subsequently be exposed to the risk of death during the 1-59 month period. Therefore, the number of deaths in this age group will increase even though the rate of mortality will remain the same.LiST often impact one or more age groups or types of mortality .For maternal mortality, stillbirths, neonatal, and child (1-59 months) mortality, the cause of death structure is fixed in the base year. An appropriate mortality rate is applied that corresponds to the relevant age period; within the 1-59 month period, rates have been adjusted to reflect the higher risk of child mortality at younger ages. Maternal and child interventions specified within LiST runs as a linked module within Spectrum and is currently linked directly to three additional modules. A required linkage is between LiST and the demographic module, DemProj. DemProj is a fully functioning demographic package that allows users to define populations via inputs including age-specific fertility, migration, population structure by age and sex, and other factors. Spectrum houses a database of the most recent population projections from the United Nations Population Division for 193 countries and regions [LiST users to select a country, base year, and end year, and LiST automatically loads in the population projection for that time period. Users can rely on this as the population projection to calculate the number of deaths by age group, but options exist to update or alter these figures within DemProj if needed. regions . The desFamPlan is the second module within Spectrum linked to LiST. FamPlan was developed to estimate the impact that scaling up family planning would have on fertility. LiST automatically loads data from FamPlan when a country is selected for analysis, and this link to FamPlan ensures that the most recent information available about family planning, contraceptive prevalence, unmet need for contraception, and the mix of contraceptive methods is used. LiST users can then create scenarios where unmet need is reduced, contraceptive use is increased, or the mix of contraceptive methods is changed. Altering these parameters in FamPlan results in changes to factors that are then inputs into both DemProj  and LiST (including distribution of risky births). Changes in FamPlan override the default fertility assumptions and assumptions about abortion within DemProj, resulting in adjusted inputs to LiST. If one scales up contraceptive prevalence to very high levels in a country with low contraceptive use, for example, the number of births would typically be expected to decrease and the number of averted under-five and maternal deaths predicted by LiST will also decrease.LiST model to produce different outputs through two main pathways. First, as fertility changes, there are accompanying changes in the distribution of births by birth risk categories. Birth risk categories are defined by parity, maternal age and birth spacing. The relationship between changes in fertility and the distribution of births into these categories of risk have been defined by previous analyses [LiST. The second LiST input that relies upon estimates from FamPlan is the number of induced abortions. Because previous work has linked the availability of contraception and abortion, this information is used to estimate how the number of abortions changes as contraception changes. This information is used in LiST to adjust estimates of maternal mortality due to abortion.Changes in family planning impact the analyses . This inLiST is the AIDS Impact Module (AIM), which is used to model the impact of changes in HIV/AIDS incidence, treatment and prevention on mortality. Developed under the auspices of UNAIDS and the UNAIDS reference group on modeling and estimates [AIM includes coverage of interventions  and uses this information to estimate prevalence and mortality by age and sex. Estimating the impact of interventions to reduce HIV/AIDS mortality in children is not done in LiST; the underlying calculations are done in AIM and then passed to LiST. When a country is selected within Spectrum, it will automatically load the most recent country-specific AIM module developed by UNAIDS and the national AIDS program [LiST module.The third module linked to stimates , this mo program . As descLives Saved Tool (LiST) has occurred under the guidance of the Child Health Epidemiology Reference Group (CHERG) of WHO and UNICEF. Along with its institutional sponsors, CHERG has developed rules of evidence to decide which interventions should be included in the model as well as how to develop the estimates of efficacy and effectiveness used in the model [LiST are drawn from various sources, most of the assumptions about the efficacy and effectiveness of interventions come from a series of journal supplements. To date, two supplements containing over 50 peer-reviewed articles have been published [LiST website (http://www.jhsph.edu/IIP/list).Development of the he model . Althougublished ,19 with ublished . The setLiST to measured changes in intervention coverage and mortality. Several studies have compared actual or recorded changes in mortality to projected estimates of mortality change generated by LiST based upon different sets of interventions in various countries. One regional study compared LiST estimates to measured declines in neonatal mortality from community-based intervention trials conducted in South Asia [LiST-produced estimates [LiST based upon coverage changes and the measured reductions observed for mortality. Additional studies presenting comparisons to LiST have been published in journal supplements [The CHERG also supports efforts to compare estimates that come from uth Asia . Anotheruth Asia . A thirdstimates . In all plements -19.P. falciparum, levels of deficiency for vitamin A and zinc, and the percent of the population living in poverty. Risk factors include stunting and wasting rates by age, birth outcomes, breastfeeding patterns and diarrhea and pneumonia incidence. Coverage data on interventions must be provided for all interventions in LiST for the baseline year. Finally, basic demographic information must be provided for LiST to operate, including population structure by age and sex as well as age-specific fertility. Fortunately, LiST (similar to the other linked Spectrum modules) can be automatically loaded with default values for 90 low- and middle-income countries for any year from 2000 to 2012, with information that is typically compiled from large population-based surveys such as Demographic and Health Surveys (DHS) or Multiple Indicator Cluster Surveys (MICS). Once the country and base year are selected, the information is automatically loaded, although the user has the option to change values if they have better data or if they would like to modify the population to reflect subnational geographic areas.The basic process to create a projection scenario in LiST is straightforward. First, one must select a baseline year for a country . For that baseline year, conditions in the country must be described in terms of a five broad sets of variables: mortality, exposure, risk factors, intervention coverage, and demography. For mortality, one must specify the neonatal and child (1-59 month) mortality, stillbirth rates, and maternal mortality rates, as well as the proportional causes of mortality or stillbirths. Exposure variables include factors such as exposure to Once the baseline year is set for a country, the user can then create a projection scenario by scaling up coverage of a single or multiple interventions over a time period. For example, one could look at the impact of scaling up vitamin A supplementation from its current  level of coverage of 50% in 2013 to 95% coverage in 2015. One could alternatively develop a treatment scenario where scale up of coverage for the treatment of diarrhea with oral rehydration solution (ORS), antibiotics for pneumonia, and treatment of malaria with artemisinin-based combination therapy (ACT) reaches 90% by 2018 from current coverage levels.LiST then re-computes all of the inputs used in the base year for all subsequent years, based on the anticipated impact of the interventions in the scale up scenario. The levels of mortality, cause of death structure, and levels of risk factors will be recomputed and applied to the new population structure that reflects not only the changes from DemProj but also any changes in the intervention coverage from the LiST model and changes made in the FamPlan and AIM modules.Once a scale up scenario has been created, LiST model is the attribution of lives saved to changes in coverage of specific interventions and risk factors. When a single intervention is scaled up, attribution is simple. However, when multiple interventions are scaled up that act on the same cause of death, a set of standardized attribution rules is needed. LiST first attributes impact to all preventive interventions , and then attributes impact to the curative interventions, also within this sequential pattern. Thus, if both a preventive and a curative intervention are scaled up simultaneously, the full effect of the change in coverage of the preventive intervention is calculated first and attributed to the preventive intervention. Then any residual deaths averted are calculated and attributed to the curative intervention.A valuable output provided by the When there are two or more interventions in either preventive or curative categories with an impact on the same cause of death, an additional step is required for the attribution calculation. First, we compute the number of lives saved by applying all preventive interventions. The attribution is based on the proportional impact of the preventive interventions, calculated as the increase in coverage times the effectiveness of the intervention. For example, we may have two interventions for reducing pneumonia mortality, with intervention A estimated at 40% effectiveness and intervention B estimated at 50% effectiveness. Current coverage of interventions A and B is 30% and 40%, respectively. If both interventions are scaled up to 50%, then the relative impact of intervention A would be (0.5-0.3) * 0.4 = 0.08, and for intervention B it would be (0.5-0.4) * 0.5. = 0.05. The total lives saved by the scale up of these two interventions would be allocated, with 61.5% attributed to intervention A (.08/(0.08+0.05)) and 38.5% to intervention B (.05/(0.08+0.05)). This same attribution approach is followed if there are three or more preventive interventions and/or curative interventions. Additional examples of detailed calculations can be found in Winfrey et al .Lives Saved Tool (LiST) draws on available datasets to predict changes in mortality due to maternal and child health interventions, family planning activities and HIV/AIDS programs. By combining these in a consistent and transparent way within the Spectrum Policy Modeling System, LiST has become a powerful software tool, able to predict the potential benefits of each of these types of activities alone or together. Also as LiST and Spectrum are freely available for download and source code is available on request, there have been several groups that have linked to this work. Recently, there has been the development of the OneHealth tool (another module within Spectrum), which links to the impact analyses performed within LiST and other modules such as AIM and FamPlan [The  FamPlan . OneHealThe marginal budgeting for bottlenecks tool (MBB) is an analytical costing and budgeting tool that helps countries develop their health plans by taking into account the most effective interventions, cost and budget marginal allocations of their implementation to health services and assess their potential impact on health coverage . This toA second tool is Mandate, the Maternal and Neonatal Directed Assessment of Technology project, is a framework for the global community to prioritize technology development and to estimate the impact of those technologies on maternal, fetal, and neonatal mortality . This piThe development of these related tools along with the widespread use of LiST by various organizations has been facilitated by the underlying collaborative approach to the development of LiST. Both the World Health Organization and UNICEF have served to guide the development of the tool through their Child Health Epidemiology Reference Group. This group also brings together a divergent set of researchers in the area of MNCH who, with limited support of project funds, provide the guidance and reviews for the assumptions used in the model. The Institute for International Programs at the Bloomberg School of Public Health, working with the Futures Institute, has been responsible for the developing and improving the model in response to both its academic partners and in response to needs to users. With the continuing support from the Bill and Melinda Gates foundation we anticipate that we will be able to continue to refine and improve LiST with the goal of supporting countries and their partners in improving programming for mothers and children.The authors declare that they have no conflict of interest.


Little work has been done to assess the quality of health care and the use of evidence-based methods by occupational physicians in Belgium. Therefore, the main objective is to describe one aspect of occupational health assessments, namely the common use of dipstick urinalysis, and to compare the current practice with international guidelines.A self-administered questionnaire was mailed to 211 members of the Scientific Association of Occupational Medicine in the Dutch speaking part of Belgium.A total of 120 occupational physicians responded, giving a response rate of 57%. Dipstick urinalysis was a routine investigation for the vast majority of physicians (69%). All test strips screened for protein and in 90% also for blood. Occupational health services offered clinical tests to satisfy customer wants as international guidelines do not recommend screening for haematuria and proteinuria in asymptomatic adults. A lack of knowledge concerning positive testing and referral criteria was demonstrated in almost half of the study participants.Belgian occupational physicians still routinely perform dipstick testing although there is no evidence to support this screening in healthy workers. To practice evidence-based medicine, occupational physicians need more instruction and training. Development and implementation of more guidelines is not only of use for the individual practitioner, it may also enhance professionalization and efficiency of occupational health care. In recent decades, evidence-based methods have been successfully applied in many areas of health care and prevention ,2. HowevIn Belgium, occupational health care is compulsory and the current legislation determines to a considerable extent its context and content . All worTo obtain some insight to what extent Belgian OPs integrate evidence in their medical decisions during consultation, we gathered data and information on one routine activity in occupational health surveillance, in particular urinalysis. Although the screening of all workers at pre-employment and annual health examinations for albumin and glucose in urine is no longer a legal requirement , dipstick testing is still common in daily practice. Dipstick urinalysis is simple and quick to perform, has no morbidity , and is among the most commonly performed screening tests ,16. HoweAssessment of albumin and/or protein excretion in the urine is a key step in the early detection and appropriate management of chronic kidney disease (CKD) -22. HoweIn this paper, the current Belgian practice to include dipstick urinalysis in occupational health assessments is described and compared with scientific evidence and international recommendations. In order to alter inappropriate screening policy and to provide better services, we need to understand why OPs still perform dipstick testing.To fulfil the objectives of our study, a questionnaire was developed on the basis of a comprehensive literature review of evidence-based occupational medicine and existing guidelines on urinalysis ,18,20,21Because the questionnaire was only available in Dutch, the study population of this survey consisted of the members (some of whom were in training) of the Flemish Scientific Association of Occupational Medicine (VWVA). These are all Dutch-speaking physicians, employed at both external and internal OHS across the northern part of Belgium. Approval was obtained from the board before physicians were contacted by e-mail. The questionnaire was administered online to 211 occupational physicians during March 2010. The survey was anonymous and the whole population received one reminder after three weeks. As the study was descriptive in nature, no statistical analyses were carried out on the data.In total, 120 physicians (57%) responded to the questionnaire. Table Regarding the practical aspects of the urine collection, subjects were requested to provide a urine specimen in a disposable container at the beginning of the medical examination. Test strips were read within a few minutes after voiding by the nurse in 85% of the samples, by the physician in 5%, an automatic analysing system was used in 10% and in another 5% it was done both by the nurse and a device (more than one answer possible).The majority of the OPs (69%) confirmed that dipstick urinalysis was part of the routine investigation for the majority of workers under occupational health surveillance. Visual Display Unit operators and apprentices were not screened, usually because of time shortage. None of the physicians indicated a strategy of solely screening workers with a high-risk profile . Standard dipstick tests always included screening for protein and glucose while additional testing for haematuria was done in 90%.According to 85% of the physicians, the group of employees screened was imposed by procedures of the occupational health service.A dipstick test result is considered positive at a colour indication of ≥ 1+ for blood and/or protein. Only 48% of the physicians gave the correct answer for haematuria and 46% for proteinuria. In the case of a positive reading for blood, 91% of the physicians checked for false positive causes (e.g. strenuous exercise), 87% asked for symptoms of urinary tract infections and 22% requested a further urine sample. When a test result was positive for proteinuria, 50% asked for high-risk factors for chronic kidney disease. To exclude transient causes of proteinuria, 15 physicians repeated the test after 2 weeks.Persons with dipstick-positive haematuria and proteinuria were promptly referred by 66 physicians. According to 36% (n = 43) of the respondents, additional risk factors (e.g. older age) were needed to send workers for further assessment.This descriptive study sought to evaluate current practice in occupational health surveillance, the focus being centred on urinalysis. Our results document the informal knowledge that dipstick urinalysis is being conducted in the vast majority of health examinations, irrespective of the workers’ risk profile.To our knowledge, this is one of the few papers exploring the quality of occupational care in Belgium and this is the most important strength of the study. However, there are a number of limitations that have to be mentioned. First, a measurement bias cannot be ruled out. The instrument used in this study was a self-developed questionnaire and its validity and reliability were not investigated. A second weakness is that only the members of the Flemish Scientific Association of Occupational Medicine participated in this survey. This organisation represents one third of all OPs in Belgium and although a relatively large number of OPs (n =120) did respond, selection bias may have been introduced. It is possible that non-members have a different opinion and that OPs who do not routinely perform urinalysis, considered this questionnaire irrelevant and did not complete the survey. Nevertheless, respondents were employed at both types of OHS, representing 11 from the 14 certified external OHS  and 20 in-house OHS. OHS are accredited and they usually have a certification for providing services to all workers as well in Flanders as in Wallonia. Therefore, we feel confident that the present results are representative for the whole group of active OPs.A possible explanation for the usual practice in relation to urinalysis may be the lack of knowledge about the appropriate use and significance of tests among health care professionals. In many countries, numbers of diagnostic tests are growing and attempts have been made to change test ordering performance effectively and bring it into line with existing evidence or guidelines on optimal testing . AlthougBesides the reduced physicians’ autonomy, some other issues must be considered; only half of the participants formulated the correct answer on the cut-off point for referral (dipstick positive at the level of +1) or follow-up. We did not ask for underlying reasons for this poor performance but previous surveys among OPs revealed that most of them consult the most up-to-date evidence in their field infrequently and that they make only sporadic use of practice guidelines. In addition, they possess limited skills in evidence-based medicine and the time required to keep up with the scientific evidence available is lacking ,4,6,7. TIn addition, further evidence-based guidelines in occupational health should be developed and implemented, as they are one of the most promising and effective tools for improving the quality of health care ,8. The dIn conclusion, the present study shows that occupational physicians tend to depend on their routines which are not always in line with evidence-based guidelines. To enhance professional performance, more efforts should be made to support occupational physicians in the uptake and maintaining of knowledge. Furthermore, to improve the quality of occupational health care, occupational health institutions, medical universities and scientific societies should be stimulated to take more initiatives to develop and implement evidence-based guidelines relevant to occupational practice.The authors declare that they have no competing interests.LB coordinated the project and drafted the manuscript. EH was responsible for the study protocol and the field work. LP helped with the review of the literature and the design of the study. Moreover, EH and LP evaluated the results and commented on the manuscript. All authors have read and approved the manuscript as submitted.


Priority setting for artemisinin-based antimalarial drugs has become an integral part of malaria treatment policy change in malaria-endemic countries. Although these drugs are more efficacious, they are also more costly than the failing drugs. When Tanzania changed its National Malaria Treatment Policy in 2006, priority setting was an inevitable challenge. Artemether-lumefantrine was prioritised as the first-line drug for the management of uncomplicated malaria to be available at a subsidized price at public and faith-based healthcare facilities.This paper describes the priority-setting process, which involved the selection of a new first-line antimalarial drug in the implementation of artemisinin-based combination therapy policy. These descriptions were further evaluated against the four conditions of the accountability for reasonableness framework. According to this framework, fair decisions must satisfy a set of publicity, relevance, appeals, and revision and enforcement conditions.In-depth interviews were held with key informants using pretested interview guides, supplemented with a review of the treatment guideline. Purposeful sampling was used in order to explore the perceptions of people with different backgrounds and perspectives. The analysis followed an editing organising style.Publicity: The selection decision of artemether-lumefantrine but not the rationale behind it was publicised through radio, television, and newspaper channels in the national language, Swahili. Relevance: The decision was grounded on evidences of clinical efficacy, safety, affordability, and formulation profile. Stakeholders were not adequately involved. There was neither an appeals mechanism to challenge the decision nor enforcement mechanisms to guarantee fairness of the decision outcomes.The priority-setting decision to use artemether-lumefantrine as the first-line antimalarial drug failed to satisfy the four conditions of the accountability for reasonableness framework. In our understanding, this is the first study to evaluate priority-setting decisions for new drugs in Tanzania against the accountability for reasonableness framework. In addition to the demand for enhanced stakeholder involvement, publicity, and transparency, the study also calls for the institution of formal appeals, revision, and regulatory mechanisms in the future change of malaria treatment policies. Plasmodium falciparum malaria-endemic countries, most being in sub-Saharan Africa, had changed their treatment policies to artemisinin-based combination therapies [Malaria case management with pharmaceuticals is a major challenge in many malaria-endemic countries. Old but cheap and effective medicines are increasingly facing resistance. By 2009, nearly all herapies ,2. On thherapies ,4. When herapies . The guiherapies . Limitedherapies . Among tTanzania has a fairly well-distributed healthcare system, within which 66% of all the healthcare facilities are owned by the government . About 8Rational malaria treatment policy formulation presents challenges to many endemic countries. At times, donors may favour an approach that conflicts with the national preferences ,14. StudThe accountability for reasonableness framework (AFR) Table  is a proDistrict and regional health planners have applauded the framework for its ability to enhance participation, transparency, and the development of relevant criteria for decision making . Where iManaging access to pharmaceuticals is a microcosm of the limit-setting problems of healthcare systems as a whole. If we are right that accountability for reasonableness is a solution to the legitimacy problem in health systems as a whole, then it should be possible to illustrate what such accountability would mean in practical terms... --.This is the first study to apply the AFR framework to evaluate priority-setting decisions that involve selection of drugs in Tanzania. The selection process for drugs to be listed on the national essential medicine list also involves priority setting. We argue that evaluation of these decisions against the AFR framework is one method of improving the process of drug selection. This study therefore reports on the evaluation of the priority-setting decision for the implementation of artemisinin-based combination therapy policy against the four conditions of the AFR framework.This was a qualitative study in which in-depth interviews were held with key informants. At least two participants were selected from the following list of institutions: Muhimbili National Hospital (MNH), National Malaria Control Programme (NMCP), WHO office in Tanzania, Ministry of Health (MoH), Tanzania Food & Drug Authority (TFDA), Medical Stores Department (MSD), and Muhimbili University of Health and Allied Sciences (MUHAS). Participants were experts on malaria research, administration of public health institutions, management of patients, and regulation and management of pharmaceuticals.The purposive sampling method was used to select the key informants from the acknowledgements list of the treatment guideline. A sample of 15 participants was selected based on Guest et al.'s recommendations, which imply that, in a piece of research that is narrow in scope and has a homogenous sample, data saturation is achieved after 12 interviews when thematic analysis is employed .Data were collected by in-depth interviews held with key informants using pretested interview guides and reviews of the treatment guideline between May and July 2010. A digital audio recorder was used to record the conversations. The in-depth interview guide consisted of questions corresponding to the AFR framework . Each inInterviews were transcribed and then analysed using the ATLAS.ti , a qualitative data analysis (QDA) software, using an editing organising-style method . First tTo ensure the validity of the data, participants were assured of the aim of the study and their names were anonymised. The in-depth interviews were held in places where interviewees felt comfortable, and the conversations were recorded by using a digital audio recorder. Interviews were transcribed by the interviewer shortly after each session. Telephone numbers of the interviewees were taken so that if any information was missing, they could be called for clarification. Transcripts were read and re-read several times so that the researcher could become familiarised with their contents before analysis. Coding of both the transcripts and the treatment guideline were done separately, and the emerging descriptions were triangulated during memo writing.Ethical clearance (Ref. No. MU/PGS/SAEC/Vol. III/185) was provided by the MUHAS Ethical Review Committee. Participants were asked for verbal informed consent and for permission to be recorded prior to the interviews.A majority of the participants reported that the decision about the selection and use of ALu was disseminated to the public by the use of radio, television, and newspaper channels in the national language, Swahili. Meetings with other stakeholders, such as pharmacists, were also held as a means of disseminating this information. They also reported that all the public healthcare facilities from the dispensary to the regional hospital level received the treatment guidelines, which contained the decision and rationales for the prioritisation of ALu.The decision about the selection of ALu, but not the reasons behind it, was communicated through advocacy campaigns by National Malaria Control Program (NMCP) and Ministry of Health (MoH) using different media channels in Swahili, the national language. The rationales were written in the treatment guidelines, which are not easily accessible to the public, patients, or other stakeholders who were not directly involved with the task force .Participants reported that the problem of parasite resistance to sulphadoxine-pyrimethamine was the major factor that caused the change of the National Malaria Treatment Policy. At the time of this policy change, three choices of artemisinin-based combination drugs recommended by WHO for management of uncomplicated malaria were available. These drugs included sulphadoxine/pyrimethamine-artesunate (SP-AS), amodiaqine-artesunate (AQ-AS), and ALu. ALu had the following advantages over the other drugs: (1) it was the only fixed combination drug among the three, (2) neither of its components had documented reports of parasite resistance, (3) it was safer, as amodiaquine's safety profile had already generated concern among healthcare providers and the general public and (4) it was the most efficacious drug.Participants reported that affordability was not discussed because of the agreement between the government and the Global Fund to provide the drug at a subsidized price at the public and faith-based healthcare facilities. This was facilitated by the agreement between WHO and the company that manufactures ALu, which made the drug available at cost price for use in the public sector for malaria-endemic developing countries. However, some participants raised concerns about the sustainability of this financing approach.... as a country you cannot just sit and wait for somebody to carry the burden of maintaining your population's health, imagine if Global Fund does not keep on sustaining this program!--Representative from MSDParticipants pointed out that, based on Global Fund requirements, the subsidized ALu could only be made available at public and faith-based primary to tertiary healthcare facilities. One participant who works at a tertiary hospital expressed concerns about the low availability of ALu in the primary healthcare facilities:I receive patients from the dispensaries who have been given sulphadoxine-pyrimethamine and amodiaquine and they sometimes ask why they are still prescribing these drugs when the first-line drug is artemether-lumefantrine!--Physician from MNHOne participant was concerned about the urban-poor populations who have to make a choice between long waiting times and unreliable public health services versus reliable but unaffordable services in the private sector. Participants from National Malaria Control Program (NMCP) said that other strategies were being considered to make sure ALu was also available at a subsidized price in the private-for-profit healthcare facilities.Participants said that fixed-combination antimalarial drugs have better compliance, hence are more effective compared to non-fixed combinations. However, artemether-lumefantrine's six-dose regimen of four tablets to be taken twice a day with a fatty meal for three successive days was a major concern.There are obvious improvements, admissions due to severe malaria nowadays are few and this could be explained by the effectiveness of artemether-lumefantrine. As a tertiary hospital we used to have a lot of patients coming in coma due to cerebral malaria; this is not research data but my own observation.--Physician from MNHAbout its cost-effectiveness, the majority of participants reported that there were no research data at the time of the policy change that indicated the cost -effectiveness of ALu.The task force committee was composed of 25 members; 21 were medical doctors and four were pharmacists. The medical doctors were paediatricians, obstetricians/gynaecologists, parasitologists, and pharmacologists from Muhimbili National Hospital (MNH) and Muhimbili University of Health and Allied Sciences (MUHAS). Others were working with the WHO country office, National Malaria Control Program (NMCP) and Integrated Management of Childhood Illnesses (IMCI) programs within Ministry of Health (MoH). The pharmacists were working with Medical Store Department (MSD) in the procurement and distribution of drugs, Tanzania Food and Drug Authority (TFDA) in food and drug regulations, and the pharmaceutical services unit at the Ministry of Health. All the committee members were from institutions based in the city of Dar es Salaam. Participants from NMCP who coordinated the policy-change process reported that they did not have written documents on procedures to select the committee members but that they 'knew' the main stakeholders. This approach was criticised by one of the participants:Sometimes I feel as if it is not adequate because if I had not contacted those people with my findings, I might not have been invited. So there might be other people who are in the field but because they had not made contact with Ministry of Health officials, they did not get the opportunity to be part of the task force committee.--Researcher from MUHASParticipants reported that patients and the public were indirectly involved through representation and consultations. It was also argued that the task force committee members were potential malaria patients, and therefore, they were themselves representatives of patients and the public. The idea of direct patient and general public involvement in the committee was opposed by some participants who labelled it as inappropriate because policy making is an expert's field.Participants reported that many consultations were held before and even after the assembly of the task force committee to get input and technical advice about policy change. Participants from National Malaria Control Program (NMCP) said that the first draft of the guideline was reviewed by experts from the National Institute for Medical Research, Malaria Consortium-Kampala, WHO Afro, Médecins sans Frontières, Ifakara Health Institute, and Eduardo Mondlane-Maputo (Mozambique). They also reported that the draft guidelines were shared by all district and regional medical officers as well as partner countries for technical advice. Councils gave input during the zonal training sessions that were conducted countrywide.The reasons for the prioritisation of ALu appeal to stakeholders because they were based on scientific evidence of clinical efficacy, safety, and formulation profiles. Financing mechanisms were already in place to ensure that the drug would be available and affordable at the public and faith-based healthcare facilities.The study found that there were no transparent procedures to engage the stakeholders. Some stakeholders were involved because of their positions in the relevant institutions, while others were involved through informal links with officials in the Ministry of Health (MoH) or National Malaria Control Program (NMCP). The committee lacked professional, institutional, and countrywide representation. It was largely made up of medical doctors and a few pharmacists; neither nurses nor medical lab personnel were included. All the physicians, specialists, and academicians within the task force committee came from one hospital, i.e. Muhimbili National Hospital (MNH) and one university, Muhimbili University of Health and Allied Sciences (MUHAS). There were other similar institutions in the country that could have provided members to increase representation.Participants said that it is not easy for anybody to appeal against the policy; however, if established facts and evidence on toxicities and level of resistance were to be provided, the policy decision could be revised.I think the best way for people to appeal is to provide scientific data in the scientific forum; it is impossible for an individual to come up and say this is not the right drug. From the community side, I think the only mechanism they have is to express their concerns in the newspapers and other media; otherwise, I don't see any other channels at the moment.--Participant from TFDAPharmacovigilance forms, which are used as post-marketing surveillance tools in monitoring drug safety, were mentioned as effective tools to generate evidence on the safety profile of ALu. However, one participant disagreed with the reliability of this approach.Most of our clinics are crowded, before you can take a minute or two to fill in the pharmacovigilance form, 20 people are already shouting at you, so it is one avenue but is not satisfactory.--Physician from MNHThere is no mechanism in place to appeal against the decision to prioritiseALu.There was no enforcement mechanism. The demand for enforcement was seen as new and was considered unnecessary by some participants. Other participants said that an independent enforcement body is necessary during a treatment policy change.I am not sure if there was a watchdog. I think it is really very important because sometimes people say the drug companies are pushing for policy change.--Pharmacologist from MUHASDespite growing concerns about the influence of pharmaceutical companies on change of treatment policies, we did not find any enforcement mechanism to ensure the other three conditions were met.This study evaluated the process of changing the Tanzania National Malaria Treatment Policy against the AFR framework. The process resembled other priority-setting decisions, in that it involved making choices among competing alternatives in the context of limited resources, conflicting evidence, diverse stakeholder involvement, and the vagaries of political cycles . The infWhen evaluated against the AFR, this study found that the publicity condition was not fully satisfied. The study found that the decision to prioritiseALu was made public, but not the reasons behind it. Publicity requires that the decision and its rationales, such as the ones for coverage of new drugs like ALu, be publicly accessible to all stakeholders, including the patients . SimilarThe study found that the rationale but not the stakeholder involvement part of the relevance condition was satisfied. ALu was the only artemisinin-based antimalarial drug that was in a fixed-combination formulation. It was also the most efficacious drug and neither of its two components had any documented reports of parasite resistance . Cost-efThe study found that stakeholders were not adequately involved and represented. Appropriately conducted stakeholder participation not only facilitates and widens discussions in the decision-making process but also enhances publicity . The tasEven though we argue in favour of wide professional and institutional representation, this should not aim to replace patients and the general public. There is evidence that health professionals' views can differ considerably from those of their patients . HoweverThe appeals and revision condition was not satisfied. To our knowledge, there are no formal appeals mechanisms in the Tanzanian healthcare system for policy decisions relating to access to new drugs or healthcare. Pharmacovigilance systems in developing countries are weak, and hence cannot be considered an efficient appeal mechanism to inform policy makers of a drug causing harm to its users. The lack of reliable appeal mechanisms suggest that good arguments and evidences against the original decision and which aim at improving faulty policy decisions can have no clear way back onto the decision table. A study by Maluka et al. reported a lack of clear formal channels for appeals at the district level in Tanzania .The enforcement condition was not satisfied. This condition recognises that public or private regulation may be necessary if self-regulation proves unsuccessful or inadequate. There are growing concerns about the influence of pharmaceutical companies, which lobby and push for national treatment policy changes, especially in developing countries ,16. HencThe qualitative research method is the best approach to study complex phenomena when a researcher wants to capture the views of individual persons, including their feelings, understandings, interpretations, beliefs, and ideologies. Through the use of this method, the participants shared their stories and conflicting views beyond what the researchers expected to hear or what is available in the literature.The study used the AFR as an evaluation framework; however, there are objections to its use as an approach to achieve justice and fairness ,42. MoreThis study applied the AFR framework to evaluate the priority-setting decision for new antimalarial drugs at the national level. The study found that the priority-setting decision in favour of ALu failed to satisfy the four conditions of fair process prescribed in the ethical framework of accountability for reasonableness. The findings of this study are consistent with the reports of other studies that evaluated priority-setting decisions against AFR at the district level. The study emphasises the need to involve a wide range of stakeholders in priority-setting decisions. It further highlights the need to make priority-setting decisions and their rationales public and to establish mechanisms for appeal, revision, and regulation in order to enhance fairness and legitimacy of the decision outcomes.The authors declare that they have no competing interests.ATM conceived and designed the study, collected the data, performed the analysis, and prepared the draft of the manuscript. EAK fine-tuned the study design and coordinated the data collection and analysis. All authors read and approved the final manuscript.


Sarcoidosis is a granulomatous multisystem disorder of unclear etiology that involves any organ, most commonly the lung and the lymph nodes. It is hypothesized that the disease derives from the interaction between single or multiple environmental factors and genetically determined host factors. Multiple potential etiologic agents for sarcoidosis have been proposed without any definitive demonstration of causality.We report the case of two patients, husband (57 years old) and wife (55 years old), both suffering from sarcoidosis. They underwent a lymph node biopsy by mediastinoscopy which showed a “granulomatous epithelioid giant cell non-necrotising chronic lymphadenitis”. They had lived up to 3 years ago in the country in a farm, in contact with organic dusts, animals such as dogs, chickens, rabbits, pigeons; now they have lived since about 3 years in an urban area where there are numerous chemical industries and stone quarries. The aim of this case report was to focus on environmental factors that might be related to the pathogenesis of the sarcoidosis. Sarcoidosis is a granulomatous multisystem disorder of unclear etiology that involves any organ, most commonly the lung and the intrathoracic lymph nodes. Also heart, skin, and central nervous system are frequently affected. The diagnosis of sarcoidosis is further hindered by the lack of any reliable and specific diagnostic test, as there are no laboratory or imaging findings that enable the definitive diagnosis. Even the histological data are not conclusive because the non-necrotising granuloma, a hallmark of morphologic appearance of the disease, is not unique for sarcoidosis. Granulomas typically consist of a compact central area of macrophages that differentiate into epithelioid cells and then fuse to form multinucleated giant cells surrounded by lymphocytes.Mycobacterium spp. being the most commonly implicated organism. The role of various non-infectious organic and inorganic environmental agents has been studied in the pathogenesis of sarcoidosis.A genetic predisposition to sarcoidosis is epidemiologically evidenced by the demonstration of familial aggregation, differences in disease susceptibility and severity between racial groups, and the significantly increased incidence in monozygotic twins of affected individuals compared to other siblings ,2. It isWe report the case of two patients, husband and wife who had lived up to 3 years ago in the open country, in contact with organic dusts (hay and molds), and animals such as dogs, chickens, rabbits, pigeons; now they live in an urban area where there are numerous chemicals industries and stone quarries.The woman, 55 years old, is a housewife and a former smoker of 1 pack/years. She underwent a hysterectomy for uterine fibromatosis, and a surgical operation for right humerus osteochondroma. She has got a herpes simplex virus type I infection. At the time of our first observation she referred in the last 2 years dry cough with little sputum, dyspnea grade II according to the American Thoracic Society (ATS) scale and mild fever. At the beginning of the symptoms she performed a chest x-ray which showed “interstitial thickening” and a microbiological sputum examination which was negative for tuberculosis and fungal infection. The general practitioner gave her a non-specific antibiotic therapy with low benefit and then a steroid therapy with improvement in symptoms. At the time of our observation, she underwent a total-body CT scan which showed “a series of lung nodules distributed in all lobes; a solid slab in the mantle of the apical segment of the left lower lobe; several small adenomegalies in the anterior mediastinum, around the trachea and below aorta artery; no evidence of effusion in the pleural cavity” in the thorax   was normal.The 6-min walking test was normal and the pulmonary function tests showed a reduction in the diffusing capacity for carbon monoxide (DLO) Table . The artCO  in severe obesity. As his wife, he has got a herpes simplex virus type I infection. He takes regular therapy with aspirin, doxazosin, allopurinol, irbesartan, erythropoietin and insulin. He referred dyspnea ATS grade II-III in the absence of cough. He also reported to have taken steroids in the past at the starting dose of 50 mg/day and gradually tapered. This therapy was recommended in the absence of a definitive diagnosis and on the basis of symptoms and radiological abnormalities of “interstitial thickening” present in the chest x-ray. At the time of our first observation, the pulmonary function tests revealed a mild restrictive pattern with reduction of DLThe environmental exposition of the two patients concerns chemical agents because of the industries near where they lived in the last years and because of the presence of a sand quarry. The industries in the area where they live include those involved in the processing of tires. Thus, factors such as the inorganic powder used in the rubber industry can play an active role in the pathogenesis of their disease. Other factors potentially involved could be silica, silicone and the fibers of the glass. Three recent longitudinal studies regarding the World Trade Center disaster have emphasized the role of airborne inorganic particulate exposure in sarcoidosis -6. TheseGeographic clustering of disease in the southern United States and in other parts of the world has promoted further speculations concerning weather, soil, and foliage in the pathogenesis of sarcoidosis . Past stInterestingly, other studies suggest the hypothesis of either a person-to-person transmission or a shared exposure to an environmental agent. In a well documented clustering that has occurred in the relatively isolated population of the Isle of Man, individuals with sarcoidosis were more likely to have had prior contact with an individual who had sarcoidosis, compared to controls (39.6% versus 1.1%). These contacts included neighbors, unrelated cohabitants, and co-workers . SimilarRhodococcussp[Finally, several observations suggest that sarcoidosis may be caused by an infectious agent. There are many known infectious agents that can cause granulomas that resemble those of sarcoidosis, including mycobacteria, herpes viruses, histoplasmosis, treponematosis, sporotrichosis, coccidioidomycosis, schistosomiasis, listeria, the agent of Whipple’s disease and ococcussp. BecauseBoth our patients have got labial herpes simplex virus and this could suggest a potential role of the infection in the development of the disease. Moreover, before moving to the urban area, the two patients lived in the countryside, reporting exposure to molds and hay. Finally, they were exposed to chemical agents derived from the industry of the tires. Among those, silica is a mix of modern tires and it is known that silica could be potentially involved in the pathogenesis of the disease. However, all the environmental factors that could be considered potential triggers of the disease are not sufficient by themselves to cause sarcoidosis and must interact with a particular immune response of the host. Therefore, the genetic predisposition of the patients plays a key role in the development and progression of the disease.In conclusion, this case report wants to focus on environmental factors that may be potential causative agents for sarcoidosis. Important tool in investigating patients with sarcoidosis is a complete medical history that includes occupational and environmental factors, lifestyle habits and any previous infection. It could be also useful to study and monitor the areas with the highest incidence of this disease.Written informed consent was obtained from the patient for publication of this Case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.The authors declare that they have no competing interests.IL and IS made substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data; LF and FV were involved in drafting the manuscript or revising it critically for important intellectual content; SV gave final approval of the version to be published.