Antimicrobial use in food-producing animals selects for antimicrobial resistance that can be transmitted to humans via food or other transmission routes. The World Health Organization (WHO) in 2005 ranked the medical importance of antimicrobials used in humans. In late 2017, to preserve the effectiveness of medically important antimicrobials for humans, WHO released guidelines on use of antimicrobials in food-producing animals that incorporated the latest WHO rankings.WHO commissioned systematic reviews and literature reviews, and convened a Guideline Development Group (GDG) of external experts free of unacceptable conflicts-of-interest. The GDG assessed the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, and formulated recommendations using a structured evidence-to-decision approach that considered the balance of benefits and harms, feasibility, resource implications, and impact on equity. The resulting guidelines were peer-reviewed by an independent External Review Group and approved by the WHO Guidelines Review Committee.These guidelines recommend reductions in the overall use of medically important antimicrobials in food-producing animals, including complete restriction of use of antimicrobials for growth promotion and for disease prevention . These guidelines also recommend that antimicrobials identified as critically important for humans not be used in food-producing animals for treatment or disease control unless susceptibility testing demonstrates the drug to be the only treatment option.To preserve the effectiveness of medically important antimicrobials, veterinarians, farmers, regulatory agencies, and all other stakeholders are urged to adopt these recommendations and work towards implementation of these guidelines. The increasing prevalence of antimicrobial resistance is a worldwide problem , 2. AntiTo address the growing public health problem of antimicrobial resistance, the 68th World Health Assembly adopted the World Health Organization’s (WHO) Global Action Plan on Antimicrobial Resistance (GAP) in May 2015 . The WHOAntimicrobials are widely used in food-producing animals for therapeutic use , prophylactic use , and growth promotion use (to improve rate of gain or feed efficiency) . Such usWith the ever growing public health threat of antimicrobial resistance and the recognized need to preserve the effectiveness of medically important antimicrobials, particularly those antimicrobials judged to be critically important to human medicine on the WHO CIA List, WHO elected to develop formal, evidence-based, guidelines on use of antimicrobials in food producing animals.WHO Handbook for Guideline Development, three groups were organized [In accordance with the rganized . A WHO SA Guideline Development Group (GDG), comprised of thirteen external experts from five WHO regions with expertise in clinical human medicine, infection prevention and control, evidence-based medicine, tropical medicine, epidemiology, veterinary medicine, microbiology, infectious diseases, public health, antimicrobial resistance, economics and veterinary ethics. The GDG assessed the available evidence and formulated recommendations. One member of the GDG was a Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodologist. GDG members were selected in a way that sought geographic representation and gender balance, and avoided conflicts of interest. An External Review Group (ERG), composed of eleven technical experts and stakeholders with interest in use of antimicrobials in food-producing animals including veterinarians, microbiologists, animal scientists, public health practitioners, food safety experts, public health policy officials, and physicians. The ERG reviewed the final draft of the guidelines to identify errors of fact and commented on the clarity of the language, contextual issues and implications for implementation.http://apps.who.int/iris/bitstream/10665/258970/1/9789241550130-eng.pdf). Following a public solicitation for applications, the WHO Steering Group selected the applications from teams at Bond University  and University of Calgary (Canada). The systematic review teams interacted regularly with the WHO Steering Group but worked independently of each other.WHO commissioned systematic reviews of the published evidence that restrictions in use of antimicrobials in food-producing animals reduced the prevalence of antimicrobial resistance in bacteria isolated from food-producing animals and humans  and March 2017 . The GDG formulated recommendations based upon the summarized evidence and judgments of the overall quality of the evidence. Using the GRADE approach, the GDG also judged the strength of each recommendation by considering the importance of the problem, the quality of evidence, the balance between benefits and harms, the values and preferences of affected populations, resource implications, the impact on equity, human rights, gender and social determinants of health, acceptability, and feasibility [As per WHO regulations, all external experts and contributors disclosed their secondary interests  prior to participating in the WHO guideline development process. When a conflict of interest was identified, WHO followed standard procedures to determine whether or not the expert was permitted to participate in the guideline development process. A biographical sketch of each nominated GDG member was posted online for public comments. The WHO Steering Group reviewed all information gathered before approving final GDG membership.Governments of Japan and The Netherlands provided funding for the guidelines but were not involved with guidelines development. WHO facilitated the development of the WHO Guidelines, in accordance with the WHO guideline development process, and provided additional funding for the guidelines.http://apps.who.int/iris/bitstream/10665/259241/1/WHO-NMH-FOS-FZD-17.2-eng.pdf.The systematic reviews yielded a large number of studies that demonstrated a consistent decrease in the prevalence of antimicrobial resistance in bacteria isolated from food-producing animals or humans following restrictions on use of medically important antimicrobials in food-producing animals. The Bond University systematic review team provided a narrative report of the quality of, and summary of findings from, 93 studies and concluded that limiting the antimicrobial use in food animals is likely to reduce the presence of antimicrobial resistance in food –producing animals and humans. The University of Calgary systematic review team provided a quantitative report from 177 studies that included an assessment of the quality of the primary studies and provided a meta-analysis of the risk differences for reductions in the prevalence in antimicrobial resistance reported with various restrictions on antimicrobial use in food producing animals . The Unihttp://apps.who.int/iris/bitstream/10665/259241/1/WHO-NMH-FOS-FZD-17.2-eng.pdf .Of the three commissioned content specific literature reviews, one review provided evidence from illustrative examples of probable transfer of resistant determinants for streptothricins, glycopeptides and colistin from food-producing animals to humans . The sechttp://apps.who.int/iris/bitstream/10665/259242/1/WHO-NMH-FOS-FZD-17.3-eng.pdf .The evidence presented to the GDG was predominately from observational and ecologic studies. Additionally, the systematic reviews found few studies from middle-income and low-income countries, and few studies included small-scale food-producing animal operations. Despite these limitations, the GDG determined that there was sufficient evidence that use of medically important antimicrobials in food-producing animals selects for antimicrobial resistance in bacteria, and that such antimicrobial resistant bacteria can be transmitted to humans, including in middle-income and low-income countries, and small-scale operations. Summaries of the information used by the GDG to develop best practice statements and recommendations related to the use of medically important antimicrobials in food-producing animals, including evidence profiles, summary of findings tables, and evidence-to-recommendations tables, are available at Any new class of antimicrobials or new antimicrobial combination developed for use in humans will be considered critically important for human medicine unless categorized otherwise by WHO.Medically important antimicrobials which are not currently used in food production should not be used in the future in food production, including in food-producing animals or plants.The GDG developed two best practice statements for classes of antimicrobials not currently used in food-producing animals.The GDG judged that these best practice statements were needed to provide a basis for taking actions to preserve the effectiveness of critically important antimicrobials for humans  that are not currently used in food-producing animals. Furthermore, given the critical need for new classes of antimicrobials for the treatment of some serious and life-threatening infections in humans, the development and eventual marketing of new classes of antimicrobials will likely be antimicrobials required for infections in humans with no or limited treatment options.Since these antimicrobials are not yet used in food-producing animals, direct evidence  is not available. Instead, the best practice statements are supported by considerable indirect evidence, including a large body of evidence from the systematic reviews and from mechanistic studies of antimicrobial resistance , 19.An overall reduction of use of all classes of medically important antimicrobials in food-producing animals is recommended. .Complete restriction of use of all classes of medically important antimicrobials in food-producing animals for growth promotion is recommended. .Complete restriction of use of all classes of medically important antimicrobials in food-producing animals for prevention of infectious diseases that have not yet been clinically diagnosed is recommended. .It is suggested that antimicrobials classified as highest-priority critically important for human medicine should not be used for treatment of food-producing animals with clinically diagnosed infectious disease. It is also suggested that antimicrobials classified as critically important for human medicine should not be used for control of the dissemination of a clinically diagnosed infectious disease identified within a group of food-producing animals. .The GDG developed four recommendations, supported by both direct and indirect evidence, concerning the use of medically important antimicrobials in food-producing animals.The GDG determined that the first three recommendations should be strong despite the low-quality evidence due to the large human health benefits of lowered prevalence of antimicrobial resistance in bacteria isolated from humans and the limited evidence of undesirable consequences of restrictions on antimicrobial use of medically important antimicrobials in food producing animals. Specifically, there was a large amount of consistent evidence from the systematic reviews and the literature reviews that resistant bacteria can spread among food-producing animals, into their environment, and to humans, and that restrictions on use of antimicrobials in food-producing animals reduces the prevalence of antimicrobial resistance in bacteria isolated from food-producing animals that are, and can be, transmitted to humans. The GDG also concluded that for the fourth recommendation, although evidence from the systematic reviews and additional studies indicates it will achieve the human health benefit of lowered antimicrobial resistance in bacteria, this recommendation should be conditional due to the very low quality of available evidence. In order to protect animal health and welfare, the GDG concluded that exceptions to recommendations 4a and 4b can be made when, in the judgement of qualified veterinary professionals, susceptibility results demonstrate that the selected drug is the only treatment option.The GDG also concluded that in order for people in all countries to realize the benefits of continued effectiveness of medically important antimicrobials, the recommendations in these guidelines should be applied in all animal production settings and in all countries.With the recognition of the need to reduce the use of medically important antimicrobials in food-producing animals, the GDG identified the following research areas which can be addressed to help facilitate reduced antimicrobial use:  identifiThe use of antimicrobials in food-producing animals has been a public health concern for decades . In 1997In accordance with the WHO guideline development process , the GRAThe GRADE approach follows a rigorous and transparent process, and is the most widely used approach for evidence appraisal for guideline development. The GRADE approach was initially developed for decision-making in clinical settings, where randomized clinical trials are commonly available. It rates evidence derived from randomized controlled trials as high quality, while evidence from epidemiological studies, surveillance programmes and other sources of observational data, in which confounding cannot be adequately controlled, is rated as “low quality”. In common with many important public health issues, due to ethical and technical complexity, there are no randomized controlled studies that have assessed associations between use of antibiotics in food-producing animals and risks of human exposure to infection by drug-resistant zoonotic pathogens. Most of the supporting scientific evidence, representing the best available evidence, was collected from epidemiological studies, surveillance programmes and observational studies. In addition to the quality of the evidence and the balance of benefits and harms of an intervention, a number of other factors are considered when GDGs formulate recommendations. These factors include the relative value placed on the potential beneficial and harmful outcomes of an intervention, the acceptability and feasibility of the intervention, resource considerations, and effects on equity across subpopulations. A “strong recommendation” means that after taking all relevant considerations into account, the GDG is reasonably certain that the desirable consequences (benefits) of an intervention outweigh the undesirable consequences (risks or harms), such that the intervention should be implemented in most settings.The GRADE approach has been used successfully in public health settings where only observational studies are available. There are challenges, however, in using the GRADE approach in all settings, especially in the formulation of recommendations on complex interventions in public health settings . AlthougUsing the rigorous and transparent WHO guideline development process, the GDG determined that three of the four recommendations on use of medically important antimicrobials in food-producing animals should be strong recommendations given (1) the large body of evidence from the commissioned systematic reviews using a rigorous and evidence based approach of the strength and consistency of the association between restrictions of antimicrobial use in food-producing animals and antimicrobial resistance in animals and humans, (2) the suggestion of a dose-response relationship with this association, (3) the large potential health benefits, and (4) the evidence of limited unintended consequences. The GDG also recommended implementation of the WHO guidelines worldwide. As with all WHO guidelines related to food safety, implementation relies on the impetus of Member States and other stakeholders, including the FAO/WHO Codex Alimentarius Commission, to translate the recommendations into national and international standards or guidance. In order to reach the overall goal of reducing antimicrobials in food-producing animals, there is a particular need to identify management alternatives for use of antimicrobials for disease prevention. The GDG acknowledged that implementation in lower-income or middle-income countries may require special considerations such as assistance in improvement of hygienic and agricultural practices including improved housing and husbandry. Furthermore, many countries may need technical and laboratory capacity building assistance for conducting the recommended bacterial culture and antimicrobial susceptibility testing. It is important for countries to conduct surveillance and monitoring of antimicrobial usage in food-producing animals to evaluate the effectiveness of any interventions.In conclusion, the WHO guidelines recommend overall reduced use of medically important antimicrobials in food-producing animals, including complete restriction of uses of medically important antimicrobials for growth promotion and for disease prevention. Exceptions for disease prevention can be accepted when based upon the judgement of a veterinary professional and if such judgement is based on recent culture and sensitivity testing results. The WHO Guidelines also suggested that antimicrobials identified as critically important for human medicine not be used in food-producing animals for treatment or disease control unless susceptibility testing demonstrates the drug to be the only treatment option. To preserve the effectiveness of medically important antimicrobials, all stakeholders should implement the recommendations in the WHO guidelines. Such implementation will support the WHO GAP to control antimicrobial resistance by reducing unnecessary use of antimicrobials in food-producing animals.


Introduction: The purpose of this research was to examine the approach, based on evidence to customer-orientation attending physicians in the region, them being the subject collection. Research method: This is a definitive-analytic and cross-sectional configuration, which was completed in 2014. The statistical community in this research consists of 212 doctors in the healthcare hubs. The working physicians chose 200 patients by means of a simple accidental sampling. The analysis means was the researcher built survey whose efficacy and reliability were verified. In this research, the fundamental equation design and partial least square technique were applied to examine the presumptions and fitness pattern and the structural design was agreed as adequate. Findings: The outcomes showed four cases linked to the character, a behavior which was meant to treat; traditional origins of evidence were employed to retrieve data based on the reliable evidence and the shortage of limitations to the performance of client orientation strategy of evidence-based influences were meaningful. Two ranges of the doctor's information, the absence of restrictions, and the finding of the sign of dimensions about the client orientation approach were according to the evidence that had no meaningful influence. Conclusion: The utilization of evidence-based training not only increased awareness, character, and abilities of the doctors but also allowed them to answer to the requirements of clients in choosing excellent decisions and presenting a better quality of healthcare, by decreasing treatment prices for patients, bringing satisfaction of patients, and finally having a better effectiveness for patients and institutions. Combining the best scientific evidence, needs and values, the environment, corporate resources, as well as human resources, can provide appropriate evidence-based decisions [2]. The job of the employees’ is the involvement and training in providing effective aids to the requirements of the customer satisfaction [3].Since the first contact doctors are in health centers, therefore, patients in public centers are considered one of the most important groups in providing a key role in the use of the evidence-based approach in their daily activities and clinical decision-making . David Lawrence Sackett explained evidence-based medication as an integrating clinical ability with the greatest clinical evidence from systematic research available to the best possible management of foreign patients [5]. Firstly, the need to learn the skills of Evidence-Based Medicine (EBM) is represented by a very high volume of medical information and is rapidly increasing. Secondly, physicians may need less time to devote to study. In addition, studies showed that the efficiency workshops are common, so they need to learn methods in order to continue education during lifetime [6].B. Customer orientation: among the competition in the international arena and in this period, the correct application of sources is considered as one of the greatly challenging elements of management and the connection among the employees and customers are seen as one of the institution's resources. The organizations should try new concepts of modern marketing, which means the art of finding, keeping and developing customer needs and new demands created for customers in order to bypass the exercise of power, but also using participation and understanding to manage relationships with customers and provide them to ensure their profitability [7]. Managers should find the time and tools available to their employees to an evidence-based approach in their daily activities application. Managers should be able to structure and culture the evidence-based practice in their own organization [8]. Customer relationship management by using information technology and organizational changes tries to re-engineer processes and turn them into customer-centric processes [9].C. The relationship between the evidence-based practice and the customer orientation on knowledge management strategy, total quality management and customer focus have a special place. The purpose of this strategy is to achieve a superior service that seeks to create a culture of customer orientation with the identification of the needs and expectations of customers and measure their satisfaction to the knowledge, attitudes, skills and behaviors that the employees nurture to achieve its ultimate goal of customer orientation [10].EBM, to take the appropriate decisions in the treatment; the same customer satisfaction being the ultimate goal which can be achieved. Therefore, the main hypothesis of this study was determined: an evidence-based approach of the doctors on the effective customer orientation.By providing the necessary resources and evidence, removing barriers to employment, promoting the culture of participation and sharing of staff, staff training encourages and motivates doctors to switch to the use of History of research11].The outcomes of the research of Heiwe et al. in the field of attitudes, knowledge and behavior of health care professionals, showed that the groups have a positive attitude towards the evidence-based practice in their decision making and clinical work. The majority of them had the power to analyze and evaluate the existing evidence, guidelines, and instructions that were available. Most of the obstacles regarding their performance problems were expressed. Finally, the researcher supported the Chief Executive Officer concerning the factors affecting the evidence-based performance, evidence-based and outcome performance and gratification of patients and contributed to productivity [12].In a qualitative research conducted in the field of evidence-based understanding of nurses, it was achieved that the evidence from the research was used in nursing. Nurses needed to recognize the value and significance of the research and the application of its results was difficult, the addition to the emphasis on the concept of evidence-based care being suggested, also the production of methods, recovery and the evaluation of research evidence in nursing education programs. Incentive policies for nurses with evidence-based practice, the improvement of their knowledge, skills, and the quality of attention should also be considered [13].In a study of Kermanshahi and Parvinian, the nurses’ views on barriers to implementing evidence-based care were examined and the outcomes revealed that nurses had barriers in implementing the evidence-based care for the management and included the insufficient number of staff and managers’ knowledge of the value of evidence-based care. In the personal-care dimension, the shortage of enough time of nurses to examine the research was one of the very significant barriers [14].The outcomes of the research of Salehi and Abedi regarding the implementation of evidence-based performance on the nurses explained that in terms of achievement in the area of evidence-based nursing, many of the staff working in this area was weak, the researchers were motivated and the organization supported this weakness [15].In a semi-experimental study entitled “The impact of evidence-based clinical training on the quality of the patient care and satisfaction”. It was found that the evidence-based education was applied to promote knowledge, skills and enhance the condition of patient care [EBM [16].There are a few studies performed on the physicians’ knowledge about EBM in the Middle East. In 2004, a study of AL Baghil and AL Almaie showed that only 40 percent of Saudi Arabia primary health care physicians have learnt something regarding 17].In another study conducted in the UK, it was reported that 40% of the general physicians had knowledge about the search methods based on evidence and 71 percent of the time, they lacked the most significant portion in the decision of not having to use evidence-based medicine [18].Other studies showed that physicians need a clear understanding of the terms used in evidence-based medicine. In a study in the field of awareness and the use of evidence-based medicine among residents of Shiraz University of Medical Sciences conducted by Amini et al., it was shown that residents with positive attitudes toward medicine based on evidence and the access to Internet for clinical decision making, practically did not use evidence-based medicine and were unaware of specific websites. The reason may be that they were not trained in this field [19].A research of Dalheim et al. on the factors affecting the improvement of evidence-based training of working nurses concluded that the colleagues' and nurses experience was used in evidence-based practice. However, because of the obstacles, evidence from research was rarely used. The most important obstacles in Evidence-Based Practice lacked time and abilities to search, records management, research, nursing age, and a quantity of years as far as the working nurses were concerned [20].In a study of MacDermid and Graham on a group of practicing midwifery profession after a period of training in EBP, it was found that participants in the study were extremely excited regarding the EBP, at the same time believing that this approach enhanced the critical thinking skills, increased confidence and a better care of the patients [21].In a study of Morris and Maynard in the field of evidence-based care in midwifery, it was proved that the overall objective was the one of empowering the evidence-based care in identifying and understanding the needs of patients, clients, and midwifery practitioners, in decision-making and the application of scientific findings in the final midwifery care .In titles of nature and purpose, the current study is functional and in titles of the method of data collection, it represents a descriptive survey of the connection between the causal variables. Doctors operating in the healthcare centers of the province 1 and 2 represented the statistical society examined in this research. The sample was random, the sampling system giving the minimum requirements for 200 physicians working in health centers 1 and 2 of Isfahan province. 200 questionnaires were distributed between respondents and the same 200 questionnaires were suitable for analysis, identifying a numerous statistical analysis and evidence-based practice to estimate the customer satisfaction questionnaire prepared. The first part of the application included demographic features and the another part evidence-based practice, which consisted of 30 questions. The evidence-based practice consisted of six levels, attitudes and behavioral intention (5 items), behavior of physicians on evidence-based practice (5 items), shortage of barriers regarding the performance based on the greatest evidence (4 items), knowledge (4 items), lack of barriers regarding investigation and evidence (5 questions), origins of evidence common for data recovery (4 items). The third section of the questionnaire was relevant to customer questions (3 items) .As it could be observed from all the variables in this research, Cronbach's alpha coefficient was of at least 0.6, 0.65, remarkably higher. To assess the validity (convergent), the exploratory factor analysis was used for factor analysis, index KMO, Bartlett test, and convergent validity .Bartlett and KMO test results showed that the index values were desirable. KMO standard variable rate of larger than 0.5 and smaller than 0.05 for the CLS was also determined by Bartlett test. Items that amounted smaller than 0.03 and which were not compatible with other items were dismissed from the analysis. To check the soundness of the (credit) converge in the PLS model, the mean-variance extracted (AVE) was used. As it can be seen in To assess the reliability of any of the markers in the latent variable PLS model, the load factor of each indicator was determined. The value of each hidden variable load factor markers had to be larger than or equivalent to 3.0. As it could be seen in the above table, all the measures linked to the underlying variable that housed more than 40%, were marked as shaded. Therefore, the model could measure latent variables that were indicators of reliability in the field. All the amounts of the indicators were expected to be less than 0.05 and the soundness of research tools were appropriate.Findings1] and 100 [2] of the city health center were employed . 193 respondents’ education level was Ph.D. and 7 were experts. Regarding the position, the organization was responsible for 63 health centers, 120 healthcare centers, and 17 family physicians. Fig. 2 revealed the connection between the 2 variables, the path coefficient of performance evidence-based approach and customer of 0.303 respectively.100 respondents in the Health Center of Isfahan city .Given the probability , it had a less significant level of 0.05. In fact, a significant number was out of range  . It can be concluded that the path coefficients were significant; having errors of 0.05, indicating that the most frequent sources of evidence used to retrieve customer orientation data had a significant influence.Given the probability , it had a significant level of more than 0.05. In fact, a significant number was out of range  (Assessment of the indices model fittingTable 6, the values of any of the indicators of the independent variables were affiliated mediators. As it can be viewed, the indicators were positive and higher than zero.To check the quality or reliability of the pattern, which included a credit check share index and index credit check, redundancy was used. In 11,18].According to the outcomes of the research, a hypothesis of a causal connection between the attitudes of the physicians on evidence-based exercise was accepted by the customer orientation. The study results showed that physicians have a positive attitude towards evidence-based exercise and believe in the physicians’ submission of evidence-based practice in high-quality services to provide better and faster health services, giving the best response to the requirements of the recipients of health care services and satisfaction customer orientation impact that made up the health care system. The outcomes of the previous study also indirectly suggested that this approach was based on evidence-based practice to have an influence on the customer orientation .According to the second hypothesis regarding the impact of behavioral intention, the behavior based on evidence-based practice to customer orientation was evident, the physicians were studied, and the behaviors were associated with evidence-based practice in order to give the best answer to the clients. These behaviors included problem-solving skills, filling gaps in professional performance by using the best evidence, using guidelines and instructions in response to the client needs and skills of the professional practice due to new evidence. As a consequence, the number of previous researches also indirectly referred to the issue of the treatment based on evidence-based practice which affected the customer orientation [18].Amini and colleagues research results were different from the conclusions of the current study, and, the researchers concluded that the residents in the research had a positive view towards evidence-based medicine and the access to the Internet for clinical decision making, practically of evidence-based medicine, and, they did not apply it since they did not consider a systematic training in this field [14].The results of the research of Salehi and colleagues regarding the implementation of evidence-based performance on the nurses were different from the conclusions of this research. In titles of performance, most of staff in the field of evidence-based nursing was weak, the research staff was motivated, and the organization supported this weakness [36].Unlike the model that predicted a causal relationship, there was no research that examined the related barriers and found no evidence of measures rejected by the customer orientation. With consideration of the measures used in this section, such as having enough time to find the evidence needed to have the confidence, having the necessary skills in the field of evidence-based practice, facilities, proficiency in English, it could be achieved that the presence of these barriers would be the best evidence that doctors can access. A large number of respondents and lack of time was the most significant factor in the judgment of not using evidence-based medicine. In 2004, Hanson and colleagues noted that only 1.9 percent of the physicians and other doctors use specific methods to find the evidence they need to learn to assess the evidence .The previous researches noted other similar obstacles such as shortage of time, shortage of skills to search, the age of employees, level of experience, loss of a systematic training, their motivation and lack of an organizational support personnel .Unlike the model, a causal relationship between practitioners in the field of evidence-based practice and customer orientation was observed and the fourth hypothesis was rejected. The study results also showed that the awareness of target groups used the low knowledge of employees in different job categories in this area [11].It can be achieved that physicians studied the need for spending programs and training courses based on approach evidence, the signification of the work and being familiar with the advantages of using evidence-based approach. Therefore, it was recommended through workshops and educational meetings and the formulation of an interaction with the care centers based on evidence and past experience with regard to the facilities given to this important issue. Based on the findings of the fifth research hypothesis, the loss of barriers in the act of the greatest evidence was accepted by the customer. Based on the outcomes of Heiwe et al. study, it can be stated that despite some obstacles, like the lack of time, the approach based on evidence in the clinical practice, the judgment that the best evidence will be capable of taking better decisions and providing a greater quality of care was reached [The sixth hypothesis, regarding the presence of a positive connection between the sources of evidence usually applied to retrieve the information on the customer, was accepted. The provision of the evidence resources needed such as manuals and instructions for entrance to the Internet, studying the data, training courses and intelligence information from colleagues shared a very significant role in the adoption of the evidence-based approach in the research group. The organization will provide the conditions and resources so that workers are directed towards the adoption of this approach. The outcomes of this research revealed that there is a meaningful causal connection between the dimensions such as “attitude”, “intent to conduct and behavior”, “lack of barriers to change based on the best evidence”, “the current evidence sources used for information retrieval”, and the evidence-based strategy to “customer” in the collection. But, there was no meaningful causal connection between the 2 dimensions, “lack of barriers and finding the evidence” and “Introduction to Evidence Based Practice”, the evidence-based strategy to “customer orientation” in the collection of physicians studied. By providing the necessary training so that the staff could provide the facilities to encourage and motivate the staff, the use of evidence-based program could be used and it would facilitate a greater efficiency and ultimately improve the organization and attract customers and clients. As physicians base their actions on the scientific evidence in the health area, they will be able to make better decisions and provide a higher level of care, so as to decrease the charge of treatment, patients gaining the satisfaction and the performance of the organization. The outcomes of this study showed that physicians make an evidence-based, customer-focused approach of the institution. RecommendationsIn the end, it was suggested that similar studies in different working groups in the healthcare organization, were appropriate and compatible with the circumstances in our nation, the improvement of care being based on the achieved evidence-based practice.


Evidence-informed decision-making for health is far from the norm, particularly in many low- and middle-income countries (LMICs). Health policy and systems research (HPSR) has an important role in providing the context-sensitive and -relevant evidence that is needed. However, there remain significant challenges both on the supply side, in terms of capacity for generation of policy-relevant knowledge such as HPSR, and on the demand side in terms of the demand for and use of evidence for policy decisions. This paper brings together elements from both sides to analyse institutional capacity for the generation of HPSR and the use of evidence (including HPSR) more broadly in LMICs.The paper uses literature review methods and two survey instruments  to explore the types of institutional support required to enhance the generation and use of evidence.Findings from the survey of research institutions identified the absence of core funding, the lack of definitional clarity and academic incentive structures for HPSR as significant constraints. On the other hand, the survey of Ministries of Health identified a lack of locally relevant evidence, poor presentation of research findings and low institutional prioritisation of evidence use as significant constraints to evidence uptake. In contrast, improved communication between researchers and decision-makers and increased availability of relevant evidence were identified as facilitators of evidence uptake.The findings make a case for institutional arrangements in research that provide support for career development, collaboration and cross-learning for researchers, as well as the setting up of institutional arrangements and processes to incentivise the use of evidence among Ministries of Health and other decision-making institutions. The paper ends with a series of recommendations to build institutional capacity in HPSR through engaging multiple stakeholders in identifying and maintaining incentive structures, improving research (including HPSR) training, and developing stronger tools for synthesising non-traditional forms of local, policy-relevant evidence such as grey literature. Addressing challenges on both the supply and demand side can build institutional capacity in the research and policy worlds and support the enhanced uptake of high quality evidence in policy decisions. Despite the role of evidence in informing effective policy- and decision-making in health and optimising the use of scarce resources , in manyWhere evidence is available, capacity to appraise and use different kinds of evidence remains weak. This is both at the level of individual decision-makers who may not have the time or incentives to interpret evidence, as well as at the level of MoHs, which in contrast to many high-income countries (HICs), may not have defined processes to consider and use evidence at different stages of the decision-making process . The oveSeguro Popular health insurance scheme and Thailand’s national Universal Health Coverage programme; two prominent examples where locally generated HPSR evidence informed the design and implementation of programmes and policies to strengthen health systems … methodologies, tools and resources in using evidence in policy-making”.A little under half (11 of 23) of respondents, reported having received training relevant to accessing or using research evidence in decision-making processes in the two years prior to the survey. Skills frequently imparted included those in data analysis, carrying out general internet searches and skills to access databases such as PubMed. One respondent reported receiving training in the production and dissemination of evidence briefs for policy and yet another reported that the training received had been to “assess Only seven MoHs reported having in place mechanisms to enable staff rotation to research institutions. Of these, secondment mechanisms were in place at three MoHs and one MoH reported allowing officials time for sabbaticals at research institutions. From the data, it would appear that, while research training programmes for MoH officials are not uncommon, mechanisms to enable more in-depth exposure to research institutions over a longer period of time are less prevalent. This is not surprising given the shortage of skilled human resources in a large number of MoHs particularly in LMICs.Finally, respondents from MoHs were asked an open ended question to identify facilitators to the uptake of evidence in decision-making in their MoHs. In line with the pre-existing literature in this area, increased communication and collaboration between researchers and decision-makers, increased availability of relevant knowledge, and the timing of research coinciding with reforms were identified as leading facilitators.Based on our findings, we suggest actions to take forward the generation of HPSR and the use of HPSR and evidence more broadly for informing health-related decision-making. These require concerted and coordinated efforts on the part of a variety of stakeholders, including funders and international agencies, national governments and the HPSR community.The challenges inherent in developing a shared definition of HPSR and improving alignment in this field, even within institutions, are reflected in the low proportion of institutions reporting having such a definition. While definitions for HPSR have been developed, notably in the Alliance’s own products, including the Methodology Reader on HPSR , there rIn addition, field building would also entail advancing research methods, developing common taxonomies and creating guidelines for the appropriate conduct and reporting of HPSR. This includes how best to judge the impact of complex interventions within dynamic and interconnected health systems, which randomised controlled trials that presume linear relationships between cause and effect fail to do . While HWith many institutions involved in HPSR having their own networks of actors, improving harmonisation of the field and strengthening advocacy for its uptake in decision-making should be performed by bringing these networks together and developing a common mission and agenda for the way forward for HPSR, including through the identification of HPSR research priorities. The importance of this has been understood by the Alliance, which has introduced a new strategic objective in its Strategic Plan 2016–2020, centred around convening partners, especially policy-makers, to enable HPSR to better inform policy- and decision-making .Funding is urgently needed to operationalise this. Funding for HPSR globally represents a figure that is merely 2% of the annual budget of the United States National Institutes for Health , 38. We There is also need for multiple stakeholders, most importantly global and national HPSR funders and HPSR research institutions to come together to put in place incentives to encourage the generation of HPSR knowledge. Possible incentives include directing funding for the development of alternative career tracks, such as Professor of Practice, for researchers engaged in policy-relevant research that will prioritise policy relevance of an individual’s research as an indicator for career advancement. Developing metrics to measure the policy relevance of an individual’s research contribution and institutionalising the use of such metrics in research institutions is thus important . This isIt is also important to do more to incentivise knowledge production beyond peer-reviewed publications and towards developing products of direct relevance to decision-makers, such as policy briefs, research summaries and the creative use of social media, if the HPSR knowledge produced is to have maximal impact in informing decision-making , 14. ThiThe findings also bring to the fore the need for the greater production and availability of researchers trained in HPSR, with the difficulty in getting trained researchers being a particularly major challenge for research institutions in LMICs. This is evident from the finding that, though the production of HPSR about and in LMICs has increased, a substantial proportion of HPSR publications on LMICs are produced by authors from HICs. Even within LMICs, the production of HPSR is highly skewed, with a small number of countries accounting for a large share of HPSR publications .Developing and offering more HPSR training programmes and funding for this is only part of the solution; it is equally important for HPSR institutions, particularly in LMICs, to attract talented researchers by putting in place clear career advancement and promotion avenues, including through mentorship programmes to support inter-disciplinary HPSR researchers who often work relatively isolated within departments focusing on particular disciplines . FurtherThe barriers faced by MoHs in obtaining research evidence demonstrate the need to increase access to research literature, both in terms of peer-reviewed publications as well as grey literature, including project reports, evaluations and other non-peer-reviewed materials. Encouraging open access publication (an area where there has been much growth in recent years) as well as enabling access to databases of peer-reviewed literature through institutional subsidies for decision-making bodies in LMICs are two potential mechanisms to facilitate access to peer-reviewed literature. It is worth noting that unintended consequences of some of these potential solutions should also be considered. For example, the higher fee of publication in open access journals could potentially create bias in the type and context of research being featured in these journals, as well as contributing to publication bias overall. This is an important consideration for funders and further stresses the need for core funding as a priority as opposed to project-based funds.Collating and making available reports and evaluations (which are the most widely used sources of evidence for MoHs according to our findings above) is a more challenging task. There is an urgent need to develop repositories of this grey literature at provincial, national and global levels to ensure that this knowledge is systematically collated and brought together and to enable its potential use by relevant stakeholders to inform decision-making by placing it online. MoHs at the provincial and national levels and leading global health agencies all have a major role in setting up these repositories and making available this important global public health good .To produce high quality reports and evaluations, it could be mandated that policy or programme documents be informed by a review of the existent and available literature and spell out how this evidence informed a given policy decision or justify why it was not used in the instances where this was the case. The development of institutions or agencies to evaluate public programmes, as has been done in a wide range of countries including Mexico, South Africa and Colombia, among others, is one potential way forward. National governments would do well to learn from the experiences of these and other countries of how systematic evaluation can improve the transparency and quality of decision-making.Finally, these mechanisms need to be sustained through sensitisation of decision-makers in MoHs to debates on what constitutes evidence, the role of evidence in informing decision-making as well as imparting them with specific skills in accessing and interpreting evidence. This should be reinforced through the establishment of incentives to demand and use research at the individual and institutional levels. Examples of the former include making research usage a part of individual performance appraisal for decision-makers in relevant positions or units within MoHs, and putting in place arrangements to allow for rotations of MoH staff within research institutions to sensitise them to the potential role of research in informing decision-making .There are some limitations of this paper. The representativeness of the sample both among research institutions and MoHs is one limitation that is inherent in the use of surveys to gather such information. Both research institutions and MoHs were sent multiple reminders to improve the response rates. The likelihood of questions being understood differently by different respondents was mitigated by pre-testing the survey instruments and making changes to enhance clarity. However, the lack of a common understanding of HPSR in itself could have had an effect on the lens through which questions were answered. Furthermore, there is the potential for results having been skewed due to a Hawthorne Effect, with respondents being aware of the promotion of use of evidence in decision-making by the Alliance and seeking to please the group conducting the survey by overemphasising the reality of evidence use while not reporting all challenges.However, in spite of these limitations, we do believe that, by bringing together the state of knowledge generation and utilisation and bridging the perspectives of researchers and decision-makers, this paper has highlighted a number of major challenges to the generation of HPSR, and utilisation of research evidence more broadly, and demonstrated the need to understand both sides of the demand-and-use equation in order to establish sustainable mechanisms to overcome these challenges, enabling the co-production of HPSR knowledge by researchers and decision-makers . In this


Leishmaniasis is a chronic intracellular parasitic infection that travelers, immigrants, deployed military personnel, and refugees from endemic global areas acquire from the bite of infected sand flies and carry with them, including to non-endemic countries where leishmaniasis may be an unfamiliar illness to medical providers. This commentary discusses the first clinical practice guidelines produced by the Infectious Diseases Society of America and American Society of Tropical Medicine and Hygiene for the diagnosis and management of leishmaniasis, targeted for clinicians in North America. Leishmania parasites and transmitted by the bite of an infected sand fly vector, is on the rise [Leishmaniasis, caused by various the rise . An immuThe United Nations High Commissioner for Refugees reported that 65 million persons were displaced in 2015 and that three countries provided one half of the worlds’ refugees: Syria, Afghanistan, and Somalia . In a GeLeishmania co-infection, initially recognized in Mediterranean intravenous drug users but now seen worldwide, and risks associated with biologic immunomodulating drugs, including post transplantation, and with the burgeoning use of tumor necrosis factor-alpha inhibitors [An additional contributor to the rise of VL is decreased host susceptibility. Globally, this is most commonly caused by malnutrition, but in high-resourced countries this can also be caused by immunosuppression. Causative factors for the latter include HIV–hibitors , 11.In 2007, the World Health Assembly passed a resolution on the control of leishmaniasis, raising awareness of these infections . SubsequLeishmania species, and type/route of treatment. Many of the guideline recommendations derive from observational trials and case reports, or consist of expert opinion. Recommendations are given based on a determination of the strength of the recommendation (strong or weak) and the quality of evidence . In the guidelines, 14% of the diagnostic recommendations and 16% of the therapeutic recommendations were rated as weak; with regards the quality of evidence, diagnostic  and therapeutic  recommendations were skewed to lower-quality studies.The IDSA-ASTMH leishmaniasis clinical practice guidelines were structured by including questions that commonly arise in clinical practice. They provide practical tables, maps of endemic areas, clinical photographs, and contact details for reference diagnostic laboratories. These guidelines are detailed; they are organized into nine diagnostic questions (22 recommendations) and 26 treatment questions (57 recommendations) covering CL, mucosal leishmaniasis (ML), VL, and leishmaniasis management in the immunocompromised host and in special populations . Only the executive summary is published in paper format, but each question has an associated evidence summary available online. The guidelines are extensively referenced (>500 references) and a supplemental appendix has a searchable document of controlled CL treatment trials, transparently allowing a provider to assess the quality of evidence, and allowing them to search by country of acquisition, Viannia subgenus infection for expert otolaryngological examination regardless of symptoms (the chosen recommendation was that these patients should be referred). Another controversial topic was whether determining the Leishmania species responsible for the infection (requiring culture or reference laboratory support) is informative enough to make it worthwhile in most cases . The use of serology alone (rK39) for the diagnosis of VL was discouraged, with the recommendations advocating for parasitic confirmation. The sole recommendation for which consensus was not reached was whether New World CL north of Costa Rica could be managed by observation without intervention—if healing on its own—because it is geographically thought to have less risk of metastasizing to cause ML; one member with a great deal of ML experience felt that all should receive treatment.In the context of a majority of low/very low quality of evidence, applying GRADE  methodology is challenging. Early on, the committee decided to address questions for clinicians, whether or not the published evidence was adequate. The guidelines took in excess of 5 years to complete and are lengthy as well as complex. For the North American audience, new areas of focus include managing immunocompromised hosts (not just HIV) and special populations, and a discussion of the new drug, miltefosine, and its current role in treatment. Local therapies are reviewed for treating uncomplicated leishmaniasis, such as Old World CL; these approaches have been underutilized in the USA. Some of the more controversial recommendations among the group included whether to refer patients with Preparing these leishmaniasis guidelines often led to more questions than answers. One area ripe for additional research is the management of leishmaniasis in the non-HIV immunocompromised host . In general, this neglected tropical disease requires fully powered sample sizes in well-done comparative clinical trials with standardized outcome measures to develop a stronger evidence base. This will likely require the collaboration of consortia across regions to refine the best treatment approaches. Until this evidence is available, the guidelines generally define simple and complicated CL as the initial decision node for local versus systemic treatment, but emphasize that treatment choice should be individualized; there is no universally applicable treatment dose, route of administration, drug, or duration of therapy.The IDSA-ASTMH clinical practice guidelines provide a sensible current approach for clinicians evaluating and treating patients with leishmaniasis. We aimed to give clear recommendations from evidence that was often inadequate, but drawing upon our collective clinical expertise in managing leishmaniasis. More leishmaniasis cases are now seen in adventurous travelers, immigrants, refugees, and military personnel. These guidelines serve as a definitive reference to assist with the management of this clinically challenging infection. Lastly, the notable absence of an effective vaccine for leishmaniasis or prophylactic treatment highlights that prevention is essential to stopping the global rise of leishmaniasis.


Public health decision-making structures in England have transformed since the implementation of reforms in 2013, with responsibility for public health services and planning having shifted from the “health” boundary to local authority  control. This transformation may have interrupted flows of research evidence use in decision-making and introduced a new political element to public health decision-making. For generators of research evidence, understanding and responding to this new landscape and decision-makers’ evidence needs is essential.We conducted a systematic scoping review of the literature, drawing upon four databases and undertaking manual searching and citation tracking. Included studies were English-based, published in 2010 onwards, and were focused on public health decision-making, including the utilisation or underutilisation of research evidence use, in local  areas. All studies presented empirical findings collected through primary research methods or through the reanalysis of existing primary data.From a total of 903 records, 23 papers from 21 studies were deemed to be eligible and were included for further data extraction. Three clear trends in evidence use were identified: (i) the primacy of local evidence, (ii) the important role of local experts in providing evidence and knowledge, and (iii) the high value placed on local evaluation evidence despite the varying methodological rigour. Barriers to the use of research evidence included issues around access and availability of applicable research evidence, and indications that the use of evidence could be perceived as a bureaucratic process. Two new factors resulting from reforms to public health structures were identified that potentially changed existing patterns of research evidence use and decision-making requirements: (i) greater emphasis among public health practitioners on the perceived uniqueness of LA areas and structures following devolution of public health into LAs and (ii) challenges introduced in responding to higher levels of local political accountability.There is a need to better understand and respond to the evidence needs of decision-makers working in public health and to work more collaboratively in developing solutions to the underutilisation of research evidence in decision-making.The online version of this article (doi:10.1186/s13012-017-0577-9) contains supplementary material, which is available to authorized users. Since 2013, the context in which local public health strategy is developed and services are commissioned in England has shifted, and decisions previously made within National Health Service (NHS) structures are now being taken by different organisations and stakeholders. The shifting culture and context of decision-making means that as generators and synthesisers of research evidence we need to respond to these changes if we are to continue to support public health decision-makers to make informed and judicious evidence-based choices [The improvement of public health outcomes through evidence-based strategies is widely recommended, offering greater access to information on what works, increased opportunities for the effective use of resources, and improved certainty around the likelihood of success implementing different intervention options . There iIn the case of public health, the complexity in targeting populations, or communities, necessitates providing evidence that is both comprehensive and sensitive to this challenge . It follSince 2013, local public health leadership has mainly transferred to local authorities (LAs), whose public health remit now includes commissioning services across most aspects of public health , which The transition to a new landscape of decision-making is perceived to have progressed reasonably smoothly in some quarters , even ifStructural changes have implications for the way in which research evidence is used in public health decision-making. For example, the appointment of DPH exposed differing levels of commitment between those LAs who followed DH guidance and created new senior directorship posts for DPH and those with different interpretations . FurtherWithin the extensive literature on evidence-informed public health policy-making more broadly, a pattern of underutilisation of research evidence persists despite its abundance , 27 and The aim of the review presented here is to offer further insight on these issues through mapping the use of research evidence in public health decision-making at a sub-national level, and where possible to compare patterns of evidence utilisation before the reconfiguration of public health services (2010–2012/13) and afterwards (2013/14–2016). Unlike previous reviews, this review adopts a broad set of inclusion criteria around study design, with both observational and experimental studies included, but a narrow scope in terms of geography and date range. Nevertheless, the patterns of evidence use and the obstacles that decision-makers in local areas face when sourcing and using evidence are expected to have a much broader resonance and be of interest to readers outside England. This study was conducted by a team of systematic reviewers who are interested in the contribution of systematic reviews to public health decision-making in England, and how this evidence contributes alongside other sources of research evidence and public health intelligence more broadly.Four databases were searched for studies published between 2010 and 2016 (June)  and specific search strategies were designed for each . This means that we did not formally employ existing taxonomies of implementation to structure or guide our synthesis; although, our aims align with an ambition of understanding the processes of translating research into practice (developing process models) and understanding influencers on evidence use (developing determinant frameworks) . In thisThe search retrieved 903 references, 43 of which were identified as duplicates. After examining the abstracts and titles of the retrieved studies, 108 potentially relevant papers were selected for full-text assessment. The papers for these 108 studies were retrieved and were subject to a second round of full-text screening from which we identified a total of 23 papers from 21 studies for synthesis  or benchmarking or drawing comparisons of effectiveness with neighbouring areas (based on evidence of effectiveness) ; in otheEvidence that was aligned to the local political ideology , 47 and One study, which took place after 2013, also found that the local political ideology and the type of case that was required to made around a given public health issue changed over a short duration , which mThe need for evidence that was transferable to the local political context may also be an underlying explanation as to why expert opinion, advice, and experience were found to be highly utilised and valued in several studies , 50, 51.There were some indications of conflicting evidence-use patterns, with usage patterns not necessarily reflective of importance. One study found that NICE guidelines were one of the most frequently used sources of evidence, but practice guidelines (including NICE guidelines) were not universally regarded as the most useful . The samSocial network analyses suggest that the most powerful influencers on public health decision-making were able to form a bridge between local authority and NHS organisations . In contA number of studies suggested that some of the most influential evidence on local public health decision-making was generated through local evaluation activities , 41, 55.The degree to which the demand for and usage of evaluation evidence, evidence from experts, and locally embedded evidence are linked trends is not clearly expressed in the literature. Frequent deployment of local experts in public health decision-making may be as a result of their ability to blend inter/national sources research evidence with knowledge gained from local evaluation/experience. Oliver and DeVocht  identifiSeveral studies suggested that decision-makers would find evidence around the economic impacts of interventions useful, but that this was not always available , 53, 55.Two studies provided further disaggregation around the type of economic evidence that decision-makers valued the most , 58, whiOne study identified evidence briefings based on systematic reviews as a promising but currently underutilised approach  while a Named barriers to evidence use included access , capacitThis systematic scoping review identified 21 studies (23 papers) that included a specific focus on the process of English public health decision-making from 2010 onwards. These studies allowed us to identify some recurring themes around the role research evidence plays in decision-making, as well as some of the major influencers on the use of research evidence use. As we discuss below, few studies provided descriptive accounts of the way in which research evidence is used in practice, which precluded the development of process models representing the way in which research evidence is translated into local public health practice . SimilarFurther caveats exist, particularly around the broad inclusion criteria with regards to study design which precluded more formal synthesis and an assessment of individual study quality. However, all but three studies supported multiple themes Table , providiConsistent across the studies was a tendency to describe research evidence as being underutilised in decision-making but generally to be absent of sufficient detail around the type, process and context of the decision being made that could illuminate a way forward. Many of the suggestions being put forward in studies tend to be from the perspective of researchers, and arguably, this has led to a pre-occupation with identifying different forms of evidence, as opposed to different form and stages of decision-making where evidence is needed but is currently not, or under-, utilised.Heterogeneity in process and structure is ostensibly a defining characteristic of public health decision-making post-2013. Local decision-makers are keen to emphasise the uniqueness of their areas , as oppoIt is difficult to fully establish how the transition into local authorities has influenced the politics of decision-making. Certainly, some studies suggested that political influence had disrupted previously established flows of evidence into different stages of decision-making , 48, 49,The demand for economic evidence, a theme discussed in this review, is likely to strengthen against the background of funding cuts to public health budgets outlined in the introduction. Meanwhile, the role of local experts in a knowledge translation role is also likely to be sustained if research evidence continues to hold either low resonance or transferability or usability among end users. However, there is much left to learn about the role that experts do indeed fulfil, given that one study suggested that experts take a directive role. Regarding our own concern around the role of systematic reviews in public health decision-making, it is notable that almost half of policy actors in one study viewed meta-analyses as useful; although, none reported using this evidence regularly .The body of available evidence did not allow for full insight on the way in which evidence is used in English public health decision-making; although, a number of distinct processes and preferences were identified. Overall, these findings suggested that much of the research evidence being produced may not match the needs of decision-makers due to its “global” nature and that decision-makers may instead look to other means and sources to bridge this need. A clear gap in the literature identified in this systematic review was an insight into the process of decision-making in the new public health landscape, and how evidence is used differentially at different stages; Phillips and Green  providedMost of the literature encountered in this review focus on attempting to establish “determinant frameworks” of barriers and facilitators, without first establishing “process models” of the use of evidence . ConstruThe challenges raised in this review are clear. These include the need for researchers to develop a much deeper understanding of evidence requirements from the perspective of decision-makers. The current body of literature and, in particular, the solutions and facilitators to increasing research evidence use identified tend towards an understanding of decision-makers needs from the researchers’ perspective. This means that we prioritise types of evidence that should “fit” into informing decisions, rather than approaching the issue from the perspective of the types of decisions where insights and knowledge from evidence is needed, but where this need is unmet.Additional file 1:Scoping review on the use of evidence in local authorities. Search strategy and results. (DOCX 17 kb)Additional file 2:PRISMA 2009 Checklist. (DOC 64 kb)Additional file 3:Preliminary textual descriptions of studies and their findings. (DOCX 41 kb)


Overall Abstract: While drugs that target the dopaminergic and glutamatergic neurotransmitter systems have been extensively investigated as treatments for psychosis, there has been increasing attention in recent years on the endocannabinoid system as a therapeutic target. The CB1 receptor, the main central cannabinoid receptor is ubiquitous and modulates the function of several neurotransmitters, including dopamine and glutamate. A growing body of evidence suggests that psychosis is associated with alterations in the endocannabinoid system, independent of exposure to cannabis.The CB1 receptor is the main molecular target for delta-9-tetrahydrocannabinol (THC), the major psychoactive ingredient in cannabis. THC is responsible for the psychotogenic effects of cannabis, and is a partial agonist at the CB1 receptor. On the other hand, Cannabidiol (CBD), the second major constituent of cannabis is a non-psychoactive compound that may have an inverse agonist/antagonist effect at CB1 receptors, in addition to a range of other possible mechanisms of action. Interest in the therapeutic potential of CBD stemmed from evidence that it has broadly opposite effects to that of THC, at both the neural and the behavioural level in healthy individuals. Consistent with these results independent evidence that CBD has antipsychotic and anxiolytic properties in patients with mental health disorders has been accumulating. The absence of significant adverse effects associated with CBD, is a critical advantage in relation to the treatment of patients in the various stages of psychosis. Given its tolerability profile, CBD is a treatment of particular interest not just in those with chronic psychosis as in schizophrenia, but also in those in the earlier stages of psychosis. However, published evidence regarding the therapeutic efficacy of CBD as a treatment in psychosis has been limited except a small randomized clinical trial (RCT) some years ago . Furthermore, the mechanisms that may underlie the beneficial effects of CBD are unclear.This symposium will bring together state of the art evidence regarding the efficacy of CBD in the different stages of psychosis – from those at clinical high-risk (CHR), through early psychosis to chronic schizophrenia. Furthermore, data from animal and human studies will be presented to give an understanding of the potential mechanisms that may underlie the therapeutic effects of CBD.The first speaker (Prof Crippa) will set the scene by presenting evidence regarding the different potential mechanisms of action that may underlie the antipsychotic effect of CBD.The second speaker (Prof McGuire) will present the results of a 6-week placebo-controlled RCT demonstrating the efficacy of CBD as an add-on to existing antipsychotic treatment in schizophrenia.The third speaker (Dr. Ranganathan) will present the results from an ongoing, placebo-controlled RCT using an within-subject, crossover design to show the effects of 4-week CBD treatment on psychotic symptoms, cognition and electrophysiological markers in patients with established psychosis.Finally, the fourth speaker (Dr. Bhattacharyya) will present the results from a recently completed proof-of-concept study demonstrating the efficacy of short-term CBD treatment on symptoms and distress in CHR patients as well as on neurocognitive substrates implicated in the CHR state.Evidence presented here will be discussed by Prof D’Souza, who is an internationally recognized expert in cannabinoid pharmacology and experimental therapeutics development.


Frequently, a set of objects has to be evaluated by a panel of assessors, but not every object is assessed by every assessor. A problem facing such panels is how to take into account different standards among panel members and varying levels of confidence in their scores. Here, a mathematically based algorithm is developed to calibrate the scores of such assessors, addressing both of these issues. The algorithm is based on the connectivity of the graph of assessors and objects evaluated, incorporating declared confidences as weights on its edges. If the graph is sufficiently well connected, relative standards can be inferred by comparing how assessors rate objects they assess in common, weighted by the levels of confidence of each assessment. By removing these biases, ‘true’ values are inferred for all the objects. Reliability estimates for the resulting values are obtained. The algorithm is tested in two case studies: one by computer simulation and another based on realistic evaluation data. The process is compared to the simple averaging procedure in widespread use, and to Fisher's additive incomplete block analysis. It is anticipated that the algorithm will prove useful in a wide variety of situations such as evaluation of the quality of research submitted to national assessment exercises; appraisal of grant proposals submitted to funding panels; ranking of job applicants; and judgement of performances on degree courses wherein candidates can choose from lists of options. This approach is represented by the cell labelled ‘simple averaging’ (SA) in the top left of a matrix of approaches listed in One solution is to seek to calibrate the assessors beforehand on a common subset of objects, perhaps disjoint from the set to be evaluated . This meΓA on the set of assessors, formed by linking two whenever they assess a common object, is sufficiently well connected, one can expect to be able to infer a robust calibration of the assessors and hence robust scores for the objects. The construction of this graph is illustrated in Γ showing which objects are assessed by which assessors.If the expertise of two assessors overlap on some subject, however, any discrepancy between their evaluations can be used to infer information about their relative standards. Thus, if the graph a for object o by sao, Fisher's approach is based on fitting a model of the form sao=vo+ba+εao with εao independent identically distributed random variables of mean zero. Then ba is the bias inferred for assessor a and vo is the value inferred for object o. Fisher's approach is known as additive incomplete block analysis (IBA) and a body of associated literature and applications has since been developed , thoughAnother ingredient that is important in many panel assessments, however, is different weights that may be put on different assessments. We refer to these weights as ‘confidences’. Fisher's IBA does not take different levels of confidence into account.If the assessors express confidences in the assessments, for example, by some pre-determined weights assigned to types of assessment or by the assessors declaring confidences in each of their scores, then it is natural to replace SA by confidence-weighted averaging. This is represented as the top right entry of calibration with confidence (CWC). We demonstrate that the method can achieve a greater degree of accuracy with fewer assessors than either SA or IBA, and we derive robustness estimates taking the confidences into account.In this paper, we present and test a method to calibrate scores taking into account confidences; that is, we complete the matrix of approaches represented in We are aware of two other schemes that incorporate confidences into a calibration process. One is the abstract-review method for the SIGKDD'09 conference  pairs by  in ref.   is taken to besao and σao so that sao−σao,sao+σao], To take into account the varying expertise of the assessors with respect to the objects, we propose that in addition to the score ented in . There aented in , which cηao independent zero-mean, random variables of common variance w. For the moment, we set w=1; extensions to other values of w are considered in appendix A, and in particular are necessary if confidence is expressed only qualitatively. In the case that confidences are reported as only high, medium or low, they can be converted into quantitative ones by for example choosing λ≈2 and setting cao=λ2,1,λ−2, respectively. The interpretation of λ is the ratio of the uncertainty for a low confidence evaluation to that for a medium one, and for a medium one to a high one. Then w is unspecified but can be fit from the data, as in appendix A.So let us suppose thatThus, our basic model is3.sao,σao):∈E} for all assigned assessor–object pairs, we wish to extract the true values vo and assessor biases ba. The simplest procedure is to minimize the sum of squarescao was defined in equation . Then these conditions can be written aso anda,o anda.Now expression  is minimvo and ba. It has an obvious degeneracy in that one could add a constant k to all the vo and subtract k from all the ba and obtain another solution. One can remove this degeneracy by, for example, imposing the conditionEquations  and 3.33.3 form Γ linking assessor a to object o if and only if ∈E, as illustrated in the left column of cao. Whether the set of equations . Thus,  that if .L, thus ensuring that a solution exists. This is true if all null forms of the adjoint operator L† send the right-hand side to zero. The null space of L† has the same dimension as that of L, because L is square, and an obvious non-zero null form α is given byV and B that α=0. So a solution exists.It remains to check that the right-hand side of equation  lies in Γ is connected, equations  satisfying equation , which gives some computational savings. Replacing one of the equations in . We treat this in appendix C. The other is to evaluate the posterior uncertainty of the outcomes, assuming normal distribution of the 4.We have tested the approach in three contexts. We report in detail on two case studies here. In the first case study, we use a computer-generated set of data containing true values of assessed items, assessor biases and confidences for the assessments and resulting scores. This has the advantage of allowing us to compare the values obtained by the new approach with the true underlying value of each item. The second case study is an evaluation of grant proposals using realistic data based on a university's internal competition. In this test, of course, there is no possibility to access ‘true’ values, so instead we compare the evidence for the models using a Bayesian approach (appendix E), and we compare their posterior uncertainties (appendix D). The third context in which we tested our method was assessment of students; we report briefly on this at the end of the section.4.1NO=3000 objects are assessed by a panel of NA=15 assessors. This choice was motivated by the number of outputs and reviewers in the applied mathematics unit of assessment at the UK's 2008 research assessment exercise. The simulation was carried out using Matlab, and the system of equations was solved using its built-in procedure, which computed the LU decomposition of L . The reondition  was not vo were assumed to be normally distributed with a mean of 50 and standard deviation set to 15, but with vo values truncated at 0 and 100. The assessor biases ba were assumed to be normally distributed with a mean of 0 and a standard deviation of 15. Each assessment was considered to be done with high, medium or low confidence, and these were modelled using scaled uncertainties for the awarded scores, of σao=5, 10 or 15, respectively. The allocated scores follow equation , each simulation generated rNO object scores sao. From these, we generated NO value estimates NA estimates of assessor biases dvo. Finally, we determined the averages of the errors dvo and dba over 100 simulations. The results for these averaged mean and maximal errors in the scores are denoted by 〈dv〉 and (dv)max, respectively, and those for the biases  are denoted 〈db〉 and (db)max.With a–d and 3a–d. For demonstration purposes, we use three confidence levels rather than a continuous distribution. This allows us to clearly control differences in confidence levels in a)–(d). These represent different profiles, with the confidence for each assessment randomly allocated using probabilities for high, medium and low confidences in the ratios: (a) 1 : 1 : 1, (b) 1 : 1 : 2, (c) 1 : 2 : 1 and (d) 2 : 1 : 1. We observe that, for each method, the scores become more accurate (errors decrease) as the number of assessors per object r increases.Results for all three methods are presented in figures 2a–d, with only two assessors per object, the SA method gives errors averaging about 10 points. Over r=6 assessors per object are required to bring the mean error down to six points. Fisher's IBA, however, achieves this level of improvement with only two or three assessors. The CWC method delivers a further level of improvement of about one point. One also notes that, for the calibration approaches, relatively little is gained on average by employing more than four assessors per object. This result can be compared with [From figure 2red with  which foa gives the improvements achieved by the calibration methods as ratios of the mean errors coming from Fisher's IBA approach to the SA approach 〈dv〉IBA/〈dv〉avg and of the mean errors coming from the CWC approach to the SA approach 〈dv〉CWC/〈dv〉avg. Smaller ratios mean greater accuracy on the part of the calibrated approaches. Figure 4b gives the analogous accuracy ratios for the maximal errors, namely (dv)max,IBA/(dv)max,avg and (dv)max,CWC/(dv)max,avg. Figure 4a demonstrates that IBA delivers mean errors between about 60 and 80% of those coming from the SA approach, the better improvements being associated with lower assessor numbers. This is also the most desirable configuration for realistic assessments, as it represents employment of a minimal number of assessors per object. The CWC approach reduces errors by about a further 10 percentage points irrespective of the number of assessors.Figure 44.2To test CWC in a realistic setting, we adapted data from a university's internal competition for research funding, in which 43 proposals were evaluated by a panel of 11 assessors. Each proposal was graded by two assessors, who in addition each specified a confidence level in their grading in the form of high, medium or low. To respect confidentiality of the competition while making the data available, we not only anonymized the proposals and assessors but also made sufficient changes to the data  so that attribution would not be possible. The actual panel used SA, but the assessors were also asked to provide confidences so that CWC could be applied for comparison. The panel awarded grants to the top 10 proposals. Our goals were firstly to see what differences would have been made by use of IBA or CWC, secondly to quantify the evidence for the three models from the data to determine which was most appropriate, and thirdly to compare the posterior uncertainties they provide.cao=λ2,1,λ−2, respectively, with λ=1.75. We chose λ=1.75 as a reasonable guess at how the assessors used the confidence scale. One could include a computation to infer λ from the data, but our preference is for panel chairs to ask assessors to provide uncertainties rather than qualitative confidence levels, as indicated in §λ.To apply CWC, we translated the qualitative confidence levels of high, medium and low to values a–c shows the resulting values inferred by the three methods, projected into the planes of ,  and , respectively. Figure 5d is a Bland–Altman or Tukey mean-difference plot [Figure 5nce plot . The corIn the absence of ‘true’ values for the proposals, how can one decide which is the best method to use, and hence which outcome is preferred?vo to be the averaged scores and ba=0. For IBA, the residual is the value of  than SA, however, one should penalize them appropriately to make a correct comparison. Also although normalizing the residual for CWC by the average confidence sounds sensible, it is not clear it is the right way to compare CWC with IBA.σO=22.5, σA=15, wmax=900, wmin=1. As the evidences come out to be small numbers (around 10−168), we took their  logarithms. The resulting log-evidences are shown in A principled answer is provided by Bayesian model comparison. In this procedure, the evidence provided by the data in favour of each model is quantified, and the best model is the one with the highest evidence. The procedure to quantify the evidence for the three models is described in appendix E. It depends on assumptions about the prior probability distribution for the parameters of the models, but we took ‘ball’ priors on the true values and on the biases (constrained by the degeneracy-breaking condition) and a truncated Jeffreys' prior on the variance of the noise. In the notation of appendix E, the parameters for the prior probability distributions were A third approach is to evaluate the posterior uncertainty in the values assigned to the objects for the three methods, as detailed in appendix D, using  for IBA As the object of the competition was only to choose the best 10 proposals to fund, rather than assign values to each proposal, it might have been more appropriate to design just a classifier system (with a tunable parameter to make the right number in the ‘fund’ class) but our goal was to use it as a test of CWC.et al. [The fact that three different methods with roughly equal evidence lead to drastically different allocation of the grants, and with large posterior uncertainties, highlights that better design of the panel assessment was required. Large variability of outcome even when just using SA but with different assessment graphs was already noted by Graves et al. . A moral4.3We also tested the method on undergraduate examination results for a degree with a flexible options system  and on tIn the former case, as surrogates for the confidences in the marks we took the number of Credit Accumulation and Transfer Scheme (CATS) points for the module, which indicate the amount of time a student is expected to devote to the module . The amount of assessment for a module is proportional to the CATS points. If it can be regarded as consisting of independent assessments of subcomponents, e.g. one per CATS point, with roughly equal variances, then the variance of the total score would be proportional to the number of CATS points. As the score is then normalized by the CATS points, the variance becomes inversely proportional to the CATS points, making confidence directly proportional to CATS points. The outcome of our analysis indicated significant differences in standards for the assessment of different modules, but as most modules counted for 15 or 18 CATS, this was not a strong test of the merits of including confidences in the analysis, so we do not report on it here.For the postgraduate module, there were four lecturers plus module coordinator, who each assessed oral and written reports for some but not all of the students, according to availability and expertise . Each assessor provided a score and an uncertainty for each assessment. The results were combined using our method and the resulting value for each student was reported as the final mark. The lecturers agreed that the outcome was fair.5.We have presented and tested a method to calibrate assessors in a panel, taking account of differences in confidence that they express in their assessments. From a test on simulated data we found that calibration with confidence (CWC) generated closer estimates of the true values than Additive incomplete block analysis (IBA) or simple averaging (SA). A test on some real data, however, provided little evidence to distinguish between the methods, though they produced wildly different rankings, suggesting that the assessment procedure for that context needed more robust design. Nevertheless, CWC came ahead on posterior precision. We note that the default of assuming all assessment confidences to be equal results in IBA, which already represents a useful improvement over SA.One of the principal conclusions from our analysis is that to achieve reliable outcomes from the methods we tested, requires good design of the assessment graph .All three methods we compared are based on least-squares fitting. They may therefore be considered overly sensitive to outliers. An alternative approach which is less sensitive to outliers is based on medians rather than means. For example, Tukey's Median Polish  is a med— It requires assessors to give reliable uncertainties; if assessors differ in their confidence estimates the method gives higher weight to those who give higher confidences. In particular, one needs to guard against an assessor giving unwarrantedly high confidence for a particular assessment. There is a case for calibrating confidences too.— Bias effects may be more subtle than just an additive effect; for example, an assessor may be more generous (or perhaps tougher) on topics in which they have high confidence, or they may use a shorter or longer part of the scale than other assessors.— Some organizations insist on round-number scores; this goes against the spirit of our approach and is awkward for assessors who may rightly wish to rate an object as between two of the allowed grades. The requirement is perhaps based on the laudable idea of not wishing to imply higher accuracy than is warranted, yet in our opinion this is better dealt with by reporting an uncertainty for each result on a continuous scale.— Some organizations may insist that scores cannot go beyond certain limits, which is awkward for an assessor if after evaluating several objects highly they find there are some they wish to rate even higher.Some other drawbacks of our CWC method are:There are a number of refinements which one could introduce to the core method, addressing some of these drawbacks. These include how to deal with different types of bias, different scales for confidence, different ways to remove the degeneracy in the equations, how to deal with the endpoints on a marking scale, and how to choose the assessment graph. Some suggestions are made in the appendices, along with mathematical treatment of the robustness of the method and of computation of the Bayesian evidence for the models.An advantage of our type of calibration is that it does not produce the artificial discontinuities across field boundaries that tend to arise if the domain is partitioned into fields and evaluation in each field carried out separately. In the UK Research Assessment Exercise 2008, for example, there is evidence that different panels had different standards [We suggest that a method such as this, which takes into account declared confidences in each assessment, is well suited to a multitude of situations in which a number of objects is assessed by a panel. We acknowledge, however, that this approach requires an investment in training assessors to estimate their uncertainties and in constructing a sufficiently strongly connected assessment graph. Different panels will deal with the trade-off between investment of effort and accuracy of results in different ways.