Dialysis has long been a critical issue in the field of nephrology, though the burden this lifesaving technology places on society can be immense. Effectively increasing the health literacy of hemodialysis patients can be beneficial for their health outcomes and self-care abilities. Thus, the aims of this study are to: (1) develop a health literacy assessment tool in Chinese for patients receiving hemodialysis treatment; (2) assess the health literacy level of the Taiwanese hemodialysis population using the tool developed.The questionnaire was developed based on Nutbeam’s three constructs of health literacy and seven sub-constructs identified for the purposes of this study. Experts were consulted for content validity assessment. The questionnaire then was used to conduct a census study at six hospitals and one dialysis clinic that provide hemodialysis treatment in the Taipei area (urban northern Taiwan). To be included, patients must have been at least 18 years old and receiving hemodialysis treatment at the time of the study. 468 eligible respondents were included in the analysis.The reliability of the tool was 0.81 and the confirmatory factor analysis indicated good construct validity. The mean literacy score for the sample was 19.7 (SD = 4.61) out of a maximum of 26 points, and the median was 21 (range from 6 to 26). Age, education level, primary language, primary caregiver identity, and willingness to receive a transplant were all factors that showed significant association to health literacy level in multiple categories.The health literacy assessment tool developed in this study is the first health literacy assessment instrument to be made available for a specific patient group in Taiwan. Hemodialysis patients’ knowledge of day-to-day care practices is satisfactory, while their critical literacy is weak. Poor lifestyle is one of the factors associated with the high prevalence of chronic diseases in Taiwan [Although the literacy rate for the general population in Taiwan is over 98 % , this don Taiwan –5, and hn Taiwan . The totn Taiwan . HoweverA statistical report produced by the Taiwanese Department of Health in 2007 ranked renal disease eighth among the top ten causes of death in Taiwan. There were 5099 deaths caused by renal disease and the mortality rate was 22.2 %—a 1.6 % increase from the previous year [The American Medical Association (AMA) has defined health literacy as “the constellation of skills, including the ability to perform basic reading and numerical tasks required to function in the health care environment ”. NutbeaStudies have shown that patients with low health literacy perform unfavorably in a variety of related areas. Several studies indicate that patients with lower reading literacy and oral literacy also tend to be lacking in health-related knowledge , 11. TheESRD, hemodialysis, peritoneal dialysis, and kidney transplant patients experienced adjusted mortality rates of 138, 171, 152 and 35 per 1000 patient-years respectively in 2013 . Other sEffectively increasing the health literacy of patients can be beneficial for the health and self-care capabilities of patients who are receiving hemodialysis treatment. However, since the current measurement of health literacy is broad and not focused on the investigation of disease-specific literacy, it can be difficult to determine what specific health literacy knowledge patients are lacking. The primary purpose of the study was to develop a health literacy assessment tool in Chinese for patients receiving hemodialysis treatment and to assess the health literacy level of the Taiwanese hemodialysis population using the tool developed.Currently available health literacy tests such as the Test of Functional Health Literacy in Adults (TOFHLA), Wide Range Achievement Test (WRAT), and Rapid Estimate of Adult Literacy in Medicine (REALM) utilize a format that assesses literacy through reading questions and Cloze tests –20. The We constructed a tool divided into two sections: the health literacy assessment and demographic information. There are a total of 52 items in the questionnaire with 26 items in each section. For the health literacy section, this study adapted Nutbeam’s model and incorporated his three key constructs of critical health literacy, interactive health literacy, and functional health literacy. These constructs were further refined to address specific health literacy issues, as shown in Fig. After the development of the tool, experts such as nephrologists, nurses, and public health professors were consulted to conduct a content validity assessment and provide constructive comments regarding clarification of descriptions, the appropriateness of questions, and the difficulty level of the questions. All items were reviewed by the experts using a 9-point Likert scale for the validity of each item; a comment section was provided for suggested modifications. Items that were rated below 7 on average were selected for further modification by the team of experts. A pilot test was also conducted with 20 dialysis patients to confirm items’ practicability and items were modified accordingly.Adult patients over 18 years of age receiving hemodialysis treatment who were able to communicate with interviewers were initially considered for inclusion in this study. Survey data were collected from six hospitals and one hemodialysis clinic in northern Taiwan. The surveys were conducted by interviewers on a one-on-one basis in order to enhance the survey quality and consistency of survey contents. Interviewers received training to improve reliability of the results including discussion of the purpose of this study, detailed explanations and descriptions of methods, and the overall intended contents of the survey session. The six interviewers were able to communicate in both Mandarin Chinese and the Taiwanese dialect in order to facilitate communication with patients using either of these languages. Surveys began in December 2008 at the seven health facilities; we approached a total of 591 patients, and 468 eligible respondents filled out and returned health literacy questionnaires by April 31, 2009. Respondents were excluded if they were unable or unwilling to participate, if they were unable to communicate verbally with the interviewers, or if they chose not to finish the survey process after beginning.This study was reviewed and approved by the National Taiwan University Hospital (NTUH) IRB, and its approval number was NTUH-200712014R. Interviewers contacted patients at outpatient clinics and obtained respondents’ informed consent through verbal explanation and written in form. Patients’ consent forms were stored in locked cabinets in the PI’s office for 2 years, then shredded and disposed of securely. All data was analyzed on an anonymous basis to ensure respondents’ confidentiality. NTUH’s IRB approved the entire procedure, including the method of obtaining informed consent, data analysis, data storage, and data management.The surveys were coded and data were analyzed using the statistical software SPSS for Windows 16.0  and LISREL 8.7 as analytical tools. The study used descriptive statistics and one-way analysis of variance (ANOVA) to discuss health literacy and explore their connection to individual capabilities and social conditions. Furthermore, construct validity was verified by performing confirmatory factor analysis.The mean age of interviewees in the present study was 61.48 years with a standard deviation of 13.74 years, and male respondents accounted for 294 (49.7 %) of the survey respondents. Health literacy was assessed based on multiple-choice questions with four choices but only one correct answer to each question. Incorrect answers, missing answers, and questions with more than one response selected were all scored as incorrect and awarded 0 points, while correct answers were awarded 1 point. In the demographic section of the survey, missing values did not disqualify the full survey case, but these missing values were excluded from analysis. The presence of trained interviewers minimized missing values and incomplete assessments.In order to check the consistency of responses, split-half methodology was applied to confirm the reliability. Results showed a score of 0.83 overall, which indicated very good consistency. Inter-rater reliability was improved by providing the interviewers’ with consistent training before data collection.Confirmatory factor analysis (CFA) was applied to confirm the instrument’s construct validity. Results of goodness of fit showed absolute indices were appropriately high, including GFI (goodness of fit index) = 0.91, AGFI (adjusted goodness of fit index) = 0.9, and CN  = 285.70. Incremental fit indices were also appropriately high, including NNFI (Non-Normed Fit Index) = 0.93 and CFI (Comparative Fit Index) = 0.94. Parsimony indices were adequate, including PNFI (Parsimony Normed Fit Index) = 0.77 and PGFI (Parsimony goodness of fit index) = 0.72. These indices confirmed high construct validity of this health literacy instrument. CFA indicated very good construct validity for this seven sub-construct health literacy framework as reported in Fig. The results showed the average total score was 19.70 (SD = 4.61) out of 26 possible points. The mean score was 3.96 out of 5 (SD = 1.16) for functional literacy, 3.58 out of 4 (SD = 0.76) for basic health knowledge, 3.07 out of 4 (SD = 1.26) for communicative literacy, 2.57 out of 3 (SD = 0.68) for interactive literacy, 3.09 out of 5 (SD = 1.37) for advanced health knowledge, 1.70 out of 3 (SD = 0.74) for critical literacy, and 1.74 out of 2 (SD = 0.47) for patient safety. Among of these 7 sub-constructs, respondents earned relatively high scores in basic health knowledge, interactive literacy, and patient safety but relatively low scores in advanced health knowledge and critical literacy.The mean difference in health literacy scores between each group was analyzed for the studied demographic variables, with health literacy as the dependent variable . According to the Claims Review and Drug Benefit Unit, Bureau of National Health Insurance, the mean age for patients receiving hemodialysis in 2008 was 61.59 years (SD = 13.30) . TherefoThis study developed a health literacy instrument based on seven sub-constructs for dialysis patients and the construct validity of the instrument was verified by confirmatory factor analysis. Based on the survey results, basic health knowledge received the highest correct answer rate and mean score while critical literacy received the lowest score among the seven sub-constructs of health literacy. Basic health knowledge was associated with knowledge of appropriate diet for patients receiving hemodialysis. While other health literacy instruments assess the ability to spell and pronounce medical terminology, this instrument placed more emphasis on assessing whether patients possessed the necessary dialysis-specific health knowledge to maintain their wellbeing. This means that patients should be more familiar with these issues and able to make the correct choices.The advanced health knowledge sub-construct covered a variety of formal medical knowledge. Access to this level of medical knowledge was not as readily available as access to basic health knowledge; it required the patient to actively interact with medical staff, as these topics are not commonly encountered in everyday situations. For example, this sub-construct included differentiating between peritoneal dialysis and hemodialysis; peritoneal dialysis is less familiar to (and less commonly used for) dialysis patients in Taiwan, and so the relevant literacy score average was lower.The critical literacy sub-construct covered the ability to process numerical and analytical data. The critical literacy of patients cared for by their children/child’s spouse or by foreigner caregivers was poorer than others. Since critical literacy is a more abstract form of health literacy, patients should try to obtain the ability to reason and rationalize their findings. Some studies conclude that critical literacy is the ability to think in the abstract and generalize their experience and judgment skills . This suThe bivariate analysis showed that the five demographic variables of age, education level, primary language, primary caregiver identity, and willingness to receive a transplant are associated with the overall health literacy of hemodialysis patients. The association of age and overall health literacy is consistent with the existing literature, which indicates that older patients tend to have poorer health literacy . FurtherCurtin and Mapes observed that patients with late-stage renal disease generally have inadequate health literacy . Fraser End-stage renal disease is not reversible. To examine these patients and the degree of their health literacy can provide an initial assessment of their knowledge and understanding of their illness as well as their ability to make optimal decision regarding their care. This assessment tool could identify the shortcoming of patients’ health knowledge and health literacy, allowing physicians and nurses to educate them in areas they fall short.Although this study is the first case of conducting a health literacy assessment specifically targeting Taiwanese hemodialysis patients, the fact that the sampling location was limited to a metropolitan setting may make it difficult to generalize the findings to broader populations. In addition, the present study cannot be directly compared to studies conducted in European and American countries, as the mean score is utilized as the health literacy determination standard in this study; this differs from the partition style  used for many assessment tools of health literacy in European and North American studies.These findings, along with hemodialysis-related health literacy in general, are of particular relevance in populations where hemodialysis or end stage renal disease (ESRD) rates are especially high. Taiwan is an ideal testing ground for hemodialysis-related studies due to the availability of data of the National Health Insurance Research Database (NHIRD) and the fact that Taiwan has the highest global prevalence (2902 per million populations in the year of 2012) of ESRD . DialysiOne possible complicating factor regarding health literacy in Taiwan is that a high prevalence of the elderly and chronically ill are cared for by foreign caregivers. As of 2003, there are over 195,000 foreigners with temporary residency working as family caregivers in Taiwan, a remarkably high number compared to the overall Taiwanese population of roughly 23 million. Possible language barrier issues can affect communication with patients as well as hospital staff, as many foreign caregivers are not proficient in Chinese. Foreign caregivers may also return to their home country or change which patients they are for, reducing the continuity of care available compared to when patients care for themselves or are cared for by their families. One suggestion for policymakers and dialysis clinic staff is to monitor who is providing care for the patient, and to provide new educational materials and training when presented with a new caregiver. Additionally, dialysis-specific educational materials should be made available in languages frequently spoken by foreign caregivers.The sampling of this survey focused only on hemodialysis centers in Taipei, the largest city in Taiwan. In contrast to other area of Taiwan, Taipei has high medical accessibility. Hemodialysis patients who live in Taipei have access to more medical and health education resources than patients in other areas. Therefore, in order to assess the health literacy of hemodialysis patients more completely in Taiwan, future studies should deliver this questionnaire to hemodialysis centers and facilities throughout Taiwan.The health literacy assessment tool developed in this study is the first health literacy assessment instrument to be made available for a specific patient group in Taiwan, to our knowledge. The concept of this instrument is based on Nutbeam’s health literacy model, and it contains questions based on health literacy topics that hemodialysis patients encounter daily. The health literacy questionnaire has high validity and reliability . Health


Justice-involved individuals are an underserved population with extremely high rates of mental health disorders. Very little mental health D/I research has been conducted in the justice system to date. This paper reports implications for implementation of evidence-based mental health practices in justice settings from results of a Hybrid Type I trial (R01 MH095230), framed within Taxman's Evidence-Based Criminal Justice Interagency Implementation Model (CJ-IIM). Implementation data from this trial include: (1) cost-effectiveness of providing an evidence-based psychosocial intervention  for major depressive disorder (MDD) in state prisons at a dose typical of community , rather than prison (monthly) settings (RCT of 180 state prisoners with MDD in 8 state prisons in 2 states); (2) acceptability of the evidence-based practice to prison mental health providers and administrators (based on a survey of n = 47), (3) provider attitudes and competencies, and (4) barriers and facilitators of implementation in this trial . Preliminary effectiveness results indicated advantages for IPT for depressive symptoms and hopelessness, with some suggestion that effects were larger as providers gained experience with the intervention; cost-effectiveness analyses are ongoing. Survey results indicated that providers and administrators viewed MDD among prisoners as an important problem and perceived current strategies for treating MDD in prison as insufficient. They tended to be oriented toward rehabilitation rather than punishment and were friendly toward evidence-based practices. However, mental health budgets that were small relative to the magnitude of inmate treatment needs translated into heavy case loads and a focus on crisis management, with inconsistent supervision and staff and leadership turnover at some facilities, posing serious barriers to adoption and sustainability. Overall, prisoners are desperate for adequate care and their providers are friendly toward innovation and desperate for ways to provide prisoners with more adequate care. However, public investment in offender health is low and therefore resource and system barriers are substantial. We discuss the implications of these findings for system-wide implementation of evidence-based mental health practices, including public media messaging and cost-effectiveness research as potential ways to address systemic barriers.


To the editor: As members of the French Ministry of Health Working Group on autochthonous urinary schistosomiasis, we read with interest the 2 recently published articles regarding schistosomiasis screening of travelers to Corsica, France . In the study based on travelers from Italy (In the study by authors from the GeoSentinel Surveillance Network (Altogether, these 2 studies identified only 1 patient with parasitological evidence of infection that was attributable to the already known 2013 focus in Cavu River. Therefore, these articles do not provide evidence of transmission of schistosomiasis in Corsica after 2013 or outside the Cavu River.


Health policymaking is a complex process and analysing the role of evidence is still an evolving area in many low- and middle-income countries. Where evidence is used, it is greatly affected by cognitive and institutional features of the policy process. This paper examines the role of different types of evidence in health policy development in Nigeria.The role of evidence was compared between three case studies representing different health policies, namely the (1) integrated maternal neonatal and child health strategy (IMNCH); (2) oral health (OH) policy; and (3) human resource for health (HRH) policy. The data was collected using document reviews and 31 in-depth interviews with key policy actors. Framework Approach was used to analyse the data, aided by NVivo 10 software.Most respondents perceived evidence to be factual and concrete to support a decision. Evidence was used more if it was perceived to be context-specific, accessible and timely. Low-cost high-impact evidence, such as the Lancet series, was reported to have been used in drafting the IMNCH policy. In the OH and HRH policies, informal evidence such as experts’ experiences and opinions, were reported to have been useful in the policy drafting stage. Both formal and informal evidence were mentioned in the HRH and OH policies, while the development of the IMNCH was revealed to have been informed mainly by more formal evidence. Overall, respondents suggested that formal evidence, such as survey reports and research publications, were most useful in the agenda-setting stage to identify the need for the policy and thus initiating the policy development process. International and local evidence were used to establish the need for a policy and develop policy, and less to develop policy implementation options.Recognition of the value of different evidence types, combined with structures for generating and using evidence, are likely to enhance evidence-informed health policy development in Nigeria and other similar contexts. There is an increasing recognition that strong and effective health systems that are evidence-informed in their operations are necessary to achieve continued improvement in health outcomes in an efficient and equitable manner , 2. The The capability of health systems in low- and middle-income countries to deliver services to the people is severely constrained by polices that are borne out of trial and error rather than evidence , 9. Howewhat constitutes actual or asserted facts planned for use in support of a conclusion”  survivaHowever, there were a few disparate views as regards labelling this singular type of evidence as the most important, because according to the respondents, “e Lancet , were imEvidence am looking more at empirical data….empirical data. But beyond looking at empirical data, I am also interested in the process of gathering that data.” “An analysis of the various responses highlight the use of a wide breath of evidence-informed policies, which included both formal and informal evidence. The nature of methodology (rigorous or not) informed the likelihood of evidence.My understanding of evidence use is having concrete data that has been collected through a process that is considered legitimate and you give reference to that data. It could have been a survey. I mean it’s a fact that figures don’t lie. --- figures about distribution, retention, rural–urban disparity and all that stuff.” “If you are writing on a national document then you use data that is representative of the whole country.” .“In response to our questions on what evidence the respondents consider as robust, we documented eight characteristics of robust evidence as perceived by our respondents, namely quality/accuracy, credibility, relevance, accessibility, comprehensiveness, context specificity, of national scale, and representativeness of evidence. The following quotes substantiate these findings:The issue of comprehensiveness of evidence was emphasized only by the respondents in the IMNCH case study and evidence being of national scale and representativeness was emphasized in the development of the OH policy. The importance of all other characteristics of evidence was shared by respondents across the three policies.Well, the survey found many discrepancies in the ratio of health workforce in relation to all health sectors. It was terrible. When the data was presented we shuddered. When we saw from literature review what other countries are doing, we were challenged to do something” “The various types of evidence mentioned previously informed different stages of the policy development process in the three case studies Table . Survey Lancet series in IMNCH policy [In addition, journal publications from the H policy  and WHO H policy  were useWhat happened was there was a stakeholders meeting and we got a lot of information from them, sat down together to brain storm on the information and that was what was utilized in the final writing” “On the other hand, reports from expert consultations were perceived by the respondents as useful in the policy drafting stage because they now built on the information provided by the surveys to improve the body of evidence used. The expert consultations brought in a practical aspect to the policy development because most of the evidence generated from this source was based on hands-on experience of the stakeholders, which added value to the evidence obtained, as illustrated below:The situation analysis and survey reports were useful to different actors for different reasons: to the academics, these types of evidence gave a credible idea of the situation and provided guidance to the direction of their technical input; the government policymakers found them useful in providing information that was representative of the country and context appropriate; to the development partners, they provided useful information to guide decisions of resource allocation and technical input; and, finally, the CSO’s found these useful for providing evidence of current health situations in terms of figures and numbers that would enable more effective lobbying.We found that global considerations, existing policy guidelines, and burden of health needs were the major contextual influences which helped set the agenda for the three health policies. The utilization of evidence in each of these three policies was influenced by different factors from these three broad areas Table .Table 5The WHO directive and with Nigeria being a major stake holder in the WHO, I think that facilitated the approval for developing of Oral Health Policy in the country.” .“A general global push towards evidence-based practice was identified by the respondents as an important contextual influence which increased the use of evidence in all three policies. For example, the international push for the development of the OH policy was predominantly from WHO, which had directed its African region countries to all develop an OH policy as part of their regional OH strategy .“The WHOAll four previous attempts at formulating an OH policy in Nigeria in the past three decades were unsuccessful. The first three attempts (between 1984 and 1999) failed because of an unfavourable political environment during military rule, whereas a fourth attempt at developing an OH policy (2004–2009) failed due to non-observance of national stipulations for policy development .Multiple evidence types were used in the development of three health policies in Nigeria. Policymakers and other actors, though guided by their perceptions of robust evidence to make decisions on which evidence to use, were also perceived importance of experiences and expert opinions possibly giving room for a ‘non-scientific’ angle to policymaking. Eight characteristics of robust evidence were perceived to be important by policy actors in all policies. These qualities were attributed to nationally-generated evidence, such as reports of surveys, and other datasets generated through government machinery. Context was an important determinant of perceived characteristic of robust evidence. The fact that methodological rigor was mentioned by some policymakers as a characteristic of robust evidence suggests that these individuals have some understanding of what constitutes methodological rigor and this degree of understanding reflects their background.Different stakeholders seemed to adopt diverse definitions of what represents evidence – possibly influenced by their personal experiences in policy development. Although the respondents never identified this lack of a shared definition of evidence as an issue of concern, it is clear that an unresolved tension existed among our informants, as people kept referring to different concepts and attributes of what represents evidence for and about policy.who were the drivers of the three policies”, was that stakeholders’ experiences were a very important form of evidence which led to its use in the OH and HRH policy formulation.The actors’ understandings of evidence appear also to have influenced which evidence was used. The fact that most respondents defined evidence as a formal entity where legitimate and concrete data are collected and processed could be a reflection of why formal types of evidence  were used most frequently in setting the agenda. For example, in the OH and HRH case studies, the use of situation analysis reports, survey reports, and published research confirmed this potential relationship between perception of what constitutes evidence and its use. This is also true for IMNCH, where evidence of best practices from international publications constituted the main form of evidence used. In addition, it could be that the actors’ beliefs had been pre-shaped by the public policymaking structure in the country which seems to rely on documented evidence to be used to either make a point or influence a policy decision. This finding is similar to what Sutcliffe and Court reported , namely In literature, evidence-informed policy was defined as public policy informed by rigorously tested established evidence in the design, implementation and refinement of policy . Our stuSimilar types of evidence were generated to formulate the three policies. This suggests that the same type of evidence is generally accessible to those formulating policies in the country or there is limited knowledge about the various types of evidence that are available and possibly gathered for policymaking. There may therefore be a need to enlighten those involved in policymaking about what constitutes evidence so as to broaden the scope of types of evidence used for future policymaking.Evidence use for policy agenda setting appeared to be extensive and adequate in all three cases and the situation analysis and survey reports were useful to different actors for different reasons. Our study revealed that evidence was used as input to decision-making for technical experts, conceptualizing the situation for government policymakers, implementing partners and CSOs, and persuading actors to buy in for certain policies, all of which was achieved by CSO lobbying. This is similar to findings by Shadish et al. , who alsFormal evidence, such as research findings and data sets, were used in agenda setting, because of their context relevance, rigour and timeliness. The ease and availability of obtaining information from these sources of evidence also played a role in their use for policy/strategy making. According to Shaxson , some keFormal evidence, like research and survey and program reports, were used in policy development, while there was little or no mention of other types of formal evidence such as health management information system data. This could be attributed to their perceived unavailability. Thus, only evidence considered reliable or accessible and truly reflecting which evidence the policy actors felt was the best was used to establish the need for policy development.The informal type of evidence used, which was the expert consultation meetings, emphasized the fact that evidence was subject to what the actors considered important and relevant and also what they perceived evidence to be. The fact that some respondents – such as influential government policymakers – felt this form of evidence was very important, was synonymous with its use in the drafting and writing up of the policy, even though other stakeholders, like academics and CSO’s, felt less strongly about this form of evidence. However, this use of evidence is consistent with what was reported in previous studies , which oContextual factors influenced policy formulation and evidence use for the three case studies, albeit differently. For instance, the interests of international partners and agencies gave the initial push for prioritization of maternal and child health on the national agenda, and the subsequent development of the IMNCH strategy. Whereas the need to develop an OH policy was underscored by the absence of a strategic framework for OH services and previous failed attempts at policy formulation, rather than an international push. National surveys and empirical studies that clearly identified health problems, policy gaps and bottlenecks, and made recommendations of strategies or guidelines for implementation, provided useful guidance during the process of drafting policy contents. A central influence on evidence process across case studies in Nigeria was the recognition of the global movement on evidence-based best practices. Although somewhat different in its nature to international treaties such as the MDGs, this movement triggered a national awareness of the need to develop comprehensive, evidence-informed policies and plans of action. Though similar to what was found in India as part of the wider study, evidence use is being progressively recognized as a highly contingent process that varies across settings and time , 42. In The reliance on international evidence for providing new policy ideas, in this case, may be linked to the strategic role policy actors (e.g. WHO) played in identifying and disseminating evidence for informing the policy process. A wider range of influences were identified at the agenda-setting stage than during policy formulation and approval. This is similar to what other authors found . SimilarOur findings suggest that recognition of the value of formal and informal types of evidence, combined with structures for generating and using evidence, are likely to facilitate generation of evidence for policy development. Evidence that is easily accessible to policymakers and is in a user-friendly form, will most likely be used in policy development. Furthermore, involvement of technical experts (including researchers) who have an appreciation for evidence and its use in policymaking, also contributes to evidence-based policymaking.Several potential implications for policy and practice emerge from our study, which should be of relevance to the policy actors interested in improving the role of evidence in health policymaking in Nigeria and other similar contexts. First, different policy actors need to be aware of the understanding of the concept of evidence by others, including their preferences for robust evidence. In the longer term, different policy actors can work towards developing a shared understanding of robust evidence. Secondly, the knowledge of different types of evidence and their importance would enhance the use of both formal and informal types of evidence which should improve the quality of evidence generated for policy. Thirdly, a decentralized consultative approach using a variety of mechanisms to obtain wider participation and input from a range of stakeholders at all levels, including national and sub-national, government and non-government, as well as the public groups. These mechanisms include consultations with multi-stakeholder groups and expert working group meetings.A possible limitation of the study is that we relied mostly on the understanding of the role of evidence as perceived by the policy actors as this creates the potential for recall bias. Whilst we attempted to look for signs of evidence use in policy documents (e.g. references to specific studies), the systematic comparison of available versus the used evidence was outside the scope of this study.Different types of evidence were used to formulate policy in the three case studies. Most evidence generated was used to set the agenda and policy discourse. Apart from the IMNCH strategy where evidence was used to select interventions, we did not find any indication that suggest evidence was used to determine policy options (‘evidence on policy’) for the OH and HRH policies.Relevance, comprehensiveness, availability, context-appropriateness, affordability, methodological rigor, timeliness, and representation of country situation were characteristics of robust evidence as perceived by policymakers. Although it is unlikely that these characteristics of robust evidence would be met at the same time, research organizations and academics in the country are challenged with the need to generate evidence that meet these criteria. Policymakers and influencers, on the other hand, need to exercise some judgment about priorities and preferences in the selection of available evidence for policymaking.Study instruments and data are available on request from the corresponding author.


Here, we report on hybrid density functional theory (h-DFT) calculations of P in the SiNC/SiO2 system matching our experimental findings. Relevant P configurations within SiNCs, at SiNC surfaces, within the sub-oxide interface shell and in the SiO2 matrix were evaluated. Atom probe tomography (APT) and its statistical evaluation provide detailed spatial P distributions. For the first time, we obtain ionisation states of P atoms in the SiNC/SiO2 system at room temperature using X-ray absorption near edge structure (XANES) spectroscopy, eliminating structural artefacts due to sputtering as occurring in XPS. K energies of P in SiO2 and SiNC/SiO2 superlattices (SLs) were calibrated with non-degenerate P-doped Si wafers. 2. Increased sample conductivity and photoluminescence (PL) quenching previously assigned to ionized P donors originate from deep defect levels due to P.Up to now, no consensus exists about the electronic nature of phosphorus (P) as donor for SiO P is of particular interest due to high solubility and diffusivity in Si2 material system is crucial. It clarifies whether conventional SiNC doping is able to further advance miniaturization of Si-based electronic structures and electronic SiNC manipulation.About 60 years ago, impurity doping of bulk Si was established to introduce majority charge carriers, creating p/n junctions as fundamental building blocks of Si-based electronic devices. The discovery of size-controlled solid-state growth of SiNCs from Si-rich SiO2 samples like quantum dot solar cells2 barriers are dominated by defect-assisted conduction−3)34567xPy) with different properties as compared to Si, SiOx and SiO2. We note that Pearson and Bardeen−3). With P concentrations in the 0.5 to 8 atom-% range, clustering with dopant inactivation, defect formation and massive out-diffusion occur already in bulk type Si layers for structure sizes of 2, in SiOx surrounding SiNCs and P gettered by dangling bonds (DBs) at NC interfaces, all being critical for the electronic structure. So far, unpaired electrons bound to P were investigated by electron paramagnetic resonance (EPR) at very low temperatures9T = 300 K). XANES is not restricted to low temperatures and yields information on the electronic state of all P at T = 300 K. Excited P K shell electrons in XANES have tremendously increased mean free paths as compared to X-ray photoelectron spectroscopy (XPS) due to their high kinetic energy Many works have claimed doping of SiNCs with P donors3456790.9 as sub-oxide shell around SiNCs and in SiO2, delivering insights into the specific electronic structure due to P. The spatial distribution of P atoms in SiNC/SiO2 systems is derived from APT data and their statistical processing to yield the P distribution profile from the SiO2 matrix to the interior of the SiNCs. We discuss P data from h-DFT and XANES together with P spatial statistics from APT and obtain a detailed picture of the electronic behaviour of prospective P donors depending on their positions and bond geometries in SiNC/SiO2 systems. The 1s core level energies from h-DFT are used to assign XANES signals to respective P configurations in h-DFT approximants.We report on h-DFT calculations of P at central lattice and interstitial sites in completely OH-terminated SiNCs, of saturated P at the surface of such NCs, in SiO2 reference , of a SiO0.9 reference and of P-doped SiO0.9 (SiO0.9:P). 3), an OH group on such corner Si atom (OH-SiNC-P(OH)4) and a H atom at the OH group substituted by P(OH)4 (OH-SiNC-O-P(OH)4). μeV/Å (11.3 μHa/Å) which is ca. 1.3% of the convergence threshold of maximum residual forces, see to Methods section at end of article. The atomic displacement associated with this minute residual force was 0.0032 Å (0.32 pm) which is ca. 94% of the convergence threshold of residual displacements of 0.003403 pm – a rather large value for such residual force. This variance is an indication of a somewhat flat energy landscape. Thereby, it is rather difficult to calculate an exact diffusion path of interstitial P. This may explain why dopant atoms on Si lattice sites were considered in ab-initio thermodynamic diffusion simulations2223242 HOMO-LUMO gap is 7.83 eV which is 89% of the experimental value of ca. 8.8 eV2 and SiO. P is surrounded by SiO2 at least to its 2 → SiO2 and 1493 kJ/mol (7.74 eV/P atom) for the reaction 5) should not be favoured over tetravalent Si (Si(–O–)4), leaving P with a DB in analogy to P donors in bulk Si. The DB of P is strongly associated with 2:P is 0.01 eV above the LUMO of the OH-SiNC approximant while the 2:P is 0.41 eV below the HOMO of the OH-SiNC approximant. The barrier height for electron (hole) transport is given by the conduction  band offset between Si and SiO2 of 3.2 eV (4.5 eV)2 reduces the transport barrier for electrons (holes) by 97% (85%), causing an extreme increase in electron conductivity and a considerably increased hole conductivity. These defect levels are an important electronic aspect of P in SiO2: It causes a massive increase in SiO2 conductivity while not working as a donor. Several works build their evidence of SiNC doping on conductivities increasing with P concentrations of 0.5 to 8 atom-%34672:P approximant we get an atomic ratio of P/The SiOns  and  . We comp0.9 and SiO0.9:P are based on 2:P, we have a DB on P occupied with one electron in the SiO0.9:P approximant at a central Si lattice site, again resulting in two different spin orientations per MO  barriers are decreased down to 32% (removed completely). For SiO0.9 and SiO0.9:P approximants, a helical arrangement of Si atoms along the E − Evac = 0.2 to -8.5 eV. The inner bonds of these Si backbones can resist electron transfer to O to some extent, diminishing the splitting of their bonding and anti-bonding MOs. Experiments yield 0.9 reference and SiO0.9:P approximants as well as their high space group symmetry which allows for mentioned Si helices. Local Si segregation suggests that SiO is not uniform2:P approximant, yielding 0.56 atom-% for SiO0.9:P.The LUMO of SiO  vector  dominateTetravalent P atoms substantially gain binding energy when gettering their DBs at NC interfaces and maximize binding energies of Si atoms providing DBs. It is thus energetically unfavourable for P at the NC interface to have a DB. This finding is supported by a maximum P density at SiNC interfaces derived from APT below.231We show the DOS of the OH-SiNC reference approximant along with the DOS of all three approximants containing bond-saturated P at the interface . Fully gEion=0.51 eV is too big to ionize SiNCs with a reasonable probability at T = 300 K; 2 species. Both cases of P in OH-SiNC introduce recombination levels into SiNCs.We consider P on a central Si lattice site OH-SiNC-P[Si] and on a central interstitial site OH-SiNC-P[is]. P on a Si lattice site generates a HOMO 0.51 eV below the LUMO energy . While tthe SiNC . Both st2 where SiNCs are enclosed by iso-surfaces with atomic concentrations of Si 2, we derive the molar SiO2 partition 2 and 2 matrix. This relatively low P concentration in SiNCs can be explained by self-purification2223242 and by the high relative SiO2 volume of 85% in our samples. Zooming into the APT scan shows P atoms within SiNCs  for calibration. We assign XANES results to P environments using 1s core levels calculated by h-DFT with all-electron MO-BSs. P 1s core level energies from h-DFT correspond to 97.864% of P K XANES energies, see 2O5 (P+5) and P2O3 (P+3) approximants calculated with the same h-DFT route . This value refers to the XANES peak at 2144.8 eV of the P doped Si wafer reference (Si:P), see 2 samples  show peaks at 2143.7 eV. The 1.1 eV shift to lower binding energies shows that P in SiNC/SiO2 is much less positively ionized, corresponding to P−1. This result is corroborated by the Mulliken charges of P obtained from h-DFT and the analytical value of P in bulk Si . The P charge is  bulk Si . A hint 2 system to monitor the electronic nature of P. On a lattice site within OH-terminated SiNCs, P introduces a deep donor level with Eion = 0.51 eV; ionisation for small SiNCs is virtually nil, but is likely to increase for SiNCs with diminishing quantum confinement. However, formation energies of P on Si lattice sites22239ion >2 eV), but forms two deep defect levels with a recombination transition at 1.72 eV. At SiNC interfaces, fully saturated P have no impact on frontier molecular orbitals, leaving HOMO and LUMO energies virtually unchanged. In SiO shells around SiNCs, P is again unable to donate an electron, but induces a deep defect level which triggers massive recombination. This defect causes PL quenching – as opposed to Auger recombination – and increases SiO shell conductivities which were both interpreted as evidence for successful SiNC doping in the literature32 are deep defects which cannot donate electrons, they tremendously improve inter-NC conductivities in particular for electrons by diminishing electron (hole) barriers by 97% (85%) of the conduction  band offset between bulk phases of Si and SiO2. Massively increased conductivities were assumed to prove successful SiNC doping62 and SiNC/SiO2 samples were measured by XANES at room temperature. In contrast to bulk Si, P atoms in SiNC/SiO2 samples could not donate electrons into 2 to 5 nm size NCs in SLs or in annealed bulk SiOx films with reasonable probabilities, confirming our h-DFT results. We conclude that conventional doping of SiNCs with P does not provide majority charge carriers to SiNCs embedded in SiO2. Alternative approaches for majority carrier introduction into embedded SiNCs and ultrasmall Si nanovolumes such as embedding material effectsWe carried out DFT calculations for the SiNC/SiOs by 97% 5% of the2 were fabricated by deposition of P-doped Si-rich oxide (SiO0.93)/ intrinsic SiO2 SLs by plasma enhanced chemical vapor deposition and subsequent annealing . During deposition, P was incorporated by adding 1% PH3 to Ar, resulting P concentrations were ca. 1 atom-% as found by secondary ion mass spectroscopy (SIMS)292 layers to prevent P diffusion into Si substrates during anneal. For APT, P doped SLs with 30 bilayers and 5 nm nominal NC size were fabricated. Samples with 50 bilayers and nominal NC sizes from 2 to 5 nm in steps of 1 nm were chosen for XANES. In addition, 300 nm thick P-doped SiO2 and SiO0.93 samples were fabricated as references.Size-controlled SiNCs in SiOApproximants were calculated with non-periodic boundary conditions and underwent geometrical optimization with the B3LYP h-DF40424345Alternative approaches to the B3LYP h-DF with similar accuracy are the Heyd-Scuseria-Ernzerhof h-DF (HSE06)492 system by APT using a Cameca LEAP 4000X HR instrument with a reflectron-type time-of-flight mass spectrometer and a pulsed UV laser . During the analyses . Monochromatic X-rays were obtained using a Si(111) double crystal monochromator with an energy resolution of about 0.2 eV at 2150 eV with fixed exit. Scans were carried out using a shallow incident angle to maximize the SL or thin layer volume of samples for excitation. Absorption was measured by monitoring the P KHow to cite this article: König, D. et al. Location and Electronic Nature of Phosphorus in the Si Nanocrystal – SiO2 System. Sci. Rep.5, 9702; doi: 10.1038/srep09702 (2015).


Friedreich ataxia (FRDA), a multisystem autosomal recessive condition, is the most common inherited ataxia in Caucasians, affecting approximately 1 in 29,000 individuals. The hallmark clinical features of FRDA include progressive afferent and cerebellar ataxia, dysarthria, impaired vibration sense and proprioception, absent tendon reflexes in lower limbs, pyramidal weakness, scoliosis, foot deformity and cardiomyopathy. Despite significant progress in the search for disease modifying agents, the chronic progressive nature of FRDA continues to have a profound impact on the health and well-being of people with FRDA. At present there is no proven treatment that can slow the progression or eventual outcome of this life-shortening condition. Thirty-nine expert clinicians located in Europe, Australia, Canada and USA critically appraised the published evidence related to FRDA clinical care and provided this evidence in a concise manner. Where no published data specific to FRDA existed, recommendations were based on data related to similar conditions and/or expert consensus. There were 146 recommendations developed to ensure best practice in the delivery of health services to people with FRDA. Sixty-two percent of recommendations are based on expert opinion or good practice indicating the paucity of high-level quality clinical studies in this area. Whilst the development of these guidelines provides a critical first step in the provision of appropriate clinical care for people with FRDA, it also highlights the urgency of undertaking high-quality clinical studies that will ensure the delivery of optimum clinical management and intervention for people with FRDA. FXN [FXN whilst in the other 4% there is compound heterozygosity for an intron 1 GAA repeat expansion in one allele and a point mutation or deletion in the other [Friedreich ataxia (FRDA), the most common of the hereditary ataxias, is an autosomal recessive, multisystem disorder affecting approximately 1 in 29,000 individuals and has a carrier frequency of 1 in 85 in individuals of Caucasian background -5. Pathohe other . The GAAhe other ,12. Sinche other ,13-15. Ahe other ,16. HoweRevalidatie Geneeskundige Richtlijn Ataxie van Friedreich” was written by a special task force under the auspices of ‘Vereniging Spierziekten Nederland’. These were the first guidelines that provided an evidence base to the clinical management of people with FRDA. These guidelines were subsequently updated and adapted for international use in September 2007 (http://www.vsn.nl/hulpverleners/protocol_detail.php?protocol_id=17). In 2009, Ataxia UK launched “Management of ataxia: towards best clinical practice”, developed to provide recommendations for the management of people with inherited ataxia, including FRDA (http://www.ataxia.org.uk/pages/resources-and-publications.html). Whilst this further initiative was welcomed, it was apparent that issues specific to FRDA required disease specific guidelines. Furthermore, it was apparent that the multiple gaps in evidence surrounding service delivery may provide a platform for ongoing research.In 2003, “An executive committee  was convened to oversee the process of guideline development. Clinicians with expertise in FRDA were recruited to contribute to the guidelines through invitations from the executive. Thirty-nine individuals participated in the writing of these guidelines. This group advanced the topics and corresponding clinical questions which would be the foundation of the guidelines. Specialist working groups (SWGs) related to specific topics were established. There were two face-to-face meetings during the guideline development phase that were attended by some of the 39 authors, otherwise communication was facilitated by teleconference and email. Each member of the SWGs was asked to formally declare any potential conflict of interest however none were present that required removal of any individual from the writing groups.An initial topic list was developed by MBD and LAC. This list was refined by discussion with the executive and the SWGs (see Table http://www.g-i-n.net/) for diagnostic and intervention studies.A literature review was conducted for each topic. Clinical databases included in the search were PubMed, MEDLINE, CINAHL, Best Practice, Cochrane Database of Systematic Reviews, EMBASE and Scopus. Guideline SWGs evaluated the available evidence according to the templates developed by the Guidelines International Network  (USA), Scottish Intercollegiate Guidelines Network (SIGN), National Institute of Health and Clinical Excellence (NICE) (UK) and the National Health and Medical Research Council (NHMRC) Australia. Given no one method was identified as clearly superior, the evidence and subsequent recommendations were graded according to the criteria developed by the NHMRC   pregnancy issues; 8) quality of life issues. There were three recommendations graded as A, six graded as B, 28 graded as C, 17 graded as D and 92 GPP. The full guidelines are available on the internet (http://www.curefa.org/physicians.html). The following provides a summation of the recommendations from each topic (Table The guidelines comprise 9 sections and 25 subsections (see Table ic Table .Table 4The molecular basis of Friedreich ataxia was established in 1996 . The timThe principle purpose of clinical management guidelines is to provide “systematically developed statements to assist the practitioner and the patient to make decisions about appropriate health care for specific clinical circumstances” . In addi


Common approaches taken for policy formulation in the face of resource constraints are to adopt utilitarian frameworks that seek maximisation of societal health benefits. However this does not always seem to generate socially and politically palatable solutions.In 2012-13 the Welsh Health Specialised Services Committee (WHSSC) developed a prioritization process for specialised health services to directly incorporates the Rule of Rescue and other psychological, emotional and social responses.A Prioritisation Panel representing a wide range of stakeholders was convened. A master list of services was achieved through matching against criteria  for evidence and prioritisation. Condition-Treatment pairs were created for the services falling under the remit of WHSSC, evidence reviews undertaken and evidence of effectiveness and cost effectiveness were collated to inform the decision making process. Discreet choice methods were used to rank order and apply a cut off point for commissioning or not. Score cards were developed to score for scientific rigour, inclusiveness, transparency, independence, challenge, review, support for implementation and timeliness. These features relate to the procedural justice requirement for ‘accountability for reasonableness’ described in the published literature.The common finding for the condition treatment pairs was lack of evidence to guide confident decision making. Through the process, the Panel was required to make judgements: scientific value judgements about interpreting the quality and significance of the evidence available and social value judgements. These latter were guided by four principles: respect for autonomy, non-maleficence, beneficence and distributive justice. A prioritisation and commissioning list was created and specific services identified for commissioning and decommissioning.The desire for rapid evidence assessment and policy development conflicted with the need for policy to be based on robust evidence and subject to appropriate consultation. One outcome of this programme was identification of the need to make appropriate arrangements for policy to be developed at the time it is needed without compromising its quality. Given the specialist nature of services being reviewed issues were encountered in enabling patient understanding of evidence. The policy implementation phase was also challenging. Reflecting on the experience of the process and outcomes has led to revisions for the 2014 Prioritisation Panel activities.


Evidence-informed health policymaking is a goal of equitable and effective health systems but occurs infrequently in reality. Past research points to the facilitating role of interpersonal relationships between policy-makers and researchers, imploring the adoption of a social network lens. This study aims to identify network-level factors associated with the exchange and use of research evidence in policymaking.Data on social networks and research use were collected from seventy policy actors across three health policy cases in Burkina Faso . Networks were graphed for actors’ interactions, their provision of, and request for research evidence. Exponential random graph models estimated the probability of evidence provision and request between actors, controlling for network- and individual-level covariates. Logistic regression models estimated actors’ use of research evidence to inform policy.θ = 6.16, p < 0.05; θ = 2.87, p < 0.05; θ = 2.31, p < 0.05). The child health network displayed clustering tendencies, meaning that actors were more likely to form ties if they shared an acquaintance . Actors’ use of research evidence was positively associated with their centrality .Network structure explained more than half of the evidence exchanges (ties) observed in these networks. Across all cases, a pair of actors was more likely to form a provision tie if they already had a request tie between them and visa versa (The exchange and use of research evidence in policymaking can be partly explained by the structure of actors’ networks of relationships. Efforts to support knowledge translation and evidence-informed policymaking should consider network factors.The online version of this article (doi:10.1186/s13012-014-0126-8) contains supplementary material, which is available to authorized users. The use of research evidence to inform health policy decision-making has been identified as a means to improve the effectiveness of health policy decisions -3, to stThe literature on evidence exchange and use in health policymaking ,8-11 conThis study applies an explicit social network approach in order to answer two research questions related to evidence exchange and use in health policymaking: first, what factors are associated with the formation of research exchange relationships between policy actors; and second, to what extent are these exchange relationships associated with the use of research evidence by policy actors in the policymaking process? These results will have important implications for the design of interventions for knowledge translation and evidence-informed health policymaking.Social network analysis (SNA) is a theory as well as a set of tools for exploring socially-influenced behaviours. Social network theory offers a persuasive explanation of why evidence exchange and use should be understood from an interpersonal, as well as structural, perspective. As seen through a social network lens, behaviours—in this case, evidence exchange and use—are predicted not only by an individual’s attributes, but by his or her position in her social environment, and the larger structure of that environment. Social network analysis has recently been applied to evidence exchange in a municipal public health department  and to iWhile social network analysis can be applied to research questions at actor, tie, or network levels, this study specifically exploits recent methodological innovations in statistical network analysis enabling the prediction of ties between pairs of actors as some function of their individual attributes and network structure. These models are referred to as the exponential random graph class of models (ERGM) ,31. The Ties can form, in theory, between any two individuals. But in practice, network scientists observe more frequent tie formation in the presence of certain network structures. The next section presents common network hypotheses adjusted to the context of Burkina Faso . Instead of measuring the existence of two ties for the same relation between a pair of actors, layering measures the co-existence of two different relations between the same pair of actors . For exaIn addition to these structural effects, we assume that the individual attributes of actors will influence their propensity to provide or request research evidence. There have been few studies exploring which individual characteristics influence evidence exchange, other than to say that evidence is more likely to be exchanged by a researcher or someone with research experience . We hypohomophily specifies that actors are more likely to form ties with ‘like’ individuals [Finally, the phenomenon of ividuals . HomophiSocial network and demographic data were collected between October 2011 and March 2012 from policy actors active in one or more of three health policy issues in Burkina Faso: community integrated management of childhood illness; home management of malaria; and removal of user fees for antiretroviral treatment for human immunodeficiency virus (HIV); henceforth referred to by their substantive categories: child health; malaria; and HIV. Policy cases were sampled according to pragmatic reasons, including large enough networks to enable statistical analysis, as well as for their diversity on network structural variables of interest. High quality and locally relevant research evidence was available to inform each of these policy cases and each decision involved some amount of uncertainty that could have been addressed using research evidence, typical of many health policy decisions made by ministries of health in Sub-Saharan Africa. That said, Burkina Faso faces many of the same challenges in using evidence to inform policy as other countries and some challenges that are context-specific; namely, slow internet connection limiting searches for evidence, and a working language (French) that offers fewer research publications. Commonalities include the fact that evidence must compete with many other inputs in the policymaking process—including institution-, interest-, and idea-related factors, and that the overall number of researchers, and thus research capacity, tends to be fewer in low-income countries. A recent rise in donor applications requiring evidence of the problem and options has perhaps introduced incentives to exchange and use research evidence.Burkina Faso is like other Sub-Saharan African countries in terms of level of development, political regime type, and dependence on foreign aid, as well as a health policy sector characterized by participation of diverse actors and frequent changes in institutions. These characteristics will improve the generalizability of results, contributing to knowledge translation efforts, and evidence-informed policymaking, in other Sub-Saharan African countries.We defined policy actors as any individual who participated in policy formulation for each policy issue. Actors were identified according to established procedures for respondent-driven censuses of social networks . Beginnii.e., layering), but were considered separate constructs, and as such could also exist in the absence of the other.Upon listing their interaction relationships, respondents were then asked to specify whether they had provided research evidence to any of the names they listed (provision ties), or requested research evidence from any of the names they listed (request ties). Ties were coded as 1 if at least one of the actor-pair reported that a tie existed. Provision and request ties were coded as directed from one actor to another based on each respondents’ reports of their exchanges and could occur in both directions. Provision and request ties could occur simultaneously  as the active sending of ties suggests positive attitudes related to evidence.Data were collected on actors’ relevant individual attributes )ij is the change in the vector of network statistics g(y) when the value of Yij changes from 0 to 1. As in other regression models, we can include covariates to control for other processes that might affect the existence of a tie. ERGMs are different from normal logistic models in that they can control for network structure, or structural effects (SE), as well as actor characteristics, or attribute effects (AE). Structural effects models (SE models) included parameters for triangle closure, reciprocity and layering. Triangle closure was modeled using the geometrically weighted edgewise shared partner distribution (GWESP) statistic, which has been shown to overcome model degeneracy by specifying decreasing marginal impact of the formation of triangles on tie formation. [where Yij is an actor pair in network Y, θ is the vector of coefficients, Δ. Covariates were retained in the final model if they improved model fit as tested by Akaike Information Criterion (AIC) and likelihood ratio tests. ERGM coefficients represent the conditional log-odds of a tie. Data were managed using Microsoft Excel and analyzed in R using the Statnet suite of packages [Provision and request ties, the dependent variables, were modeled separately for each of the three policy networks, conditional on the existence of an interaction tie. Covariates were each modeled separately to determine which were most significant according to p-values and significant covariates were then entered into the full model step-wise based on their packages , includipackages . The ERGpackages .Goodness of fit was tested by comparing simulated networks to the observed networks to determine how well the model could reproduce global network properties , an effect that was statistically significant across issues. Only the child health network demonstrated a tendency for triangle closure  where the odds of a provision tie were 10 times greater if that tie closed a triangle between three actors, conditional on the rest of the model. This suggests that evidence provision may have been used strategically to reinforce a cohesive paradigm. In the malaria network, the odds of a provision tie were 2.77 times more likely  if actors had research experience and were half as likely  if they worked for a CSO/NGO compared to working for the government. As hypothesized, there was no evidence of reciprocity in any of the issues, suggesting that evidence was provided and requested in a hierarchical manner.Models for child health and malaria networks fit best when they combined structural and attribute effects , meaning that the odds of tie formation were 4.62 times greater if the tie closed a triangle between three actors, conditional on the remainder of the model. Although this coefficient is not as large as in the provision network, request ties still seemed to occur to either strengthen or reinforce cohesion and shared norms in this case. As in the provision models, malaria actors were more likely to have request ties if they had research experience , suggesting that this policy issue, in particular, had narrowly defined roles for who exchanged evidence. The malaria network demonstrated a significant negative effect of homophily within organizations , meaning that actors were more likely to request research evidence outside of their organizations as compared to within, which runs counter to our hypotheses but presents a picture of interorganizational exchange of evidence for this case. The odds of forming a request tie were 3.36 times higher  if an actor belonged to the ‘other’ organization category in the HIV network, a category which includes consultants and researchers. This is to be expected in a network that had high representation of CSO/NGO actors, who typically perceived a smaller role for research evidence as compared with lived experiences.Request ties were best fit in models combining structural and attribute effects , consistent with social network theories of the significant role of networks and structure in predicting individual-level behaviours. Some individual attributes mattered, particularly the role of research experience in the malaria domain, but should not be solely relied upon to design or target knowledge translation interventions. In terms of evidence use, network position—as judged by connectedness to others—predicted use better than any individual characteristic—not job level, not organizational affiliation, not experience as a researcher. This finding is consistent with other findings that show interpersonal relationships with researchers to be the best predictor of evidence use by policy-makers [This study illuminated the conditions under which evidence was provided and requested in three policy cases, and confirmed that evidence exchange is closely correlated to its use in health policymaking. Evidence provision and request ties were best predicted by structural factors, particularly layering  will require knowledge of specific issues and context.Linked studies exploring the contextual factors surrounding evidence use in these cases add clarity to the motivations for evidence exchange and use; for example that dense exchange networks for child health were associated with symbolic use, that there was little motivation for evidence use in the malaria case, and that evidence was used instrumentally to change policy in the HIV case. Future examples of policy networks will enable the refinement of theories related to network-based markers of evidence use and exchange. Finally, this study is limited, as are most social network analyses, by challenges in collecting complete data on whole networks. Missing data may affect our results.In considering how to design network-based interventions for various settings, we suggest the aphorism: ‘know your network.’ Any knowledge translation intervention should begin with a baseline mapping of relevant policy network(s). While well-designed sociometric surveys remain the gold standard for network mapping, we acknowledge that sampling or ego-based approaches may still add-value above and beyond the status quo. Many local stakeholders have excellent intuition about their networks that can be harnessed to this end.Deliberative dialogues could use this information to ensure that dialogue attendees are in strategic network positions—not just in strategic organizational positions. Dissemination of research evidence should include a message to share the evidence with a colleague or friend, and an encouragement to also request evidence from those same people. Ultimately, cultural shifts are needed to increase the perception that anyone can provide (or request) evidence; these shifts have occurred in other settings by building capacity and shifting incentives .This study explores the exchange and use of research evidence among policy actors in Burkina Faso. It is among the first of its kind of describe structural and attribute-related factors associated with exchange relationships among policy actors. Study findings suggest that while research exchange networks and their outcomes are highly issue-dependent, networks have a significant influence on knowledge exchange and use. Network variables—including the propensity to send complementary ties, to join sets of three actors, and overall connectedness—were more important than individual characteristics in predicting whether research evidence was provided or requested between actors, and were certainly more important in predicting an actors’ use of evidence. These findings can be leveraged to design knowledge transfer interventions which focus on facilitating or reinforcing exchange relationships.


Cost-effectiveness analyses (CEAs) that use patient-specific data from a randomized controlled trial (RCT) are popular, yet such CEAs are criticized because they neglect to incorporate evidence external to the trial. A popular method for quantifying uncertainty in a RCT-based CEA is the bootstrap. The objective of the present study was to further expand the bootstrap method of RCT-based CEA for the incorporation of external evidence.We utilize the Bayesian interpretation of the bootstrap and derive the distribution for the cost and effectiveness outcomes after observing the current RCT data and the external evidence. We propose simple modifications of the bootstrap for sampling from such posterior distributions.In a proof-of-concept case study, we use data from a clinical trial and incorporate external evidence on the effect size of treatments to illustrate the method in action. Compared to the parametric models of evidence synthesis, the proposed approach requires fewer distributional assumptions, does not require explicit modeling of the relation between external evidence and outcomes of interest, and is generally easier to implement. A drawback of this approach is potential computational inefficiency compared to the parametric Bayesian methods.The bootstrap method of RCT-based CEA can be extended to incorporate external evidence, while preserving its appealing features such as no requirement for parametric modeling of cost and effectiveness outcomes. Randomized controlled trials (RCTs), especially ‘pragmatic’ RCTs that measure the effectiveness of interventions in realistic settings, are an attractive opportunity to provide information on cost-effectiveness. In the C) between two competing treatments over the difference in their health outcome (effectiveness) (∆E). With patient-specific cost and health outcomes at hand, estimating the population value of the ICER from an observed sample becomes a classical statistical inference problem. However, given the awkward statistical properties of cost data and some health outcomes such as quality-adjusted life years (QALYs), and issues around parametric inference on ratio statistics, many investigators choose resampling methods for quantifying the sampling variation around costs, health outcomes, and the ICER. If u > P* , then ignore the bootstrap sample and jump to step a.d. Randomly draw θ* and jump to 1.2 Store the value of M random draws from the posterior distribution of θ having observed the RCT data and the external evidence. All the subsequent steps of the CEA, such as calculating the average cost and effectiveness outcomes, interval estimations, and drawing the cost-effectiveness plane and the CEAC, remain unchanged. Of note, this algorithm requires that P* be valid probabilities bounded between 0 and 1. As such, the external likelihood should be scaled .P(θ|D) is most often continuous , the external likelihood P(De|θ), should also be continuous, otherwise the chance of samples from P(θ|D) hitting non-zero areas of P(De|θ) will be infinitely small. Next, θe should be identifiable (unique) within each D*. This assumption holds for the most typical form of external evidence such as rates or measures of relative risk. If u >P, then ignore the bootstrapped sample and jump to step a.e. Randomly draw D*.f. . Calculate mean costs, exacerbations, and QALYs for each arm from 2 Store the average values for costs, exacerbation rates, and QALYs; then jump to 1.The simulation was stopped after 10,000 accepted bootstraps for the rejection sampling method incorporating the external evidence were generated. To obtain the results using the importance sampling method, we used the same set of bootstraps generated in the above algorithm, including all the accepted and rejected bootstraps.λ) for one unit of the health outcome[In addition to the ICER, we also reported the expected values of the cost and health outcomes for each trial arm, and also plotted the CEAC, without and with the incorporation of the external evidence. The CEAC between two treatments is the probability that a treatment is cost-effective compared to another at a given value of the decision-maker’s willingness-to-pay , and shifted the outcomes of the T1 arm in the opposite direction. This is an expected finding given the strong evidence in favor of T3 for the effect size of T3 versus T1 from the external source.The impact of incorporating external evidence is more evident on the ICER. The ICER of T3 versus T1 decreased by 52% after the incorporation of external evidence. Again, this is reflective of the fact that external evidence is more in favor of T3 than the likelihood (RCT data) is.Figure P  is performed via P(θ|D), and the latter can easily be sampled through (Bayesian) bootstrapping.Contemporarily, when an economic evaluation is conducted alongside a single RCT, the practice of evidence synthesis is not an integral part of the analysis. In our opinion, this is partly because parametric Bayesian modeling, the hitherto only available method, results in problem-specific and complex statistical models. In this work we propose simple and intuitive algorithms for the incorporation of external evidence in RCT-based CEAs that use bootstrapping to draw inference. Rejection and importance samplings which form the basis of the proposed method are popular paradigms in which sampling from a ‘difficult’ distribution is replaced by sampling from a proposal  distribution. Here, sIn synthesizing evidence for RCT-based CEAs, a carefully crafted parametric model with comprehensive analysis of model convergence and sensitivity of results to parametric assumptions has indisputable strengths over resampling approaches, including the higher computational efficiency of MCMC or likelihood-based methods and the ability to synthesize and propagate all evidence in a single analytical framework,42. NeveOur paper provides a conceptual framework and further research into theory, as well as practical issues in using this method, should follow. The apparent simplicity of the bootstrap may conceal the assumptions being made, especially with small datasets,43. FurtFurther research is needed to improve sampling efficiency and to incorporate external evidence in other paradigms such as cluster or crossover RCTs. Importantly, the theoretical construct of the proposed method does not necessarily restrict it to RCT-based CEAs. A similar concept can be used to reconcile evaluations based on observational data with external evidence. This will inevitably invoke questions about the applicability of different metrics of the effect size in non-randomized studies , and the validity of the bootstrap as the sampling method . In addition, further empirical research is required to evaluate the real-world applicability and feasibility of the method and to demonstrate its comparative performance against conventional methods of evidence synthesis .This paper deliberately stays away from the debate on whether to incorporate external evidence for a given situation an d focuses on the ‘how to’ question. The ‘whether to’ question is context-specific and great care is required for the sensible use of external evidence in each setting. For the case study, for example, the substantial discrepancy in the results between the external and current RCTs (with regard to the efficacy of triple therapy versus monotherapy) should more than anything generate misgivings about the suitability of borrowing evidence from that external source. However, the case study was undertaken as a step in the direction of proof of concept, applicability, and face validity of the proposed methods. This is not a withdrawal from the deep considerations required for sensible evidence synthesis.Faced with the escalating costs of RCTs and the requirement by many decision-making bodies for formal economic evaluation of emerging health technologies, trialists and health economists are hard-pressed to generate as much relevant information for policymakers as possible. As such, and despite criticisms, it appears that RCT-based CEAs are here to stay. The incorporation of external evidence helps optimize adoption decisions. Aside from their theoretical contribution, if their real-world applicability is proven the proposed methods can provide the large camp of analysts using bootstrap for RCT-based CEAs with a statistically sound, easily implementable tool for such purpose.CEA: Cost-effectiveness analysis; CEAC: Cost-effectiveness acceptability curve; COPD: Chronic obstructive pulmonary disease; ICER: Incremental cost-effectiveness ratio; MCMC: Markov chain Monte Carlo; OR: Odds ratio; RCT: Randomized controlled trial; RR: Rate ratio; QALY: Quality-adjusted life year.The authors declare that they have no competing interests.This work was part of MS’ PhD research. MS developed the research question and the methodology. MS and SB designed the case study. CM and SA helped with the acquisition of the data and provided content advice for the case study. MS performed the computer simulations. MS and SB developed the first draft of the manuscript. All authors critically revised the manuscript and approved the final version.File name: R code.r. Description: This is the R code used for the case study.Click here for file


Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder with overlapping morphological features of myelodysplastic and myeloproliferative disease and a potential risk of transformation to acute myeloid leukemia. Presence of Auer rods in CMML is a rare finding and the presence of an occasional Auer rod gives the diagnosis of CMML-2 in spite of the presence of <5% blasts in peripheral blood/bone marrow ,2. A 39-Conflict of Interest StatementThe author of this paper has no conflict of interest, including specific financial interests, relationships, and/or affiliations relevant to the subject matter or materials included in this manuscript.


Better understanding of clinical reasoning could reduce diagnostic error linked to 8% of adverse medical events and 30% of malpractice cases. To a greater extent than the evidence-based movement, the clinical reasoning literature asserts the importance of practitioner intuition—unconscious elements of diagnostic reasoning. The study aimed to analyse the content of case report summaries in ways that explored the importance of an evidence concept, not only in relation to research literature but also intuition.The study sample comprised all 789,712 abstracts in English for case reports contained in the database PUBMED for the period 1 January 1983 to 31 December 2012. It was hypothesised that, if evidence and intuition concepts were viewed by these clinical authors as essential to understanding their case reports, they would be more likely to be found in the abstracts. Computational linguistics software was used in 1) concept mapping of 21,631,481 instances of 201 concepts, and 2) specific concept analyses examining 200 paired co-occurrences for ‘evidence’ and research ‘literature’ concepts.‘Evidence’ is a fundamentally patient-centred, intuitive concept linked to less common concepts about underlying processes, suspected disease mechanisms and diagnostic hunches. In contrast, the use of research literature in clinical reasoning is linked to more common reasoning concepts about specific knowledge and descriptions or presenting features of cases. ‘Literature’ is by far the most dominant concept, increasing in relevance since 2003, with an overall relevance of 13% versus 5% for ‘evidence’ which has remained static.The fact that the least present types of reasoning concepts relate to diagnostic hunches to do with underlying processes, such as what is suspected, raises questions about whether intuitive practitioner evidence-making, found in a constellation of dynamic, process concepts, has become less important. The study adds support to the existing corpus of research on clinical reasoning, by suggesting that intuition involves a complex constellation of concepts important to how the construct of evidence is understood. The list of concepts the study generated offers a basis for reflection on the nature of evidence in diagnostic reasoning and the importance of intuition to that reasoning. It hadgements . Such evdgements ,8.This tension between scientific ‘evidence-based’ thinking and intuitive thinking is suggested also by the clinical reasoning literature. Yet this emerging body of literature offers little clear consensus on what is clinical reasoning . Since 1Better understandings of clinical reasoning could help manage diagnostic error. Diagnostic error has been linked to 8% of adverse medical events and 30% of malpractice cases . DiagnosBias, associated with non-analytical reasoning, has been described in one review as neutralised by reflective reasoning that is particularly important for diagnostic accuracy in complex cases ,20. EmotAlternative theories to resolve such tensions include the supposedly analytical and intuitive elements of clinical decision-making in ‘balanced’ models ,28. ThesThe language in which practitioner case reports are summarised offers elements of ‘real world’ case scenarios. Such scenarios have been the foundation of teaching clinical reasoning: hypothesis generation, pattern recognition, formulation of context, diagnostic test interpretation, differential diagnosis as well as diagnostic verification . We aimeThe description of the method that follows draws upon the method described in our previous Bayesian-based machine-driven studies of other large language databases .The research question was: ‘How important is a concept of evidence in published summaries of clinical cases? What other concepts do practitioners associate with an evidence concept in their case summaries, particularly concepts to do with research literature and intuition?’The study design involved treating abstracts of case reports as indicative evidence of what authors of those reports selected as important to understanding them. It was assumed that, if evidence and literature concepts were viewed by these clinical authors as essential to understanding their case reports, they would be more likely to be found in the abstracts of those reports. The study sample comprised all abstracts in English for case reports contained in the database PUBMED for the period 1 January 1983 to 31 December 2012. Case reports are defined in the PUBMED database as ‘Clinical presentations that may be followed by evaluative studies that eventually lead to a diagnosis’. This provided a total of 789,712 distinct abstracts all of which were included in the study. At approximately three abstracts per page, this corpus equates to approximately 263,237 pages or approximately 877 books, assuming 250 pages per book.Abstracts were grouped in five-year sub periods specified in Table http://dirt.projectbamboo.org/ lack validation studies. Across four criteria—cost, usability, as well as published validation studies and applications—Leximancer compares favourably with a wide range of other competing commercial text analytics products described in business intelligence product assessments [The analytic approach involved the application of a machine-driven, computational linguistics approach. This entailed content analysis of concepts in the abstracts using the software Leximancer v4.0 . This Bayesian-based software has been extensively applied in hundreds of studies across different disciplines, including in health -41. Manyessments .A text block of about a paragraph in size is the unit of analysis in Leximancer. Each paragraph may contain one or more concepts. Leximancer ‘learns’ from an uploaded language dataset to create a network of such concepts. The key output of the Leximancer software is a concept map with supporting data. The concept map provides a visual representation of all found and/or user-selected concepts in a corpus, based on their proximity or overall co-occurrence. In summary, concept mapping in Leximancer can be described as an iterative numerical model that simulates relationships between concepts to produce a complex network system with associated visualisations of data . FurtherThe analysis involved two standardised stages to quantify the conceptual content of the abstracts using the software (Leximancer version 4), as follows.This stage obtained a conceptual overview of the case report abstracts. The software produced a concept map with supporting frequency and co-occurrence statistics for all concepts mapped from the abstracts. In this study, the automated features of the software were used to derive the concept map. Very similar concepts were merged either automatically by the software or by the researchers. Thus the concept of ‘evidence’ is likely to include the concept of ‘evidence-based’. However, the concept ‘literature’ will not necessarily include the concept ‘review’ though the two may often be semantically proximate, something the method was designed to also assess. Concepts that did not contribute to an understanding of the content of the abstracts were not used as mapping concepts. That is, ideationally void concept words such as ‘appropriate’ were not used as mapping concepts. Terms such as ‘aims’, ‘methods’ or ‘findings’, which form structural features of abstracts, were also not used as mapping concepts. This does not mean this content was excised from the analysis, merely that such concept words were not used as organising terms under which the content of the abstracts was grouped. Accordingly, in Stage 1 the concept map was used to display all found concepts and their semantic proximity to one another across the entire database of 789,712 abstracts. In this stage, the software mapped 21,631,481 instances of 201 concepts found in 4,808,728 text blocks.This stage involved identification and extraction of data for two key concepts: the concepts of ‘evidence’ and ‘literature’. In this stage, 59,341 instances of the evidence concept were analysed to identify concepts that were most to least frequently paired with the evidence concept. Accordingly, 200 types of paired co-occurrences for the evidence concept were extracted and examined. The data providing frequencies and likelihood of paired co-occurrences were obtained. Overall likelihoods of the evidence concept occurring for each sub period of the study were also obtained. The 167,737 instances of the literature concept were similarly analysed.Manual scanning was also performed to do checks of the validity of the data analyses. The multiple data viewing windows in Leximancer facilitated these checks. That is, Leximancer allows the analyst to see all text blocks for a concept and also extract each instance of a concept to view it in the original data file. These checks were performed to help to ensure that the text blocks selected by Leximancer as part of a concept definition of, for example, ‘evidence’, did in fact always include the word ‘evidence’ or a term associated with it semantically. It is estimated that a total of 5% of the corpus or approximately 44 books were manually scanned for this purpose.Our method offers indicative evidence of how medical practitioners, engaged in the evidence-making fora of journals, conceptualise evidence when summarising the most important aspects of a case report. It does not offer conclusive evidence of how they use evidence in practice or even in the detail of case reports. Rather, the study suggests how they conceptualise that evidence when summarising clinical cases in the genre ‘case report abstracts’. This is a critical distinction. Further, the study is not indicative of all case reports written for journals, only of those with structured abstracts. Only 60.1% of all 1,312,960 case reports for the period 1983–2012 listed in PUBMED have abstracts used in this study.Leximancer, like other such machine-based data mining tools, offers scoping of large datasets but not fine-grained explanations of their conceptual nuances. Accordingly, the study was designed to offer broad, not nuanced, findings about how practitioners publishing case reports conceptualise evidence in summaries of those reports i.e. typical semantic features. It is useful to questioning broad assumptions about the nature of those concepts and their presence over time.Strengths of the study include the novelty of both the database and the method. The study sample as a whole represents 48% of the total 1,638,946 case reports in the PUBMED database for all years (i.e. not just for the study period) and all languages where an abstract in English exists—a substantial corpus. The PUBMED database of case report abstracts has not previously been analysed for this purpose using data mining methods, although the field of computational ‘text analytics’ offers many opportunities for such investigations.The study is a content analysis of published material in peer reviewed journals. No data were collected from human subjects.The concept map in Figure →different → process→changes → specific→single → study.Figure This suggests that evidence as a concept is not only attached to empirical studies but also to dynamic concepts to do with growth, difference and processes.→knowledge→young → syndrome→described→presented→congenital→rareIn contrast, the literature concept is part of another kind of typical storyline: literature → review → report → cases. Through report and cases, the literature storyline branches out  to:This indicates that the research literature has tended to be constructed in terms of literature reviews closely aligned to the way in which case reports themselves are conceptualised—as might be expected if literature reviews are commonly used to justify the unusualness of a case. Literature is linked to specific syndromes or particular knowledge and descriptions, making sense of presentations, and congenital and rare disease.Notably, the two concepts of evidence and literature are not semantically similar i.e. they are not proximate to one another. In summary, evidence is linked to amorphous clinical reasoning storylines like process through the amorphous concept of suggest—a term linked to diagnostic hunches. In contrast, literature → review is not linked to such amorphous clinical reasoning concepts. This suggests clinical reasoning involving research literature is possibly narrower and more descriptive than clinical reasoning involving evidence which is dynamic and involves process understandings.Table However, Table Table The least common eight paired co-occurrences for the literature concept or those ranging from 2-1% are more narrow biomedical and clinical concepts such as ‘serum’ (1%) and ‘tissue’ (2%). It appears therefore that the more a concept relates to the broader concepts of clinical management the more likely it is to be linked to the literature concept. The more a concept relates to the biomedical and clinical detail of patient management, the less likely it is to be found with the literature concept. Overall, the distribution of concepts in terms of the likelihood percentages suggests that most of these clinical concepts are not very likely to be found with the literature concept. Scrutiny of the placement of reasoning concepts such as ‘detected’ (2%) and ‘suspected’ (3%) further confirms that diagnostic reasoning concepts to do with underlying processes are not found with the literature concept.Examination of the likelihood figures by sub period of the analysis suggests that there is a difference by sub period in the likelihood of the literature concept being found. That is, references to literature have not remained static with a 4% likelihood overall of being found in any one text block over the years 2003–2012 and a 3% likelihood over the years 1983–2002. That is, it appears that summaries of case reports are increasingly using the literature concept.Table The background section suggested that clinical reasoning literature does not support simplistic mistrust of practitioner intuition or the more unconscious elements of diagnostic reasoning. It suggests that intuitive ‘System 1’ thinking has a role as important as rational ‘System 2’ thinking that includes explicit use of research .This study suggests that evidence is a fundamentally patient-centred, intuitive concept in summaries of what is important to case reports. Evidence is far more linked to amorphous, dynamic concepts suggestive of suspected underlying processes and diagnostic hunches. Its typical storylines across multiple concepts include, but are not limited to, research studies. The evidence concept is as likely to be found with scientific concepts such as ‘data’ as it is with concepts such as ‘signs’ that may be associated with medical intuitions.The study also suggested that, at least in abstracts, the use of research literature in clinical reasoning is linked to more superficial reasoning concepts or specific knowledge and descriptions or presenting features of cases. The more a concept relates to the broader concepts of clinical management, the more likely it is to be linked to the literature concept (itself most often found in the concept review i.e. as in literature review). The more a concept relates to the biomedical and clinical detail of patient management, the less likely it is to be found with the literature concept.The study suggests that the use of research literature in diagnostic reasoning may have become more prevalent, in contrast to intuitive practitioner evidence-making, at least in these data. Of course, such a finding may be an artefact not simply of changes in the practice of clinical reasoning but rather in the requirements of journals in reporting cases. Literature is by far the most dominant concept with an overall relevance of 13% versus 5% for evidence. Further, literature has been increasing in relevance since 2003 while the concept of evidence has remained static.These findings should be interpreted in light of the fact that clinical case summaries include a wide range of reasoning concepts. The fact that the most frequent reasoning concepts are concepts to do with what can be associated or described or understood causally and so on raises questions about the role of the literature concept in a constellation of more superficial reasoning concepts. The fact that the least present types of reasoning concepts relate to diagnostic hunches to do with underlying processes, such as what is suspected, also raises questions about whether intuitive practitioner decision-making, found in a constellation of dynamic, process concepts, has become less important.These findings raise more questions than the method can answer. Clearly, the research literature is a critical part of clinical reasoning, but how is it used in practice in relation to more intuitive aspects of clinical reasoning? This study has suggested that literature, primarily literature reviews often used to establish the unusualness of a case, is selected by clinical authors of case reports as important to summary representations of those cases but also that intuition may have a critical role. Future work applying this method should involve examining relationships between intuition and literature reviews, as well as other kinds of evidence, in different kinds of informal unstructured texts gained from clinical reasoning situations. In the meantime, this study adds support to the existing corpus of research on clinical reasoning, by suggesting that intuition involves a complex constellation of concepts important to how the construct of evidence is understood. The list of concepts the study generated offers a basis for teachers, students and clinicians to reflect on the nature of evidence in diagnostic reasoning and the importance of intuition to that reasoning.