The process and effectiveness of knowledge translation (KT) interventions targeting policymakers are rarely reported. In Cambodia, a low-income country (LIC), an intervention aiming to provide evidence-based knowledge on pneumonia to health authorities was developed to help update pediatric and adult national clinical guidelines. Through a case study, we assessed the effectiveness of this KT intervention, with the goal of identifying the barriers to KT and suggest strategies to facilitate KT in similar settings.An extensive search for all relevant sources of data documenting the processes of updating adult and pediatric pneumonia guidelines was done. Documents included among others, reports, meeting minutes, and email correspondences. The study was conducted in successive phases: an appraisal of the content of both adult and pediatric pneumonia guidelines; an appraisal of the quality of guidelines by independent experts, using the AGREE-II instrument; a description and modeling of the KT process within the guidelines updating system, using the Unified Modeling Language (UML) tools 2.2; and the listing of the barriers and facilitators to KT we identified during the study.The first appraisal showed that the integration of the KT key messages in pediatric and adult guidelines varied with a better efficiency in the pediatric guidelines. The overall AGREE-II quality assessments scored 37% and 44% for adult and pediatric guidelines, respectively. Scores were lowest for the domains of ‘rigor of development’ and ‘editorial independence.’ The UML analysis highlighted that time frames and constraints of the involved stakeholders greatly differed and that there were several missed opportunities to translate on evidence into the adult pneumonia guideline. Seventeen facilitating factors and 18 potential barriers to KT were identified. Main barriers were related to the absence of a clear mandate from the Ministry of Health for the researchers and to a lack of synchronization between knowledge production and policy-making.Study findings suggest that stakeholders, both researchers and policy makers planning to update clinical guidelines in LIC may need methodological support to overcome the expected barriers. Pneumonia still imposes a major burden to populations and health systems in low-income countries (LIC) although interventions to prevent and treat pneumonia are known -4. In CaIn August 2011, the MoH undertook the revision of the pediatric and adult guidelines for 180 diseases and health problems commonly treated in the country, including the management of community-acquired pneumonia ,11. ThisUpdating guidelines is a difficult task, particularly in LIC. Reliable guidelines must be epidemiologically relevant and reflect state-of-the art of medical practice. They have to be developed in a transparent way to facilitate their implementation and considering their acceptability and financial implications is also important . HoweverIn September 2011, the IPC researchers were informed by the World Health Organization (WHO) Cambodian office that a revision of the national guidelines was being undertaken. Although there was no official demand for it from the MoH, the IPC researchers endeavored to provide the MoH with locally relevant and evidence-based knowledge on pneumonia. IPC researchers facilitated the creation of a multidisciplinary working group of national and international clinicians, biologists, health program managers and epidemiologists involved in pneumonia management in Cambodia, dubbed the CALIBAN network  (List 1).Detailed description of the intervention1. Characteristics of those who delivered the interventiona. • Intervention delivered by the CALIBAN group which included:– European epidemiologists from a Cambodian-French research agency (n = 2)– Cambodian clinicians from the Ministry of Health (n = 4)– Cambodian clinicians and biologists from the National Institute of Public Health (n = 1)– Cambodian and international clinicians and biologists from NGO hospitals (n = 8)– International clinician affiliated with the University of Health Sciences (n = 1)– European clinicians from a Cambodia-based research agencies (n = 1)– Foreign health program managers from the World Health Organization (n = 1)• Among the Cambodian clinicians, were the two experts in charge of drafting the updated appointed to review the pediatric and the adult pneumonia guidelines.– One of them, a pulmonologist, agreed to chair the CALIBAN group.– Another CALIBAN Cambodian clinician was also a member of the Task force in charge of updating the guidelines.Characteristics of the intervention’s targetsb. • National Health program managers, policymakers and clinicians, some of them belonging to the working group delivering the interventionSettingc. • A low- income country, with limited but improving research capacitiesMode of actiond. • Build a working group of stakeholders involved in pneumonia management in the country• Collect, appraise, analyze, synthesize data existing on pneumonia etiologies and antimicrobial profiles, in the literature and among the working group• Collectively produce a corpus of evidence• Produce a report and a synthesis with key messages adapted to policymakers’ needs• Disseminate the report and synthesis• Push for uptake of this evidence and its translation into guidelines recommendations• Document the process• Using:– Direct interactions with the intervention recipients ,– Written communications – Data collection, analysis and synthesis, shared with the intervention’s recipientsDuratione. • 8 monthsAdherencef. • Limited participation of nationals while conducting the interventionAssumed output2. a. Built up of shared knowledge on pneumonia based on local evidenceb. Uptake of the key messages about pneumonia etiologies and antimicrobial resistance and translation into the CPGshttp://www.webcitation.org/6Qo38T6HW).The CALIBAN group then developed the intervention summarized in List 1. A systematic review and synthesis of literature on pneumonia etiologies and antimicrobial resistance levels in Cambodia and its neighboring countries was conducted . The CALThis work describes the retrospective evaluation of this ‘knowledge translation’ (KT) intervention. KT is the process by which ‘stakeholders are aware of and use research evidence to inform their health and healthcare decision making’ . It invoWe describe this KT intervention and assess its impact on the updating of guidelines from several angles. Our objective was to identify the barriers to KT encountered in this LIC setting, and to suggest strategies to facilitate KT in similar settings.We retrospectively searched for all relevant sources of data documenting the CALIBAN intervention and the pneumonia guidelines. We used contact with key informants, the IPC and CALIBAN archives, the National Institute of Public Health and MoH websites. Data collected included project protocols, reports, published literature, and meeting minutes from CALIBAN. It also included the successive drafts of guidelines, email correspondence between researchers, the CALIBAN network and the Task force, as well as notes taken during interviews with a key informant from the NGO who assisted the guidelines update. The review of these documents enabled us to describe and model the KT intervention.Firstly, we compared the CALIBAN key messages with the updated adult and pediatric guidelines released in 2013 to assess the extent to which the newly issued recommendations were in line with the key messages .We also assessed how well the CALIBAN KT messages were integrated by examining the rigor and transparency of the guidelines updating process. For this purpose, we used the internationally validated AGREE-II instrument . Each guSecondly, we modeled and analyzed the CALIBAN KT process within the ‘guidelines updating’ system, using the Unified Modeling Language (UML) graphical tools. The purpose was to describe how this intervention worked and to provide a framework for assessing its effectiveness.UML is an object-oriented modeling tool developed in 1997 for documenting, designing, and evaluating complex systems . It is ahttp://www.webcitation.org/6Qo2KJcEe) . It also refers to additional guidelines to treat pneumonia due to the less frequent pathogens cited by CALIBAN and which require specific treatments.Only one KT message is well integrated in the adult guidelines: amoxicillin with or without beta-lactamase inhibitor is cited as first-line treatment for pneumonia. The guideline cites atypical pathogens as possible pneumonia etiologies although the CALIBAN group could not firmly document their prevalence in the country. The second-line option given for non-severe pneumonia are macrolides which are not effective against the most prevalent pathogens in adult pneumonia in Cambodia. Macrolides are also inappropriately recommended as single-drug for patients hospitalized in intensive care with very severe pneumonia. Moreover, the guidelines recommend fluoroquinolones for first-line treatment for severe pneumonia in hospitalized patients and for second-line or alternative treatment for uncomplicated cases. These fluoroquinolones are expensive, have side effects, and should be preserved to avoid resistance and remain a powerful tool against tuberculosis, which is highly prevalent in Cambodia. Finally these guidelines do not mention the possible use of Amikacin in case of severe pneumonia due to Gram-negative bacteria, although this was among the CALIBAN key messages.The AGREE-II assessment showed that both guidelines did not meet some development and editorial independence standards of rigor Table . Rigor rThe AGREE-II criteria on editorial independence scored 12% and 11% for adult and pediatric guidelines, respectively. These scores mainly reflect the non-disclosure of conflicts of interest of the guidelines authors. Potential conflicts of interest such as those from drug companies could not be assessed because they were not disclosed.By modeling UML use cases, we identified six main actors directly or indirectly interacting within the ‘guidelines updating’ system Figure . The MoHThe activity diagram shows the activities of four actors directly involved in the updating of the adult pneumonia guidelines  scored better, demonstrating the positive effect of funding and international attention  behind closed doors’ .http://www.webcitation.org/6Qo0xEWDn). In 2011, WHO published a handbook for guidelines development in LMIC, based on the experience of a European low-resource setting [3. Seek methodological support. Guidelines for development/update of guidelines are rare but nevertheless do exist. In 2007, the ADAPTE collaboration developed a systematic approach, a manual and tools to facilitate the adaptation of existing guidelines to different contexts .1. Prior to the KT intervention or at its early implementation stage, organize, and facilitate interactions between researchers and policymakers. This potentially makes policymaking and research more compatible.2. ‘Blur the boundaries’ , constit3. Identify and involve effective KT coordinators/facilitators—sometimes called ‘knowledge brokers’ . Their t4. Document and report additional case reports to further support the development of guidelines for developing/updating guidelines.Finally there are also some institutional lessons that could be derived from this case report:1. Declaring conflicts of interest should be mandatory for researchers, tasks forces, and expert committees involved in guideline development, especially with regard to guidelines that make recommendations on medication alternatives.2. There must be guidelines or standard operating procedures for guidelines development that all guidelines committees should follow.3. The use of available evidence as well as the grading of evidence should be part of the above guidelines.4. Task forces should be provided with tools to grade locally acquired evidence. Otherwise they may overstate the contribution of western textbooks.The main limitation of this analysis is that it was conducted from the perspective of those who designed and implemented the KT intervention since it was the only source available. We used the quality and content appraisals of the updated pneumonia guidelines as a proxy for KT impact. Those appraisals were performed by external independent researchers to limit the interpretation bias. The modeling analysis was conducted by five professionals from various backgrounds to also limit potential bias of analysis. Three of them did not participate to any stage of the CALIBAN KT intervention . Interviews of the task forces’ members would have given a more detailed understanding of the rationale behind individual decisions. Unfortunately, due to technical and institutional reasons we could not have access to this information, However, such an understanding is readily available through studies exploring policymakers perspectives on KT interventions . An addiThis case study provides an overview of a partly successful collaboration between researchers and policymakers in a LIC and highlights the main missed opportunities of a KT experience. Longterm and close interaction between researchers and policymakers was the main facilitating factor of KT. Other efforts made by the researchers such as building accurate robust local evidence, formatting it to the needs of policymakers, inviting policymakers to participate in the KT intervention were not sufficient. Stakeholders—policymakers and researchers—planning to update clinical guidelines in LIC should receive methodological support to overcome the expected barriers.WHO: World Health Organization; MoH: Ministry of Health; NGO: Non-governmental organization; CPG: Clinical practice guidelines; KT: Knowledge translation.All authors declare that they have no competing interests.SG led the data collection and analysis and wrote the manuscript. RF, HB, and AT iteratively commented the manuscript drafts and oversaw its development. HB, TL, JvG, RF, and AT were involved in the data analysis. TL oversaw the UML data modeling. AT and SG initiated and led the CALIBAN intervention. JvG was a CALIBAN member. All authors critically read the manuscript and have given final approval. The views expressed in this article are those of the authors and not necessarily those of their institutions. All authors declared no conflicts of interest.vs 2013 Pneumonia guidelines.CALIBAN key messages Click here for fileLegend of the Activity diagram.Click here for fileUnified Modeling Language Activity diagram - Knowledge translation and Clinical Practice Guidelines updating.Click here for file


Inadequate health literacy affects more than 90 million Americans and it has been associated with adverse outcomes in the medicine field including increased hospitalization rates and greater mortality. Since surgical patients are often required to make complex decisions and adhere to complex instructions, health literacy may have a profound impact in the surgical practice. The main objective of the current study was to systematically evaluate the role of health literacy in surgical patients.A systematic search was performed to identify studies that evaluated the role of health literacy in the perioperative setting following the PRISMA guidelines. Only studies that examined health literacy using a validated instrument in the perioperative setting were included.Ten studies including data on 1147 patients were included. The median (IQR) number of patients in the included studies was 101 (30 to 152). The majority of studies used the Short Test of Functional Literacy in adults (STOFHLA) to evaluate patients’ health literacy. Five studies evaluated the patients preoperatively, four studies evaluated patients in the postoperative period and in one study the time of evaluation in relation to the surgical procedure was not defined. The lowest prevalence of inadequate health literacy was detected in kidney transplant patients, 6 out of 124 (5 %), while the highest prevalence of inadequate health literacy was detected in orthopedic patients having total joint replacement, 86 out of 126 (60 %). Inadequate health literacy in the preoperative period was associated with poor medical information comprehension and it may adversely affect adherence to preoperative medications and even modulate surgical disparities. Inadequate health literacy in the postoperative period was associated with poor comprehension of discharge instructions and worse kidney function in transplant recipients.Health literacy seems to have a very significant impact in the care of surgical patients. More studies to establish the impact of poor health literacy on perioperative outcomes are needed. Health literacy is the ability to comprehend and use health information in order to make appropriate health decisions . It has Health literacy is likely to have a very important role in the care of perioperative patients. In addition of an understanding of the health information they are provided, numeracy skills are required to make decisions regarding elective surgical procedures. Frequently, patients are required to follow complex preoperative and postoperative instructions and lack of adherence to those instructions can result in negative outcomes or cancellation of surgical procedures , 8. DespThe main objective of the current systematic review was to evaluate health literacy in surgical patients. We also sought to examine the current reported prevalence of patients with inadequate health literacy in the same population.We performed a quantitative systematic review following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA) . The curth, 2013. Free text and MeSH terms ‘literacy’, ‘health’, ‘surgery’, ‘perioperative’, ‘preoperative’, ‘postoperative’ and ‘operation’ were used individually and in pairwise combinations. No language restriction was used. An attempt to identify additional studies not found by the primary search methods was made by reviewing the reference lists from identified studies. No search was performed for unpublished studies. This initial search yielded 291 manuscripts.Published reports of studies evaluating health literacy in the perioperative setting were searched using the National Library of Medicine’s Pubmed database, the Cochrane Database of Systematic Reviews and Google Scholar inclusive to November 15The study’s inclusion and exclusion criteria were determined before the systematic search. Two authors (GDO and RJM) independently evaluated the abstract and results of the 291 articles obtained by the initial search. Articles that were clearly not relevant based on our inclusion and exclusion criteria were excluded at this phase. Disagreements on inclusion of the articles were resolved by discussion among the evaluators. If an agreement could not be reached, the dispute was resolved with the help of a third investigator. The third investigator was blinded regarding evaluation of the first two authors.We included published manuscripts that evaluated health literacy in perioperative patients. Included studies had to report on health literacy using a validated instrument. Inclusion of studies was not limited by the timing of healthy literacy evaluation in relation to the surgical procedure (preoperative or postoperative). Studies that examined topics related to health literacy but did not include reports on patients were excluded. Excluded also were studies that performed simple readability tests of patient education materials. No minimum sample size was required for inclusion in the systematic review.The Newcastle-Ottawa scale was used to assess the methodological quality of cohort and case–control studies . The NewTwo authors (GDO and RJM) independently evaluated the full manuscripts of all included studies and performed data extraction using a data collection form specifically developed for this review.Discrepancies were resolved by discussion between the two investigators (GDO and RJM). If an agreement could not be reached between the two investigators, the decision was made by another investigator. Data extracted from studies included the health literacy instrument used, type of surgical specialty, time in relation to surgical procedure , type of intervention, evaluated outcomes, study design, sample size, number of subjects with inadequate literacy, and follow-up period.Data were initially extracted from tables or text. For data not available in tables, the data was abstracted from available figures. Dichotomous data on the presence or absence of adverse effects was extracted and converted to incidence, while continuous data was recorded using mean and standard deviation.Quantitative analysis was not performed due to the large heterogeneity of study designs, interventions and measured outcomes.Of the 291 initially evaluated abstracts, 32 studies were initially selected. Twenty-two studies were subsequently excluded: ten studies did not evaluate patients –21, nineOne study developed and validated a rapid estimated of adult literacy specific for vascular surgery patients  . The insFive studies evaluated patients during the preoperative period , 40, 43.Two prospective cohort studies examined the association of health literacy and important perioperative outcomes , 43. CheOnly one randomized trial evaluated the effect of low literacy consent on patient’s comprehension of the consent process in patients undergoing laparoscopic tubal ligation . Women wFour studies investigated the role of health literacy in the postoperative care of surgical patients , 41, 44.n = 8) and by a large proportion of patients lost to follow up.One study evaluated the prevalence of inadequate health literacy in patients who underwent total laryngectomy . The estβ = −0.3, 95 % CI −0.05 to −0.00; P = 0.03).One cross-sectional study evaluated the role of health literacy on patients ability to understand discharge instructions after cardiac surgery . The autOne author performed a focus group study to evaluate the effect of pictograph –based discharge instructions in patients that underwent hip replacement surgery . AlthougThe most important finding of the current systematic review was the paucity of studies examining health literacy in the perioperative setting. In addition, current studies in surgical settings had very limited sample sizes especially when compared to studies in the medical setting , 45. SevMost of the included studies were observational and only one study examined a low-literacy patient communication intervention using a randomized controlled design . The stuHealth literacy is considered a major driving factor in explaining disparities in health care . MultiplIt was interesting to note that the reported rates of inadequate health literacy varied substantially among different surgical procedures. Poor health literacy had low prevalence in recipients of kidney transplants (4 %) but it had high prevalence among orthopedic patients having hip and knee replacements , 41. SinCurrently, approximately 70 % of surgical procedures are performed in the ambulatory setting . The ambOur systematic review should only be interpreted in the context of its limitations. Due to the low number of interventions and a variety of outcomes examined, we were unable to perform a quantitative analysis. Consequently, we were not able to examine the data for publication bias. We cannot, therefore, exclude the possibility of negative studies that were “file-drawer” and could have refuted the influence of inadequate health literacy on surgical outcomes. We were also not able to detect which levels of health literacy are critical for optimal outcomes in perioperative patients. The time constraints commonly seen in the surgical setting may require greater levels of health literacy from surgical patients than what has been established for optimal outcomes in the non-surgical specialties.In summary, we evaluated the role of health literacy for patient care in the perioperative setting. The evaluated studies suggest that poor health literacy may be associated with inadequate comprehension of the surgical procedure and discharge instructions. In addition health literacy may be implicated with poor adherence to preoperative instruction which may jeopardize patient safety. Lastly, surgical disparities may also be, in part, explained by inadequate literacy. The lack of large studies confirming those preliminary findings and the lack of interventions to address limited perioperative health literacy call for an extreme need to develop a research agenda in order to minimize the effects of poor health literacy in the care of surgical patients.


Venous thromboembolism (VTE), comprised of deep vein thrombosis (DVT) and pulmonary embolism (PE), has gained increasing recognition over the last two decades as a serious medical condition and a public health concern . Since VWhat has changed about VTE that has elevated its importance in the spectrum of medical conditions? Many factors may be responsible, including a better understanding of the pathophysiology of VTE, a better recognition of risk factors leading to VTE, and a better understanding and recognition of hereditary and acquired thrombophilias. Undoubtedly, however, recent improvements in the treatment of VTE play an important role and make it more important than ever that healthcare providers are well educated about recent changes. We now have interventions such as thrombolysis, mechanical clot retrieval, new venous stents and vena cava filters or combinations of these , some ofThere are many therapeutic decision points in the course of VTE treatment. To aid clinicians, professional groups have published treatment guidelines based on the best medical evidence or rendered consensus opinions when good quality evidence is lacking. The most prominent of these guidelines are those published by the American College of Chest Physicians, starting in 1989 with updates every 3–4 years, the last being in 2012. With the rapidly changing management of VTE, in part, spurred by the introduction of the DOACs, the Anticoagulation Forum detected an urgent need for practical knowledge about the changing management paradigm. The Anticoagulation Forum is the largest peer organization of anticoagulation service providers in North America (ACForum.org). Its 6000+ members are comprised of physicians, nurses, and pharmacists representing over 2000 anticoagulation services (clinics). The AC Forum’s goal is to create a community where physicians, pharmacists and nurses can access the latest research, engage in educational programs, and find tools to evaluate and enhance their practice.In an effort to bring practical and implementable information to its members and the provider community at large, the AC Forum initiated this guidance project by assembling experts in the disciplines of VTE research, education and care, asking them to consider practical everyday questions about the treatment of VTE using the best medical evidence and existing guidelines, but not hesitating to offer consensus opinions when high-quality evidence is not available. This special issue of the Journal of Thrombosis and Thrombolysis includes 12 manuscripts focused on the epidemiology and management of VTE with a particular emphasis on the management of drugs employed in its treatment, with both traditional agents as well as the new DOACs.


Introduction: It has been found that the decision-making process in medicine is affected, to a large extent, by one’s experience, individual mentality, previous models, and common habitual approaches, in addition to scientific principles. Evidence-based medicine is an approach attempting to reinforce scientific, systematic and critical thinking in physicians and provide the ground for optimal decision making. In this connection, the purpose of the present study is to find out to what extent the education of evidence based medicine affects clinical decision making.Methods: The present quasi-experimental study was carried out on 110 clinical residents, who started their education in September, 2012 and finally 62 residents filled out the questionnaires. The instrument used was a researcher-made questionnaire containing items on four decision-making approaches. The questionnaire was used both as a pre-test and a post-test to assess the residents’ viewpoints on decision making approaches. The validity of the questionnaire was determined using medical education and clinical professionals’ viewpoints, and the reliability was calculated through Chronbach alpha; it was found to be 0.93. The results were analyzed by paired t-test using SPSS, version 14.Results: The results demonstrated that evidence-based medicine workshop significantly affected the residents’ decision-making approaches (p<0.001). The pre-test showed that principles-based, reference-based and routine model-based approaches were more preferred before the program (p<0.001). However, after the implementation of the program, the dominant approaches used by the residents in their decision making were evidence-based ones. Conclusion: To develop the evidence-based approach, it is necessary for educational programs to continue steadily and goal-orientedly. In addition, the equipment infrastructure such as the Internet, access to data bases, scientific data, and clinical guides should develop more in the medical departments. Physicians have to make decisions in their practice ranging from diagnosis to analysis and treatment of the disease. In the process of clinical decision making, a body of variables such as signs and symptoms, medical knowledge, prior experience, the models doctors have acquired from their professors and even conjectures, emotions and impulses can affect a physicians’ decision . ParalleWith increasing volumes of medical data, students and scholars of this field more than ever need to retrieve the reliable and necessary data for diagnostic and treatment decisions from among large quantities of published articles. As a result, they should be able to criticize and analyze the reliability of the sources and the data. According to some evidence, most students search information from public Internet sites such as Google, and Wikipedia . HoweverIranian medical universities have also adopted evidence-based medicine as a new approach in medical education. A variety of workshops have been held to develop the concept and philosophy of evidence-based medicine throughout the country. In the Iranian comprehensive health map, change in health education system and delivery of services by those who are knowledgeable, competent and accountable to the needs of the society is stressed .Although different clinical groups including professors, clinical residents, medical students and other medical and paramedical staff play a part in development of evidence-based medicine, the role of clinical residents is of critical importance, because they not only deliver specialized clinical services, but also have a direct influence on the education and model adoption of junior residents and students. It has been revealed that medical students receive most of their information through interaction with clinical residents more than the time they spend with full-time faculty members , 13.The term “resident” or medical specialty student implies living in the hospital. Rider, et al. call medical residents “hospital instructors” . TherefoAccording to Sánchez et al.’s findings at Mexico National University, senior residents maintained that they spend more than 32.5% of their time teaching medical and paramedical students and junior residents. Sánchez believes that universities of medical sciences should assess the residents’ educational needs and arrange well to meet them . In addiRegarding the model role of clinical residents in development of evidence-based education in junior students, identifying their treatment methods and clinical decisions is very significant in both patients’ health and medical education. Therefore, the present study aimed to investigate the clinical decision making by clinical residents of Shiraz University of Medical Sciences before and after implementing evidence-based medicine. The present quasi-experimental study was carried out using a researcher-made questionnaire in 2013. The participants comprised all of the 110 clinical residents at Shiraz University of Medical Sciences, entering the university in October, 2012. They took part in a 30 hour educational program over five days in a row. The contents of the program included the main topics of evidence-based medicine to the suggested content by Ministry of Health and Treatment. The method of education was planned based on active learning and the five steps of evidence-based medicine. In all steps, the main approach of education was planned and implemented based on active learning, raising advanced clinical questions, searching data sources, assessing the retrieved articles, selecting options, final decision making and ultimately assessing of performance. In order to find out the residents’ viewpoints on decision making methods, we used a questionnaire containing two sections. To prepare the questionnaire, we first raised an open ended question: “How are the clinical decisions usually made on wards?” A specialized focal group including 10 faculty members with pediatrics, social medicine, cardiology, nephrology, neurology, surgery, medical education, gastroenterology, and gynecology specialties answered the question. Having summarized the responses, the researchers came up with 10 decision making approaches, forming the main items of the questionnaire. The items were categorized into four general topics including “scientific principles”, “Evidence-Based Medicine approach”, “Subjective Personal Experiences”, and “Modeling”.The rate of using decision-making methods was calculated using Likert-scale scoring system, i.e. “rarely=1”, “sometimes=2”, and “usually=3” before and after the implementation of the program. The second section of the questionnaire included eight items as complementary data about prerequisites of evidence-based medicine. Five medical education professionals with clinical specialty helped to prepare the items.One month after the program, the questionnaires were sent to the clinical wards. To observe the ethical considerations, the questionnaires were filled out and collected anonymously. Of the 110 questionnaires sent, 62 were completed fully and precisely and returned. For descriptive statistics, frequency and standard deviation were calculated and for the inferential statistics, Paired sample t-test and Independent sample t-test were used through SPSS, version 14 . Of the 62 participants of the study, 19 (%31.7) were male, and 41 (%68.3) female. The age range of the participants was from 25 to 40 with a mean of 31.1±4.1. The results showed that the evidence-based medicine training program affected the residents’ decision making significantly. Furthermore, %53 of the residents asserted, after the program, that they used evidence-based medicine approach in teaching junior residents and medical students to a great extent. They also stated that they encouraged the students to make use of this approach. The mean scores of the residents’ viewpoints on decision making approaches before and after the training program are shown in The results of T-paired test showed that residents’ clinical decision making using evidence-based approach improved significantly in comparison to that before the training program (p<0.001). Furthermore, decision making approaches based on “personal judgment and experience” and “modeling” decreased in comparison to the use of the methods before the program (p<0.001). However, the use of logical and sensible methods such as consulting scientific references or pocket guidebooks did not change significantly (p=0.52).Analyzing the prerequisite skills for the application of evidence-based medicine, we found that about 43% of the residents most often had enough skills to search the required articles. 16.6 percent of the residents could most often and 67.2 percent of them could sometimes download their required articles. 77.4 percent of the participants most often had access to the Internet. Only 18 percent of the residents did have the experience of publishing a research article. Also, only 22.6 percent of the residents did state that the computers in the ward were equipped with up-to-date CDs (as an up-to-date source of scientific articles). And only 37.2 percent of them did say that there were clinical guidelines on their wards. The residents were asked an open-ended question: “what sites and databases did you use to search articles?” before and after the training program. Most residents answered that they usually used general sites such as Google or Yahoo before the program but after the program they got familiar with specialized databases to some extent. Experts believe that evidence-based medicine is an approach which can reinforce systematic, critical and scientific thinking and provide the ground for optimal clinical decisions. Decision making, selection and application of documentary evidence are the main parts of evidence-based medicine because this can finally affect the patients’ health , 27, 28 Comparing the use of decision making approaches after the program, we found that the training course significantly affected the residents’ use of decision making approaches, or the training program at least directed them to more proper decision making approaches. Although there was no significant difference between the use of logical and sensible methods based on scientific approaches before and after the training program, the decision making approaches based on experience and personal judgment as well as getting model from the environment, which are not scientifically based and may merely arise from habituation and observations, were significantly used less often after the training. Furthermore, the use of evidence-based approach increased significantly after the training. The residents stated that they made use of this approach in teaching undergraduates.A lot of studies have demonstrated the positive effects of evidence-based medicine on residents’ attitudes, knowledge, and skills -36. SuchResearch activities are in close connection with evidence-based medicine as they follow the scientific approach, from asking questions to looking for and studying scientific sources to organized methodology to presenting results to critical thinking and finally to knowledge publication. As a result, it is necessary to include the required courses in the general medicine curriculum to reinforce the students’ thinking and research skills. This can provide a ground for further development in postgraduate studies. The science-oriented research approach is currently used in most universities throughout the world. Wadland et al. (1999) have stressed the improvement of proposal writing and research skills for medical students. Barnet et al. (2000) and Dorsch et al. (2004) consider evidence-based approach as the basis of life-long learning , 31, 35.Overall, it seems that training the EBM courses has had a positive influence on the residents' approach to the use of scientific evidence and recommended to continue the EBM courses for other residents. Also, for further development and reinforcement of evidence-based approach in clinical decision making, the provision of infrastructures such as the Internet and accessible databases, scientific gatherings among residents such as journal clubs on evidence-based medicine and compiling educational guidelines in clinical departments are necessary.


Allergen immunotherapy (AIT) is widely used in clinical practice for patients with moderate to severe allergic rhinitis due to inhalant allergens and may be delivered via subcutaneous (SCIT) and sublingual routes (SLIT). However, the quality of evidence for individual AIT products is very heterogeneous, and extensions of overall conclusions (“class effects”) on the efficacy and disease-modifying effects to all AIT products are unjustified. In contrast, each product needs to be evaluated individually, based on available study results, to justify efficacy and specific claims on sustained and disease modifying effects per allergen and targeted patient group . WAO intends to support the current development to evidence-based AIT, which ultimately will lead to a more efficacious treatment of allergic patients and the appropriate recognition of AIT. Allergen immunotherapy (AIT) is a recommended therapeutic option for patients with moderate to severe allergic rhinitis with, or without, mild to moderate asthma due to inhalant allergens –4. AIT iThere are currently two routes of administration of AIT: subcutaneous (SCIT) and sublingual immunotherapy (SLIT). Several clinical trials and metaanalyses provide evidence to support the efficacy and safety of AIT and its widespread use in clinical practice . HoweverIt is likely that there has been an underreporting of negative results in the past, since only a few clearly negative studies have been published. This highlights the fact that: 1) not all AIT products are effective, or equally effective, and 2) the efficacy claims based on a “class effect”, without supporting evidence for an individual product , are inappropriate. In fact, it should be understood that the optimistic assumptions for AIT (“class effect”) mentioned above, may be unjustified in a general sense, as the evidence  relies on the results generated with a limited number of products that have undergone well-designed studies. It has been clearly demonstrated in the past that such assumptions may be incorrect with respect to some products that are not well studied . So far,In the last decade, substantial progress has been made in the development of selected AIT products and based on the current state-of-the-art, there are high quality, adequately powered, double-blind, placebo-controlled, randomized (DBPCR) clinical trials in which a small number of products have been evaluated. From these studies, it is possible to estimate the therapeutic efficacy of specific products as well as their safety profile. On the basis of these studies, recommendations for the use of individual products can be made in specific patient groups. This systematic and rigorous evaluation is mandatory and vital, not only for newly developed products, but also for those already in the market for a long time. For many products, specifically for mixtures of allergens, conclusive and reliable studies have never been performed and claims for their efficacy are unjustified. Furthermore, evaluation needs to be performed not only on a product line basis, but also per allergen, as single products of a product line contain different allergens . FinallyDermatophagoides pteronyssinus and farinae), bee and wasp venom . These rules also apply to mixtures involving at least one of the mentioned common allergens. This approach led to the elimination of more than 6,000 products for which efficacy had never been demonstrated. Importantly, these rules do not apply for less frequent allergens  since the authorities recognize that the financial burden would be too great or study participants are impossible to be found for products with small market indications. Apart from efficacy and safety, the quality of allergen extracts is subjected to control by the authority, including testing every new batch of allergen extract (batch release) for consistency.As an example, an evidence-based evaluation approach was officially adopted in Europe by the German authorities  in 2008, to be followed for all products in the market as named patient products and for products to be newly registered for the treatment of allergies due to the most frequent allergens: grass pollen, tree pollens , house dust mite  and aim to exclude ineffective, unsafe, or low quality products from market access. In the medium- to long-term period, these measures will support and encourage the use of AIT, since clear evidence of efficacy and safety is the mandatory basis for the application of AIT in the treatment of allergic patients and for reimbursement. In many countries such regulations do not exist , or the WAO intends to support and encourage this important evidence-based development in the field of AIT for frequently encountered allergens, by providing this document that details the expectations that a product should fulfill, in order to be recommended for safe and effective use. In contrast, differentiation and/or marketing of products merely based on application routes and claims of safety and efficacy for a particular product that has not been substantiated with objective evidence should be discouraged.The minimum requirements for a product that can be recommended for use, should include publication in the peer-reviewed literature of at least one successful state-of-the-art DBPCR trial in adults for the first year of treatment –13, possClaims on sustained effects of a product should be based on at least one DBPCR study, with appropriate sample size calculation, over 3 years of treatment. Demonstration of a disease modifying effect is based on studies with a blinded follow-up for at least two consecutive years after AIT discontinuation, while monitoring of symptoms is maintained. Claims for efficacy and safety in children should be based on appropriate DBPCR studies in the pediatric age group. Furthermore, for specific claims, e.g. in asthmatics, appropriate DBPCR studies should be performed in an appropriate patient group, with objective measurements.In this document, we have refrained from mentioning individual products. Rather, we have attempted to elaborate upon the criteria for evidence-based recommendation of products. This information/evidence can then be used by:  physicia


The presence and association of fungi with sessile marine animals such as coral and sponges has been well established, yet information on the extent of diversity of the associated fungi is still in its infancy. Culture – as well as metagenomic – and transcriptomic-based analyses have shown that fungal presence in association with these animals can be dynamic and can include “core” residents as well as shifts in fungal communities. Evidence for detrimental and beneficial interactions between fungi and their marine hosts is accumulating and current challenges include the elucidation of the chemical and cellular crosstalk between fungi and their associates within the holobionts. The ecological function of fungi in association with sessile marine animals is complex and is founded on a combination of factors such as fungal origin, host health, environmental conditions and the presence of other resident or invasive microorganisms in the host. Based on evidence from the much more studied terrestrial systems, the evaluation of marine animal–fungal symbioses under varying environmental conditions may well prove to be critical in predicting ecosystem response to global change, including effects on the health of sessile marine animals. There is no consensus on the definition of marine fungi, even though it is clear that the grouping of marine fungi is primarily based on an ecological rather than a taxonomical basis . CommonlSymbiodinium and marine prokaryotic and viral communities and their possible contributions to the niches they reside in received increased attention during the last decades  or the presence of Symbiodinium partners in the sample  states (Astrangia) go through seasonal changes in algal presence/activity  states . In whatactivity , fluctua animals . An addi pigment . Hence, Aspergillus sydowii, a common terrestrial fungus suggested to cause an epidemic in the sea fan Gorgonia ventalina that can also confer symptoms to G. flabellum  nature of association . Perhapslabellum . The ecolabellum . Howevergillosis . Furthergillosis  suggestsgillosis . These dTaken together, most studies performed on coral-associated fungi have focused on either parasitic or opportunistic interactions. Even though the majority of these describe either the fungal species associated with coral or potential detrimental outcomes of fungal presence within the animals, the importance of another key form of interactions – mutualism, has yet to be probed in detail, even though support for this notion has been clearly discussed . EvidencIrcinia variabilis (formerly Psammocinia sp.), mainly by using a “sample compressing” method, in combination with fungicides-amended media  cultured from Didemnum spp. In earlier studies, Aspergillus and Cladosporium. At least one case of an acidian-associated fungus (Camarosporium sp.) was included in that report. Other reports, mainly related to bioprospecting for novel natural compounds include representatives of known fungal genera such as Penicillium in the case of isocoumarin derivatives . D-glucans  in the demosponge S. domuncula and that this is followed by a transduction of signals which include tyrosine protein phosphorylation. Such a recognition event can lead to exclusion/killing of the fungus or, conversely, the establishment of a symbiotic interaction. Regardless, the richness of the microbial community associated with sponges is clear evidence for the discriminatory function of some of the chemicals and corresponding cellular reactions produced.Most of the emphases in the study of sessile marine animal–fungal interactions have been dedicated to the outcome of such interactions in respect to the hosts and by far less on the tolerance/susceptibility and physiological adaptation of the fungi involved. Chemical defense mechanisms have been considered as part and parcel of the success and survival strategies evolved in many sessile marine invertebrates. It is thus highly probable that some of the chemicals produced are directly involved in determining the composition and activity of resident and introduced microbiota . The antifungal nature of some of the chemicals produced by such animals and their accompanying microflora can provide a potentially hostile environment for fungi . Though Understanding of the effects of antifungal compounds (and other responses) produced by sessile marine holobionts and the role of fungal-produced compounds warrants additional research. This includes, in addition to chemical structure elucidation, the mode of anti-fungal action and the cellular signals involved both in the host and the fungus. Perhaps most challenging of all, is determining the significance/ecological roles of these compounds in the holobiont under varying environmental conditions.2 levels and warming) of plants associated with four classes  of endophytes . For the fungal groups analyzed, presence of the symbionts did not significantly influence the effect of CO2 on host plant performance. Warming had a differential effect, based on the symbiont class. An increase in temperature can promote plant growth and in the case of the presence of beneficial endophytes such an increase can further enhance plant biomass accumulation. Adversely, the presence of a potentially detrimental endophyte  can result in a reduction in plant biomass accumulation under elevated temperature conditions. The changes analyzed involve an array of factors ranging from the genetic background of the host to the colonization capacity of the symbiont as well as interactions with other fungal strains/taxa  planulae was not only dependent on their proximity to adults of other taxa, but also significantly reduced in water collected near conspecific adults when compared to sterile water. The latter data support the prediction that mortality is due to the activity of host-specific detrimental microorganisms. Whether or not fungi are involved in the described mortality and if such occurrences are relevant to coral that reproduce mainly by fragmenting  has yet to be determined, yet the foundations for examining the model with regard to fungal activity have been set.In conclusion, fungi have gained recognition as both resident and functional components of sessile marine animal microbiomes. The extent of their diversity and function has only begun to be revealed and determining their contributions and effects on the health, maintenance, survival and proliferation of sessile marine animals is a timely task, especially under a changing environment. It is tempting to try and extrapolate from terrestrial to marine environments. One can speculate that fungi may well contribute to sessile marine animal communities in related ways and that changes in the prevalence of fungi associated with marine species may have significant effects on maintaining the biodiversity of the latters. Based on the vast evidence on the complexity and diversity of plant-microbe interactions, we can expect an equivalently rich variety of relationships in sessile organisms of the marine environment.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


To investigate the relationship between literacy and numeracy and their association with health task performance.n = 304) completed commonly used measures of literacy and numeracy. Single factor literacy and numeracy scores were calculated and used to predict performance on an established set of health self-management tasks, including: (i) responding to spoken information; (ii) comprehension of print and (iii) multimedia information; and (iv) organizing and dosing medication. Total and sub-scale scores were calculated.Older adults . In multivariable models adjusted for age, gender, race, education, and comorbidity, lower literacy  and numeracy  were independently associated with worse overall task performance and all sub-scales . Multivariable analyses with both constructs entered explained more variance in overall health task performance compared with separate literacy and numeracy models .Literacy and numeracy measures were highly correlated (Literacy and numeracy were highly correlated, but independent predictors of health task performance. These skill sets are complementary and both are important for health self-management.Self-management interventions may be more effective if they consider both literacy and numeracy skills rather than focusing on one specific ability. Several health literacy measures exist, but the most common are the Rapid Estimate of Adult Literacy in Medicine (REALM) Intervention strategies to mitigate issues with literacy are likely to be different from those addressing numeracy problems. For example, where a patient with poor literacy is experiencing difficulty, a response may be to simplify the text Existing studies have examined the role of both literacy and numeracy measures on health-related outcomes. For example, in a cohort of inpatients hospitalized with acute coronary syndromes and/or acute decompensated heart failure, higher subjective numeracy and higher objective health literacy were independently associated with lower odds of making post-discharge medication errors The literacy and cognitive function among older adults (LitCog) cohort provides an opportunity to investigate this area as several measures of objective literacy and numeracy were recorded at baseline 22.1A full description of the recruitment procedures and methods has been published elsewhere 2.2In-person structured interviews were held in a private room at Northwestern Memorial Hospital or at one of the four FQHCs. Two sessions were undertaken lasting 2.5 hours and spaced 7–10 days apart. Trained interviewers administered a series of assessments and questionnaires related to literacy, numeracy, performance on common health tasks, and participant characteristics. Prior to the interview, prospective participants were told that the study includes people who have been seen at the clinics in the Access Community Health Network and their doctor agreed that they were eligible to take part. They were informed that the overall aim of LitCog was to aid the creation of better health learning tools to assist patients with their day-to-day healthcare. Free parking or travel reimbursement was provided to encourage participation.2.2.1A single factor score for literacy was computed using three different assessments. This was done to provide one factor that could represent the multitude of skills that the following measures assess under the umbrella term ‘literacy’. The Rapid Estimate of Adult Learning in Medicine (REALM) assesses correct pronunciation of a list of 66 words related to healthcare 2.2.2A single factor score for numeracy was computed using three different assessments, again because each numeracy measure is likely to represent a different skill set. All instructions for the numeracy assessments were read to participants verbally, thereby limiting the need for literacy in these tasks. The Newest Vital Sign requires participants to review a nutrition label and answer items based on how they would interpret and react to the information 2.2.3The Comprehensive Health Activities Scale (CHAS) was developed as an outcome for the LitCog cohort. It has been described in detail elsewhere 2.2.4categorized as 0, 1 and 2 or more comorbidities.The following participant characteristics were recorded: age , gender, race , and education  were recorded. The following comorbidities were also self-reported: arthritis; asthma; bronchitis or emphysema; cancer; coronary heart disease; depression; diabetes; heart failure; and hypertension. These data were 2.3α = 0.05, 90% power, and 7 predictors in a multivariable regression analysis suggested a sample of 304 participants would be sufficient to detect a small effect size of 0.06 The sample size for LitCog was based on the primary outcomes of the main LitCog analysis 2.4β) are reported throughout. The multivariable models were adjusted for age, gender, race, education, and comorbidity. Models were run entering literacy (Model 1) or numeracy (Model 2) to establish the extent to which they predicted health task performance . Model 3 then entered both literacy and numeracy to examine their combined effects on health task performance. F-tests determined if the variance explained by each of the models (R2) significantly changed with the addition of the other variable (i.e. Model 1 vs. Model 3 and Model 2 vs. Model 3). Statistical significance was set at p < 0.05 for all analyses. Analyses were performed in SPSS version 22.0.Participant characteristics were presented using descriptive statistics. Factor scores for literacy  and numeracy  were computed to reduce the skills to two measures for subsequent regression models and avoid multicollinearity. Maximum likelihood estimation was used because it is a valid and statistically efficient way of creating single factor solutions when assessing multiple theoretically similar constructs that are strongly interrelated 33.1As shown in p < 0.001), and African American participants scored lowest (p < 0.001) and was lowest in those with more chronic conditions (p = 0.002). Similar observations were apparent for associations between numeracy and comorbidities (p < 0.001), education (p < 0.001) and race (p < 0.001). Numeracy was also lower among women (p = 0.008) and older participants (p < 0.001).The average literacy score on the single-item factor was 0.19 (SD = 0.70) and it ranged from −3.8 (low literacy) to 0.75 (high literacy). The average numeracy score was 0.00 (SD = 0.89) and it ranged from −2.27 (low numeracy) to 1.71 (high numeracy). Higher scores indicated better performance. Literacy scores were associated with race  and the TOFHLA-R   and all numeracy measures . As shown in p < 0.001 for all).As shown in D = 7.0) . Scores 3.33.3.1M = 67.2 out of 100, SD = 18.9). After adjusting for age, gender, race, education, and comorbidity, higher literacy scores predicted better health task performance  . When literacy and numeracy were included concurrently, both were significant predictors of performance .Health task scores ranged from 6.3 to 97.8 (< 0.001) . When nuR2 change statistic was observed. There were significant differences in variance explained between Model 1 and Model 3  and Model 2 and Model 3  change = 99.33, p < 0.001) indicating models containing literacy and numeracy are better than those considering each variable alone.To test whether including both literacy and numeracy significantly improved the explanatory power of the models, the 3.3.2M = 72.5, SD = 20.9); organizing and dosing medication ; responding to spoken instructions ; and recalling multimedia information . This indicates that participants found tasks related to recalling multimedia information more difficult.For comparison, the scores on each of the sub-scales were standardized to range from 0 to 100. As shown in β range = 0.39–0.63, all ps < 0.001) and higher numeracy  were associated with better performance on all tasks. When entered together, literacy and numeracy were both significantly associated with performance on all tasks . Significantly more variance was explained in models including literacy and numeracy together compared with each alone (data not shown).For all sub-scales, the importance of both literacy and numeracy was similar to the pattern observed for the overall scale see . Higher 44.1In this sample of older American adults, higher literacy and numeracy skills were independent and comparable predictors of successful health task performance. This finding was maintained when both were entered into the same model, and after controlling for participant characteristics such as age, gender, race, education, and comorbidity. Entering both skills into the model in tandem led to a significant increase in the amount of variance explained in health task performance. Considering literacy or numeracy skills in the performance of routine health tasks may be important, but researchers and clinicians should be mindful of both skills to maximize the chances of successful intervention.These findings support our earlier work and that of others demonstrating the importance of health literacy in common self-management health tasks, such as recalling spoken instructions and comprehending written information The IOM definition outlines health literacy as a skills-based construct that facilitates effective health self-management Our findings also have implications for health literacy measurement by demonstrating the importance of using assessments that include tests of both literacy and numeracy skills. Studies using literacy assessments such as the REALM, which served as the foundation of the health literacy field for decades, may need to be complemented by numeracy scales to ensure all elements of health literacy are captured. Researchers developing new health literacy measures may wish to consider taking the approach of the TOFHLA by offering two separate sub-scales that reflect literacy and numeracy abilities.Finally, it was noticeable that average performance scores on these simple tasks were well below the maximum. This was particularly striking given the high levels of education reported in our sample, where nearly 60% had a college degree or more. This is higher than city-wide estimates for Chicago, where approximately 35% of adults are reported to have a Bachelor's degree or higher This study had limitations. The outcome measure used in the study was a series of hypothetical tasks confined to a laboratory setting. Although every effort was made to ensure the validity of the scenarios, participants may have reacted differently when performing the tasks and making decisions in everyday life. The sample was also older, predominantly White and reported high levels of education and health literacy which may limit the generalizability of the findings beyond this cohort. There were particularly obvious ceiling effects on the TOFHLA-R and REALM assessments and therefore careful consideration should be given when using these assessments among older adults. Visual acuity was not controlled for in these analyses, and so it is possible that a proportion of the variance attributed to literacy and numeracy was actually due to problems with vision. Finally, these observations were cross-sectional which limits inferences about causality.4.2In this sample of older American adults, literacy and numeracy skills were independent and comparable predictors of successful health task performance. Considering both abilities together significantly increased the amount of variance explained. These findings suggest that literacy and numeracy should be considered in health literacy measurement and in future intervention strategies.4.3A systematic review of complex health literacy interventions demonstrated that all 15 identified trials focused on literacy rather than numeracy The authors report no conflicts of interest.National Institutes of Health under award number R01AG030611. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr. Smith is currently supported by a Cancer Research UK Postdoctoral Fellowship (C42785/A17965).Research reported in this publication was supported by the National Institute of Aging of the


Inappropriate use of stress ulcer prophylaxis (SUP) is common in many hospitals. High-quality clinical practice guidelines (CPGs) produce better patient outcomes and promote cost-effective clinical care. Thus, the objective of this study was to evaluate the quality of CPGs for SUP.A search was conducted for SUP CPGs using PubMed, Embase, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature database (CBM), guideline websites and Google . The quality of CPGs was independently assessed by two assessors using the Appraisal of Guidelines for Research & Evaluation II (AGREE II) instrument, and the specific recommendations in the CPGs were summarized and evaluated.A total of 7 CPGs for SUP were included. The highest median scores were in the clarity of presentation domain (89%), and the lowest median scores were in the editorial independence domain (0%). The rigor of development, stakeholder involvement, and applicability domains all scored below 40%. The specific recommendations for SUP varied, and the recommendations were inconsistent with the supporting evidence.The overall quality of CPGs for SUP was relatively low, and no specific SUP CPG can be recommended. Not only should the AGREE II instrument be used to determine the quality of CPGs, but also the recommendations should be appraised based on supporting evidence, which would contribute to the development of high-quality CPGs. Stress ulcer prophylaxis (SUP) is commonly used to decrease gastrointestinal bleeding in both critically and non-critically ill patients –3. To heMany studies suggested that the inappropriate use of SUP, based on these guidelines, is common in hospital –12. CPGsTo the best of our knowledge, there has been no evaluation of SUP guidelines. Thus, we conducted this study to evaluate the quality of a group of international CPGs for SUP and to help develop, update or improve SUP guidelines, and to help clinicians reduce the inappropriate use of SUP.We searched PubMed, Embase, China National Knowledge Infrastructure (CNKI) and Chinese Biomedical Literature Database (CBM) for SUP guidelines . The text words and Medical Subject Headings (MeSH) terms were as follows: (guideline or guidelines or consensus) and “stress ulcer prophylaxis”. The CPGs search was conducted on major guideline websites, including the National Guideline Clearinghouse, National Institute for Health and Clinical Excellence, Scottish Intercollegiate Guidelines Network, Guidelines International Network and China Guideline Clearinghouse. The search term was “stress ulcer prophylaxis”. Google was also searched using the terms “guideline” and “stress ulcer prophylaxis”, and we reviewed the first 100 results. No restriction on language was applied.CPGs for SUP included those that provided clinical recommendations and strategies to assist health care practitioners in making decisions and those that were endorsed by medical specialty associations or relevant professional societies. We excluded guidelines that were not original, were duplications, or were explanations of CPGs.Two assessors, one with experience in developing and evaluating guidelines (Z.K.Y) and another assessor (Y.L), used the online training tools recommended by the AGREE collaboration before conducting appraisals. They independently evaluated the included guidelines using the AGREE II instrument , which cAfter determining the quality of SUP guidelines using the AGREE II instrument, the specific recommendations made in the included guidelines were summarized and evaluated, including indications for SUP, agents for SUP and duration of prophylaxis.A total of 600 records were identified, of which, 185 were duplications, 385 were either not relevant to SUP or not guidelines after screening titles and abstracts, and the remaining 30 records were retrieved for full text. Finally, 7 CPGs . Only the AHSP CPG scored above 60% for this domain [–61%. OnlThe median score for the rigor of development domain was 27% (range 6–77%). The ASHP and DASAIM CPGs scored above 60% ,21. OnlyThe median score for the clarity of presentation domain was 89% (range 67–94%). All guidelines scored above 60%. Most guidelines provided specific, unambiguous and easily identifiable recommendations.The median score for the applicability domain was 38% (21–54%). No guideline scored above 60%. No guideline systematically described the facilitators and barriers of its applications very well. Most guidelines did not sufficiently consider the costs of applying their recommendations, and no guideline involved a health economist in finding and analyzing cost information.The median score for the editorial independence domain was 0% (0–33%). No guideline clearly provided funding information. Only the DASAIM CPG described the competing interests of the guideline development group members . The AHSIn 2RAs) for SUP, five CPGs  recommended using both PPIs and H2RAs, and the ASHP CPG did not recommended using PPIs. Three CPGs  recommended using antacids for SUP, while two CPGs  recommended using sucralfate for SUP. The EAST CPG recommended cytoprotective agents for SUP, and the NMJC CPG recommended mucosal protective agents.Recommendations on agents for SUP were not consistent across these guidelines. The DASAIM CPG recommended using proton pump inhibitors (PPIs) rather than histamine 2 receptor antagonists . However, after excluding trials at high risk or unclear risk of bias, the results suggested that there was no significant difference between PPIs and H2RAs  [The DASAIM CPG recommended using PPIs rather than H = 0.21) . TherefoRecommendations on duration of prophylaxis are moderately consistent. Five CPGs  recommended that prophylaxis should be discontinued when there was no risk factor for SUP, three CPGs  recommended that prophylaxis be discontinued when the patient can tolerate enteral feeding, and two CPGs (DASAIM and NMJC) did not provide recommendations on duration of prophylaxis. When we evaluated the original studies supporting the recommendations, we found no-high quality studies on duration of prophylaxis.The DASAIM, ASHP and EAST CPGs were recommended with modifications ,18,21, wThis is the first study to systematically evaluate the quality of SUP guidelines. The overall quality of these CPGs was relatively low; the clarity of presentation domain showed the highest scores, while the editorial independence domain showed the lowest scores. Not only should the AGREE II instrument be used to determine the quality of CPGs, but also the recommendations should be appraised based on supporting evidence.These guidelines had high clarity of presentation scores, indicating that this domain was more easily achieved than other domains. The editorial independence domain was poorly described. No guideline provided funding information, and only two guidelines described competing interests. Perhaps guideline developers do not like disclosing their funding information, or perhaps they do not realize the importance of conflict of interest disclosures and management. Studies have shown that financial conflicts of interest are prevalent among CPGs in a variety of clinical areas ,26, and The rigor of development, stakeholder involvement and applicability domains all scored below 40%, and there were serious methodological flaws in these three domains. The median score for the rigor of development domain was 27%. Most guidelines described neither systematic methods for evidence searching nor methods for formulating recommendations very well. Only the DASAIM CPG indicated that the guideline was reviewed by external experts, and no guideline provided procedures for updating guidelines. The median score for the applicability domain was 38%. Most guidelines did not consider the potential resource implications of applying recommendations, nor did they pay proper attention to potential barriers to guideline implementation.The median score for the stakeholder involvement domain was 39%. No guideline considered the views and preferences of target populations; however, the involvement of patients in decision making might promote patient guideline adherence and improve clinical outcomes . Most gu2RAs. Guideline developers should critically appraise the validity of systematic reviews and other sources of evidence formulating recommendations.The specific recommendations made in the included CPGs varied, probably due to the lack of high-quality studies on the indications for SUP and the duration of prophylaxis. Guideline developers failed to critically appraise the validity of the evidence, which led to the inconsistency between the recommendations and the supporting evidence. The DASAIM CPG rated the quality of evidence and graded the strength of recommendations using the GRADE approach, and recommendations were formulated based on a systematic review, thus scoring the highest in the rigor of development. However, high AGREE II domain scores do not imply that a guideline should be recommended. When we appraised the DASAIM CPG, we found that some recommendations were not consistent with the supporting evidence. The outcomes of trials with low risk of bias did not suggest that PPIs were better than HAll potentially relevant studies were retrieved by searching medical databases, five guideline websites and Google. This study also has limitation. The AGREE II instrument established an evaluation system for guideline development and reporting, but the appraisal of guideline recommendations is not stated.In conclusion, the overall quality of CPGs for SUP was relatively low, no specific SUP CPG can be recommended to guide clinical practice. Not only should the AGREE II instrument be used to determine the quality of CPGs, but also the recommendations should be appraised based on supporting evidence, which would contribute to the development of high-quality SUP CPGs.S1 Fig(DOC)Click here for additional data file.S1 Table(DOC)Click here for additional data file.


Bone has the capacity to regenerate and not scar after injury – sometimes leaving behind no evidence at all of a prior fracture. As surgeons capable of facilitating such healing, it becomes our responsibility to help choose a treatment that minimizes functional deficits and residual symptoms. And in the case of the geriatric hip fracture, we have seen the accumulation of a vast amount of evidence to help guide us. The best method we currently have for selecting treatment plans is by the practice of evidence-based medicine. According to the now accepted hierarchy, the best is called Level I evidence  – but this evidence is best only if it is available and appropriate. Lower forms of accepted evidence include cohort studies, case control studies, case series, and case reports, and last, expert opinion – all of which can be potentially instructive. The hallmark of evidence-based treatment is not so much the reliance on evidence in general, but to use the best available evidence relative to the particular patient, the clinical setting and surgeon experience. Correctly applied, varying forms of evidence each have a role in aiding surgeons offer appropriate care for their patients – to help them best fix the fracture. The management of fragility hip fractures, now 300,000 plus in the US yearly, may seem superficially to be among the most studied and settled questions in orthopedic surgery: even the geographic variations in incidence of operative management of fragility hip fractures show low variation . Many suYet even if we accept that fragility fractures of the hip should be treated surgically, numerous questions remain. Which procedure is best: joint replacement or fixation? If replacement is chosen, should it be total or hemiarthroplasty? Which surgical approach is better? Should the implant be cemented? And how soon should the patient be taken to the operating room? Figure . These qThe purpose of this presentation is to illustrate the methods (and limitations) of the evidence-based medicine approach in the management of fragility hip fractures.The commonly quoted definition is attributed to Sackett : “EvidenThis assumes that physicians’ decisions should rely on evidence of the highest quality. Accordingly “levels of evidence” hierarchies have been devised, the essence of which “is that, in general, controlled studies are better than uncontrolled studies, prospective studies are better than retrospective studies, and randomized studies are better than non-randomized studies” . NeverthAlso, randomized controlled studies can be misleading; lower level studies can be informative; expert opinion is inextricably tied to the evaluation and implementation of evidence; useful information may be found in places not even on the evidence hierarchy; perfect information about treatment options and outcomes is insufficient.When a study is defined prospectively, the researcher will be aware of, and required to explain, subject drop out rates, lost to follow-up status, or failure of subjects to receive the treatment they were assigned to receive.When the study is “double blinded,” neither the subjects nor the examiner knows which treatment the subject got and thus helps avoid patients’ or surgeons’ aspirations coloring the outcomes.Randomization refers to the allocation of subjects to groups according to a purely chance process. A pure experiment would expose two cohorts of identical subjects to identical stimuli but for the item of interest. Because that cannot happen outside of the laboratory, the random allocation of a large number of subjects is used to ensure that our groups are as equal as possible, especially with regard to feature whose importance is unknown.The use of a control group allows one to state the relative efficacy of the intervention. For example, one recent study  reportedThe prospective, double-blinded randomized controlled trial is the most powerful design to avoid biases (and ultimately wrong conclusions).your patient (who may never have met inclusion criteria for the study). Larger studies that are able to stratify based on secondary independent variables of interest  can help determine whether the conclusions apply to your particular population, though such sub-group analyses must be carefully interpreted  is better than mid-level evidence . Nevertheless, these mid-level sources of evidence play an important role in the practice of evidence-based medicine, chiefly because high-level evidence is so rare. Brooke et al. , for exaThe lack of high quality evidence is not an indictment of researchers; sometimes mid-level evidence is best. Consider how the dangers of smoking were detected. No study took 10,000 twins, forced 5,000 of them to smoke on a regular basis for 40 years and thereafter assessed the rate of lung cancer in the two groups. Constrained by practicality, the toxic effect of cigarette smoke was found by case–control methods: studies looked at groups of people who currently have lung cancer (cases) or do not have it (controls), and assessed whether there was a higher rate of cigarette smoking in the lung cancer group. It is just not feasible to run a trial over four decades or to force a potentially detrimental “treatment” upon patients.Ideally, evaluation of a novel surgical intervention will have a control group; and when the outcome is pain relief, the addition of a sham control group would be even better . However, while randomization is a powerful tool in study design, it is not always feasible or ethical to proceed with a randomized, controlled trial. For example, while theory would suggest that the timing of operative debridement of an open fracture wound is best determined with a randomized trial, it is unacceptable to mandate that patients with open fractures suffer an unnecessary delay in their treatment simply because they were randomized to that treatment arm.Observational designs can be useful tools when outcomes are rare rendering clinical trials too costly and too inefficient to answer a question in a timely manner. Most randomized trials fall victim to so-called Type II error , simply due to an inability to recruit enough patients. On average, surgical trials are 1/10th the size needed to confirm important treatment effects.A “differential expertise bias” is inherent in most, if not all, studies in orthopedic surgery involving surgical treatment. This is a particular concern when subjects are randomized between two groups and the skill with which they are treated may vary according to their randomization, either because the surgeon may not be equally adept with both techniques, or because different surgeons are used in the different treating arms of the study [In one study  comparinAlthough the levels of evidence hierarchy suggests that evidence is improved the more it is resistant to human biases, the role of experts and importance of expertise is central to the practice of evidence-based medicine. Bear in mind that clinical studies are not the findings of naturalists, collecting observations on pure biological phenomena; they are the answers to questions posed by people (researchers) recording the effects of interventions created by people (inventors) and practiced by people (surgeons) in the service of other people (patients). That is, the questions addressed in clinical papers are the questions defined by the experts; the treatments under scrutiny are the treatments devised and implemented by experts. The role of experts cannot be excised.Furthermore, and perhaps no less importantly, clinical studies are read and employed only to guide the application of one’s individual skills, i.e., personal expertise. Consider that one study in the literature  has suggOverall, the literature can at best inform the reader, which of the available choices is optimal; and if what the literature suggests is not available – because of the reader’s particular expertise or lack thereof – then clearly some other solution must be applied.The appraisal of evidence also relies on expertise. Recall that “the probability that a research finding is indeed true”  is not mHence, because studies can be falsely negative or falsely positive, findings should not be accepted as canonical facts; rather, a study simply changes the likelihood that what it found is actually true. Consider a recent study  that exaThe probability that cementing is superior, after considering this study, depends on two factors: how good the study was and how likely it was – before the study was done – that cementing was indeed superior. The first factor requires contemplation of potential biases and errors in the study, and the nature (level) of the evidence at hand. One must scrutinize the study with all of the tools of evidence-based medicine and make some assessment that the study as described would possibly produce false negative or false positive results. Yet the ultimate truth-value of the study depends also on the reader’s pre-test probability assessment of the results. And at some point, that prior probability is based on expert opinion – if not one’s own, than of one’s teachers, or of textbooks and the like. Medical literature cannot be interpreted without any idea of prior probability. A mere change of the prior probability from 20 to 30% determines whether the study’s findings are more likely than not to be true. And these probabilities must rest at least in part on expert opinion.The diagnosis of a displacement of a femoral neck fracture seems to be straightforward. Nevertheless, this is a diagnosis that is made with far from perfect accuracy. Two studies examining the accuracy of displacement of femoral neck fractures implicitly found that at least 15% of cases were mislabeled. These studies, it should be pointed out, did not set out to measure accuracy, but rather reliability. However, while reliability is not equivalent to accuracy, it is a necessary condition for it. One could not be consistently accurate without being consistent in general.A reliability analysis regarding a binary feature  can also provide an upper bound on the average accuracy of the two viewers. That is because when two surgeons disagree about displacement, one of them must be wrong. Accordingly, each instance of disagreement represents one error (out of the two paired observations) and as such the square root of the agreement rate is an approximate upper bound on the average accuracy. Thus, when Oakes et al.  report aOne proposed approach centers on the observation that if errors are random, chance events, then greater reliability (and in turn greater accuracy) might result from having multiple readers . In a reThe amalgamation of a consensus diagnosis  is a form of crowd intelligence. Crowd intelligence was first suggested by Galton , who notNature .Thus, if one knows how much each outcome is worth, and knows the likelihood that each outcome could be attained, one can measure the value of each option. Accordingly, picking the best option is simply choosing the one with the highest expected utility. Figure With that equation in hand, one sees that even if we stipulate that the rate of revision operations is 10 times higher with fixation operations  . If there is a 58% of attaining success with ORIF, then the value of this option is (100 × 0.58) + (0 × 0.42), i.e., 58 utility points. For arthroplasty, the expected utility is (60 × 0.96) + (0 × 0.04) or 57.8 points.A surgeon practicing evidence-based medicine cannot impose his or her values on the patient, but rather must attempt  to disceThe management of fragility fractures of the hip follows rule that are perhaps easy to state, but perhaps not so easily applied. We can agree that patients must be taken to the operating room as soon as possible – but how soon is that? We might agree that displaced fractures should be treated with joint replacement, but we might not agree that a given fracture is displaced. We can agree on the theoretical superiority of a particular technique, method or approach, but we also agree that a particular surgeon managing a particular case should be granted broad deference to his judgment and skills. For instance, a cemented total hip replacement inserted via the lateral approach might be most reliable, unless the surgeon is more proficient at some other technique. And we all agree that surgeons must respect patients’ autonomous decisions, even if our tools for discerning patient preferences are imperfect at best.It may be tempting to shift the uncertainty upstream – to strive to make the best decisions to help prevent the fracture in the first place and thereby avoid the dilemmas associated with treatment. Then again, the area of prevention, too, is fraught with its own decision making dilemmas. Whitaker et al.  recentlyWith that in hand, we would be wise to emphasize the first clause of Sackett’s definition “The practice of evidence-based medicine means integrating individual clinical expertise with the best available external clinical evidence from systematic research.” In the end, the practice of medicine relies as much on individual clinical expertise – the art of medicine – as it does numbers, data and study conclusions. Improving the quality and quantity of clinical evidence collected – only when combined with improving the education and expertise of practitioners in applying that evidence – will lead to better surgical decision making and thereby inform us how best to fix the fracture.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.