Psychological distress is common among medical students but manifests in a variety of forms. Currently, no brief, practical tool exists to simultaneously evaluate these domains of distress among medical students. The authors describe the development of a subject-reported assessment  intended to screen for medical student distress across a variety of domains and examine its preliminary psychometric properties.Relevant domains of distress were identified, items generated, and a screening instrument formed using a process of literature review, nominal group technique, input from deans and medical students, and correlation analysis from previously administered assessments. Eleven experts judged the clarity, relevance, and representativeness of the items. A Content Validity Index (CVI) was calculated. Interrater agreement was assessed using pair-wise percent agreement adjusted for chance agreement. Data from 2248 medical students who completed the MSWBI along with validated full-length instruments assessing domains of interest was used to calculate reliability and explore internal structure validity.Burnout , depression, mental quality of life (QOL), physical QOL, stress, and fatigue were domains identified for inclusion in the MSWBI. Six of 7 items received item CVI-relevance and CVI-representativeness of ≥0.82. Overall scale CVI-relevance and CVI-representativeness was 0.94 and 0.91. Overall pair-wise percent agreement between raters was ≥85% for clarity, relevance, and representativeness. Cronbach's alpha was 0.68. Item by item percent pair-wise agreements and Phi were low, suggesting little overlap between items. The majority of MSWBI items had a ≥74% sensitivity and specificity for detecting distress within the intended domain.The results of this study provide evidence of reliability and content-related validity of the MSWBI. Further research is needed to assess remaining psychometric properties and establish scores for which intervention is warranted. Medical school is a profoundly difficult time for physicians in training. Approximately 25% of medical students are depressed , 50% expdistress to broadly refer to depression, anxiety, burnout, and related mental health problems). Prompt identification of students in distress would allow schools to identify the challenges faced by their medical student population, provide assistance to those in greatest need, and help prevent the serious consequences by alleviating student suffering. The ability to accurately identify student distress would also allow schools to monitor their learning environment and evaluate the effectiveness of programs intended to promote the well-being of students - accreditation requirements for U.S. medical schools [These facts highlight the compelling need for medical schools to identify student distress  used to assess distress are long, cumbersome to analyze, and typically measure only 1 domain of distress . In the absence of such an instrument, we have set out to develop a shorter measure of student distress  intended to screen for the common dimensions of distress experienced by medical students and identify the subset of students whose distress places them at risk for serious consequences. This article describes the development of this instrument as well as some evidence for its reliability and validity.The methods consist of a two-stage process. First, in the development stage we identified relevant domains of distress, generated items, and wrote, ordered, and assembled the instrument into a usable form. Second, the judgment stage consisted of expert review of item for clarity, relevance, and representativeness in conjunction with administering the MSWBI to >4000 medical students to obtain data for estimating reliability and validity.To complete a thorough literature review to identify common aspects of student distress we repeated the MEDLINE search conducted to inform our systematic review on medical student distress  using thThe Ad Hoc panel of Deans consisted of 8 Deans/Associated Deans from 7 diverse  medical schools. The Deans were asked: if there is a need for a short instrument to screen for distress among medical students, if the manifestations of distressed selected by the content experts were appropriate, if there were other aspects of distress that should be included, and if any of the domains suggested by the content experts were inappropriate. Additional qualitative feedback was also requested. The nominal group members reviewed the Deans' feedback and finalized the construct definition by consensus.Anonymized medical student responses to previously administered comprehensive instruments assessing three of the identified aspects of student distress - burnout , qualitWe calculated Spearman Correlation Coefficients to identify questions on the Maslach Burnout Inventory with the highest correlation coefficient to burnout   and emotmedical student, resident, intern, internship and residency, physicians, and fatigue, sleep deprivation, or stress. The search was limited to articles published in English within the last 10 years (1996 to 2006). Extracted from these articles were the standardized tools used to assess fatigue or stress. A brief review of the non-physician literature on instruments used to assess fatigue, sleep deprivation, or stress was also conducted. The identified instruments were reviewed by nominal group members who selected scales and items that best captured the relevant domain using an iterative process.For the remaining two aspects of distress- stress and fatigue - a thorough literature review was conduced on MEDLINE for peer-reviewed articles reporting primary data on stress and fatigue in medical students, residents, and physicians. Medical subject heading terms used were combinations of st through 4th year medical students, who attended medical schools not previously part of our multi-institutional study group, reviewed the new items. These students were asked to comment on the suitability and readability of the items. The students were also asked if other aspects of distress should be included. Some questions were revised to improve clarity based on student feedback.Considering each domain and sub-domain of student distress and the best corresponding item(s) from existing instruments, 7 new items for the MSWBI were written, ordered, and assembled in a usable form by the first author (LND). All response options were a yes/no option consistent with a screening instrument format. These new items were further refined to improve clarity by nominal group members after having evaluated the reasonableness of relationship between the intended domain and new item. As it is important for members of the target audience of the instrument to be involved in content validation of the instrument  five 1stThe judgment stage consisted of expert review of domain relevance and representativeness of items in conjunction with numerical summarization of the instrument using a statistical index of item-domain congruence  and examLastly, in 2007, 2248 medical students attending Mayo Medical School, University of Washington School of Medicine, University of Chicago Pritzker School of Medicine, University of Minnesota Medical School, University of Alabama School of Medicine, University of California San Diego School of Medicine, and the Uniformed Services University of the Health Sciences completed a web-based survey containing the MSWBI along with the Maslach Burnout Inventory, the PRIME MD, SF-8, the Epworth Sleepiness Scale ,31, and Institutional review board approval was obtained at each institution involved in the 2004, 2006, and 2007 study prior to surveying of their students. The surveys were administered electronically. On each occasion students were sent an e-mail message with cover letter that informed them about the study and linked to the web-based survey. Participation was elective and all responses were anonymous. The University of Illinois at Chicago institutional review board  approved the remainder of the study pertaining to instrument development and validation.From the literature review depression, fatigue, quality of life, burnout, global mental health, anxiety, cynicism, stress, healthy habits, and substance use were identified as aspects of student distress  and "I feel emotionally drained from medical school". The modified-Maslach Burnout Inventory items with the highest correlation coefficient to overall burnout and depersonalization were "I've become more callous toward people since I started medical school" and "I worry that medical school is hardening me emotionally".For the SF-8 the item "During the past 4 weeks, how much difficulty did you have doing your daily work, both at home and away from home, because of your physical health?" had the highest correlation with physical quality of life  whereas the item "During the past 4 weeks, how much have you been bothered by emotional problems ?" had the highest correlation with mental quality of life (r = .94 for both data sets).Among the PRIME MD questions the item "During the past month have you often been bothered by feeling down, depressed, or hopeless" had the highest correlation coefficients of 0.91 and 0.92.The nominal group members chose the Epworth Sleepiness Scale among the fatigue instruments identified as it assesses daytime sleepiness and has been previously used in residents and medical students ,31. The After assembly of the MSWBI consensus was reached among the nominal group members that an obvious and logical relationship existed between the domains and the new items. Group members refined the items to improve clarity. All 5 students reviewed the MSWBI and agreed that 5 of 7 items were suitable for inclusion; one student disagreed with the fatigue item and 2 students thought the item assessing depressive symptoms was redundant with the item assessing global mental quality of life. Three items were identified with poor readability and suggestions for revisions were provided. Based on this feedback, these items were re-written to improve clarity. The students did not identify any additional domains of distress that should be added. The final questions derived from development stage are shown in Table The majority of items . Percent of time responding medical students endorsed each possible paired combination of Medical Student Well-Being Index items (e.g. item by item percent pair-wise agreements) are shown in Table Distress is pervasive among medical students with some students suffering serious consequences. Given the high prevalence of distress it may be impractical or impossible to intervene on an individual level with every student in distress. Ideally, schools need to be able to identify students with degrees of distress that may place them at risk for serious personal or professional consequences. Given the impracticality of administering existing long diagnostic instruments evaluating the individual domains of distress and the reluctance on behalf of students to seek help for their distress a short, pragmatic instrument that screens for the common dimensions of distress experienced by medical students and identifies students at greatest risk for serious personal and professional consequences would be of use to medical schools. Using appropriate methods of content development ,28 we deAlthough the MSWBI needs further validation before widespread use can be recommended, it has the potential to be a useful tool for medical schools and their students. Unlike long surveys designed to be diagnostic tools to evaluate individual domains of distress, the MSWBI has only 7 items, covers multiple aspects of distress, and is easy to administer and complete. For screening questionnaires to be helpful they need to be brief, easy to administer, valid, reliable, and sensitive. Content-related evidence, response process validity evidence, and internal structure validity evidence are part of a broader set of construct-related evidence . ConsideThis study has several limitations. First, distress is a multi-dimensional construct. We may have left out some aspects of distress that are important, or included some that should have been left out, or both . Second,There are also several strengths of our study. First, to our knowledge, this is the first study to use established and validated methods to develop a screening instrument for distress among medical students. Second, we used a rigorous and standard process for development and judgment of the instrument ,28. We cTo our knowledge, this is the first study to use established and validated methods to develop a screening instrument for distress among medical students. Given the importance of well-being in physicians across training this brief 7-item instrument has potential to be useful. The ability of the MSWBI to identify those individuals whose distress is placing them at risk for serious adverse consequences such as suicidal ideation, leaving medical school, or substance abuse warrants further exploration. Early identification of students whose degree of distress places them at risk for adverse consequences is vital to ensuring prompt intervention and appropriate allocation of resources to assists those in greatest need. The MSWBI is a promising screening tool to identify medical student whose degree of distress places them at risk for adverse outcome. Continued research is needed to further validate and refine the MSWBI to maximize its sensitivity and usefulness as a screening instrument.(CVI): Content Validity Index; (ESS): Epworth Sleepiness Scale; (MSWBI): Medical Student Well-Being Index; (SF-8): Medical Outcomes Study Short Form; (PSS10): Perceived Stress Scale 10-item; (PRIME MD): Primary Care Evaluation of Mental Disorders; (QOL): Quality of lifeThe authors declare that they have no competing interests.LND conceived of the study, acquired the data, interpreted the data, drafted the manuscript and revised it. DWS and JAS acquired the data, conducted the data analysis, interpreted the data, and revised the manuscript. SMD participated in study design and interpretation of data and revised the manuscript. TDS conceived of the study with LND, interpreted the data, and critically revised the manuscript. All authors approved the final manuscript.Liselotte N. Dyrbye, MD MHPE is assistant professor of medicine, Mayo Clinic College of Medicine, Department of Medicine. Dr. Dyrbye is the Associate Director, Research Applications, Mayo Clinic's Program on Physician Well-being. She has 24 peer-reviewed publications of which 11 pertain directly to trainee or physician well-being.Daniel W. Szydlo, BA was a statistician, Mayo Clinic Department of Health Sciences Research at the time of the study. He is now a graduate student at University of Washington, Seattle, Washington.Steven M. Downing, PhD is associate professor of medical education, University of Illinois-Chicago College of Medicine, College of Medicine. Dr. Downing's research interest in educational measurement and assessment in medical education has resulted in more than 100 research papers, book chapters, and presentations.Jeff A. Sloan, PhD is professor of oncology, Mayo Clinic Department of Health Sciences Research. Dr. Sloan is statistician with extensive expertise in quality of life research.Tait D. Shanafelt, MD is associate professor of medicine, Mayo Clinic College of Medicine, Department of Medicine. Dr. Shanafelt is the Director of the Mayo Clinic's Program on Physician Well-being and has published extensively in the field of trainee and physician well-being.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6920/10/8/prepub


Over the past decade, several large epidemiologic investigations of meat intake and prostate cancer have been published. Therefore, a meta-analysis of prospective studies was conducted to estimate potential associations between red or processed meat intake and prostate cancer. Fifteen studies of red meat and 11 studies of processed meat were included in the analyses. High vs. low intake and dose-response analyses were conducted using random effects models to generate summary relative risk estimates (SRRE). No association between high vs. low red meat consumption  or each 100 g increment of red meat  and total prostate cancer was observed. Similarly, no association with red meat was observed for advanced prostate cancer . A weakly elevated summary association between processed meat and total prostate cancer was found , although heterogeneity was present, the association was attenuated in a sub-group analysis of studies that adjusted for multiple potential confounding factors, and publication bias likely affected the summary effect. In conclusion, the results of this meta-analysis are not supportive of an independent positive association between red or processed meat intake and prostate cancer. Worldwide, prostate cancer is the second most common cancer among men, with only lung cancer accounting for more cancer diagnoses annually, although the incidence of prostate cancer varies considerably by geographic region . Indeed,Although diet and prostate cancer has been investigated in numerous epidemiologic studies, few foods have been identified as potentially contributing to increasing or decreasing the risk of this malignancy. High intake of foods containing lycopene and selenium may decrease risk of prostate cancer while diets high in calcium may increase risk ,13, althOver the last decade, several large cohort studies of meat intake and prostate cancer have been published, and in a recent systematic review of dietary factors, it was suggested that high meat consumption may increase the risk of prostate cancer, although the authors did not quantify the relationship . In theiprostate cancer AND (meat OR beef OR pork OR lamb), yielding 143 articles. A supplemental search was conducted using fat AND prostate cancer, which yielded 482 additional articles. In addition, the bibliographies of review articles pertaining to diet and prostate cancer were examined in an effort to identify all available literature that may not have been identified by the PubMed search. Prospective epidemiologic studies, published in the English language, that reported results for the association between red meat or processed meat consumption and prostate cancer were included in this meta-analysis. Case-control studies, ecologic assessments, correlation studies, and other publications of aggregate-level analyses were excluded, as were experimental animal studies and mechanistic studies. Studies that reported only data for a broad classification of meat, such as 'total meat' categories, which included poultry or fish, were excluded. Studies were required to report point estimates  and measures of variability  for a high category of red or processed meat intake compared with the lowest category of intake, or data were required to be available for such calculations.A PubMed search of articles published through January, 2009, was conducted to identify studies eligible for review. The primary search string included the following terms: Qualitative information and quantitative data were extracted from each study that met the criteria for inclusion. Specifically, information was extracted pertaining to: the year of the study, the study population , geographic location of the study, years of follow-up, methods of dietary exposure ascertainment, red meat and processed meat dietary variables and how these variables were defined, the analytical comparison , the number of exposed cases, the relative risk estimates and 95% confidence intervals, and the factors that were adjusted or controlled for in the analyses. A thorough review of each article was conducted to identify cohorts that may have been analyzed in multiple publications. If results were reported in multiple publications, the inclusion of data was based on 1) the size of the study population, 2) duration of follow-up with an emphasis on the most recent publication with the longest follow-up, 3) classification and analytical categorization of red or processed meat, and 4) level of control for potential confounding factors.Random effects models were used to calculate summary relative risk estimates (SRRE), 95% confidence intervals, and corresponding p-values for heterogeneity. This type of model assumes that the study-specific effect sizes come from a random distribution of effect sizes according to a specific mean and variance . Red meaPublication bias was assessed by generating funnel plots for a visual examination, conducting correlation and regression tests for significance, and using a 'trim and fill' procedure to evaluate symmetry around the summary effect . All anaThe characteristics and findings of the prospective studies of red and processed meat and prostate cancer are summarized below and in Table In a recent analysis of the Agricultural Health Study, which followed a cohort of 57,311 licensed pesticide applicators from Iowa and North Carolina, Koutros et al.  reportedIn the largest study of red/processed meat and prostate cancer to date, Cross and colleagues  analyzedIn an analysis of the prospective American Cancer Society's (ACS) Cancer Prevention Study II (CPS II) Nutrition Cohort, Rodriguez et al.  reportedIn an analysis of over 1,300 prostate cancer cases in the multi-center Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, RRs comparing the highest vs. lowest intake levels of red meat were below 1.0 and non-significant for all prostate cancer cases, incident cases only, and advanced cases only  . AssociaIn their analyses of data from the Health Professionals Follow-Up Study, Michaud et al.  observedPark et al.  examinedAllen et al.  evaluateIn the Netherlands Cohort Study (NLCS), Schuurman et al.  reportedIn a modestly sized study of almost 4,000 participants from the CLUE II cohort, red and processed meat intake was analyzed for approximately 200 cases of prostate cancer . MultivaChan et al.  evaluateIn a prospective study of diet and prostate cancer among Japanese men exposed to radiation during the bombings of Hiroshima or Nagasaki, the association between "almost daily" consumption of pork (versus < 2 times/week) was associated weakly and non-significantly with risk of prostate cancer  . No otheIn a nested case-control study conducted within the Physicians' Health Study cohort, the RR <1) , although this result was adjusted for age only.Le Marchand et al. , in a muIn a cohort of 17,633 white male Lutheran Brotherhood Insurance policy holders ("The Lutheran Brotherhood Cohort Study"), Hsing and colleagues  observedNo association between consumption (high vs. low intake) of red meat and total prostate cancer was observed in the meta-analysis of 15 prospective studies   , and none of the associations were statistically significant . Furthermore, the three studies that were not as fully-adjusted were published prior to the year 2000 and were not as large as the other studies. In addition, there was evidence of publication bias in the meta-analysis of processed meat. Theoretically, if all relevant studies were included in the meta-analysis, it would be expected that the funnel plot would be symmetric , which was not the case for processed meat  . HoweverAlthough an evaluation of correlates of meat consumption and prostate cancer is beyond the scope of the current assessment, a few factors thought to contribute to positive associations are worth mentioning. Few studies examined fat intake from animal sources, particularly red meat sources, and prostate cancer. Le Marchand et al.  reportedInvestigations of cooking practices, meat doneness, and dietary mutagens have not produced patterns of associations consistent with increasing the risk of prostate cancer, although the available epidemiologic data are limited to few studies. Barbequed and pan-fried meat has been associated inversely with prostate cancer in three large prospective studies ,29,41. HIn the current quantitative assessment of red meat and processed meat intake and prostate cancer, data from prospective studies were analyzed, with the majority of data coming from large cohorts published within the past eight years. Collectively, most meta-analysis summary associations for red and processed meat were null, or just above or below the null value, and not statistically significant. Summary results for processed meat were weakly elevated; however, the association across the more recently published studies that adjusted for key factors was attenuated and not statistically significant. Furthermore, there was evidence of publication bias across the cohort studies of processed meat. In conclusion, the results of this meta-analysis of prospective studies do not support an independent positive association between intake of red meat or processed meat and prostate cancer.The authors received partial funding support from the Cattlemen's Beef Board, through the National Cattlemen's Beef Association (NCBA). NCBA did not contribute to the writing, analysis, or interpretation of research findings. All data included in this manuscript were extracted from peer-reviewed published literature.DDA contributed to the methodological design, writing, analysis, and completion of the manuscript; PJM contributed to the writing and technical overview; CAC contributed to the database management and editorial review; BS contributed to the data extraction and technical editing. All authors read and approved the final manuscript


Julian Little and colleagues present the STREGA recommendations, which are aimed at improving the reporting of genetic association studies. The rapidly evolving evidence on genetic associations is crucial to integrating human genomics into the practice of medicine and public health ,2. GenetDespite the many similarities between genetic association studies and “classical” observational epidemiologic studies  of lifestyle and environmental factors, genetic association studies present several specific challenges including an unprecedented volume of new data ,6 and thSTrengthening the REporting of Genetic Association studies (STREGA) initiative builds on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modelling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct, or analysis.Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The Although several commentaries on the conduct, appraisal and/or reporting of genetic association studies have so far been published , their rDespite increasing recognition of these problems, the quality of reporting genetic association studies needs to be improved . For exaThe main goal of this article is to propose and justify a set of guiding principles for reporting results of genetic association studies. The epidemiology community has recently developed the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) Statement for cross-sectional, case-control, and cohort studies ,56. GiveA multidisciplinary group developed the STREGA Statement by using literature review, workshop presentations and discussion, and iterative electronic correspondence after the workshop. Thirty-three of 74 invitees participated in the STREGA workshop in Ottawa, Ontario, Canada, in June, 2006. Participants included epidemiologists, geneticists, statisticians, journal editors and graduate students.Before the workshop, an electronic search was performed to identify existing reporting guidance for genetic association studies. Workshop participants were also asked to identify any additional guidance. They prepared brief presentations on existing reporting guidelines, empirical evidence on reporting of genetic association studies, the development of the STROBE Statement, and several key areas for discussion that were identified on the basis of consultations before the workshop. These areas included the selection and participation of study participants, rationale for choice of genes and variants investigated, genotyping errors, methods for inferring haplotypes, population stratification, assessment of Hardy-Weinberg equilibrium (HWE), multiple testing, reporting of quantitative (continuous) outcomes, selectively reporting study results, joint effects and inference of causation in single studies. Additional resources to inform workshop participants were the HuGENet handbook ,58, examIn Recommendation for reporting of methods  frequencies and disease risks differ. When the groups compared in the study differ in their proportions of the population subgroups, an association between the genotype and the disease being investigated may reflect the genotype being an indicator identifying a population subgroup rather than a causal variant. In this situation, population subgroup is a confounder because it is associated with both genotype frequency and disease risk. The potential implications of population stratification for the validity of genetic association studies have been debated . ModelliRecommendation for reporting of methods . It is common in such studies to use statistical methods to estimate haplotypes , and theInformation on common patterns of genetic variation revealed by the International Haplotype Map (HapMap) Project  can be aRecommendation for reporting of methods  has been to construct quantile-quantile (Q/Q) plots whereby observed association statistics or calculated ribution ,130. TheRecommendation: State if the study is the first report of a genetic association, a replication effort, or both. , item 3Articles that present and synthesize data from several studies in a single report are becoming more common. In particular, many genome-wide association analyses describe several different study populations, sometimes with different study designs and genotyping platforms, and in various stages of discovery and replication ,130. WheThe choices made for study design, conduct and data analysis potentially influence the magnitude and direction of results of genetic association studies. However, the empirical evidence on these effects is insufficient. Transparency of reporting is thus essential for developing a better evidence base . TranspaThe STREGA Statement proposes a minimum checklist of items for reporting genetic association studies. The statement has several strengths. First, it is based on existing guidance on reporting observational studies (STROBE). Second, it was developed from discussions of an interdisciplinary group that included epidemiologists, geneticists, statisticians, journal editors, and graduate students, thus reflecting a broad collaborative approach in terminology accessible to scientists from diverse disciplines. Finally, it explicitly describes the rationale for the decisions  and has http://www.strega-statement.org/. We welcome comments, which will be used to refine future versions of the recommendations. We note that little is known about the most effective ways to apply reporting guidelines in practice, and that therefore it has been suggested that editors and authors collect, analyze, and report their experiences in using such guidelines [The STREGA recommendations are available at idelines . We considelines . We emphWe hope that the recommendations stimulate transparent and improved reporting of genetic association studies. In turn, better reporting of original studies would facilitate the synthesis of available research results and the further development of study methods in genetic epidemiology with the ultimate goal of improving the understanding of the role of genetic factors in the cause of diseases.Table S1Editable version of (97 KB DOC).Click here for additional data file.


Environmental genomics and genome-wide expression approaches deal with large-scale sequence-based information obtained from environmental samples, at organismal, population or community levels. To date, environmental genomics, transcriptomics and proteomics are arguably the most powerful approaches to discover completely novel ecological functions and to link organismal capabilities, organism–environment interactions, functional diversity, ecosystem processes, evolution and Earth history. Thus, environmental genomics is not merely a toolbox of new technologies but also a source of novel ecological concepts and hypotheses. By removing previous dichotomies between ecophysiology, population ecology, community ecology and ecosystem functioning, environmental genomics enables the integration of sequence-based information into higher ecological and evolutionary levels. However, environmental genomics, along with transcriptomics and proteomics, must involve pluridisciplinary research, such as new developments in bioinformatics, in order to integrate high-throughput molecular biology techniques into ecology. In this review, the validity of environmental genomics and post-genomics for studying ecosystem functioning is discussed in terms of major advances and expectations, as well as in terms of potential hurdles and limitations. Novel avenues for improving the use of these approaches to test theory-driven ecological hypotheses are also explored. All individuals and populations of individuals forming species live and forage within space and time limits. Understanding the interactions and functions of these organisms within their environment is the purpose of ecology, for which a large range of research strategies has been developed. However, exhaustive analysis of all the functional compartments in a given ecosystem presents a major challenge. Microorganisms , which are essential entities of biogeochemical cycles on the planetary scale e.g. . One of transcriptomics and proteomics; see the glossary for italicized terms) consists in studying large-scale sequence-based information obtained from a variety of environmental samples, at organism, population or community levels, in order to gain novel insights into evolutionary ecology, organism–environment interactions and processes of ecosystem functioning. As such information contains both synchronic (related to current functioning at a given point in time) and diachronic  aspects, the deciphering of genomes, transcriptomes and proteomes is the most powerful and most large-scale approach to date that may link ecology, evolution and Earth history.In the wider sense, environmental genomics in association with post-genomics  mixed prokaryotic-eukaryotic microorganism communities, (2) small-size eukaryotes, especially pico- and nano-eukaryotes, (3) intricate multi-species networks of higher eukaryotic organisms, such as root mats or mixed-species insect swarms, (4) higher eukaryotic organism tissues containing their naturally associated parasitic or mutualistic symbionts and (5) non-model species that cannot be grown or raised under laboratory conditions. In other fields of research such as toxicology and ecotoxicology, environmental genomics generally refers to gene–environment or genome–environment interactions, thus including the study of model species, such as yeast or This review is focussed on environmental genomics and post-genomics in an ecological context, where analyses of large-scale sequence information can reveal how functions and signals are propagated and integrated at the different ecological levels – individual, population, community, ecosystem – and across various temporal and spatial scales. The aim of environmental genomics, transcriptomics and proteomics in an ecological context is to understand the ecosystem ‘dark matter’ ; Box S1,Given the great expectations associated with this recent field of research, we also discuss the validity of environmental genomics and post-genomics for studying ecosystem functioning, in terms of major advances and limitations, and then explore new avenues for improving these approaches to test theory-driven ecological hypotheses.has been framed in terms of functional redundancy […], thus placing the ecological function as a cornerstone, while individuals are only considered as vectors of this ecological function. Hence, the consequences at the ecosystem level of changes at the population level are poorly known . However, linking diversity with the entire set of functions carried out by organisms in their natural habitat remains a major challenge.Clear connections exist between the hierarchic levels of ecological organization from individual to population to community to ecosystem. However, ecosystem ecology, which requires a mechanistic approach, is mainly based on physiological ecology . Ecosystem ecology is thus disconnected from the other ecological levels, and from the rest of ecology, although ignoring the question ‘who’s doing what?’ could be justified by the scale of the analysis. Along with this fact, and as pointed out by ly known . Environ(meta)transcriptomics and (meta)proteomics approaches. It has also been shown that environmental genomics approaches can be coupled with direct probing or labelling of ecological processes. In an elegant work, For over two decades, culture-independent molecular analyses have been used to analyse microbial community and population diversity, and also to study particular functions, such as denitrification or nitrogen fixation. In current environmental genomics studies, the metabolic and physiological potentialities of uncultured (micro)organisms are revealed by analyses of metagenomes see , advanceOne of the most innovating aspects of environmental genomics is the capacity to predict new functions and to infer relationships between functions, whether novel or not, and particular species or specific communities. A classic example is the discovery of a new class of light-driven proton pumps in uncultured marine proteobacteria organisms. These factors drive the selection of guilds that are best adapted for habitat colonisation. Thus, application of environmental genomics on a ‘global’ scale  offers an unprecedented way of linking environmental parameters with the specific and functional diversity of microbial assemblages  inhibits nitrogen fixation .Environmental genomics has become a standard approach in the study of aquatic habitats, owing to their relative simplicity. In comparison, soils and sediments appear to be more spatially heterogeneous and phylogenetically diverse. Estimates of soil diversity are often in the range of hundreds to thousands of microbial species per gram of soil , sequencOlavius algarvensis and a microbial consortium consisting of two sulphur-oxidizing gammaproteobacteria and two sulphate-reducing delta-proteobacteria. The worm is characterized by the complete absence of a digestive apparatus and a reduced excretory system. Thus, nutrition of the host, as well as the degradation of toxic by-products of its metabolism, is entirely dependent on the activity of the bacterial consortium. Analysis of the metagenomic data provided valuable insights into the metabolism of the different bacterial partners and into the network of interactions established between the worm and its symbionts. The host is supplied with C, N, S and P compounds by the symbiotic bacteria, and host organic osmolytes and waste products are used as C and N sources for symbiont metabolism. Analysis of the protein-coding genes of the symbionts has confirmed the existence of syntrophic cycling of sulphur elements between the sulphur-oxidizing and the sulphate-reducing symbionts.The use of high-throughput sequencing technologies has also led to tremendous progress in understanding the intricate associations between symbiotic microorganisms and their eukaryotic hosts. Finally, organism-centered studies of isolable multicellular eukaryotes  have shoTechnological and conceptual limitations of environmental genomics  are not open-reading frames.The first task of finding genes in environmental genomics or metagenomics data is sometimes compounded by the great diversity of genomes that is revealed and by the myriad novel genes they contain . Whereasit should be emphasised that every gene annotation based on in silico methods is hypothesised and such annotation is subject to revision, until the gene has been cloned, expressed, and the function of the gene product directly evaluated”. Thus, most bona fide annotations are derived from genes of model organisms, where biochemical analysis and reverse genetics can readily be carried out. Furthermore, the sequenced organisms available in databases represent a small and strongly biased subset of the biodiversity revealed by cultivation-independent methods. However, it is worth noting that several recent initiatives such as the Moore Foundation Marine Microbial Genome Sequencing Project, the Genomic Encyclopedia of Bacteria and Archaea Project, or the Fungal Genome Initiative will contribute to improve the list of sequenced organisms and to obtain a better coverage of the known biodiversity.Another major challenge in environmental genomics is the subsequent step of correctly identifying functions on the basis of sequence data. Classically, the identification of gene functions is heavily dependent on comparisons, using standard tools such as BLAST  of the complete gene sequence of Nicotiana tabacum ornithine decarboxylase (polyamine biosynthesis pathway) versus the Arabidopsis thaliana protein database yields a significant identification with diaminopimelate decarboxylase (lysine biosynthesis pathway). This instance of heterologous mis-identification between related species may be ascribed to the fact that Arabidopsis thaliana lacks an archetypal ornithine decarboxylase . These enable phylogenetic analysis and utilisation of gene clusters, such as COGs ’ ’  by analyBesides these considerations, novel fields of research that cannot be studied by other means than environmental genomics are now open to investigation. Pioneer papers, at the intersection of ecology and evolutionary biology, have paved the way for the genomics of co-evolution including mutualism, symbioses and parasitism. For instance, To date, functional and mechanistic objectives have not taken into account variation at the population level although this information is generally accessible in a number of environmental genomics projects. Usually, deep sequence coverage can detect single nucleotide polymorphisms (SNPs) and structural variations, such as copy number variants (CNVs) (One major result of environmental genomics projects is the possibility of reconstructing and modelling potential metabolic and regulatory networks. However, these data cannot be readily used to formalise models of ecosystem functioning, as no data can be directly assigned to parameter variables: spatio-temporal variations must be taken into account if ecosystem functioning is to be comprehensively modelled from three-dimensional data matrices, as shown in


AKR mice of which more than 90% die of lymphatic thymus leukaemia, had their mean survival time increased by weekly intraperitoneal inoculation of either of the two polycations DEAE-dextran and polybrene. Administration of the neutral dextran had no effect, whereas the polyanion dextran sulphate accelerated leukaemia development.Adult BALB/c mice infected with Rauscher leukaemia virus and treated from the time of palpable spleen enlargement, showed a life prolonging effect of the polycations DEAE/dextran and polybrene, and of neutral dextran. BALB/c mice treated from the time of leukaemia infection, however, showed a life prolonging effect with polyanion dextran sulphate and also of neutral dextran.


There is an extensive body of literature on health system quality reporting that has yet to be characterized. Scoping is a novel methodology for systematically assessing the breadth of a body of literature in a particular research area. Our objectives were to showcase the scoping review methodology in the review of health system quality reporting, and to report on the extent of the literature in this area.A scoping review was performed based on the York methodology outlined by Arksey and O'Malley from the University of York, United Kingdom. We searched 14 peer reviewed and grey literature databases limiting the search to English language and non-English language articles with English abstracts published between 1980 and June 2006 with an update to November 2008. We also searched specific websites, reference lists, and key journals for relevant material and solicited input from key stakeholders. Inclusion/exclusion criteria were applied to select relevant material and qualitative information was charted from the selected literature.A total of 10,102 articles were identified from searching the literature databases, 821 were deemed relevant to our scoping review. An additional 401 were identified from updates, website searching, references lists, key journals, and stakeholder suggestions for a total of 1,222 included articles. These were categorized and catalogued according to the inclusion criteria, and further subcategories were identified through the charting process. Topic areas represented by this review included the effectiveness of health system report cards (n = 194 articles), methodological issues in their development (n = 815 articles), stakeholder views on report cards (n = 144 articles), and ethical considerations around their development (n = 69 articles).The scoping review methodology has permitted us to characterize and catalogue the extensive body of literature pertaining to health system report cards. The resulting literature repository that our review has created can be of use to researchers and health system stakeholders interested in the topic of health system quality measurement and reporting. The results, in the form of report cards, are fed back to health service providers and sometimes other groups to potentially change practice patterns to improve effectiveness and efficiency of care. Reporting on health system quality has become a common tool to increase accountability, improve efficiency, determine funding, and attract consumers in many healthcare systems worldwide [Health system quality reporting refers to measuring healthcare service provision  call for special policy-relevant research syntheses and overviews. The CIHR's call for scoping review studies identified a number of priority topic areas, including health system performance evaluation, which had previously been identified by national multidisciplinary and multi-sectoral health system stakeholders to be areas of special interest. Our scoping review's aim was to document and catalogue the extent of published material relating to the production, reporting, and dissemination of health system report cards. This paper demonstrates the steps taken to conduct our scoping review, and outlines a conceptual categorization of the large body of literature on healthcare quality reporting.Arksey and O'Malley from the Centre for Reviews and Dissemination at the University of York published a pivotal paper in 2005 on the conduct of scoping reviews [The York framework recommends that in the development of the research question, all aspects of the research area should be considered to generate a breadth of coverage. Drawing on the expertise of our research team and an initial scan of the literature, we defined our overriding research question as follows: What is the extent of published evidence on best practices relating to the production, reporting, and dissemination of health system report cards? The rationale behind this broad question was the increased use of health system quality reports and the apparent lack of consensus in the literature on how best to design them. Although extensive, the existing literature on health system report cards is heterogeneous in its areas of focus and also its methodological rigor, with, for example, an abundance of quasi-experimental evaluations and studies . Therefo1. Methodological issues in health system report card development. Specific examples of methodological issues that have been addressed at least to some extent in the literature include: What data sources can be used for studying quality of care? Does the accuracy of process and outcomes of care measurements vary across different data sources? What is the best approach to developing and validating quality indicators in specific clinical areas? What clinical areas have published widely endorsed and/or applied quality indicators? What statistical methods should be used to risk-adjust data in health outcome report cards? What is the optimal format for presenting and reporting outcome or process data? Do data framing effects influence reactions to data presented in the reports? How, and to whom, should health system reports be disseminated? What are the pros and cons of public reporting relative to reporting to providers only, or providers and health system administrators?2. Evidence of effectiveness/efficacy of report cards for enhancing quality. More specifically, do report cards actually affect quality of care and outcomes?i.e., patients, providers, and/or decision makers) in the health system?3. Research into stakeholder views of report cards. What opinions do the general public, providers, and health system decision makers have of health system report cards? Do health system report cards influence the decision making of the various players .To be comprehensive, the York framework recommends searching several literature sources, including electronic databases, reference lists of relevant literature, hand-searching key journals, and existing networks, relevant organizations, and conferences . For ourWe enlisted the services of a library scientist (DLL) to conduct the electronic database search. The research team devised a broad list of terms pertinent to health system report card research, including report cards, performance indicators, scorecards, system performance, quality improvement, health, healthcare, and medical care. These terms were combined to create keywords that could be used to search both peer-reviewed and grey literature electronic databases: quality indicators, healthcare AND reports/reporting, quality of healthcare AND reports/reporting, benchmarking AND reports/reporting, report card/cards AND health/healthcare/medical, performance reports/reporting AND health/healthcare/medical care, quality reports/reporting AND health/healthcare/medical care, health system evaluation/quality/performance/rating, health system reports/reporting, healthcare evaluation/quality/performance/rating AND reports/reporting, healthcare system reports/reporting, consumer reports AND health/healthcare/medical care, public performance reports/reporting AND health/healthcare/medical care, public reporting AND health/healthcare/medical care. Keywords were then mapped to database thesauri search terms, where available, and were also searched as text word terms in all databases. The goal was to conduct a sensitive rather than specific search of the literature; thus search terms were of necessity kept very broad, resulting in many irrelevant studies being eliminated at the study selection phase (see below).http://www.nyam.org/library/greyreport.shtml, PapersFirst, ProQuest Dissertations and Theses, University of York Health Technology Assessment (HTA) database http://www.crd.york.ac.uk/crdweb/, University of Laval KUUC Knowledge Utilization Database http://kuuc.chair.ulaval.ca/english/index.php, and WorldCat.A total of 14 peer-reviewed and grey literature databases were searched using these search strings. The peer-reviewed databases searched were: ABI Inform, Cumulative Index of Nursing and Allied Health Literature (CINAHL), Cochrane Library, EconLit, EMBASE, MEDLINE, PsycINFO, and Social Sciences Abstracts. The grey literature databases searched were: Grey Literature Report. All literature database searches were limited to the English language and non-English language articles with English abstracts, and published between 1980 and June 2006. The literature search was subsequently updated to November 2008.Once the relevant studies were selected from the literature database search, we carried out a selective search of relevant websites. Through consultation with our stakeholders, and members of the research team and colleagues, we compiled a list of relevant websites to search Table . We atteOnce hand searching a website's links was complete, we used the website's search engine to attempt to uncover additional material. Once again, different types of search engines required different search tactics. For all websites, we searched the terms 'healthcare quality,' 'performance report,' and 'report card'. For websites that were not specifically healthcare-focused, we added the word 'health' to the specific term. We kept a log of the website searches, saving the links to relevant pages and tracking our progress through the websites.In an attempt to be as comprehensive as possible in our search, we also collected literature from reference lists of relevant articles, specific journal issues with related material, and suggestions from colleagues.Our employ of broad terms in the electronic database searches generated a list of over 10,000 abstracts. In order to sort out the irrelevant material from this list, we developed a screening tool with specific inclusion and exclusion criteria based on the focus areas identified with our research question. Three members of the research team piloted the inclusion/exclusion criteria with a sub-sample of abstracts retrieved from the MEDLINE database. Multiple sample tests of criteria were carried out, and feedback from these tests was used to refine the abstract screening process. Once a final set of inclusion/exclusion criteria were agreed upon, the inter-rater reliability for this process was confirmed using a kappa analysis of 35 abstracts (kappa = 0.79).One member of the research team was responsible for reading the abstracts of all the articles identified in the search of electronic database, applying the inclusion/exclusion criteria in the abstract screening tool. For inclusion in the scoping review, the abstracts had to indicate that the articles contain: Original research (including systematic reviews) on 1) efficacy or effectiveness of health system report cards or 2) stakeholder views of health system report cards; or original research and/or a focused discussion of 3) ethical considerations or 4) methodological approaches to health system report cards. In addition to peer-reviewed articles, we also included research reports, theses, and policy analyses if they met the other inclusion criteria.Excluded from the review were obvious commentaries, editorials, or non-systematic reviews regarding health system report cards (except for inclusion criteria three and four), articles describing the audit of a particular healthcare service, but lacking the feedback component of the report card process, and articles on non-healthcare-related quality reporting.A similar screening process was used for literature uncovered through website searching, reference lists, and recommendations. For material from websites, less formal, interpretive descriptions of a study or investigation that may be on a home page or a web page that may or may not be linked to the report document were also excluded.According to the York methodology of scoping reviews, the charting process is multi-staged, involving extraction of information from individual articles. We collected descriptive characteristics such as general citation information, clinical area, level of reporting, country of origin, and key findings from the included articles to create a detailed spreadsheet database.a priori sub-categories provided a structure to the findings and a clearer way of describing the literature.The purpose of this final stage of scoping is to provide a structure to the literature uncovered. Due to the broad scope of our research question and the subsequent large volume of literature uncovered in our searches, we contained this final stage to a narrative synthesis where we organized these findings into specific categories based on our focus areas and abstract screening tool: evidence of effectiveness of report cards; stakeholder views of report cards; methods associated with report cards; ethical considerations for report cards. Focusing on the descriptive nature of the material in the charting phase allowed for the identification of additional categories and themes in the literature. Creation of these e.g. reference lists) were charted for a total of 942 articles in the initial round of searching. Updating the electronic databases search yielded an additional 3,014 articles, of which 280 were charted, for a total of 1,221 articles charted. Each of the selected articles were categorized into the four focus areas: evidence of report card effectiveness in improving the quality of healthcare (n = 194); stakeholders' opinions, views and understanding of report cards (n = 144); articles addressing various methods  of report cards (n = 815); and ethical considerations or issues that have arisen due to health system report card use  of material uncovered originated from the United States (US), where there is a culture of healthcare report cards. Approximately 11% of the material originated from the United Kingdom (UK), 4% from Europe, 2% from Scandinavia, and 7% from Canada. Another 2% originated from Australia and New Zealand, and 1.3% from Asia. Approximately 5% came from miscellaneous countries such as Israel, United Arab Emirates, Brazil, Mexico and several African countries. Publications from the World Health Organization and the Organisation for Economic Co-Operation and Development each accounted for about 1% of the literature found.e.g., nursing home, long-term care facility or psychiatric facility). One hundred and fifty-nine articles focused on quality of care provided by groups of healthcare providers such as clinical departments, groups of physicians, nurses or other providers , and 167 articles pertained to healthcare quality provided by individual physicians, nurses, or other providers. Twenty-two articles spanned two or more of these healthcare levels, and for 125 articles it was either not an applicable or relevant categorization  or it was not immediately apparent at what level the article reported on healthcare quality.The majority of the literature pertained to four broad levels within healthcare: system, facility, group, or individual. More specifically, 328 articles pertained to quality reporting at the level of healthcare system or healthcare plan. Four hundred and forty-three articles described an aspect of quality reporting at the level of hospitals or other healthcare facilities  or cardiac surgery . 'Mental healthcare' includes in-patient and out-patient psychiatric care. 'Surgery' includes articles pertaining to quality of surgeries other than cardiac or oncologic surgeries. 'Oncology/cancer care' includes articles describing outcomes following surgical oncology procedures and screening for different types of cancer .It was noted that particular clinical areas had larger volumes of literature pertaining to performance reporting. Table Not all literature included in the review pertained to a specific clinical area. Furthermore, some literature pertained to more than one clinical area, such as nursing home care and geriatrics.Several organizations commonly reported research pertaining to their healthcare performance measurement and quality improvement initiatives. As expected, many of these organizations are based in the US, several of which are agencies within the federal government departments. For example, within the US, the Department of Health and Human Services, the Agency for Healthcare Research and Quality, the Centers for Medicare and Medicaid Services and Prevention, and the Centers for Disease Control all have healthcare performance reporting and quality improvement initiatives that were uncovered in the scoping review. Within the US Department of Veterans Affairs, the Veterans Health Administration is also involved in numerous quality-of-care monitoring and performance improvement initiatives.There are also several non-governmental organizations in the US that published material pertaining to our scoping review focus areas, including the Joint Commission on Accreditation in Healthcare, the National Committee for Quality Assurance and RAND Health. Specific projects based in the US, separate from these and federal government organizations and prevalent in the selected literature include the New York State Cardiac Surgery Reports, the Northern New England Cardiovascular Disease Study Group, the Pennsylvania Consumer Guide to Coronary Artery Bypass Graft Surgery, the Cleveland Health Quality Choice Coalition, the Nursing Outcomes Coalition, and the National Database of Nursing Quality Indicators.Outside of the US, a few other groups and projects were reported several times in our selected literature. From the UK, the Healthcare Commission published material pertaining to methods and evidence of effectiveness of healthcare report cards utilizing data from the National Health Services (NHS). The Australian Council on Healthcare Standards reported on the development of comparative indicators. The Institute of Clinical Evaluative Sciences based in Canada has also published several reports pertaining to report card methods. On an international level, the World Health Organization published material pertaining to report card framework and statistical analyses and the Organization for Economic Cooperation and Development published material pertaining to quality indicator development.Below we provide an illustrative overview of the information identified in each focus area. For each topic area, we do not cite all identified references because of their large number. Instead, we refer readers to the corresponding topic tabs in the literature database for our scoping review .et al. [A number of other identified articles assess the impact of health system reports on quality of care, with quality measured using a variety of indicators including outcome and process measures. This body of literature includes a Cochrane Collaboration systematic review by Jamtvedt et al.  focusinge.g., patients and purchasers), physicians, other healthcare providers , and healthcare managers. There were generally three areas of focus in the studies that we identified: stakeholder opinions of report cards; their understanding of report card information; and how they use the information in report cards to make decisions.We identified a total of 144 articles reporting on the views held by various stakeholders regarding health system report cards. This includes studies focusing on consumers  were also uncovered in our literature search update. The clinical area of cardiac care  has undergone considerable report card activity, and thus the majority of articles within this focus area are in the context of cardiac care. In particular, the ethical impacts of the highly-publicized surgeon-specific New York State Coronary Artery Bypass Graft Report are most commonly discussed. There are also several publications that discuss ethical frameworks for report cards. Once again, cardiac care report cards were most often represented. However an ethical framework for mental health care quality reporting was also published.Studies on ethical considerations of report cards were not abundant, with 69 articles identified. The most commonly discussed topics were the unintended consequences of report cards, and more specifically, the impact of report cards on vulnerable patient populations. Discussions of ethical considerations of pay-for-performance schemes or performance-based contracting  discussed and argued for risk adjusting rather that the use of raw rates in order to produce performance measures that accurately reflected quality of care and could be used for comparisons. However, some more recent articles addressing the same issue were also found suggesting that despite earlier work demonstrating the need for risk adjustment, some performance measurements and report cards still do not risk adjust sufficiently.Our review identified 122 studies addressing statistical methods for health system report cards. These primarily focused on risk adjustment methods. Earlier material  score, were discussed in some of the identified articles. Risk adjustment for patient characteristics, and specifically socio-economic factors, were addressed, as were risk adjustments for hospital characteristics, such as peer group, acceptance of patient transfers, number of emergency surgeries, or the institutional protocols regarding do not resuscitate orders. Adjustment methods for specific data types, such as administrative data or patient surveys, were also addressed.This subsection of the Methods focus area identified a total of 346 studies. This group of studies was further subdivided into three groups: quality indicator development (n = 168), quality indicator validation (n = 148), and uptake or combined development and validation of quality indicators (n = 30).Publications in this topic area described the development of quality indicators in a variety of healthcare settings and clinical areas. Quality indicator development for overall hospital performance, health system performance assessment, and consumer/patient satisfaction with care were commonly covered in the literature. There was substantial literature regarding the development of performance indicators for cardiac care, surgery outcomes, mental health, and nursing homes/long-term care. Some indicators for cancer care were also found. Other clinical areas with quality indicator development include nursing care, mental health treatment, surgery, primary care, and public health.i.e., a combination of Delphi panel and nominal group technique), and adaptation of indicators from clinical guidelines.Many of the indicator projects described above utilized the Delphi method or a modification of the technique for quality indicator development. However, other methods have been used to develop quality indicators, including modified nominal group technique, the RAND Appropriateness Method . For the clinical areas still in the preliminary stages of developing quality report cards, it is hoped that report card developers look to clinical areas with more advanced activity to draw on their experiences and avoid 'reinventing the wheel' of report card development.Similar volumes of literature were uncovered for quality reporting at the system, hospital, and provider levels, indicating that the practice of quality reporting is occurring throughout the different levels of healthcare. Finally, our results reveal that certain clinical areas, such as cardiac care, cardiac surgery, and primary care or general practice, have greater report card activity relative to other clinical areas  that it is not feasible to chart articles in more depth, while still maintaining the breadth of perspective required for scoping. Others have published scoping reviews with smaller volumes of relevant literature that contain succinct, detailed syntheses of the uncovered literature [First, although we created a comprehensive database of existing literature on health system quality report cards, this was by no means a rapid process (taking more than a year to complete). The volume of literature that we amassed in this scoping review is so great  at information sharing events relating to the Canadian Cardiovascular Outcomes Research Team (CCORT--see http://www.ccort.ca), the Society for General Internal Medicine http://www.sgim.org, and the National meeting of the national APPROACH network (see http://www.approach.org). Further engagement of stakeholders has also occurred through the sharing of a scoping review report with the Institute for Health Services and Policy Research at the Canadian Institutes of Health Research. Knowledge exchange relating to our work will also be enhanced by the academic dissemination of our findings through this article and its accompanying on-line literature database.Another general challenge is that of knowledge translation. We have undertaken stakeholder-targeted dissemination activities of our findings that may contribute to collective knowledge of various aspects of health system report cards. Since completion of our review, we have interacted with various stakeholders . Development of guidelines to aid in the reporting of scoping reviews would improve their transparency and perhaps acceptance in the medical literature.Finally, as scoping reviews become more common, there is the challenge of determining the quality of the review. Guidelines exist for the reporting of many types of health research studies. Such guidelines have been developed to help ensure quality and transparency of health research Scoping reviews may be useful for mapping literature and identifying where more in-depth reviews and syntheses can be carried out. The timeliness and depth of the scoping review results is dependent on the volume of literature that exists in the particular topic area to be scoped. Our scoping review has produced a comprehensive literature database from a large body of literature pertaining to health system quality report cards. The resulting literature repository that our review has created may be of use to researchers and health system stakeholders interested in the topic of health system quality measurement and reporting.The authors declare that they have no competing interests.SB participated in the design and coordination of the study, carried out the website searching, title and abstract review, article review, collation and organization of material, statistical analysis, drafted and revised the manuscript. DL participated in the design and coordination of the study, carried out the database literature searches, website searching, title and abstract review and helped to draft the manuscript. SL participated in the design and coordination of the study. JK helped with the conception of the study and participated in the design and coordination of the study. WG conceived of the study, secured funding for the study, participated in the design and coordination of the study, participated in some title abstract review, and helped draft and revise the manuscript. All authors read and approved the final manuscript.Reference Database. This file contains the references selected from the scoping review of the literature pertaining to health system report cards. The file contains tabs that are labeled according to the categories listed in Figures Click here for file


Despite substantial attention paid to Arab-Americans (AAs) in the media and in public discourse, there is limited research about the health of AAs in the United States (US) in the public health literature. This review aims to synthesize the extant peer-reviewed literature concerned with the health of AAs living in the US.We summarize existing research on the prevalence, relative burden compared to other ethnic and racial groups, and determinants of diseases within each morbidity cluster among AAs living in the US.Available evidence suggests that the health of AAs may differ from that of other ethnic and racial groups in the US, and that exposures specific to this ethnic group, such as immigration, acculturation, and discrimination may be important in the etiology of several diseases among AAs.Given the growth of this ethnic group and its marginalization in the current sociopolitical climate, more research about the health of AAs in the US seems warranted. We summarize relevant methodological concerns and suggest avenues for future research. Arab-Americans (AAs) are residents of the United States (US) who trace their ancestral, cultural, or linguistic heritage or identity back to one of 22 Arab countries. Many recent high profile events–including the ongoing Arab-Israeli conflict, the September 11, 2001 attacks, and the war in Iraq–have put this group under increasing scrutiny in the popular press [There are many reasons why health indicators among AAs may be different than those in the general population at large. First, AAs are disproportionately recent immigrants to the US . Second,The aim of this review was to systematically assess the peer-reviewed literature concerned with the health of AAs living in the US and to summarize the prevalence and correlates of key health indicators among AAs. We considered the peer-reviewed epidemiologic and public health literature about AA health since 1980. In so doing, we aimed to synthesize current knowledge about the health of AAs, inform practitioners to particular health risks within the Arab-American (AA) community, and encourage research that can address unanswered questions about the health of this ethnic group.Arab immigration to the US occurred in three waves. The first began in 1875 and was comprised largely of Syrian and Lebanese Christian immigrants, most of whom were uneducated and worked unskilled jobs in the US. Following World War I, the Quota and Johnson-Reed Acts of 1924 limited the number of Arab immigrants allowed entry into the US each year, bringing to a close the first generation of Arab immigration.Post World War II pro-immigration policy ushered in the second wave of Arab immigrants. The demographic characteristics of Arab immigrants during this wave differed substantially from the first: the majority came to the US fleeing post-war political upheavals in Egypt, Syria, Iraq, and Palestine. In contrast to those who immigrated during the first wave, this group was better educated, spoke fluent English, and worked white-collar jobs in the US.The third wave of Arab immigration to the US began in 1965 after the Immigration Act of that year ended the quota system favoring European immigrants. This generation was the best educated compared to Arab immigrants during the other two waves . The 199Approximately 94% of AAs in the US live in metropolitan areas, which is substantially higher than the 80% of the general US population living in metropolitan areas . MichigaAs compared to the general US population, AAs are on the whole better educated, more affluent, and more likely to be entrepreneurs or own businesses . The larThis review assesses current knowledge about the health of AAs and will encompass the peer-reviewed literature published between 1980 and 2008. We limited our review to these years in order to reflect current thinking about the relation between ethnicity and health. The literature reviewed was identified through the MEDLINE, Web of Science, BIOSYS previews, and Current Content Connect databases using the Web of Knowledge interface, and it covered empirical studies about any aspect of AA health in the US. All queries were carried out by the primary author during the month of July, 2008. A detailed account of the search strategy and results is provided in the additional files We restricted our review to those studies that empirically and specifically assessed the health of AAs living in the US. The search was limited to English-language studies. Keywords and terms used for the search included the following: Arab, America*, Middle*Eastern, Chaldean, Diabet*, glucose, metaboli*, "heart disease", infarct*, heart, MI, CVD, atherosclero*, stroke, ischemi*, cancer, neoplas*, tumor, leukemia, lymphoma, depress*, anxiety, PTSD, post*trauma*, substance, mood, schizophren*, mental, psych, matern*, pregnan*, ped*, preterm, birth, abuse, tobacco, smok*, water*pipe. We also assessed the references of all papers reviewed to identify any papers that were not detected using the systematic searches.The original search provided 88 publications of which 54 were removed because they were either meeting abstracts or were not empiric in design . This review, therefore, covers 34 studies, which are reviewed in detail in Table S1, included in the additional files [additional file There is little consensus in the literature about the burden of cardiovascular disease (CVD) and its risk factors among AAs relative to other groups. The prevalence of hypertension among AAs is between 13–20% . The preTwo studies have assessed the determinants of CVD risk factors among AAs. In one study, elevated body mass index (BMI) was associated with elevated blood pressure, increased blood glucose, increased total cholesterol and decreased high-density lipoprotein (HDL)-cholesterol among AAs . Length Two studies assessed the prevalence of tobacco use among AA adults. In one study, tobacco use was found to be more prevalent among AA adults than among the general US adult population. In a randomly selected sample of 237 AA adults in Michigan, 39% of respondents were current smokers, as compared to 29% both in Michigan and nationally . Eleven Several studies have assessed the prevalence and determinants of tobacco use among AA adolescents. The prevalence of ever smoking a cigarette among AA teens was between 29–45% across several studies, while the prevalence of one-month history of smoking was between 7–17% in the extant studies about the prevalence of adolescent tobacco use among AAs -25. RateThere are several risk factors for tobacco use among AA adolescents that have been identified; these include male gender, peer-smokers, lack of religious influence, lack of perceived negative consequences of smoking, poor grades, high stress, family members who smoke, reporting many hours of smoking exposure daily, receiving offers to smoke, tobacco-related advertisements and mail, belief that tobacco can help make friends, and having a US-born mother -25. AmonSeveral studies have assessed the prevalence and determinants of diabetes and related endocrine diseases among AAs in the US. However, there is little consensus in the literature about the burden of diabetes among AAs relative to the general US population. In cross-sectional analyses using convenience samples in metropolitan Detroit, the prevalence of diabetes among AAs was shown to be between 16–33% ,31,32. TOne study considered the prevalence of metabolic syndrome among AAs, which was comparable to the general US population  standards) using NHANES III data ,36. MetaThree studies explicitly assessed the determinants of diabetes and related health indicators among AAs. In one study, age at immigration, duration in the US, activity in Arab organizations, and consumption of Arabic food were all shown to be associated with increased risk for dysglycemia after adjusting for age and BMI . AnotherBerlie and colleagues  assessedThree studies have assessed the determinants of AA mental health in the US and three have assessed the mental health of Iraqi refugees specifically. A study among AAs in northcentral Florida showed that self-reports of recent discrimination were positively correlated with psychological distress and negatively correlated with self-esteem and environmental mastery . A separThree studies assessed the mental health of Iraqi refugees. In a chart review of 375 AA mental health clinic patients, Iraqi patients were more likely to be diagnosed with post-traumatic stress disorder (PTSD), more likely to have physical complaints, and more likely to have full remission after care than other AA patients . A diffeWe are aware of only one study that was specifically concerned with cancer among AAs. Schwartz and colleagues  calculatTwo studies assessed the prevalence and two assessed the determinants of adverse birth outcomes among AA women. AAs are at lower risk for adverse birth outcomes than the general US population. One study considered all births in Michigan between 1993–2002. Among this sample, the prevalence of preterm birth (PTB) among women of Arab ancestry was 8%, and the prevalence of PTB among foreign-born AA women was significantly lower than that among non-Hispanic white women (9%) . AnotherTwo studies assessed the determinants of adverse birth outcomes among AA women. According to El Reda and colleagues , determiIn a specific analysis concerning risk for adverse birth outcomes in the context of maternal stress, Lauderdale  assessedThe literature about the health and illness psychology of AAs is concerned with self-reported health and activity limitations, health care needs, HIV/AIDS knowledge and attitudes, and attitudes toward domestic abuse among AAs.Read and colleagues  assessedIn a subjective health care needs assessment among 15 men and 32 women in California, Laffrey and colleagues  found thKulwicki and Cass  assessedOne study assessed attitudes toward domestic abuse among AAs . Fifty-eMiscellaneous reports about the health of AAs were concerned with proportional cause-specific mortality, asthma, cystic fibrosis (CF) carrier frequency, trace element profiles, and dermatologic diseases.Nasseri  exploredThe prevalence and correlates of asthma among AAs were studied by Johnson and colleagues . They foWei and colleagues  studied Trace element profiles in the toenails of 259 AA adults and children living in metropolitan Detroit, MI were also assessed by Slotnick and colleagues . CompareEl-Essawi and colleagues  assessedIn this systematic review about the health of AAs in the US, we found that 1) there is little consensus about the relative burdens of CVD or diabetes among AAs compared to other groups, however the best available evidence suggests that the prevalence of hypertension among AAs is between 13–20% and the prevalence of diabetes is between 5–33%; 2) there is limited information about the prevalence of cancers or common mental disorders in this group; 3) there is evidence suggesting that AAs have lower prevalence of adverse birth outcomes and adolescent tobacco use compared to the general US population and to majority groups in the US; 4) the determinants of common morbidities among AAs are similar to those within the general population, although there is evidence that acculturation, immigration, and discrimination-associated stress are involved in the etiologies of CVD, diabetes, mental illness, and/or adverse birth outcomes among AAs.There are several methodological limitations to the extant literature that challenge our current understanding of the health of AAs in the US and hinder the systematic comparison of the health of AAs to the health of other ethnic groups in the US. We will discuss each of these limitations in turn aiming to describe how these limitations influence our interpretation of the literature.First, the central limitation to our understanding of the health of AAs in the US is the relative paucity of published studies concerning the health of this ethnic group. Our search of the literature yielded only 34 studies. This challenges our inference about the health of AAs in the US in several ways. First, there is little consensus about the prevalence and correlates of major morbidities such as diabetes and CVD among AAs relative to other ethnic groups. Because these diseases account for much of the chronic disease burden in the US, understanding the prevalence and correlates of these diseases among AAs is a primary concern. Second, there is little to no research about the prevalence and correlates of several important health indicators, such as all-cause mortality, common mental disorders, site-specific cancers, HIV/AIDS and other infectious diseases, and chronic pain conditions. Third, the literature about AA health has yielded few studies explicitly concerned with the health effects of potentially important exposures, such as immigration, acculturation, and discrimination among AAs. For example, as an ethnic group, AAs have been systematically targeted for discrimination–more so since the terrorist attacks of September 11, 2001 and the subsequent wars in Afghanistan and Iraq . HoweverThe second methodological limitation to our understanding of AA health is the paucity of prospective studies that include data about AAs. Twenty-seven out of 34 studies that assessed the health of AAs in the US used cross-sectional analyses. The remaining 7 studies used either retrospective cohort analyses or medical chart reviews. We did not identify any studies that prospectively assessed the health of Arab-Americans in the US. Prospective cohort studies about the health of AAs in the US would be important for several reasons. First, without the use of prospective studies it is impossible to establish population-based incidence rates for health indicators among AAs. Second, prospective studies would allow inference about the causal and temporal mechanisms that underlie associations between Arab ethnicity and health indicators. Third, prospective studies are needed to help understand whether some of the observed associations between social exposures such as immigration, acculturation, and discrimination and health play different roles across the life course ,72. A coA third limitation is that many of the extant studies about the health of AAs use place of birth to demarcate Arab ethnicity. The use of place of birth as a marker for ethnicity unfortunately confounds ethnicity with migrant status which presents particular challenges. Migrant status in and of itself may be a determinant of AA health, positively or negatively -81. In aFourth, many of the extant studies concerning the health of AA have used convenience samples in one area with a high AA concentration. Twenty-six of the 34 (76%) studies reviewed above sampled AAs in Michigan; 24 of those 26 in Michigan sampled AAs in the southeast part of the state, which includes metropolitan Detroit and Dearborn, MI. Because of its high concentration of AAs, metropolitan Detroit is an attractive study locale for investigators interested in the health of AAs. However, it is possible that health indicators among AAs in Michigan are not representative of those among the US population of AAs. For example, although national data show that AAs are on average more affluent and educated than the general US population ,35,50,52There are several cautions that should be noted when interpreting the findings of this review. First, we organized our findings around eight morbidity clusters. It is important to note that this organization was likely influenced by the search terms used in the article search methodology. Second, because our inclusion criteria restricted the articles reviewed herein to those published in peer-reviewed journals, there may be publication bias regarding the articles discussed in this review. Therefore, our findings may not accurately reflect current knowledge about Arab-American health in the US. Third, while several of the topics discussed in articles reviewed in the "Miscellaneous Reports" portion of the results may represent defined morbidity clusters in their own right, there was not sufficient published research to establish any of them as such with regard to the health of AAs living in the US.We suggest that five directions for future research emerge from this review. First, investigators interested in the health of AAs or in understanding the health effects of social exposures such as immigration, acculturation and/or discrimination might consider undertaking prospective cohort studies of the health of AAs in the US. Second, because the majority of studies published concerning the health of AAs in the US are set in southeast Michigan, investigators interested in the health of this ethnic group could consider studies using national and statewide datasets or studying the health of AAs in different localities. Third, devising better and more efficient methods of determining Arab ethnicity, such as validated name algorithms ,87, may AAs: Arab-Americans; AA: Arab-American; US: United States; MI: Michigan; NHANES III: Third National Health and Nutrition Examination Survey; NHIS: National Health Interview Survey; PTSD: Post-traumatic stress disorder; CVD: Cardiovascular disease; HDL: High density lipoprotein; BMI: Body mass index; ATP III: Adult Treatment Plan III; WHO: World Health Organization; ADA: American Diabetes Association; A1c: Hemoglobin A1c; FL: Florida; PIR: Proportional incidence ratio; DC: District of Columbia; PTB: Preterm Birth; LBW: Low birth weight; HIV/AIDS: Human immunodeficiency virus/acquired immunodeficiency syndrome; PMR: Proportional mortality ratio; COPD: Chronic obstructive pulmonary disorder; SES: Socioeconomic status; CF: Cystic fibrosis; NIDDM: non-insulin dependant diabetes mellitus.The authors declare that they have no competing interests.AMES conceived the study, carried out the search, and wrote the manuscript. SG edited the manuscript and participated in its design and coordination. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:El-Sayed and Galea review search strategy. Details about the search strategy employed during the literature search and results thereof.Click here for fileArab-American Health Table S1. Details about each of the studies.Click here for file