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Background Patients at higher than average risk of heritable cancer may process risk information differently than the general population. However, little is known about clinical, demographic, or psychosocial predictors that may impact risk perception in these groups. The objective of this study was to characterize factors associated with perceived risk of developing cancer in groups at high risk for cancer based on genetics or family history. Methods We searched Ovid MEDLINE, Ovid Embase, Ovid PsycInfo, and Scopus from inception through April 2009 for English-language, original investigations in humans using core concepts of "risk" and "cancer." We abstracted key information and then further restricted articles dealing with perceived risk of developing cancer due to inherited risk. Results Of 1028 titles identified, 53 articles met our criteria. Most (92%) used an observational design and focused on women (70%) with a family history of or contemplating genetic testing for breast cancer. Of the 53 studies, 36 focused on patients who had not had genetic testing for cancer risk, 17 included studies of patients who had undergone genetic testing for cancer risk. Family history of cancer, previous prophylactic tests and treatments, and younger age were associated with cancer risk perception. In addition, beliefs about the preventability and severity of cancer, personality factors such as "monitoring" personality, the ability to process numerical information, as well as distress/worry also were associated with cancer risk perception. Few studies addressed non-breast cancer or risk perception in specific demographic groups (e.g. elderly or minority groups) and few employed theory-driven analytic strategies to decipher interrelationships of factors. Conclusions Several factors influence cancer risk perception in patients at elevated risk for cancer. The science of characterizing and improving risk perception in cancer for high risk groups, although evolving, is still relatively undeveloped in several key topic areas including cancers other than breast and in specific populations. Future rigorous risk perception research using experimental designs and focused on cancers other than breast would advance the field.

ObjectivesTo synthesize the available evidence regarding the outcomes associated with nonoperative management, open repair, and endovascular repair of thoracic aortic transection.MethodsWe searched electronic databases (MEDLINE, EMBASE Cochrane, Web of Science, and Scopus) for studies that enrolled patients with aortic transection and measured the outcomes of interest. Two reviewers determined study eligibility and extracted data. We estimated the event rate associated with the different approaches from case series and the relative risk from comparative studies. Estimates from each study were pooled using the random effects model.ResultsWe found 139 studies that fulfilled the inclusion criteria, the majority of which were noncomparative surgical case series, retrospective, and none were randomized. Studies included 7768 patients, the majority of which were males. The mortality rate was significantly lower in patients who underwent endovascular repair, followed by open repair and nonoperative management (9%, 19%, and 46%, respectively, P < .01). No significant difference in event rate across the three groups was noted for the outcomes of anterior stroke, posterior stroke, or any stroke. The risk of spinal cord ischemia and end-stage renal disease were higher in open repair compared with the other 2 groups (9% vs 3% and 3%, P = .01 for spinal cord ischemia and 8% vs 5% and 3%, P = .01 for end-stage renal disease). Compared with endovascular repair, open repair was associated with an increased risk of graft infection and systemic infections. Meta-analyses of comparative studies demonstrated that compared with open repair, endovascular repair is associated with reduced mortality and spinal cord ischemia (relative risk, 0.61; 95% confidence interval, 0.46-0.80; and relative risk, 0.34; 95% confidence interval, 0.16-0.74; respectively). Inferences are limited by methodological quality, survival, and publication biases.ConclusionsVery low-quality evidence suggests that, compared with open repair or nonoperative management, endovascular repair of thoracic aortic transection is associated with better survival and decreased risk of spinal cord ischemia, renal injury, and graft and systemic infections. Nonoperative management is associated with the least favorable outcomes.

Study objective We assess the methodological quality and prognostic accuracy of clinical decision rules in emergency department (ED) syncope patients. Methods We searched 6 electronic databases, reviewed reference lists of included studies, and contacted content experts to identify articles for review. Studies that derived or validated clinical decision rules in ED syncope patients were included. Two reviewers independently screened records for relevance, selected studies for inclusion, assessed study quality, and abstracted data. Random-effects meta-analysis was used to pool diagnostic performance estimates across studies that derived or validated the same clinical decision rule. Between-study heterogeneity was assessed with the I 2 statistic, and subgroup hypotheses were tested with a test of interaction. Results We identified 18 eligible studies. Deficiencies in outcome (blinding) and interrater reliability assessment were the most common methodological weaknesses. Meta-analysis of the San Francisco Syncope Rule (sensitivity 86% [95% confidence interval {CI} 83% to 89%]; specificity 49% [95% CI 48% to 51%]) and the Osservatorio Epidemiologico sulla Sincope nel Lazio risk score (sensitivity 95% [95% CI 88% to 98%]; specificity 31% [95% CI 29% to 34%]). Subgroup analysis identified study design (prospective, diagnostic odds ratio 8.82 [95% CI 3.5 to 22] versus retrospective, diagnostic odds ratio 2.45 [95% CI 0.96 to 6.21]) and ECG determination (by evaluating physician, diagnostic odds ratio 25.5 [95% CI 4.41 to 148] versus researcher or cardiologist, diagnostic odds ratio 4 [95% CI 2.15 to 7.55]) as potential explanations for the variability in San Francisco Syncope Rule performance. Conclusion The methodological quality and prognostic accuracy of clinical decision rules for syncope are limited. Differences in study design and ECG interpretation may account for the variable prognostic performance of the San Francisco Syncope Rule when validated in different practice settings.

Background Emerging epidemiological evidence suggests that statin use may reduce the risk of infections and infection-related complications. Our objective was to examine the association between statin use and the risk of infections and related outcomes. Methods We searched several electronic databases from inception through December 2007 for randomized trials and cohort studies that examined the association between statin use and the risk or outcome of infections. Data on study characteristics, measurement of statin use, outcomes (adjusted for potential confounders), and quality assessment were extracted. Results Sixteen cohorts were eligible and differed in representativeness, outcome assessment, and comparability of exposed (statin) and unexposed (nonstatin) groups. Nine cohorts addressed the role of statins in treating infections: bacteremia (n = 3), pneumonia (n = 3), sepsis (n = 2), and bacterial infection (n = 1). The pooled adjusted effect estimate was 0.55 (95% confidence interval, 0.36-0.83; I 2 = 76.5%) in favor of statins. Seven cohorts addressed infection prevention in patients with vascular diseases (n = 3), chronic kidney disease (n = 1), diabetes (n = 1), intensive care unit–acquired infections (n = 1), and in general practice (n = 1). The pooled effect estimate was 0.57 (95% confidence interval, 0.43-0.75; I 2 = 82%) in favor of statin use; there was some evidence of publication bias for this analysis (Egger test; P = .07). Meta-regression did not identify potential effect modifiers that explain the between-study heterogeneity. Conclusions Results for our meta-analysis suggest that statin use may be associated with a beneficial effect in treating and preventing different infections. Given the presence of heterogeneity and publication bias, there is a need for randomized trials to confirm the benefit of statin use in this context.

The increasing use of Internet-based learning in health professions education may be informed by a timely, comprehensive synthesis of evidence of effectiveness.To summarize the effect of Internet-based instruction for health professions learners compared with no intervention and with non-Internet interventions.Systematic search of MEDLINE, Scopus, CINAHL, EMBASE, ERIC, TimeLit, Web of Science, Dissertation Abstracts, and the University of Toronto Research and Development Resource Base from 1990 through 2007.Studies in any language quantifying the association of Internet-based instruction and educational outcomes for practicing and student physicians, nurses, pharmacists, dentists, and other health care professionals compared with a no-intervention or non-Internet control group or a preintervention assessment.Two reviewers independently evaluated study quality and abstracted information including characteristics of learners, learning setting, and intervention (including level of interactivity, practice exercises, online discussion, and duration).There were 201 eligible studies. Heterogeneity in results across studies was large (I(2)or = 79%) in all analyses. Effect sizes were pooled using a random effects model. The pooled effect size in comparison to no intervention favored Internet-based interventions and was 1.00 (95% confidence interval [CI], 0.90-1.10; P.001; n = 126 studies) for knowledge outcomes, 0.85 (95% CI, 0.49-1.20; P.001; n = 16) for skills, and 0.82 (95% CI, 0.63-1.02; P.001; n = 32) for learner behaviors and patient effects. Compared with non-Internet formats, the pooled effect sizes (positive numbers favoring Internet) were 0.10 (95% CI, -0.12 to 0.32; P = .37; n = 43) for satisfaction, 0.12 (95% CI, 0.003 to 0.24; P = .045; n = 63) for knowledge, 0.09 (95% CI, -0.26 to 0.44; P = .61; n = 12) for skills, and 0.51 (95% CI, -0.24 to 1.25; P = .18; n = 6) for behaviors or patient effects. No important treatment-subgroup interactions were identified.Internet-based learning is associated with large positive effects compared with no intervention. In contrast, effects compared with non-Internet instructional methods are heterogeneous and generally small, suggesting effectiveness similar to traditional methods. Future research should directly compare different Internet-based interventions.

ContextRandomized clinical trials (RCTs) that stop earlier than planned because of apparent benefit often receive great attention and affect clinical practice. Their prevalence, the magnitude and plausibility of their treatment effects, and the extent to which they report information about how investigators decided to stop early are, however, unknown.ObjectiveTo evaluate the epidemiology and reporting quality of RCTs involving interventions stopped early for benefit.Data SourcesSystematic review up to November 2004 of MEDLINE, EMBASE, Current Contents, and full-text journal content databases to identify RCTs stopped early for benefit.Study SelectionRandomized clinical trials of any intervention reported as having stopped early because of results favoring the intervention. There were no exclusion criteria.Data ExtractionTwelve reviewers working independently and in duplicate abstracted data on content area and type of intervention tested, reporting of funding, type of end point driving study termination, treatment effect, length of follow-up, estimated sample size and total sample studied, role of a data and safety monitoring board in stopping the study, number of interim analyses planned and conducted, and existence and type of monitoring methods, statistical boundaries, and adjustment procedures for interim analyses and early stopping.Data SynthesisOf 143 RCTs stopped early for benefit, the majority (92) were published in 5 high-impact medical journals. Typically, these were industry-funded drug trials in cardiology, cancer, and human immunodeficiency virus/AIDS. The proportion of all RCTs published in high-impact journals that were stopped early for benefit increased from 0.5% in 1990-1994 to 1.2% in 2000-2004 (P

Historically medical science journals in the 19th century were primarily published in German or English. With the Internet era, it appears that English has become the language of science. There is a growing concern that non-English journals are on the decline with a clear and present danger of loss in diversity as well as originality of research. The first 40 general and internal medicine journals listed under the ISI are published in English. Purpose Full Text on the Net bias (FUTON Bias) is the “tendency to peruse what is more readily available on the net.” We sought to determine if Full Text on the Net bias (FUTON Bias) might explain the decline of non-English journals and elucidate ways in which non-English journals might enhance visibility of research and scholarship. Methods We identified all non-English journals (Spanish, Dutch, Italian, French and German) listed in ISI under Medicine, General and Internal (n = 21). We excluded Schweizerische Medizinische Wochenschrift as it has been published in English since 2001 as Swiss Medical Weekly. The on-line status of the remaining journals was ascertained in MEDLINE as FUTON, abstracts or references only. All Impact Factors from 1988 to 2003 were abstracted. Summary of Results We observed that traditionally non-English journals that also published in English (multi-lingual) had an increase in their impact factors while those that chose not to do so maintained their base impact factors. This confirms the existence of a language bias: non-English journals tend to have lower impact factors, even in the Internet era. Interestingly however, the rise in impact factors of such multi-lingual journals paralleled in time and inception the rise of those providing FUTON and the availability of the Internet as a mode of scientific dissemination Also, the mean impact factor of multi-lingual FUTON journals was approximately threefold higher than multilingual journals that provided only abstracts or references. Conclusion Our study suggests that non-English journals may better serve national and international audiences by becoming FUTON. Financial considerations may limit the ability of some of these journals in providing “free” FUTON. However, these non-English journals may be able to effectively disseminate scientific knowledge, improve the visibility of research and impact factors as well as stem their decline by at least providing articles on the net as FUTON. The innate tendency to pick the “low-hanging fruit of convenience” greatly enhances the odds that a FUTON article will be read or cited. By the same token, invisible research, defined as not readily accessible on-line, may possibly be ignored or overlooked and therefore disregarded.

Introduction Full Text on the Net bias (FUTON Bias) is the “tendency to peruse what is more readily available on the Internet.” This innate tendency to pick the “low-hanging fruit of convenience” greatly enhances the odds that a FUTON article will be read or cited. By the same token, invisible research, defined as not readily accessible on-line, may possibly be ignored or overlooked and therefore disregarded. Purpose We sought to determine if there was any effect on the increase in impact factor (IF) of immunology journals which were available FUTON and whether going on-line affected the IF. Methods A comprehensive search was made to identify all rheumatology and immunology journals worldwide using MEDLINE, PubMed, and EMBASE databases and several search engines. The on-line status of these journals in MEDLINE (as FUTON, abstracts only, and no abstracts or citations) was ascertained. Impact factors for all available journals from 1990 to 2003 were abstracted. Journals that went on-line in the first half of the Internet era (prior to 1998), as opposed to those that went on-line later, were compared using sign rank and rank sum tests. Summary of Results In general impact factors have increased with the availability of the World Wide Web. As expected the “prior to 1998 era” journals (n = 69) tended to have higher mean impact factors than the post 1998 era journals (n = 58) available as FUTON (2.994 ± 0.793 vs. 0.1.392 ± 0.0.195). Interestingly while FUTON and “abstract only” journals continued to improve their impact factors every year after they went on-line those that had only references or citations without abstracts failed to improve their impact factors. Also “abstract only” journals failed to catch up with the impact factors of their peer journals available as FUTON (p Conclusion This suggests that although the Internet has increased awareness of the existence of a journal, those allowing FUTON access are likely to make substantial leaps in their impact factors and continue to outstrip their peers who fail to provide such access. Also, barrier free access will threaten journals that insist on subscription who need to recognize the looming threat of becoming obscure. The FUTON bias like the “Tower of Babel” bias influences visibility of research and limits consideration of relevant medical literature impeding the progress of evidence based medicine.

Infective endocarditis (IE) is a life-threatening disease associated with serious complications. The GBD 2010 (Global Burden of Disease, Injuries, and Risk Factors) study IE expert group conducted a systematic review of IE epidemiology literature to inform estimates of the burden on IE in 21 world regions in 1990 and 2010. The disease model of IE for the GBD 2010 study included IE death and 2 sequelae: stroke and valve surgery. Several medical and science databases were searched for IE epidemiology studies in GBD high-, low-, and middle-income regions published between 1980 and 2008. The epidemiologic parameters of interest were IE incidence, proportions of IE patients who developed stroke or underwent valve surgery, and case fatality. Literature searches yielded 1,975 unique papers, of which 115 published in 10 languages were included in the systematic review. Eligible studies were population-based (17%), multicenter hospital-based (11%), and single-center hospital-based studies (71%). Population-based studies were reported from only 6 world regions. Data were missing or sparse in many low- and middle-income regions. The crude incidence of IE ranged between 1.5 and 11.6 cases per 100,000 people and was reported from 10 countries. The overall mean proportion of IE patients that developed stroke was 0.158 ± 0.091, and the mean proportion of patients that underwent valve surgery was 0.324 ± 0.188. The mean case fatality risk was 0.211 ± 0.104. A systematic review for the GBD 2010 study provided IE epidemiology estimates for many world regions, but highlighted the lack of information about IE in low- and middle-income regions. More complete knowledge of the global burden of IE will require improved IE surveillance in all world regions.

Summary Background Bartonella henselae , Bartonella quintana , and Bartonella bacilliformis are responsible for the majority of cases of bartonellosis in humans. These species have various unique epidemiologic characteristics, clinical manifestations, and treatment approaches. The objective of this study was to summarize the evidence on the treatment for the three most common species of Bartonella in humans. Methods We searched electronic databases through August 2011 for randomized controlled trials and observational studies designed to evaluate the efficacy and safety of the regimens used to treat diseases produced by B. henselae , B. quintana , and B. bacilliformis . Study selection and appraisal were done in duplicate. Results We found two randomized and seven non-randomized studies at high risk of bias. For cat scratch disease, antibiotics did not significantly affect the cure rate or time to achieve cure. In chronic bacteremia, gentamicin and doxycycline significantly increased the resolution rate. The recommended treatment was not better than other regimens for infectious endocarditis and bacillary angiomatosis. Conclusions Current clinical practice for the treatment of bartonellosis relies mostly on expert opinion and antimicrobial susceptibility data. Randomized controlled trials are needed in the field to compare different treatment options.

Objectives Hemodialysis centers regularly survey arteriovenous (AV) accesses for signs of dysfunction. In this review, we synthesize the available evidence to determine to what extent proactive vascular access monitoring affects the incidence of AV access thrombosis and abandonment compared with clinical monitoring. Methods We searched electronic databases (MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science, and SCOPUS) and sought references from experts, bibliographies of included trials, and articles that cited included studies. Two reviewers independently assessed trial quality and extracted data. We used random effects meta-analysis to estimate the pooled relative risk (RR) and 95% confidence interval (CI) across studies and conducted subgroup analyses to explain heterogeneity. The I 2 statistic was used to assess heterogeneity of treatment effect among trials. Results Nine studies (1363 patients) compared a strategy of surveillance vs clinical monitoring. A vascular intervention to maintain or restore patency was provided to both groups if needed. Surveillance followed by intervention led to a nonsignificant reduction of the risk of access thrombosis (RR, 0.82; 95% CI, 0.58-1.16; I 2 = 37%) and access abandonment (RR, 0.80; 95% CI, 0.51-1.25; I 2 = 60%). Three studies (207 patients) compared the effect of vascular interventions vs observation in patients with abnormal surveillance result. Vascular interventions after an abnormal AV access surveillance led to a significant reduction of the risk of access thrombosis (RR, 0.53; 95% CI, 0.36-0.76) and a nonsignificant reduction of the risk of access abandonment (RR, 0.76; 95% CI, 0.43-1.37). Conclusion Very low quality evidence yielding imprecise results suggests a potentially beneficial effect of AV access surveillance followed by interventions to restore patency. This inference, however, is weak and will require randomized trials of AV access surveillance vs clinical monitoring for rejection or confirmation.

International audience; BACKGROUND: Measuring disease and injury burden in populations requires a composite metric that captures both premature mortality and the prevalence and severity of ill-health. The 1990 Global Burden of Disease study proposed disability-adjusted life years (DALYs) to measure disease burden. No comprehensive update of disease burden worldwide incorporating a systematic reassessment of disease and injury-specific epidemiology has been done since the 1990 study. We aimed to calculate disease burden worldwide and for 21 regions for 1990, 2005, and 2010 with methods to enable meaningful comparisons over time. METHODS: We calculated DALYs as the sum of years of life lost (YLLs) and years lived with disability (YLDs). DALYs were calculated for 291 causes, 20 age groups, both sexes, and for 187 countries, and aggregated to regional and global estimates of disease burden for three points in time with strictly comparable definitions and methods. YLLs were calculated from age-sex-country-time-specific estimates of mortality by cause, with death by standardised lost life expectancy at each age. YLDs were calculated as prevalence of 1160 disabling sequelae, by age, sex, and cause, and weighted by new disability weights for each health state. Neither YLLs nor YLDs were age-weighted or discounted. Uncertainty around cause-specific DALYs was calculated incorporating uncertainty in levels of all-cause mortality, cause-specific mortality, prevalence, and disability weights. FINDINGS: Global DALYs remained stable from 1990 (2*503 billion) to 2010 (2*490 billion). Crude DALYs per 1000 decreased by 23% (472 per 1000 to 361 per 1000). An important shift has occurred in DALY composition with the contribution of deaths and disability among children (younger than 5 years of age) declining from 41% of global DALYs in 1990 to 25% in 2010. YLLs typically account for about half of disease burden in more developed regions (high-income Asia Pacific, western Europe, high-income North America, and Australasia), rising to over 80% of DALYs in sub-Saharan Africa. In 1990, 47% of DALYs worldwide were from communicable, maternal, neonatal, and nutritional disorders, 43% from non-communicable diseases, and 10% from injuries. By 2010, this had shifted to 35%, 54%, and 11%, respectively. Ischaemic heart disease was the leading cause of DALYs worldwide in 2010 (up from fourth rank in 1990, increasing by 29%), followed by lower respiratory infections (top rank in 1990; 44% decline in DALYs), stroke (fifth in 1990; 19% increase), diarrhoeal diseases (second in 1990; 51% decrease), and HIV/AIDS (33rd in 1990; 351% increase). Major depressive disorder increased from 15th to 11th rank (37% increase) and road injury from 12th to 10th rank (34% increase). Substantial heterogeneity exists in rankings of leading causes of disease burden among regions. INTERPRETATION: Global disease burden has continued to shift away from communicable to non-communicable diseases and from premature death to years lived with disability. In sub-Saharan Africa, however, many communicable, maternal, neonatal, and nutritional disorders remain the dominant causes of disease burden. The rising burden from mental and behavioural disorders, musculoskeletal disorders, and diabetes will impose new challenges on health systems. Regional heterogeneity highlights the importance of understanding local burden of disease and setting goals and targets for the post-2015 agenda taking such patterns into account. Because of improved definitions, methods, and data, these results for 1990 and 2010 supersede all previously published Global Burden of Disease results. FUNDING: Bill & Melinda Gates Foundation.

Background Studies suggest that the 9p21-3 locus may influence susceptibility to myocardial infarction. We performed a systematic review and meta-analysis to assess whether this locus is associated with severity of coronary atherosclerosis and adverse clinical outcomes in those with known coronary disease. Methods Multiple electronic databases were searched from inception through August 2012. Studies examining 9p21-3 genotype in patients with known coronary artery disease were included. We extracted the association of the 9p21-3 locus with measures of severity of coronary atherosclerosis [number of diseased vessels, Gensini Score, Duke CAD Prognostic Index (DPI)], angiographic outcomes [change in minimum lumen diameter (∆MLD) and number of new lesions at follow-up], and key clinical outcomes (all-cause mortality, recurrent myocardial infarction and the need for coronary revascularization). Relative risks (RR) and weighted mean difference (WMD) were pooled using the random effects models. Results 23 cohorts enrolling 16,860 participants were analyzed. There was no significant difference between HR and LR genotypes in terms of all-cause mortality, recurrent myocardial infarction or the frequency of coronary revascularization. HR genotype was associated with increased risk of triple vessel disease (RR = 1.34; 95% CI 1.08-1.65; P = 0.01) and increased baseline Gensini Score (WMD = 5.30; 95% CI 0.66-9.93; P = 0.03). However there was no association with DPI (WMD = 4.00; 95% CI 2.94-10.94; P = 0.26). HR genotype did not predict ∆MLD or number of new lesions at follow-up. Conclusions Patients of coronary atherosclerosis who carry the high risk genotype of the 9p21-3 allele may be more likely to have multi-vessel CAD. However the effect of this allele on CAD progression and disease specific clinical outcomes are not observed possibly due to diminishing genetic risk following dietary modification and therapy.

The purpose of the present study was to systematically review the effect of cyclophosphamide treatment on pulmonary function in patients with systemic sclerosis and interstitial lung disease. The primary outcomes were the mean change in forced vital capacity and in diffusing capacity for carbon monoxide after 12 months of therapy in patients treated with cyclophosphamide. Three randomized clinical trials and six prospective observational studies were included for analysis. In the pooled analysis, the forced vital capacity and the diffusing capacity for carbon monoxide predicted values after 12 months of therapy were essentially unchanged, with mean changes of 2.83% (95% confidence interval = 0.35 to 5.31) and 4.56% (95% confidence interval = -0.21 to 9.33), respectively. Cyclophosphamide treatment in patients with systemic sclerosis-related interstitial lung disease does not result in clinically significant improvement of pulmonary function.