Critical appraisal of RCTs by 3rd year undergraduates after short courses in EBM compared to expert appraisal.

Introduction: An essential aim of courses in evidence-based medicine (EBM) is to improve the skills for reading and interpreting medical literature adequately. Regarding the conceptual framework, it is important to consider different educational levels. Aim: Our primary aim was to investigate the applicability of different instruments for the assessment of methodological study quality by 3rd grade students after short courses in EBM. Our secondary outcomes were agreement with expert assessments and student's knowledge and competences. Methods: We conducted four short courses in EBM of 90 minutes each for health care management and medical students focused on critical appraisal of the literature. At the end, the students assessed five publications about randomized controlled trials (RCTs) using five different instruments; the results were compared to expert assessments. Results: In total, 167 students participated in our EBM courses. Students' assessments showed a non-systematic over- and underestimation of risk of bias compared to expert assessments with no clear direction. Agreement with expert assessments ranged between 66% to over 80%. Across RCTs, evidence was found that the choice of instrument had an impact on agreement rates between expert and student assessments (p=0.0158). Three RCTs showed an influence of the instrument on the agreement rate (p<0.05 each). Discussion: Our results contrast sharply with those of many other comparable evaluations. Reasons may be a lack of students' motivation due to the compulsory courses, and the comparison to a reference standard in addition to self-ratings causing objectivity. Conclusion: Undergraduates should become familiar with the principles of EBM, including research methods, and the reading of scientific papers as soon as possible. For a deeper understanding, clinical experience seems to be an indispensable precondition. Based on our results, we would recommend an integration of lectures about EBM and critical appraisal at least twice during studies and with greater intensity shortly before graduation.

[Rapid Reviews: Sisyphos' Salvation? - An Inventory]. / Rapid Reviews: Sisyphos' Erlösung? ­ Eine Bestandsaufnahme.

Objective and Methods: The aim of this article is to perform an inventory on the subject of rapid reviews. Results: Carrying out a systematic review or health technology assessment (HTA) is costly and time-consuming. Usually, it takes between six months and one year to complete a systematic review, and at least one year to complete an HTA. Since questions relating to health care can be urgent, decision-makers sometimes need information in a timely manner. Rapid reviews are a kind of systematic reviews, which are conducted within shorter timeframes and, so, are less expensive. They are characterised by methodological restrictions, which can apply at different stages of the review process. Frequently, limitations are imposed with respect to literature search and retrieval. However, the screening of the title and abstract, full text screening, data extraction and quality assessment can also be affected by restrictions. Conclusions: The use of rapid review methodology saves time and costs. In situations that require quick decisions, rapid reviews are the only option for taking decisions. However, methodological restraints may result in greater vulnerability to bias.

[Assessment of risk of bias in controlled studies]. / Bewertung des Risikos für Bias in kontrollierten Studien.

BACKGROUND: Practicing physicians are faced with many medical decisions daily. These are mainly influenced by personal experience but should also consider patient preferences and the scientific evidence reflected by a constantly increasing number of medical publications and guidelines. With the objective of optimal medical treatment, the concept of evidence-based medicine is founded on these three aspects. It should be considered that there is a high risk of misinterpreting evidence, leading to medical errors and adverse effects without knowledge of the methodological background. OBJECTIVES: This article explains the concept of systematic error (bias) and its importance. Causes and effects as well as methods to minimize bias are discussed. This information should impart a deeper understanding, leading to a better assessment of studies and implementation of its recommendations in daily medical practice. CONCLUSION: Developed by the Cochrane Collaboration, the risk of bias (RoB) tool is an assessment instrument for the potential of bias in controlled trials. Good handling, short processing time, high transparency of judgements and a graphical presentation of findings that is easily comprehensible are among its strengths. Attached to this article the German translation of the RoB tool is published. This should facilitate the applicability for non-experts and moreover, support evidence-based medical decision-making.

The evidence for the use of growth factors and active skin substitutes for the treatment of non-infected diabetic foot ulcers (DFU): a health technology assessment (HTA).

AIMS: Assessment of the safety, efficacy and effectiveness of growth factors alone or in combination with other technologies in the treatment of DFU including medical, economical, social, ethical and juridical aspects. METHODS: We systematically searched relevant data bases limited to English and German language and publications since 1990. Review and assessment of the quality of publications followed methods conforming to widely accepted standards for evidence-based medicine and health economics. RESULTS: We identified 25 studies comparing becaplermin, rhEGF, bFGF and the metabolically active skin grafts Dermagraft and Apligraf with standard wound care (SWC) alone or extracellular wound matrix. Study duration ranged from 12 to 20 weeks and the study population comprised between 17 and 382 patients. Treatment with becaplermin, rhEGF, Dermagraft and Apligraf resulted in a higher incidence of complete wound closure and shorter time to complete wound healing with statistically significant differences. Regarding the proportion of adverse events there was no difference between treatment groups. The methodological quality of the studies was affected by significant deficiencies. Economic evaluations showed becaplermin being cost-effective. CONCLUSIONS: Add-on therapy with growth factors and active skin substitutes for treating uncomplicated DFU could be an alternative to SWC alone. For explicit recommendations further studies with stronger evidence are necessary.

[Health economics of chronic infectious diseases: the example of hepatitis C]. / Gesundheitsökonomische Aspekte chronischer Infektionskrankheiten am Beispiel der chronischen Hepatitis C.

Based on the German Hepatitis C Model (GEHMO) we developed a Hepatitis C Policy Model and applied it to the heterogeneous German hepatitis C population within the German health care context. We used Markov cohort simulation to predict absolute clinical and economic outcomes for a 20-year time horizon. For the cost-effectiveness analysis, a lifelong time horizon was used. Four different strategies were compared: (1) no antiviral treatment, (2) interferon monotherapy, (3) combination therapy with interferon plus ribavirin, and (4) combination therapy with pegylated interferon plus ribavirin. Based on our model, antiviral therapy with pegylated interferon and ribavirin could prevent about 17,000 cases of cirrhosis, 580 liver transplants, and 7,600 HCV-related deaths and is expected to save about 53,000 life years at total costs of 1.3 billion Euros within the next 20 years. Pegylated interferon plus ribavirin was the most effective treatment with an incremental cost-utility ratio of 23,000 Euros per quality-adjusted life year saved.

Histone H1-mediated transfection: serum inhibition can be overcome by Ca2+ ions.

PURPOSE: One of the drawbacks of polycationic and cationic liposomal gene transfer is its sensitivity to serum. Gene therapy requires the transfectant-DNA complex to be resistant to serum as well as blood. Since Ca2+ has proved to be an efficient cofactor of polycationic gene transfer, we decided to investigate its effects on transfection in the presence of serum. METHODS: We studied transgene expression of luciferase gene (pCMV Luc) on ECV 304 human endothelial cells using H1 histone and DOSPER as transfectants in the presence of 0-100% fetal calf serum. RESULTS: H1-and DOSPER-mediated transfection was found to be inhibited by serum above the concentration of 10%. If 2 mM Ca2+ or 2 mM Ca2+/0.1 mM chloroquine was included in the culture medium which replace the transfection mixture and was left on the cells for 24 hours postincubation, the inhibiting effect of even 100% serum was overcome. CONCLUSIONS: A high serum level does not interfere with binding and uptake of H1- and DOSPER-DNA complexes, but inhibits subsequent steps such as endosomal escape. Ca2+ in the form of nascent calcium phosphate microprecipitates and other lysosomolytical agents facilitate endosomal/lysosomal release by their fusigenic and membranolytic activity.

A new efficient method for transfection of neonatal cardiomyocytes using histone H1 in combination with DOSPER liposomal transfection reagent.

Although cationic lipids are successfully used for gene transfer in vitro, primary cells such as neonatal cardiomyocytes frequently resist efficient transfection. We show here that the polycationic lipid DOSPER in combination with histone H1 was much more efficient in transfection of neonatal cardiomyocytes than DOSPER alone or other cationic lipids. This has been shown for transfection with the reporter plasmids pSV beta-gal and pCMV luc. If viral transfections are not possible, this mild method is an alternative to transfect cardiomyocytes.