The systematic guideline review: method, rationale, and test on chronic heart failure

Background: Evidence-based guidelines have the potential to improve healthcare. However, their de-novo-development requires substantial resources-especially for complex conditions, and adaptation may be biased by contextually influenced recommendations in source guidelines. In this paper we describe a new approach to guideline development-the systematic guideline review method (SGR), and its application in the development of an evidence-based guideline for family physicians on chronic heart failure (CHF). Methods: A systematic search for guidelines was carried out. Evidence-based guidelines on CHF management in adults in ambulatory care published in English or German between the years 2000 and 2004 were included. Guidelines on acute or right heart failure were excluded. Eligibility was assessed by two reviewers, methodological quality of selected guidelines was appraised using the AGREE instrument, and a framework of relevant clinical questions for diagnostics and treatment was derived. Data were extracted into evidence tables, systematically compared by means of a consistency analysis and synthesized in a preliminary draft. Most relevant primary sources were re-assessed to verify the cited evidence. Evidence and recommendations were summarized in a draft guideline. Results: Of 16 included guidelines five were of good quality. A total of 35 recommendations were systematically compared: 25/35 were consistent, 9/35 inconsistent, and 1/35 un-rateable (derived from a single guideline). Of the 25 consistencies, 14 were based on consensus, seven on evidence and four differed in grading. Major inconsistencies were found in 3/9 of the inconsistent recommendations. We re-evaluated the evidence for 17 recommendations (evidence-based, differing evidence levels and minor inconsistencies) - the majority was congruent. Incongruity was found where the stated evidence could not be verified in the cited primary sources, or where the evaluation in the source guidelines focused on treatment benefits and underestimated the risks. The draft guideline was completed in 8.5 man-months. The main limitation to this study was the lack of a second reviewer. Conclusion: The systematic guideline review including framework development, consistency analysis and validation is an effective, valid, and resource saving-approach to the development of evidence-based guidelines

Recent advances reveal IL-8 signaling as a potential key to targeting breast cancer stem cells

Breast cancer stem-like cells (CSCs) are an important therapeutic target as they are purported to be responsible for tumor initiation, maintenance, metastases, and disease recurrence. Interleukin-8 (IL-8) is upregulated in breast cancer compared with normal breast tissue and is associated with poor prognosis. IL-8 is reported to promote breast cancer progression by increasing cell invasion, angiogenesis, and metastases and is upregulated in HER2-positive cancers. Recently, we and others have established that IL-8 via its cognate receptors, CXCR1 and CXCR2, is also involved in regulating breast CSC activity. Our work demonstrates that in metastatic breast CSCs, CXCR1/2 signals via transactivation of HER2. Given the importance of HER2 in breast cancer and in regulating CSC activity, a pathway driving the activation of these receptors would have important biological and clinical consequences, especially in tumors that express high levels of IL-8 and other CXCR1/2-activating ligands. Here, we review the IL-8 signaling pathway and the role of HER2 in maintaining an IL-8 inflammatory loop and discuss the potential of combining CXCR1/2 inhibitors with other treatments such as HER2-targeted therapy as a novel approach to eliminate CSCs and improve patient survival

Evidence for single-limb exercises on exercise capacity, quality of life, and dyspnea in patients with chronic obstructive pulmonary disease or chronic heart failure

Background: Although single-limb exercise (SLE) has been used for patients with chronic obstructive pulmonary disease (COPD) and for patients with chronic heart failure (CHF), the evidence for SLE has not been evaluated systematically and remains unclear. Objectives: Determine the evidence for the effect of SLE compared to any comparator on outcome measurements for exercise capacity, quality of life (QoL) or dyspnea in patients with COPD or CHF. Methods: PubMed, PEDro, and CENTRAL databases were searched from inception until 31 May 2011. Searches started 1 April 2011. English language randomized controlled trials (RCTs) were included. Extraction of data was performed by two review authors. Data and evidence for SLE were summarized in accordance with grading of recommendations assessment, development and evaluation (GRADE) guidelines. Authors of included studies were contacted for missing data. Results: Six RCTs (two COPD and four CHF) were included. Low to very low-quality evidence indicates that SLE significantly improved exercise capacity, but not dyspnea, in patients with COPD, and significantly improved exercise capacity outcomes compared to a control in patients with CHF. However, when SLE was compared to non-SLE regimes in patients with CHF, positive effects were found irrespective of training regime regarding exercise capacity and QoL. Conclusions: SLE appears to be effective in both conditions especially regarding exercise capacity, and might be included in exercise programs in patients with COPD or CHF. However, the evidence is low to very low according to GRADE and more clinical studies of high quality are required