bluuebunny/crossref_metadata_2025_split huggingface dataset:
008 Principles for the Development of Specialty Society Clinical Guidelines
Authors: Fulda G , Wolfkiel C , Begolka W Smith , Campos-Outcalt D , Groman R , Rubin K , Davidson C , May C , Starkey M , Qaseem A 
Published: August 2013

BackgroundIn 2011 the Institute of Medicine (IOM) issued a report “Clinical Practice Guidelines We Can Trust” and “Standards for Systematic Reviews”. These documents represent an idealised approach to guideline development. The Council of Medical Specialty Societies (CMSS) was challenged to provide leadership on a pragmatic pathway for developing “Trustworthy” guidelines. CMSS representing 38 societies and the Clinical Practice Guideline (CPG) group is the largest of nine component groups.ContextThe IOM Trustworthy report contains 20 standards addressing transparency, conflict of interest and other recommendations. Guidelines International Network (GIN) published a set of 11 key components for high quality and trustworthy guidelines. Reconciling and applying these standards is challenging for specialty societies who by their very nature may be insular and sometime resource limited.Description of Best PracticeThe CPG writing group including representatives from AAD, AAFP, AANS AAP, ACC, ACP, ACOEM and SCCM developed a set of 80 principles that were approved as policy by the CMSS Board in late 2012. These Principles include areas that a specialty society should, must or may consider in developing their own guidelines development methodology.Lessons for Guideline Developers, Adaptors, Implementers, and/or UsersThese areas correspond to those outlined by the IOM and GIN but are intended to detail more specific issues that specialty societies are confronted by such as balancing panel expertise and potential bias. The overriding CMSS concepts include a practice approach to extensive evidence review, transparent conflict of interest management and broad stakeholder involvement. The CMSS Principles are intended to be interpreted transparently by member societies developing clinical practice guidelines.
010 “Ethics Consultation” and “Clinical Ethics Committees“ (CECs) in Medicine: Entirely “experimental” and not yet “fit for purpose”
Authors: Stratling M , Sedemund-Adib B 
Published: August 2013

BackgroundInternationally multiple initiatives are under way (e.g. Germany, Switzerland, UK) to recommend “Clinical Ethics Consultation” and “Clinical Ethics Committees“ (CECs) in guidelines.ObjectivesThese aim to improve ethical discourse and decision making in medicine.MethodsAppraisal of available evidence and literature [1].ResultsFor CE-Consultation, mostly CECs are implemented. Empirically their acceptance is poor, despite a large “demand”. Historically this international paradox is stable (“failure to thrive phenomenon”). Repeated initiatives and “re-brandings” can be identified. They made no tangible difference. Theories and methods are heterogeneous, patchy and contradictory. Their efficacy is unproven. A multitude of issues concerning quality, competence, qualifications, relevance, transparency, independence, conflicts of interests and legitimacy are unresolved.DiscussionFrom the perspective of clinically and scientifically oriented Ethics in Medicine, present CE-Consultation represents a “cluster” of highly “experimental” tools, techniques and methods. The available evidence consistently suggests grave deficits. In developing medical guidelines and recommendations, professional bodies are duty-bound to adhere to robust, evidence-based processes. Applying such criteria, CE-Consultation and CECs fail to meet all requirements. The apparent intention to apply a “double-standard” to promote a “laudable” medico-“ethical” intention raises grave (not least ethical and scientific) concerns. These are presented and discussed in detail.Reference1. Strätling M. (2012) MedR 30: 428–436.
016 Retirement of Performance Measures In A National Pay for Performance (P4P) Scheme
Authors: Sutcliffe D , Hobbs L , Flatt G , Shaw E , Stokes T , Baillie N 
Published: August 2013

BackgroundP4P schemes, providing financial incentives across a range of improvement indicators, are widely used and can improve health outcomes. These systems can work at different levels, including at the national level. It is important that performance measures (PMs) used in such systems have a robust and up-to-date evidence base to support continued use and they remain fit for purpose; this involves selecting PMs for ‘retirement’.ObjectivesTo: i) describe methods used in selecting PMs for retirement, ii) present alternative methods for selecting PMs for retirement.MethodsIdentifying PMs for retirement have been based on several methods including: i) reported trends in achievement and exception reporting ii) review of paired PMs iii) review of supporting evidence and/or technical specifications iv) modified Delphi.ResultsWe will present results of using these methods, and discuss alternatives to these (e.g., the Nominal Group Technique), and implications for retirement of PMs.DiscussionThese methods have been successful in identifying indicators for retirement. To ensure continual improvements in quality of care delivered through the P4P scheme and provide opportunities for new areas to be added, the review and retirement of PMs remains important.Implications for Guideline Developers/UsersGuideline developers should be aware of key PMs based on guidance recommendations and have systems to ensure that underpinning evidence is up-to-date. PM developers should have processes to ensure that PMs are based on up-to-date evidence and remain fit for purpose.
023 Feasibility and Efficiency of Strategies For Updating Clinical Practice Guidelines
Authors: García L Martínez , Sanabria A , Araya I , Vernooij R , Solàà I , Lawson J , Navarro T , Haynes B , Román J Gracia San , Kotzeva A , Marti T , Alonso-Coello P 
Published: August 2013

BackgroundExhaustive search strategies (ESS) for updating clinical practice guidelines (CPGs) recommendations are laborious and expensive. Highly sensitive and specific alternative search strategies are necessary to improve the efficiency in recommendations updating.ObjectivesTo compare alternative search strategies against ESSMethodsWe ran three different search strategies in a convenience sample of four CPGs from the CPGs National Programme in Spain: 1) Original ESS (gold standard); 2) Search strategy in the McMaster Premium LiteratUre Service (PLUS) database; and 3) Restrictive strategy with the least number of MeSH terms and text words from the original ESS. We retrieved the key references (which triggered an update) from the original ESS and evaluated their presence in the PLUS and restrictive strategies results. We calculated the sensitivity, specificity, precision, and accuracy for the PLUS and restrictive strategies compared to the ESS.ResultsThe overall number of references in the PLUS strategy was lower than in the ESS (39,133 versus 2,635). The PLUS strategy retrieved a range of 1.12% to 12.1% of the total number of references retrieved by the ESS per guideline.DiscussionOur project assessed two novel restrictive search strategies for the updating of CPGs, which could reduce the workload while displaying similar results. Full final findings of this project will be presented at the GIN meeting.Implications for Guideline Developers/UsersOur project has important implications for updating CPGs, informing on the feasibility and efficiency of two novel search strategies.
024 Maximising efficiency in updating guidelines through prioritisation of clinical questions
Authors: Amos Q , Chan W , Tom G 
Published: August 2013

BackgroundTo maximise efficiency in updating clinical guidelines it is important to understand which of its component clinical questions impact patient care most. Evaluating, editing, and prioritising of each clinical question is required to identify those that warrant updating.ObjectivesTo describe the methods used by a US health care delivery organisation to prioritise questions within an integrated cardiovascular guideline to determine those that were most important for updating.Methods127 clinical questions within an integrated cardiovascular guideline were ranked (using a Likert scale of 1–9) by importance for literature monitoring by clinical experts in each disease domain of the guideline. Examples of factors that influenced rankings included existence of high quality systematic reviews, knowledge that current evidence was relatively unchanged, and the notion that the question was no longer clinically relevant. Questions ranked 7–9 in importance for literature monitoring were considered most important for updating. Conversely, questions with low rankings were considered for retirement.ResultsOf 127 questions ranked, 16 were identified as important for literature updating; 12 were retired. We were able to address the most important questions and avoid updating delays of 6–18 months.DiscussionHaving these questions prioritised at the outset of updating allowed the healthcare organisation to ensure that the most important clinical questions were being addressed thus making the most efficient use of resources.Implications for Guideline Developers/UsersEvaluating, editing, and prioritising clinical questions improves efficiency when updating guidelines.
028 How Do Clinicians Like and Understand Trustworthy Guidelines? Randomised Controlled Trial Using Clickers in Educational Sessions
Authors: Vandvik P , Brandt L , Kristiansen A , Alonso P , Agoritsas T , Akl E , Guyatt G 
Published: August 2013

BackgroundClinical practice guidelines (CPG) often have shortcomings in presentation formats that limit dissemination at the point of care. As part of the DECIDE project we have developed multilayered CPG presentation formats. Comprehensive user-testing of the formats has provided us with alternative presentation formats now ready for randomised trials but also an important insight: Insufficient conceptual understanding of guideline methodology (e.g. strength of recommendations and quality of evidence) may hamper application of CPG recommendations in practice.ObjectivesTo determine physicians’ understanding, attitudes and preferences concerning trustworthy guidelines in traditional and new presentation formats (DECIDE A and B).MethodsIn this randomised controlled trial we will recruit 100 physicians attending a standardised lecture with 3 components: 1) presentation of clinical scenario, 2) explanations of key concepts of trustworthy CPG (e.g. GRADE, AGREE II) and 3) presentation of a current trustworthy CPG relevant to the scenario, displayed in traditional PDF format and DECIDE A and B formats. Throughout the lecture participants will answer questions with ‘Clickers’ and be randomly assigned to alternative presentation formats by concealed allocation and blinding, through the use of eyepatches.ResultsWe will present results from the trial at the conference.DiscussionIf our approach of integrating randomised trials into educational sessions is feasible and provides valid results we will conduct multiple such trials in DECIDE.Implications for Guideline Developers and UsersOptimised GL presentation formats and sufficient conceptual understanding, as researched in this trial, should facilitate the uptake of trustworthy CPG and application of research evidence in practice.
035 What Do Guideline Appraisal Tools Assess? A Systematic Review
Authors: Siering U , Eikermann M , Hausner E , Hoffmann-Eber W , Neugebauer E 
Published: August 2013

BackgroundClinical practice guidelines should provide a rational basis for healthcare decisions; however, their quality is often poor.ObjectivesTo systematically identify and describe guideline appraisal tools and draw conclusions for guideline appraisal.MethodsWe conducted a systematic search in MEDLINE, EMBASE and the Cochrane Library for English and German-language guideline appraisal tools published after 1995. Reference lists of included publications were also screened. Dimensions of guideline quality were then generated from these publications and from articles by Cluzeau 1999, Graham 2000 and Vlayen 2005. Finally, the questions contained in the appraisal tools were allocated to the quality dimensions and summarised.ResultsOverall, 40 appraisal tools were included and 13 quality dimensions identified. The main focus was the identification, assessment and presentation of evidence in guidelines. Questions on dealing with norms and values in guideline development, patient involvement, conflicts of interest, or implementation of guidelines into clinical practice were rare. The tools often assessed the appropriate documentation of the guideline development process (e.g. reporting of the search strategy), without addressing the appraisal of content of the development process (e.g. appropriateness of the search strategy) and the appraisal of clinical content.DiscussionBecause many appraisal tools do not contain questions on norms and values or on potential conflicts of interest of guideline authors, important aspects potentially influencing the reliability of guidelines are not covered. In addition, an appraisal of content of the guideline development process and an appraisal of clinical content are often lacking.
046 Guideline Development Tool (GDT) – Web-Based Solution for Guideline Developers and Authors of Systematic Reviews
Authors: Brozek J , Akl E , Falck-Ytter Y , Kunstman P , Meerpohl J , Mustafa R , Nowak A , Oxman A , Santesso N , Wiercioch W , Schünemann H 
Published: August 2013

BackgroundGuideline developers and other health care decision makers benefit from following a structured process of specifying the health care questions they intend to answer and the outcomes of interest, assessing the confidence in the available evidence, gathering information about the values and preferences of the target population, and presentation of their results and decisions to the target users. Many guideline developers use the GRADE Profiler (GRADEpro) software used to conduct this work.ContextGRADE’s approach is currently being further defined in the DECIDE (Developing and Evaluating Communication Strategies to Support Informed Decisions and Practice Based on Evidence) project.Description of Best PracticeThe Guideline Development Tool (GDT) is the extension of the GRADE Profiler (GRADEpro) software. The GDT provides an integrated platform-independent web-based solution for health care decision makers offering support for the whole process of making decisions and developing recommendations including question formulation, generation and prioritisation of outcomes, support for teamwork, management of potential conflicts of interest, presentation of results (including the functionality of GRADEpro) and decision support. We tested the software with individual users and in workshops as well as in guideline development processes.Lessons for Guideline Developers, Adaptors, Implementers, and/or UsersFollowing a structured and systematic process, transparency and clarity of presentation facilitates the use of results of systematic reviews and facilitates development, updating and adaptation of evidence-based recommendations and decisions. Storing all information in a uniform, structured, transparent and annotated way also greatly facilitates updating and adaptation of systematic reviews and guidelines.
054 Transforming Evidence From Multiple Guidelines Into User Friendly Clinical Practice Tools For Remote Cancer Treatment-Related Symptom Management: The Costars Project
Authors: Stacey D , Carley M , Harrison M 
Published: August 2013

ObjectivesTo transform evidence from guidelines for clinical practice tools for remote management of patients experiencing symptoms related to cancer treatment. Clinical practice protocols are defined as user-friendly knowledge translation tools to support patient care. These tools narrow the know-do gap by presenting the best available evidence from guidelines while using a format that is sensitive to how nurses think and what nurses do.MethodsMixed methods descriptive study guided by CAN-IMPLEMENT©. The process involved: a) conducting a systematic search for guidelines; b) developing symptom-specific protocols using evidence from quality appraised clinical practice guidelines; c) reaching consensus on the clinical practice protocol template, and d) validating the clinical practice protocols.ResultsClinical practice protocols were developed and validated for 13 symptoms using 42 clinical practice guidelines with a median of 3 guidelines per protocol (range 1 for bleeding to 7 vomiting). For the first two protocols, source guideline AGREE rigour subscale ratings ranged from 8% to 86% (median 60.1; diarrhoea; 40.5 fever). The protocols were developed using guidelines, symptom severity questions included the Edmonton Symptom Assessment System, and iterative feedback from practicing nurses. Usability testing revealed: high readability, just the right amount of information, and appropriate terms. Access to protocols needs to be tailored to individual practices (e.g. electronic application, access to paper-based versions). Nurses requested training and support to implement them.DiscussionThese tools, created from guidelines, transform evidence into user-friendly protocols for use by nurses when guiding patients at home to better manage their cancer treatment-related symptoms.
055 Use of Non-Randomised Studies In The Guideline Process: The GRADE Approach
Authors: Santesso N , Mustafa R , Schunemann H 
Published: August 2013

BackgroundThe GRADE approach to guideline development requires a review of the best available evidence which includes randomised controlled trials (RCTs) and non-randomised studies (NRS).ObjectivesDescribe the use of NRS as a replacement, a sequence, or a complement for RCTs, in a World Health Organization guideline using the GRADE approach.MethodsWe searched the literature using no study type limits for the effect of screening and treatment of precancerous lesions on patient or population important outcomes and for baseline risks. We assessed quality of the evidence using GRADE.ResultsDepending on the outcomes, we found few to no RCTs. When there was low/very low overall quality evidence from RCTs, we used NRS studies with no independent control groups to compare proportions between groups and calculate a relative effect of treatment and this evidence replaced the RCT evidence with similar/higher quality evidence. We found no evidence in RCTs for long-term outcomes, such as spontaneous abortion. Therefore, we used data from NRS (cohort studies) for premature delivery (a surrogate) to provide sequential evidence. For evidence about baseline risk of precancerous lesions and other outcomes, we used NRS a complement to the RCT data.DiscussionData from NRS provided evidence in three ways. One key criterion to consider when grading this evidence is indirectness due to indirect comparisons, surrogate outcomes or varying population risks.Implications for Guideline Developers/UsersGuideline developers can use GRADE and these methods when there is no evidence or low/very low quality evidence from RCTs.
A Novel Class of Anticancer Compounds Targets the Actin Cytoskeleton in Tumor Cells
Authors: Stehn Justine R. , Haass Nikolas K. , Bonello Teresa , Desouza Melissa , Kottyan Gregg , Treutlein Herbert , Zeng Jun , Nascimento Paula R.B.B. , Sequeira Vanessa B. , Butler Tanya L. , Allanson Munif , Fath Thomas , Hill Timothy A. , McCluskey Adam , Schevzov Galina , Palmer Stephen J. , Hardeman Edna C. , Winlaw David , Reeve Vivienne E. , Dixon Ian , Weninger Wolfgang , Cripe Timothy P. , Gunning Peter W. 
Published: August 2013

Abstract
The actin cytoskeleton is a potentially vulnerable property of cancer cells, yet chemotherapeutic targeting attempts have been hampered by unacceptable toxicity. In this study, we have shown that it is possible to disrupt specific actin filament populations by targeting isoforms of tropomyosin, a core component of actin filaments, that are selectively upregulated in cancers. A novel class of anti-tropomyosin compounds has been developed that preferentially disrupts the actin cytoskeleton of tumor cells, impairing both tumor cell motility and viability. Our lead compound, TR100, is effective in vitro and in vivo in reducing tumor cell growth in neuroblastoma and melanoma models. Importantly, TR100 shows no adverse impact on cardiac structure and function, which is the major side effect of current anti-actin drugs. This proof-of-principle study shows that it is possible to target specific actin filament populations fundamental to tumor cell viability based on their tropomyosin isoform composition. This improvement in specificity provides a pathway to the development of a novel class of anti-actin compounds for the potential treatment of a wide variety of cancers. Cancer Res; 73(16); 5169–82. ©2013 AACR.
Pertuzumab: Optimizing HER2 Blockade
Authors: Metzger-Filho Otto , Winer Eric P. , Krop Ian 
Published: August 2013

AbstractPertuzumab has been approved by the U.S. Food and Drug Administration for use in combination with trastuzumab and docetaxel for the first-line treatment of patients with advanced HER2-positive (HER2+) breast cancer. Pertuzumab is a recombinant humanized monoclonal antibody that binds to the extracellular dimerization domain II of HER2 and inhibits heterodimerization of HER2 with other HER family members, including EGF receptor (EGFR), HER3, and HER4. The HER2–HER3 heterodimer is a robust activator of phosphoinositide 3-kinase (PI3K) pathway signaling and functions as the most transforming and mitogenic of the receptor complexes formed by the HER family of proteins; thus, blockade of HER2–HER3 likely represents the most relevant action of pertuzumab. In the seminal phase III study, patients with HER2+ metastatic breast cancer were randomized to receive trastuzumab and docetaxel, with or without pertuzumab: Addition of pertuzumab significantly prolonged progression-free survival with an increase of 6.1 months (12.4 vs. 18.5 months, respectively). In a subsequent analysis with 30 months of median follow-up, pertuzumab conferred a 34% reduction in the risk of mortality. Here, we review the mechanism of action of pertuzumab, the rationale for combining it with trastuzumab/pertuzumab, clinical data, and future directions for this work. Clin Cancer Res; 19(20); 5552–6. ©2013 AACR.
Developing Lipid Nanoparticle-Based siRNA Therapeutics for Hepatocellular Carcinoma Using an Integrated Approach
Authors: Li Leiming , Wang Rongqi , Wilcox Denise , Sarthy Aparna , Lin Xiaoyu , Huang Xiaoli , Tian Lu , Dande Prasad , Hubbard Robert D. , Hansen Todd M. , Wada Carol , Zhao Xiaobin , Kohlbrenner William M. , Fesik Stephen W. , Shen Yu 
Published: August 2013

Abstract
Successful siRNA therapeutics requires the optimal integration of multiple components, including an efficient delivery system, a disease indication that is appropriate for siRNA-based therapy, and a potent and nontoxic siRNA against a robust therapeutic target. Although all currently available delivery systems have limitations, it is important to recognize that a careful selection of the disease indication, therapeutic target, and siRNA molecule could partially compensate for deficiencies associated with the delivery system and makes it possible to advance a therapeutic siRNA regimen. In this study, we present the development of siRNA therapeutics for hepatocellular carcinoma using an integrated approach, including the development of an efficient lipid nanoparticle delivery system, the identification of a robust therapeutic target that does not trigger liver toxicity upon target knockdown, and the selection of potent and nonimmunogenic siRNA molecules against the target. The resulting siRNA-containing lipid nanoparticles produced significant antitumor efficacy in orthotopic hepatocellular carcinoma models, and, thus, represent a promising starting point for the development of siRNA therapeutics for hepatocellular carcinoma. Mol Cancer Ther; 12(11); 2308–18. ©2013 AACR.