Impact of Clinical Practice Guidelines on the Diagnostic Strategy for Carcinomas of Unknown Primary Site: a Controlled ‘Before-After’ Study.

Clin Oncol (R Coll Radiol). 2008 Jul 19;

Authors: Sève P, Mackey J, Sawyer M, Lesimple T, de la Fouchardière C, Broussolle C, Dumontet C, Ray-Coquard I

PMID: 18644703 [PubMed - as supplied by publisher]

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Executive summary: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).

Chest. 2008 Jun;133(6 Suppl):71S-109S

Authors: Hirsh J, Guyatt G, Albers GW, Harrington R, Schünemann HJ

PMID: 18574259 [PubMed - in process]

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Antithrombotic and thrombolytic therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).

Chest. 2008 Jun;133(6 Suppl):110S-112S

Authors: Hirsh J, Guyatt G, Albers GW, Harrington R, Schünemann HJ

Since publication of the seventh American College of Chest Physicians (ACCP) supplement on antithrombotic and thrombolytic therapy, the results of clinical trials have provided important new information on the management of thromboembolic disorders, and the science of developing recommendations has advanced. In the accompanying supplement, we provide the new and updated recommendations and review several important changes that we have made in our guideline development process. We again made a conscious effort to increase the participation of female authors and contributors from outside North America, the latter reflecting the widespread use and dissemination of these guidelines internationally. The grading system for the recommendations was adopted in 2006 by the ACCP for all its guidelines, is similar to the increasingly widely used Grades of Recommendation, Assessment, Development, and Evaluation approach, and is described in detail in one of the introductory chapters. While most of the evidence on which recommendations are made remains low quality in fields of pediatric thrombosis, thrombosis in pregnancy, and thrombosis in valvular heart disease, rigorous studies in other fields have resulted in new and strong evidence-based recommendations for many indications.

PMID: 18574260 [PubMed - in process]

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Methodology for antithrombotic and thrombolytic therapy guideline development: American College of Chest Physicians Evidence-based Clinical Practice Guidelines (8th Edition).

Chest. 2008 Jun;133(6 Suppl):113S-122S

Authors: Schünemann HJ, Cook D, Guyatt G

The American College of Chest Physicians (ACCP) invited a panel of experts, researchers, information scientists, and guideline methodologists to develop the eighth edition of ACCP evidence-based guidelines on antithrombotic and thrombolytic therapy. The process began with guideline authors specifying the population, intervention and alternative, and outcomes for each clinical question and defined criteria for eligible articles, including methodologic criteria, for each recommendation. The McMaster University Evidence-Based Practice Center, in collaboration with the guideline authors and methodologists, developed strategies and executed systematic searches for evidence. The resulting guidelines are organized in chapters that present a clear link between the evidence and the resulting recommendations. The panel identified questions in which resource allocation issues were particularly important and obtained input from consultants with expertise in economic analysis for these issues. Authors paid careful attention to the quality of underlying evidence and the balance between risks and benefits, both reflected in grades of recommendations. For recommendations that are particularly sensitive to underlying values and preferences, the panel made explicit the values underlying the recommendations. Thus, the process of making recommendations for the ACCP guidelines included explicit definition of questions, transparent eligibility criteria for including studies, comprehensive searches and methodologic assessment of studies, and specification of values and preferences and resource implications underlying recommendations where particularly relevant. In combination with our previous practice of grading recommendations according to their strength and the methodologic quality of the supporting studies, these methods establish our guideline methodology as evidence based.

PMID: 18574261 [PubMed - in process]

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Grades of recommendation for antithrombotic agents: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).

Chest. 2008 Jun;133(6 Suppl):123S-131S

Authors: Guyatt GH, Cook DJ, Jaeschke R, Pauker SG, Schünemann HJ

This chapter describes the system used by the American College of Chest Physicians to grade recommendations for antithrombotic and thrombolytic therapy as part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Clinicians need to know if a recommendation is strong or weak, and the methodologic quality of the evidence underlying that recommendation. We determine the strength of a recommendation by considering the balance between the desirable effects of an intervention and the undesirable effects (incremental harms, burdens, and for select recommendations, costs). If the desirable effects outweigh the undesirable effects, we recommend that clinicians offer an intervention to typical patients. The uncertainty associated with the balance between the desirable and undesirable effects will determine the strength of recommendations. If we are confident that benefits do or do not outweigh harms, burden, and costs, we make a strong recommendation in our formulation, Grade 1. If we are less certain of the magnitude of the benefits and risks, burden, and costs, and thus their relative impact, we make a weaker Grade 2 recommendation. For grading methodologic quality, randomized controlled trials (RCTs) begin as high-quality evidence (designated by “A”), but quality can decrease to moderate (”B”), or low (”C”) as a result of poor design and conduct of RCTs, imprecision, inconsistency of results, indirectness, or a high likelihood for reporting bias. Observational studies begin as low quality of evidence (C) but can increase in quality on the basis of very large treatment effects. Strong (Grade 1) recommendations can be applied uniformly to most patients. Weak (Grade 2) suggestions require more judicious application, particularly considering patient values and preferences and, when resource limitations play an important role, issues of cost.

PMID: 18574262 [PubMed - in process]

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Strategies for incorporating resource allocation and economic considerations: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).

Chest. 2008 Jun;133(6 Suppl):132S-140S

Authors: Matchar DB, Mark DB

Although clinical guidelines may have substantial implications for allocation of health-care resources, these issues typically are not considered in the guideline development process or are only considered informally. This is a particular challenge for guidelines intended to be applicable in a diversity of settings. Based on theoretical and practical issues, we develop and apply a basic strategy for incorporating resource considerations into clinical guidelines. Formal economic assessments, such as cost-effectiveness analyses, provide a powerful tool to account for the health and economic implications of clinical guidelines. An acceptable tradeoff of money for health can depend highly on local considerations, and it is feasible to incorporate resource considerations into clinical guidelines. Although use of a “bright line” criterion for what constitutes an acceptable tradeoff of money for health has some appeal, this approach can lead to guidelines that are sensible in some contexts but unrealistic in others. One way to address this tension is through “resource aware” guidelines in which the recommendations are primarily based on scientific evaluations of efficacy supplemented by a review of evidence about the health and economic tradeoffs associated with various options. This approach limits the possibility that the guideline committee can make a universal recommendation based on resource considerations, but we expect it will encourage more thoughtful discussion of economic issues; greater sensitivity to the diversity of investment in health resource internationally; and, perhaps, innovative ways of overcoming resource barriers to the use of the most effective therapies.

PMID: 18574263 [PubMed - in process]

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Parenteral anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).

Chest. 2008 Jun;133(6 Suppl):141S-159S

Authors: Hirsh J, Bauer KA, Donati MB, Gould M, Samama MM, Weitz JI

This chapter describes the pharmacology of approved parenteral anticoagulants, including the indirect anticoagulants, unfractionated heparin (UFH), low-molecular-weight heparins (LMWHs), fondaparinux, and danaparoid as well as the direct thrombin inhibitors hirudin, bivalirudin, and argatroban. UFH is a heterogeneous mixture of glycosaminoglycans that bind to antithrombin via a unique pentasaccharide sequence and catalyze the inactivation of thrombin factor Xa and other clotting factors. Heparin also binds to cells and other plasma proteins, endowing it with unpredictable pharmacokinetic and pharmacodynamic properties, and can lead to nonhemorrhagic side effects, such as heparin-induced thrombocytopenia (HIT) and osteoporosis. LMWHs have greater inhibitory activity against factor Xa than thrombin and exhibit less binding to cells and proteins than heparin. Consequently, LMWH preparations have more predictable pharmacokinetic and pharmacodynamic properties, have a longer half-life than heparin, and have a lower risk of nonhemorrhagic side effects. LMWHs can be administered once or twice daily by subcutaneous injection, without anticoagulant monitoring. Based on their greater convenience, LMWHs have replaced UFH for many clinical indications. Fondaparinux, a synthetic pentasaccharide, catalyzes the inhibition of factor Xa, but not thrombin, in an antithrombin-dependent fashion. Fondaparinux binds only to antithrombin; therefore, HIT and osteoporosis are unlikely to occur. Fondaparinux has excellent bioavailability when administered subcutaneously, has a longer half-life than LMWHs, and is given once daily by subcutaneous injection in fixed doses, without anticoagulant monitoring. Three parenteral direct thrombin inhibitors and danaparoid are approved as alternatives to heparin in HIT patients.

PMID: 18574264 [PubMed - in process]

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Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).

Chest. 2008 Jun;133(6 Suppl):160S-198S

Authors: Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G

This article concerning the pharmacokinetics and pharmacodynamics of vitamin K antagonists (VKAs) is part of the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). It describes the antithrombotic effect of the VKAs, the monitoring of anticoagulation intensity, and the clinical applications of VKA therapy and provides specific management recommendations. Grade 1 recommendations are strong and indicate that the benefits do or do not outweigh the risks, burdens, and costs. Grade 2 recommendations suggest that the individual patient’s values may lead to different choices. (For a full understanding of the grading, see the “Grades of Recommendation” chapter by Guyatt et al, CHEST 2008; 133:123S-131S.) Among the key recommendations in this article are the following: for dosing of VKAs, we recommend the initiation of oral anticoagulation therapy, with doses between 5 mg and 10 mg for the first 1 or 2 days for most individuals, with subsequent dosing based on the international normalized ratio (INR) response (Grade 1B); we suggest against pharmacogenetic-based dosing until randomized data indicate that it is beneficial (Grade 2C); and in elderly and other patient subgroups who are debilitated or malnourished, we recommend a starting dose of

PMID: 18574265 [PubMed - in process]

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Antiplatelet drugs: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).

Chest. 2008 Jun;133(6 Suppl):199S-233S

Authors: Patrono C, Baigent C, Hirsh J, Roth G

This article about currently available antiplatelet drugs is part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). It describes the mechanism of action, pharmacokinetics, and pharmacodynamics of aspirin, reversible cyclooxygenase inhibitors, thienopyridines, and integrin alphaIIbbeta3 receptor antagonists. The relationships among dose, efficacy, and safety are thoroughly discussed, with a mechanistic overview of randomized clinical trials. The article does not provide specific management recommendations; however, it does highlight important practical aspects related to antiplatelet therapy, including the optimal dose of aspirin, the variable balance of benefits and hazards in different clinical settings, and the issue of interindividual variability in response to antiplatelet drugs.

PMID: 18574266 [PubMed - in process]

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New antithrombotic drugs: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).

Chest. 2008 Jun;133(6 Suppl):234S-256S

Authors: Weitz JI, Hirsh J, Samama MM

This chapter focuses on new antithrombotic drugs that are in phase II or III clinical testing. Development of these new agents was prompted by limitations of existing antiplatelet, anticoagulant, or fibrinolytic drugs. Addressing these unmet needs, this chapter (1) outlines the rationale for development of new antithrombotic agents, (2) describes the new antiplatelet, anticoagulant, and fibrinolytic drugs, and (3) provides clinical perspectives on the opportunities and challenges faced by these novel agents.

PMID: 18574267 [PubMed - in process]

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