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Physicians: .25 AMA PRA Category I CreditsTM
Family Physicians: .25 Prescribed credits
Nurse Practitioners: .25 Contact hours
Release Date: July 31, 2014
Expiration Date: July 31, 2015
Estimated Completion Time: 15 minutes
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Upon successful completion of this educational program, the reader should be able to:
1. Discuss the significance of this article as it relates to your clinical practice.
2. Be able to apply this knowledge to your patient's diagnosis, treatment and management.
Alan Ehrlich, MD
Assistant Clinical Professor in Family Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA; Senior Deputy Editor, DynaMed, Ipswich, Massachusetts, USA
Michael Fleming, MD, FAAFP
Assistant Clinical Professor of Family Medicine and Comprehensive Care, LSU Health Science Center School of Medicine, Shreveport, Louisiana, USA; Assistant Clinical Professor of Family Medicine, Department of Family and Community Medicine, Tulane University Medical School, New Orleans, Louisiana, USA; Chief Medical Officer, Amedisys, Inc. & Antidote Education Company
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AAFP: This enduring material activity, DynaMed EBM Focus Volume 9, has been reviewed and is acceptable for up to 15.25 Prescribed credits by the American Academy of Family Physicians. AAFP certification begins March 5, 2014. Term of approval is for one year from this date. Each EBM Focus is approved for .25 Prescribed credits. Credit may be claimed for one year from the date of each update. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
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Program ID: 1405237K
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Last week 709 journal articles were evaluated via DynaMed's Systematic Literature Surveillance and summaries of 231 articles were added to DynaMed content.
Based on criteria for selecting concepts of high clinical importance, two articles were selected by the DynaMed Editorial Team.
The EBM Focus this week highlights results from 2 recent systematic reviews each evaluating the safety and efficacy of thrombolytics vs. anticoagulants in patients with intermediate-risk pulmonary embolism (PE), and reaching different conclusions due to differing methodology.
After diagnosing a patient with a PE, the next step is to do a risk assessment to guide decision making regarding anticoagulation vs. thrombolysis. The decision depends on several factors, including the hemodynamic stability of the patient and their estimated risk of bleeding. The current American College of Chest Physicians (ACCP) guidelines (Chest 2012 Feb;141(2 Suppl):e419S full-text) suggest use of thrombolytics for:
- patients with acute PE associated with hypotension and without high bleeding risk
- select patients with acute PE not associated with hypotension and with low bleeding risk whose initial clinical presentation, or clinical course after starting anticoagulant therapy, suggests high risk of developing hypotension
However, the evidence for the comparative safety and efficacy of thrombolytics vs. anticoagulants in most patients with intermediate-risk PE has been limited. Intermediate-risk PE (also referred to as submassive PE) has been defined as hemodynamic stability with right ventricular dysfunction or myocardial injury, and this definition is consistent in guidelines from both the American Heart Association (AHA, Circulation 2011 Apr 26;123(16):1788 full-text) and the European Society of Cardiology (ESC, Eur Heart J 2008 Sep;29(18):2276 full-text). A previous Cochrane review of 8 randomized trials with 679 adults with PE found insufficient evidence to support the use of thrombolytic therapy, but did not include an analysis specific to patients with intermediate-risk PE (Cochrane Database Syst Rev 2009 Jul 8;(3):CD004437). Two recent systematic reviews have compared thrombolytics vs. anticoagulants in this specific patient population.
The first systematic review identified 6 randomized trials comparing thrombolytics (alteplase or tenecteplase) vs. heparin in 1,510 patients with intermediate-risk PE. The systematic review found no significant differences in either all-cause mortality (risk ratio 0.72, 95% CI 0.39-1.31) in analysis of all trials or risk of major bleeding (risk ratio 2.07, 95% CI 0.58-7.35) in an analysis of 5 trials with 1,474 patients. However, the confidence intervals for both mortality and major bleeding could not rule out clinically important differences between the thrombolytics and heparin (J Thromb Haemost 2014 Jul;12(7):1086).
The second systematic review identified 16 randomized trials comparing thrombolytics vs. anticoagulants, and included a separate analysis of 8 trials with 1,775 patients who had intermediate-risk PE. This systematic review included all of the trials included in the systematic review mentioned above, as well as 2 additional trials for their mortality analysis and 3 additional trials for their major bleeding analysis. The inclusion of these trials resulted in statistically significant differences for both decreasing mortality (OR 0.48, 95% CI 0.25-0.92) and increasing major bleeding (odds ratio 3.19, 95% CI 2.07-4.92) in analyses of all 8 trials (JAMA 2014 Jun 18;311(23):2414).
Although there are small differences between the 2 systematic reviews in the specific analyses used, the main reason for their opposing findings is the choice of which trials to include. Although exclusions were not described in detail, the smaller systematic review does describe exclusion of the Moderate Pulmonary Embolism Treated with Thrombolysis (MOPETT) trial due to inclusion criteria that do not specifically address right ventricle dysfunction or myocardial injury. This trial randomized 121 patients to either alteplase or heparin/enoxaparin, but used inclusion criteria that do not match the definitions of right ventricle dysfunction or myocardial injury described in the AHA or ESC guidelines above. As a consequence, inclusion of this trial may not be appropriate for conclusions in patients with intermediate-risk PE, suggesting that the mortality benefit for thrombolytics may not be valid. At the same time, this systematic review excluded 2 additional trials from their major bleeding analysis without explanation, calling into question the finding of no between-group difference for this outcome.
This analysis highlights an important aspect of critical appraisal of systematic reviews, namely the need to clearly define the population of interest and to determine how closely the studies included in the review adhere to this definition. The fact that the mortality and major bleeding outcomes are dependent on what exact studies are included in the analysis adds a level of uncertainty to the findings that makes it difficult to draw strong conclusions for either safety or efficacy. Future randomized trials, like the large high-quality PEITHO trial (N Engl J Med 2014 Apr 10;370(15):1402), will certainly help clarify this. At this point, any mortality advantage for thrombolytics is uncertain, while at the same time there is a reasonable concern of increased risk of major bleeding with thrombolytics compared to anticoagulants in this patient population.
For more information see the Thrombolytics for venous thromboembolism topic in DynaMed.
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EBSCO Health Launches Pediatric Clinical Information Mobile App
PEMSoft Now Available For iPhone, iPad, and Android Devices
A mobile app designed specifically for pediatricians, emergency department physicians, physicians-in-training and other medical providers caring for children with acute illnesses and injury, is now available from EBSCO Health, the leading provider of clinical decision support solutions for the healthcare industry.
Designed by pediatricians, emergency physicians and other medical specialists, PEMSoft is a pediatric evidence-based point-of-care medical reference tool for hospitals, emergency departments, clinics, pediatric group practices, transport services, and medical schools. The vast content in PEMSoft addresses the entire spectrum of neonatal, infant, child, adolescent and young adult health. PEMSoft authors adhere to a strict evidence-based editorial policy focused on systematic identification, evaluation and consolidation of practice-changing clinical literature.
The PEMSoft Mobile app includes explicit step-by-step emergency critical care procedures, information about common pediatric signs and symptoms and content covering pediatric injuries and management approaches. More than 3,000 evidence-based pediatric topics and a similar number of medical illustrations, clinical images and videos are also available via the mobile app.
The PEMSoft Mobile App is accessible from both Apple and Android devices.
For more information and technical support, visit the PEMSoft Mobile Access page. To view the official press release, click here.
Call for Peer Reviews
We are currently seeking subspecialty reviewers for our Patient Education Resource Center (PERC). PERC provides fact sheets and discharge instructions for patients leaving the hospital or emergency room. These hand-outs fulfill the meaningful use requirements for the Medicare & Medicare Services Incentive Programs.
Click here to speak with us about becoming a peer reviewer.