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Physicians: .25 AMA PRA Category I CreditsTM
Family Physicians: .25 Prescribed credits
Nurse Practitioners: .25 Contact hours

Release Date: March 19, 2015
Expiration Date: March 19, 2016

Estimated Completion Time: 15 minutes

There is no fee for this activity.

To Receive Credit

In order to receive your certificate of participation, you should read the information about this activity, including the disclosure statements, review the entire activity, take the post-test, and complete the evaluation form. You may then follow the directions to print your certificate of participation. To begin, click the CME icon above.

Program Overview

Learning Objectives

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.

Faculty Information

Alan Ehrlich, MD
Assistant Professor in Family Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA; Executive 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


Dr. Ehrlich, Dr. Fleming, DynaMed Editorial Team members, and the staff of Antidote Education Company have disclosed that they have no relevant financial relationships or conflicts of interest with commercial interests related directly or indirectly to this educational activity.

No commercial support has been received for this activity.

Accreditation Statements

ACCME: This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Antidote Education Company and EBSCO Publishing. Antidote is accredited by the ACCME to provide continuing medical education for physicians. Antidote Education Company designates this enduring activity for a maximum of 0.25 AMA PRA Category 1 CreditsTM. Physicians should only claim credit commensurate with the extent of their participation in the activity.

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.

AANP: This program is approved for 0.25 contact hour(s) of continuing education by the American Association of Nurse Practitioners. This program was planned in accordance with AANP CE Standards and Policies and AANP Commercial Support Standards. Program ID: 1405237S2

Last week 601 journal articles were evaluated via DynaMed's Systematic Literature Surveillance and summaries of 299 articles were added to DynaMed content.

Based on criteria for selecting "articles most likely to inform clinical practice," one article was selected by the DynaMed Editorial Team.

Thrombolysis 3-4.5 Hours After Stroke Onset May Increase Mortality Without Clear Benefit

Reference: BMJ 2015;350:h1075

Thrombolysis with alteplase (tissue-type plasminogen activator, t-PA) given up to 3 hours after the onset of acute ischemic stroke is associated with an increased likelihood of survival without disability at 90 days. Multiple systematic reviews have suggested the benefit of t-PA is found for use up to 4.5 hours after stroke onset. The data supporting t-PA for up to 4.5 hours after stroke onset has led to strong recommendations for such use in guidelines in the United States, United Kingdom, Canada, Europe, France, Japan, Australia, and South Africa. Drug licensing for t-PA after stroke is limited to the first 3 hours in the US but is extended to 4.5 hours in the UK and Australia.

A recent analysis of the data looking specifically at the 3-4.5 hour timeframe (with coauthors including DynaMed Editors Brian S. Alper, MD, MSPH, FAAFP, Meghan Malone-Moses, MPH, and James S. McLellan, PhD) found consistent evidence that t-PA use during this time window increases the risk for symptomatic intracranial hemorrhage and fatal intracranial hemorrhage within 7 days (level 1 [likely reliable] evidence), with a best current estimate of the number needed to harm (NNH) of 44 for fatal intracranial hemorrhage. t-PA during this time window might also increase 90-day mortality (level 2 [mid-level] evidence) (NNH 49), but this result was not statistically significant (hazard ratio 1.14, 95% CI 0.95-1.36).

The evidence for the effects of t-PA use on functional independence, however, is uncertain and inconsistent. The one trial reporting significant benefit (ECASS III with 821 patients, N Engl J Med 2008 Sep 25;359(13):1317) had baseline differences in prior stroke history potentially biasing the conclusion. In ECASS III, t-PA was associated with an increased likelihood of survival without any disability (NNT 14). The benefit observed in this trial was no longer statistically significant in a 2014 report limited to the 89% of ECASS III patients without a history of prior stroke. The largest trial (IST-3, Lancet 2012 Jun 23;379(9834):2352) was unblinded. In the subgroup of 1,177 patients treated 3-4.5 hours after stroke, t-PA was associated with a decreased likelihood of survival without moderate or severe disability (NNH 16).

Analyses of these trials and others have been reported in reviews suggesting an overall benefit of t-PA use at 3-4.5 hours after stroke onset. Guidelines have used these results to recommend such therapy, but the conclusions of these reviews and original trial reports do not clearly match the underlying data when viewed precisely for the 3-4.5 hour time window. This examination of the inconsistencies between the data and their interpretation calls for a re-evaluation of guidelines and drug licensing considerations. Until policy-makers can fully evaluate the underlying data and update recommendations, clinicians should be aware of the potential for harm and uncertainty regarding benefit when considering t-PA more than 3 hours after stroke onset.

For more information, see the Thrombolytics for acute stroke topic in DynaMed.

DynaMed Introduces New and Improved Mobile App

DynaMed users can now access valuable, evidence-based content anywhere with the new DynaMed mobile app. The new app has been redesigned to make it easier and faster for physicians to find answers to clinical questions. The app features an improved user experience, seamless authentication and easy access to the latest clinical content. It provides offline access, and the ability to denote favorites, email topics and write and save notes about particular topics. Users download the complete DynaMed content set and periodically receive notifications to update the content.

The DynaMed app is a complimentary part of personal and institutional DynaMed subscriptions. The app has also been designed for easy, one-time authentication via email, making the process as convenient as possible.

The app can be downloaded from the iTunes Store or Google Play. For more information, please visit the DynaMed Mobile Access page.

DynaMed Careers

The DynaMed editorial team is seeking specialist editors in the following fields: Gastroenterology, Nephrology, Oncology (especially Breast cancer, Pancreatic cancer), Ophthalmology, and, Pediatric Neurology.

If interested, please send a recent copy of your CV to Rachel Brady at rbrady@ebsco.com.

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