September 06, 2012Volume 7 - Issue 36

DynaMed Weekly Update

For the week ending August 31, 2012

Last week 534 articles were evaluated via DynaMed's Systematic Literature Surveillance and 214 were added to DynaMed content.   


Based on the editors' criteria of selecting "articles most likely to change clinical practice," two articles of significant interest was selected for the DynaMed Weekly Update.

Feature Articles

Tiotropium May Increase Time to Severe Exacerbation in Patients with Poorly Controlled Asthma


Many patients with asthma have poorly controlled disease despite combined use of inhaled glucocorticoids and long-acting beta-2 agonists (LABAs), and for these patients, few treatment options exist. Anticholinergic agents, such as tiotropium, have been widely used for bronchodilation in COPD, but have been less commonly used for asthma. A recent report of 2 identical randomized trials evaluated the efficacy of tiotropium for controlling exacerbations in patients with poorly controlled asthma.


A total of 912 patients (mean age 53 years) who were taking inhaled glucocorticoids and LABAs were randomized to inhaled tiotropium 5 mcg (in 2 puffs) vs. placebo by Respimat Soft Mist inhaler once daily for 48 weeks. All patients had an Asthma Control Questionnaire score ≥ 1.5 (on 7 point scale) and had at least 1 exacerbation treated with systemic glucocorticoids within the last year. The primary outcome was time to severe asthma exacerbation defined as either the initiation of systemic glucocorticoids for ≥ 3 days or a doubling of systemic glucocorticoid dose for ≥ 3 days in patients with ongoing or preexisting systemic treatment.


Data from the 2 trials were pooled for analysis. Median time to severe exacerbation was not reached in either the tiotropium or placebo groups. The time until 25% of the group had a severe exacerbation was 282 days with tiotropium vs. 226 days with placebo (hazard ratio 0.79, 95% CI 0.62-1) (level 2 [mid-level] evidence). The tiotropium group had 0.53 severe exacerbations per patient year, compared to 0.66 with placebo (p = 0.046). Tiotropium was associated with significant improvements in forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and peak expiratory flow (PEF) in both trials. There were no significant differences in hospitalizations for asthma or adverse events, and no deaths occurred in either group (N Engl J Med 2012 Sep 2 early online). It should be noted that tiotropium delivered via Respimat Soft Mist inhaler has previously been associated with increased risk of all-cause and cardiovascular mortality in patients with COPD (BMJ 2011 Jun 14;342:d3215). This inhaler is currently available in 55 countries, but not in the United States.


For more information, see the Tiotropium topic in DynaMed.




Mepolizumab Decreases Exacerbation Risk in Patients with Severe Eosinophilic Asthma


Recurrent exacerbations are common in a large subgroup of patients with asthma characterized by eosinophilic airway inflammation. This form of asthma is frequently unresponsive to corticosteroid treatment. Mepolizumab is a monoclonal antibody that targets interleukin 5, a protein regulating eosinophil production, maturation, and activation. Mepolizumab has previously shown clinical benefits in 2 small randomized trials and a trend toward reduced exacerbations in a larger trial in patients with severe eosinophilic asthma. The recently reported DREAM trial evaluated the efficacy of mepolizumab in 621 patients from 13 countries, and is the largest trial to date.


Patients aged 12-74 years were randomized to IV mepolizumab at 1 of 3 doses (75 mg vs. 250 mg vs. 750 mg) vs. placebo, with infusions once every 4 weeks for 1 year. All patients had a history of ≥ 2 exacerbation requiring steroids in previous year and had signs of eosinophilic inflammation. The primary outcome was incidence of clinically significant exacerbation, defined as a validated episode of worsening asthma symptoms requiring oral corticosteroid treatment for ≥ 3 days, hospital admission, or emergency department visit. The trial was completed by 84% of the randomized patients, and 99% were included in a modified intention-to-treat analysis.


At 1 year, the rate of exacerbations was significantly reduced with each mepolizumab dose compared to placebo (level 1 [likely reliable] evidence). Mean rates of exacerbations per patient per year were 1.24 with mepolizumab 75 mg, 1.46 with mepolizumab 250 mg, 1.15 with mepolizumab 750 mg, and 2.4 with placebo (p ≤ 0.0005 for each comparison). Mepolizumab was also associated with significant reductions in serum eosinophil counts. There were no significant differences in symptom scores, quality of life, or adverse events (Lancet 2012 Aug 18;380(9842):651). Mepolizumab has not been FDA-approved for asthma. It is currently available for compassionate use in patients with hypereosinophilic syndrome.


For more information, Asthma in adults and adolescents see the topic in DynaMed.  

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DynaMed Events

Medicine 2.0 2012, September 15th - 16th, 2012    

Editor-in-Chief Dr. Brian Alper and Senior Deputy Editor Dr. Alan Ehrlich will be presenting at the 5th Annual World Congress on Social Media, Mobile Apps, and Internet/Web 2.0 in Medicine and Public Health, held at the Joseph B. Martin Conference Center at Harvard Medical School in Boston, MA. The topic of the presentation is "How Much Does Practice-Guiding Medical Knowledge Change in One Year?"


Visit the Medicine 2.0 '12 website to learn more about the event and for registration information.


Cochrane Colloquium, September 30th - October 3rd, 2012 
Editor-in-Chief Dr. Brian Alper will be presenting at the 20th Cochrane Collaboration Colloquium held at the Pullman Hotel in Auckland, New Zealand. The topic of the presentation is "Practice-driving evidence: how frequently does it change?"   


Visit the Cochrane Colloquium website to learn more about the event and for registration information.


First International Conference on Evidence Based HealthCare (ISEHCON), October 7th - 8th, 2012   

Editor-in-Chief Dr. Brian Alper will be leading a workshop at the First International Conference on Evidence Based Healthcare at the India International Centre in New Delhi, India. The topic of the workshop will be "Best Sources for Evidence-Based literature for Healthcare Practitioners".   


Visit the International Society for Evidence Based Health Care website to learn more about the event and for registration information.

Call for Peer Reviewers

We are currently seeking reviewers for:  

Chronic thromboembolic pulmonary hypertension 

Pulmonary arteriovenous malformations 


Learn more about the DynaMed Contribution Opportunities:

DynaMed Peer Review 

Editorial Policies for Reviewers 

About DynaMed Weekly Update

Prepared by the clinician members of the DynaMed Editorial Team, DynaMed Weekly Update is a compilation of one to five articles selected from DynaMed's Systematic Literature Surveillance as articles most likely to change clinical practice.

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CME Information


0.25 AMA PRA Category I Credit(s)™
Family Physicians: 0.25 Prescribed credits
Nurse Practitioners: 0.25 Contact hours
Release Date: September 06, 2012
Expiration Date: September 06, 2013
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 at the end of the article.

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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 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

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.


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AAFP: Enduring Material activity, DynaMed Weekly Update, has been reviewed and is acceptable for up to 13 Prescribed credits by the American Academy of Family Physicians. AAFP certification begins March 7, 2012. Term of approval is for one year from this date with the option of yearly renewal. Each Weekly Update is worth .25 Prescribed credits. Physicians should claim only the credit commensurate with the extent of their participation in the activity.


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