Primecuts: This Week in the Journals

May 24, 2010

By Mary Whitman, MD

Faculty Peer Reviewed

We start this week with news that the American Heart Association (AHA) is teaming up with Nintendo of America to promote its “active gaming” Wii console and games, such as WiiFit.  While some argue that the AHA should be promoting more energetic exercise, we agree with their statement, “Participating in an actual sport is usually more vigorous than active gaming, but active gaming compares very well with sitting on the couch.”[1]  As a sedentary lifestyle is one of the risk factors for cardiovascular disease and stroke, we should be encouraging our patients to be more physically active, in whatever way possible.

            Speaking of stroke, there are several articles in this week’s journals dealing with short and long-term therapy for acute stroke.  Ever since 1995, when the NINDS-2 study[2] showed a benefit of alteplase (tissue plasminogen activator, tPA) when delivered within 3 hours of stroke symptom onset, it has been the standard of care to administer this therapeutic to patients who present within this window, despite the heightened risk of hemorrhage.  Additional studies have suggested that it may be possible to extend the time window while maintaining benefit. A study published in this week’s The Lancet[3] has reanalyzed the pooled data from all 8 trials of alteplase therapy in acute stroke, and showed there is a benefit of alteplase therapy when delivered up to 270 min (4.5 hr) from symptom onset, although the greatest benefits are seen with more rapid delivery. A total of 3,670 patients were included in these studies, with outcomes analyzed at 90 days. A favorable outcome, which was defined as a Rankin score of 0-1, suggesting retention or restoration of all pre-stroke activities, was present in 41.6% of patients treated with alteplase vs 34.8% of patients who received placebo.  The shorter the time interval between onset of symptoms and treatment, the higher the odds ratio of favorable outcome, and the lower the number needed to treat (NNT= 4.5 for 1-90 minutes, NNT= 9.0 for 91-180 minutes, and NNT= 14.1 for 181-270 minutes).  The results did not show any significant therapeutic benefit if alteplase was given greater than 271 minutes after symptom onset, even suggesting an increase in mortality in this group.  These results suggest that we should establish processes that will increase the likelihood that patients can be treated as soon as possible after symptom onset of stroke, much as has been done with STEMI protocols.

            In Archives of Internal Medicine, Bravata et al[4] performed a retrospective chart analysis of 1,487 patients at 5 hospitals, examining the factors associated with improved in-hospital outcome for acute stroke.  After controlling for stroke severity and co-morbidity, three processes were found to be associated with lower rates of death or institutionalization: swallowing evaluation, DVT prophylaxis, and treating episodes of hypoxia with supplemental oxygen.  Factors that were not found to be significantly associated with an improved outcome included neurologic assessment, early mobilization, blood pressure management according to clinical guidelines, and fever management (with acetaminophen). Somewhat disturbingly, only 77% of patients had oxygen saturation measured daily for the first 14 days. Of the 192 with at least one episode of hypoxia, only 90 (47%) were treated with oxygen for each episode. Sixty-nine patients (36%) with documented hypoxia never received oxygen. It seems intuitive that patients who were allowed to remain hypoxic without intervention would have worse outcomes.  Thus, it is somewhat unclear how specific these findings are to patients admitted with acute stroke. It appears that the factors studied were primarily basic healthcare processes that should be done for all patients regardless of admitting diagnosis.

            Elsewhere, we find some optimistic news in the fight against infectious diseases.  This week’s Nature reported about the discovery of a new serine protease, named Esp, that is produced by certain strains of Staphylococcus epidermidis (SE). This enzyme appears to inhibit Staphylococcus aureus (SA) nasal colonization and biofilm formation.[5]  In this study, the authors examined the rates of nasal colonization with SA and SE in healthy volunteers.  In their sample, about one-third of volunteers were colonized with SA, and over 90% were colonized with SE. Examining the SE from subjects who were not co-colonized with SA, they found that some strains were capable of inhibiting the growth of SA in culture. Through additional analysis, they determined that this inhibition was conveyed through production of the protease Esp. Addition of purified Esp to cultures of SA (MSSA or MRSA) inhibited its growth. Most excitingly, inoculating the Esp-producing (“inhibitory”) strains of SE into the noses of volunteers colonized with SA decreased rates of nasal colonization with SA. These findings portend a potential future area for antibiotic development.  While SA colonization is not harmful in itself, it is a risk factor for Staphylococcus infections, and colonization of health workers is likely involved in nosocomial spread of the pathogen. There may come a day when a nasal inoculation of inhibitory SE is routinely given to health care workers or patients upon admission to the hospital. It might prove to be a more effective strategy than donning those ubiquitous “contact isolation” gowns!

            A paper in Clinical Infectious Diseases this week shows us the importance of isolating patients with Clostridium difficile infections[6]. The investigators intensively sampled the air and environmental surfaces around patients with known C. difficile infection, and showed that C. difficile spores may be found in the surrounding air;  in an initial sample of 50 patients, with air sampling for 1 hour, 6 (12%) had air-borne C. difficile spores.  With longer sampling times, however, the majority of patients were found to emanate aerosolized spores. Detection of aerosolized C. difficile spores was more common during periods of activity, such as when beds are made, curtains are drawn, during meal times, and during visiting hours.  They also detected microbiologically related C. difficile spores on commonly touched surfaces, suggesting the possibility that the spores become aerosolized from the environmental surfaces when those surfaces are disturbed.  Further, aerosolized spores can likely settle and recontaminate surfaces after they have just been cleaned.  The authors argue that their results support isolating patients in private rooms as soon as they develop diarrhea to prevent spread of infection.  However, they did not show that the levels of aerosolized spores are high enough, or travel far enough, to infect other patients.  Thus, there is not enough evidence at the present time to initiate airborne precautions for C. difficile­-infected patients.

Dr. Whitman is a first year resident at NYU Langone Medical Center

Peer reviewed by Michael Poles, MD, Gastroenterology section editor for Clinical Correlations.



[2] The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995; 333: 1581-87.

[3] Lees KR, Bluhmki E, von Kummer R, Brott TG, Toni D, Grotta JC, Albers GW, Kaste M, Marler JR, Hamilton SA, Tilley BC, Davis SM, Donnan GA, Hacke W. Time to treatment with intravenous alteplase and outcome in stroke: and updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPIITHET trials.  The Lancet. 2010 375:1695-703.

[4] Bravata DM, Wells CK, Lo AC, Nadeau SE, Melillo J, Chodkowski D, Struve F, Williams LS, Peixoto AJ, Gorman M, Goel P, Acompora G, McClain V, Ranjbar N, Tabereaux PB, Boice JL, Jacewicz M, Concato J. Processes of Care Associated with Acute Stroke Outcomes. Archives of Internal Medicine. 2010. 170:804-810.

[5] Iwase T, Uehara Y, Shinji H, Tajima A, Seo H, Takada K, Agata T, Mizunoe Y. Staphylococcus epidermidis Esp inhibits Staphylococcus aureus biofilm formation and nasal colonization. Nature. 2010. 465:346-349.

[6] Best EL, Fawley WN, Parnell P, Wilcox MH. The Potential for Airborne Dispersal of Clostridium difficile from Symptomatic Patients. Clinical Infectious Diseases. 2010:50(11):1450-1457.

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