Friday, January 18, 2013

Lactate – Is There Any Death It Doesn't Predict?

Turns out – apparently, no!

Continuing the run on pulmonary embolism articles, we find that – in addition to all the things we know prognosticates increased mortality in PE patients – elevated plasma lactate levels also predict poor outcomes.  This is generally unsurprising, because elevated lactate levels are associated with increased mortality, even in unselected ED patients.  What is interesting, however, is that lactate levels >2 mmol/L were more associated with 30-day mortality than shock/hypotension, hypoxia, or right-ventricular dysfunction.  It's a small cohort, but it's a reasonable finding, regardless.

However, what's sort of odd regarding the Editor's Summary for this article is that it specifically mentions the lactate level does not outperform a simplified pulmonary embolism severity index clinical tool.  The "truth" is that an AUC of 0.84 is better than an AUC of 0.71 – but that (0.72 to 0.95) and (0.60 to 0.83) overlap.  Rather than trash the lactic acid level compared with the PESI, it might have been more accurate to simply state the current study was underpowered to confirm the advantage of lactic acid over PESI, and further research is necessary.

Can you buy stock in lactate level assays?  It's clearly the new favorite all-purposes prognostication tool.


"Prognostic Value of Plasma Lactate Levels Among Patients With Acute Pulmonary Embolism: The Thrombo-Embolism Lactate Outcome Study" 
http://www.ncbi.nlm.nih.gov/pubmed/23306454

Wednesday, January 16, 2013

Inadequate "Overuse" Reduction Strategies

This study was featured in Academic Emergency Medicine as one of their CME articles – theoretically, an article with additional value presented with incentives to motivate a closer reading of the content.  I don't mean to imply this is somehow a bad article – but it's just interesting to step back out of the tunnel vision of statistics and boggle at the inadequacy of the current state of medicine. 

 This is a prospective study of patients evaluated for pulmonary embolism attempting to evaluate how many patients were "inappropriately" scanned.  This definition of "inappropriate" scanning was determined by patients who were either PERC negative or had low-risk Wells' score followed by a negative d-Dimer.  Overall, of 152 patients, 11.8% were ultimately diagnosed with PE.  However, the authors state that application of the PERC rule might have eliminated 9.2% of these scans while Wells'/d-Dimer would have obviated 13.8%.

While I certainly don't discount the beneficial effect of even small reductions in the number of individuals evaluated for pulmonary embolism, these are still terrible numbers.  90% of CT scans for PE are negative?  And using these decision instruments gets us to ~75% negative scans?  This would be comically wasteful performance and innovative performance improvement in any other industry.

We pretty clearly need to do better.

"Overuse of Computed Tomography Pulmonary Angiography in the Evaluation of Patients with Suspected Pulmonary Embolism in the Emergency Department"
www.ncbi.nlm.nih.gov/m/pubmed/23167851/

Monday, January 14, 2013

tPA Is The Hand That Feeds

No biting!

There are still a few hold-outs on the 0 to 3 hour window, but most folks would agree that battle is lost – the best we can hope for is further clarifying the patients with the greatest likelihood of clinically significant benefit vs. those with the greatest level of potential harms.

But, greater than 3 hours is still a battlefield.  This article in the January Annals uses the gloriously unbalanced ECASS III data for a cost-effectiveness analysis which, unsurprisingly, concludes in favor of tPA treatment.  The problem is, of course, the assumption that ECASS III is infallible – a highly suspect position, considering the baseline differences between groups in ECASS III.  Then, accounting for the the 1200 patients in IST-3 enrolled in the 3 to 4.5 window who did poorly with tPA, I'm guessing an updated meta-analysis wouldn't look quite as favorable.  But, I will give these authors a bit of a break, as this article was accepted for publication before IST-3 results were available.

Finally, in lieu of my usual rant, I'll just copy and paste the disclosures portion of the article:
"This project was funded through a contract with Genentech, Inc. Drs. Boudreau and Veenstra and Mr. Guzauskas served as a consultant for Genentech, Inc. Ms. Villa is employed by Genentech, Inc. Dr. Fagan is a consultant for Genentech, Inc."

"A Model of Cost-effectiveness of Tissue Plasminogen Activator in Patient Subgroups 3 to 4.5 Hours After Onset of Acute Ischemic Stroke"