Saturday, June 11, 2011

rFactor VII Is Not Safe (Despite Their Conclusions)

When NovoNordisk writes an article analyzing safety data from the CONTROL trial, you get a skewed perspective on the data.  Specifically, if you only read the abstract, you're going to think that it's safer in some ways(ARDS was less), and there was no difference in adverse events (except for all that investigator-reported AMI/NSTEMI).  So, that sounds favorable.

But, the real reason there's no significant differences in outcomes - and the reason why they terminated the trial early - is because the interim data is underpowered to detect a difference.  As you see, the 30-day mortality is 12% vs 11% in favor of placebo - and that wasn't helping NovoNordisk, so they quit before they could reach sufficient statistical power to prove their product was unhelpful.  However, they can now benefit from that same lack of power to detect differences by applying it to the safety aspect, and trumpeting its equivalency in terms of AEs.

When taken in the context of the original trial, this is just a flawed piece of pharmaceutical propaganda to try and prevent the building crackdown on off-label Factor VII use.

http://www.ncbi.nlm.nih.gov/pubmed/21610529

Friday, June 10, 2011

The Single Troponin After 8 Hours of Symptoms

The ACEP guidelines still have, as level B recommendations, that a single cardiac biomaker "8 to 12 hours" after symptom onset is adequate to exclude the diagnosis of NSTEMI.

This study looked at all of Highland's patients that received more than one troponin measurement in their ED.  Then, they looked at all the patients with initially negative troponins, and subsequently positive ones.  And, finally, they tried to see how many of those had symptoms >8 hours.  Their definitions are that troponins <0.06 ng/mL are negative, between 0.06 and 0.6 are indeterminate, and >0.6 are positive.

After starting with 5,596 patients, they had 125 that were negative initially, and then positive.  And, for symptoms greater than 8 hours, a grand total of seven troponins ≤0.06 ng/mL and then subsequently positive, and 18 others that were indeterminate and then subsequently positive.  They then say only two had a diagnosis of ACS.

Regardless, despite the size of the study, when you start talking about these sorts of tiny numbers and getting into splitting hairs on the diagnosis, you're basically working on anecdotal evidence.  So, take it with a grain of salt - you're usually safe in a patient with that symptom duration, but you're working off mostly consensus opinion as opposed to great evidence.

More interesting, really, would be some kind of follow-up on the 1,086 patients that were discharged after a single negative troponin (many of which probably fulfilled the >8 hour criterion) - but there's no way to actually make that sort of follow happen realistically.

http://www.hindawi.com/isrn/cardiology/2011/364728/

Thursday, June 9, 2011

CT Coronary Angiography Screening Is Not Beneficial

Disclaimer: I despise CCTA for low-risk chest pain in the ED.  It leads to additional unnecessary testing, interventions, and harms that outweigh the risk of coronary events in its target population.  Our liability-sensitive practice has us evaluating an ever-increasing cohort of low- and (mostly) zero-risk young chest pain patients, and this is purported to be a test of choice for identifying a zero-zero risk population.

But there are just far too many false positives that have coronary artery disease of uncertain clinical significance.

This is a Korean study that compared 1000 matched controls that did not undergo CCTA with 1000 who did.  215 asymptomatic patients had positive CCTA - defined as any atherosclerotic plaque.  52 had >50% stenosis and 21 had >75% stenosis.

Their control cohort and their CCTA cohort were very similar - and 55-59% low risk, 34-29% intermediate, and 10% high risk based on NCEP risk stratification.

And their control group had a grand total of 1 cardiac event within their 18 month follow-up period, as did a single person in their positive CCTA group.  However, the CCTA group ended up with more additional testing and cardiac revascularization procedures during their follow-up time frames - with no change in outcomes.

Now, these are asymptomatic patients chosen for screening - not the same as our chest pain patients in the ED - but it's another call for caution regarding overtesting and overtreating.

Tuesday, June 7, 2011

Move Over MRSA - It's VISA and VRSA Time

Is it too late to buy stock in the company that makes linezolid?

This group up in Detroit reviewed 320 patients with MRSA bacteremia and found that 52.5% experienced Vancomycin failure.  Their conclusion states several significant OR for failure, but review of the between-group differences doesn't show a lot of significant differences.  Nursing homes, for example, were the only p < 0.05, and predicted vancomycin success with a p of 0.02.

What is more important than their clinical predictors, however, is their review of the bactericidal activity of vancomycin - and that higher MICs and higher troughs are needed to effectively treat patients.  I've seen our pharmacists recognize this at my hospital as well - the 1g IV Vancomycin standard initial load is transitioning to a weight-based dose.

But, more importantly, what we're probably really observing is the initial stages of the end of vancomycin's utility for MRSA.  And, I hate to see what happens when TMP/SMX stops working, too....

http://www.ncbi.nlm.nih.gov/pubmed/21460309

Monday, June 6, 2011

Overdiagnosis of Pulmonary Embolism

Another over-testing over-diagnosis article effectively illustrating issues endemic to our current medical culture.

They do a retrospective national database review regarding the impact of the introduction of CTPA protocol for rule-out PE, and note that we've diagnosed three times as many PEs in 2006 as we did in 1998.  And, by detecting more PEs, we managed to reduce mortality attributed to PE...along the same gradually decreasing trendline that was present prior to the introduction of CTPA.

Figure 2 is the truly damning graphic - look at all those extra PEs we're finding and treating for effectively no substantial benefit.  Their secondary analysis was in-hospital anticoagulation complications on patients with any diagnosis of PE, which has jumped 71%.  Thank goodness we can put them on dagibatran now instead of coumadin and not be able to reverse their life-threatening bleeding episodes....

Again, we are testing people who shouldn't be testing, finding disease of uncertain clinical significance, and harming them with overtreatment - and let's not even start with the costs.

http://www.ncbi.nlm.nih.gov/pubmed/21555660

Sunday, June 5, 2011

Physician Perception of Ethnicity Preferences at End Of Life

I'm not sure what this paper definitely adds to the body of literature, but it's been awhile since I read anything on this topic, so I thought it was interesting.

I will give the disclaimer that this has been my limited anecdotal experience during my time in MICU, SICU, PICU etc., that certain ethnic groups were less likely to be amenable to withdrawal of care discussions, transitions to comfort care, hospice, etc., much to our absolute frustration that we were expending inordinate resources to torture some poor ventilated husk of person with no chance of functional recovery.  This study, in a small single-center sample, more or less confirms that we all share that same perception - but, in theory, it doesn't change our practice.

This study surveyed physicians regarding their perceptions of black vs. white end-stage cancer patients, and they tended to believe that a black person would be more likely to want continued aggressive treatment at the end of life.  The remainder of their article, which is a little more difficult to interpret, basically said that regardless of the perceptions, they still recommended the same (in statistical aggregate) treatment to the black vs. white hypothetical cohorts.

While this study didn't find any measurable treatment differences, we've seen all throughout the literature that perception tends towards reality, and that there are many cases of measurable outcomes differences for different ethnicities.  This study just leaves me with a sour taste and more questions than answers.

http://www.ncbi.nlm.nih.gov/pubmed/21460710