Saturday, September 8, 2012

Dabigatran - It's Everywhere!

Dabigatran, you may know it at Pradaxa, the first in a string of potential blockbuster oral anticoagulants, has a few problems.  Lack of effective reversal options, poor prescriber understanding of drug-drug and GFR interactions, and reduced dosing options should make physicians wary of this medication.

Well, it's not.

This is a dataset gleaned by an ongoing physician audit covering ~4800 U.S. practioners between 2007 and 2011, used to estimate prescription trends for the U.S.  Warfarin prescriptions were reasonably stable between 2007 and 2010, but then have dropped approximately 20% over the course of 2011.  The medication taking up the slack?  Dabigatran.

If you accept the findings from RE-LY, then you're probably OK with its use in non-valvular atrial fibrillation.  Unfortunately, 37% of the prescriptions were off-label, outside the FDA approved indications. Then, within the remaining 63%, there's no breakdown for whether it was valvular or non-valvular atrial fibrillation.  So, the percentage of off-label use is probably even higher than found in the data.

It would seem to be prudent to be cautious with a new medication that's already being investigated by the FDA for serious bleeding complications.  Luckily for the manufacturer, that's not happening, and prescription expenditures for dabigatran already exceed those for warfarin – over $160 million per quarter.

"National Trends in Oral Anticoagulant Use in the United States, 2007 to 2011"

Thursday, September 6, 2012

More Failed Therapies for Sinusitis

For routine, office-based diagnoses of acute sinusitis, we've seen that antibiotics are unlikely to be beneficial.  The other theory behind treatment is attenuation of the inflammatory response, promoting sinus drainage.  Intranasal steroid sprays have inconclusive data.  This is a trial of systemic steroids, theorizing that intranasal steroids suffer from inadequate tissue penetration.

There are a lot of issues with this trial.  Whether it's clinically significant or not, the 30mg/day dose of prednisolone is below the typically used doses of 50mg or 60mg.  There were 54 treatment locations and 68 family physicians involved in this study over a 2 1/2 year period – and only managed to enroll 185 patients.  For a problem "frequently encountered" in primary care, it's a little hard to have confidence there aren't biases present with enrollment.

The authors followed many different clinical outcomes, as well as the SNOT-20 score, at several different time points, and the easiest way to sum it up is to say there are probably no clinically relevant differences between groups.  The trends nearly all favored prednisolone, but the absolute differences in outcomes provided NNT between 10 and 33.  A larger trial might have detected a statistically significant benefit to steroids – or it might not – but most enrolled patients had symptom improvement, regardless.

"Systemic corticosteroid monotherapy for clinically diagnosed acute rhinosinusitis: a randomized controlled trial"

Tuesday, September 4, 2012

It's Too Hot To Fight & Other Fables

There's a mythology regarding temperature and violent crime – both increase in tandem up until a certain point, at which it becomes "too warm".  This study, a retrospective analysis of violent crime from a six-year period in Dallas, TX, generally confirms the increase in violence as the temperature increases.

The authors additionally propose, however, a curvilinear relationship based on the data that interprets an inflection point at 80-89 degrees a bit aggressively, considering they only have one data point above 80-89 with which to define the further trend.  The absolute differences between total numbers of violent assaults in each temperature bracket are small enough, it's a little hard to confidently say there's a point at which it becomes too hot for violent crime.  It makes sense, of course, but that's more editorializing.

Perhaps they could attempt to externally validate these findings in Iraq – which seems awfully hot and violent.  They also note there is a strong correlation between temperature and hours of daylight – but it seems as though that'd be rather difficult to control for one or the other.

And, tying this entire issue into climate change is another unusual matter entirely....

"Temperature and Violent Crime in Dallas, Texas: Relationships and Implications of Climate Change"