Thursday 7 May 2015

Epistaxis treatment using injectable form of tranexamic acid topically: why not

 I've done my share of bootlegging. Up 'ere, if you engage in what the federal government calls 'illegal activity,' but what we call 'just a man tryin' to make a livin' for his family sellin' moonshine liquor,' it behooves oneself to keep his wits. Long story short, we hear a story too good to be true... it ain't.       Lt Aldo Raine “Inglourious Basterds” 2009

This study out of Tehran, Iran looked at using the injectable form of tranexamic acid (TXA) to control uncomplicated anterior epistaxis.

This was a single centre unblinded randomized controlled trial. In the experimental group a 15cm piece of cotton pledget was soaked in tranexamic acid (500mg/5ml) and was inserted in the nostril. It was removed shortly after it was determined that the bleeding had stopped. The control group had standard anterior nasal packing that was removed after 3 days.

216 patients were randomized and there was no loss to follow up. The methods did not really specify a primary outcome but they did report numerous “efficacy variables.”

Within 10 minutes of treatment, the bleeding had stopped in 71% of the TXA group compared with 31% of the control. In addition, 95% of those treated with TXA were discharged from the ED in 2 hours or less compared to 6% in the controls.

This treatment effect is way too good to be true. There must have been some systematic bias that accounted for the profound differences in early discharge of the TXA group. This is never really explained in the discussion section of the paper. 

The numerous grammatical errors in the text do make the paper appear a bit sloppy and hard to read. It should be the job of the journal editor to ensure that these errors do not make it to print. But heck, this isn't exactly a high impact journal.

Unfortunately, this study excluded complicated epistaxis. These are precisely the patients who may require some extra finesse and it would be nice to know if there was some efficacy of TXA in this population.

Despite all of this, I think the notion of topical TXA treatment for epistaxis is compelling. Many other large studies over decades have shown it to be reasonably safe. Not only is TXA unlikely to cause harm but it is dirt cheap. We have vials of TXA in my ED that cost $6 a vial.

The bottom line? I think it is reasonable to try the injectable form of TXA topically as an adjunct to help control epistaxis. Why not?  But please don’t expect the miracle cure that this paper purports.


Zahed R, Moharamzadeh P, AlizadehArasi S, et al. A new and rapid method for epistaxis treatment using injectable form of trenexamic acid topically: a randomized controlled trial. Am J Emerg Med 2013; 31:1389-1392.

Yes you can perform RSI through an intraosseous line

Not every research question can be answered by a randomized controlled trial. Often they are not feasible or ethical and out of necessity other study designs are utilized.  I like this clever little study investigating whether one can use an intraosseous line for induction of anaesthesia.

Where else would you conduct this study other than Afghanistan? This was a prospective observational study of previously healthy young patients (mostly soldiers) who had just suffered severe trauma. Upon presentation to a British combat hospital, 34 patients underwent RSI using an IO line.

These patients were quite sick with a median injury severity score of 25. As expected, the predominant mechanism of injury was blast.

First pass intubation success rate was 97% (95% CI 81%-100%) with mostly great visualization of the cords.

One could reasonably argue that this study has some limitations. The numbers were small. Mostly young previously healthy soldiers would make external validity an issue. Perhaps they were looking at the wrong primary outcomes and they should have focused on time to intubation and/or relaxation.

But given the big picture, I think they put in a decent effort. Research on resuscitation is always challenging and getting numbers is hard. How many IO lines have you put in? Most health care practitioners would have other priorities when caring for a very sick patient (who has just been blown up) rather than focusing attention on ticking boxes on a study form. In the end, I think their outcome measures were quite pragmatic.

Sure, this study is not definitive evidence but I think it is enough to suggest the efficacy of the IO route for rapid sequence induction.


Barnard EBG, Moy, RJ, Kehoe AD, et al. Rapid sequence induction of anaesthesia via the intraosseous route: a prospective observational study. Emerg Med J. 2014 Jun 24. pii: emermed-2014-203740. doi: 10.1136/emermed-2014-203740. [Epub ahead of print]

Wednesday 6 May 2015

Research Misconduct Identified by the US FDA Remains Hidden- Fraud Under the Rug

Every year the US Federal Drug Administration inspects several hundred clinical sites performing biomedical research on humans. They classify their inspections mostly as “no action indicated” but occasionally discover a severe problem they label as “official action indicated” or OAI.

The worst of these OAI’s could include submission of false information and/or failure to report adverse events.

The author of this paper is a profession or journalism from NYU with a special interest in research misconduct. With much of his graduate students doing the leg work, he attempted to find the OAI’s, describe the violations and determine whether subsequent published articles acknowledged the FDA’s findings. One would think that the FDA had ethical and or legal obligations to make these serious infractions public.

Without going in to too many specifics, they found it quite difficult to even find the OAI’s as there is no public repository for this information. In addition, the FDA reports they discovered were highly redacted. This made it hard to determine what infractions were related to actual articles in the peer reviewed literature. Nevertheless they found 78 publications that resulted from trials in which the FDA found significant violations. How many of these papers mentioned the FDA’s concerns? Only 4%.

There are numerous examples of transgressions listed in the paper. My favourite was a researcher who pled guilty to fraud and criminally negligent homicide in the conduct of a trial. She was sentenced to 71 months in prison. Although this was clearly documented by the FDA, there is no mention of any of this in the published studies based on her trial.

How could all of this happen? It turns out the FDA does not officially make OAI’s public. They don’t tell journal editors nor do they link their discovered information back to The author of this paper makes some very sensible suggestions on how the FDA might improve their processes. Fortunately it looks like they might be listening.

All of this might sound a bit like a conspiracy theory. But fraud in medical research is a real entity and very easy to execute. There are strong incentives in our “publish or perish” climate to resort to devious means of research. This says nothing of bias, spin and the billions of dollars that pharmaceutical industry stand to profit from research that goes their way.

What are we to take home from all of this? At the core of biomedical research lurks a perverse incentive encouraging fraud and it happens more than we like to know. Be sceptical of studies that look to good to be true. Sorry, but sometimes data is simply made up.

Hopefully the FDA will change their ways.


Seife C. Research Misconduct Identified by the US Food and Drug Administration; Out of Sight, Out of Mind, Out of the Peer-Reviewed Literature. JAMA Intern Med 2015 Apr 1; 175(4):567-77.

Does over-reliance on pulse oximetry lead to increased hospitalization of infants with bronchiolitis?

This was a unique study out of a single paediatric care ED in Toronto, Canada. The authors were obviously of the opinion that they were admitting too many children to hospital that could otherwise go home based on low pulse ox readings. Does a single number change our practice?

The study design involved a little deception. (Who doesn't like a little deception?) Infants with moderate bronchiolitis were randomized in a double blind fashion to getting an accurate pulse oximetry measurement vs. one that displayed a result 3% points higher than the real measurement. In case you are wondering, they had the manufacturer alter the machines and they bribed the ethics committee (okay... I made that last bit up).

The primary outcome was hospitalization within 72 hours. There were other common sense secondary outcome measurements.

213 infants were randomized and there was no loss to follow-up. 41% of patients with the true oximetry group were hospitalized as compared to 25% in the altered oximetry group. Absolute difference 16% or NNT to prevent a hospitalization is 7. The overall strategy seemed pretty safe. Wow, pretty compelling results.

But before you consider throwing away your pulse oximeter, consider the following. The mean true pulse ox reading in all of the patients enrolled was about 97%. Very few of these infants were really that sick with a mean respiratory rate about 50. Only 28 infants in this study had true readings below 94%. There probably is no problem when you are considering a pulse ox of 97% being inaccuragely displayed as 100%. So this study is clearly not powered to investigate safety.

Nevertheless, I think this study is quite interesting and emphasizes a key point. Are we too reliant on single numbers when it comes to patient treatment decisions? The answer is probably yes.


Schuh S, Freedman S, Coates A, et al. Effect of Oximetry on Hospitalization in Bronchiolitis. A Randomized Clinical Trial. JAMA. 2014;312(7):712-718.