Epidemiology: Legends & Facts – The Publication Bias – #FOAMed, #FOAMcc

So until a few years ago I reluctantly admit I was one of those who read the title, abstract, intro and quite diagonally went thru methods and results before starting to pay attention at the discussion.  On one hand I got to read a lot more articles per unit time, but my analysis was rudimentary at best…

That was until a colleague, good friend, judoka and microbiologist extraordinaire Peter Barriga started to shine some light into my epidemiological darkness while teaching me some judo.  So while waiting for his textbook to come out, here are a few principles that I’ve found very interesting, revealing, but also somewhat frightening: in part, they explain the lack of strength and consistency found in much of the medical literature

So let’s look at the publication bias.  This refers to the likelihood that a study will be published in a major medical journal.  Not surprisingly, journals are generally more interested in positive studies than negative ones.  After all, who would be interested in reading a journal where more than half the studies concluded with “well, this didn’t work…”   It would feel like a waste of reading time.

Now, let’s look at our whole p value, a number (0.05) which we are culturally in love with. What does it really mean?  It means that there is a 1 in 20 or less likelihood of the result being purely chance. So let’s say a popular drug for sepsis is studies by 20 teams,  the same study done 20 times could yield 1 positive and 19 negative results – by chance alone.

The question then becomes, which study is picked by a big journal to be published… One of the 19 negative studies or…the positive one?

Fortunately nowadays due to the information age, a study registry exists where all studies – including negative ones – can be found, so that anyone interested enough in a particular topic can dig up all the data and have an accurate assessment, but is that the case for most physicians?  Or do most pick up the big titles of the big journals…?

Hmmm… So I think it is incumbent on all of us to examine the main things we do in our practice, and make sure we have carefully looked at the available data surrounding it, and not just blindly applied guidelines, recipes or whatever our seniors and mentors are doing or have shown us.

more to come on how to make our practice GEBM (good evidence based medicine) rather than just EBM…



Steroids for cardiac arrest…really? My take on the VSE study – #FOAMed, #FOAMcc

So I’ve been asked a few times for my opinion about the VSE study in the last couple of months, so here we go.

JAMA2013;310(3):270-279. doi:10.1001/jama.2013.7832.

First of all, lets look at it from a theoretical perspective.  How would steroids contribute to ROSC (return of spontaneous circulation)?  Hard to believe they possibly could, given the ultra-short timeframe to ROSC – minutes mostly – and the much longer action of steroids.  However, it is quite possible – and in view of this study perhaps likely – that there is an effect on shock and RONF (return of neurological function).

Why?  Post arrest shock results in MSOF due to a cascade of inflammation resulting from the hypoxic insult. Remember that we are not designed to survive these events. Being designed to fight off moderate trauma and infection (eg being bitten by an animal or clubbed by another caveman) our physiological reaction often overshoots the mark resulting in more damage than good, as it does in sepsis (variably depending on our different geno/phenotypes).  So whether liver, kidney or brain damage, some component is not only related to pure hypoxia but also to an inflammatory cascade that has a prolonged effect. This is the same thing we are targeting with cooling, on top of a simple metabolic supply/demand issue, so in terms of biological plausibility, it makes some sense.

In the post-ROSC phase, there is always the possibility of relative adrenal insufficiency – after all, the adrenals have taken a hit as all the other organs did – so again there is biological plausibility.

There’s quite a bit of debate out there as to whether or not to apply this.  I’m pragmatic, not a purist, and my beliefs lie in evidence, biological plausibility and the risk/benefit ratio.  In this case, I think the decision is actually quite simple.  The way I see it, the steroids are harmless and probably helpful, so I have been giving solumedrol in the last few months.

If anything, I’m more concerned about the harm I may be doing with epinephrine/vasopressin, especially in terms of RONF.  I do hope an epi (various doses) vs placebo study is done, because it is difficult to withhold, knowing that there is greater immediate effect on ROSC… Hard decision as the clinician at the bedside, and hopefully this will become clearer in the near future.

For those unclear about the whole epi debate, the physiological issue is that the relationship between pressure and perfusion is represented by an inverted U curve – at very high pressures (from vasoconstriction) perfusion is decreased (think of the extremities on high dose pressers with a decent BP).  So although we may help coronary perfusion pressure and thus ROSC, end-organ damage is greater…and nothing matters much without a brain.


So bottom line:  I’d go ahead with the steroids, and for now the V and E, but I wouldn’t be surprised to drop or decrease those soon.

More to come on resuscitation and its future (the present for some of us…) in posts and podcasts!

Hope this helps!