Dear SIRS: Your Septic System Stinks

I perused with interest the April 2nd JAMA article on the temporal improvement in severe sepsis outcomes in Australia and New Zealand (ANZ) by Kaukonen et al this week.  Epidemiological studies like this remind me why I'm so fond of reading reports of RCTs:  because they're so much easier to think about.  Epidemiological studies have so many variables, measured and unmeasured, and so much confounding you have to consider. I spent at least five hours poring over the ANZ report, and then comparing it to the recent NEJM article about improved diabetes complications between 1990 and 2010, which is similar, but a bit more convincing (perhaps the reason it's in the NEJM).

I was delighted that the authors of the ANZ study twice referenced our delta inflation article and that the editorialists agree with the letter I wrote to AJRCCM last year advocating composite morbidity outcomes in trials of critical illness.  These issues dovetail - we have a consistent track record of failure to demonstrate mortality improvements in critical care, while we turn a blind eye to other outcomes which may be more tractable and which are often of paramount concern to patients.

Stowaway and Accidental Empiricist Humbles Physiological Theorists: The Boy in the Wheel Well

Kessler Peak in the Wasatch:  10,400 feet

Several years ago, I posted about empirical confirmation of West's theoretical blood gas results at altitude on Everest.  (Last week, an avalanche on Everest took more lives in a single day than any other in the history of the mountain.)  The remarkably low PaO2 values (mean 26 mm Hg) demonstrated by those authors, (and the correspondingly low estimated SaO2 values) are truly incredible and even bewildering especially from the perspective of clinical practice where we often get all bent out of shape with PaO2 values under 55 mm Hg or so.  Documentation of the PaO2 values in the "natural experiment" that mountaineers subject themselves to serves as fodder for ponder for those of us who are prone to daydreaming about physiology:  is tolerance of these low values possible only because of acclimatization and extreme physical fitness?  (but they're exercising, not just standing there!)  what is the lower safe limit of hypoxemia?  does it vary by age?  the presence of other illnesses?  is there a role for permissive hypoxemia in the practice of critical care?

Underperforming the Market: Why Researchers are Worse than Professional Stock Pickers and A Way Out

I was reading in the NYT yesterday a story about Warren Buffet and how the Oracle of Omaha has trailed the S&P 500 for four of the last five years.  It was based on an analysis done by a statistician who runs a blog called Statistical Ideas, which has a post on p-values that links to this Nature article a couple of months back that describes how we can be misled by P-values.  And all of this got me thinking.

We have a dual problem in medical research:  a.)  of conceiving alternative hypotheses which cannot be confirmed in large trials free of bias;  and b.) not being able to replicate the findings of positive trials.  What are the reasons for this?

Absolute Confusion: How Researchers Mislead the Public with Relative Risk

This article in Sunday's New York Times about gauging the risk of autism highlights an important confusion in the appraisal of evidence from clinical trials and epidemiological studies that appears to be shared by laypersons, researchers, and practitioners alike:  we focus on relative risks when we should be concerned with absolute risks.

The rational decision maker, when evaluating a risk or a benefit, is concerned with the absolute magnitude of that risk or benefit.  A proportional change from an arbitrary baseline (a relative risk) is irrelevant.  Here's an example that should bring this into keen focus.

If you are shopping and you find a 50% off sale, that's a great sale.  Unless you're shopping for socks.  At $0.99 a pair, you save $0.50 with that massive discount.  Alternatively, if you come across a 3% sale, but it's at the Audi dealership, that paltry discount can save you $900 on a $30,000 Audi A4.   Which discount should you spend the day pursuing?  The discount rate mathematically obscures the value of the savings.  If we framed the problem in terms of absolute savings, we would be better consumers.  But retailers know that saying "50% OFF!" attracts more attention than "$0.50 OFF!" in the sock department.  Likewise, car salesmen know that writing "$1000 BELOW INVOICE!" on the windshield looks a lot more attractive than "3% BELOW INVOICE!"