Hickam's Victims: Misdiagnosis & Treatment of an Incidentaloma in Guillain-Barre Syndrome and Careless Citation Practices

I'm following citations to our paper explicating Hickam's Dictum (HD) and Ockham's Razor (OR) as applied to diagnostic decision making, published two years ago. It was my hope that this paper would lead to a more thoughtful consideration of these allegedly conflicting clinical saws, but alas I was too sanguine about that prospect. It would seem that most people citing our paper are not even reading it. Rather, it appears that they conclude that they have identified a case of HD, write a case report about it, then seek supporting references and cite our paper without reading it or applying its insights to their case.

Nonetheless, I'm happy to have our paper cited for any perspicatious and curious readers of these case reports. And, the problem of careless citation practices is rampant. Often when I check citations to see if they support the referenced statements, I'm gobsmacked: not only do many citations fail to support the authors' statements, sometimes they directly undermine them. Commonly, an author makes claims as though starting from truth rather than uncertainty, then searches for supporting references, but does not carefully evaluate the references or their relation to his claim -- or even read the papers he's referencing. Rather, he reads the title or abstract ingenuously and cites the paper. This is not scholarship, this is confirmation bias and motivated reasoning in action. It is abetted and exacerbated by the tendency of authors to overextend themselves in their abstracts, arriving at conclusions that are broader and firmer than warranted by the data. This phenomenon has a tendency to magnify and replicate flimsy claims, so we wind up with wholly unsupported concepts that persist for decades, viz, immune dysregulation in sepsis. (Just think about this for a second and decide if it makes sense:"Some people die of sepsis; therefore, evolution of mamallian immunology stalled, failed, or overshot, and the immune system is dysregulated.") Yet this concept accompanies almost every single article about sepsis for going on a generation; you gotta reference it in your sepsis paper. So, you go to pubmed, type it in, find the latest abstract that mentions  it, import it into EndNote, cite it. Done. Specious concept propagated yet again.

In this case report alleging the simultaneous presentation of Guillain-Barre Syndrome (GBS) and a pancreaticoduodenal artery aneurysm PDAA with "impending rupture," the author invokes Hickam's dictum becaues the patient has two diseases that were discovered at the same time. The schema outlined in Figure 3 of our paper shows that there are four possibilities for the relations between two (or more) disease: incidentalomas, pre-existing diseases, diseases causally connected to the principal diagnosis, and lastly, two symptomatic, independent, temporally coincident diseases. This last possibility is decidecly the least common, but it's what the author settled upon.

The patient had a preceeding viral illness (setting the stage for GBS) and a week later developed numbness and back pain, two common symptoms of GBS. She went to an ER and because of the back pain, had a CT of the abdomen, and a PDAA was discovered. The case report describes it as having an "impending rupture," but we are not told how this determination was made. (Can it be made?) It was embolized and her back pain (maybe? kinda?) resolved. Days after the embolization, they discovered the true cause of her numbness and back pain: GBS.

Not described in the report is the well-established fact that the vast majority of unruptured PDAA are totally asymptomatic and discovered incidentally on imaging as in this case. Furthermore, when they are symptomatic they cause epigastric and abdominal pain, not back pain. Risk of rupture is not clearly correlated with size, so size alone cannot be used to infer "impending rupture." Just that background knowledge is enough to establish that this is an incidentaloma. 

In real time, considering that these aneurysms take years to form and are mostly incidentally discovered and don't cause back pain should lead the wary clinician to question whether this is an incidentaloma and the real disease is still lurking in the background. Her symptoms should be more carefully explored, information about the patient and the diagnostic possibilities further investigated and synthesized.

If we find incidentalomas and treat them with invasive therapies without careful consideration, we are liable to cause iatrogenic problems. Though PDAAs warrant embolization because of a high risk of later rupture, we may not want to place it high on the list of management priorities depending on the acute disease (here, GBS) we're dealing with. Imagine that this lady had presented just a bit later when she had respiratory muscle weakness, and had been taken for urgent embolization, and then she coded during conscious sedation for the procedure. Or, imagine if, as almost happened in this case, that the principal diagnosis (the one which explains the chief complaint: GBS) was missed and she had respiratory arrest because PDAA with "impending rupture" was misidentified as the principal problem and her weakness was misattributed to residual sedation effects.

Analysis of this case report makes clear that this is not a purely pedagogical or pedantic exercise. Knowledge structured according to our Figure 3 heightens awareness that we can always be chasing incidentalomas or anchoring on known diseases, missing the true principal diagnosis, or failing to make connections between causally related facets of the presenting illness, invoking multiple diagnoses --sometimes highly unlikely combinations of rare diseases -- rather than a unifying one.

Some of these case reports alleging HD are downright embarrassing. They expose fundamental errors of diagnostic logic that persist even after the effort to write up the case for full publication has been undertaken. As we showed in our paper -- the one that apparently nobody reads -- most of the time when you invoke HD it means you missed the big picture and were surprised by an unsurprising set of multiple diagnoses because of incomplete or flawed understanding of the case. 

Medicine is hard.

Epistemic Arrogance. Case Records of the Massachusetts General Hospital. Diagnosis is Stochastic, NOT Deterministic

This post was spurred by my reading the July 24^th NEJM case records, “A Man with Cough, Dyspnea, and Hypoxemia.”  When I was still using twitter, I mused that the discussants have too high a rate of getting the right diagnosis. This implies that there is no stochastic or aleatory uncertainty in diagnosis; that if you have the requisite information and reasoning process, you can connect the dots, every single time, to the final diagnosis. In this view, there is no randomness to diagnosis, no inherent and irreducible probabilistic (or stochastic, or aleatory) uncertainty. Of course, this is pure codswallop: stochastic uncertainty is what makes diagnosis so hard.

You cannot say that the result in any case was not possible with the information presented, but with a population of cases you can make inferences about whether the percentage of correct discussant diagnoses is improbable. The fact that the discussant gets the right diagnosis almost 100% of the time (I have tabulated the % correct for over 10 years of these cases – it rounds to 100%) in the CRMGH (Case Records of the Massachusetts General Hospital) is like finding too little variability in a research study (or  studies; or Bernie Madoff’s annual returns) and concluding that the results (returns) were manipulated. We use our well-justified first principles assumption of stochasticity, find that there is not enough variability, and conclude that something is being manipulated to remove the aleatory uncertainty. (I use stochastic, aleatory, and probabilistic herein as interchangeable adjectives for uncertainty.) And so must it be in the CRMGH. How the aleatory uncertainty is being removed is anybody’s guess and any insider’s knowledge, I suppose. Possibilities include both implicit and explicit cues. An implicit cue may be the selection of, say, a specialist in heritable cardiomyopathies as the discussant in a case where the final diagnosis is a genetic cardiomyopathy. Explicit cues may be that somebody tells the discussant the final diagnosis at the outset or tells them to revise their discussion if they get it wrong in draft. Hospitals are not closed systems either. People hear if there was a case of Creutzfeld-Jacob diagnosed recently, and the director of the microbiology lab knows if a particular rare species was recently cultured. Tales of rare diagnoses spread, as they are the currency of clinical acumen. I can’t say that any of these mechanisms -- from subtle queueing to explicit cheating -- are occurring. I only know that the near 100% hit rate means that randomness has been removed from an inherently random process.

The Test is Not the Truth: One Week in the Lonely Life of a Bayesian Clinician

DAH from GPA or CPE/ESRD?

If there is one thing you should remember about clinical decision making it is this:  the test is not the truth.  A diagnostic test raises or decreases the prior or pre-test probability (PTP) of the disease under consideration.  The amount of increase or decrease in probability with a positive or negative test depends on the starting probability and the likelihood ratio of the test.  (LR+ = sensitivity/1-specificity; LR- = 1-sensitivity/specificity).  If we don't attend to the PTP of disease, serious diagnostic errors and therapeutic misadventures may result.  This is especially true when a low PTP disease is diagnosed on the basis of a test with poor sensitivity and specificity (and a LR not much greater than 1 or 2 or even 4 or 5).  Several examples of this came up a while back.

A woman presented with thunderclap headache and had recurrent seizures during initial evaluation.  A differential diagnosis was formulated and it included PRES (posterior reversible encephalopathy syndrome) with a PTP of about 20%.  Subarachnoid hemorrhage was excluded with CT and LP and the PTP of PRES rose to about 40% (since it occupied some of the probability space previously occupied by SAH once the latter was excluded.)  The subsequent MRI images were consistent with PRES.  Nonetheless, a vascular MRI was ordered to "exclude the possibility of cerebral vasculitis".  The problems are twofold.  First, the probability of PRES is now on the order of 70% if the sensitivity and specificity of MRI are on the order of 80%, and it is 85% if sensitivity and specificity are each 90%.  (Go ahead and plug some numbers into the calculator on the sidebar of the blog.)  This probability meets or exceeds the probability threshold to both consider the diagnosis made, and to take action based on it.  In this case inaction and supportive care are indicated.  Even if a vascular MRI were consistent with cerebral vasculitis, which has a PTP an order of magnitude or more less than PRES, the diagnosis is still PRES.  The truth is not in the test, the truth is in the rationally considered diagnostic process of which the test is one part.