Hickam's Victims: Histoplasmosis and PJP in an immunocompromised host

Here's a great case report of histoplasmosis and PJP co-infection in an immunocompromised host. The authors did a pretty good job of documenting both diagnoses and discussing the case in relation to Hickam's Dictum (HD). However, the discussion would have benefited from incorporation of our framework from Hickam's Dictum: An Analysis of Multiple Diagnoses. 

As recent readers of this blog know, I'm interested in whether our framework can be useful in real time diagnosis of cases where multiple diagnoses are being considered to explain clinical findings. In this case, an immunocompromised patient (SLE, RA; receiving prednisone and cyclophosphamide) presented with two weeks of fever and chills without other symptoms. So, we can be pretty confident she's infected, and is highly predisposed to opportunistic infections as well as garden variety ones.

Her chest imaging (in the thumbnail) showed a predominant finding of pulmonary micronodules along with ground glass opacieies (GGO) and lymphadenopathy. We can make a differential right here based on a miliary pattern, and it would include mycobacterial diseases, fungal diseases, lymphoma, etc.

What would not be atop the differential diagnosis is PJP pneumonia because this would be an unusual presentation for that. We would expect PJP to present with subacute dyspnea on exertion and other chest symptoms, and with just GGO or interstitial opacities. The radiology in this case is not consistent with PJP, though it could rarely present in this fashion (an multifarous others). 

Alas, a bronchoalveolar lavage (BAL) was performed and PJP was found (we are not told what finding on the BAL supported this). Treatment for PJP was initiated but she didn't improve, was intubated, and, without molecular diagnostics available at their hospital, they did transbronchial biopsies and very clearly documented the presence of both PJP (right) and Histoplasma capsulatum (left), the latter being a perfectly satisfactory explanation for the clinical presentation and imaging findings: 

Based on our framework, we expect immunocompromised patients to not uncommonly have more than one pathogen because of Reichenbach's Common Cause Principle, which states that if an unusual coincidence occurs between events A&B, one either caused the other, or both share a common cause, C. So whenever we have an underlying disease like immunosuppresion, we should be prepared for multiple downstream infectious (or other) complications stemming from it. Alternatively, it's possible that her entire presentation is explained by histoplasmosis and the PJP represents an asymptomatic incidentaloma, albeit a consequential one that must be treated in the context of immunosuppression (and absence of prophylaxis). In short, we expect HD in immunocompromised patients. No surprises there.

One lesson from this case is that whenever you go testing (fishing) for things with a big net, you have to carefully discern whether what you dredge up is a suitable explanation for the clinical presentation. In this case, garden variety pneumonia (for which she was treated with 2 antibiotic regimens on days 1-2) was never a suitable explanation. BAL was not performed until day 7, and the premature settling upon PJP delayed further the ultimate diagnosis until biopsies on day 12. 

The biggest lesson here is not whether multiple diagnoses occur, they commonly do! The pivotal question that must be answered is: does the diagnosis rendered explain the context, the chief complaint, and the data adequately?  If not, you may be chasing a red herring (incidentaloma), anchoring on a known pre-existing disease, or failing to connect the causal dots, all the while missing or delaying the principal diagnosis  And, in this case, its treatment  

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.

Hickam's Victims: An M&M of an MM misdiagnosis

In this case report, the authors describe the case of a 42-year-old-woman who presented with abdominal pain, rash, fever, loose stools and anorexia. Her serum eosinophil count was 2.07x10^9 (25%), and she had increased light chains - both kappa and lambda. Bone marrow biopsy showed lots of eosinophils and immature plasma cells. I will leave it to the oncology nerds to reference the report for details, but just note that the presence of both kappa and lambda is a red flag, and so are the eosinophils if you're going to call this multiple myeloma (MM). And the presenting symptoms are another red flag because they're not consistent with MM.

Nonetheless, the patient was diagnosed with MM and underwent treatment for it for seven years. The treatments included bortezomib, and she developed peripheral neuropathy. The treatment did not relieve her symptoms including asthma, rash, diarrhea, etc., and her eosinophils and kappa and lambda levels were unchanged. Never deterred, her oncologists changed her chemotherapy regimen several times, and performed over a dozen bone marrow biopsies, all showing persistent eosinophilia.

After these seven years of misdiagnosis and status iatrogenicus, she sought a second opinion, and the correct diagnosis was made: EGPA. She was treated for EGPA, and her symptoms resolved (except for the bortezomib-induced peripheral neuropathy).

One pivotal error the oncologists made was to assign a disease based on laboratory findings suggesting a disease that is an unlikely (even preposterous) explanation for the clinical presentation. This is all too common. The coronavirus is positive? The diagnosis is coronavirus, despite an incompatible clinical and radiographic picture. The PJP PCR is positive? It's PJP despite no symptoms and natural history to suggest this, and a negative 1,3-beta-D glucan. I recently conferred with a colleague talking about very odd sputum culture results, in a patient whose "pneumonia would not clear". I looked up the unfamiliar to me bugs: they are not human pathogens. Nonetheless, they are being treated. I looked at the CT: cystic disease pathognomonic of lymphangioleiomyomatosis (LAM). But it need not be microbiology results as the current case makes clear.

Omission Bias in Therapeutic Medical Decision Making

Having studied so-called heuristics and biases, aka cognitive biases and System 1 & System 2 processes in medical decision making on and off for 25 years, and thinking constantly about them in the full-time practice of clinical medicine, I have come to the conclusion that they are hard to spot in the wild. Except one: Omission Bias.

Omission bias represents a preference for inaction that preserves the status quo over action which changes it, and it is insidious because each day we encounter countless status quo states in medicine, established earlier and perhaps by different providers, but often by ourselves. The status quo inures us to what is, obscuring the question of what ought to be.

In this recent paper, and an accompanying editorial, omission bias is (partly) explained and several recurring examples in the ICU are discussed. But this is the tip of the iceberg. I venture a guess that every day, there is a decision that is made, or not made, that instantiates this bias. In addition to those discussed in the linked papers, here I will point out some common scenarios outside of the ICU where this bias lurks, preying on the desultory physician.

The patient presented to the ER (or elsewhere) for pneumonia, and was started on Zosyn (or cefepime) and vancomycin. Despite having no risk factors for pseudomonas, anaerobes, or MRSA, the team continues those antibiotics rather than change them to standard CAP coverage. The prospect of not covering something, always nagging at the physician, now looms larger because if the patient does unexpectedly have a resistant organism causing pneumonia, the anticipatory regret of not leaving things as they were deters the change.

The patient was started on unfractionated heparin for intermediate (or low) risk DVT/PE, when LMWH is the preferred drug, because of the misguided worry that "an intervention may be needed." Even if that were a legitimate concern at the outset, the patient has made it through the night and has improved, yet UFH is continued, requiring those pesky aPTT checks and the unpredictable pharmacokinetics of the drug.

Aortic Aneurysm Mimicking Recurrent Achalasia after Mediastinitis Complicating Botulinum Toxin Injections.......for Achalasia (Hickam's Victims series)

In this case report, the authors describe a case of a young woman with achalasia who got repeated episodes of mediastinitis complicating botulinum toxin injection. Later she presented with "pseudoachalasia" or presumed recurrence of achalasia, but imaging showed that, lo and behold, she had developed a complication of her mediastinitis, viz an aortic arch aneurysm that required surgical repair. The authors claim that Ockham's razor suggested recurrent achalasia, whereas Hickam's dictum prevailed because the patient had more than one disease. They would have benefited from reading our paper elaborating and operationalizing both clinical saws. The case is easily synthesized into a unifying diagnosis -- a unifying causal pathway -- which obviates invoking multiple diagnoses. The symptoms of the aortic aneurysm mimicked achalasia because they are in the same anatomic location as the mediastinitis causing them, which was in turn caused by the botulinum injections treating the original achalasia. A coauthor and I wrote a letter to the editor, which was not published, but is pasted below. While this critique may seem punctilious or pedantic, there are tangible consequences of this failure of synthesis: the patient went unnecessary testing for Marfan's syndrome and other genetic conditions of the vasculature, and case reports of this very condition (aneurysm after botulism injection induced mediastinitis) were apparently ignored, an omission that may have compromised surgical planning.

Goodrich et al¹ present an interesting case of a young woman with achalasia who developed pseudoachalasia mimicking recurrence of achalasia. The pseudoachalasia was caused by an aneurysm of the posterior aortic arch, and Hickam’s dictum is invoked to remind readers that new symptoms ought not to be reflexively attributed to recurrences of known diseases, an approach they suggest is encouraged by Ockham’s razor. A recent paper operationalized the application of Hickam’s dictum and Ockham’s razor to the problem of multiple diagnoses². According to this framework, multiple diagnoses are almost always due to a primary diagnosis that explains the chief complaint and one or more of: incidentalomas, known pre-existing diseases, or phenomena causally connected to the primary diagnosis. This latter category comprises Occam’s razor which, rather than suggesting a simple or single diagnosis, is better understood as favoring a single causal pathway that links findings together into a unifying diagnosis. When viewed through this lens, the posterior aortic aneurysm was caused by mediastinitis episodes that in turn were caused by treatment of achalasia -- a single, unifying diagnosis. While patients indeed may “have as many diseases as they damn well please” it is prudent to first try to link phenomena into a unifying causal pathway. Such an approach would have led to multiple case reports of aortic aneurysms associated with botulinum toxin injection for achalsaia,^3-5 informed operative planning (e.g., presaging adhesions), and obviated searches for unlikely genetic diseases (e.g., Marfan’s syndrome) in a patient without other features of these conditions.

1.           Goodrich HWF, Muniraj T, Masoud AE. Pseudoachalasia in an Achalasia Patient: A Ticking Time Bomb. ACG Case Rep J. Dec 2025;12(12):e01927. doi:10.14309/crj.0000000000001927

2.           Aberegg SK, Poole BR, Locke BW. Hickam's Dictum: An Analysis of Multiple Diagnoses. J Gen Intern Med. Oct 28 2024;doi:10.1007/s11606-024-09120-y

3.           Berman SS, Sabat JS. Mycotic aneurysm of the distal thoracic aorta after botulinum toxin injection for esophageal dysmotility. J Vasc Surg Cases Innov Tech. Sep 2020;6(3):388-391. doi:10.1016/j.jvscit.2020.04.005

4.           Chao CY, Raj A, Saad N, Hourigan L, Holtmann G. Esophageal perforation, inflammatory mediastinitis and pseudoaneurysm of the thoracic aorta as potential complications of botulinum toxin injection for achalasia. Dig Endosc. Jul 2015;27(5):618-21. doi:10.1111/den.12392

5.           Tan MZ, Whitgift J, Warren H. Mediastinitis, pseudo-aneurysm formation, aortic bleed, and death from endoscopic botulinum toxin injection. Endoscopy. 2016;48 Suppl 1:E186-7. doi:10.1055/s-0042-107074

Hickam Tricked 'em with the 'ol Red Herring Ruse (Hickam's Victims series)

One of my favorite Charlie Munger quotes goes something like this:

"Warren, over the years you and I have appreciated the great value in learning from mistakes; Another thing we realized is that it's a lot more pleasurable to learn from other people's mistakes."

In light of that sage advice, here's another recent case report invoking Hickam's dictum. In this case, a 38-year-old man from Pakistan who has sex with men presents with uveitis and a rash on his palms and soles. He has a positive interferon-gamma release assay. This caused diagnostic confusion which resulted in the unnecessary invocation of Hickam's dictum. There is, after all, a simple explanation for the two findings, as I explicated in an online comment:

"This is an interesting case. Neither Ockham's razor, nor Hickam's dictum, nor Crabtree’s bludgeon need be invoked to sort it out.

The annual incidence of syphilis in men who have sex with men in the USA is a whopping 309 cases per 100,000 persons per year - almost as common as community acquired pneumonia in unselected adults. Compare that to 2.9 syphilis cases/100,000 person-years in men who have sex only with women. A risk factor that increases the incidence of disease over 100-fold should point even the novice diagnostician straight to the diagnosis. Combined with a rash on the palms and soles? The diagnosis is all but made. Positive RPR? We’re finished here! For guidance on using incidence/disease frequency as a surrogate for disease probability, see: https://pubmed.ncbi.nlm.nih.gov/34854514/

Next, IGRA (e.g., quantiferon Gold) is NOT a diagnostic test for active tuberculosis infection (indeed, active infection is a cause of false negative IGRA), it is used clinically as a marker of prior tuberculosis exposure. In Pakistan, the annual incidence of tuberculosis is 230 cases per 100,000 persons per year, so it is hardly surprising that this patient has a positive quantiferon-gold. This is a red herring rather than an instantiation of Hickam’s dictum. Likewise, the dermatologist consultation was a false negative test for secondary syphilis. It is unbelievable that they attributed this rash to psoriasis, but this highlights that we should not put too much credence into any single piece of data or consultation if it flies in the face of the totality of the evidence. Similarly, angiotensin converting enzyme (ACE) levels are notoriously both insensitive and non-specific.

In the end, there is a simple unifying (and unsurprising) diagnosis in this case: syphilitic rash and uveitis in a man who has sex with men. For an explication of Ockhams razor and Hickams dictum (and the limits of their inferential powers), see: https://pubmed.ncbi.nlm.nih.gov/39467949/

Interestingly, Hickam started in the Boston hospital system, went to Emory, then to Duke, and finally to Indiana. Though not formally specialty trained, he did pioneering work in ophthalmology research, as well as cardiopulmonary research. An entire edition of the Archives of Internal medicine was dedicated to him after his death by reprinting seven of his original papers – the entire issue of the journal."

Hickam's Victims: The Unwary Diagnostician

In this case report, the authors describe a woman, some 82 years of age who had immigrated from Korea 30 years prior to presenting with syncope and dehydration, which was soon discovered to be Salmonella enterica subspecies typhi. Despite urine culture growing gram negative rods, 

"CT of chest, abdomen, and pelvis without contrast was ordered to better characterize the source of her sepsis."

Ignoring that we already have a source for her sepsis (indeed the most common source: urosepsis), and that gram negative sepsis almost never originates from the chest, we will move on after noting that they found multiple cavitary lesions in the upper lobes of the lungs. The authors state that they tried to link the cavitary lung disease with the urinary tract infection (staghorn calculi were found too!) and Salmonella bacteremia, because of an inclination towards Ockham's razor, but alas learned that the chest disease was tuberculosis (who knew!?) so they invoke Hickam's dictum. I rather think that this is a case of Crabtree's bludgeon which states that:

"No set of mutually inconsistent observations can exist for which some human intellect canno t conceive a coherent explanation, however complicated."

Alas, much about the epidemiology and natural history of both Salmonella and tuberculosis in this case report was neglected, so I penned this letter to the editor, below. I did not receive confirmation of my submission, and this journal's website is a bit inchoate, so I assume my letter was lost....

Added on 10/6/2025: Actually, my letter was not lost, as I received an acceptance letter today, but only after the invoice charging me $1530.00 USD as a publication fee for a letter to the editor! But let me tell you, the reviews, wherever they came from, were over the moon with my "clinical acumen" and "insightful analysis".

I replied saying nevermind, I can't afford that charge to publish a *letter* They replied saying "how much can you afford?" I offered $200 and it was immediately accepted. Never overlook the value of flattery, or the cold hard dollar. 

So I will link the letter, after it is published. In the meantime, comment below if you have your own insights about the case.

Added 10/21/2025: Published letter linked here. Text below:

Letter to the Editor: Guo and Liu reported an interesting case of a woman who presented with Salmonella enterica serovar typhi bacteremia and was also concurrently diagnosed with pulmonary tuberculosis [1]. Readers of this report may appreciate two additional perspectives beyond those discussed by the authors. First, humans are the only reservoir for S. enterica serotype typhi; all disease results from human shedding of the bacterium and it is not endemic in the U.S [2]. Because the patient was a Korean resident 30 years ago when it was endemic there [3], it is most likely that she acquired the infection prior to immigration to the U.S., and the reported infection arose from a chronic carrier state. The source of carriage is usually the gallbladder, which was not mentioned in the report, but could have been the source of seeding the urinary tract. Second, as was recently reported [4], the juxtaposition of Hickam’s dictum and Ockham’s razor as conflicting clinical maxims oversimplifies their application to the diagnostic process. Multiple diseases in the same patient are commonplace, and concurrent diagnosis must consider timing of symptoms, probability, and causal connections between diseases in addition to the much rarer situation where two independent diseases present with nearly simultaneous symptoms [4]. The only plausible causal connection between Salmonella and tuberculosis in the case reported is that they were probably both acquired in Korea – a common cause that would seem to satisfy Ockham’s razor. But because the symptoms the patient sought care for are directly attributable to Salmonella bacteremia, the tuberculosis infection likely represents a chronic infection, or an incidentaloma, albeit a consequential one. Within a framework that considers symptom timing as a non-arbitrary marker of disease onset, physicians are alerted to the omnipresent possibility of discovering asymptomatic diseases such as incidentalomas if causal connections between two diseases discovered concurrently cannot be made. This framework obviates the impossible task of discerning which of two allegedly conflicting clinical axioms – Hickam’s dictum or Ockham’s razor – applies in a given case, since diagnosticians can never know, a priori, which one to invoke. In the final analysis, this patient had chronic, asymptomatic tuberculosis reactivation, which was accidentally discovered during her acute illness with Salmonella, both of which were acquired remotely in Korea.

1. Guo S, Liu M. A rare concurrent presentation of typhoid fever with bacteremia and pulmonary tuberculosis. Arch Clin Biomed Res 9 (2025): 226-228. 

2. Tagg KA, Kim JY, Henderson B, et al. Azithromycin-resistantpositive Salmonella enterica serovar Typhi in the United States. J Glob Antimicrob Resist 39 (2024): 69-72. 

3. Yoo S, Pai H, Byeon JH, et al. Epidemiology of Salmonella enterica serotype Typhi infections in Korea for recent 9 years: trends of antimicrobial resistance. J Korean Med Sci 19 (2004): 15-20.

4. Aberegg SK, Poole BR, Locke BW. Hickam’s dictum: an analysis of multiple diagnoses. J Gen Intern Med 39 (2024): 1-4.

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.

A Foolish Consistency: Policy, Practice, and Rationality in Medical Decision Making

"A foolish consistency is the hobgoblin of little minds, adored by little statesmen and philosophers and divines" - Ralph Waldo Emerson

As I was making coffee this morning, I grabbed a filter and realized that two may be stuck together. I faced a common dilemma: do I bother to separate them so as to not waste a filter? A trivial example, I will use it as an analogy for decisions we face every day in life and medicine.

Folks approach this kind of decision (or the decision to brush one's teeth, or wear a seatbelt) in various ways. Paul may have a "Paulicy" of never wasting anything, and separates them; doesn't-give-a-damn Sam would never bother; Sometimes Suzie separates them when she has time, and doesn't when she's in a hurry.

The decision hinges on the value of a filter in terms of cost, waste, etc. The value of a single filter is a rounding error, but clearly a lifetime of wasting filters can add up to a lot of filters magnified by the number of people wasting them. Why not go to great lengths to save every filter possible?

In this kind of situation, a rational agent may decide to institute a policy of doing things in a certain way, but accept deviation from that policy under special circumstances. My favorite example of this situation is in medicine with central lines. A left-sided line is not supposed to come at a 45-degree angle to the wall of the SVC; rare cases are reported where, over time, it can erode through the great veins and cause fatal hemorrhagic mediastinum. But what is the probability of that? Something on the order of one instance per 10,000 lines. Supposing you have just placed a left internal jugular hemodialysis catheter and the tip is at the proscribed 45-degree angle. You can't retract that catheter, and you can't advance it either. Do you replace it with a longer one? What if your right internal jugular 20 cm catheter is "too deep" into the right atrium; do you retract it and use the little clamp, knowing that often the line slides in it, increasing risk for infection? What if the upper great veins are suboptimal targets, but you've read the Parienti paper in NEJM and know that the risk of infectious and thrombotic complications doubles (but increases only a percent or so, absolute) with femoral vein catheters? Should the femoral vein be verboten?

In cases such as this and many more analogous ones, a rational agent may employ a general policy of always trying a priori to avoid the 45-degree angle; select the appropriate length catheter; and favor the upper access sites, but to allow exceptions whenever the probability of an untoward outcome in an individual case is low, and the costs of avoiding it are higher. In the case of the 45-degree dialysis catheter, the risks of infectious and mechanical complications of repositioning or replacing it exceed the benefits, especially if it is going to be in place for a short period of time. Reluctance to use the femoral site which has but a 1% increase in adverse events compared to the jugular can lead to far greater complications from forcing patients to lie flat for prolonged periods, or from failed attempts under more difficult operating conditions with non-collaborator patients (delirious, thrashing). The policy to default to a preferred standard becomes irrational when, in a specific case the preferred standard doesn't deserve its status.

The same situation is true with many policies. Studies have shown that a policy of routine use of right heart catheters in sepsis or ARDS does not benefit patients (it also does little harm). So, we have policy of NOT doing routine Swan-Ganz catheters. But that hardly means that in specific circumstances we should not do them. The same holds true for so much of what we do in medicine. Part of the problem is that physicians memorize the policy and the direction of harm/benefit ("there's an increased risk of DVT with femoral lines!"), but they don't know the magnitude of the effect.

So, to be a rational agent, you should establish a policy of what is best, under optimal conditions, for all-comers. But when you have more information a posteriori (because the line went into the wrong place; or you forgot your helmet; or your kid fell asleep in the car seat), default to the policy only if a cost-benefit analysis justifies it. Also, be on the lookout for situations where the all-comer policy does not apply. Like the 90-year-old patient with a small (250cc) complicated parapneumonic effusion. Policy says drain. Rational practice says hold tight; it's a small target, risk of complication or failed drainage higher, benefits of avoiding a small fibrothorax (losing 250cc of vital capacity) in someone with reduced life expectancy and limited mobility are small.

I was not in a hurry, so I separated the filters. Had I been running late or the kids were screaming, I may not have.

Edit to add later in the day: it occurred to me that I do a lot of anal-retentive things in my home, many concerned for the environment or recycling. Example: we don't use paper towels, or disposable plates/silverware. 

The consequence is when we have a get-together, guests can be out of sorts with my "environmental policies." Even though our family, as a routine policy, is (I hope) happy to adapt to these well-intentioned standards, the social costs of this routine policy are off-putting to my guests. So, I keep things in perspective: this is just one gathering, a roll of paper towels here and there is no big deal to avoid the off-putting social costs. So we use disposable stuff on occasion when the convenience in a specific instance overrides the general routine policy goals. Same would be true if you had a general policy of "no shoes in the house" that you let lapse when you invited guests into your home.

Many doctors would do well to make such exceptions to their general policies, in the name of building (or not spending) "social capital."

Bayesian Implications for Factitious Disorder

The next time you encounter a patient with an odd constellation of rare or poorly defined diseases (POTS and MCAS is a common duo), especially if a psychogenic one is on the list (e.g., PNES - not, I presume, intended to be sounded out, as it was proposed as a less offensive alternative to pseudoseizures), do yourself a favor and read one of Mark Feldman's excellent books on factitious disorder, such as the most recent, Dying to Be Ill.

These patients are wellsprings of iatrogenesis, but it is a special variety because the patients actively deceive physicians into unwittingly fostering complications through well-intentioned attempts to diagnose and treat disease. Several biases in medical decision making are exploited by patients with factitious disorder (and its close sibling, malingering, where the reward for the sick role is external - e.g., relief from work, military service or thwarting criminal justice proceedings - rather than internal), and I address some of them in this post.

Numeracy in Medicine: Clinical Wagers to Estimate Probability in Diagnosis

As has become my custom, I offered a wager on rounds the other day. An nonagenarian had gastrointestinal hemorrhage. He presented with syncope and gross (red) blood per rectum. History was significant for Apixaban for atrial fibrillation, and NSAID use. My questions to the team were: what are the possible etiologies of the bleeding; and which among are most likely? After the diagnostic possibilities were enumerated, I offered my wager: a $10 stake that it is peptic ulcer disease (PUD) at 4:1 odds. If the patient has PUD, a taker of my wager owes me $10. If the patient does not have PUD, I owe the taker the $10 stake multiplied by the odds: $40.

There are several pedagogical and practical reasons I engage my team in these games, most of them pedagogical. First, making a wager about clinical outcomes gives you skin in the game. It is remarkable how, when I assign a stake and odds, the interest level goes up and my would-be wager-takers become carefully attuned to the differential diagnosis and other pieces of data that until then had been glossed over or wholly neglected. Recently, when making a wager about results of a pending echocardiogram, the resident did a much deeper chart dive than had previously been done and found a remote echo which bore on the probabilities for the current wager. I had to reassign the odds in light of this new information. Related to this deeper search for available information about the case, there can be a search for information about the diseases under consideration. It would be folly to try to make a bet about the probability of a disease that you understand incompletely, or not at all. Skin in the game will likely lead you to www.uptodate.com where you can ascertain knowledge about the considered diseases to apply it to the wager.

Cheating in Medical School? A Personal Tale in the Wake of the Dartmouth Scandal

A recent NYT article about cheating at Dartmouth reminded me of some hermetic knowledge of cheating in medical school that I have kept mostly secret for almost a quarter century. Without commenting on the Dartmouth case, I will relate this tale to demonstrate that cheating in medical school is real, and my experience is the opposite that of Dartmouth - administrators turned a blind eye to cheating, denying its existence until confronted by direct evidence of it.

In 1996, the "final exam" after an 8-week internal medicine rotation was a so-called "shelf board" exam, which I have always understood as meaning a copy of some prior year's board examination, or a preparation test for it. In medical school in late August 1996, I had the top score on this examination during the first "rotation" of 8 blocks that we did during the third year. I was pleased by this and considered it vindication of my method of not "studying to the test" but instead reading Harrison's Principles of Internal Medicine (13th edition) cover to cover during the second and third years of medical school. I later noted that the top score crept up as the year went on, and I was bemused. Were others reading Harrison's Principles of Internal Medicine? Doubtful. There were rumors of a "question bank" that previous takers of the exam compiled as the year went on, and shared with one another. If the "shelf exam" was only changed each year this would make sense. Alternatively, the kids were just getting smarter as the year progressed.

Applying Applied Physiology to COVID: Silent Hypoxia and The Work of Breathing

Enough time has passed and enough clinical experience with the behavior of COVID gained that we can now apply some applied physiology to our understanding of this aweful illness.  I don't have the answers any more than the next person, but I do know that whatever the behavior of COIVD, it can be viewed through the lens of what we do know about applied lung physiology, and some inferences can be made.  This post will be about that physiology and those inferences, using the frameworks in these lectures about applied physiology.

One of the striking early observations about patients presenting with COVID was their apparent lack of distress despite very low oxygen saturations.  This was termed "silent hypoxia" at some point, and I leave it to internet sleuths to trace its origins.  It led to a policy of early intubation of some COVID patients:

“Never in my life have I had to ask a patient to get off the telephone because it was time to put in a breathing tube,” said Dr. Richard Levitan, who recently spent 10 days at Bellevue Hospital Center in Manhattan.

There are two simple explanations for the observed phenomenon of silent hypoxia: first is that hypoxia is not nearly as potent a stimulus of respiration as is hypercarbia, as I took great pains to explain in the Applied Physiology lectures, using the example of shallow water breath hold divers who do not pre-oxygenate and emerge with sats on the order of 50%, the same as climbers on Mt Everest.  (See also this post on the boy in the wheel well, unpressurized, from California to Hawaii.)  I thank Matt Wong (@EM_phile on Twitter) for pointing me to this video which provides a striking illustration of lack of dyspnea with sudden and severe hypoxemia.  This video is compulsory viewing:

Dyspnea is driven far more by ventilation demands and the work of breathing than it is by hypoxia alone.  This is underrecognized.  I wager this stems in part from the fact that in most diseases that cause hypoxia, there is significantly elevated work of breathing because of parenchymal disease/infiltration (elastic loads) and airway secretions (resistive loads), combined with minute ventilation loads from high CO2 production, dead space ventilation (Vd/Vt) and metabolic acidosis.  If COVID does not have all of those loads, patients may not experience substantial subjective dyspnea despite low oxygen.

Are the "Vent Protocols" causing harm in COVID?

Here is a response to Deborah Mayo's excellent blog post posing this question.  I encourage you to first read her post.  Here, I explicate my view of the problems that are raised in that post.  I don't have time for a lot of hot links and stuff, so post your specific comments below.

There is a lot correct here, and @learnfromerror has done a far better job of summarizing it than I could ever explain a normal distribution. But there is a lot missing, because the commentators have not gotten to the crux, and have made slogans for their points that are distracting and misguided if not totallly incorrect.

First, and this is very very important, is that *there are NO protocols for intubation* as the NYC ER doctor suggests. I talk about that on my other blog a lot. ARDS trials enroll patients who are *already intubated* and the criteria for that intubation are absent from the study protocols. It is assumed in an ARDS study that if you are intubated, you were appropriately intubated. Therefore, there is no “problem with the protocols” for ventilators, there is a glaring and longstanding problem with the criteria (or the absence of criteria) for intubating patients. Is it blood gas values, or vital signs, or physical examination signs, or subjective distress or some combination? There is ZERO standardization in this area. COVID has brought this underappreciated problem to the fore.

Why is this just coming out now? Ah, that’s another crux of the problem and a reason that COVID has become a perfect storm for ventilator management. Usually, if you intubate a little old lady with influenza, even if you do it for shaky reasons, she can be extubated (tube removed) in a couple of days or a week with little harm done (or with a level of harm that we take for granted, probably mistakenly). Not so with COVID. The natural history of the disease has 2 important features that make the decision to intubate likely to culminate in a massive therapeutic misadventure: 1.) the duration of the illness is protracted, two to perhaps as long as four weeks; and 2.) the level of sedation needed to counteract the massive air hunger these patients have, for the duration they need it, is through the roof.  This problem is compounded by the mandate to use small tidal volumes which are poorly tolerated in the face of massive air hunger. So, 2 weeks after intubation, they are veritable zombies, cannot be weaned from sedatives (a prerequisite from being weaned from the ventilator), and are stuck on the vent, assuming that before this stage other complications have not set in and/or death ensued.

Another facet of the perfect storm, which I think is also the Rosetta Stone, and a key to untangling this giant mess we find ourselves in, is that this normal lung compliance that people are talking about is *the reason why* there is this so-called “silent hypoxemia” of the type mentioned by the ER doc in Mayo’s post. Failure to recognize this connection betrays a common misunderstanding of respiratory physiology (my attempt to disabuse people of these errors can be found here: https://pulmccm.org/ards-review/great-lecture-applied-respiratory-physiology/). Dyspnea is not driven by hypoxemia as much as it is by hypercarbia, which can be compensated for by hyperventilation which these patients are doing! To a person who has a firm grasp on applied respiratory physiology, this is no surprise – the patients have compliant lungs, so they don’t have workload imbalance and can sustain ventilation in the face of significant hypoxemia (which is a MINOR driver of dyspnea) very well. In sum, I am not surprised by these clinical presentations, nor am I surprised that this quagmire has allowed problems with the understanding of applied respiratory physiology to surface.

This disease is very difficult for these and many other reasons. When the choice is let a hypoxemic person who is defending her CO2 - like the little old lady the ER doc talks about - ride it out (which she can probably do for a very long time, see my tweets about sustaining very high Ve indefinitely [50% of the 15-second MVV]), versus intubating her for a marginal gain in gas exchange accompanied by a massive cost in sedation and paralysis, the choice is clear, let them ride it out, don't incur that cost.

The problem is not with the “vent protocols” the problem lies in a widespread lack of understanding of applied respiratory physiology which leads to questionable calls regarding intubation which are usually, in non-pandemic times, lost in the signal and noise of the fray. Not so with COVID – premature or unnecessary intubations precipitate a cascade of status iatrogenicus.

"I'm Not Comfortable With"....Analyzing Decisions Involving Risk

A woman with upper gastrointestinal bleeding is admitted to the ICU with significant hemoglobin drop from baseline several months before.  The INR was >10 on admission, presumably reflecting sphlanchnic hypoperfusion during the bleeding episode (decreasing clearance or increasing effect of warfarin) in addition to consumption of clotting factors during bleeding.  The INR is reversed with vitamin K, and an EGD is performed showing a nonbleeding vessel which was clipped.  The following day, the patient is up and walking around and eating a full liquid diet with no further evidence of bleeding.  MAPs are in the mid to low 60s, and she is "called out" for a transfer to the regular medical ward.  The resident is reportedly "not comfortable with" having the patient on the floor with the low mean arterial pressures.  How best to analyze the situation?

(I will only briefly note that the expression of discomfort describes an emotional reaction that may or may not be concordant with a logical and factual analysis of the situation at hand.  In this case I suspect it has something to do with the availability heuristic, where dramatic events [gushing blood] are estimated to have higher probabilities than they warrant.)

The discomfort seems to stem from a concern that the patient will deteriorate on the regular medical ward and require interventions that are not available there, prompting readmission to the ICU and incurring the risk of a missed opportunity to provide necessary care during any delays in executing the transfer.  Factors that may raise that concern are marginal hemoglobin values (7-8) especially considering a baseline of almost twice that several months before, the size of the GIB and the resulting hemodynamic instability, the marginal MAPs at the time of transfer.  Mitigating factors are the absence of ongoing bleeding, the inference that any marginal MAPs must be from a residual volume deficit (she does not have coincident sepsis), that the vessel was successfully clipped, and the patient is up and walking about in spite of the measured MAPs.  But how are we to integrate this into an estimate of the risk that may be incurred from transfer?

The Bermuda Triangle of Guidewires: Do They Just Fly Away Never to Be Seen Again?

In last week's NEJM, author Matt Bivens reports an extraordinary experience: while inserting a venous catheter, he let go of the guidewire and moments later looked and saw it migrating into the patient's jugular vein, on its own.  He grabbed it as it was running away, just before it escaped from him.  While I can imagine, as he did, how it may have happened, it is an exceptional claim.  Some aspect of the venous circulation or respiratory motion must have been pulling the wire downstream into the patient, if this story is true.  I say "if" because it is truly extraordinary.  Not only must the venous circulatory flow have been "grabbing" the wire, carrying it downstream, it had to do so with enough force to overcome the friction of the wire as it traversed the tissues of the neck.  (Not mentioned is the size of the patient's neck or whether this happened pre- or post-dilation, or whether the patient was in Trendelenberg - if so the catheter had to be pulled up hill!)

I have never seen or felt a guidewire move in such a way, over 20 years and thousands of lines.  However, I did turn my back on an intern circa 2000 and that intern pushed and/or flushed the guidewire into the patient.  So I was interested in the 4 references in the article purporting to show that guidewires have wings or feet or that the venous circulation can pull them and overcome the tissue resistance and mass of the wire.  Here is a summary: