Patrick McKenzie on X:

I hate to sound intellectually vacuous but choose to get more done. At the relevant margins, get more done. Life : culture / peers will routinely tell you it is OK to get less done and you should politely insist on getting more done. The amount of doneness you get is not fixed.

I have been thinking along these lines ever since reading, some dozen years ago, an article about a particularly successful cystic fibrosis center, whose outcomes were an order of magnitude better than average. This was before any new drugs or promising trials were available, and the only reason why they were so much better was that they did more of everything: more frequent follow-up, more intensive manual therapy, more changes to treatment regimen with subtle changes in condition, less complacency.

Nowhere is this more evident than on the inpatient service. It is incredibly easy to coast with reflexive and defensive medicine, putting out small fires like hospital-acquired infections or patient falls, passing on the buck to the next team, shrugging your shoulders about that 60-year-old with questionable CHF (or is it COPD/asthma) exacerbation who is not following the script and doesn’t seem to be getting any better despite being treated for everything. Patients hang around a bit longer, suffer a bit more iatrogenesis, die a bit sooner, not enough for it to be obvious in any particular case but just enough for the outcomes to be worse in aggregate.

Make no mistake: this is how many (most?) American hospitals operate, for the simple reason that there simply aren’t enough doctors and nurses around for the level of attention sick patients with many active complex disorders deserve. But doing more is the American ethos (see the X-post above); not being able to provide more focused care, we dig into the seemingly infinite supply of more drugs, more procedures, more iatrogenesis to which to expose patients, making their condition all the more complex.

Outside of medicine, this is also the difference you can see in “good” and “bad” (for collaboration) institutions: good ones throw water at embers before they become a fire, communicate more frequently and openly, do not leave documents for review “for after the long weekend”. They do more; or rather, each individual there does more and does not pass on the buck to forces unknown which are beyond their control (and the bigger the institution is, the more numerous and more complacent those forces are; incredible how that works). The not-so-good institutions also do more: of emailing, usually, to tell you that something can’t be done.

So yes, choose to get more done, and also make sure you are doing more of the right thing.

I had a bad reaction to a tweet an X-post ⊕ Let this be the last time I cross out the word “tweet” in reference to posts on X. I actually quite like calling them X-posts, since ex post philosophizing is the most common mode of discourse there.yesterday saying that:

…effective drugs suffer from the silent hero problem that Taleb wrote about in The Black Swan. Many can prevent far worse downstream outcomes (hospitalization, surgeries, chronic pain, early death), but we don’t tend to reward acts of prevention like we do acts of correction. Thus, surgeons are revered and drugs are reviled.

Why would I have a problem with a statement as obvious as that? Yes, humans overvalue procedures and neglect the importance of drugs, especially those with a delayed effect, no matter how large the effect may be. Well, the ellipsis hides the first part, which was agreement to a quoted post which is one of those newfangled blog posts disguised as an X-post so apologies for the long quote:

Drug industry’s [lack of] popularity is thanks to its own success. … If you have a disease for which there is a medicine, you don’t know anything other than the bill at the pharmacy counter.

If you have a disease without a cure, all your faith is put into the drug industry because no one else is coming to help and nothing else matters.

And if you don’t have a disease (yet), you really don’t care other than your fear of the bill you might one day get at the pharmacy counter.

The great irony here is that the pharmaceutical industry doesn’t control what you pay at the pharmacy counter: your insurance plan does.

Followed by a graph that shows plumetting public opinion of the pharmaceutical industry according to Gallup polling, from ~40% positive, 37% negative in 2014 (peak recent positivity) to 18% positive 60% negative in the most recent year, which I presume is 2023 but the image doesn’t say.

This is an example of a reverse-BS sandwich, where three interesting (and perhaps even true) observations are layered in between two nonsensical pieces of dreck.

Let’s start with the middle first. Per the second statement, if you have a disease, and there is a cure, the only thing you “know” is what you have to pay for it at the counter. I would argue that this is only half-true: as a patient, I would also know how I should take the drug (pill, self-injection, infusions at an infusion center, hospitalization, etc), how often and how easily (from a four-times-a-day horse-pill to an ocassional subcutaneous injection), how quickly it works, and what the side effects are. For any particular disease there may be several options, with more convenient and/or less toxic ones costing more; and people may be ready to pay more for the convenience and/or fewer potential side effects. The price difference may not even be that high, like in the case of four-times-daily versus once-daily antibiotics. So there is quite a bit of nuance there, but hey, it’s X: if there needs to be some simplification to make a valid point, that’s OK.

But then after reading the statement that follows I’m not sure if there is any point to be made. It’s an attempt at a dichotomy — separating diseases into those with and without… something. For there are many diseases for which there are medicines, but those medicines are not cures: the terms aren’t interchangeable. And for incurable diseases, the pharmaceutical industry is emphatically not the only place in which people put their faith: see complementary and alternative medicine, support groups, religion. There are many people of different persuasions, motivations, ambitions, and fee schedules who will happily give their support. But lest this is construed as nitpicking I will squint once again and let it pass, assuming that the preceding statement talked about cures, and not medicines in general.

The next statement is absolutely true. Healthy people in general have a hard time imagining what disease is like, and we all know what a financial nightmare American health care can be.

The first sentence is a strong statement of causation: that the pharmaceutical industry is unpopular thanks to — which I interpret as because of — making such good drugs. I’ll attempt to construct the three that follow into supporting arguments:

1. You have a disease for which there is a cure. You take the cure for granted and you don’t like the pharmaceutical industry because you have to pay for their drug.
2. You have a disease for which there is no cure. You don’t like the pharmaceutical industry because you had put all your faith in them because of their past successes (see above), and they have failed you.
3. You don’t have a disease. You don’t like the pharmaceutical industry because you are scared of what may happen to your finances if and when you do get sick.

Do get in touch if I didn’t get this right, but if I did, I’m afraid it’s bad reasoning. It does point to prices as the reason for pharmaceutical industry’s unpopularity, but neglects the price of the vast majority of medicines which are not cures, yet which people take with flimsy or no evidence because of medicalization of normal variability, use of bad surrogate endpoints, and, for terminal diseases like most metastatic cancers, lack of alternatives. The industry isn’t unpopular because it charges to much for life-saving drugs (if anything, it charges too litle), but because it puts out — pushes, even — wimpy drugs that treat nothing in particular.

Yes, if it weren’t for the “silent hero” problem people may be more appreciative of the benefits and the industry may be slightly less unpopular. But make no mistake: the industry as a whole is unpopular because it overweighed the amount of slack it would get riding the coat tails of the many truly miraculous drugs it came out with in the last 20 years, from antiretroviral therapy for HIV, to hepatitis C treatments, immune checkpoint inhibitors, SARS-CoV-2 vaccines, and, most recently, semaglutide (Ozempic).

As for the final statement, well, it’s wrong in two ways: one — the wholesale price sets a ceiling that the patient would pay. Medical insurance could not make the patient pay more for a drug than the drug actually costs. Second, many pharmaceutical companies will be all too happy to cover the entirety of your co-pay for their specialty product, since it is usually significantly less than the margin they get on the agreed-upon price for their drug.

So anyway, I hope you can now see why a simple scroll down the time line is not an easy exercise for me, or really for anyone with more than a passing knowledge of the American drug price problem. There are no purely good participants on any side (even patients, which is a bit of anathema but take a look at the average American’s overflowing medicine cabinet and compare it to that of someone from Europe), and there are very few truly evil parties anywhere (although, yes, some do come to mind). So instead of rapid-fire whataboutist replies, I write articles like this to vent. I hope you don’t mind.

A recent podcast episode and a recent blog post show how screwed up the American drug market is, and in how many different ways.

In his Healthcare Unfiltered interview focused on generic drug shortages, the FDA Commissioner Robert Califf blamed Group Purchasing Organizations for driving down the cost of generic drugs to below what’s economically feasible. The manufacturers don’t have an incentive to shore up their process, the fragile production line fails, and presto, you have a shortage. Which is fine if you are manufacturing a placebo, but in recent years the FDA’s Drug Shortages Database has been ever-growing, and as of today includes potentially currative cancer drugs like cisplatin and carboplatin, many antibiotics, and even some formulations of sugar-water. Not to be confused with placebo.

This all reminds me a bit of my childhood in Serbia back in the mid-1990s, when bread was dirt cheap and never available. But that was too much price regulation. Here, we have too efficient of a market leading to a shortage. Only, I am sure there will be hands raised wanting to tell me that — well, actually — this was a clear example of over regulation, since new factories can’t just pop up too meet the demand and make use of the temporary market inefficiency, being dependent as they are on pesky FDA regulations — like the ones about drugs being safe. If only we could price in the risk of death by sepsis, we’d be in great shape!

So, on one end we have Medicare/Medicaid paying through the nose for brand name drugs because it is forbidden by law from negotiating for a better price, and on the other private GPOs negotiating too well for generics, to the point of extinction, forcing payers to get those expensive brand name drugs. Heads, brand-name pharmaceutical industry wins, tails, payers loose.

It was encouraging to see some movement in the price negotiation area: the comically misnamed Inflation Reduction Act allows for CMS to negotiate the price of some drugs, and the list of those drugs was recently made availalbe. Ideal? Far from it — in an ideal world the federal government would not be involved in any of this; but it’s not the world we live in. This is where the blog post comes in: from Alex Tabarrok, about how we are bad at pricing drugs because of unknown externalities (true!) but also with a side-comment reframing measures the IRA takes allowing nogiation as “price controls”, linking to [a policy paper][10] which suggests yet another set of measure to mitigate the adverse effects of IRA’s proposed solutions to the drug pricing problem. ⊕ Efficient markets for me, but not for thee, as Tabarrok’s writing partner would quip. And so the measures pile up from both the pro- and anti-regulation side. Ad infinitum, I suppose.

See also: better drugs don’t cost more, and a list of a few earnest but misguided attempts at cost control.

To convince myself that I am not completely clueless in the ways of medicine, I occasionally turn to my few diagnostic successes. ⊕ To be clear: this is cherry-picking, and I make no claim for being a master diagnostician. Yes, a bunch of my colleagues had missed the first patient’s friction rub that was to me so evident; but say “friction rub” to a third-year medical student and they will know immediately the differential diagnosis and the treatment. How many friction rubs have I missed actually hearing? Plenty, I am sure! Like this one time when a 20-something year old man who languished in the hospital for days with severe but mysterious chest pain. Our first encounter was on a Saturday, when I saw him as the covering weekend resident; he was discharged Sunday, 24 hours after I started treatment for the acute pericarditis he so obviously had.

Once, during a mandatory ER rotation, I figured out that a patient who came in complaining of nausea and vomiting actually had an eye problem: bilateral acute angle closure glaucoma. I pestered the skeptical ophthalmology resident to come in on a Sunday afternoon, confirm the diagnosis, treat the glaucoma, likely save the patient’s vision, and get a case report for a conference out of it.

And I will never forget the case of the patient who was in the steaming hospital room shower whenever I saw him; he had come in for kidney failure from severe vomiting and insisted he never used drugs, illicit or otherwise. Still, it was obvious with anyone with a sense of smell that he had cannabinoid hyperemesis syndrome and would have to quit.

Superficial commonalities aside — all three were men with an acute health problem — what ties these together is that I had to use senses other than sight to figure them out: ⊕ This being the 21st century taste is no longer allowed, but I will leave to your imagination how doctors of old could tell apart the “sweet” diabetes (mellitus) from the “flavorless” one (insipidus). hearing the friction rub, feeling the rock-hard eyeballs, smelling the pungent aroma of cannabis. And all three cases came to mind when I read a tweet an X about ChatGPT’s great diagnostic acument.

I can’t embed it — and wouldn’t even if I could — but the gist of Luca Dellanna’s extended post is that he:

1. Had a “bump” on the inside of his eyelid that was misdiagnosed by three different doctors.
2. Saw the fourth doctor, who made the correct diagnosis of conjunctival lymphoma.
3. Got the same, correct diagnosis from ChatGPT on his/its first try.

A slam-dunk case for LLMs replacing doctors, right? Well, not quite: the words Luca used to describe the lesion, “a salmon-pink mass on the conjunctiva”, will give you the correct response even when using a plain old search engine. And he only got those words from the fourth doctor, who was able to convert what they saw into something they could search for, whether in their own mind palace or online.

Our mind’s ability to have seamless two-way interactions with the environment is taken for granted so much that it has become our water. This is the link to the complete audio and full text of David Foster Wallace’s commencement speech that became the “This is Water” essay, and if you haven’t read it yet, please do so now. But it is an incredibly high hurdle to jump over, and one that is in no danger of being passed just yet. It is the biggest reason I am skeptical of any high proclamations that “AI” will replace doctors, and why I question the critical reasoning skills and/or medical knowledge of the people who make them.

In fact, the last two years of American medical education could be seen as simply a way of honing this skill: to convert the physical exam findings into a recognizable pattern. A course in shark tooth-finding, if you will. This is, alarmingly, also the part of medical education that is most in danger of being replaced by courses on fine arts, behavioral psychology, business administration, medical billing, paper-pushing, box-checking, etc. But I digress.

Which is not to say that LLMs could not be a wonderful tool in the physician’s arsenal, a spellcheck for the mind. But you know what? Between UpToDate, PubMed, and just plain online search doctors already have plenty of tools. What they don’t have is time to use them, overburdened as they are with administrative BS. And that is a problem where LLMs can and will do more harm than good.

Continuing the daily cadence of one photo followed by a complaint about America’s most hated board of medicine, ABIM has once again shown its complete deafness of tone. While almost 10% of its customers — for we are not members of this private club — rebelling against its practices, it still sent out an automated extortion reminder threatening to remove certification if you don’t pay up. Well, I don’t think I shall.

The campaign to end mandatory maintenance of certification is, as of yesterday, at 20,000 signatures. This is just shy of 10% of the people affected; what are the other 90+ percent thinking? Still, it was enough to make the professional societies pay attention.

Derek Lowe writes about a recent Cancer Cell paper pitting glioblastoma cells against each other in a mouse model:

A single clonal line that hit on high Myc expression could outcompete fifteen thousand others from a standing start!

As someone who’s treated patients with Burkitt lymphoma, the Myc-dependent cancer, I can absolutely believe this.

Aaron Goodman’s petition to eliminate Maintenance of Certification requirements for ABIM-certified physicians is on track to reach 20,000 signatures, which would be just terrific. But it was at 16,000 2 weeks ago, and the pace has certainly slowed down. Do the other 200,000+ certificate holders think mandatory MOC is a good idea, on top of the state-mandated Continuing Medical Education?

Jason Snell notes that the iMac’s strongest legacy was Apple itself:

The company was close to bankruptcy when Jobs returned, and the iMac gave the company a cash infusion that allowed it to complete work on Mac OS X, rebuild the rest of the Mac product line in the iMac’s image, open Apple Stores, make the iPod, and set the tone for the next twenty five years.

I’m currently reading The Dao of Capital, which is all about the Austrian school of economics and the roundaboutness of true entrepreneurs, and this made what Apple is doing even more salient. Can you name a more roundabout tech company than Apple? ⊕ To be clear, I suspect little of this was premeditated in the long term — i.e. no, Jobs and Ive probably did not have a Vision Pro in mind as the ultimate goal when they thought of the iMac — but the ethos of seeing everything as a potential intermediary and not commoditizing it fully à la Samsung is very much the Apple way. Using the iMac as the intermediate step towards the iPod, which was itself an intermediate step towards the iPhone, which was supposedly to be an intermediate step towards the iPad but turned into something much greater, though it also did end up being an intermediate step towards Apple silicone, all the while peppering these intermediary products with technology — LiDAR, ultra-wide lenses, spatial audio — that would become the key building blogs of Vision Pro, which is itself an intermediary towards who knows what. Very Austrian.

Thinking more closely to home, I can think of a few biotech companies that may be doing something like this — maybe, if you squint — but none come close. The addiction to immediate profits that the distorted American health care market provides is much too great.(↬Daring Fireball)

Jake Seliger is a writer with an aggressive, incurable cancer, a wife — Bess — who is an ER doctor, and a blog:

We spend so much time buying, storing, corralling, searching, sorting, and thinking about stuff, and then we perish and what happens?

I mean that in a literal way: I die from that squamous cell carcinoma in my neck and lungs, and then what? What happens to Bess?

Have a tissue ready.