Posts in: medicine

For your weekend reading enjoyment, FT’s Janan Ganesh on (un)healthy eating:

  • It is easier to fast than to eat healthily.
  • You must be willing to upset people.
  • Beware pasta.
  • Don’t expect to “burn it off”.
  • Know thy weight.

Sound advice. I may have also posted a few excerpts.

BS bonanza

Doximity is beta testing ChatGPT for doctors:

Physicians can use the free DocsGPT to prepare referrals, certificates of medical necessity and prior authorization requests or to write a letter about a medical condition. A growing menu of prompts offers many options, and users can type in a custom request.

Next up: medical insurance companies using their own AI to process the AI-generated BS they receive from healthcare workers into something more easily understandable.

At least the economists must be happy!

March lectures of note

Available to general public!

ChatGPT and Potential Healthcare Implications of Large Language Models

Tests for Early Cancer: Facts vs. Opinions Can We Detect Early Cancer?

It’s a Bacterial World

Bias of the day: immortal time

This is when you do a retrospective study, select cohorts according to exposure, but measure outcomes — usually death, or hospitalization, or something else bad — in a way that guarantees one or more of the cohorts have a period of time when that outcome couldn’t have happened. That’s how you get “immortal”, or “guaranteed” time.

Three classic examples: Courtesy of Bing.

  • A study that evaluated the hypothesis that menopause occurring before age 40 years is associated with the development of cardiovascular disease (CVD). The study counted women who had premature menopause as exposed to CVD risk from their date of birth, ignoring the fact that they could not have developed CVD before menopause.
  • A study that assessed the effect of statins on diabetes progression and insulin use. The study classified patients as statin users based on their first prescription after hospital discharge, but included the time between discharge and prescription as exposed time, even though they were not taking statins during that period.
  • A study that examined the association between beta-blocker use and mortality in patients with heart failure. The study defined beta-blocker exposure based on pharmacy claims after hospitalization, but did not account for the time lag between hospital discharge and drug initiation, which could have biased the results in favor of beta-blockers.

To these three classics we can now add two more, one highly publicized, the other less so, both surprising considering the journals and the supposed peer review they must have gone through:

  • A study that compared hospitalization rates of those who had a positive SARS-CoV-2 test and did not take the Covid-19 drug Paxlovid to those who took Paxlovid regardless of test status. The study counted the day of the positive test as “Day 0” for the untreated cohort; however, for patients who started taking Paxlovid and did not have records of a positive test “Day 0” was one day before treatment start. See this Twitter thread for relevant excerpts and a more detailed explanation. As the study excluded patients who were already hospitalized when they started Paxlovid, but included untreated patients who had a positive test and were hospitalized on the same day, this guaranteed 1 day of “immortal time” for the Paxlovid cohort.
  • A study that used “real world data” to compare standard blood thinners to a procedure called left atrial appendage occlusion (LAAO) for prevention of death and stroke in patients with atrial fibrillation. However, patients who underwent LAAO had to live long enough with atrial fibrillation without getting a stroke to “graduate into” the procedure. Not only is immortal time here so glaring, the study is eerily similar to the original heart transplantation study in which this bias was first identified.

Cardiologist John Mandrola explains in depth why the LAAO paper, and the way it was spun, is particularly egregious.

Note that this is only a problem in retrospective — or, how they now like to be rebranded, “real-world” — studies. As the most recent cases show, these are not only worthless for informing anyone’s real-world decision, but also contribute to the noise, the chaos, and the general fear-uncertainty-doubt of medicine. A voluntary moratorium would not be out of line.

Finished reading: Fundamentals of Clinical Trials by Lawrence M. Friedman 📚

It is assigned reading for a course I’m helping prepare, so I thought I’d better read the book we’ll ask our students to use. Like many textbooks, it suffers from MANE — many authors no editors — and like many academic texts, it can get way too pedantic. Still, it is hard to argue with its overarching themes: that randomized controlled trials are the pinnacle of medical evidence generation, and that much of the trial paperwork done in the name of quality is unnecessary. I have more comments on that last point, but that is for another time.

Is the Sunshine Act a joke?

I don’t see patients with leukemia any more, but if I did, and was willing to “provide information to [Name Redacted] as it relates to my practice patterns and actively engage in the scientific exchange”, someone is willing to pay me a $1000 “fee” along with providing air travel and a one-night stay at a 4-star Florida hotel. Importantly, that someone states:

As this meeting is not commercially supported, there is no Sunshine Act reporting required.

What this means, as Bing AI will helpfully clarify for those who don’t know, is that:

…the meeting is not funded by any manufacturers of drugs, devices, biologics or medical supplies, and therefore there is no need to report any payments or transfers of value from the manufacturers to the physicians or teaching hospitals who attend the meeting. The Sunshine Act is a federal law that requires such reporting to increase transparency around the financial relationships between physicians, teaching hospitals and manufacturers.

So the clarify further using my non-artificial intelligence: US physicians are required to report payments from drug, device, etc. manufacturers and these reports are available to public. Shell companies insert themselves between said manufacturers and physicians so that they could wine and dine them in the name of “scientific exchange”. Money involved is completely off the books.

And so the letter of the law is followed while the spirit withers away…

Et tu, FT?

The allure to report anything as a medical breakthrough is strong. So strong that even the Financial Times can’t avoid it:

New diagnostic technology that uses fibre optics to find the causes of heart disease has begun Emphasis mine. clinical testing at London’s St Bartholomew’s Hospital.

The iKOr device, developed at Barts Health and University College London, measures blood flow around the heart. Researchers say it could eventually help many thousands of patients suffering from cardiovascular symptoms such as chest pains, whose cause cannot be identified with current techniques.

“This new device is a game-changer in how we manage heart disease, making it a lot easier to assess the health of a person’s heart,” said Anthony Mathur, clinical director for interventional cardiology at Barts.

Three patients have undergone testing to date, out of 10 planned in the first phase. Another 100 may, subject to regulatory approval, before the device could potentially become commercially available, if it’s demonstrated to work. There is, it goes without saying, no clinical data published to date.

How does this change the game, exactly, when we don’t yet know if it works? The use of undeserved superlatives in cancer drug reporting is well documented so it’s not a surprise to see cardiology, that other lucrative medical subspecialty, being much the same.

What is a surprise is seeing the usually reliable FT falling down to the level of The New York Times in spreding medical jingoism. How interesting that in both cases it was a local hospital — Memorial Sloan Kettering for NYT, St Bart’s for FT — serving as the source. So interesting that I have to think there were some personal behind-the-scenes goings on.

February lectures of note

NIH has always made most of its lectures available to public. With the pandemic, the production values have gotten better, and more people have gotten used to viewing lectures online. Here are a few interesting ones scheduled for this month. Some of them are part of NIH’s Demystifying Medicine series which is open to public and tries to target the curious layperson Alas, not always successfully. to the best of presenters' abilities.

Fact Stranger than Fiction: Adventures in the Genomics of Inflammation

Somatic Mutations in “Benign” Diseases

  • Speaker: Neal Young, MD
  • Date: Tuesday, February 14, 2023, 3:00 - 4:00 p.m. ET
  • Register here.

The Use of JAK Inhibitors in Autoimmune Disease

Clinical Center Grand Rounds: How Nucleic Acid Structure and Chromatin Environment Influence Gene Transcription

Yes, yes, America has terrible health care — even a tech podcast says so — while paying an order of magnitude more for it than other rich countries. But hear me out: what if the costs are so high because Americans are (unsuccessfully) trying to buy their way out of poor policy decisions, from dependence on cars, to the early 2000s' promotion of opioids, to the widespread availability of cheap but nutrient-less calories, and no amount of fiddling with who pays for what in healthcare will be able to fix that?

Which is to say: it’s fine to look at specific costs and specific outcomes — I have done so myself — but what exactly is the action item after reading a report like The Commonwealth Fund’s cited by Ars Technica?

Nitpick of the day: clinical trial versus clinical study

At the very start of the textbook Fundamentals of Clinical Trials the authors make a distinction between clinical trials — comparing two or more different interventions — and clinical studies, which merely describe an intervention without comparing it to anything. So, there can be no such thing as a “Phase 1 trial”, since they typically involve a single drug at different doses and schedules. The only true trials, according to the authors, would fall under Phase 3, or Phase 2b at the earliest.

This is stupid, misleading, and not at all how the words “trial” and “study” are used by anyone else, including the biggest and most important drug regulatory agency in the world. There are many such pointless exercises of professorial power in medicine, including my favorite: whether the correct pronunciation of “+” in “7+3” is “plus” or “and”. They amount to nothing more than purity tests that award the wielders of the right language a false sense of precision. As Nassim Taleb wrote, nitpicking is the enemy of thought.

The rest of the book is good enough, but more on that later.