Did you know that the T in DST stands for Torture? Just ask people with school-age children. It also doesn’t save anything, it shifts hours around, so the S is for Shifting. Only, to be more precise, you should really swap the f with another t.

That’s more like it.

Swatch Internet Time may have been a gimmick, but having a universal time with shifting opening hours (why not wake up at “midnight” and have school and work start at “2am”) would be preferable to… this. That is what, in effect, the strange beasts who like DST are doing, their jobs allowing them to sleep in and start their days whenever the sun actually comes up. No such luck form farmers, bakers, doctors, and most other professions that have to deal with the physical reality.

Science can do many things, but until we all move to an indoor habitat and bask in artificial sunshine it cannot increase the number of daylight hours. Pretending that it can — and codifying it into law — is a triumph of stupidity.

Adam Mastroianni:

We all know that talk is cheap, so we tend to believe what we see more than what we hear. Your real friends are the ones who show up to help you move, not the ones who tell you how they’ll always be there for you. A good boss is the one who gives you time off when your mom dies, not the one who says, “I care about you!” and then asks you if you might have time to polish the PowerPoint between the wake and the funeral.

Unfortunately, when we want to transmit wisdom, words are often all we have.

Which continues to be an immense, unsolvable, and underappreciated problem.

Working with lymphocytes in one way or another for the last 15 years, I am obligated to link to yesterday’s xkcd comic despite at least two (probably) unintentional but still glaring mistakes: a “B” making its way into the plasma and T-reg cells. What is with this pro-B bias?

As far as discoveries go, 2023 is shaping up nicely. Yesterday we had electricity from air, today there is some movement on superconductors.

Sure, none of these will be immediately life-changing. But I vaguely remember reading about some new super-slick materials years ago, and today I don’t have to worry about how to get leftover ketchup out from the bottom of the bottle.

Progress!

From Phys.org:

In this Nature paper, the researchers extracted the enzyme responsible for using atmospheric hydrogen from a bacterium called Mycobacterium smegmatis. They showed that this enzyme, called Huc, turns hydrogen gas into an electrical current. Dr. Grinter notes, “Huc is extraordinarily efficient. Unlike all other known enzymes and chemical catalysts, it even consumes hydrogen below atmospheric levels—as little as 0.00005% of the air we breathe.”

1. Biotech for the win (?)
2. Or does this pave the way for a dystopian post-biology future in which insatiable human appetites deplete all hydrogen from the atmosphere?
3. Mycobacterium smegmatis becoming the savior of humanity and a household name would provide fodder for middle school humor for generations to come.

Yes, there is dire inequality in clinical trial enrollment, but this is the precisely wrong way to address the lack of diversity.

Legislating behavior leads to made-up plans that are at best a waste of an intern’s time and at worst a six-figure donation to “providers” selling their “solutions”. If you will ultimately grade on the outcome — and you should! — well, what do you care how it was achieved, provided that all the other laws and guidances were followed?

Silly, silly games.

Almost 5 years old, but still worth sharing: the first ever video of mating anglerfish.

Most of what we know about deep-sea anglerfish comes from dead animals pulled up in nets. Scientists have identified more than 160 species, but only a handful of videos exist—and this is the first to show a sexually united pair. “So you can see how rare and important this discovery is,” Pietsch says. “It was really a shocker for me.”

Isn’t nature just swell?

Available to general public!

ChatGPT and Potential Healthcare Implications of Large Language Models

• Speaker: George Shih, MD
• Date: Monday, March 6, 2023, 1:00 p.m. ET
• Available via WebEx.

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

• Speaker: Philip Castle, PhD, MPH
• Date: Tuesday, March 7, 2023, 4:00 p.m. ET
• Available for viewing here

It’s a Bacterial World

• Speaker: Andrew Knoll, PhD
• Date: Tuesday, March 21, 2023, 4:00 p.m. ET
• Available for viewing here

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.