Posts in: medicine

A Wall Street Journal article on physician work-life balance prompted lots of online chatter, including people remembering their parents' dedication to the calling. But times have changed. The choice now isn’t between spending time with family and patients, it’s between spending it with family and corporations. If practicing medicine were more meaningful, there would be less of a retreat to family life by people who self-selected for delayed gratification and frank masochism.

Hell froze: I am about to link to hype-master Eric Topol in a non-judgmental way, because the article he is hyping is one that I co-authored. It’s titled “Engineering CAR-T therapies for autoimmune disease and beyond” and it came out yesterday in Science Translational Medicine as their one free article from the issue. I’ll stop there because it’s work-related and it’s good to have some boundaries.

Bench to bedside in a bad way (on the virtue of clinical trials)

Andrew Gelman recently wrote about Columbia surgery professor’s research missconduct. I haven’t looked into the details but it seems like the retracted papers were all about lab research with no true clinical relevancy. In that context, this part of the post stuck out:

Can you imagine, you come to this guy with cancer of the spleen and he might be pushing some unproven treatment supported by faked evidence? Scary.

I can’t tell whether this was supposed to be a joke or if Gelman truly believes that faking mouse experiments directly leads to using unproven treatments, but in case it’s the latter I have to say that the logic is stretched. Yes, the kind of person who has no qualms about fake data is probably not all that rigorous about the evidence for surgical procedures, but for all we know he could be a master surgeon with excellent technique and great outcomes who also happens to have been a bad judge of character and trusted a bad actor. I suspect it’s the latter: the kind of multi-tasking surgery “superstar” that the professor in question seems to be tends to spend a lot more time in the the operating room (or, for another kind of a superstar, the board room), than the lab.

Now, if he were a medical oncologist or any other kind of doctor that gives cancer treatment then maybe things would have been more dubious — that kind of research tends to jump to clinic too quickly and without merit. But unless you’re transplanting pig’s hearts and working on other large animals, the lab is so far removed from the operating room that it is extremely unlikely any such evidence could be used to back up actual surgical treatment.

Incidentally, that last link is to Siddharta Mukherjee’s abomination of an article titled “The Improvisational Oncologist” (subtitle: “In an era of rapidly proliferating, precisely targeted treatments, every cancer case has to be played by ear.") from the May 2016 edition of The New York Times Magazine (it’s a gift link so feel free to read it; caveat lector) and it describes actual scientific and medical malpractice of bringing half-baked — though, admittedly, not faked — ideas from the lab into clinic. Gelman didn’t comment on his blog back then, but he did praise Mukherjee the following year for a New York Times opinion piece “A Failure to Heal” (another gift link there) that is about — wait for it — clinical trials that show the treatment that you thought would work doesn’t. These kinds of trials tend to be called “negative” but there’s nothing negative about them! They bring positive value to the world. Maybe our improvisational oncologist learn something in those 18 months that separate the two texts?

To be clear, what Mukherjee artfully called “improvisational oncology” was (lab) bench to (hospital) bedside medicine, which is distinct from bench to bedside research: the concept of bringing laboratory findings to clinical practice quickly, but still with some semblance of a clinical trial that includes a pre-specified protocol, informed consent and regulatory oversight. You know, all the stuff that decreases the odds of laboratory malfeasance endangering patient care. I say decreases the odds and not prevents them completely because we do have a case of a bad actor completely destroying an entire field of clinical research (Alzheimer’s disease). Can you imagine the damage that kind of shenanigans would do if we didn’t have clinical trials standing between the lab and the commercial drug market?

COI statement: I am involved in a [course about clinical trials][6 and think they are the best thing that has happened to medicine since a cloth merchant wanted to take a closer look at some garments so there is some bias involved, but then again say what you’ll do and do as you say is both a major tenet of clinical trialists and good general practice.

Speaking of blogs of old, Joel Topf’s Precious Bodily Fluids has been online since 2007. As most, he went from writing several times per week to every few weeks to not even every month as life moved to Twitter but he just published a new post that includes Neal Stephenson’s treatise on the Hole Hawg and for that alone is worth a shout out.

The Forever Plague and its enemies

Halloween is nigh. This year, our eldest decided to dress up as a plague doctor, and looking through costume options reminded me of one of the worst pieces of doomscrolling churnalism that proliferated after covid. It is titled Get Ready for the Forever Plague, by one Andrew Nikiforuk, “an award-winning journalist whose books and articles focus on epidemics, the energy industry, nature and more”. Of course, back in March 2020 he was just “an award-winning journalist who has been writing about the energy industry for two decades”. So it goes.

Such is the nature of echo chambers that he continues to write, putting out articles like this month’s As COVID Surges, the High Price of Viral Denial. At first glance they are meticulously sourced, a hyperlink to a peer-review journal underlining each claim:

COVID can even whittle away your intelligence. A recent New England Journal of Medicine study looked at the memory, planning and spatial reasoning of nearly 113,000 people who had previously had COVID. Almost all had significant deficits “in memory and executive task performance” regardless of the variant.

Alas, the linked NEJM article says no such thing. In fact:

Participants with resolved persistent symptoms after Covid-19 had objectively measured cognitive function similar to that in participants with shorter-duration symptoms, although short-duration Covid-19 was still associated with small cognitive deficits after recovery. Longer-term persistence of cognitive deficits and any clinical implications remain uncertain.

And as for the “regardless of the variant” claim:

The largest deficits in global cognitive scores were observed in the group of participants with SARS-CoV-2 infection during periods in which the original virus or the alpha variant was predominant as compared with those infected with later variants.

Crucially, the control group was people with no documented covid infection; we have no idea how covid-19 compares to other coronavirus infections, other viral infections in general, and even any illness requiring hospitalization. Staying in the ICU takes a toll regardless of what put you there, and last I checked covid has been putting fewer and fewer people in the hospital, let alone the intensive care unit.

This is a common theme for most covid-19-related research. Here, again, is Nikiforuk’s latest article:

No COVID infection is completely benign because each infection plays a role in deregulating the immune system. Even a mild infection, as one recent study noted, can increase “autoantibodies associated with rheumatic autoimmune diseases and diabetes in most individuals, regardless of vaccination status prior to infection.”

Two things here. One, autoantibodies associated with a disease do not imply a disease: I myself have had high titer for antibodies associated with Sjogren’s syndrome for more than a decade without ever having symptoms of the disease (how I found out about those antibodies is a story for another day). Two, note that the study compared autoantibody levels of three groups of people: those with long covid and persistent neurologic and fatigue symptoms (“neuro-PASC”), covid convalescents, and healthy controls with no known exposure. Ideally it would have included people with non-covid “neuro-PASC” and/or convalescents of other, non-covid viral infections. But at the very least it should have mentioned prior similar research in other viral diseases and put the findings in context of other viruses and hypothesis for autoimmunity. Presented like this, SARS-CoV-2 is a celestial bugaboo unchained from other parts of reality — no wonder that the lab leak hypothesis is so tempting!

Because there are two things that could be happening here. Either a humanity-ending event occurred somewhere near the end of 2021 and we are living a somewhat prolonged but inevitable decline in which so many people will have symptoms of long covid that civilization as we know it will end (queue “the Forever Plague”). Or maybe, just maybe, we experienced a once-in-a generation spread of a new virus — new to us but something humanity has had to deal with throughout its existence — at a time when we have the means to analyze its genome, our genome, its proteins, Kudos to the Nature group of journals for their SEO. our proteins, the cells it infects, our cells responding to the infection, the microbiome, the food, the water, the air, the animals and yes, even art. And all that without the context of other viruses and other pandemics.

Last week’s EconTalk with Marty Makary featured several topics relevant to zombie medicine. One was a zombie’s return to the world of the living, with hormone replacement therapy for women not being as bad as we thought, particularly for preventing hot flashes in early menopause (before age 60). The other was the emergence of a new zombie: removing ovaries to prevent ovarian cancer when it is now thought that most ovarian cancers arise from the Fallopian tubes, not the ovaries themselves. I wouldn’t call it a full blown zombie just yet as there is an ongoing randomized controlled trial comparing the two approaches and who knows, its results may kill the old practice outright.

John Carroll, the founder of Endpoints News has stage 4 Merkel cell carcinoma and quite a story to tell:

If I had stayed at Valley Baptist and been treated with chemo, I likely would have seen Merkel cell carcinoma rear back up within a few months, putting me on a statistically short path to the grave.

[…]

My case manager said that if I wanted to leave they would have to arrange a transfer. But I already had the lay of the land from the small army of assistants and nurses who kept the hospital on its rickety track. A nurse told my wife and I — sotto voce — that as we were headed into the weekend, that could take days.

You should just go, she said quietly.

My wife drove the get away car after I signed the AMA (against medical advice), and a friend in the industry helped text my way into MD Anderson as we made the six-hour trip north.

At the other end of that journey was immunotherapy, from a company that Carroll disparaged as a journalist. So it goes…

It’s been exactly 3 years since Norm Macdonald died from acute myeloid leukemia, which was itself a know. complication of treatment he received for multiple myeloma.

But none of that is important. Anwyay, here’s Norms last stand-up performance on Letterman.

Three weeks into the new school year, and we have our first sore throat. So it begins…

A few good links for the weekend: