Posts in: medicine

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:

ChatGPT, the blog expert

The latest episode of The Talk Show was with Taegan Goddard, who all the way back in 1999 founded the blog Political Wire which is apparently a continuous intravenous drip for people interested in US politics. Now, I’ve had other preocupations back then and not being an American citizen still have little to no interest, so this blog wasn’t even on my radar until listening to the episode. But now I wonder: are there any more relevant blogs I’ve missed out on, about medicine and biotechnology in particular?

ChatGPT’s first pass was mediocre. I’ll save you the verbalist padding, but here are its suggestions in response to my prompt: “Is there a website/blog like politicalwire.com or daringfireball.net but for biotechnology?”

It’s a 20% hit rate: only Derek Lowe’s In the Pipeline comes close to what I asked for. The others are all medium to big news outlets that yes, focus on biotech, but that’s not what I asked for. The second try, after I asked for more like Lowe’s, was a tad better:

That’s more like it! 80% now, and if I were feeling generous I’d give it a full 100% since In the Pipeline is, in fact, a Sci Trans Med blog. But then I asked for too much, and it hallucinated 3 more, two of which were hallucinations (BioPunk and BiotechBits, which were at least plausible names) and one was a sub-blog of Endpoints that also didn’t exist.

So, now I have two new blogs to follow (Timmerman Report and The Niche; Biotech Strategy is behind a paywall and I’ve already been following the others), and an ever-increasing urge to update the Blogroll, which has been under construction for the past five months with no end in sight.

Not one week after I first wrote about zombie medicine, this happened:

So many examples out there: icing injuries, treating mild fevers in kids, Paxlovid. Someone really ought to collect these and write a book.

Zombie medicine: it's everywhere, it's evil, and it's coming to get you (and your money)

In their excellent but unfortunately titled book Ending Medical Reversal, Adam Cifu Dr. Cifu talked to Russ Roberts recently, in one of the best episodes of EconTalk so far this year. Dr. Prasad’s interview with Russ was also quite good, though the topic was not my cup of tea. and Vinay Prasad note the practice of “medical reversals”, which is a tendency of medicine to reverse practice — or self-correct — once evidence suggests that something that was thought to work actually doesn’t. Typical examples are starting prophylactic anti-arrhythmics after a heart attack, using estrogen to treat symptoms of menopause and performing kyphoplasty to treat vertebral compression fractures. The RCTs that led to reversals are: CAST, Women’s Health Initiative and ACTRN12605000079640, and guess which one of these was done in New Zealand. For each of those, there was a randomized controlled trial that showed no benefit — or, even worse, more harm — of the intervention compared to placebo. And presto, medical reversal was official and doctors around the world stopped doing what they now knew was harmful.

Just kidding: it took years to stop those practices, and kyphoplasty/vertebroplasty is still being performed, in select cases, based on little to no evidence. There is a long tail of doctors who either don’t believe RCTs in general, or don’t know about some of those in particular, or what is most common know and believe in RCTs when they affect someone else’s practice but find a million faults in those that investigate their own bread and butter. These doctors perform what I’d like to call Zombie Medicine, a term inspired by Lisa Feldman Barret’s Zombie Ideas (↬Andrew Gelman): Incidentally, “Zombie Medicine” would have made a much better book title than “Ending Medical Reversal”. Add a subtitle (Zombie Medicine: How Doctors' Inertia and Bad Science Harm Patients and Waste Billions) and you have a best-seller. Maybe for the second edition?

Zombie ideas abound in our culture, nibbling away at the brains of their victims. The mistaken belief that vaccinations cause autism — a celebrated zombie idea — is responsible for rising rates of vaccine-preventable diseases. The belief that a person’s personality type, assessed by the Myers-Briggs Type Indicator (MBTI), predicts job performance is another zombie idea that continues to lure otherwise capable managers into making decisions that benefit neither employees nor their companies.

But inertia to a big, unexpected medical reversal isn’t even the most common type of zombie medicine. There are some undead concepts so ingrained that a million RCTs couldn’t reverse them: the belief that atelectasis (partial lung collapse, common after surgery due to immobility) causes fevers (high body temperature, common after surgery due to infection, transient bacteraemia, and general inflammation), that early cancer detection is an absolute good, that Vitamin C cures anything other than scurvy, that vitamin D prevents anything other than osteoporosis and rickets. And it’s insidious, for I bet every reader will have felt a pang for at least one of these concepts. (“Wait, why does he think this is zombie medicine when I know it’s true!?") That’s how zombie practices become undead: with a sliver of doubt, a shimmer of hope, a dollop of wishful thinking.

And on the very edge of zombification sit tempting ideas that have greater than 99% chance of being false, but that you know will never truly die: that mTOR inhibitors can prolong human life spans, that with enough sequencing we will find genetic causes of most diseases, that the gut microbiome influences anything other than gastrointestinal health and quality of stool. This kind of zombie medicine adds another item to the list of harms: opportunity cost in both money and time.

The first step in addressing a problem is to identify it, the second is to name it. Now comes the time to make lists.