Research Translation Podcast

Last month the Journal of Studies on Alcohol and Drugs (‘JSAD’) published a large data review comparing mortality rates in light-to-moderate drinkers with mortality among people who don’t drink alcohol. The NY Times and others gleefully picked up the story, trumpeting the most provocative finding: Up to 1 in 25 moderate drinkers will die because of their alcohol intake. SAD! As always, the study d...

What you see below is not grape soda. It is urine from a human being—Purple Urinary Bag Syndrome, as it’s called, is quite something to behold. But it is brief, and happens when bacteria interact with the plastic of a urinary bag. Treating the underlying infection (typically mild, if there is one) is all that’s required. The color is a distraction. At the Royal Psychiatric Clinic in Munich, German...

In part 2 of this series I described a trial in which researchers developed a novel vaccine for Alzheimer’s patients, designed to rid the brain of amyloid. The vaccine worked, clearing amyloid—but their dementia progressed, unabated. This was, in other words, a full debunking of any notion that amyloid plaques are the cause of Alzheimer’s and that removing them can cure the disease. Interestingly,...

Over the first three parts in this series we followed the rise and fall of the Amyloid Hypothesis. The plaques failed. The idea of toxic precursors failed. The most influential oligomer paper in the field was ultimately retracted. By any ordinary standard of scientific reasoning, this should have marked the end of amyloid as a central explanation for Alzheimer’s Disease. Instead, something remarka...

Neuroscientists are not famous for being dumb. So when the following timeline unfolded, they should have understood exactly what it meant: First, autopsy studies in 1991 and 1992 found that amyloid plaques—supposedly the cause of Alzheimer’s, as the centerpiece of the Amyloid Hypothesis—did not scale with the disease. Then, in 2001 and 2002 , researchers published data showing that an Alzheimer’s...

Last week we reviewed two seminal studies from the 1990s, both showing mathematically that amyloid plaques are, at best, an inconsistent bystander in Alzheimer’s Disease. Plainly, they are not the driving cause. Hardcore believers may have ignored or rationalized the findings from these small but pivotal autopsy studies. A decade later however, there would be no refuge and no rescue when two trial...

Note: If you haven’t, please read Jeanne Lenzer’s recent piece, “ The Campaign to Turn Healthy People into Alzheimer’s Patients .” Jeanne is a brilliant and ferocious journalist, and her piece prompted me to dig into the research history behind it. The next few weeks will be like the Cholesterol Mistake Series : short pieces describing precisely how Alzheimer’s research has been misinterpreted and...

Cancer screening has always hidden its dark side. Behind the simple messaging and pink ribbons is a long history of complicated truths, failed trials, and titanic spending. Now, with a novel blood test flooding the market and media misrepresenting new data, it’s a good time to clarify the simplest truth of all about cancer screening: the balance sheet. To read it correctly, however, you must first...

Dr. Katz, the attending ER doctor, walked ahead of me as we left the bedside of a woman with abdominal pain and vomiting. “What’s the most common reason for emergency surgical admission to the hospital?” Wanting to impress him, I stumbled. “Um, appendicitis?” “In the top three, but no.” Dr. Katz sat down and began typing. I tried again. “Gall bladder?” He didn’t look up. “Also top three—one left.”...

Paxlovid is dead. Again. Last month Pfizer’s pill for Covid failed in two large trials published together in the New England Journal of Medicine . The bigger one, with roughly 1,700 participants per group, found 14 people assigned to Paxlovid were hospitalized versus 11 in the control group. No benefit—and leaning in the wrong direction. This was a long time coming. But it’s definitely been coming...

During the Cholesterol Mistake series, we’ve walked through the unraveling of a medical dogma. First, we saw how the Lipid Hypothesis violates the seminal rule of risk factors. Next, we watched the goalposts shift from extending life to chasing non-fatal laboratory endpoints. Then, in trial appendices, we found the Big Mistake: tallying checkbox diagnoses while ignoring what matters to people. Alo...

Today’s piece is an interlude in the Cholesterol Mistake series (parts 1 , 2 , 3 , and 4 ) which was inspired by the new AHA lipid guidelines. I got sidetracked by the figure below from those guidelines, and ended up in the weeds—deep enough to go much longer than normal. Apologies for length, hope the payoff is worthy. Next week part 5, back to brevity! “He says the chest pain started suddenly an...

Readers: What follows is part 4 of a series intended to defog the strange misunderstanding that is cholesterol in modern medicine. Part 1 explains a mistake that birthed the Lipid Hypothesis, part 2 explains how we failed in measuring success, part 3 walks through the data, which reveals a yawning gap between doctor- and patient-centered science, and today’s part 4 is about how good, smart people...

I hope you will forgive the mini-barrage. I don’t usually clutter inboxes, but the timely publication of a trial that fits, hand-in-glove, with the current series was too much temptation. To understand what’s gone wrong in cholesterol research, and what my 4-part series is about, you don’t need a theory. You just need a trial. The one published last night in the New England Journal of Medicine, an...

The AHA’s cholesterol guideline cites a large review of trials from 2012 as the principal evidence for treating cholesterol in healthy people. The following table is from that review, webfigure 9, in the supplement . It’s okay for your eyes to glaze over, I’ll summarize the important parts. People in statin trials were assessed for their 5-year risk of having a heart problem. The table, which show...

Author note: What follows is part 2 of a series intended to summarize and explain just how, historically, we went off the rails with cholesterol. Check out part 1 here . In the early 1990s, Eugene Braunwald and the cardiology community had a problem. In the throes of a major heart attack new clot-buster drugs and angioplasty procedures were working—saving lives. Cardiologists could see it even mon...

The AHA’s new cholesterol guideline is asking professionals to start earlier, screen more, and treat cholesterol more aggressively, decades before any heart or vascular disease could plausibly occur. What follows, therefore, is the first of a series in which I will attempt to show how doctors (and most others) have misunderstood the science on cholesterol, from the beginning. I will be citing and...

In the early 19th century, the French physician Pierre-Charles-Alexandre Louis did something medicine had rarely done before: he counted. At the time, bloodletting was standard. It was elegant, logical, and universally accepted. If an imbalance of humors caused disease, removing blood should fix it. The theory made sense. The practice was everywhere. Louis compared outcomes among patients with pne...

Earlier this week media reported that Robert F. Kennedy Jr., the Secretary of Health and Human Services, had surgery to repair a torn rotator cuff. That’s interesting. Not just because I wrote about rotator cuff surgery last week . Kennedy has spent years arguing that medical treatments should be recommended only after they’re proven to work in rigorous trials. Which raises the inevitable question...

I used to do a lot of push-ups. Then, one day, my right shoulder abruptly said no más . Coincidentally, days later I saw my doctor. To be clear, I live by “ See doctors, not too much, only when sick ,” but my insurance policy insists on an annual visit. So once a year I skulk into the office and prove why doctors make awful patients—particularly when they’re washed-up, windbag, wiseacres who don’t...

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When Arthur Conan Doyle wanted Sherlock Holmes to show off, he didn’t give him a bloody fingerprint or a dropped monocle. He gave him a dog that didn’t bark. In Silver Blaze , the silence was the clue. The horse didn’t vanish because of a stranger—the stable dog knew the intruder. The absence of noise told Holmes everything. That’s where we are with the newest trial of PCSK9s, a class of drug that...

When readers sent me media articles touting baloxavir (‘Xofluza’), I started looking. In the interim, Sensible Medicine , a wonderful Substack by evidence-based doctors, published a podcast , and today a written piece , recommending the drug. I believe they have it deeply wrong. Fun! Check it out, tell me what you think. When I was seven years old I tried hard to see through a frosted glass window...

Below marks my first critique of politics, and you’ll see why. For background: I have no political affiliation and do not care for party politics. Years ago I became deeply disenchanted with parties of all stripes. I do not seek a packaged bundle of beliefs or positions—I have my own. I care what works, one issue at a time, and I’m open. What I cannot stand, the attribute that repels me most, is t...

This week is an audio hodgepodge—lagniappe, if you will—a chance to discuss and explore recent headlines. Enjoy! Here are some of the relevant RT and news links. WSJ on vitamins - Vitamins piece on RT NYT on recent vaccine changes - Vaccines piece on RT (Covid for children, and related discussion) NY Times on Alcohol and Cancer, Alcohol and cardiovascular disease - Alcohol , alcohol , alcohol , an...