Category: Science

Expert Medical Advice Often Flip-Flops

(p. D6) A History of Medical Flip-Flops

Shifting medical advice is surprisingly common, and it tends to fall into three categories: emerging guidance, replacement advice and reversals.

Emerging guidance comes during times of crisis — like pandemics — and is destined to change quickly. In the past several months, guidance about the best way to treat Covid patients, masks to prevent transmission and the limits of vaccine protection have all shifted as knowledge of the coronavirus and its variants has evolved.

Sometimes it’s hard to tell the difference between replacement advice, which is issued when research improves on advice that came before it, and a full reversal, which comes about because a common medical practice got ahead of the science and never actually worked or even caused harm. Here are some examples of true medical flip-flops in recent years.

MENOPAUSE HORMONES TO PROTECT THE HEART: In 2002, decades of advice about the heart benefits of menopause hormones seemed to change overnight when a major study called the Women’s Health Initiative was halted after researchers detected more heart attacks in the women taking hormones. In hindsight, doctors had misinterpreted data from observational research. The current advice: Hormones can relieve menopause symptoms but shouldn’t be used for chronic disease prevention.

VIOXX AS A LOWER-RISK ARTHRITIS TREATMENT: In 1999, the Food and Drug Administration approved Vioxx as a breakthrough pain reliever because it lowered the risk of gastrointestinal problems. But by 2004, Merck had withdrawn the drug because studies showed it significantly raised the risk of heart attack.

ARTHROSCOPIC SURGERY ON AGING KNEES: For years, the partial removal of torn meniscus tissue was the most common orthopedic procedure in the United States, with about 700,000 performed a year. In 2013, a researcher in Finland compared the operation to a “sham” procedure and found there was no benefit. Most doctors now recommend physical therapy instead.

VITAMIN MEGADOSES TO LOWER CANCER AND HEART RISK: For years, doctors believed various vitamins could lower risk for cancer and heart disease, but a number of studies showed just the opposite. A study of beta carotene and vitamin A found that the supplements actually increased the risk of lung cancer in male smokers. A study of vitamin E and selenium, thought to protect against prostate cancer, increased risk for the disease.

STENTS FOR STABLE HEART DISEASE: Doctors used to insert stents — tiny wire mesh tubes that prop open arteries — in millions of otherwise stable patients with heart disease. A study found that the surgical procedure was no better than drug therapy for preventing heart attacks.

Dr. Vinay Prasad, associate professor at the University of California San Francisco, and Dr. Adam S. Cifu, a professor of medicine at the University of Chicago Department of Medicine, coined the term “medical reversal” and concluded that about 40 percent of common medical practices that they reviewed turned out to be useless or harmful. In their book, “Ending Medical Reversal: Improving Outcomes, Saving Lives,” they noted that most of these failed treatments were initially embraced because they were based on logical reasoning.

“The thing that’s often behind reversal: All of these things have a good story, they have good pathophysiological rationale,” Dr. Cifu said. “They should work. But things only work if they’ve been shown in people to work, and people are so complicated.”

For the full story, see:

Tara Parker-Pope. “Shifting Medical Advice Is a Feature, Not a Bug.” The New York Times (Tuesday, November 2, 2021): D6.

(Note: the online version of the story was updated Oct. 24, 2021, and has the title “Is the New Aspirin Advice a Medical Flip-Flop, or Just Science?” The paragraphs on menopause hormones to protect the heart and on vitamin megadoses to lower cancer and heart risk appear in the online version, but not in the print version.)

The book co-authored by Prasad and mentioned above is:

Prasad, Vinayak K., and Adam S. Cifu. Ending Medical Reversal: Improving Outcomes, Saving Lives. Baltimore: Johns Hopkins University Press, 2015.

The “Gold Standard” of Randomized Clinical Trials “Has Its Own Issues”

(p. R2) . . ., closely held Epic Systems Corp., maker of one of the most widely used electronic health record systems, searched a segment of its database in the spring of 2020 to find that routine breast, colon and cervical cancer screenings in the U.S. had each dropped by more than 85% during the first weeks of the Covid-19 pandemic. The report helped spur efforts to persuade people to make up for missed screenings.

But researchers have a much more ambitious vision for this data: to help guide how doctors treat individual patients in real time.

“The evidence from real-world data is a different and exciting new path,” says Jackie Gerhart, a physician who works with the informatics team at Epic. “You can get a lot of outcomes information from medical records that can help change care for individual patients.”

. . .

To be sure, patient records are observational, and thus subject to confounders and other shortcomings that can undercut their reliability in pointing to treatment options.

But the gold standard has its own issues. Randomized clinical trials, which control for differences in patient health status and other variables, are the preferred evidence to inform patient care. Yet such trials generally exclude an especially common group of patients—those with multiple ailments. Moreover, the elderly, children, women, minority groups and people who live far from medical research centers have long been underrepresented in such studies.

As a result, the highest-quality evidence that medicine produces doesn’t apply to most patients doctors see in daily practice. “There are so many clinical situations where the evidence that is needed does not exist,” says Nigam Shah, professor of medicine and biomedical data science at Stanford University Medical School.

Researchers have believed for at least a half-century that data in patient medical records could help fill the gaps.

. . .

The struggles of International Business Machines Corp.’s Watson raises [a] . . . yellow flag. It had ambitions to develop a tool for cancer doctors that would mine patient health records and thousands of pages of research from the peer-reviewed medical literature for treatment advice. But it hit walls, including accuracy and the complexity of combining data from electronic health records, billing claims and published research to provide a cohesive product. Doctors who used the service rarely changed treatment plans. IBM says it discontinued Watson for Oncology at the end of 2020.

For the full story, see:

Ron Winslow. “Mining the Gold in Patient Records.” The Wall Street Journal (Thursday, December 9, 2021): R2.

(Note: ellipses, and bracketed word, added.)

(Note: the online version of the story has the date December 3, 2021, and has the title “Medical Records Data Offers Doctors Hope of Better Patient Care.” In a couple of passages there are a few extra words in the online version, which is the version quoted above.)

“Unprecedented” and “Huge” Serendipitous Discovery of 60 Million Icefish Nests

(p. D3) As soon as the remotely operated camera glimpsed the bottom of the Weddell Sea, more than a thousand feet below the icy ceiling at the surface, Lilian Boehringer, a student researcher at the Alfred Wegener Institute in Germany, saw the icefish nests. The sandy craters dimpled the seafloor, each the size of a hula hoop and less than a foot apart. Each crater held a single, stolid icefish, dark pectoral fins outspread like bat wings over a clutch of eggs.

Aptly named icefishes thrive in waters just above freezing with enormous hearts and blood that runs clear as vodka. . . .

The sighting occurred in February 2021 in the camera room aboard a research ship, the Polarstern, which had come to the Weddell Sea to study other things, not icefish. It was 3 a.m. near Antarctica, meaning the sun was out but most of the ship was asleep. To Ms. Boehringer’s surprise, the camera kept transmitting pictures as it moved with the ship, revealing an uninterrupted horizon of icefish nests every 20 seconds.

. . .

The nests persisted for the entire four-hour dive, with a total of 16,160 recorded on camera. After two more dives by the camera, the scientists estimated the colony of Neopagetopsis ionah icefish stretched across 92 square miles of the serene Antarctic sea, totaling 60 million active nests. The researchers described the site — the largest fish breeding colony ever discovered — in a paper published Thursday in the journal Current Biology.

“Holy cow,” said C.-H. Christina Cheng, an evolutionary biologist at the University of Illinois-Urbana-Champaign, who was not involved with the research. “This is really unprecedented,” she said. “It is crazy dense. It is a major discovery.”

. . .

“The seafloor is not just barren and boring,” Dr. Purser said. “Such huge discoveries are still there to be made, even today in the 21st century.”

For the full story, see:

Sabrina Imbler. “Deep in Frigid Waters, Icefish Colonies Thrive.” The New York Times (Tuesday, January 18, 2022): D3.

(Note: ellipses added.)

(Note: the online version of the story has the date January 13, 2022, and has the title “‘Major Discovery’ Beneath Antarctic Seas: A Giant Icefish Breeding Colony.”)

Testing for Rare DNA Microdeletion Birth Defects Can Result in More False Positives Than True Positives

(p. 12) Between 2011 and 2013, a small California-based biotech company, Sequenom, tripled in size. The key to its success: MaterniT21, a new prenatal screening test that did remarkably well at detecting Down syndrome.

Older screening tests took months and required multiple blood tests. This new one generated fewer false positives with a single blood draw.

The test could also determine the sex of a fetus. It quickly became a hit. “You had people walking in saying, ‘I want this sex test,’” recalled Dr. Anjali Kaimal, a maternal-fetal medicine specialist at Massachusetts General Hospital.

Competitors began launching their own tests. Today, analyst estimates of the market’s size range from $600 million into the billions, and the number of women taking these tests is expected to double by 2025.

As companies began looking for ways to differentiate their products, many decided to start screening for more and rarer disorders. All the screenings could run on the same blood draw, and doctors already order many tests during short prenatal care visits, meaning some probably thought little of tacking on a few more.

For the testing company, however, adding microdeletions can double what an insurer pays — from an average of $695 for the basic tests to $1,349 for the expanded panel, according to the health data company Concert Genetics. (Patients whose insurance didn’t fully cover the tests describe being billed wildly different figures, ranging from a few hundred to thousands of dollars.)

But these conditions were so rare that there were few instances for the tests to find.

Take Natera, which ran 400,000 tests in 2020 for DiGeorge syndrome, a disorder associated with heart defects and intellectual disability.

That number of tests would be expected to identify about 200 cases of the disorder according to a Times analysis of the company’s studies. It would also generate at least an equal number of false positive results.

That is a best-case scenario based on Natera’s recent claim to have improved its algorithm. In clinical trials, its test (p. 13) generated three times as many false positives as true ones. The company’s four other microdeletion screenings, which it said were run at least 24,000 times in 2020, would be expected to find about eight true postitves and bewen 17 and 134 fase ones, according to the analysis.

For the full story, see:

Sarah Kliff and Aatish Bhatia. “Prenatal Tests for Rare Defects Often Produce False Positives.” The New York Times, First Section (Sunday, January 2, 2022): 1 & 12-13.

(Note: the online version of the story has the date Jan. 1, 2022, and has the title “When They Warn of Rare Disorders, These Prenatal Tests Are Usually Wrong.” The last three paragraphs above appear in the online version, but not in this form in the print version. In the print version, the information in the last three paragraphs quoted above, appears mostly as part of an extended graphic.)

Bret Baier Documents How Fauci and Collins Dishonestly Dismissed the Hypothesis That COVID-19 Originated in Wuhan Lab

Bret Baier gave a serious report on the substantial and growing evidence that Anthony Fauci, Francis Collins, and other “experts” and officials lied, early and intentionally, in their dismissal of the likely Wuhan lab origin of Covid-19. (The report aired on Bret Baer’s “Special Report” nightly news program on Tues., January 25, 2022 on Fox News.)

“Unexpected” Discovery of Large “Pristine” Coral Reef “Unscathed by Climate Change”

(p. A7) An underwater mapping project recently took an unexpected twist off the coast of Tahiti, where deep sea explorers said this week that they had discovered a sprawling coral reef resembling a bed of roses that appeared to be largely unscathed by climate change.

Extending for about three kilometers (1.86 miles), the reef is remarkably well preserved and is among the largest ever found at its depth, according to those involved in the mapping project sponsored by UNESCO, the U.N. Educational, Scientific and Cultural Organization.

Some even described the condition of the reef, hidden at depths between 30 meters (about 100 feet) and 100 meters in the crystalline waters of the South Pacific, as “pristine.”

Alexis Rosenfeld, an underwater photographer from Marseille, France, said on Thursday that the reef lived up to what he had envisioned when he first explored it shortly after its discovery in November [2021].

. . .

John Jackson, a film director with 1 Ocean who is involved with the project, compared the reef’s shape to lacework. In an interview on Thursday [January 20, 2022], he said that significant work remained when it came to underwater exploration, pointing out that only about 20 percent of the world’s seabeds had been mapped.

For the full story, see:

Neil Vigdor. “‘Pristine’ Coral Reef Resembling Bed of Roses Is Found Off the Coast of Tahiti.” The New York Times (Saturday, January 22, 2022): A7.

(Note: ellipsis, and bracketed year and date, added.)

(Note: the online version of the story has the date Jan. 20, 2022, and has the title “Sprawling Coral Reef Resembling Roses Is Discovered Off Tahiti.”)

Mars Can Be Terraformed to Reduce Costs of Colonization

(p. D5) Since joining NASA in 1980, Jim Green has seen it all. He has helped the space agency understand Earth’s magnetic field, explore the outer solar system and search for life on Mars. As the new year arrived on Saturday, he bade farewell to the agency.

Over the past four decades, which includes 12 years as the director of NASA’s planetary science division and the last three years as its chief scientist, he has shaped much of NASA’s scientific inquiry, overseeing missions across the solar system and contributing to more than 100 scientific papers across a range of topics. While specializing in Earth’s magnetic field and plasma waves early in his career, he went on to diversify his research portfolio.

. . .

Ahead of a December [2021] meeting of the American Geophysical Union in New Orleans, Dr. Green spoke about some of this wide-ranging work and the search for life in the solar system. Below are edited and condensed excerpts from our interview.

. . .

    You’ve previously suggested it might be possible to terraform Mars by placing a giant magnetic shield between the planet and the sun, which would stop the sun from stripping its atmosphere, allowing the planet to trap more heat and warm its climate to make it habitable. Is that really doable?

Yeah, it’s doable. Stop the stripping, and the pressure is going to increase. Mars is going to start terraforming itself. That’s what we want: the planet to participate in this any way it can. When the pressure goes up, the temperature goes up.

The first level of terraforming is at 60 millibars, a factor of 10 from where we are now. That’s called the Armstrong limit, where your blood doesn’t boil if you walked out on the surface. If you didn’t need a spacesuit, you could have much more flexibility and mobility. The higher temperature and pressure enable you to begin the process of growing plants in the soils.

There are several scenarios on how to do the magnetic shield. I’m trying to get a paper out I’ve been working on for about two years. It’s not going to be well received. The planetary community does not like the idea of terraforming anything. But you know. I think we can change Venus, too, with a physical shield that reflects light. We create a shield, and the whole temperature starts going down.

For the full story, see:

Jonathan O’Callaghan, interviewer. “Inhabiting Mars? He Calls It ‘Doable.’” The New York Times (Tuesday, January 4, 2022): D5.

(Note: ellipses, and bracketed year, added.)

(Note: the online version of the story has the date Jan. 2, 2021, and has the title “NASA’s Retiring Top Scientist Says We Can Terraform Mars and Maybe Venus, Too.” The first three paragraphs, and the block-indented sentence and question, are by the interviewer Jonathan O’Callaghan. The answer after the question is by Jim Green.)

Musk Wants to Use His Billions “to Get Humanity to Mars”

(p. B1) In the negotiations over President Biden’s infrastructure bill, Senator Ron Wyden, Democrat of Oregon and chairman of the Finance Committee, proposed the idea of a tax on billionaires specifically. Thursday morning, Mr. Biden announced his framework for paying for the bill, which promised additional taxes on the income of “the wealthiest 0.02 percent of Americans.”

Mr. Wyden’s proposed tax will likely never make it into law.

. . .

(p. B5) Elon Musk, in a tweet, seemed to come out against the proposal. “Eventually, they run out of other people’s money and then they come for you,” he wrote. It is fairly safe to say that Mr. Musk will never run out of money. A back-of-the-envelope calculation from Forbes’s real-time net worth tracker suggests that he could spend $1 million a year for 100,000 years and still have more money than Bill Gates, with an estimated $136.2 billion.

. . .

Abigail Disney, granddaughter of Roy Disney and a longtime critic of income inequality, said in an interview that she believes the immense displays of wealth by the country’s richest during the pandemic — particularly the ostentatiousness of last summer’s space race — helped foster a serious discussion about the tax burdens on billionaires.

. . .

In comments denouncing the proposed billionaire tax, Mr. Manchin described the ultrawealthy as people who “create a lot of jobs and invest a lot of money and give a lot to philanthropic pursuits.”

That was an implicit endorsement of the idea, often repeated in discussions around high-net worth giving, that regular people pay taxes while rich people pursue philanthropy, giving not to the Treasury but to their preferred causes. “My plan is to use the money to get humanity to Mars and preserve the light of consciousness,” Mr. Musk said in a subsequent tweet in response to the tax proposal.

“That idea that ‘it’s my money and I should decide what to do with it’ is very dominant, and it goes along with the culture of individualism that allows people to feel that they’ve done this on their own and haven’t benefited from social goods like roads and education and laws,” Professor Sherman said.

Ms. Disney, who is an active member of the Patriotic Millionaires, said she sees that thinking as a primary obstacle to raising taxes on the richest Americans. “Billionaires may be brilliant — and I don’t doubt Elon Musk’s I.Q. — but they don’t do anything on their own,” she said. She also questioned the prevailing wisdom among the country’s wealthiest that they know best and the government shouldn’t be trusted with their money.

“The last time I was in the Bay Area, I went walking in the marina and saw seven consecutive boats named after characters from Ayn Rand,” Ms. Disney said. “They need to come to their senses.”

For the full story, see:

Nicholas Kulish, Ephrat Livni and Emma Goldberg. “Billionaires Of America Are Thriving.” The New York Times (Friday, October 29, 2021): B1 & B5.

(Note: ellipses added.)

(Note: the online version of the story was updated Nov. 2, 2021, and has the title “Who Are America’s Billionaires, Anyway?”)

Proof Vikings Were in North America 1,000 Years Ago

(p. A8) A new look at wooden artifacts found amid the ruins of an ancient homestead shows that Vikings had crossed the Atlantic Ocean and settled in North America as far back as 1021—exactly 1,000 years ago and almost five centuries before Columbus’s famous voyage.

. . .

To pinpoint the year that Vikings occupied the site, the scientists scoured the ancient settlement for wooden artifacts, hoping to find any made from trees that had grown during an unusually intense burst of cosmic radiation known to have occurred in the year 993.

. . .

Using the carbon spike as a reference point, they counted the tree rings in each specimen until they reached the bark, indicating the year the tree was cut down—in this case 1021.

For the full story, see:

Robert Lee Hotz. “Viking Artifacts Pinpoint Europeans.” The Wall Street Journal (Thursday, October 21, 2021): A8.

(Note: ellipses added.)

(Note: the online version of the story has the date October 20, 2021, and has the title “Viking Artifacts Give Precise Date for Europeans’ Earliest Presence in North America.”)

Virtual Reality (VR) Used to Better See Cancer Cell Mutations

(p. R3) Chemist and entrepreneur Jackie von Salm recently walked inside a receptor in the brain to inspect a new drug compound. As she looked at the brightly colored, cascading ribbons around her, she noted something: Part of the atomic structure, a series of thick, orange rods and hexagons, jutted toward her in an odd way, suggesting that the compound, a derivative of the psychedelic DMT, might be effective at treating addiction without having hallucinogenic effects.

“This is weird,” says Dr. von Salm, the co-founder and chief scientific officer of Psilera Inc., a Tampa, Fla.-based company working to turn psychedelics into treatments for addiction, neurodegenerative diseases and mood disorders. “But it might be really unique and special.”

The odd positioning of the compound might be the right shape to latch onto serotonin receptors in the brain that are involved with hallucination and addiction. That insight was possible thanks to a technology more closely associated with gamers than scientists: Virtual reality.

Dr. von Salm is one of a growing number of drug-discovery researchers who are using VR to see, in new ways, the molecules they have long studied on computer screens. Their goal is to investigate subtle changes in the distance, shape and chemical properties of atomic structures that could give them clues about how well a drug might work and speed up the drug-discovery process.

. . .

Since 2018, cancer researchers at the University of California San Francisco have been using VR to better understand the genetic mutations in cancer cells that might make a patient resistant to treatment. For example, in VR, it was clear that the reason a drug didn’t bind properly to its protein target in the cancer cell was because of the movement of a portion of the protein called the P-loop. The movement was caused by a mutation in the target.

On a computer monitor, it was difficult to see the tiny change in the movement. “When there are changes like that, the VR is critical,” says Beth Apsel Winger, a hematologist and oncologist at the university’s department of pediatrics.

For the full commentary, see:

Sara Castellanos. “VR Rx.” The Wall Street Journal (Friday, Sept. 10, 2021): R3.

(Note: ellipsis added.)

(Note: the online version of the commentary has the date September 7, 2021, and has the title “Virtual Reality Puts Drug Researchers Inside the Molecules They Study.”)

Absence of Covid-19 in 9,000 Chinese Samples from Late 2019 Supports Lab-Leak Theory

(p. A17) Where did Covid-19 come from? The answer can be found in the SARS-CoV-2 virus itself. To get to the truth, we need only unleash the power of science.

Based on experience with SARS-1 in 2003 and MERS in 2012, we know that many people are infected by a host animal long before a coronavirus mutates to the point where it can jump from human to human. An extensive data set from late 2019—more than 9,000 hospital samples—is available of people exhibiting flulike (thus Covid-like) symptoms in China’s Hubei and Shaanxi provinces before the epidemic started. Based on SARS-1 and MERS, the natural zoonotic theory predicts 100 to 400 Covid infections would be found in those samples. The lab-leak hypothesis, of course, predicts zero. If the novel coronavirus were engineered by scientists pursuing gain-of-function research, there would be no instances of community infection until it escaped from the laboratory. The World Health Organization investigation analyzed those stored samples and found zero pre-pandemic infections. This is powerful evidence favoring the lab-leak theory.

Within months of the SARS-1 and MERS outbreaks, scientists found animals that had hosted the viruses before they made the jump to humans. More than 80% of the animals in affected markets were infected with a coronavirus. In an influential March 2020 paper in Nature Medicine, Kristian Andersen and co-authors implied that a host animal for SARS-CoV-2 would soon be found. If the virus had been cooked up in a lab, of course, there would be no host animal to find.

Chinese scientists searched for a host in early 2020, testing more than 80,000 animals from 209 species, including wild, domesticated and market animals. As the WHO investigation reported, not a single animal infected with SARS-CoV-2 was found. This finding strongly favors the lab-leak theory. We can only wonder if the results would have been different if the animals tested had included the humanized mice kept at the Wuhan Institute of Virology.

For the full commentary, see:

Richard Muller and Steven Quay. “Science Closes In on Covid’s Origins.” The Wall Street Journal (Wednesday, Oct. 6, 2021): A17.

(Note: the online version of the commentary has the date October 5, 2021, and has the same title as the print version.)