Category: Health

Rigid Merged Health Systems Cause Slow Covid-19 Testing

(p. A1) When a stay-at-home order in March all but closed the revered labs of the gene-editing pioneer Jennifer Doudna, her team at the University of California, Berkeley dropped everything and started testing for the coronavirus.

They expected their institute to be inundated with samples since it was offering the service for free, with support from philanthropies. But there were few takers.

Instead, the scientists learned, many local hospitals and doctors’ offices continued sending samples to national laboratory companies — like LabCorp and Quest Diagnostics — even though, early on, patients had to wait a week or more for results. The bureaucratic hurdles of quickly switching to a new lab were just too high.

. . .

(p. A5) In normal times, scientists at the Innovative Genomics Institute at Berkeley spend their time advancing the gene-editing technology called Crispr that the lab’s founder, Dr. Doudna, is known for.

But after the pandemic shut down the institute’s research in March, Dr. Doudna called for volunteers to redirect most of the labs’ work to coronavirus testing. The country was clamoring for more tests, after all, and her lab was full of researchers with the technical skills to make it happen.

Unlike many other major research institutions, Berkeley does not have a medical school or run its own hospital. So Dr. Urnov reached out to others in the area, who were still ordering from LabCorp and Quest, despite lengthy delays in processing results at the time.

“We would come to these entities and say, ‘Hi, we hear you have problems,’” Dr. Urnov recalled. “And they said, ‘Well, you have to basically work with our EHR,’” the acronym for electronic health records.

For the full story, see:

Katie Thomas. “In Testing Chaos, Some Labs Drowned While Others Sat Idle.” The New York Times (Friday, May 22, 2020): A1 & A5.

(Note: ellipsis added.)

(Note: the online version of the story has the date May 21, 2020 and has the title “These Labs Rushed to Test for Coronavirus. They Had Few Takers.”)

“For Every Scientist Employed by the F.D.A., There Are Three Lawyers”

(p. 5) Imagine that the fateful day arrives. Scientists have created a successful vaccine. They’ve manufactured huge quantities of it. People are dying. The economy is crumbling. It’s time to start injecting people.

But first, the federal government wants to take a peek.

That might seem like a bureaucratic nightmare, a rubber stamp that could cost lives. There’s even a common gripe among researchers: For every scientist employed by the F.D.A., there are three lawyers. And all they care about is liability.

For the full commentary, see:

Stuart A. Thompson. “How Long Will a Vaccine Really Take?” The New York Times, SundayReview Section (Sunday, May 3, 2020): 4-5.

(Note: the online version of the commentary was updated April 30, 2020 and has the same title as the print version.)

Hydroxychloroquine Clinical Trials Suspended on Basis of Lancet Article Containing “Major Inconsistencies”

(p. A11) A group of scientists who raised questions last week about a study in The Lancet about the use of antimalarial drugs in coronavirus patients have now objected to another paper about blood pressure medicines in the New England Journal of Medicine, which was published by some of the same authors and relied on the same data registry.

Moments after their open letter was posted online Tuesday morning [June 2, 2020], the editors of the N.E.J.M. posted an “expression of concern” about the paper, and said they had asked the paper’s authors to provide evidence that the data are reliable.

The Lancet followed later in the day with a statement about its own concerns regarding the malarial drugs paper, saying that the editors have commissioned an independent audit of the data.

. . .

In their letter to the N.E.J.M., critics of the work wrote: “Serious, and as yet unanswered, concerns have been raised about the integrity and provenance of these data.”

The letter points out “major inconsistencies” between the number of coronavirus cases recorded in some countries during the study period and the number of patient outcomes reported by the researchers over the same period.

. . .

Many of the scientists who first raised concerns about the database are involved in clinical trials of chloroquine and hydroxychloroquine, and they were forced to pause the studies for safety reviews after The Lancet study was published.

James Watson, a senior scientist with MORU Tropical Health Network, said his unit had to immediately suspend work on a large randomized clinical trial to see if chloroquine or hydroxychloroquine can protect health care workers exposed on the job to the coronavirus from infection.

“I saw very quickly this paper didn’t hold up to much scrutiny at all,” he said. “We started wondering, ‘Who’s been collecting this data, and where did it come from?’ We were quite surprised to see a global study with only four authors listed and no acknowledgment of anyone else.”

. . .

David Glidden, a professor of biostatistics at University of California, San Francisco, who reads all new publications about Covid-19 antiviral therapies as a member of a National Institutes of Health clinical guidelines panel, said he was immediately struck by the vagueness of the descriptions in both papers.

For the full story, see:

Roni Caryn Rabin. “Scientists Question Medical Data From Single Company Used in Two Studies.” The New York Times (Wednesday, June 3, 2020): A11.

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

(Note: the online version of the article was updated June 2, 2020, and had the title “Scientists Question Medical Data Used in Second Coronavirus Study.”)

Trump Walks the Walk on Hydroxychloroquine

(p. A6) WASHINGTON—President Trump said he is taking hydroxychloroquine, an antimalarial drug that he has cited as a possible defense against the novel coronavirus but that some scientists have cautioned needs further study and could be dangerous.

“I happen to be taking it, hydroxychloroquine,” he told reporters at the White House on Monday. He said he had consulted with the White House doctor and suggested he is taking the drug as a preventive measure. Mr. Trump said he has been checked regularly for Covid-19, has tested negative and has no symptoms. He said he has been taking hydroxychloroquine for about a week and a half.

. . .

On Monday [May 18, 2020], Mr. Trump continued to stress anecdotal evidence in favor of the drug and told reporters, “I was just waiting to see your eyes light up when I said this.” He also expressed confidence in the drug’s safety. “I’m not going to get hurt by it. It’s been around for 40 years for malaria, for lupus, for other things.”

For the full story, see:

Catherine Lucey, Jared S. Hopkins. “President Trump Says He Is Taking Hydroxychloroquine as Preventive.” The Wall Street Journal (Tuesday, May 19, 2020): A6.

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

(Note: the online version of the story has the date May 18, 2020, and has the title “Trump Says He Takes Contested Drug for Prevention.”)

The key reference on advocates of a drug who take it first themselves, without confirmation from randomized double-blind clinical trials, is:

Altman, Lawrence K. Who Goes First?: The Story of Self-Experimentation in Medicine. Berkeley, CA: University of California Press, 1998.

Cancer Mortality Declines Mainly Due to Less Smoking and Better Lung Cancer Treatment

(p. A12) . . . the American Cancer Society reported that the United States had experienced the sharpest one-year drop in cancer death rate ever recorded, . . . .

. . .

The society’s latest annual report on cancer statistics, released on Wednesday, noted that the death rate had dropped steadily over 26 years, from 1991 to 2017. The largest single-year decline ever reported, when the rate fell 2.2 percent, occurred from 2016 to 2017.

. . .

Experts attributed the decline in mortality to reduced smoking rates and to advances in lung cancer treatment. New therapies for melanoma of the skin have also helped extend life for many people with metastatic disease, or cancer that has spread to other parts of the body.

For the full story, see:

Michael Levenson. “Cancer Death Fell Sharply, And Trump Took Credit.” The New York Times (Monday, January 13, 2020): A12.

(Note: ellipses added.)

(Note: the online version of the story has the date Jan. 12, 2020 and has the title “Trump Took Credit for Lower Cancer Death Rates. Advocates Say Not So Fast.” Where there was a minor wording difference between the print and online versions, the quotation above follows the online version. )

The report from the American Cancer Society, mentioned above, is:

Siegel, Rebecca L., Kimberly D. Miller, and Ahmedin Jemal. “Cancer Statistics, 2020.” CA: A Cancer Journal for Clinicians 70, no. 1 (2020): 7-30.

Coffee Gives Us “More Ideas, More Talk, More Energy, More Time, More Life”

(p. C4) After five centuries, we still have questions about coffee, but we agree on what we need it to do. Most of us drink coffee not because we have a finely calibrated understanding of its role in blocking the adenosine that makes us feel tired and increasing the dopamine that makes us feel good. Instead, we drink coffee because . . . of our bottomless desire for more ideas, more talk, more energy, more time, more life.

For the full commentary, see:

Augustine Sedgewick. “How Coffee Became a Modern Necessity.” The Wall Street Journal (Saturday, April 4, 2020): C4.

(Note: ellipsis added.)

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

Sedgewick’s commentary is related to her book:

Sedgewick, Augustine. Coffeeland: One Man’s Dark Empire and the Making of Our Favorite Drug. New York: Penguin Press, 2020.

Sarilumab Showed “Hint” of Promise for Critically Ill Covid-19 Patients

(p. A10) . . . , preliminary results on treatments with . . . sarilumab, marketed as Kevzara and made by Regeneron and Sanofi, indicate that it does not help patients who are hospitalized but not using ventilators.

. . .

The patients fell into two groups — “severe,” meaning they required oxygen but did not need a ventilator or so-called high flow oxygen, and “critical,” those who needed a ventilator, high flow oxygen or were in intensive care.

. . .

The results for the critically ill patients are not conclusive but there is a hint that such patients may be helped, so the study will continue with only critically ill patients. More than 600 have been enrolled. Results are expected in early June [2020].

For the full story, see:

Gina Kolata. “Drug Shows Slim Promise For Critical Covid Cases.” The New York Times (Tuesday, April 28, 2020): A10.

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

(Note: the online version of the story has the date April 27, 2020, and has the title “Arthritis Drug Did Not Help Seriously Ill Covid Patients, Early Data Shows.”)

Paul Marks Purged Old Guard in Order to Recruit New Talent for His Vision of Cancer Research

One important question, not addressed in the obituary quoted below, is the extent to which Marks’s vision for cancer research was farsighted and the extent to which it was misguided. Another important related issue is Marks’s role in support of Nixon’s centrally planned war on cancer.

(p. B11) Paul A. Marks, who transformed Memorial Sloan Kettering Cancer Center into one of the world’s leading institutions for research and treatment of cancer, died on April 28 at his home in Manhattan. He was 93.

. . .

Memorial Sloan Kettering today is very different from the institution Dr. Marks joined in 1980 as president and chief executive. It was still reeling from a scientific scandal in the 1970s involving crudely falsified data. It was also behind the times, focused more on surgical interventions than on the developing frontiers of biological science.

“Frankly, it was an institution that really needed surgery from top to bottom, and Marks was the right guy,” James Rothman, chairman of the Yale School of Medicine’s department of cell biology, said in a phone interview.

. . .

The timing was ideal, said Richard Axel, a neuroscientist and molecular biologist in the department of neuroscience at Columbia University Medical Center. Dr. Marks, he said, energized the institution to pursue the alterations in DNA that cause tumors, doing so at the very moment that it was becoming possible “to truly study DNA, to pet it, to clone it, to determine its sequence.”

What followed was a purge of much of the institution’s old guard, with attendant turmoil and alienation for many of those involved. Dr. Marks instituted a tenure system with a tough review process, and dozens of scientists left between 1982 and 1986. A 1987 article about Dr. Marks in The New York Times Magazine noted that “there are researchers who call Marks ‘Caligula,’ ‘Attila the Hun’ or simply ‘the monster.’”

The article described a scene in his laboratory during his Columbia days when Dr. Marks “grabbed a man by the throat and dragged him across a table.” His wife, Joan Marks, then head of graduate programs at Sarah Lawrence College in Bronxville, N.Y., said in the article, “He can be brutal,” adding, “He really doesn’t understand why people don’t work 97 hours a day, and why they don’t care as much as he cares.”

In his memoir, “On the Cancer Frontier: One Man, One Disease, and a Medical Revolution” (2014, with the former Times reporter James Sterngold), Dr. Marks said he had been embarrassed to see the incident recounted in the article. While he didn’t deny that it had happened, he said that he had actually grabbed the man by both arms, not the throat, and shaken him.

For all of the sharpness of his elbows, Dr. Rothman of Yale said, there was also charm. Dr. Marks, he said, “projected at once a kind of a deep warmth and, at the same time, a formidable aspect.”

Dr. Marks was known for a sharp eye in recruiting talent. “He had an uncanny ability to attract these great scientists from all over the nation,” said Joan Massagué, the director of the Sloan Kettering Institute, the institution’s experimental research arm.

For the full obituary, see:

John Schwartz. “Paul Marks, 93, Administrator Who Pushed Memorial Sloan Kettering to Top-Tier Status.” The Wall Street Journal (Thursday, May 7, 2020): B11.

(Note: ellipses added.)

(Note: the online version of the obituary was updated May 6, 2019 and has the title “Paul Marks, Who Pushed Sloan Kettering to Greatness, Dies at 93.”)

Marks’s memoir, mentioned above, is:

Marks, Paul, and James Sterngold. On the Cancer Frontier: One Man, One Disease, and a Medical Revolution. New York, NY: PublicAffairs, 2014.

Physicians Fighting Covid-19 Use Social Media “to Share Improvised Solutions”

(p. A9) In mid-March [2020], as U.S. hospitals scrambled for ventilators to treat a surge of coronavirus cases, a Vermont pulmonologist proposed a different treatment on a blog popular with emergency-medicine doctors.

Joshua Farkas observed in the post on the EMCrit blog that many Covid-19 patients seemed to benefit from less-invasive alternatives to help their breathing, including pressure therapy used to treat sleep apnea—sometimes referred to as CPAP, for continuous positive airway pressure.

. . .

The post helped galvanize an emerging theory about the treatment of Covid-19 patients, which in recent weeks has taken hold in U.S. hospitals. In New York City, where ventilators are in perilously short supply, doctors say they have since embraced CPAP and other treatments to improve breathing in Covid-19 patients.

The shift is one example of how health-care workers are writing the playbook for treating coronavirus patients on the fly, knowing they can’t wait for peer-reviewed articles or studies in established medical journals. Instead they are tapping into social media, podcasts, inside-baseball medical blogs and text-message groups to share improvised solutions to supply shortages and patient care, forcing hospitals to quickly re-evaluate their practices.

“This has been a rapidly evolving process,” said Dr. Farkas, who has treated Covid-19 patients in the intensive-care unit at the University of Vermont in Burlington. “As we struggle with how to treat a disease that so recently was totally unknown, this rapid exchange and updating of information is crucial.”

. . .

Last week, Michelle Romeo, a chief emergency-medicine resident at NYU Langone and Bellevue hospital in Manhattan, tweeted photos of a jury-rigged breathing device involving a mask used for BiPAP—an airway pressure therapy similar to CPAP.

At Mount Sinai Hospital in Manhattan, pulmonologists worked with the hospital’s sleep lab to figure out a way to use BiPAP machines like a ventilator. The result was posted on Reddit, and got “all kinds of different responses,” said Valerie Burgos-Kneeland, a registered nurse in the hospital’s Medical Intensive Care Unit. “It’s kind of been an opportunity for people to get creative.”

For the full story, see:

Rebecca Davis O’Brien. “Doctors Improvise, Share Treatments.” The Wall Street Journal (Friday, April 10, 2020): A9.

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

(Note: the online version of the story has the date April 9, 2020, and has the title “Doctors Are Improvising Coronavirus Treatments, Then Quickly Sharing Them.”)

Drugs Targeting Cytokines Tried Against Covid-19

(p. A9) Doctors have used the term “cytokine storm” to describe an overactive immune response triggered by external pathogens such as bacterial and viral infections.

Proteins called cytokines are part of the immune system’s arsenal for fighting disease. When too many are released into the bloodstream too quickly, however, it can have disastrous results, including organ failure and death.

As with other diseases, it is a mystery why cytokine storms are experienced by some but not all Covid-19 patients, doctors say. Genetics may be a factor.

. . .

Drugs called corticosteroids can be used to treat patients with cytokine storms, but studies are mixed on their effectiveness, with some studies indicating that Covid-19 patients may be at a higher risk of death when treated with steroids. Some doctors are reluctant to use steroids because they broadly dampen the immune response, which is risky in patients fighting infections.

Drugs targeting specific cytokines rather than the entire immune system may be more effective, doctors say.

Among the most promising targeted treatments, doctors say, is Roche’s rheumatoid-arthritis drug tocilizumab, which is marketed under the brand name Actemra. The drug was approved in 2017 to treat cytokine storms caused by cancer treatments known as CAR-T cell therapies.

For the full story, see:

Jared S. Hopkins, Joseph Walker. “Haywire Immune Reaction Linked to Most Severe Cases.” The Wall Street Journal (Friday, April 10, 2020): A1 & A9.

(Note: ellipsis added.)

(Note: the online version of the story has the date April 9, 2020, and has the title “Haywire Immune Response Eyed in Coronavirus Deaths, Treatment.”)

“Real World Evidence” on Effectiveness of Experimental Drugs Can Be Extracted From Electronic Health Records

(p. A7) . . . analysis of compassionate-use data, about the experimental drug remdesivir from Gilead Sciences Inc. published in the New England Journal of Medicine, came under criticism. Scientists pointed out that the Covid-19 patients received the drug in centers around the world where care may have differed, data on some patients was incomplete and there was no comparison group.

That study’s first author, Jonathan Grein, of Cedars-Sinai Medical Center in Los Angeles, said given how little is known about the coronavirus and how to treat it, “I think at this point any information is potentially helpful.” He said the study, funded by Gilead Sciences, noted the findings were limited and preliminary. “It is a starting point, an opportunity to aggregate our initial experiences,” he said.

. . .

The FDA . . . has worked closely with companies trying to extract “real world evidence” about patients’ experiences with new or experimental drugs from sources such as electronic health records.

For the full story, see:

Amy Dockser Marcus. “Hundreds Get Plasma in National Study.” The Wall Street Journal (Wednesday, April 22, 2020): A7.

(Note: ellipses added.)

(Note: the online version of the story has the date April 21, 2020, and has the title “Hundreds Receive Plasma From Recovered Coronavirus Patients in National Study.”)