World Child Mortality Cut in Half

(p. A1) Two decades ago, nearly 10 million children did not live to see a 5th birthday.

By 2017, that number — about 1 in every 16 children — was nearly cut in half, even as the world’s population increased by more than a billion people.

. . .

From 2000 to 2017, all but one of the 97 low-to-middle-income countries that account for the vast majority of deaths of young children lowered their child mortality rates, according to a report released Tuesday [Sept. 17, 2019] by the Bill and Melinda Gates Foundation, along with a research team at the Institute for Health Metrics and Evaluation at the University of Washington, led by Stephen Lim, the institute’s senior director of science and engineering.

For the full story, see:

Alicia Parlapiano, Josh Katz, and Margot Sanger-Katz. “Fewer of the World’s Children Are Dying, but Many Remain at Risk.” The New York Times (Wednesday, Sept. 18, 2019): A1 & A12.

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

(Note: the online version of the story has the date Sept. 17, 2019, and has the title “Almost Everywhere,Fewer Children Are Dying.” In the last paragraph quoted above, the wording follows the online version, and not the print version. The order of the authors’ names in the online version is: Josh Katz, Alicia Parlapiano and Margot Sanger-Katz.)

Genetic Diversity Limits Number of Patients for Large Randomized Trials

(p. A9) . . . in the era of personalized medicine, where care can be tailored to a person’s genetic make-up and doctors analyze a patient’s DNA to figure out treatments, big trials are falling out of favor.

. . .

To Ursula Matulonis, who treats ovarian cancer and other women’s cancers at Dana-Farber Cancer Institute in Boston, the debate over trial size has a special urgency: Many of her patients are desperately sick.

“You can’t wait years to get these medications approved. What we are dealing with are women with cancers and their lifespans are limited. They need medications and they need them now, and they are not looking to wait for five years,” says Dr. Matulonis, chief of gynecologic oncology.

That is why flexibility in a trial’s size is crucial, she contends. “As we become more genetically astute, and understand a type of cancer better, I think those large randomized trials will be hard to do. There won’t be that many patients,” that fit into one big group, she added.

One of her patients, Janet Sheehan, is grateful for the small clinical trial she has taken part in for the past five years. Ms. Sheehan, a 63-year-old nurse near Boston, was diagnosed with advanced ovarian cancer a dozen years ago. It has come back three times, and at one point she learned that she had a mutation in the BRCA1 gene which indicates a strong predisposition to breast and ovarian cancer. Dana-Farber suggested in 2013 that she go on a randomized 90-person trial for a drug named Olaparib that showed promise among women with a BRCA1 gene mutation.

She has been taking capsules twice a day and going for check-ups every 28 days since then. Despite side-effects, she has been able to work and carry on. “I have seen my children [grow] and I have seen grandchildren I didn’t have then,” she says. Ms. Sheehan was on a randomized trial where both groups of patients received treatment with Olaparib. One group got the drug only, the other received Olaparib in combination with another drug, her doctor said, adding, “there was no placebo.”

In remission, Ms. Sheehan has become a fan of small trials that offer women such as herself options. She also is a realist. If Olaparib fails, she hopes other trials now going on may yield treatments for her.

For the full commentary, see:

Lucette Lagnado. “Is the Big Clinical Trial Obsolete? The New York Times (Wednesday, May 30, 2018): A9-A10.

(Note: ellipses added; bracketed word in original.)

(Note: the online version of the commentary has the date May 29, 2018, and has the title “Are Big Clinical Trials Relevant? Researchers Disagree.” The sentence that starts with “In remission,” was in the online version, but not the print version. )

How Drinking Coffee Makes Us Younger and More Open-Minded

(p. C2) . . . , if a baby monkey heard a new sound pattern many times, her neurons (brain cells) would adjust to respond more to that sound pattern. Older monkeys’ neurons didn’t change in the same way.

At least part of the reason for this lies in neurotransmitters, chemicals that help to connect one neuron to another. Young animals have high levels of “cholinergic” neurotransmitters that make the brain more plastic, easier to change. Older animals start to produce inhibitory chemicals that counteract the effect of the cholinergic ones. They actually actively keep the brain from changing.

. . .

In the new research, Jay Blundon and colleagues at St. Jude Children’s Research Hospital in Memphis, Tenn., tried to restore early-learning abilities to adult mice. As in the earlier experiments, they exposed the mice to a new sound and recorded whether their neurons changed in response. But this time the researchers tried making the adult mice more flexible by keeping the inhibitory brain chemicals from influencing the neurons.

In some studies, they actually changed the mouse genes so that the animals no longer produced the inhibitors in the same way. In others, they injected other chemicals that counteracted the inhibitors. (Caffeine seems to work in this way, by counteracting inhibitory neurotransmitters. That’s why coffee makes us more alert and helps us to learn.)

In all of these cases in the St. Jude study, the adult brains started to look like the baby brains.

For the full commentary, see:

Alison Gopnik. “MIND & MATTER; How to Get Old Brains to Think Like Young Ones.” The New York Times (Saturday, July 8, 2017): C2.

(Note: ellipses added.)

(Note: the online version of the commentary has the date July 7, 2017, and has the same title as the print version.)

The article co-authored by Jay Blundon and mentioned above,is:

Blundon, Jay A., Noah C. Roy, Brett J. W. Teubner, Jing Yu, Tae-Yeon Eom, K. Jake Sample, Amar Pani, Richard J. Smeyne, Seung Baek Han, Ryan A. Kerekes, Derek C. Rose, Troy A. Hackett, Pradeep K. Vuppala, Burgess B. Freeman, and Stanislav S. Zakharenko. “Restoring Auditory Cortex Plasticity in Adult Mice by Restricting Thalamic Adenosine Signaling.” Science 356, no. 6345 (June 30, 2017): 1352-56.

Manic Energy from Bipolar Disorder May Enable “Heights of Success”

(p. A17) Dr. Ronald R. Fieve, who was a pioneer in the prescription of lithium to treat mania and other mood disorders — while avowing that some gifted individuals, like Abraham Lincoln, Theodore Roosevelt and Winston Churchill, might have benefited from being bipolar — died on Jan. 2 [2018] at his home in Palm Beach, Fla.

. . .

He cited estimates that as many as one in 15 people experienced a manic episode during their lifetimes, and that bipolar disorder — characterized by swings from elation, hyperactivity and a decreased need for sleep to incapacitating depression — was often misclassified as schizophrenia or other illnesses, or undiagnosed altogether.

He cautioned, however, that some highly creative, exuberant and energetic people have derived benefits from the condition because they have what he called “a hypomanic edge.”

“I have found that some of the most gifted individuals in our society suffer from this condition — including many outstanding writers, politicians, business executives and scientists — where tremendous amounts of manic energy have enabled them to achieve their heights of success,” Dr. Fieve told a symposium in 1973.

But without proper treatment, he said, those individuals afflicted with manic depression “more often than not either go too ‘high’ or suddenly crash into a devastating depression that we only hear about after a successful suicide.”

In contrast to antidepressant drugs or electroshock treatments, he said, regular doses of lithium carbonate appeared to stabilize mood swings without cramping creativity, memory or personality.

. . .

Before it was approved to treat depression, lithium was found in the late 1940s to be potentially unsafe as a salt substitute. But Dr. Fieve pointed out that lithium had been found in natural mineral waters prescribed by Greek and Roman physicians 1,500 years earlier to treat what were then called manic insanity and melancholia.

For the full obituary, see:

Sam Roberts. “Dr. Ronald Fieve, Pioneer In Lithium, Is Dead at 87.” The New York Times (Wednesday, Jan. 17, 2018): A17.

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

(Note: the online version of the obituary has the date Jan. 12, 2018, and has the title “Dr. Ronald Fieve, 87, Dies; Pioneered Lithium to Treat Mood Swings.”)

“If You Do No Harm, Then You Do No Harm to the Cancer, Either”

(p. B16) James F. Holland, a founding father of chemotherapy who helped pioneer a lifesaving drug treatment for pediatric leukemia patients, died on Thursday [March 22, 2018] at his home in Scarsdale, N.Y.

. . .

“Patients have to be subsidiaries of the trial,” he told The New York Times in 1986. “I’m not interested in holding patients’ hands. I’m interested in curing cancer.”

He acknowledged that some patients become guinea pigs, and that they sometimes suffer discomfort in the effort to eradicate tumors, but he said that even those who die provide lessons for others who will survive.

“If you do no harm,” Dr. Holland said, “then you do no harm to the cancer, either.”

. . .

Dr. Holland acknowledged that while experimenting with drug treatment sometimes amounts to trial and error, the primary killer is typically the disease itself.

“The thing to remember,” he said, “is that the deadliest thing about cancer chemotherapy is not the chemotherapy.” Continue reading ““If You Do No Harm, Then You Do No Harm to the Cancer, Either””

To Be Dangerous with Crispr Takes a Lot of Genetics Knowledge

(p. A11) “I frankly have been flabbergasted at the pace of the field,” says Jennifer Doudna, a Crispr pioneer who runs a lab at the University of California, Berkeley. “We’re barely five years out, and it’s already in early clinical trials for cancer. It’s unbelievable.”

. . .

Scientists have fiddled with genes for decades, but in clumsy ways.

. . .

Crispr is much more precise, as Ms. Doudna explains in her new book, “A Crack in Creation.” It works like this: An enzyme called Cas9 can be programmed to latch onto any 20-letter sequence of DNA. Once there, the enzyme cuts the double helix, splitting the DNA strand in two. Scientists supply a snippet of genetic material they want to insert, making sure its ends match up with the cut strands. When the cell’s repair mechanism kicks in to fix the cut, it pastes in the new DNA.

. . .

A . . . Crispr worry is that it makes DNA editing so easy anybody can do it. Simple hobby kits sell online for $150, and a community biotech lab in Brooklyn offers a class for $400. Jennifer Lopez is reportedly working on a TV drama called “C.R.I.S.P.R.” that, according to the Hollywood Reporter, “explores the next generation of terror: DNA hacking.”

Ms. Doudna provides a bit of assurance. “Genetics is complicated. You have to have quite a bit of knowledge, I think, to be able to do anything that’s truly dangerous,” she says. “There’s been a little bit of hype, in my opinion, about DIY kits and are we going to have rogue scientists—or even nonscientists—randomly doing crazy stuff. I think that’s not too likely.”

For the full interview, see:

Peterson, Kyle, interviewer. “THE WEEKEND INTERVIEW; The Gene Editors Are Only Getting Started; Would you eradicate malaria-carrying insects? Change your baby’s DNA? Scientists soon may have the power to do both.” The Wall Street Journal (Saturday, July 8, 2017): A11.

(Note: ellipses added.)

(Note: the online version of the interview has the date July 7, 2017, and the same title as the print versio.)

Doudna’s book, mentioned above, is:

Doudna, Jennifer A., and Samuel H. Sternberg. A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution. New York: Houghton Mifflin Harcourt, 2017.

Mandated Long Clinical Trials Favor Trivial Incremental Drugs and Impede Magic Bullet Cures

(p. B1) AstraZeneca PLC’s new cancer research chief, José Baselga, wants the company to prioritize early-stage cancers over advanced disease when developing new cancer drugs. If successful, his unorthodox strategy could reap rewards for both patients—the potential to cure cancer is much greater when it is treated early—and company coffers.

The approach turns the tried-and-tested model of cancer drug development on its head. Typically, drug companies aim their new cancer drugs at patients with advanced forms of the disease who have exhausted other treatment options. Of the more than 30 new drugs for solid tumors approved for sale in the U.S. since the start of 2014, just two targeted early cancer.

That is largely because there is a clear-cut case for testing new drugs on patients with advanced cancer, as they don’t have other options. What’s more, measuring a new medicine’s effect in advanced cancer is straightforward: a meaningful extension in survival can usually be measured in months. Such patients are also often more willing to try experimental drugs, and regulators have smoothed the path for treatments that show they can prolong lives by delaying tumor growth in advanced cancer.

. . .

(p. B5) “One thing with early stage disease, you have to be able to cure patients,” said Daniel Chen, who spent more than a decade running cancer drug development projects at Roche Holding AG. “The majority of cancer drugs delay cancer growth, they don’t cure patients.” Dr. Chen is now chief medical officer at biotech startup IGM Biosciences Inc.

Running clinical trials could also be difficult, as it would involve persuading patients to try experimental drugs when they might already be cured.

Another challenge is measuring the drug’s effectiveness. In patients whose cancer is diagnosed and treated early, it would take years to determine whether a new drug meaningfully extended survival, making for very long clinical trials.

For the full story, see:

Denise Roland. “Drug Giant Tests Bold Tactic to Battle Cancer.” The Wall Street Journal (Tuesday, May 28, 2019): B1 & B5.

(Note: ellipsis added.)

(Note: the online version of the story has the date May 27, 2019, and has the title “Drug Giant Tries New Tactic to Fight Cancer.”)

IBM’s Watson AI Platform Is Not Curing Cancer

(p. B1) Can Watson cure cancer?

That’s what International Business Machines Corp. IBM 0.03% asked soon after its artificial-intelligence system beat humans at the quiz show “Jeopardy!” in 2011. Watson could read documents quickly and find patterns in data. Could it match patient information with the latest in medical studies to deliver personalized treatment recommendations?

“Watson represents a technology breakthrough that can help physicians improve patient outcomes,” said Herbert Chase, a professor of biomedical informatics at Columbia University, in a 2012 IBM press release.

Six years and billions of dollars later, the diagnosis for Watson is gloomy. Continue reading “IBM’s Watson AI Platform Is Not Curing Cancer”

New Opiod Regulations Make Life Harder for Those in Severe Pain

(p. C4) There’s a great deal in “Dopesick” that’s incredibly bleak, but the most chilling moment for me was a quote from one of Macy’s journalist friends. Synthetic opioids had allowed this woman, despite a severe curvature of her spine, to lead an active life without risky surgery. She resented new rules that made it more onerous for her to get the pills. “My life,” she told Macy, “is not less important than that of an addict.”

For the full review, see:

Jennifer Szalai. “BOOKS OF THE TIMES; A Ground-Level Look At the Opioid Epidemic.” The New York Times (Thursday, July 26, 2018): C1 & C4.
(Note: ellipsis added.)

(Note: the online version of the review has the date July 25, 2018, and has the title “BOOKS OF THE TIMES; ‘Dopesick’ Traces the Opioid Crisis, From Beginning to Blow Up.”)

The book under review, is:

Macy, Beth. Dopesick: Dealers, Doctors, and the Drug Company That Addicted America. New York: Little, Brown and Company, 2018.

Obamacare Architect Ezekiel Emanuel “Will Be Satisfied” with 75 Years

(p. A13) Ezekiel Emanuel, a 61-year-old oncologist, bioethicist and vice provost at the University of Pennsylvania, says he will be satisfied to reach 75. By then, he believes, he will have made his most important contributions, seen his kids grown, and his grandkids born. After his 75th birthday, he won’t get flu shots, take antibiotics, get screened for cancer or undergo stress tests. If he lives longer, that’s fine, he says. He just won’t take extra medical steps to prolong life.

“People want to live to 100 but your horizon of what life is becomes much, much narrower,” he says.

For the full story, see:

Clare Ansberry. “TURNING POINTS; The Advantages—and Limitations—of Living to 100.” The New York Times (Tuesday, May 21, 2019): A13.

(Note: the online version of the story has the date May 20, 2019, and has the same title as the print version.)

Fire Marshall Regulations Reduce Use of Hospital Hand Sanitizers, Helping Spread Dangerous Bacteria

(p. A11) With the use of alcohol-based hand sanitizer — often more effective and convenient than soap and water — it’s far easier to keep hands clean than clothing.

But the placement of alcohol-based hand sanitizer for health workers isn’t as convenient as it could be, reducing its use. The reason? In the early 2000s, fire marshals began requiring hospitals to remove or relocate dispensers because hand sanitizers contain at least 60 percent alcohol, making them flammable.

Fire codes now limit where they can be placed — a minimum distance from electrical outlets, for example — or how much can be kept on site.

Hand sanitizers are most often used in hallways, though greater use closer to patients (like immediately before or after touching a patient) could be more effective.

. . .

Although there have been fires in hospitals traced to alcohol-based hand sanitizer, they are rare. Across nearly 800 American health care facilities that used alcohol-based hand sanitizer, one study found, no fires had occurred. The World Health Organization puts the fire risk of hand sanitizers as “very low.”

For the full commentary, see:

Frakt, Austin. “Lab Coat Can Host Dangerous Bacteria.” The New York Times (Tuesday, April 30, 2019): A11.

(Note: ellipsis added.)

(Note: the online version of the commentary has the date April 29, 2019, and has the title “Why Your Doctor’s White Coat Can Be a Threat to Your Health.” The last two sentences quoted above, occur in the online, but not the print, version of the article.)

The the rarity of hand sanitizer hospital fires was documented in:

Boyce, John M., and Michele L. Pearson. “Low Frequency of Fires from Alcohol-Based Hand Rub Dispensers in Healthcare Facilities.” Infection Control & Hospital Epidemiology 24, no. 8 (Aug. 2003): 618-19.