Faced With a Drug Shortfall, Doctors Scramble to Treat Children With Cancer

A critical drug that serves as the backbone of treatment for most childhood cancers, including leukemias, lymphomas and brain tumors, has become increasingly scarce, and doctors are warning that they may soon be forced to consider rationing doses.

Persistent shortages of certain drugs and medical supplies have plagued the United States for years, but physicians say the loss of this medication, vincristine, is uniquely problematic, as there is no appropriate substitute.

“This is truly a nightmare situation,” said Dr. Yoram Unguru, a pediatric oncologist at the Herman and Walter Samuelson Children’s Hospital at Sinai in Baltimore. “Vincristine is our water. It’s our bread and butter. I can’t think of a disease in childhood cancer that doesn’t use vincristine.”

Shortages of the chemotherapy drug, which is on back order, will likely affect children throughout the country, he said, obligating physicians to make difficult decisions.

“There is no substitution for vincristine that can be recommended,” Dr. Unguru said. “You either have to skip a dose or give a lower dose — or beg, borrow or plead.”

Vincristine is one of the drugs used to manage acute lymphoblastic leukemia, the most common childhood cancer. Vincristine is also an important agent in the treatment of Wilms tumor, a rare kidney cancer that mostly affects children.

The Children’s Oncology Group, a collaboration of researchers at hospitals and cancer centers, has made recommendations for altering clinical trial treatment protocols involving vincristine, including checking the hospital pharmacy’s supply before trial enrollment; considering using half the dose if the full amount is not available; skipping doses during the maintenance phase of treatment; or in some cases omitting the drug altogether.

“We are all devastated,” said Dr. Michael Link, a pediatric oncologist at the Stanford University School of Medicine and a former president of the American Society of Clinical Oncology.

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Without vincristine, many children with acute lymphoblastic leukemia will still be cured, “but this is a difficult disease to treat in general, and with one hand tied behind your back, it makes it much more difficult,” Dr. Link said.

Until earlier this year, there were two suppliers of vincristine: Pfizer and Teva Pharmaceutical Industries. In July, Teva made a “business decision to discontinue the drug,” according to the Food and Drug Administration.

Since then, Pfizer has been the sole supplier, and the company lately has experienced manufacturing troubles.

“Pfizer has experienced a delay, and we are working closely with them and exploring all options to make sure this critical cancer drug is available for the patients who need it,” the F.D.A. said in a brief statement.

Jessica Smith, a spokeswoman for Pfizer, said the company would expedite additional shipments of the drug over the next few weeks to “support three to four times our typical production output,” in an effort to make up for Teva’s withdrawal from the market.

Teva did not return numerous calls for comment.

The American Society of Health-System Pharmacists tracks more than 200 medications in short supply, among them everyday necessities like antibiotics, dextrose and several vaccines, including the rabies vaccine.

The shortages tend disproportionately to involve older, generic injectable drugs, which are difficult to manufacture but command low prices, a combination that often leads manufacturers to get out of the business of making them.

Those withdrawals may leave just one or two companies continuing to supply the drugs in the United States. Their factories must run at peak production to turn a profit and provide a sufficient supply, but the moment there is a quality problem and production shuts down, shortages follow.

Generic drugs play a vital role in the treatment of cancer. Of the 19,000 American children and adolescents younger than 19 who develop cancer every year, 85 percent are cured. But treatment hinges largely on inexpensive, older drugs like vincristine, which have been off patent for decades.

Shortages cause disruption in treatment. According to a survey published in the New England Journal of Medicine in 2013, 83 percent of oncologists said that they were unable to prescribe the chemotherapy agent they wanted to use because of a shortage, and that they had to substitute a different drug or delay treatment.

Dr. Unguru said the survival rate for acute lymphoblastic leukemia, which accounts for nearly one-quarter of all cancers in children, is nearly 90 percent. But eight of the 10 drugs most commonly used to treat it have been unavailable at times over the past decade.

A drug shortages task force established in 2018 by the former F.D.A. Commissioner Scott Gottlieb is supposed to submit a report with findings and recommendations to Congress by the end of the year.

“This shouldn’t be happening in the United States,” said Dr. Peter Adamson, chair of the Children’s Oncology Group.

“It’s hard enough for any family having a kid with cancer, and having a child with cancer likely to be cured except we can’t give them the drug is beyond the imagination. How can we do that to families?”

Rx for Doctors: Stop With the Urine Tests

It’s such a common routine in a doctor’s office or clinic or hospital that patients tend to comply without thinking: Step on the scale, roll up your sleeve for the blood pressure cuff, urinate into a cup.

But that last request should prompt questions, at the least. The urine test is the first step into what’s sometimes called “the culture of culturing.”

In patients who have none of the typical symptoms of a urinary tract infection — no painful or frequent urination, no blood in the urine, no fever or lower abdominal tenderness — lab results detecting bacteria in the urine don’t indicate infection and thus shouldn’t trigger treatment.

Older people, and nursing home residents in particular, often have urinary systems colonized by bacteria; they will have a positive urine test almost every time, but they’re not sick.

Yet such test results, signifying what’s known in doctor-talk as asymptomatic bacteriuria, frequently lead to unnecessary treatment with antibiotics. Public health leaders and researchers have battled for years to persuade providers to stop reaching for their prescription pads every time a urine test comes back positive.

They have been only modestly successful. A recent study in 46 Michigan hospitals, for instance, found that of 2,733 patients with asymptomatic bacteriuria (average age: 77), almost 83 percent received a full course of antibiotics. The odds of this overtreatment rose 10 percent with each decade of age.

“We now recognize that there’s a strong cognitive bias,” said Dr. Christine Soong, head of hospital medicine at Sinai Health System in Toronto and co-author of a recent editorial on the subject in JAMA Internal Medicine. “Once a clinician sees bacteria in the urine, the reflex is, you can’t ignore it. You want to treat it.”

Now, the campaign has changed from trying to prevent needless treatment to trying to curtail the testing that prompts it. If concerned doctors can’t dissuade their colleagues from treating these non-infections, they’re trying to discourage them from ordering urine tests in the first place.

The very reserved headline on Dr. Soong’s editorial was: “De-adoption of Routine Urine Culture Testing — A Call to Action.” It probably should have been: “For Crying Out Loud, Stop With the Pee in the Cup.”

What’s raising this issue once more are the latest guidelines from the United States Preventive Services Task Force, the independent expert panel that reviews medical evidence and advises on prevention and screenings.

The task force concluded last month that for virtually everyone except pregnant women, screening for and treating asymptomatic bacteriuria provides no benefit and has potential harms. This didn’t come as news — the task force reached essentially the same determination in 1996, in 2004 and in 2008.

The Infectious Diseases Society of America, which updated its recommendations this spring, also cautioned against screening and treating, except for pregnant women and patients about to undergo invasive urologic procedures. The Choosing Wisely campaign has similarly weighed in against routine urine testing in older adults.

Why this strenuous effort? All of it is aimed at reducing the persistent overuse of antibiotics.

They’re lifesaving drugs, useful when patients actually have urinary or other bacterial (not viral) infections. But studies have shown that with asymptomatic bacteriuria, withholding antibiotics doesn’t endanger patients. Providing the drugs, however — especially to older people — definitely does pose risks.

“The public thinks it’s good to take an antibiotic,” said Dr. Heidi Wald, a geriatrician and chief quality and safety officer at SCL Health in Denver. “People don’t understand the risks of overuse.”

Antibiotics can cause side effects ranging from nausea and rashes to impaired kidney function and interactions with other commonly used drugs, like cardiac medications and antidepressants.

“The problem I worry about most in the frail elderly is C. difficile,” Dr. Wald said, referring to a virulent, hard-to-eradicate infection that has rampaged through the Medicare population.

Antibiotics affect the human microbiome, wiping out the protective microbes in the gastrointestinal tract and increasing people’s vulnerability to C. difficile, which the Centers for Disease Control and Prevention has called an “urgent threat.”

In the Michigan hospital study, patients treated for asymptomatic bacteriuria fared no better on a variety of measures than those who weren’t treated. “But they stayed in the hospital a day longer,” said Dr. Lindsay Petty, the study’s lead author and an infectious disease specialist at the University of Michigan.

She theorized that their doctors were awaiting urine culture results. The patients, meanwhile, faced additional risks of disrupted sleep, infections, physical deconditioning from time spent in bed and other hazards, while generating needlessly higher hospital bills.

Beyond its effect on individuals, “antibiotic resistance is one of the greatest public health crises of our time,” Dr. Petty said. When bacteria develop resistance to overused drugs, doctors are left with fewer and riskier weapons with which to fight infections.

Because U.T.I.s occur so commonly — 40 percent to 60 percent of women, in whom they’re far more common than in men, will experience at least one in their lifetimes — it’s easy for doctors and patients to engage in so-called scapegoating, blaming a supposed U.T.I. for problems that may have little to do with the urinary tract.

In older patients, particularly, confusion and hospital delirium can lead family members to urge doctors to order urine cultures, especially when dementia makes it difficult for patients to describe their symptoms.

But “the idea of attributing delirium to a U.T.I. is losing ground,” Dr. Wald said. When older patients grow confused, “maybe they’re dehydrated,” she said. “Maybe it’s a new medication.” Hospitalization itself might be to blame.

Doctors understand, after vigorous education efforts, that they need to prescribe fewer antibiotics; virtually every hospital has an antimicrobial stewardship program aimed at that goal. “This isn’t a knowledge gap,” Dr. Soong said.

But since many doctors can’t seem to overlook positive tests, even in asymptomatic patients — fearful, perhaps, of missing an infection — health care systems are working to curb their impulse to treat.

Some organizations have created pop-up alerts in electronic records when health care professionals attempt to order urine tests, reminding them of the proper criteria.

At Dr. Soong’s hospital, withholding the results of urine cultures, unless doctors actually called the microbiology lab to request them, reduced prescriptions for asymptomatic bacteriuria to 12 percent from 48 percent of non-catheterized patients, with no loss of safety.

“The extra step of having the clinician call eliminated a lot of frivolous testing,” Dr. Soong said.

Similarly, another Toronto emergency room reported success using containers with a preservative, allowing urine specimens to be held at room temperature for 48 hours, processed only at a doctor’s request. That two-step approach cut antibiotic prescriptions for emergency room patients in half.

There’s a role here for patients and families, as well. What if we asked why we were being asked to urinate into a cup?

“Asking further questions is always appropriate,” Dr. Petty said. “’Why do you think I need this test? What would you do with the results?’”

(Hint: “It’s just routine” is not a good answer. “The symptoms you’ve described could mean a urinary tract infection” is a better one.)

“Such questions should be welcome,” Dr. Petty said. “It’s a way for patients to protect themselves.”

The New Makers of Plant-Based Meat? Big Meat Companies

Beyond Meat and Impossible Foods, scrappy start-ups that share a penchant for superlatives and a commitment to protecting the environment, have dominated the relatively new market for vegetarian food that looks and tastes like meat.

But with plant-based burgers, sausages and chicken increasingly popular and available in fast-food restaurants and grocery stores across the United States, a new group of companies has started making meatless meat: the food conglomerates and meat producers that Beyond Meat and Impossible Foods originally set out to disrupt.

In recent months, major food companies like Tyson, Smithfield, Perdue, Hormel and Nestlé have rolled out their own meat alternatives, filling supermarket shelves with plant-based burgers, meatballs and chicken nuggets.

Once largely the domain of vegans and vegetarians, plant-based meat is fast becoming a staple of more people’s diets, as consumers look to reduce their meat intake amid concerns about its health effects and contribution to climate change. Over the last five months, Beyond Meat’s stock price has soared and Impossible Foods’ deal to provide plant-based Whoppers at Burger King has prompted a wave of fast-food chains to test similar products. Analysts project that the market for plant-based protein and lab-created meat alternatives could be worth as much as $85 billion by 2030.

Now, at supermarkets across the United States, shoppers can find plant-based beef and chicken sold alongside the packaged meat products that generations of Americans have eaten.

“There is a growing demand out there,” said John Pauley, the chief commercial officer for Smithfield, one of the largest pork producers in the country. “We’d be foolish not to pay attention.”

In September, Nestlé released the Awesome Burger, its answer to the meatless patties of Beyond Meat and Impossible Foods. (“We do feel like it’s an awesome product,” a Nestlé spokeswoman said.) Smithfield started a line of soy-based burgers, meatballs and sausages, and Hormel began offering plant-based ground meat.

There are also blended options — a kind of faux fake meat that falls somewhere in the existential gray area between the Beyond Burger and a cut of beef. Tyson is introducing a part-meat, part-plant burger. And Perdue is selling blended nuggets, mixing poultry with “vegetable nutrition” in the form of cauliflower and chickpeas.

Many supporters of meatless alternatives have hailed the new products as a sign that plant-based meat has gained widespread acceptance.


“When companies like Tyson and Smithfield launch plant-based meat products, that transforms the plant-based meat sector from niche to mainstream,” said Bruce Friedrich, who runs the Good Food Institute, an organization that advocates plant-based substitutes. “They have massive distribution channels, they have enthusiastic consumer bases, and they know what meat needs to do to satisfy consumers.”

But the emergence of these meat companies in the plant-based-protein market has also prompted suspicion and unease among some environmental activists, who worry the companies could co-opt the movement by absorbing smaller start-ups, or simply use plant-based burgers to draw attention away from other environmental misdeeds.

“That’s a legitimate concern,” said Glenn Hurowitz, who runs the environmental advocacy organization Mighty Earth. For years, big oil companies bought clean-energy start-ups and essentially shut them down, he noted.

“Making admittedly modest investments in plant-based protein is a legitimately good thing for these businesses to do,” Mr. Hurowitz said, but “it doesn’t entirely balance out all the pollution they’re causing.”

Many of the major food companies began investing in plant-based meat or other vegan alternatives years ago. But the pace has accelerated over the past few months.

“The entire end-to-end process happened in less than a year,” said Justin Whitmore, Tyson’s executive vice president for alternative protein. “We’ll move with the consumer, and we have the capacity that helps us move quickly.”

Veggie burgers have been on store shelves for decades, but companies are only now developing vegetarian products that try to match the experience of eating actual meat, using ingredients such as pea proteins and genetically engineered soy.

Pat Brown, the chief executive of Impossible Foods, has long described the project of creating faux meat as an environmental imperative. “Every aspect of the animal-based food industry is vastly more environmentally disruptive and resource-inefficient than any plant-based system,” he said. Mr. Brown has even set a deadline: Eliminate animal products from the global food supply by 2035.

Not all his new rivals are quite so idealistic. Their goal is not to upend the meat industry in the name of sustainability. It is mainly to make money.

“We’re a meat company, first and foremost,” said Mr. Pauley, the Smithfield official. “We’re not going to apologize for that.”

A spokeswoman for Tyson, the largest meat producer in the United States and the creator of a new line of plant-based chicken nuggets, put it more bluntly. “Right now,” said the spokeswoman, Susan Wassel, “it’s really about the business opportunity.”

Some of the major food companies, including Tyson and Smithfield, have their own sustainability goals. Last month, Nestlé announced a set of environmental initiatives meant to reduce its carbon footprint, including a focus on plant-based products. But as awesome as it may be, the company’s Awesome Burger is not intended to fundamentally change the way we eat.

“We believe in diversity,” said Benjamin Ware, Nestlé’s manager of responsible sourcing. “Products based on animal agents will still have a place in the future, with all the good nutritional aspects.”

That is not necessarily a problem for the future of meatless meat. Any time a plant-based product is added to the grocery aisle is a victory for the movement, many advocates say, regardless of what motivates the company that made it.

“The most important thing to the conventional meat industry is satisfying consumer demand as much as they possibly can,” said Mr. Friedrich, the executive director of the Good Food Institute. “They see that a better technology always replaces an antiquated technology.”


Still, Mr. Brown said he had no plans to collaborate with the major meat producers, whose marketing power and supply-chain infrastructure could help plant-based start-ups reach more customers. He said it was an “encouraging sign” that such companies were investing in plant-based protein, but he emphasized that the success of the movement depended on products that truly recreated the taste and texture of meat.

“If the products are not that great, if they’re just basically repurposed veggie burgers, the harm it does to us is not competition,” he said. “It’s reinforcing consumers’ belief that a plant-based product can’t deliver what a meat lover wants.”

For now, though, it’s too early to tell how consumers will respond to the wider range of options, said Alexia Howard, an analyst at Bernstein who tracks the plant-based meat industry.

“We’ll inevitably see some chipping away of market share,” Ms. Howard said. “But it’s who has the best product that will ultimately survive.”

Beyond Meat is not worried. Ethan Brown, the chief executive (and no relation to his counterpart at Impossible Foods), said the company’s narrow focus on plant-based products would set it apart from other purveyors of meatless meat.

“If Nestlé or Perdue or Tyson think it’s a good idea to buy our product and reverse-engineer it, they’re chasing a ghost,” he said. “We’ve moved on from those models into new models and new iterations.”

As for burgers that combine meat with vegetables, he added, “I haven’t ever heard a consumer tell me they want a blended product.”

Eric Christianson, the chief marketing officer at Perdue, described the company’s investment in blended products as a simple business decision. Because so many companies are producing meatless meat, he said, Perdue decided to focus on a different category — almost-meatless meat.

“There’s a real opportunity to meet the needs of your mainstream consumers — your mom with kids — by bringing the chicken that they love along with the vegetable nutrition that they need,” Mr. Christianson said.

Beyond Meat and Impossible Foods are not interested in such compromises. But in some ways, the plant-based meat start-ups are beginning to resemble major food companies themselves. Beyond Meat is valued at nearly $9 billion, making it about a third the size of Tyson.

“I don’t want to collaborate with them,” Ethan Brown said. “I want to be them.”

Impossible Foods is aiming to expand to other plant-based products, like fishless fish, and make inroads in China. At times, however, the company has struggled to make the transition from start-up to major company. Over the summer, it was unable to meet the rising demand for its patties, leading to shortages at restaurants and forcing staff members to work 12-hour shifts to keep the company’s production facility in Oakland, Calif., running.

Pat Brown, the chief executive, said Impossible Foods had solved that supply-chain problem by collaborating with the OSI Group, a global food processing firm that has worked with big-name brands like McDonald’s and Starbucks. Now, Impossible is poised to quadruple its manufacturing capacity. And the days of marathon factory shifts are over.

“Everybody,” Mr. Brown said, “was happy to see that era come to an end.”

For ‘Erin Brockovich’ Fans, a David vs. Goliath Tale With a Twist

EXPOSUREPoisoned Water, Corporate Greed, and One Lawyer’s Twenty-Year Battle Against DuPontBy Robert Bilott with Tom Shroder

Robert Bilott never set out to be anyone’s hero. He made his living defending chemical companies at an old-line corporate law firm based in Cincinnati when, just a few months shy of making partner, he received a call from a West Virginia farmer who was convinced that the runoff from a nearby DuPont plant was killing his cows. The man had heard Bilott was an environmental lawyer, apparently not understanding that he wasn’t the kind of attorney who brought cases on behalf of aggrieved individuals; instead, Bilott defended companies against such complaints. The caller, however, dropped a magic name: that of Bilott’s grandmother, a beloved figure in his life. The farmer’s case, filed in 1999, and a second, larger class action suit that grew out of it, would dominate the next 20 years of Bilott’s life.

Bilott skillfully tells the story of his epic battle with DuPont and its lawyers in “Exposure,” which lands in bookstores just ahead of a new movie, “Dark Waters,” starring Mark Ruffalo as Bilott and Anne Hathaway as his put-upon wife. The screenplay is based on a 2016 article in The New York Times Magazine (“The Lawyer Who Became DuPont’s Worst Nightmare”), not Bilott’s manuscript. But as you read “Exposure,” it’s easy to imagine scenes in the film version of Bilott’s life. You see the time he was unable to reach his office phone because of the small skyscrapers of boxes and documents that blocked his way, and the time he was rushed to the hospital because of the physical toll the case was taking on his life. In a made-for-Hollywood twist, DuPont bests Bilott by exploiting his pre-existing relationship with a DuPont lawyer and then he bests DuPont’s attorneys through clever legal maneuvers of his own.

If Bilott makes for an unlikely warrior in the battle for safe drinking water, DuPont plays to type as the faceless behemoth that seems to care more about its bottom line than the health of its employees or the tens of thousands of people who lived near the giant plant it operates outside of Parkersburg, W.Va. Because, of course, it wasn’t just the cows that were suffering. Scientists inside the company were concerned enough about a particularly noxious chemical called PFOA — used to manufacture Teflon, among other products — that they began testing DuPont’s workers for exposure. But when the results suggested potential health problems, corporate’s answer was to stop the testing. The ever-thorough Bilott discovers old laboratory animal studies that DuPont and 3M, which manufactured PFOA, had conducted decades earlier. The results showed dogs and monkeys dying from exposure to PFOA, cancer in rats along with birth defects in its unborn. Yet Bilott found no follow-up investigations. At least within the pages of “Exposure,” plausible denial seems to be DuPont’s corporate motto. Ultimately, Bilott discovers dangerously high concentrations of PFOA leaching into the surrounding community’s drinking water.

Bilott is an engaging narrator who breaks our hearts with tales of clients suffering excruciating ailments and amazes us with endless 14-hour days scouring technical reports in search of that one clue that might help him make his case. The naïve corporate defense attorney we meet at the book’s start is gone by the end, and he seems no longer surprised when he realizes that regulators, including the Environmental Protection Agency, are in DuPont’s pocket. By the time he learns PFOA and its chemical cousins are in the blood of virtually all of us, he knows it’s fallen to him to do the E.P.A.’s job. The book ends with him filing a federal class action suit against eight chemical companies on behalf of every American. His education is complete.

Air Pollution Is Linked to Miscarriages in China, Study Finds

ImageChinese women wearing masks to protect against pollution in Beijing in 2015. The government has made inroads against China’s pollution problem. 

CreditKevin Frayer/Getty Images

BEIJING — Researchers in China have found a significant link between air pollution and the risk of miscarriage, according to a new scientific paper released on Monday.

While air pollution is connected to a greater risk of respiratory diseases, strokes and heart attacks, the new findings could add more urgency to Beijing’s efforts to curb the problem, which has long plagued Chinese cities. Faced with a rapidly aging population, the government has been trying to increase the national birthrate, which dropped last year to the lowest level since 1949.

In a study published in the journal Nature Sustainability, scientists from five Chinese universities examined the rate of “missed abortions” in the first trimester, which can occur in up to 15 percent of pregnancies. Also known as silent or missed miscarriages, they happen when the fetus has died but there are no physical signs of miscarriage, leading the parents to mistakenly think the pregnancy is progressing normally.

Zhang Liqiang, a researcher at Beijing Normal University and lead author of the study, said such miscarriages can be “especially traumatic” for expecting parents, who often only find out about them days or weeks later. He also added that they weren’t well studied, part of the reason for the researchers’ focus.

Using the clinical records of 255,668 pregnant women from 2009 to 2017 in Beijing, the study assessed their exposure at home and at work to air pollution that comes from industries, households, cars and trucks. The researchers looked at four types of air pollutants: a deadly fine particulate matter known as PM2.5, sulfur dioxide, ozone and carbon monoxide. The levels were calculated based on historic data gathered by the network of air monitoring systems around the Chinese capital, which is notorious for its gray, soupy skies.

Among the women included in the study, 17,497, or 6.8 percent, experienced silent miscarriages in their first trimester. Taking into consideration different ages, occupations and air temperature, the researchers found that “in all groups, maternal exposure to each air pollutant was associated with the risk.”

Mr. Zhang, the lead author, said that more research was needed to ascertain the exact link between the different pollutants and the risk of missed miscarriages. In the paper, the authors of the study, which was supported by grants from three Chinese government-backed research foundations, also acknowledged that data limitations made it difficult to account for other possible contributing factors, like levels of indoor air pollution from stoves, construction materials and tobacco smoke.

Nevertheless, outside experts agreed that the findings add to the growing body of evidence about the negative effect of air pollution on the health of pregnant women and their fetuses.

“There has been a lot of evidence suggesting a link between air pollution and pregnancy outcomes in general, particularly the risk of a premature birth and a low weight baby,” said Tom Clemens, a lecturer at the University of Edinburgh who has researched the subject and was not involved in the study. “This is one of the first studies to link particle pollution to this particular outcome of pregnancy so in that sense it’s very important.”

Health concerns about air pollution have grown rapidly in China over the past decade. One recent study suggested a link between air pollution and cognitive decline. Others have shown that China’s air pollution accounts for as many as one million premature deaths a year.

Much of the anxiety has focused on children. Chai Jing, a former reporter for the Chinese state news media, once said she was motivated to make a documentary about the country’s devastating air pollution after she had complications during a pregnancy. After its release in 2015, the documentary, “Under the Dome,” quickly went viral before Chinese Communist Party censors abruptly ordered its removal from online platforms.

The public’s fears surrounding air pollution — and the implicit threat to broader social stability — have pushed government officials to try and address the issue. Those efforts, including limiting the construction of coal-fired power plants and capping the number of cars on the road, have largely succeeded. A report released last month by the Swiss firm IQAir AirVisual said that Beijing was on track this year to drop off the list of the world’s 200 most polluted cities.

But the problem persists. Earlier this month, a pale gray haze formed the backdrop to the all-important celebrations in Beijing marking the 70th anniversary of the founding of the People’s Republic of China, despite the government’s best efforts to rein in pollution. Footage of the parade showed Chinese military aircraft streaking multicolored smoke trails across grimy skies.

In the Nature Sustainability paper, the researchers said that since 2013, the risk of missed miscarriages in the first trimester had declined along with the decrease in air pollutant concentration — further evidence, they said, of the link between the two.

They concluded their paper by framing the issue in the context of another official priority: China’s declining birthrate. Alarmed by the prospect of a shrinking work force, the government has in recent years encouraged women to have more babies, in part by easing one-child policy restrictions. But those efforts so far haven’t done much to change the trend.

“China is an aging society and our study provides an additional motivation for the country to reduce ambient air pollution for the sake of enhancing the birthrate,” the researchers wrote.

Zoe Mou contributed research.

Staying on Guard Against Skin Cancer

“If you see something, say something,” a catchy warning from the Department of Homeland Security about possible terrorist threats, applies as well to skin lesions that, if ignored, could become fatal.

Susan Manber, now a 55-year-old from Cortlandt Manor, N.Y., knows this well. She credits her astute daughter with having saved her life nearly six years ago when Sarina, then 13, remarked, “Mom, what’s that thing on your nose?”

That “thing” was a tiny white nodule on the rim of one nostril, a weird place, Ms. Manber thought, for a pimple.

In a few weeks this seemingly innocent pimple had developed a tiny purple center, prompting her to see a dermatologist, who thought it wasn’t anything to worry about but sent her to a specialist to have it removed and biopsied.

The report that came back on New Year’s Eve 2013 could not have been more shocking: a very rare and aggressive form of skin cancer called Merkel cell carcinoma. It’s a diagnosis made only 2,500 times a year in the United States, and until recently had a life expectancy of five months from diagnosis.

Ms. Manber endured seven surgeries, including removal of the left side of her nose (which was rebuilt using ear cartilage) and cancer-containing lymph nodes in her neck, combined with radiation and chemotherapy.

Treatment with immunological agents available since 2016 has improved the prognosis for this cancer, though it is still three times more deadly than melanoma.

Ms. Manber, who was finally able to return to work as a health communications specialist two years ago, now advocates for the Skin Cancer Foundation’s new, simplified campaign to get people to take skin cancer more seriously. In honor of the foundation’s 40th anniversary, it has a new alert message: “The Big See” — “see” as in look, and “C” as in cancer. If you see something anywhere on your skin that is new, changing, not healing or doesn’t seem right to you, Dr. Deborah S. Sarnoff, the foundation’s president, urges you to get it checked out as soon as possible.

While all forms of skin cancer, including basal cell carcinoma, can be fatal if ignored long enough, the most common life-threatening form is melanoma, which is diagnosed 192,000 times a year in the United States and claims 9,000 lives. For many years, the “ABCDE” test for worrisome lesions was used to alert people to this dangerous disease: A for asymmetry, B for irregular border, C for color (tan, brown or black), D for diameter (usually larger than ¼-inch) and E for evolving.

Perhaps, the foundation realized, the alphabet warning was too complex and limiting. “Many melanomas and most nonmelanoma skin cancers don’t fall under the ABCDE pattern,” the foundation reported recently in its journal. “When we educate people about the warning signs of skin cancer, we often hear from them, ‘Mine didn’t look like that.’”

The Big See message can alert people to all forms of skin cancer, often unnoticed for many months or years and dismissed as “no big deal.” Last year, for example, I had a small sore on my leg that never healed, but waited six months to find out it was a basal cell carcinoma that required surgical removal.

More than five million nonmelanoma skin cancers are diagnosed annually in America, and every hour more than two people die from skin cancer even though it is the cancer everyone can see. No scans or special or invasive detection tests are required, just your eyes or those of a friend or companion who, if they see something, should say something.

Complementing the foundation’s new The Big See message is a “What’s that?” alert and a talking mirror being placed in retail locations nationwide in which a lively comedian tells people about skin cancer.

As Ms. Manber said in an interview, “Most people don’t realize that just five sunburns can double your chances of developing melanoma. They don’t know that one person in five will get skin cancer.” Now determined to raise awareness about detecting this disease, she joins skin cancer specialists in urging people to install a full-length mirror in their home to facilitate frequent skin checks. By standing with your back to the full-length mirror and holding a hand mirror, I’ve found that even a person who lives alone can do a full body self-exam.

Ms. Manber is equally passionate about the importance of protecting one’s skin from the damaging rays of sunlight, which can penetrate all windows (except windshield glass in cars), pass through cloud cover and be reflected by water, sand and concrete. Thus, shade is not completely protective. The damage to DNA caused by ultraviolet A (UVA) and ultraviolet B (UVB) rays starts within minutes of sun exposure, and the body’s immune defenses do not repair all of it, which can result in cancer-causing mutations over time.

UVB causes sunburn, and UVA, in addition to causing sunburn and tanning, ages and wrinkles the skin, creating what my husband called elephant hide.

People with fair complexions, blue eyes, freckles or a family history of skin cancer are especially susceptible to the cancer-inducing rays of sunlight. They and anyone spending many hours outdoors in daylight are advised to always use a broad-spectrum sunscreen with an SPF of at least 30 and reapply it every two hours and after swimming. They are also urged to wear protective clothing and a hat when out during the day, and be particularly careful about avoiding sun exposure when it is most intense — between 10 a.m. and 4 p.m.

Protecting babies and children is especially important. Before 6 months of age, they should be kept out of the sun by using clothing, hats, blankets and stroller shades; after 6 months, add sunscreen to the mix. And don’t forget sunglasses for toddlers on up.

Needless to say, tanning beds are a major no-no for everyone; their use before the age of 35 can increase the risk of melanoma by 75 percent, the foundation reported.

But as you might guess, extreme sun avoidance can have its own risks: a decrease in the body’s ability to form biologically active vitamin D, which is critical to bone health and, according to a Swedish study that followed nearly 30,000 women for 20 years, is tied to a small but significant increase in deaths from cardiovascular disease and other noncancer-related disorders. Compared to the women in the study who were most exposed to sun, the life expectancy of sun avoiders was 0.6 to 2.1 years shorter. Also, as you might expect, not every expert endorses this finding.

Helping Teenagers Quit Vaping

For many years, my lead-in question with adolescents, after I asked the parent to leave the room at pediatric appointments, was whether the kid had ever tried smoking cigarettes. It made a reasonable lead-in because it felt less highly charged than asking about marijuana or other substances, and in recent decades, the answer was very often no. Youth tobacco smoking in the United States was on the decline.

And then came vaping, e-cigarettes and Juuls. And like many parents, many pediatricians are flying a little bit blind here, not sure what questions to ask or how to respond to the answers we get. This was brought home to me vividly when an adolescent patient told me that he was vaping pretty regularly — even in school, keeping it hidden.

He told me he had tried to stop a couple of times and he couldn’t do it — high school, he said, was just too stressful.

There are frightening numbers about e-cigarette use in the young, and increasing reports of serious illness, lung damage and death related to vaping. What can we do to help an adolescent or a young adult shake a nicotine habit?

The announcement last week of the death of a 17-year-old, the first teenager known to die from a vaping-related illness, may help shift young people’s thinking about the risk.

“There’s a perception it’s safe, safer than cigarettes; youth in general agree cigarettes are not safe,” said Dr. Sarah M. Bagley, an addiction specialist who is assistant professor of medicine and pediatrics at Boston Medical Center/Boston University School of Medicine.

“Everybody who comes in smoking cigarettes knows it’s going to kill them,” said Dr. Sharon Levy, the director of the adolescent substance use and addiction program at Boston Children’s Hospital. “Till very recently, people thought vapes were the healthy alternative.” Those sobering messages are not necessarily turning up on the news sources that her adolescent patients follow, she said. “There are kids who come to our clinic thinking we’re making a big deal about nothing.”

“How do we help kids quit vaping, the million-dollar question,” Dr. Levy said. There is not a research literature yet, and understanding vaping habits is more complicated than counting the number of cigarettes a day.

Dr. Scott Hadland, a pediatrician and adolescent addiction specialist at the Grayken Center for Addiction at Boston Medical Center, said, “Before you can have these conversations with young people, you need to understand what a vaping device is, what some of the brands are, the types of cartridges.” Are they buying it from a “legitimate” source or buying it illegally? For some, vaping is about marijuana, not nicotine.

And when there is secretive vaping going on all day in school, he said, young people may be more likely to develop a physiological dependence on nicotine than they were with traditional cigarettes.

Someone who is using a high-concentration nicotine cartridge every day or two, Dr. Hadland said, is probably taking in the equivalent of about a pack of cigarettes a day, much more than adolescents typically smoke.

Nicotine is a stimulant, and like other stimulants, at low doses it can make people feel more alert and attentive; higher doses, Dr. Levy said, do just the opposite, making people jittery, revved up and unable to concentrate. The high-concentration cartridges deliver a bigger, faster hit of nicotine than was possible with traditional cigarettes. “What Juul did was it perfected nicotine delivery,” Dr. Levy said.

“My sense, and there are not data to guide this yet, is that the more severe the nicotine use disorder, the more necessary to give medication,” Dr. Hadland said. That includes nicotine replacement, with patches, and then lozenges or gum to deal with breakthrough cravings. It can also include a medication called Chantix, which can help with cravings, but has not been found to be effective for those 16 and under, and is generally used cautiously in older adolescents and younger adults. The antidepressant medication Wellbutrin is also sometimes used.

“Nicotine replacement doesn’t work as well as it does in adults, but it does increase the quit rate,” Dr. Levy said. “We do a lot of coaching of our pediatric colleagues, we tell them go ahead and be generous,” that is, for example, helping parents understand that because vaping can mean an adolescent is accustomed to a very high dose of nicotine, that kid may go through a lot of lozenges.

All of these medications are more effective with cognitive behavioral therapy to help you deal with your emotions and manage cravings, Dr. Levy said. Counseling is an important part of treatment, and one reason I try hard to refer my patients to specialty clinics is that I want them to have experienced counselors. And treatment is much more likely to be successful when there is support from a parent.

Because of the high nicotine concentrations and the physiological dependence, Dr. Hadland said, young people who are trying to quit vaping may experience symptoms that go well beyond the cravings that those who smoke traditional cigarettes experience when they try to quit. In addition to those very strong cravings, there may be general irritability, headaches or a sense of feeling sick to your stomach.

“For some, this withdrawal is almost paralyzing,” Dr. Hadland said. “They can’t go about their day, can’t go to school — it’s not something I had ever seen with regular cigarettes, it feels different to me as a clinician.” For the first time, he said, he has to write school letters asking that patients can wear the patch and chew gum when necessary.

[The site smokefree.gov offers specific advice for helping teenagers quit vaping. Other resources include the Great American Smokeout, the American Lung Association, the National Cancer Institute.]

Assessing the degree of nicotine dependency or addiction means not only looking for withdrawal symptoms, Dr. Hadland said, but also at whether someone has tried to cut back without success, and at whether there is a general sense of being out of control — spending more and more money on the habit, finding it is causing conflict with family members, getting in the way of participation in sports.

With 14-year-old patients, he said, sometimes the approach is: “Are you willing to give your Juul and your cartridges to your parents so they can get rid of them — they say yes — you can almost cut the supply off by getting rid of the access.” But for older people, he said, it becomes a lot more difficult, and it can be really hard for them to give up their devices.

Even with medications and counseling, many young people will struggle hard to quit their nicotine habits. Many will face daily temptations in high school, where vaping may be common and normalized, Dr. Bagley said. They need family support and understanding, and may do better with rewards and positive reinforcement.

To fix that high school environment, we should be thinking about what was so effective in communicating the message that cigarettes were dangerous, Dr. Bagley said, and formulating a better public health response to vaping.

But in the meantime, parents need to have those conversations, even if your child insists that the vape pen in his backpack belongs to someone else. “That’s an opportunity to say, these things are dangerous, get rid of this,” Dr. Levy said. “The sense you want to give is, your child does not have your permission to do this.” If kids say they can quit, she said, take them to a health care provider and make sure they get help — if they say they aren’t willing, if they say vaping is safe, consider taking them to talk to a pediatrician.

Five Reasons the Diet Soda Myth Won’t Die


CreditWilfredo Lee/Associated Press

There’s a decent chance you’ll be reading about diet soda studies until the day you die. (The odds are exceedingly good it won’t be the soda that kills you.)

The latest batch of news reports came last month, based on another study linking diet soda to an increased risk of death.

As usual, the study (and some of the articles) lacked some important context and caused more worry than was warranted. There are specific reasons that this cycle is unlikely to end.

1. If it’s artificial, it must be bad.

People suspect, and not always incorrectly, that putting things created in a lab into their bodies cannot be good. People worry about genetically modified organisms, and monosodium glutamate and, yes, artificial sweeteners because they sound scary.

But everything is a chemical, including dihydrogen monoxide (that’s another way of saying water). These are just words we use to describe ingredients. Some ingredients occur naturally, and some are coaxed into existence. That doesn’t inherently make one better than another. In fact, I’ve argued that research supports consuming artificial sweeteners over added sugars. (The latest study concludes the opposite.)

2. Soda is an easy target

In a health-conscious era, soda has become almost stigmatized in some circles (and sales have fallen as a result).

It’s true that no one “needs” soda. There are a million varieties, and almost none taste like anything in nature. Some, like Dr Pepper, defy description.

But there are many things we eat and drink that we don’t “need.” We don’t need ice cream or pie, but for a lot of people, life would be less enjoyable without those things.

None of this should be taken as a license to drink cases of soda a week. A lack of evidence of danger at normal amounts doesn’t mean that consuming any one thing is huge amounts is a good idea. Moderation still matters.

3. Scientists need to publish to keep their jobs

I’m a professor on the research tenure track, and I’m here to tell you that the coin of the realm is grants and papers. You need funding to survive, and you need to publish to get funding.

As a junior faculty member, or even as a doctoral student or postdoctoral fellow, you need to publish research. Often, the easiest step is to take a large data set and publish an analysis from it showing a correlation between some factor and some outcome.

This kind of research is rampant. That’s how we hear year after year that everyone is dehydrated and we need to drink more water. It’s how we hear that coffee is affecting health in this way or that. It’s how we wind up with a lot of nutritional studies that find associations in one way or another.

As long as the culture of science demands output as the measure of success, these studies will appear. And given that the news media also needs to publish to survive — if you didn’t know, people love to read about food and health — we’ll continue to read stories about how diet soda will kill us.

4. Prestigious institutions and the press

To do the kinds of analyses described here, you need large data sets that researchers can pore over. Building the data set is the hardest part of the work.

Analyzing the numbers on hundreds of thousands of people isn’t child’s play. But gathering the data is much more expensive and time-consuming.

Because of this, a few universities produce a disproportionate amount of the research on these topics. They also tend to be the universities with the most resources and the most recognizable names. Because they’re also usually prestigious, they attract more researchers and more funding to build bigger and newer data sets.

They also get more media attention because of having access to more researchers, prestige and funding. If the research is coming out of a super-respected institution, it must be important.

Lather. Rinse. Repeat.


CreditHannah Yoon for The New York Times

5. We still don’t understand the limitations of observational studies

No matter how many times you stress the difference between correlation and causation, people still look at “increased risk” and determine that the risk is causing the bad outcome. For reporting on hundreds of thousands of people, observational studies are generally the only realistic option. With very few exceptions, they can tell us only if two things are related, not whether one is to blame for the other (as opposed to randomized control trials).

With respect to diet sodas, it’s plausible that the people who tend to drink them also tend to be worried about their weight or health; it could be a recent heart attack or other health setback that is causing the consumption rather than the other way around. But you shouldn’t assume that diet sodas cause better health either; it could be that more health-conscious people avoid added sugars.

Many of these new observational studies add little to our understanding. At some point, a study with 200,000 participants isn’t “better” than one with 100,000 participants, because almost all have limitations — often the same ones — that we can’t fix.

Dr. John Ioannidis wrote in a seminal editorial: “Individuals consume thousands of chemicals in millions of possible daily combinations. For instance, there are more than 250,000 different foods and even more potentially edible items, with 300,000 edible plants alone.”

And yet, he added, “much of the literature silently assumes disease risk” is governed by the “most abundant substances; for example, carbohydrates or fats.” We don’t know what else is at play, and using observational studies, we never will.

(Observational research is still the best way to study population-wide risk factors; sophisticated techniques like regression discontinuity can even create quasi-randomized groups to try to get closer to understanding causality. Too few employ such techniques.)

Moreover, too many reports still focus only on the relative risk and not on the absolute risk. If a risk increases by 10 percent, for example, that sounds bad. But if the baseline risk is 0.1 percent, that 10 percent increase winds up moving the baseline to only 0.11 percent.

It would probably be a public service if we stopped repeating a lot of this research — and stopped reporting on it breathlessly. If that’s impossible, the best people can do is stop paying so much attention.

Your Paycheck May Impact Your Heart Health

Fluctuations in earnings may affect your heart health.

Previous research has found that higher income is associated with lower rates of cardiovascular disease. Now a new study reports that changes in income also have a significant effect.

The report, in JAMA Cardiology, prospectively followed 8,989 people, recording changes in income between two interviews that were taken an average of six years apart. They followed their health for the next 17 years.

Compared with people whose income remained relatively stable, those whose income dropped by 50 percent or more were 17 percent more likely to have heart failure, fatal coronary heart disease, a heart attack or a stroke. Those whose income went up by 50 percent were 14 percent less likely to have a cardiovascular event.

The association of cardiovascular health with income change was significant even after controlling for many health and behavioral characteristics. But it is also possible that getting sick itself causes the decline in income.

“Incomes going down can be an enormous life stress,” said the senior author, Dr. Scott D. Solomon, a professor of medicine at Brigham and Women’s Hospital in Boston. “We don’t often think about the social factors that can contribute to cardiovascular health. It’s a different way of thinking that we as cardiologists are not used to.”

Kipchoge’s Inspiring Marathon Run, Just in Time for Chicago

Welcome to the Running newsletter! Every Saturday morning, we email runners with news, advice and some motivation to help you get up and running. Sign up here to get it in your inbox.

Dear Readers,

Eliud Kipchoge of Kenya has done what a lot of people thought a human could not do: He ran a marathon in under two hours. Early Saturday morning, Kipchoge ran 26.2 miles in 1 hour, 59 minutes, 40 seconds. It’s not an officially recognized world record because it wasn’t a marathon like most of us know. It wasn’t a competition. Everything was engineered to help him break two hours, from the location in Vienna to the flock of pacers who helped him along the way.

It’s a dazzling achievement in sports history that may inspire runners in the Chicago Marathon and in future races to push themselves to new levels. If you missed it, you can watch the finish here. You also have two more special opportunities to watch running in the next few days.

The Chicago Marathon, a World Major marathon, is being run on Sunday starting at 7:20 a.m. Chicago time, which is 8:20 a.m. for East Coast viewers. The race is living in the fallout of Alberto Salazar being barred from coaching for four years by the United States Anti-Doping Agency. Two of his athletes, Galen Rupp and Jordan Hasay, still plan to run, as does the former Salazar-coached athlete Mo Farah. And that story just took another turn: This week, Nike said that it is shutting down Salazar’s elite training group, the Nike Oregon Project team.

The Times’s deputy sports editor, Matt Futterman, who is running the Chicago Marathon himself, wrote about the recent decision and had a longer article that ran this week about the toll it’s taken on whistle-blowers, including statements from Salazar. Expect some fireworks at pre- and post-race news conferences.

If you live in the United States or Mexico, you can stream the race live at nbcchicago.com. NBC Sports Gold will also be airing the race if you have a cable subscription. (If you are in Chicago, spectator information is here.)

On Monday, the documentary “Skid Row Marathon” is in theaters for one night only. It’s about a criminal court judge who started a running club on Skid Row in Los Angeles, and how running helped transform lives of members in the club. It won the audience award for best documentary film at the 2017 Los Angeles Film Festival. Here’s where to find out if there’s a screening near you.

For additional suggestions, sign up for our Sports newsletter. Every week, they round up the best of the best sporting events to watch.

And check out my story about a couple of guys who run around Brooklyn in tuxedo running shirts, taking photos of themselves with wedding couples. Writing the story was a good reminder that running doesn’t have to be all business. It can be fun too — and bring a smile to a lot of people’s faces.

It’s not the only thing you can do while running to mix things up, either. A lot of runners pick up trash while they’re running. It’s called plogging and, according to PBS NewsHour, started in Sweden. I’ve picked up trash while running before, but I’ve never done it in an organized fashion, as plogging is often done.

Have you tried plogging? Are there other things you’ve done while running to turn it into more of a game? Let me know — I’m on Twitter @byjenamiller.

Run Well!

Jen A. Miller

Author, “Running: A Love Story

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