Science
Opinion: A route to safer chemotherapy
I have been a cancer doctor for 40 years and have seen our treatments evolve to embrace precision medicine and immunotherapy, which can be less harmful to patients than conventional forms of chemotherapy. And yet conventional cytotoxic chemotherapy — designed to attack and kill rapidly dividing cells — is still a mainstay of cancer treatment for millions of patients globally.
Cytotoxic drugs kill cancer cells, but they also kill normal cells, leading to a host of serious and even life-threatening side effects. Bone marrow suppression, a common side effect of chemotherapy, reduces the number of white cells needed to fight bacterial infections. Chemotherapy can destroy cells lining the bowel and around the mouth, making eating and even drinking nearly impossible.
Generally, these side effects are reversible as the normal white blood cells are replenished, but in the most severe cases, they can be fatal if, for example, bacteria from the gut escape into the bloodstream through a weakened bowel wall and white cell counts are too low to fight the infection. Sepsis in such a case could be catastrophic.
The toxic death rate, where chemotherapy is directly responsible for a patient’s death, can range from 0.5% to 3.1% but has been reported as high as 13%, depending on the intensity of the chemotherapy regimen, age and fitness of the patient and their genetic makeup.
We can reduce this terrible result with greater use of pharmacogenetics, which studies how our genes affect the way we respond to medications in terms of toxicity and effectiveness. It is becoming more possible to devise genetic tests that can indicate whether an individual would be likely to suffer very serious side effects. This would permit healthcare providers to tailor dosages to avoid the worst hazards of chemotherapy drugs and lessen the number of patients dealing with potentially deadly side effects.
One prominent example involves two related and widely used anticancer drugs, 5-fluorouracil, or 5-FU, and capecitabine (which functions like 5-FU), often used to treat colorectal, breast, stomach and pancreatic cancer.
In the United States, about 275,000 patients with cancer receive 5-FU each year. As many as 25% of those patients require hospitalization with severe side effects, and more than 1,300 patients are estimated to die each year from the drug’s toxicity.
The side effects are most severe for patients who have low levels of dihydropyrimidine dehydrogenase, an enzyme that is produced by the liver and that breaks down 5-FU in the body. This enzyme, also known as DPD, is usually caused by inherited changes in a particular gene. Currently, there are internationally accepted dosing guidelines for 5-FU, adjusted according to DPD genetic test results, ranging from avoiding the drug completely (risk of death is high) to conventional dosing.
While the genetic DPD tests are not perfect — they may miss some patients — nevertheless they have been shown to save lives, reduce the number of patients admitted to hospitals and reduce healthcare costs.
In the United Kingdom, the National Health Service now requires that all new patients receiving 5-FU or capecitabine take some form of a pharmacogenetic test, a policy change that was driven by pressure from families who lost a loved one and advocacy from professional medical societies.
In March, the U.S. Food and Drug Administration approved safety labeling changes regarding DPD deficiency for 5-FU, but that alone isn’t sufficient. It did not issue a national policy to require pharmacogenetic or related tests to detect the problem.
The National Health Service sets a sound example that the FDA could follow. Mandating a simple genetic blood test could help cancer patients get the care they need and better protect them from medical tragedies brought on by the treatment itself.
David Kerr is a professor of cancer medicine at the University of Oxford in Great Britain.
Science
Political stress: Can you stay engaged without sacrificing your mental health?
It’s been two weeks since Donald Trump won the presidential election, but Stacey Lamirand’s brain hasn’t stopped churning.
“I still think about the election all the time,” said the 60-year-old Bay Area resident, who wanted a Kamala Harris victory so badly that she flew to Pennsylvania and knocked on voters’ doors in the final days of the campaign. “I honestly don’t know what to do about that.”
Neither do the psychologists and political scientists who have been tracking the country’s slide toward toxic levels of partisanship.
Fully 69% of U.S. adults found the presidential election a significant source of stress in their lives, the American Psychological Assn. said in its latest Stress in America report.
The distress was present across the political spectrum, with 80% of Republicans, 79% of Democrats and 73% of independents surveyed saying they were stressed about the country’s future.
That’s unhealthy for the body politic — and for voters themselves. Stress can cause muscle tension, headaches, sleep problems and loss of appetite. Chronic stress can inflict more serious damage to the immune system and make people more vulnerable to heart attacks, strokes, diabetes, infertility, clinical anxiety, depression and other ailments.
In most circumstances, the sound medical advice is to disengage from the source of stress, therapists said. But when stress is coming from politics, that prescription pits the health of the individual against the health of the nation.
“I’m worried about people totally withdrawing from politics because it’s unpleasant,” said Aaron Weinschenk, a political scientist at the University of Wisconsin–Green Bay who studies political behavior and elections. “We don’t want them to do that. But we also don’t want them to feel sick.”
Modern life is full of stressors of all kinds: paying bills, pleasing difficult bosses, getting along with frenemies, caring for children or aging parents (or both).
The stress that stems from politics isn’t fundamentally different from other kinds of stress. What’s unique about it is the way it encompasses and enhances other sources of stress, said Brett Ford, a social psychologist at the University of Toronto who studies the link between emotions and political engagement.
For instance, she said, elections have the potential to make everyday stressors like money and health concerns more difficult to manage as candidates debate policies that could raise the price of gas or cut off access to certain kinds of medical care.
Layered on top of that is the fact that political disagreements have morphed into moral conflicts that are perceived as pitting good against evil.
“When someone comes into power who is not on the same page as you morally, that can hit very deeply,” Ford said.
Partisanship and polarization have raised the stakes as well. Voters who feel a strong connection to a political party become more invested in its success. That can make a loss at the ballot box feel like a personal defeat, she said.
There’s also the fact that we have limited control over the outcome of an election. A patient with heart disease can improve their prognosis by taking medicine, changing their diet, getting more exercise or quitting smoking. But a person with political stress is largely at the mercy of others.
“Politics is many forms of stress all rolled into one,” Ford said.
Weinschenk observed this firsthand the day after the election.
“I could feel it when I went into my classroom,” said the professor, whose research has found that people with political anxiety aren’t necessarily anxious in general. “I have a student who’s transgender and a couple of students who are gay. Their emotional state was so closed down.”
That’s almost to be expected in a place like Wisconsin, whose swing-state status caused residents to be bombarded with political messages. The more campaign ads a person is exposed to, the greater the risk of being diagnosed with anxiety, depression or another psychological ailment, according to a 2022 study in the journal PLOS One.
Political messages seem designed to keep voters “emotionally on edge,” said Vaile Wright, a licensed psychologist in Villa Park, Ill., and a member of the APA’s Stress in America team.
“It encourages emotion to drive our decision-making behavior, as opposed to logic,” Wright said. “When we’re really emotionally stimulated, it makes it so much more challenging to have civil conversation. For politicians, I think that’s powerful, because emotions can be very easily manipulated.”
Making voters feel anxious is a tried-and-true way to grab their attention, said Christopher Ojeda, a political scientist at UC Merced who studies mental health and politics.
“Feelings of anxiety can be mobilizing, definitely,” he said. “That’s why politicians make fear appeals — they want people to get engaged.”
On the other hand, “feelings of depression are demobilizing and take you out of the political system,” said Ojeda, author of “The Sad Citizen: How Politics is Depressing and Why it Matters.”
“What [these feelings] can tell you is, ‘Things aren’t going the way I want them to. Maybe I need to step back,’” he said.
Genessa Krasnow has been seeing a lot of that since the election.
The Seattle entrepreneur, who also campaigned for Harris, said it grates on her to see people laughing in restaurants “as if nothing had happened.” At a recent book club meeting, her fellow group members were willing to let her vent about politics for five minutes, but they weren’t interested in discussing ways they could counteract the incoming president.
“They’re in a state of disengagement,” said Krasnow, who is 56. She, meanwhile, is looking for new ways to reach young voters.
“I am exhausted. I am so sad,” she said. “But I don’t believe that disengaging is the answer.”
That’s the fundamental trade-off, Ojeda said, and there’s no one-size-fits-all solution.
“Everyone has to make a decision about how much engagement they can tolerate without undermining their psychological well-being,” he said.
Lamirand took steps to protect her mental health by cutting social media ties with people whose values aren’t aligned with hers. But she will remain politically active and expects to volunteer for phone-banking duty soon.
“Doing something is the only thing that allows me to feel better,” Lamirand said. “It allows me to feel some level of control.”
Ideally, Ford said, people would not have to choose between being politically active and preserving their mental health. She is investigating ways to help people feel hopeful, inspired and compassionate about political challenges, since these emotions can motivate action without triggering stress and anxiety.
“We want to counteract this pattern where the more involved you are, the worse you are,” Ford said.
The benefits would be felt across the political spectrum. In the APA survey, similar shares of Democrats, Republicans and independents agreed with statements like, “It causes me stress that politicians aren’t talking about the things that are most important to me,” and, “The political climate has caused strain between my family members and me.”
“Both sides are very invested in this country, and that is a good thing,” Wright said. “Antipathy and hopelessness really doesn’t serve us in the long run.”
Science
Video: SpaceX Unable to Recover Booster Stage During Sixth Test Flight
President-elect Donald Trump joined Elon Musk in Texas and watched the launch from a nearby location on Tuesday. While the Starship’s giant booster stage was unable to repeat a “chopsticks” landing, the vehicle’s upper stage successfully splashed down in the Indian Ocean.
Science
Alameda County child believed to be latest case of bird flu; source unknown
California health officials reported Tuesday that a child in Alameda County tested positive for H5 bird flu last week.
The source of infection is not known — although health officials are looking into possible contact with wild birds — and the child is recovering at home with mild upper respiratory symptoms.
Health officials have confirmed the “H5” part of the virus, not the “N1.” There is no human “H5” flu; it is only associated with birds.
The child was treated with antiviral medication, and the sample was sent to the U.S. Centers for Disease Control and Prevention for confirmatory testing.
The initial test showed low levels of the virus and, according to the state health agency, testing four days later showed no virus.
“The more cases we find that have no known exposure make it difficult to prevent additional” infections, said Jennifer Nuzzo, professor of epidemiology and director of the Brown University School of Public Health’s Pandemic Center. “It worries me greatly that this virus is popping up in more and more places and that we keep being surprised by infections in people whom we wouldn’t think would be at high risk of being exposed to the virus.”
A statement from the California Department of Public Health said that none of the child’s family members have the virus, although they, too, had mild respiratory symptoms. They are also being treated with antiviral medication.
The child attended a day care while displaying symptoms. People the child may have had contact with have been notified and are being offered preventative antiviral medication and testing.
“It’s natural for people to be concerned, and we want to reinforce for parents, caregivers and families that based on the information and data we have, we don’t think the child was infectious — and no human-to-human spread of bird flu has been documented in any country for more than 15 years,” said CDPH Director and State Public Health Officer Dr. Tomás Aragón.
The case comes days after the state health agency announced the discovery of six new bird flu cases, all in dairy workers. The total number of confirmed human cases in California is 27. This new case will bring it to 28, if confirmed. This is the first human case in California that is not associated with the dairy industry.
The total number of confirmed human cases in the U.S., including the Alameda County child, now stands at 54. Thirty-one are associated with dairy industry, 21 with the poultry industry, and now two with unknown sources.
In Canada, a teenager is in critical condition with the disease. The source of that child’s infection is also unknown.
Genetic sequencing of the Canadian teenager’s virus shows mutations that may make it more efficient at moving between people. The Canadian virus is also a variant of H5N1 that has been associated with migrating wild birds, not cattle.
Genetic sequencing of the California child’s virus has not been released, so it is unclear if it is of wild bird origin, or the one moving through the state’s dairy herds.
In addition, WastewaterScan — an infectious disease monitoring network led by researchers from Stanford University and Emory University, with laboratory support from Verily, Alphabet Inc.’s life sciences organization — follows 28 wastewater sites in California. All but six have shown detectable amounts of H5 in the last couple of weeks.
There are no monitoring sites in Alameda Co., but positive hits have been found in several Bay Area wastewater districts, including San Francisco, Redwood City, Sunnyvale, San Jose and Napa.
“This just makes the work of protecting people from this virus and preventing it from mutating to cause a pandemic that much harder,” said Nuzzo.
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