Individuals with severe sickle cell disease express high risk tolerance for gene therapies

Individuals living with severe sickle cell disease (SCD) are highly interested in new, potentially curative gene therapy treatments and are willing to accept associated risks for a chance at a cure, according to a study published today in Blood Advances.
SCD is an inherited red blood cell disorder affecting approximately 100,000 people in the United States. According to the Centers for Disease Control and Prevention (CDC), SCD affects one out of every 365 Black or African American births and one out of every 16,300 Hispanic American births. Those living with the disease are born with a genetic mutation that causes their red blood cells to be ‘sickled’ in shape, leading to pain crises and sometimes severe health complications like organ damage and failure.
The current standard of care for SCD includes medications like hydroxyurea that help with symptom management, and procedures such as bone marrow transplant that, when successful, can cure SCD, but is dependent on finding a matched donor and carries a high risk of rejection.
New and emerging gene therapies for SCD extract hematopoietic stem cells (HSCs) from patients with SCD and edit the DNA within the HSC to remove the mutation that causes the development of abnormal red blood cells. The patients then receive high dose chemotherapy followed by reinfusion of their gene-corrected HSCs which will subsequently produce normal (“SCD free”) mature red blood cells. However, the risk-benefit tradeoff of these new therapies is not yet well established. Over the last few years, gene therapy products for blood disorders, cancer, and other rare diseases have also emerged.
“In recent decades, U.S. survival rates for SCD patients have significantly risen, but the average life expectancy is about 60 years — substantially lower than that of the general population,” said Juan Marcos Gonzalez, PhD, an expert in clinical decision sciences and health-preference measurement at Duke University School of Medicine and the study’s lead author. “Although current therapies are beneficial, many patients will not qualify for a bone marrow transplant and the other therapies will not eliminate SCD symptoms entirely.”
Amidst several gene therapies pending U.S. Food and Drug Administration (FDA) approval, Dr. Gonzalez and his team initiated a study to understand patient views on these novel treatments. They used a discrete-choice experiment survey, which presented participants with pairs of hypothetical gene therapy treatments along with a ‘no gene therapy’ option. The gene therapy choices were characterized by their potential to eliminate SCD symptoms, extend life expectancy, and their associated risks, including treatment-related mortality, infertility, and increased cancer risk.
Across three U.S. clinical sites and with the support of Cayenne Wellness, a patient-driven organization, 174 adult patients and 109 parents of children living with SCD completed the survey. Most survey respondents were willing to choose gene therapy over alternatives. However, when gene therapy posed a 10% or greater risk of death, adults with mild symptoms required a higher likelihood of eliminating SCD symptoms (around 67% on average) than parents of children (around 8%) to ultimately choose gene therapy. In contrast, adults experiencing moderate symptoms required lower success rates. To accept gene therapies posing 10% or 30% mortality risks, these patients required 34% and 37% chance of having their SCD symptoms fully resolved, respectively.

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Outlook on exercise may curb aging anxiety

A positive attitude about physical activity may be related to lower anxiety about aging. Researchers who analyzed results from a multi-state survey say gender, age, marital status and income affect perspectives on exercise and aging but that reframing messages about both can lead to healthy behaviors.
Since 2011, roughly 10,000 people in the U.S. have turned 65 every day. The Baby Boomer generation and those born before 1946 make up the country’s fastest growing age group, which is on track to outnumber children by 2035.
“As this large demographic ages, it’s really important to support health promoting behaviors and have an approach that focuses on prevention — not just treatment — when it comes to chronic diseases. To do that, we need to know what their needs are and how best to address those needs,” says Sarah Francis.
Francis holds many titles at Iowa State University: professor and Jane Armstrong Endowed Chair of Food Science and Human Nutrition, College of Human Sciences’ interim associate dean for Iowa State Extension and Outreach and interim director for Human Sciences Extension and Outreach. But Francis introduces herself as a healthy aging advocate, implementation scientist and registered dietitian.
In 2010, she joined a U.S. Department of Agriculture multistate project that brought together experts in physical activity, clinical nutrition and community health programming to support healthy aging. Part of their research has focused on identifying factors that influence physical activity, like “aging anxiety.” Francis explains this anxiety encompasses fears and concerns about losing autonomy and relationships, physical and psychological changes, and discomfort or lack of enjoyment being around older people.
“Previous research has shown that if you have high anxiety about aging, you have poor health outcomes. But if you view it more positively as a life stage, you have better health outcomes. You’re more likely to make lifestyle changes that benefit you in the long run,” says Francis.
A cross-section of experiences, perspectives
To understand how aging anxiety relates to physical activity and other factors, like age, gender, marital status and income, the team designed a 142-question online survey and recruited participants through Qualtrics. Francis explains they wanted a cross-section of urban, suburban and rural residents and included people as young as 40 to understand how different aspects of aging anxiety shift with age. In total, 1,250 people from Washington, D.C. and six states, Iowa, Illinois, Maryland, Rhode Island, South Dakota and West Virginia, responded to the survey.

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Scientists train AI to illuminate drugs' impact

An ideal medicine for one person may prove ineffective or harmful for someone else, and predicting who could benefit from a given drug has been difficult. Now, an international team led by neuroscientist Kirill Martemyanov, Ph.D., based at The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, is training artificial intelligence to assist.
Martemyanov’s group used a powerful molecular tracking technology to profile the action of more than 100 prominent cellular drug targets, including their more common genetic variations. The scientists then used that data to develop and train an AI-anchored platform. In a study that appears in the Oct. 31 issue of the journal Cell Reports, Martemyanov and colleagues report that their algorithm predicted with more than 80% accuracy how cell surface receptors would respond to drug-like molecules.
The data used to train the algorithm was gathered over a decade of experimentation. Their long-range goal is to refine the tool and use it to help power the design of true precision medications, said Martemyanov, who chairs the institute’s neuroscience department.
“We all think of ourselves as more or less normal, but we are not. We are all basically mutants. We have tremendous variability in our cell receptors,” Martemyanov said. “If doctors don’t know what exact genetic alteration you have, you just have this one-size-fits-all approach to prescribing, so you have to experiment to find what works for you.”
One-third of all drugs work by binding to cell-surface receptors called G protein-coupled receptors, or GPCRs. These are complexes that cross the cell membrane, with a “docking station” on the cell’s exterior and a branch that extends into the cell. When a drug pulls into its GPCR dock, the branch moves, triggering a G protein inside the cell and setting off a cascade of changes, like falling dominoes.
The result of activating or blocking this process might be anything from pain relief, quieting allergies or reducing blood pressure. Besides medications, other things like hormones, neurotransmitters and even scents dock with GPCRs to direct biological activities.
Scientists have catalogued about 800 GPCRs in humans. About half are dedicated to senses, especially smell. About 250 more receive medicines or other known molecules. Martemyanov’s team had to invent a new protocol to observe and document them. They found many surprises. Some GPCRs worked as expected, but others didn’t, notably those for neurotransmitters called glutamate.

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How cruise ships can steer clear of viral spread

In Physics of Fluids, researchers examine how ventilation can affect transmission of airborne viruses in a typical cruise ship cabin based on guidelines developed before and after the pandemic. They conducted simulations for virus droplets from a cough in a typical cabin that accommodates two or more people, with different ventilation rates and different positions of the person emitting the cough. Computational fluid dynamics testing ranged from 1.5 to 15 air changes per hour to capture all possible scenarios, from minimal ventilation to rates exceeding the most recent recommendations.
When Covid 19 began to spread across the globe, its effects were significantly pronounced on cruise ships. Indeed, compared to other population segments, cruise ship passengers became disproportionately infected and often, ironically, stranded on board to quarantine. That’s why focus has been directed at addressing the need for improved ventilation on cruise ships since dispersing fresh air in cabins and other enclosed spaces is critical for mitigating viral spread.
In Physics of Fluids, by AIP Publishing, a group of researchers from Cyprus examined how ventilation can affect transmission of airborne viruses in a typical cruise ship cabin based on guidelines developed before and after the pandemic.
“The most recent standards and regulations on room safety regarding the airborne transmission of viruses focus on high rates of air exchange,” said author Dimitris Drikakis. “But this can be inefficient in terms of energy consumption, can compromise passenger comfort as it generates strong air drafts, and most importantly, can spread saliva droplets up to five times more when passengers cough.”
Drikakis and his team conducted simulations for virus droplets from a cough in a typical cruiser cabin that accommodates two or more people, with different ventilation rates and different positions of the person emitting the cough. Computational fluid dynamics testing ranged from 1.5 to 15 air changes per hour (ACH) to capture all possible scenarios, from minimal ventilation to rates exceeding the most recent recommendations.
“The study reveals that a higher ventilation rate is not the best strategy to avoid spreading airborne diseases,” Drikakis said. “Complete evaporation of the saliva droplets may not necessarily mean all viruses or bacteria become instantly inactive. Therefore, we should aim at minimum droplet spreading inside the cabin and different ventilation strategies for occupied cabins.”
After analyzing the results, the team determined the ideal use of ventilation systems to operate at medium flow rates of around 3 ACH when a cabin is occupied, to increase to 15 ACH for at least 12 minutes after it has been vacated. In this way, the air would be completely refreshed for the next occupants. They also recommend the same minimum time of 12 minutes as a “clearance wait time” for similar-sized rooms with a minimum of 15 ACH.
“Our main argument for the proposed values is the necessity to minimize droplet spreading while maintaining good ventilation levels, comfort and energy consumption,” said Drikakis. “Keeping ventilation at the proposed values reduces energy consumption and improves passenger comfort in contrast to the use of higher ventilation rates.”

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Bariatric Surgery at 16

Last fall, Alexandra Duarte, who is now 16, went to see her endocrinologist at Texas Children’s Hospital, outside Houston. From age 10, she had been living with polycystic ovary syndrome and, more recently, prediabetes. After Alexandra described her recent quinceañera, the doctor brought up an operation that might benefit her, one that might help her lose weight and, as a result, improve these obesity-related problems.Listen to This ArticleOpen this article in the New York Times Audio app on iOS.Alexandra, who smiles shyly and speaks softly but confidently, says she was “a little skeptical at first because, like, it’s a surgery.” But her mother, Gabriela Velez, suggested that her daughter consider it. “Ever since I was a toddler, my mom knew that I was struggling with obesity,” Alexandra says.Through the years, Alexandra seemed to have tried everything. She went through periods when she avoided all carbs and days when she drank only water. She turned to commercial products, from Herbalife to diet pills to meal-replacement shakes. Desperation — and hope — led her to try gimmicky lotions that promised to burn fat. Puberty seemed to make things worse. Her doctors dispensed “basically the same talk everyone else gives me,” she says: Follow the government’s MyPlate plan; eat lots of vegetables; have anything, but don’t overdo it.Her mother diligently prepared her meals, cooking vegetables in ways that she liked. Alexandra herself worked on “getting fuller on less,” trying to limit each meal to a single plateful. Almost everyone in her immediate family carries extra weight — including her younger twin brothers, who put on more weight during the pandemic — but neither her father nor the twins nor another brother copied her efforts. Seeing them eat ice cream and cake made her vegetables less enticing. “I have a huge sweet tooth,” she says.The teasing started in fifth grade. Alexandra couldn’t eat without her classmates staring at and judging her. Though she sought counseling for her sadness and anxiety, these troubles still caused her to leave school for a month. The bullying finally stopped after she switched schools in 10th grade, but Alexandra’s parents knew how deeply she continued to suffer. How much more could their daughter endure? After the doctor suggested bariatric surgery, an operation on the gastrointestinal tract that helps patients lose weight, they spoke to friends who had successfully been through the procedure as adults. They decided it was a smart option for her. Alexandra wasn’t sure, however.When the family met the surgeon, Jose Ruben Rodriguez, he was quick to tell them that the operation was no “shortcut.” Indeed, Alexandra first had to complete the hospital’s strict, comprehensive behavior and lifestyle program, which lasts six to nine months; this effort would demonstrate her commitment to improving her health while also preparing her for surgery and life afterward. Many teenagers find this step too challenging: Rodriguez estimates that less than one-third of them end up receiving the surgery after their initial appointment. For Alexandra, the program’s tasks mimicked what she had tried already: keeping food journals, drinking more water, setting sleep schedules (which in turn often means restricting access to phones). She was also instructed to exercise; as someone who loves dancing to K-pop songs in her bedroom and going to the gym with friends, Alexandra didn’t find that difficult, either. “I guess for some people it could be intense,” she says, “but it honestly to me felt a little bit easy.”Alexandra also saw a dietitian, a psychologist, a gynecologist and a social worker. She was tested too: blood draws, ultrasound, X-rays, sleep study. With each appointment, she felt increasingly comfortable with the prospect of an operation. It was especially helpful to hear Rodriguez explain the procedure, called a sleeve gastrectomy, and describe the experiences of other teenagers who had been through it. After several months of deliberating, she decided to go ahead. The other would-be fixes “never really solved the problem,” Alexandra says. “No matter how many pounds I lose, I gain it back. And it’s sometimes even more. It made me feel discouraged with my efforts, like maybe I wasn’t trying hard enough.”Alexandra before her bariatric surgery at Texas Children’s Hospital.Helen OuyangAlexandra is one of the roughly 20 percent of children in the United States living with obesity, up from 5 percent in the 1970s. Another 16 percent or so are considered overweight. The prevalence of obesity increases as children get older: to more than 22 percent among adolescents from around 13 percent in 2-to-5-year-olds. At 5-foot-1 and 209 pounds, Alexandra had a body mass index that placed her well above the threshold for severe obesity, which is 120 percent of the 95th percentile, according to the C.D.C.’s Extended B.M.I.-for-Age Growth Chart. Without treatment, Alexandra would almost inevitably have obesity into adulthood. And the longer that continued, the more at risk she would be for chronic health issues, like joint pain and problems with breathing and sleeping. Worse, some children in her situation can develop what were once considered adult illnesses: hypertension, diabetes, fatty liver disease. Obesity can also magnify mental-health problems. Teenagers with obesity are more likely than those without obesity to contemplate suicide.Severe obesity is the fastest-rising subcategory among youth — “an epidemic within an epidemic,” as the American Academy of Pediatrics calls it. During the pandemic, the rate of increase in children’s B.M.I. doubled; the greatest gains were in those who were already overweight. Worldwide, the rates of pediatric obesity, which is not solely an American affliction, could double by 2035.In response to so many grim facts, the A.A.P. in January released its first “clinical practice guideline” for those who care for children who have obesity. The academy now recommends that they immediately start “intensive health behavior and lifestyle treatment,” which it labels “the foundation” of obesity management; this approach supersedes the former strategy of “watchful waiting.” For older youth in certain circumstances — those with a higher B.M.I., say — drugs and, in cases of severe obesity, surgery should be made available as options. “The guideline supports what the evidence supports,” Sarah Hampl, its lead author, told me, when she described the yearslong review process. “We didn’t go beyond that.”Semaglutide, one of the newest drugs being used for weight loss, was approved for adolescents 12 and older at the end of December, shortly before the A.A.P. guidelines were released. (Ozempic is the brand name of one semaglutide formulation that has dominated headlines and social media for its off-label use in helping adults swiftly and effortlessly shed pounds.) The drugs seem to offer a promising remedy, though it is too early to know if their use among adolescents will be as widespread. Also, it is unclear if the drugs will be sufficient to treat severe obesity; for now, surgery, a treatment of longer standing whose rates have increased substantially among teenagers over the last decade, remains the most effective intervention for them. As soon as the recommendations were announced, they were met with fierce criticism for their screening and treatment methods, especially drugs like semaglutide and the surgery Alexandra opted for. Critics claimed that these approaches are far too aggressive and subject children’s bodies to unnecessary scrutiny and manipulation, potentially distorting how they view themselves, and that treatments could lead to eating disorders that cause more damage than obesity itself. Some critics challenged B.M.I. — a controversial measurement — and argued that doctors should not be diagnosing obesity in children at all. But, Hampl emphasizes, “the decision for treatment is really in the hands of the families,” rather than the doctors.In June, grasping her white stuffed puppy with floppy ears and her red blanket printed with gray hedgehogs, Alexandra waited in the pre-op area. She was nervous, but “not as nervous as she is,” she said, pointing to her mother. Gabriela nodded and said, “I think I’m thinking too much.” Alexandra’s father sat quietly beside her as she tried to keep busy by drawing in her sketchbook, eventually burying her face in her stuffed animal. The tenacity of body weight can be traced to our biology. Humans evolved to resist losing body fat so that we don’t become extinct, says Rudolph Leibel, chief of the pediatric molecular genetics division at Columbia University’s medical center. Scientists are still trying to unravel that evolutionary process. According to the “thrifty gene” hypothesis, which has been around for over a half-century, we gain weight (and keep it on) to help us prepare for and survive periodic famines. In 2008, John Speakman, an eminent British biologist, coined the “drifty gene” hypothesis: As human survival came to depend less on escaping predators, random gene mutations allowed our upper weight limits to drift higher. Today our brains may be regulating our body weight so that it stays within a range between upper and lower thresholds — while perhaps fighting harder to keep us above the bottom one. After all, starvation poses more immediate danger than obesity. “You cannot get a person to chronically defend a lower level of body fat by chronically restricting their calories,” Leibel says. But, he adds, that level may be pushed up “by virtue of environment.”Our brains are “nonconsciously defending that higher weight,” Stephan Guyenet, a neurobiologist and the author of “The Hungry Brain,” told me — and they are even capable of slowing down our metabolism to that end. The hypothalamus, seated deep in our brains, is the master of this tightly regulated system. Cone-shaped and no larger than an almond, it’s involved in determining if we’re hungry and accordingly prompts us to increase our food intake, or if we’re satisfied, decrease it. It also helps control our metabolism. The hypothalamus responds to signals sent from parts of the body including our fat cells and guts — signals like leptin, an important hormone that Leibel helped discover, which increases when body fat rises, telling our brains to stop eating. A small number of children with severe obesity are born with leptin deficiency, a gene mutation identified by Sadaf Farooqi, a professor at the University of Cambridge’s Institute of Metabolic Science. Their appetites seem to be bottomless. Though it’s rare, Farooqi cites the extreme effect of this mutation as a clear illustration of the “very strong” impact that biology has upon appetite. When Farooqi treated children with this deficiency by injecting them with leptin, they reduced their consumption; too much leptin made them stop eating entirely. “We can literally control how much they’re eating by the dose of leptin we’re giving them,” she says. In other words, appetite is not entirely within our conscious control or willpower. Ghrelin, a hunger hormone, increases when food intake is restricted, making us eat more. Insulin, another important hormone, helps turn the food we eat into energy and controls things like blood sugar that influence how much we eat.“Hunger is absolutely instinctual,” Guyenet told me. “We don’t decide whether we’re going to be hungry or not, whether we’re going to have a craving or not.” And while we might be able to control our intake for a meal or a week, we probably can’t do so every time we eat, for a lifetime. Even our brain’s reward system, which interacts closely with the hypothalamus, motivates us to seek high-calorie food. “There’s just a lot of different ways your brain can kind of sneak calories,” he says. “These regulatory systems have their tendrils everywhere.” A new, 12-year-old patient at Dr. Whitney Herring’s pediatric obesity clinic in Madison, Miss., holding a plate with sections for various food groups, represented by silicone examples. The plates help families manage portion sizes for balanced meals.Kholood Eid for The New York TimesGenetics may determine more than 70 percent of children’s body weight. Single-gene mutations are extremely rare (the most common one affects up to 5 percent of children with severe obesity); Farooqi says that nearly all children with obesity are living with the “cumulative effect of many different genetic variants, resulting in a bigger appetite.” So far, about 1,000 have been identified, most of which act on appetite and hunger, and there are probably many thousands more. Each variant might have a very slight impact — the strongest might be responsible for one person being five pounds heavier than the next — but, Farooqi says, “when you add them up together, they probably explain why some people are much more likely to get obese than others.” But if our genes didn’t change significantly in the last century, why, then, are children getting bigger? No one knows for sure. One likely explanation, however, is the evolutionary mismatch between our genes and our surroundings. Children who end up with obesity were always at the highest genetic risk for that outcome, even if it wasn’t certain to develop, but now, Farooqi says, “the environment is likely unmasking their genetic susceptibility.” The most substantial transformation in their surroundings has been to the food they eat, which in the past was different in its composition and far more limited. Leibel refers to “a revolution in human environments” and notes that our genes haven’t changed “fast enough to accommodate something that’s really an invention of the past 75 years.” The amount of readily accessible food has expanded immensely, making it easier than ever to eat — open a phone app, say, or go to a drive-through. Plenty of Americans can consume as much as they want, whenever they want. Today nearly 70 percent of what children eat is ultraprocessed food, which the NOVA classification system, a commonly used framework, defines as having been formulated from “ingredients mostly of exclusive industrial use, typically created by series of industrial techniques and processes” — which makes them extremely flavorful. These foodstuffs include things our great-grandparents would not have consumed: packaged chips, energy drinks, ready-to-heat-and-eat meals. They are thought to be an important driver of the childhood-obesity epidemic, in part because they seem to make us eat more. Kevin Hall, a researcher at the National Institutes of Health, found that even when meals are matched for calories, carbohydrates, protein, fat, sugar, salt and fiber, study participants who are instructed to eat freely will still, without realizing it, consume an average of 500 calories more a day if the food is ultraprocessed. “Any kid is going to choose an ultraprocessed food,” says Marion Nestle, an emerita professor of nutrition, food studies and public health at N.Y.U. and the author of “Food Politics.” Nestle traces the deregulation of food marketing to the Reagan presidency and the shareholder-value movement. “After 1980, kids were fair game,” she told me. Corporations began aggressively marketing their products to children, potential lifetime customers who are easily influenced. Ultraprocessed foods appeal to parents too: They’re cheap, last for years in pantries and freezers and require little preparation. “All food companies are trying to sell products,” Nestle says. “That’s the system, and if the system makes kids fat, well, too bad. Collateral damage.” In the United States, that damage is inflicted more harshly on some groups of children than others: The obesity epidemic disproportionately spares white and Asian children and those from socioeconomically advantaged families. Living in the highest-opportunity neighborhoods, especially at birth, could be associated with as much as an 80 percent lower risk of obesity. Among Black children, however, the protective effect of income against obesity seems to be weaker.Over the past few decades, the variety of food items in some supermarkets has risen to more than 40,000 from 7,000. These “modern industrial products should not be recognized as foods at all,” says David Ludwig, a pediatrics professor at Harvard and co-director of Boston Children’s Hospital’s obesity-prevention center. “It’s up to parents and all of us to fight back and not to normalize these.” The A.A.P. urges doctors to “demand more of our government” to modify the food being sold to children. But Barry Popkin, a nutrition professor at the University of North Carolina who has worked with countries on their food policies, remains skeptical that similar regulations could be enacted soon in the United States, like Colombia’s tax on ultraprocessed foods or Chile’s restrictions on them in schools and on advertising. “We need our F.D.A. to be bold,” Popkin says. “We need a food czar who’s tough, not these namby-pamby bureaucrats that don’t really want to ruffle any feathers.” At Texas Children’s Hospital, Alexandra lay asleep in the operating room, on a tilted bed, with her feet lower than her head. Gravity now worked to the surgeon’s advantage, pulling her intestines away from her stomach. Rodriguez, wearing a “Peanuts”-themed cap with his scrubs, made five half-inch incisions throughout her abdomen, while the music of Bruno Mars and Elton John softly played in the O.R. Rodriguez then inserted a camera and his tools through the cuts. Alexandra’s insides appeared on four surrounding screens.Rodriguez pulled back her liver, its edges rounded from fat, and pushed aside mounds of squishy yellow fat — findings that he sees only in his bariatric patients — to reveal her stomach, pink and patterned with red vessels like fine tree branches. The anesthesiologist had snaked a tube through Alexandra’s mouth into her stomach. Rodriguez could now follow the contour of the tube with a surgical device that sequentially cut, stapled and sutured stomach tissue. Next came what Rodriguez regarded as the hardest step, wrestling the excised portion of the organ, about 80 percent of the whole, out through one of the tiny incisions. To make sure that what remained of her stomach had been fully stitched up, the anesthesiologist pumped air through the tube into the organ, which now resembled a slim shirtsleeve — hence the procedure’s name, sleeve gastrectomy — and Rodriguez flushed water into her abdomen: Bubbles would indicate a leak somewhere. The water was still. The operation was completed in under an hour. Most of Alexandra’s stomach now sat on a tray, cool and dusky. Dr. Jose Ruben Rodriguez, center, during Alexandra’s surgery.From Texas Children’s HospitalIn another room, with children’s artwork adorning the bright aqua walls, Alexandra’s parents sat on orange chairs and waited, until Rodriguez came in and knelt next to them. “There’s no blood loss at all, which is nice,” he told them in Spanish. In the postoperative area, Alexandra, still confused from the anesthesia, writhed around. With every movement, she hurt. “It’s so hard to see her like this,” Gabriela said, as she smoothed her hand over her daughter’s forehead and begged her to lie still. Alexandra let out a moan.“When we first started, the hospital businesspeople told us there’s not enough surgeries to justify building a program,” Rodriguez told me. “Obviously, that’s not how things turned out. It’s the exact opposite.” The number of teenagers who underwent bariatric surgery more than doubled nationwide between 2010 and 2017 and continues to rise. According to Teen-LABS, which is funded by the National Institutes of Health and which has been conducting the most research on the procedure in the United States, adolescents who have had bariatric surgery — most of them white and female — experienced weight loss similar to what adults lost: around 25 percent of their B.M.I. And while nearly 90 percent of these teenagers needed diabetes medications before the operation, none did afterward; five years later, they were more likely to have their diabetes and hypertension in remission compared with people who had surgery as adults. “There’s a greater positive impact for operating on youth with these two conditions than waiting until adulthood,” says Thomas Inge, chair of surgery at Lurie Children’s Hospital, in Chicago, and the principal investigator of Teen-LABS. “You get more out of the same operation.” Even 10 years after the procedure, the data indicates that there are long-term benefits from surgery. Teenagers do not seem to experience more complications than adults.“Patients lose weight, and they’re less hungry while they’re doing it,” says Randy Seeley, a professor at the University of Michigan who researches the surgery’s effects on a molecular level. Seeley emphasizes that weight loss doesn’t simply result from a newly tiny stomach that limits how much people can eat. Many chemical changes are also responsible, some of which resemble what happens when people are on Ozempic, although these similarities are not thought to be the main mechanism behind surgery’s effectiveness. The crucial roles instead seem to be played by bile acids and antimicrobial peptides in the gut, each of which increase markedly after surgery; Seeley is still sorting out the exact mechanisms of their influence. Also, a majority of the stomach that secretes ghrelin, the hunger hormone, is removed in sleeve gastrectomies. “Why bariatric surgery works so well is because you’re changing lots of things at the same time,” Seeley says. Most important, bariatric surgery seems to reset, to a lower bound, the body weight that the brain tries to maintain. There is less of the persistent metabolic slowing that accompanies traditional weight loss. Based on fMRI scans, the response to food cues in the brain — around the hypothalamus and in the reward and cognitive-control regions — appears to be different in post-surgical patients than it is for those on low-calorie diets. But how altering the anatomy of the gut changes the brain is still a mysterious phenomenon — mostly “a black box,” Seeley says. And it still seems to surprise everyone, even those who perform the operation. “I’m just a basic gastrointestinal surgeon,” Inge says. “Never thought I’d get to claim to be a brain surgeon. But, hey, that’s where it seems like the impact is.”Only a tiny fraction of the teenagers with severe obesity who qualify actually receive the operation. The obstacles in front of them are hard to get past: finding a pediatric bariatric surgeon, navigating the long, arduous process of insurance authorization — assuming the procedure is even covered by the insurer. “We’ve seen all sorts of shenanigans for trying to not approve kids,” Inge says. Some parents, desperate to help their struggling children, feel they have no choice but to pursue treatment without insurance coverage. In 2021, after A’kaysha Studstill tried to take her own life by overdosing, she and her mother, Anastasia, traveled from Florida to Tijuana, Mexico, for bariatric surgery; the trip, including the sleeve gastrectomy, cost around $6,500. “People questioned me taking her out of the country,” Anastasia says. “But you don’t know what I’m dealing with. The bullying — she would shut down for days. She was going to kill herself.” This summer, A’kaysha told me she had lost a third of her weight. Wearing a crisscross black halter top, she beamed while packing up her room to start her freshman year at Florida State University. “There’s always more options than just giving up,” she said. “You don’t have to diet and starve yourself.”Several studies have shown an increased risk of suicide in adults after bariatric surgery. This association may not be a result of patients already at higher suicide risk, like A’kaysha, choosing to go through with the operation. Meg Zeller, a professor at Cincinnati Children’s Hospital who researches the relationship between mental health and pediatric bariatric surgery and has studied the Teen-LABS cohort, has not found this link, but she cautions that adolescent data is “just a different ballgame” compared with the abundance of long-term data generated by adult cases. Data from eight years out shows that alcohol-use disorder is higher after bariatric surgery, possibly because the operation causes alcohol to be metabolized more slowly. While feelings of stigma and body image can improve, Zeller told me that anxiety or depression may not subside to the extent that diabetes often does. All teenagers experience life changes and increased vulnerability, she explains. “We’re talking about intervening at a time in someone’s life when lots of challenges can exist that are unique to that age group.”The morning after her operation, Alexandra, her hair in pigtails, shuffled slowly around her hospital room. She steadily took tiny sips of water. “There’s no going back now,” she said. If our biology, ingrained by evolution, is no longer well engineered for our modern surroundings, can pharmaceuticals help redesign us? One medicine that Alexandra took, metformin, which reduces glucose, has a moderate benefit for teenagers like her who also have prediabetes and polycystic ovary syndrome. But the latest glucagon-like peptide-1 receptor agonists — as a group, commonly referred to as Ozempic — are the true game changers, a class of drugs that are making possible a degree of weight loss not seen before with medications. The pharmaceutical company Novo Nordisk manufactures GLP-1s for weight loss, one of which is semaglutide and sold under the brand name Wegovy. (Ozempic is the brand name for a lower-dose version of semaglutide that is prescribed to treat diabetes by increasing insulin but has become so popular in the last year for cosmetic weight loss that it has helped Novo Nordisk’s market value surpass the gross domestic product of Denmark, where the company is headquartered.) GLP-1s are the “new frontier of anti-obesity medications,” says Aaron Kelly, co-director of the University of Minnesota’s Center for Pediatric Obesity Medicine. In a 16-month study that appeared in December in The New England Journal of Medicine, co-authored by Kelly, adolescents lost 16 percent of their B.M.I. on semaglutide compared with the placebo group, which gained 0.6 percent. The treatment group also registered improved cholesterol and liver tests. (Both cohorts underwent lifestyle therapy.)Semaglutide, currently administered through weekly injections at home, suppresses appetite primarily by acting on GLP-1 receptors in the brain. It may also reduce cravings by modifying the brain’s pleasure pathways. Outside the brain, it slows down the transit of food through the gut, so the feeling of fullness lasts longer. “When you put those three things together — the appetite, the satiety and the suppression of cravings — all of a sudden, you get a medication that has pretty profound effects on reducing weight,” Kelly explains. “I think we’re entering a new phase of pediatric obesity medicine, where we’re going to continue to see increasingly effective and durable treatments.” Gage Robbins, 17, who has been going to Herring’s program since March, with Lasheba Lankston, a medical assistant. He was prescribed semaglutide, but his insurance doesn’t cover it.Kholood Eid for The New York TimesFor several years, Eriyanna Stovall, who just turned 14, has tried unsuccessfully to reduce her meal portions. Her attempts at more healthful eating were also thwarted by the temptation of junk food in the house that her younger siblings, who do not have obesity, love to eat. “I would crave junk food 24/7,” Eriyanna says. She snacked late at night on Doritos and strawberry shortcake in her bedroom. Her mother, who is a nurse, raised the A.A.P. guidelines with their pediatrician, but she doesn’t prescribe weight-loss medications. When I spoke with Eriyanna in May, she had been on Wegovy for a month, after the family found an obesity specialist. “At first, I was really scared because I don’t like shots,” she told me. “But it felt like a little instant pinch.” For the first two weeks, Eriyanna didn’t notice a change. Then her mother observed that she was full after finishing half her plate, instead of asking for her usual seconds. Since the surgery, fruits and vegetables “are tasty to me now,” Eriyanna says. “I think the medicine did something to my taste buds.”The major studies of children and these drugs have enrolled many fewer adolescent subjects than adults, but no new safety concerns have emerged. In addition to semaglutide’s principal side effects of nausea, vomiting and diarrhea — reported by two-thirds of study participants — more serious ones include gallstones and pancreatitis. Wegovy comes with a caution about possible thyroid cancer, and the F.D.A. mandates that it include a warning about the possibility of suicidal ideation, because it acts on the brain; further studies are being conducted in Europe. If patients discontinue the medicines, the weight returns. Compared with fen-phen, a popular weight-loss drug in the 1990s that was eventually linked to heart-valve problems, doctors are less concerned about semaglutide, because older drugs in its class have been used to treat diabetes for nearly two decades. But for any new medicine, the long-term risks remain uncertain. For now, most adolescents who qualify for semaglutide probably won’t be able to get the drug at all. “I always say it’s an insurance game,” Treah Haggerty, a family-medicine obesity doctor at West Virginia University Medicine, told me. “What hoops can you jump through?” If families pay out of pocket, monthly costs could reach $1,400. “We’re creating haves and have-nots,” Haggerty says. Even with insurance, parents may still encounter drug shortages; Novo Nordisk is already restricting the U.S. supply of starter doses into 2024, effectively limiting new patients. Eriyanna was forced to stop Wegovy when the drug became unavailable to her this summer. She switched to an older, less effective GLP-1, but then that went on back-order too. “We are so devastated,” her mother texted me recently. “It seems like a very big mountain we are climbing.”For every child given a diagnosis of being overweight or having obesity — even those who choose medication or surgery — the A.A.P. encourages immediately starting intensive health behavior and lifestyle treatment, like the one Alexandra undertook. For younger children, this may be the only therapy available to them. Amanda Staiano, a developmental psychologist who helped write the A.A.P. section on lifestyle programs, describes them as “trying to re-engineer the child’s environment and helping with positive parenting strategies.” This spring, Micheal and Christi Pientowski took their 5-year-old daughter, Emmie, to one such program in Madison, Miss., a state with one of the highest childhood-obesity rates in the country. They were referred by Emmie’s pediatrician because she was gaining weight rapidly; her B.M.I. was pulling upward away from her growth curve on the C.D.C.’s B.M.I. chart.At their first appointment, Emmie’s parents told the doctor, Whitney Herring, that they were worried about Emmie’s appetite. “She eats, then she’ll immediately be like, ‘Can I have a snack?’ or ‘When are we eating?’” Micheal said. “If we didn’t stop her, she would keep asking for more and more,” Christi added. “She would get mad at us for having more than she did.” “We wanted Emmie to see somebody before kindergarten,” Micheal says. “We know how kids are these days. We just don’t want her to be bullied.” Herring told them not to expect a fast fix. “Even with the body mass index coming down, that is often not a quick process,” she said. If kids see any reduction in B.M.I. from lifestyle treatment, the average is a 1 to 3 percent change in percentile, though other health indicators may improve. Herring asked about Emmie’s meals.“We’re working on it,” Christi said. “The only vegetable that she will eat is carrots.”“What about at school?” Herring asked. Christi described a lunch with green beans and peas. The doctor turned to Emmie, who is blond with ruddy cheeks and dimples. “Do you like those at school?” “No! I never eat those.” “Do you ever have broccoli at school?” “No!” “We are very picky, too,” Christi said. She avoided most vegetables herself. (Some families have trouble affording vegetables or lack the time to prepare them.)At school, children like Emmie may not touch their lunch, or they might snack from vending machines. But improving school meals involves more than just substituting asparagus for fries. Judith Siebart, a dietitian who worked with schools nationally, recalls being told, “We can serve all these healthy foods, but if the kids don’t eat it, what have we gained?” Next, Rebecca Bagwell, the program’s dietitian, wheeled in a cart stacked with silicone foods. She pulled out a seven-inch plate sectioned into different proportions for various foods groups, following MyPlate suggestions. Emmie chose what she liked — chicken, mac and cheese — as Bagwell piled them on the plate in generous portions. “So do you feel like you would want more or less than this?” Bagwell asked.Emmie looked at the plate. “More?”Some of Herring’s patients have trouble getting exercise. One boy, who told me the farthest he has walked is down his block, signed up for track team. But the school never started practice. His experience is not uncommon among poorer youth, whose sports participation rates are lower. And while two-thirds of ninth graders attended physical education weekly in 1991, only one-third did so in 2019. Though exercise alone may not result in profound weight loss, it has extraordinary health benefits — and helps our brains regulate appetite.Drew Keith, 13, has been a patient of Herring’s since June. He has lost 21 pounds through lifestyle changes.Kholood Eid for The New York TimesHerring has expanded her program to cover three different parts of the state, but she still expects as much as 30 percent of her appointments to be no-shows — a problem for many lifestyle treatment programs. From parents missing work to children missing school, families have trouble going to them — if they can find one at all. Herring reckons that the A.A.P.’s recommendation that patients attend at least 26 hours in person over three to 12 months is not feasible for most: “I have yet to find even the most motivated person who’s willing to do two visits a month.”Many primary-care doctors do not have a program like Herring’s to refer their patients to. “It puts more pressure on me to make sure that I’m not only identifying these kids,” says Sarah Hart, a pediatrician in Kentucky, “but in the short time that I do have with them, how can I really home in and find those areas that we can make a real sustainable change?” It can seem like an impossible ambition to achieve in 15-minute primary-care appointments.How the medical community approaches patients’ weight — and whether it should even be diagnosing or treating obesity — has led to all sorts of criticism, which has been growing ever since the American Medical Association declared in 2013 that obesity is a disease. While some people felt relief in knowing that they had a medical disorder, many others felt injury in being considered diseased. As weight became a preoccupation in doctors’ offices and the size of people’s bodies became subject to medical treatment — even if they seemed otherwise healthy — patients felt increasingly more stigmatized and concerned that the care they received was biased. Remedies that were meant to help with obesity instead seemed to be hurting the people with the condition. One of the most vehement responses to the A.A.P. guidelines came from the Collaborative of Eating Disorders Organizations. “This idea of weight loss for higher-weight children — I think all of us were just completely taken aback,” says Johanna Kandel, chief executive of the National Alliance for Eating Disorders, who helped spearhead an open letter from CEDO that responded to the guidelines. Calling them “harmful” and “irresponsible,” the letter’s foremost concern was that screening and treating children for obesity can lead to eating disorders, for which youth at higher weights are already at increased risk. Tracy Richmond, who directs the Boston Children’s eating-disorder program, explains that weight loss in children can trigger eating disorders by making them “hyperfixated on weight and body,” which can then “spiral out of control.” As children continue to restrict their intake, they can become “undernourished relative to where their body would like to be,” a type of anorexia, even if their B.M.I. may not have fallen into the low range. Other eating disorders — bulimia, binge eating — also may emerge.CEDO’s open letter registered its unequivocal opposition to treating children with obesity with drugs or surgery on the grounds that the long-term effects of these procedures on pediatric patients haven’t been well studied and could also worsen disordered eating. But criticism was also directed at pushing children to make lifestyle changes — what the journalist Virginia Sole-Smith calls “textbook diet culture marketing” in her 2023 book, “Fat Talk” — because these can also eventually lead to eating disorders. (Sole-Smith has written for this magazine.) While research has shown that intensive treatments focusing on health and lifestyle behaviors decrease eating disorders, some experts have pointed out that those studies don’t track children long enough to know if they end up developing disorders; most of this research followed the children for only a year or less. Such concerns raised by CEDO are particularly worrisome, given that the rate of eating disorders doubled in teenage girls during the pandemic.Focusing on weight in medical settings can also worsen the care children receive. Two-thirds of people with obesity report experiencing bias from doctors. In extreme cases, this can result in devastating consequences, including missed or delayed diagnoses — even death. The health care system may blame parents for their children’s weight and accuse them of overfeeding or not providing enough healthful food. A few states have even moved children with severe obesity into foster care.Takira Edwards, 18, has diabetes, high blood pressure and polycystic ovary syndrome. In July, Herring referred her for evaluation for bariatric surgery. She has an appointment in November.Kholood Eid for The New York TimesThe pushback against conceiving weight as medical problem has brought intense scrutiny to the act of measuring obesity. The backlash against B.M.I. — calculated as weight in kilograms divided by height in meters squared — has been especially forceful. B.M.I. doesn’t take into account whether the weight comes from muscle or fat or where in the body it’s distributed. In June, the A.M.A. began to move away from the measurement when it acknowledged that “B.M.I. cutoffs are based primarily on data collected from previous generations of non-Hispanic white populations and does not consider a person’s gender or ethnicity.” For now, the A.A.P. still endorses B.M.I., in part because alternative measurements can’t readily be performed in most pediatricians’ offices.Diagnosing people whose B.M.I.s exceed a certain level with obesity — a disease — can increase weight stigma outside medical settings as well. “Our entire concept of ‘fat is bad’ is so rooted in anti-Blackness, white supremacy,” Sole-Smith writes. “When we strive for thinness, we’re reinforcing every other form of stigma at the same time.” People in larger bodies may be perceived as “lazy,” “stupid” or “sloppy” and are constantly vulnerable to insults, slights and jokes. Stigma can also be surprisingly insidious. “If parents say, ‘Fruits and veggies are awesome because it helps us lose weight,’ the weight stigma starts to creep in,” says A. Janet Tomiyama, a psychology professor at U.C.L.A. Experiencing stigma or discrimination because of body size can worsen or even cause health problems.When it comes to individuals, it’s undeniable that people with obesity can be metabolically healthy, just as normal-weight individuals can be unhealthy. Some studies have even shown that normal-weight individuals may not live as long as those with higher B.M.I.s. Findings like these, along with a greater awareness of the drawbacks that can accompany the medicalizing of obesity, have fueled popular body-positivity movements like Health at Every Size, which seek to disentangle weight from health. But despite the risks that can accompany obesity treatments — and despite the fact that the data doesn’t always present a clear picture — the prevailing attitude within the medical establishment is that, on balance, the potential negative consequences of obesity are too evident to ignore. When Andrew Stokes, a demographer and public-health professor at Boston University, used people’s weight histories and adequately accounted for important factors like smoking and illnesses, he found that obesity was associated with significantly shorter life spans. Studies can’t prophesy what will happen to any one person, he says, but “this is about probabilities and relative risks.” He adds that obesity is “a cumulative process.” Children with obesity may not be dying of heart attacks, but the Bogalusa Heart Study — one of the longest-running epidemiological studies, it recruited children in the 1970s and followed them through middle age — has nonetheless found that childhood obesity is already associated with cardiovascular and kidney changes that then developed into diseases in adulthood. These findings have been confirmed by autopsies of youth who died in accidents. During the pandemic, obesity was the most common medical condition associated with deaths of people under 21. Lila Monahan, a primary-care pediatrician who uses B.M.I. as a screening tool to help prevent diseases, asks why you would wait until someone started developing abnormalities. She says that’s “like saying someone has high blood pressure, but they’re not having heart attacks, so why are we even measuring their blood pressure?” Ariya Thompson, 6, had been gaining excess weight, but she wasn’t referred to Herring until she was found to have abnormalities on her blood work, including one concerning for prediabetes.Kholood Eid for The New York TimesThough the A.A.P. guidelines include advice on how to minimize weight bias and avoid stigmatizing patients, and even though they recommend screening children with obesity for eating disorders — and were even vetted by eating-disorder experts, Hampl told me — such safeguards may not be enough. The potential harm that the CEDO letter warns about became a reality a few years ago for a fifth-grader whose middle name is Esther. Her school in New Jersey sent home a letter to be signed, a “B.M.I. report card,” that said her B.M.I. was greater than the 95th percentile for her age. The signature that was required was not her parents’ but her doctor’s. The pediatrician told her mother, Lynn (also a middle name), that the weight gain “was not a big deal” and mentioned an academic medical center’s program that “you guys may want to look into.” The first session taught Esther to assign traffic lights to foods: vegetables, green; candy, red. “They weren’t like, ‘Oh you’re too heavy,’” Lynn says, “It was more like, ‘This is a way to be healthier and change your lifestyle so you can keep this as part of your routine for the rest of your life.’” Esther seemed uncomfortable, though, and cried in the car afterward. “The whole family can do better to eat healthy,” Lynn reassured her.Esther refused to go back. But that summer, she told her parents she was trying to be “healthier.” She started eating less and walking to school. Then her weight began to drop. The following spring, Esther was diagnosed with anorexia. Over all, she needed four hospitalizations and five months in a residential treatment facility across the country during the pandemic. There, she kicked so hard to resist a feeding tube that she nearly broke Lynn’s ribs. Later, Esther’s heart rate plunged dangerously. “We almost lost her,” Lynn says, her voice cracking. Esther is better now, but her family remains unsettled. The pandemic’s social isolation was central to her daughter’s eating disorder, Lynn says, but the lifestyle program “was probably the catalyst for it.”“I’m feeling more confident in myself — like, I’m no longer wanting to hide away in a jacket or hoodie,” Alexandra told me in October. Four months after her surgery, she has lost more than 50 pounds and is thrilled to feel good wearing a dress for the first time in a long time, for homecoming. “I’m so proud of her,” Alexandra’s mother says. “She’s doing so great.” Alexandra’s improved health means she has been able to stop taking her diabetes pills. She will, like all patients who receive bariatric surgery, have to take vitamins for the rest of her life, in part because her altered gastrointestinal tract does not absorb nutrients as well. A decision she made at 16 will continue to affect her entire life. For someone like Fatima Cody Stanford, a specialist at Harvard who cares for both children and adults with obesity, that’s a positive thing: Redirecting Alexandra’s health in this way is how clinicians should approach childhood obesity. Stanford, who has been using many of the therapies in the A.A.P. guidelines for over a decade, sometimes sees her pediatric patients or their families defer more aggressive treatment, then grow up into adults with obesity, which may pose even greater dangers to their health and be harder to treat — a progression Stanford would like to interrupt when people are still young. “Many people still have this really strong intrinsic belief that if it’s not diet and exercise, then you must have just failed as a human being, particularly in the pediatric population,” she says. As increasingly more effective remedies become available to children like Alexandra, more of them might be set up to lead longer, healthier lives — the reason the A.A.P. put out such comprehensive and urgent guidelines. Yet they are also the same children that others fear will be deeply harmed the most by these very recommendations, and in ways that they may not grasp at such a young age.Alexandra still exercises most days, but it’s tough to balance a routine with a demanding junior year — two A.P. classes, SAT prep, competing for a summer language program in South Korea. After her operation, dining out with her family has become less enjoyable. She feels full so easily now; even when meals taste delicious and she wants to eat more, she can’t, because she is no longer hungry. Sugar also makes her feel nauseated, so she avoids sweets even though she really wants them sometimes. But, Alexandra says, she was so disheartened before the surgery, putting so much effort into losing weight and feeling like she was “accomplishing nothing.” Now, she says, “it’s refreshing to see the hard work I’m putting in is finally showing results.”Helen Ouyang is a physician and associate professor at Columbia University and a contributing writer for the magazine. Her writing has been a finalist for the National Magazine Award and anthologized in “The Best American Science and Nature Writing.” Kholood Eid is a Palestinian American photographer, filmmaker and educator based in New York. She was part of the team at The Times that won a 2020 Robert F. Kennedy Journalism Award for a series investigating online child sexual abuse.

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Chris Mason: Covid inquiry WhatsApps paint picture of chaos

Published7 hours agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesBy Chris MasonPolitical editorAs two of Boris Johnson’s closest aides during the pandemic – Dominic Cummings and Lee Cain – prepare to give evidence at the Covid inquiry later, our political editor Chris Mason reflects on what we’ve heard so far.Shambolic dysfunction in Downing Street, with thousands upon thousands of lives at stake.That is the claim, to the Covid inquiry, from some of those who worked very closely alongside Boris Johnson during the pandemic.They are painting a picture of chaos, and of a prime minister they claim was temperamentally unsuited to the scale of the challenge the pandemic confronted him with. We will see how Mr Johnson and others respond to this in the coming weeks. Follow live: Cain and Cummings face inquiryThis inquiry is giving us a look into the workings of government, with the bonnet up. And, bluntly, it is not a pretty sight: a health emergency, the liberty and education of millions curtailed, the economic future of the country on the line too.Learning lessons afterwards is what a public inquiry is all about – and the UK, in modern times, had never been confronted with anything like Covid-19.For those of us poring over the evidence now gushing towards us, there is a clear risk of hindsight bias. We know now what came next; we didn’t – and they didn’t – know then.What stands out to me so far is a combination of factors which affords us a unique and real time rolling insight into the moods, whims, frustrations and anger of key players at the time.The pandemic, with its need for social distance, coincided with a written communications tool – WhatsApp – becoming a mainstream platform for communication.But not just any communication: an informal, minute-by-minute written down substitution for what might otherwise have been said out loud ad-libbed remarks, lost to the ether moments after their utterance.Instead, as patchy as it might be in the places, we get a glimpse of the tone and mood of senior figures, and not just their point of view. It is often many of the things many of us can be some of the time: unvarnished, crude and shorn of the usual gloss applied to communications for public consumption.And it’s fascinating. We are getting a sense of the organisational oddities, human failings and frailties, and decision-making processes of those whom fate chose to be in positions of power when the pandemic struck – and so compelled to make decisions of a magnitude none of them can have anticipated ever having to make.And there is plenty more to come – Boris Johnson’s former director of communications, Lee Cain, and his former chief of staff, Dominic Cummings.All of this matters, for three reasons: the accountability of individuals; the lessons future governments can learn; and, also, the implications for the politics of today.Because after we have heard from the Downing Street advisers, it will be the turn, before Christmas, to hear from the politicians.Yes, Boris Johnson, but also, too, Rishi Sunak – the chancellor then, the prime minister now.The electorate will be reminded now of events then, and decisions then, which he took.And a final thought: given the unprecedented scale of what confronted the government then, how much of the chaos we are now getting a glimpse of would have been likely under any prime minister, or collection of senior individuals in government? And how much was a direct consequence of Boris Johnson, Rishi Sunak, Dominic Cummings and others, and the relationships between them?It is a question that will always be – to a great extent – unanswerable.But it is one worth keeping in mind as the inquiry progresses.Listen to the Covid Inquiry Podcast on BBC SoundsMore on this storyJohnson can’t lead, top official said over CovidPublished11 hours ago

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Soy expansion in Brazil linked to increase in childhood leukemia deaths

Over the past decades, Brazil has become the world’s leading soybean producer, as well as the leading consumer of pesticides. Despite concerns about potential public health consequences, little is known about the effects of pesticide exposure in the general population. A new study from the University of Illinois Urbana-Champaign in collaboration with the University of Denver and University of Wisconsin-Madison looks at how soy expansion and increased pesticide use in Brazil’s Cerrado and Amazon biomes correlate with increased childhood cancer mortality.
“The Brazilian Amazon region is undergoing a transition from low-input cattle production to intensified soy culture with high use of pesticides and herbicides. The expansion has happened really quickly, and it appears educational efforts and training for pesticide applicators didn’t match the growth in pesticide use. When not used properly, there are health implications,” said Marin Skidmore, assistant professor in the Department of Agricultural and Consumer Economics, part of the College of Agricultural, Consumer and Environmental Sciences (ACES) at U. of I. Skidmore is lead author on the paper, published in Proceedings of the National Academy of Sciences (PNAS).
“As this transition was happening, there were documented cases of pesticide poisoning of agricultural workers and evidence of chemicals in the blood and urine samples of non-agricultural workers in the surrounding communities,” Skidmore said. “This indicates that this rollout had happened in a potentially dangerous way that was leaving people exposed.”
The researchers investigated public health consequences of exposure to pesticides, focusing on children as the most vulnerable population. They specifically looked at deaths from acute lymphoblastic leukemia (ALL), the most common childhood bloodborne cancer.
Their study drew from data on health outcomes, land use, surface water, and demographics in the Amazon and Cerrado biomes. The sample primarily consisted of areas that are classified as “rural” and have at least 25% of land cover in agriculture.
Soy production in the Cerrado area tripled from 2000 to 2019, and in the Amazon region there was a 20-fold increase, from 0.25 to 5 million hectares. Pesticide use in the study region increased between three- and ten-fold during the period as well. Brazilian soy farmers apply pesticides at a rate 2.3 times higher per hectare than the United States.
“Our results show a significant relationship between Brazil’s soy expansion and childhood deaths from ALL in the region,” Skidmore said. “Results suggest that about half of pediatric leukemia deaths over a ten-year period may be linked to agricultural intensification and exposure to pesticides.”
Skidmore and her colleagues show that a 10-percentage point increase in soy production is associated with an additional 0.40 deaths from ALL of children under 5 and an additional 0.21 deaths under 10 per 10,000 population. In total, they estimate that 123 children under 10 died from ALL associated with pesticide exposure between 2008 and 2019, out of a total of 226 reported deaths from ALL in the same period.

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Hearing Aids Are More Affordable, and Perhaps More Needed, Than Ever

Over-the-counter devices have been available for a year now. New research suggests they may have unexpected benefits.A year ago, the Food and Drug Administration announced new regulations allowing the sale of over-the-counter hearing aids and setting standards for their safety and effectiveness.That step — which was supposed to take three years but required five — portended cheaper, high-quality hearing aids that people with mild to moderate hearing loss could buy online or at local pharmacies and big stores.So how’s it going? It’s a mixed picture.Manufacturers and retailers have become serious about making hearing aids more accessible and affordable. Yet the O.T.C. market remains confusing, if not downright chaotic, for the mostly older consumers the new regulations were intended to help.The past year also brought renewed focus on the importance of treating hearing loss, which affects two-thirds of people over age 70. Researchers at Johns Hopkins University published the first randomized clinical trial showing that hearing aids could help reduce the pace of cognitive decline.Some background: In 2020, the influential Lancet Commission on Dementia Prevention, Intervention and Care identified hearing loss as the greatest potentially modifiable risk factor for dementia.Previous studies had demonstrated a link between hearing loss and cognitive decline, said Dr. Frank Lin, an otolaryngologist and epidemiologist at Johns Hopkins and lead author of the new research.“What remained unanswered was, If we treat hearing loss, does it actually reduce cognitive loss?” he said. The ACHIEVE study (for Aging and Cognitive Health Evaluation in Elders) showed that, at least for a particular group of older adults, it could.Of nearly 1,000 people ages 70 to 84 with untreated mild to moderate hearing loss, half received hearing assessments from audiologists, were fitted with midpriced hearing aids and were counseled on how to use them for several months. The control group participated in a health education program.Over three years, the study found that hearing-aid use had scant effect on healthy volunteers at low risk of cognitive loss. But among participants who were older and less affluent, hearing aids reduced the rate of cognitive decline by 48 percent, compared with the control group, a difference the researchers deemed “clinically meaningful.”This subset of participants had lower income and “were older, less educated, with higher rates of diabetes and hypertension,” Dr. Lin said. Because such factors are also associated with dementia, “the people at higher risk really stand to benefit the most,” he said.In trying to slow cognitive decline, “with a lot of other therapies and treatments, we learn that they can be too little, too late,” he added. ACHIEVE indicates that “they can still see the benefits later in life.” Another three years of follow-up should reveal any further effects of hearing-aid use on both groups.The researchers also plan to publish findings on how hearing-aid use affects brain atrophy, social isolation, depression and quality of life.Some experts object to emphasizing a connection between dementia and hearing loss, “as though it plants a dementia seed and the hearing aid keeps it from germinating,” said Dr. Jan Blustein, a medical researcher at the N.Y.U. Grossman School of Medicine.Because of the stigma of dementia, “people who would potentially get treatment for hearing loss may be less likely to,” Dr. Blustein said.She added that enabling greater social interaction, with its known beneficial effects on cognition and mental health, is reason enough to promote hearing-aid use. Researchers at the University of Colorado also recently reported that consistent hearing-aid use by older adults was associated with a lower risk of falls.But acquiring quality hearing aids over the counter, as opposed to more expensive prescription devices through an audiology practice, can still feel challenging.The F.D.A. reviews “self-fitting” hearing aids, the kind users can customize with a smartphone app; it has found eight brands in compliance with regulations since 2022. A small study recently published in JAMA Otolaryngology found that patients who were given a commercially available, self-fitting hearing aid in a clinical trial could, after six weeks, hear as well as patients fitted with the same device by audiologists.But not everyone with hearing loss feels comfortable with online sales and do-it-yourself adjustments via apps. And devices that aren’t self-fitting, and instead use preset controls, don’t undergo F.D.A. review at all.“It’s still Day 1 of the market’s opening,” said Barbara Kelley, executive director of the Hearing Loss Association of America, an advocacy and support group. “The price points are all over. There’s still confusion among consumers.”Adding to that uncertainty, some marketers have resorted to misleading advertising — some claim that their devices restore natural hearing, for instance. No hearing aid can do that.“There are bad actors,” said Kate Carr, president of the Hearing Industries Association, which represents major manufacturers. “One company was advertising ‘C.I.A. technology.’” In response, the F.D.A. published a guide for consumers this year.Still, progress. Self-fitting O.T.C. aids that perform well are now widely available for about $1,000 a pair; prescription hearing aids purchased through audiologists cost several times more.Perhaps because older Americans don’t know about or mistrust the new over-the-counter devices, or because they still find the price a barrier, initial sales appear modest. (Traditional Medicare doesn’t cover hearing aids; Medicare Advantage plans offering hearing benefits still leave patients paying most of the costs.)Lexie Hearing, a major manufacturer, sells self-fitting O.T.C. devices for $799 to $999 a pair online and in 14,000 stores nationwide. According to Seline van der Wat, the chief operating officer, the company is on track to sell 90,000 pairs this year. But Lexie, whose hearing aids are designed and engineered by Bose, is encouraged by its findings that 94 percent of those buyers are first-time purchasers.“We’re finally able to access a part of the market that was previously unpenetrated because of the costs,” she said. The company projects sales of 260,000 pairs next year and a million per year in 2027.Other device makers and distributors are ramping up, too. Best Buy announced that 200 more of its stores began carrying O.T.C. hearing aids this summer, and that number will reach 600 this fall. The global vision company EssilorLuxottica plans to introduce hearing aids embedded in eyeglass earpieces late next year.Several traditional manufacturers have also begun selling over-the-counter devices, sometimes teaming up with better-known consumer companies to promote brand recognition: WS Audiology with Sony, Sonova with Sennheiser. Some experts expect Apple, Sanyo or other consumer-electronics giants to enter the field.To help guide buyers, HearAdvisor — a company founded by two audiologists and a hearing scientist — has built an independent acoustic lab in Rockford, Ill., to evaluate and rank both prescription and O.T.C. hearing aids for those with mild to moderate loss.“We’re trying to be the Good Housekeeping seal of approval for hearing aids,” Andy Sabin, a co-founder, said.After testing about 50 devices to date, HearAdvisor gave its “Expert Choice” award to 13. In general, O.T.C. devices that cost $1,000 or more perform well, Dr. Sabin said, while those sold online today for under $500 “are most often junk.” A few may actually reduce intelligibility.Wirecutter, a division of The New York Times, has also evaluated hearing aids, and the Hearing Loss Association has planned a series of webinars called OTC 101. The first, on Nov. 1, will feature F.D.A. regulators.The United States is the first country to develop a regulated O.T.C. hearing aid market, and “the tech companies and the retailers are still experimenting,” Dr. Lin pointed out. He predicts increased innovation and lower prices ahead.At the moment, though, he said, “it’s still very much a work in progress.”

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F.D.A. Experts Will Vote on a Cure for Sickle Cell Disease

The treatment from the company Vertex would be the first medicine to use the gene editing tool CRISPR.The LatestOn Tuesday, Oct. 31, an advisory committee to the Food and Drug Administration will consider a gene editing treatment for sickle cell disease, a potentially deadly, excruciatingly painful, lifelong condition in which blood cells are deformed.If the panel finds the safety data acceptable and does not think the treatment needs additional study, and the F.D.A.’s commissioner concurs with its assessment, it will be the first medicine to use the revolutionary tool, CRISPR, to snip out a piece of DNA. Other comparable treatments for sickle cell could follow.“This is a huge deal,” said Dr. John Tisdale, director of the cellular and molecular therapeutics branch at the National Heart, Lung and Blood Institute.A sickle cell disease patient received a blood transfusion to alleviate his pain at a hospital in Kansas City, Mo.Tammy Ljungblad/The Kansas City Star/Tribune News Service, via Getty ImagesWhy It Matters: A disease with a toll that is difficult to imagine.An estimated 100,000 people in the United States have sickle cell disease, most of whom have African ancestry. Sickle cell shortens lives, injures organs and bones and causes episodes of searing pain that can repeatedly send patients to emergency rooms, or lead to lengthy hospital stays.A report by the Institute for Clinical and Economic Review said that for people who don’t have sickle cell disease, “it is hard to understand the physical, emotional and mental toll.” People with the disease, the report added, “not only described intense fatigue, anxiety and depression, but at times extreme hopelessness.”One patient, Mariah Jacqueline Scott, 32, who lives in Highland Park, N.J., has had two hip replacements, two shoulder replacements, a splenectomy, a gall bladder removal and a tonsillectomy because of the disease. She spent the year after her daughter was born in and out of the hospital being treated for extreme pain caused by blocked blood vessels. She had her second shoulder replacement after her shoulder collapsed while she was holding her baby.The only cure has been a bone-marrow transplant, which requires finding a donor, undergoing intensive chemotherapy and taking immunosuppressive drugs. But gene editing offers an alternative. Vertex and CRISPR Therapeutics, the makers of the treatment being taken up by the F.D.A. committee on Tuesday, said that in clinical trials, symptoms of the disease went away after patients had the treatment. So far, the patients appear to be cured. The technique activates a gene that can make normally functioning blood cells.Ms. Scott said she knew gene editing was arduous, but she was seriously considering undergoing the treatment when it became available.Facts to Keep in Mind: Gene therapies bring their own challenges.Vertex’s therapy starts when doctors remove stem cells from the blood and send them for treatment. Next comes intense chemotherapy to completely clear the bone marrow before the treated cells are injected. After that, patients must spend at least a month in a hospital while the treated cells repopulate the bone marrow.Because each patient’s cells must be treated individually there are questions about how quickly companies can ramp up production.“Manufacturing is very complicated,” said Dr. Stephan Grupp, chief of the cellular therapy and transplant section of Children’s Hospital of Philadelphia, who consults for Vertex.Treatment will be extremely expensive, potentially in the millions of dollars per patient, and the companies will not say how many patients they expect to be able to treat at first.Gene editing can also impose personal hardship on patients and their families. A hospital with the expertise to administer the treatment and care for patients may be far from home. And patients must stay there for a long period of time.What’s next: More F.D.A. decisions and more drugs.If the advisory committee recommends the Vertex treatment, the F.D.A. will decide whether to approve it on Dec. 8.On Dec. 20, the F.D.A. will decide on another application for sickle cell gene therapy made by Bluebird Bio. Two other companies and an academic center, Boston Children’s Hospital, are testing their own sickle cell gene therapies.While these therapies could reduce the suffering of sickle cell patients in the United States and other wealthy countries, there is an even greater need for them in some developing countries like Nigeria. However, they will be difficult to export to developing countries because the treatments are extremely expensive and they can only be administered at hospitals where doctors have expertise in a number of advanced techniques.One company, Beam, is testing a way to provide gene editing that requires nothing more than a single infusion in a doctor’s office. Vertex has what it calls an “aspirational” method that would deliver gene editing in a pill.

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Protein interaction causing rare but deadly vaccine-related clotting found

A mechanism that led some patients to experience cases of deadly clotting following some types of Covid-19 vaccination has been identified in new research.
In a paper published in Blood, scientists from the University of Birmingham funded by the National Institute for Health and Care Research and the British Heart Foundation have been able to identify how deadly blood clots, in the disease known as Vaccine-Induced Immune Thrombocytopenia and Thrombosis (VITT), occur.
Previous studies have shown that patients with VITT produce antibodies that stick to a protein called Platelet factor 4 (PF4) to create a large cluster of molecules called an immune complex. Following the development of a complex, platelets and cells of the immune system causing clotting and inflammation are activated, but the precise nature of what PF4 does in this event was unknown.
In this latest study, the team used blood taken from healthy donors, as well as serum and plasma from patients with VITT, and have been able to learn for the first time how PF4 was directly involved in the activation of platelets and resulted in thrombotic events. By sticking to a receptor called c-Mpl on the surface of platelets, PF4 triggered the production of the small cells known to cause clotting.
Dr Pip Nicolson, Associate Clinical Professor in Cardiovascular Medicine at the University of Birmingham and senior author of the study said: “The major advances seen in vaccine development during the global Covid-19 pandemic were thrown into sharp relief following the tragic, rare cases of vaccine-induced immune thrombosis. While there were alternative vaccines available to continue to provide protection against the coronavirus in some countries around the world, understanding the mechanisms behind these cases is critical to ensuring that the technology for delivering vaccines can be used with confidence in the future.”
Dr Richard Buka, Research Fellow in the Institute of Cardiovascular Sciences and co-lead author “As well as identifying a new way in which platelets are being activated in a potentially deadly manner in VITT, our research has also been able to find how this mechanism may lead to new drugs to protect against blood clots in VITT and blood clots in general.”
Variations on a drug used to treat bone marrow cancers could be developed to protect VITT patients from deadly clotting, the research also found.
The team used ruxolitinib, a drug used to treat some types of blood cancer, to block the receptor being triggered by PF4 following the vaccine-induced event. Although they note that the current form of the drug is unsuitable for use in VITT patients, the team nevertheless identified that blocking the pathway through ruxolitinib slowed down platelet aggregation and demonstrates a potential future way to protect patients from blood clots.
Dr Samantha Montague, Research Fellow in the Institute of Cardiovascular Sciences at the University of Birmingham and co-lead author of the paper said: “It is gratifying that we have been able to identify a new, important biological mechanism through trying to thoroughly understand a new disease. This work helps us to understand more fundamental things about how blood clots form and may also be relevant in other related diseases that are more common.
“Our ongoing research funded by the British Heart Foundation is looking at how we can identify patients who may develop VITT, with a view that future vaccine programmes around the world can be delivered while understanding and managing the potential risk for those few at greatest risk.”

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