health

to-pee-or-not-to-pee?-that-is-a-question-for-the-bladder—and-the-brain

To pee or not to pee? That is a question for the bladder—and the brain

💦 —

The basic urge to pee is surprisingly complex and can go awry as we age.

Cut view of man covering urine with hands. He has some pain and problem. Isolated on striped and blue background

You’re driving somewhere, eyes on the road, when you start to feel a tingling sensation in your lower abdomen. That extra-large Coke you drank an hour ago has made its way through your kidneys into your bladder. “Time to pull over,” you think, scanning for an exit ramp.

To most people, pulling into a highway rest stop is a profoundly mundane experience. But not to neuroscientist Rita Valentino, who has studied how the brain senses, interprets, and acts on the bladder’s signals. She’s fascinated by the brain’s ability to take in sensations from the bladder, combine them with signals from outside of the body, like the sights and sounds of the road, then use that information to act—in this scenario, to find a safe, socially appropriate place to pee. “To me, it’s really an example of one of the beautiful things that the brain does,” she says.

Scientists used to think that our bladders were ruled by a relatively straightforward reflex—an “on-off” switch between storing urine and letting it go. “Now we realize it’s much more complex than that,” says Valentino, now director of the division of neuroscience and behavior at the National Institute of Drug Abuse. An intricate network of brain regions that contribute to functions like decision-making, social interactions, and awareness of our body’s internal state, also called interoception, participates in making the call.

In addition to being mind-bogglingly complex, the system is also delicate. Scientists estimate, for example, that more than 1 in 10 adults have overactive bladder syndrome—a common constellation of symptoms that includes urinary urgency (the sensation of needing to pee even when the bladder isn’t full), nocturia (the need for frequent nightly bathroom visits) and incontinence. Although existing treatments can improve symptoms for some, they don’t work for many people, says Martin Michel, a pharmacologist at Johannes Gutenberg University in Mainz, Germany, who researches therapies for bladder disorders. Developing better drugs has proven so challenging that all major pharmaceutical companies have abandoned the effort, he adds.

Recently, however, a surge of new research is opening the field to fresh hypotheses and treatment approaches. Although therapies for bladder disorders have historically focused on the bladder itself, the new studies point to the brain as another potential target, says Valentino. Combined with studies aimed at explaining why certain groups, such as post-menopausal women, are more prone to bladder problems, the research suggests that we shouldn’t simply accept symptoms like incontinence as inevitable, says Indira Mysorekar, a microbiologist at Baylor College of Medicine in Houston. We’re often told such problems are just part of getting old, particularly for women—“and that’s true to some extent,” she says. But many common issues are avoidable and can be treated successfully, she says: “We don’t have to live with pain or discomfort.”

A delicate balance

The human bladder is, at the most basic level, a stretchy bag. To fill to capacity—a volume of 400 to 500 milliliters (about 2 cups) of urine in most healthy adults—it must undergo one of the most extreme expansions of any organ in the human body, expanding roughly sixfold from its wrinkled, empty state.

To stretch that far, the smooth muscle wall that wraps around the bladder, called the detrusor, must relax. Simultaneously, sphincter muscles that surround the bladder’s lower opening, or urethra, must contract, in what scientists call the guarding reflex.

It’s not just sensory neurons (purple) that can detect stretch, pressure, pain and other sensations in the bladder. Other types of cells, like the umbrella-shaped cells that form the urothelium’s barrier against urine, can also sense and respond to mechanical forces — for example, by releasing chemical signaling molecules such as adenosine triphosphate (ATP) as the organ expands to fill with urine.

Enlarge / It’s not just sensory neurons (purple) that can detect stretch, pressure, pain and other sensations in the bladder. Other types of cells, like the umbrella-shaped cells that form the urothelium’s barrier against urine, can also sense and respond to mechanical forces — for example, by releasing chemical signaling molecules such as adenosine triphosphate (ATP) as the organ expands to fill with urine.

Filling or full, the bladder spends more than 95 percent of its time in storage mode, allowing us to carry out our daily activities without leaks. At some point—ideally, when we decide it’s time to pee—the organ switches from storage to release mode. For this, the detrusor muscle must contract forcefully to expel urine, while the sphincter muscles surrounding the urethra simultaneously relax to let urine flow out.

For a century, physiologists have puzzled over how the body coordinates the switch between storage and release. In the 1920s, a surgeon named Frederick Barrington, of University College London, went looking for the on-off switch in the brainstem, the lowermost part of the brain that connects with the spinal cord.

Working with sedated cats, Barrington used an electrified needle to damage slightly different areas in the pons, part of the brainstem that handles vital functions like sleeping and breathing. When the cats recovered, Barrington noticed that some demonstrated a desire to urinate—by scratching, circling, or squatting—but were unable to voluntarily go. Meanwhile, cats with lesions in a different part of the pons seemed to have lost any awareness of the need to urinate, peeing at random times and appearing startled whenever it happened. Clearly, the pons served as an important command center for urinary function, telling the bladder when to release urine.

To pee or not to pee? That is a question for the bladder—and the brain Read More »

fda’s-review-of-mdma-for-ptsd-highlights-study-bias-and-safety-concerns

FDA’s review of MDMA for PTSD highlights study bias and safety concerns

Complicated —

FDA advisors will meet June 4 to discuss and vote on the therapy’s effectiveness.

MDMA is now in the FDA's hands.

Enlarge / MDMA is now in the FDA’s hands.

The safety and efficacy data on the use of MDMA (aka ecstasy) for post-traumatic stress disorder therapy is “challenging to interpret,” the Food and Drug Administration said in a briefing document posted Friday. The agency noted significant flaws in the design of the underlying clinical trials as well as safety concerns for the drug, particularly cardiovascular harms.

On Tuesday, June 4, the FDA will convene an advisory committee that will review the evidence and vote on MDMA’s efficacy and whether its benefits outweigh its risks. The FDA does not have to follow the committee’s recommendations, but it often does. If the FDA subsequently approves MDMA as part of treatment for PTSD, it would mark a significant shift in the federal government’s stance on MDMA, as well as psychedelics, generally. Currently, the US Drug Enforcement Administration considers MDMA a Schedule I drug, defined as one with “no currently accepted medical use and a high potential for abuse.” It would also offer a new treatment option for patients with PTSD, a disabling psychiatric condition with few treatment options currently.

As Ars has reported previously, the submission of MDMA for approval is based on two clinical trials. The first trial, published in Nature Medicine in 2021, involved 90 participants with moderate PTSD and found that MDMA-assisted psychotherapy significantly improved Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) scores compared with participants who were given psychotherapy along with a placebo. In the second study, published in September in Nature Medicine, the finding held up among 104 participants with moderate or severe PTSD (73 percent had severe PTSD).

In the briefing documents released Friday, the FDA highlighted that there was a high potential for bias to have crept into those results. Though the trials were designed to be double-blind (meaning that therapists and trial participants were not told who received MDMA), the FDA noted that MDMA “produces profound alterations in mood, sensation, suggestibility, and cognition.” Blinding is “nearly impossible,” the FDA wrote.  And indeed, approximately 90 percent of those assigned to take MDMA and 75 percent of those assigned to a placebo were able to accurately guess their treatment assignment, the FDA notes. As such, it is “reasonable to assume” that bias and “expectation bias” affected the results of the trials, the FDA concluded.

The agency also noted concerns that MDMA caused “significant increases in blood pressure and pulse,” which could trigger cardiac events, such as heart attacks. However, the trial data was limited for assessing the risks of these adverse events.

The FDA also dinged the studies for not including data on whether participants experienced effects such as “euphoria” after taking MDMA—an anticipated effect that could indicate the drug’s potential for abuse.

In all, the FDA’s review presented a complicated picture of MDMA’s risk-benefit assessment, one that should make for an interesting discussion Tuesday. The FDA’s criticisms follows an even more critical report released earlier this month by the Institute for Clinical and Economic Review (ICER), which identified “substantial concerns about the validity of the results” from the clinical trials.

Like the FDA, ICER found the trials to be “essentially unblinded.” However, ICER went further, having conducted a number of interviews with trial participants and others involved, finding that the trials largely pulled from an existing community of psychedelic advocates and supporters, introducing significant bias. “Concerns have been raised by some that therapists encouraged favorable reports by patients and discouraged negative reports by patients including discouraging reports of substantial harms, potentially biasing the recording of benefits and harms,” the report said. MDMA is known to induce confusion, depression, and paranoia in some. One participant reported feeling “relentlessly suicidal” after the trial, as a result of participating in it, but that result was not reflected in the trial’s reported results.

Various people told ICER that the community involved in the trials regarded psychedelics “more like a religious movement than like pharmaceutical products.” Some participants felt as though “they could be shunned if they reported bad outcomes or that it could lead to future patients being denied the benefits of MDMA-AP.”

In all, ICER concluded that the evidence available to assess for MDMA treatment is “insufficient.”

Editor’s Note: This story was corrected to report that the participant’s suicidal thoughts occurred after the trial, as a result of participation, not during the trial.

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modern-lives-are-messing-up-menstrual-cycles—earlier-starts,-more-irregularity

Modern lives are messing up menstrual cycles—earlier starts, more irregularity

downward trend —

Earlier and irregular periods are both linked to poor health outcomes.

Panty liners, hygienic tampons, and sanitary pads.

Enlarge / Panty liners, hygienic tampons, and sanitary pads.

People in the US are starting their menstrual cycles earlier and experiencing more irregularities, both of which raise the risk of a host of health problems later in life, according to an Apple women’s health study looking at data from over 70,000 menstruating iPhone users born between 1950 and 2005.

The mean age of people’s first period fell from 12.5 years in participants born between 1950 and 1969 to 11.9 years in participants born between 2000 and 2005, with a steady decline in between, the study found. There were also notable changes in the extremes—between 1950 and 2005, the percentage of people who started their periods before age 11 rose from 8.6 percent to 15.5 percent. And the percentage of people who started their periods late (at age 16 or above) dropped from 5.5 percent to 1.7 percent.

In addition to periods shifting to earlier starting ages, menstrual cycles also appeared to become more irregular. For this, researchers looked at how quickly people settled into a regular cycle after the start of their period. Between 1950 and 2005, the percentage of people obtaining regularity within two years fell from 76.3 percent to 56 percent.

The study, published by researchers at Apple and Harvard in the journal JAMA Network Open, notes that both of these findings bode poorly for long-term health. Early starting age of menstrual cycles is linked to adverse health outcomes, including cardiovascular diseases, cancers, spontaneous abortion, and premature death, the researchers write. And a longer time to regularity is linked to fertility problems, longer menstrual cycles, and an increased risk of metabolic conditions and all-cause mortality.

Looking across race and ethnicity categories, researchers found that the trends affected all groups. However, Black and Hispanic participants had consistently earlier menstrual starting ages than white and Asian participants. Black participants also saw a larger magnitude shift toward earlier starting ages compared with white participants.

It’s unclear what’s driving the menstrual changes, but the authors speculate that there could be a multitude of factors. The most prominent potential factor is childhood obesity, which has increased in the US over the course of the study period and is known to be linked to earlier puberty. However, the authors note that obesity doesn’t explain the totality of the shifts—an exploratory analysis indicated that obesity only accounted for 46 percent of the trends seen in the study. And other studies have indicated that the shift toward earlier menstrual cycles began before the upward trend of obesity in the US.

The authors of the current study point to various potential environmental factors, including endocrine-disrupting chemicals, metals, air pollutants, dietary patterns, psychosocial stress, and adverse childhood experiences.

The study has limitations, of course, including that it relied on self-reported data and was limited to people who own iPhones, who generally skew toward higher socioeconomic status. Thus, the findings may not be generalizable to the population overall. Still, the data fits with other studies, and the researchers called for more awareness among health care practitioners and more studies to look at trends and health outcomes.

Modern lives are messing up menstrual cycles—earlier starts, more irregularity Read More »

as-bird-flu-spreads-in-cows,-us-close-to-funding-moderna’s-mrna-h5-vaccine

As bird flu spreads in cows, US close to funding Moderna’s mRNA H5 vaccine

New jab —

If trials are successful, US government likely to buy doses for vaccine stockpile.

Testing for bird flu, conceptual image

Digicom Photo/Science Photo Library via Getty

The US government is nearing an agreement to bankroll a late-stage trial of Moderna’s mRNA pandemic bird flu vaccine, hoping to bolster its pandemic jab stockpile as an H5N1 outbreak spreads through egg farms and among cattle herds.

The federal funding from the government’s Biomedical Advanced Research and Development Authority, known as BARDA, could come as early as next month, according to people close to the discussions.

It is expected to total several tens of millions of dollars and could be accompanied by a commitment to procure doses if the phase-three trials are successful, they said.

Talks between the government and Pfizer over supporting the development of its mRNA vaccine targeting the H5 family of viruses are also ongoing. Pfizer, like Moderna, played a pivotal role in supplying mRNA vaccines for Washington’s jab rollout during the COVID-19 pandemic.

Bird flu has been detected on poultry farms in 48 states and in dairy cow herds across nine states as part of one of the worst outbreaks in recent history, according to the US Centers for Disease Control and Prevention. The CDC has also reported two cases affecting dairy workers in recent months, adding to concerns of the virus spreading in human populations.

US health authorities continue to classify the public health risk from bird flu as low, but their efforts to build up and diversify the pandemic vaccine stockpile have gathered pace. Federal health officials said last week that the government was moving ahead with plans to fill 4.8 million vials from its existing portfolio of protein-based bird flu vaccines and was in discussions with Moderna and Pfizer.

The possibility of contributing to the US pandemic vaccine stockpile also represents a commercial opportunity for the mRNA vaccine makers, whose market valuations have fallen significantly from pandemic highs. Moderna’s share price is up nearly 37 percent since the start of April.

Moderna has completed dosing of a mid-stage trial of its H5 pandemic flu vaccine, with interim data expected soon. Pfizer said in a statement on Wednesday that it “would be prepared to deploy the company’s capabilities to develop a vaccine for strategic stockpiles,” confirming that it had launched a phase-one trial for a pandemic flu vaccine last December.

Applications for BARDA grant funding for an mRNA-based pandemic flu vaccine closed in December last year, according to a project proposal seen by the Financial Times. But the bird flu outbreak has increased the urgency of talks, with federal officials acknowledging that the speed with which mRNA vaccines were designed and deployed during the COVID-19 pandemic showed their value compared with more traditional vaccine technology.

The jabs from GSK, Sanofi, and CSL Seqirus, which make up the US government’s existing pandemic vaccine portfolio, provide immunity to the current strain of bird flu, according to laboratory testing, but rely on a more time-intensive manufacturing process using egg- and cell-based cultures.

The US health department, Moderna, and Pfizer declined to comment on the potential funding.

© 2024 The Financial Times Ltd. All rights reserved. Not to be redistributed, copied, or modified in any way.

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“deny,-denounce,-delay”:-the-battle-over-the-risk-of-ultra-processed-foods

“Deny, denounce, delay”: The battle over the risk of ultra-processed foods

A shopping cart by a store shelf in a supermarket

When the Brazilian nutritional scientist Carlos Monteiro coined the term “ultra-processed foods” 15 years ago, he established what he calls a “new paradigm” for assessing the impact of diet on health.

Monteiro had noticed that although Brazilian households were spending less on sugar and oil, obesity rates were going up. The paradox could be explained by increased consumption of food that had undergone high levels of processing, such as the addition of preservatives and flavorings or the removal or addition of nutrients.

But health authorities and food companies resisted the link, Monteiro tells the FT. “[These are] people who spent their whole life thinking that the only link between diet and health is the nutrient content of foods … Food is more than nutrients.”

Monteiro’s food classification system, “Nova,” assessed not only the nutritional content of foods but also the processes they undergo before reaching our plates. The system laid the groundwork for two decades of scientific research linking the consumption of UPFs to obesity, cancer, and diabetes.

Studies of UPFs show that these processes create food—from snack bars to breakfast cereals to ready meals—that encourages overeating but may leave the eater undernourished. A recipe might, for example, contain a level of carbohydrate and fat that triggers the brain’s reward system, meaning you have to consume more to sustain the pleasure of eating it.

In 2019, American metabolic scientist Kevin Hall carried out a randomized study comparing people who ate an unprocessed diet with those who followed a UPF diet over two weeks. Hall found that the subjects who ate the ultra-processed diet consumed around 500 more calories per day, more fat and carbohydrates, less protein—and gained weight.

The rising concern about the health impact of UPFs has recast the debate around food and public health, giving rise to books, policy campaigns, and academic papers. It also presents the most concrete challenge yet to the business model of the food industry, for whom UPFs are extremely profitable.

The industry has responded with a ferocious campaign against regulation. In part it has used the same lobbying playbook as its fight against labeling and taxation of “junk food” high in calories: big spending to influence policymakers.

FT analysis of US lobbying data from non-profit Open Secrets found that food and soft drinks-related companies spent $106 million on lobbying in 2023, almost twice as much as the tobacco and alcohol industries combined. Last year’s spend was 21 percent higher than in 2020, with the increase driven largely by lobbying relating to food processing as well as sugar.

In an echo of tactics employed by cigarette companies, the food industry has also attempted to stave off regulation by casting doubt on the research of scientists like Monteiro.

“The strategy I see the food industry using is deny, denounce, and delay,” says Barry Smith, director of the Institute of Philosophy at the University of London and a consultant for companies on the multisensory experience of food and drink.

So far the strategy has proved successful. Just a handful of countries, including Belgium, Israel, and Brazil, currently refer to UPFs in their dietary guidelines. But as the weight of evidence about UPFs grows, public health experts say the only question now is how, if at all, it is translated into regulation.

“There’s scientific agreement on the science,” says Jean Adams, professor of dietary public health at the MRC Epidemiology Unit at the University of Cambridge. “It’s how to interpret that to make a policy that people aren’t sure of.”

“Deny, denounce, delay”: The battle over the risk of ultra-processed foods Read More »

family-stricken-with-rare-brain-worms-after-eating-undercooked-bear

Family stricken with rare brain worms after eating undercooked bear

Unbearably gross —

In the parasite vs. bear vs. human battle, the grizzly parasite comes out on top.

American black bear seen along the Red Rock Parkway inside Waterton Lakes National Park in Alberta, Canada.

Enlarge / American black bear seen along the Red Rock Parkway inside Waterton Lakes National Park in Alberta, Canada.

In the summer of 2022, a family gathered in South Dakota for a reunion that included a special meal—kabobs made with the meat of a black bear that one of the family members had “harvested” from northern Saskatchewan, Canada, that May. Lacking a meat thermometer, the family assessed the doneness of the dark-colored meat by eye. At first, they accidentally served it rare, which a few family members noticed before a decision was made to recook it. The rest of the reunion was unremarkable, and the family members departed to their homes in Arizona, Minnesota, and South Dakota.

But just days later, family members began falling ill. One, a 29-year-old male in Minnesota, sought care for a mysterious illness marked by fever, severe muscle pains, swelling around his eyes (periorbital edema), high levels of infection-fighting white blood cells (eosinophilia, a common response to parasites), and other laboratory anomalies. The man sought care four times and was hospitalized twice in a 17-day span in July. It wasn’t until his second hospitalization that doctors learned about the bear meat—and then it all made sense.

The doctors suspected the man had a condition called trichinellosis and infection of Trichinella nematodes (roundworms). These dangerous parasites can be found worldwide, embedded into the muscle fibers of various carnivores and omnivores, according to the Centers for Disease Control and Prevention. But, it’s quite rare to find them in humans in North America. Between 2016 and 2022, there were seven outbreaks of trichinellosis in the US, involving just 35 cases. The majority were linked to eating bear meat, but moose and wild boar meat are also common sources.

Trichinella nativa infections—Arizona, Minnesota, and South Dakota, 2022.” height=”396″ src=”https://cdn.arstechnica.net/wp-content/uploads/2024/05/mm7320a2-F-large-640×396.webp” width=”640″>

Enlarge / Microscopic examination of encapsulated larvae in a direct black bear meat muscle squash prep (A), larvae liberated from artificially digested bear meat (B), and motile larvae viewed with differential interference contrast microscopy (C and D)from black bear meat suspected as the source of an outbreak of human Trichinella nativa infections—Arizona, Minnesota, and South Dakota, 2022.

Once eaten, larvae encased in the meat are released and begin to invade the small intestines (the gastrointestinal phase), causing pain, diarrhea, nausea, and vomiting. Then, the larvae develop into adults in the gut, mate, and produce more larvae there. The second generation of worms then go wandering through the lymphatic system, into the blood, and then throughout the body (systemic phase). The larvae can end up all over, reaching skeletal muscles, the heart, and the brain, which is rich in oxygen. The systemic phase is marked by fever, periorbital edema, muscle pain, heart inflammation, and brain inflammation. The larvae can also provoke severe eosinophilia, particularly when they move into the heart and central nervous system.

The man’s symptoms fit the case, and several tests confirmed the parasitic infection. Of eight interviewed family members present for the bear-meat meal, six people had illnesses matching trichinellosis (ranging in age from 12 to 62), and three of them were hospitalized, including the 12-year-old. Four of the six sickened people had eaten the bear meat, while two only ate vegetables that were cooked alongside the meat and cross-contaminated. Experts at the CDC obtained leftover frozen samples of the bear meat, which revealed moving larvae. Testing identified the worm as Trichinella nativa, a species that is resistant to freezing.

In an outbreak study published Thursday in the CDC’s Morbidity and Mortality Weekly Report, health officials from Minnesota and the CDC reported that the three hospitalized patients were treated with the anti-parasitic drug albendazole and recovered. The remaining three cases fortunately recovered without treatment. The health experts noted how tricky it can be to identify and diagnose these rare cases but flagged periorbital edema and the eosinophilia as being key clinical clues to the grizzly infections. And, above all, people who are going to eat wild game meat should invest in a meat thermometer and make sure the meat is cooked to at least ≥165° F (≥74° C) to avoid risking brain worms.

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new-research-shows-gas-stove-emissions-contribute-to-19,000-deaths-annually

New research shows gas stove emissions contribute to 19,000 deaths annually

New research shows gas stove emissions contribute to 19,000 deaths annually

Ruth Ann Norton used to look forward to seeing the blue flame that danced on the burners of her gas stove. At one time, she says, she would have sworn that preparing meals with the appliance actually made her a better cook.

But then she started learning about the toxic gasses, including carbon monoxide, formaldehyde and other harmful pollutants that are emitted by stoves into the air, even when they’re turned off.

“I’m a person who grew up cooking, and love that blue flame,” said Norton, who leads the environmental advocacy group known as the Green & Healthy Homes Initiative. “But people fear what they don’t know. And what people need to understand really strongly is the subtle and profound impact that this is having—on neurological health, on respiratory health, on reproductive health.”

In recent years, gas stoves have been an unlikely front in the nation’s culture wars, occupying space at the center of a debate over public health, consumer protection, and the commercial interests of manufacturers. Now, Norton is among the environmental advocates who wonder if a pair of recent developments around the public’s understanding of the harms of gas stoves might be the start of a broader shift to expand the use of electrical ranges.

On Monday, lawmakers in the California Assembly advanced a bill that would require any gas stoves sold in the state to bear a warning label indicating that stoves and ovens in use “can release nitrogen dioxide, carbon monoxide, and benzene inside homes at rates that lead to concentrations exceeding the standards of the Office of Environmental Health Hazard Assessment and the United States Environmental Protection Agency for outdoor air quality.”

The label would also note that breathing those pollutants “can exacerbate preexisting respiratory illnesses and increase the risk of developing leukemia and asthma, especially in children. To help reduce the risk of breathing harmful gases, allow ventilation in the area and turn on a vent hood when gas-powered stoves and ranges are in use.”

The measure, which moved the state Senate, could be considered for passage later this year.

“Just running a stove for a few minutes with poor ventilation can lead to indoor concentrations of nitrogen dioxide that exceed the EPA’s air standard for outdoors,” Gail Pellerin, the California assembly member who introduced the bill, said in an interview Wednesday. “You’re sitting there in the house drinking a glass of wine, making dinner, and you’re just inhaling a toxic level of these gases. So, we need a label to make sure people are informed.”

Pellerin’s proposal moved forward in the legislature just days after a group of Stanford researchers announced the findings of a peer-reviewed study that builds on earlier examinations of the public health toll of exposure to nitrogen dioxide pollution from gas and propane stoves.

New research shows gas stove emissions contribute to 19,000 deaths annually Read More »

“outrageously”-priced-weight-loss-drugs-could-bankrupt-us-health-care

“Outrageously” priced weight-loss drugs could bankrupt US health care

Collision course —

Prices would need to be dramatically slashed to avoid increasing the national deficit.

Packaging for Wegovy, manufactured by Novo Nordisk, is seen in this illustration photo.

Enlarge / Packaging for Wegovy, manufactured by Novo Nordisk, is seen in this illustration photo.

With the debut of remarkably effective weight-loss drugs, America’s high obesity rate and its uniquely astronomical prescription drug pricing appear to be set on a catastrophic collision course—one that threatens to “bankrupt our entire health care system,” according to a new Senate report that modeled the economic impact of the drugs in different uptake scenarios.

If just half of the adults in the US with obesity start taking a new weight-loss drug, such as Wegovy, the collective cost would total an estimated $411 billion per year, the analysis found. That’s more than the $406 billion Americans spent in 2022 on all prescription drugs combined.

While the bulk of the spending on weight-loss drugs will occur in the commercial market—which could easily lead to spikes in health insurance premiums—taxpayer-funded Medicare and Medicaid programs will also see an extraordinary financial burden. In the scenario that half of adults with obesity go on the drug, the cost to those federal programs would total $166 billion per year, rivaling the programs’ total 2022 drug costs of $175 billion.

In all, by 2031, total US spending on prescription drugs is poised to reach over $1 trillion per year due to weight-loss drugs. Without them, the baseline projected spending on all prescription drugs would be just under $600 billion.

The analysis was put together by the Senate’s Health, Education, Labor, and Pensions (HELP) committee, chaired by staunch drug-pricing critic Bernie Sanders (I-Vt). And it’s quick to knock down a common argument about the high prices for smash-hit weight-loss drugs. That is, with their high effectiveness, the drugs will improve people’s health in wide-ranging ways, including controlling diabetes, improving cardiovascular health, and potentially more. And, with those improvements, people won’t need as much health care, generally, lowering health care costs across the board.

But, while the drugs do appear to have wide-ranging, life-altering benefits for overall health, the prices of the drugs are still set too high to be entirely offset by any savings in health care use. The HELP committee analysis cited a March Congressional Budget Office (CBO) report that found: “at their current prices, [anti-obesity medicines] would cost the federal government more than it would save from reducing other health care spending—which would lead to an overall increase in the deficit over the next 10 years.” Moreover, in April, the head of the CBO said that the drugmakers would have to slash prices of their weight-loss drugs by 90 percent to “get in the ballpark” of not increasing the national deficit.

The HELP committee report offered a relatively simple solution to the problem: Drugmakers should set their US prices to match the relatively low prices they’ve set in other countries. The report focused on Wegovy because it currently accounts for the most US prescriptions in the new class of weight-loss drugs (GLP-1 drugs). Wegovy is made by Denmark-based Novo Nordisk.

In the US, the estimated net price (after rebates) of Wegovy is $809 per month. In Denmark, the price is $186 per month. A study by researchers at Yale estimated that drugs like Wegovy can be profitably manufactured for less than $5 per month.

If Novo Nordisk set its US prices for Wegovy to match the Danish price, spending to treat half of US adults with obesity would drop from $411 billion to $94.5 billion, a roughly $316.5 billion savings.

Without a dramatic price cut, Americans will likely face either losing access to the drugs or shouldering higher overall health care costs, or some of both. The HELP committee report highlighted how this recently played out in North Carolina. In January, the board of trustees for the state employee health plan voted to end all coverage of Wegovy and other GLP-1 drugs due to the cost. Estimates found that if the plan continued to cover the drugs, the state would need to nearly double health insurance premiums to offset the costs.

“Outrageously” priced weight-loss drugs could bankrupt US health care Read More »

ultra-spicy-one-chip-challenge-chip-contributed-to-teen’s-death,-report-says

Ultra-spicy One Chip Challenge chip contributed to teen’s death, report says

Tragic —

The high dose of capsaicin paired with a heart defect appear to have contributed.

Ultra-spicy One Chip Challenge chip contributed to teen’s death, report says

An autopsy report of a Massachusetts teen who tragically died hours after eating an ultra-spicy tortilla chip suggested that his death was due to the high dose of spice in the chip and a congenital heart defect, according to reporting by the Associated Press.

Harris Wolobah, a previously healthy 14-year-old from Worcester, died September 1, 2023 hours after eating the chip—a 2023 Paqui One Chip Challenge chip—which were sold individually, wrapped in tin foil, and seasoned with two of hottest peppers in the world, the Naga Viper pepper and the Carolina Reaper pepper. Paqui sold the chip with a challenge in which eaters were dared to consume the chip, wait as long as possible before eating or drinking anything, and post the aftermath on social media, where the challenge went viral.

Harris’ mother, Lois Wolobah, immediately suspected the chip was involved in his untimely death. At the time, she reportedly said she picked him up from school after getting a call from the nurse. He was clutching his stomach and, about two hours later, lost consciousness and was rushed to the hospital, where he died. She reported that he had no known medical conditions at the time.

According to the autopsy report, Harris died of cardiopulmonary arrest “in the setting of recent ingestion of food substance with high capsaicin concentration,” the AP reported. Capsaicin is the compound in peppers that gives them their heat.

The report also noted that Harris had an enlarged heart and a congenital anomaly called “myocardial bridging.” This is a common and generally benign condition in which one or more of the arteries delivering blood to the heart go through the heart’s muscle instead of lying on its surface, according to Stanford Medicine. In Harris’ case, the condition involved his left anterior descending coronary artery. An analysis on the American Academy of Cardiology’s website noted that myocardial bridging is “clinically silent” in the majority of cases.

Dr. James Udelson, chief of cardiology at Tufts Medical Center, confirmed to the AP that the chip could have played a role in the teen’s death. “It is possible that with significant stimulation of the heart, the muscle beyond the bridge suddenly had abnormal blood flow (‘ischemia’) and could have been a cause of a severe arrhythmia,” Udelson told the AP in an email. “There have been reports of acute toxicity with capsaicin causing ischemia of the heart muscle.”

A second expert, Dr. Syed Haider, a cardiologist at MedStar Washington Hospital Center, added to the AP that the large doses of capsaicin can increase how the heart squeezes, putting extra pressure on the artery.

Even if Harris’ heart defect made him more vulnerable to the effects of the chip, other case studies have found dangerous and life-threatening effects of high doses of capsaicin in people without heart anomalies. Ultra-hot peppers have also been linked to conditions in which arteries in the brain constrict, causing thunderclap headaches and neurological symptoms.

Paqui, a subsidiary of Hershey, pulled the chip from the market shortly after Harris’ death.

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It could soon be illegal to publicly wear a mask for health reasons in NC

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Senators skeptical of legal trouble for harmless masking after moving to make it illegal.

It could soon be illegal to publicly wear a mask for health reasons in NC

The North Carolina State Senate on Wednesday voted 30–15, along party lines, in favor of a Republican bill that would make it illegal for people in the state to wear a mask in public for health reasons. The bill is now moving to the House, where it could potentially see changes.

The proposed ban on health-based masking is part of a larger bill otherwise aimed at increasing penalties for people wearing masks to conceal their identity while committing a crime or impeding traffic. The bill was largely spurred by recent protests on university and college campuses across the country, including North Carolina-based schools, against the war in Gaza. In recent months, there have been demonstrations in Raleigh and Durham that have blocked roadways, as well as clashes on the nearby campus of the University of North Carolina at Chapel Hill. Some demonstrators were seen wearing masks in those events.

But the bill, House Bill 237, goes a step further by making it illegal to wear a mask in public for health and safety reasons, either to protect the wearer, those around them, or both. Specifically, the bill repeals a 2020 legal exemption enacted amid the COVID-19 pandemic, which allowed for public health-based masking for the first time in decades.

Prior to 2020, laws dating back to 1953 largely prohibited public masking. The prohibition was part of a crackdown on “secret societies” at the time, or more specifically, an attempt to curtail the activities of the Ku Klux Clan in the state. Exemptions only existed for things like holiday costumes, theater productions, gas masks, and members of public parades or ceremonies that had obtained permits.

On Wednesday, North Carolina residents with compromised immune systems spoke—while masked—during a public comment section. Simone Hetherington told lawmakers that masking was the only way to protect herself in public from illness and feared passage of the bill would prevent her from doing so, according to reporting by the Associated Press.

But, according to The News & Observer, Republicans were dismissive of that possibility, arguing that in the decades prior to the pandemic, when public masking was largely illegal, they couldn’t recall anyone being prosecuted for wearing a mask for health reasons.

Raleigh-based news outlet WRAL quoted Sen. Sydney Batch, a Democrat from Wake, who criticized the bill along with fellow Democratic colleagues. Batch, a cancer survivor, spoke of how her husband and children wore masks to protect her while she underwent cancer treatments that weakened her immune system. “This bill criminalizes their behavior and mine,” she said. “We talk a lot about freedoms in this chamber. I hear it all the time. I should have the freedom—my children and my husband should have the freedom—to wear masks in order to protect and save my life, without fear of being arrested and charged.”

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Raw-milk fans plan to drink up as experts warn of high levels of H5N1 virus

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Raw milk fans called warnings “fear mongering,” despite 52% fatality rate in humans.

A glass of fresh raw milk in the hand of a farmer.

Enlarge / A glass of fresh raw milk in the hand of a farmer.

To drink raw milk at any time is to flirt with dangerous germs. But, amid an unprecedented outbreak of H5N1 bird flu in US dairy cows, the risks have ratcheted up considerably. Health experts have stepped up warnings against drinking raw milk during the outbreak, the scope of which is still unknown.

Yet, raw milk enthusiasts are undaunted by the heightened risk. The California-based Raw Milk Institute called the warnings “clearly fearmongering.” The institute’s founder, Mark McAfee, told the Los Angeles Times this weekend that his customers are, in fact, specifically requesting raw milk from H5N1-infected cows. According to McAfee, his customers believe, without evidence, that directly drinking high levels of the avian influenza virus will give them immunity to the deadly pathogen.

Expert Michael Payne told the LA Times that the idea amounts to “playing Russian roulette with your health.” Payne, a researcher and dairy outreach coordinator at the Western Institute for Food Safety and Security at UC Davis, added, “Deliberately trying to infect yourself with a known pathogen flies in the face of all medical knowledge and common sense.”

Much remains unknown about the biology of avian influenza in cattle. Until March 25, when the US Department of Agriculture confirmed the virus in a dairy herd in Texas, cattle were generally considered virtually resistant to H5N1. But since then, the USDA has tallied 42 herds in nine states that have contracted the virus. Epidemiological data so far suggests that there has been cow-to-cow transmission following a single spillover event and that the 42 outbreak herds are connected by the movement of cattle between farms.

The limited data on the cows so far suggests that the animals largely develop mild illness from the infection and recover in a few weeks. Their mammary glands are the primary target of the virus. A preprint published earlier this month found that cows’ udders are rife with the molecular receptors that bird flu viruses latch onto to spark an infection. Moreover, the glands contain multiple types receptors, including ones targeted by human flu viruses as well as those targeted by bird flu viruses. Thus, dairy cows could potentially act as a mixing vessel for the different types of flu viruses to reassemble into new, outbreak-sparking variants.

With the virus apparently having a field day in cows’ udders, researchers have found raw milk to be brimming with high levels of H5N1 viral particles—and those particles appear readily capable of spilling over to other mammals. In a case study last month, researchers reported that a group of about two dozen farm cats developed severe illness after drinking milk from H5N1-infected cows. Some developed severe neurological symptoms. More than half the cats died in a matter of days.

Deadly virus

Data on flu receptors in the two animals may explain the difference between cows and cats. While the cow’s mammary gland had loads of multiple types of flu receptors, those receptors were less common in other parts of the cow, including the respiratory tract and brain. This may explain why they tend to have a mild infection. Cats, on the other hand, appear to have receptors more widely distributed, with infected cats showing viral invasion of the lungs, hearts, eyes, and brains.

Raw milk devotees—who claim without evidence that drinking raw milk provides health benefits over drinking pasteurized milk—dismiss the risk of exposure to H5N1. They confidently argue—also without evidence—that the human digestive system will destroy the virus. And they highlight that there is no documented evidence of a human ever becoming infected with H5N1 from drinking tainted milk.

The latter point on the lack of evidence of milkborne H5N1 transmission is true. However, the current outbreak is the first known spillover of highly pathogenic avian influenza (HPAI) to dairy cow mammary glands. As such, it presents the first known opportunity for such milk-based transmission to occur.

Before pasteurization became routine for commercial milk production, raw milk was a common source of infections, serving up a cornucopia of germs. According to the FDA, in 1938, milkborne outbreaks accounted for 25 percent of all foodborne disease outbreaks. In more recent times, milk has been linked to less than 1 percent of such outbreaks. The Centers for Disease Control and Prevention notes that areas where raw milk was sold legally between 1998 and 2018 had 3.2 times more outbreaks than areas where the sale of raw milk was illegal.

In a Q&A document, the Food and Drug Administration notes that it does “not know at this time if HPAI A (H5N1) viruses can be transmitted through consumption of unpasteurized (raw) milk and products (such as cheese) made from raw milk from infected cows.” However, the agency goes on, because of that lack of data and the potential for infection, the FDA recommends halting all sales of raw milk and raw milk products from H5N1 infected or exposed cattle. In general, the agency recommends against consuming raw milk.

Globally, as of March 28, there have been 888 cases of H5N1 reported in humans in 23 countries. Of those 888 cases, 463 were fatal. That represents a 52 percent fatality rate; however, it’s possible that there are asymptomatic or undiagnosed cases that could alter that rate. In the US, only one human so far is known to have been infected with H5N1 in connection with the dairy cow outbreak—a farm worker who developed pink eye. The man had no respiratory symptoms and recovered. He did not consent to further follow-up, and researchers did not get consent to test the man’s household contacts to see if they, too, were infected.

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More children gain hearing as gene therapy for profound deafness advances

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The therapy treats a rare type of deafness, but experts hope it’s a “jumping point.”

Opal Sandy (center), who was born completely deaf because of a rare genetic condition, can now hear unaided for the first time after receiving gene therapy at 11-months-old. She is shown with her mother, father, and sister at their home in Eynsham, Oxfordshire, on May 7, 2024.

Enlarge / Opal Sandy (center), who was born completely deaf because of a rare genetic condition, can now hear unaided for the first time after receiving gene therapy at 11-months-old. She is shown with her mother, father, and sister at their home in Eynsham, Oxfordshire, on May 7, 2024.

There are few things more heartwarming than videos of children with deafness gaining the ability to hear, showing them happily turning their heads at the sound of their parents’ voices and joyfully bobbing to newly discovered music. Thanks to recent advances in gene therapy, more kids are getting those sweet and triumphant moments—with no hearing aids or cochlear implants needed.

At the annual conference of the American Society for Gene & Cell Therapy held in Baltimore this week, researchers showed many of those videos to their audiences of experts. On Wednesday, Larry Lustig, an otolaryngologist at Columbia University, presented clinical trial data of two children with profound deafness—the most severe type of deafness—who are now able to hear at normal levels after receiving an experimental gene therapy. One of the children was 11 months old at the time of the treatment, marking her as the youngest child in the world to date to receive gene therapy for genetic deafness.

On Thursday, Yilai Shu, an otolaryngologist at Fudan University in Shanghai, provided a one-year progress report on six children who were treated in the first in-human trial of gene therapy for genetic therapy. Five of the six had their hearing restored.

That trial, like the one Lustig presented, involved treating just one ear in all of the children—a safety precaution for such early trials. But Shu and colleagues have already moved on to both ears, or bilateral treatment. After presenting a progress report on the first trial, Shu presented unpublished early data on five additional patients who participated in the first in-human trial of bilateral treatment. All had bilateral hearing restoration and speech perception improvement.

“The opportunity of providing the full complexity and spectrum of sound in children born with profound genetic deafness is a phenomenon I did not expect to see in my lifetime,” Lustig said in a statement.

Jumping point

Shu and Lustig’s trials are separate but the treatments are, in broad strokes, similar. Both are aimed at restoring hearing loss caused by mutations in the OTOF gene the codes for the protein otoferlin. Normally, otoferlin is a critical protein for transmitting sound signals to the brain, specifically playing a key role in synaptic transmission between the ear’s inner hair cells and the auditory nerve. Using gutted adeno-associated viruses as vectors for gene delivery, the therapies provide the inner ear with a functional version of the OTOF gene. Once in the ear, the gene can be translated into functional otoferlin, restoring auditory signaling.

In the trial Lustig presented, the two patients saw a gradual improvement of hearing as otoferlin protein built up after treatment. For the 11-month-old, normal levels of hearing were restored within 24 weeks of treatment. For the second patient, a 4-year-old, improvements were detected at a six-week assessment. In the trial Shu presented, children began seeing hearing improvements at three- and four-week assessments. The children will continue to be followed into the future, which holds some uncertainties. It’s unclear if they will, at some point in their lives, need additional treatments to sustain their hearing. In mice, at least, the treatment lasts for the duration of the animals’ lives—but they only live for a few years.

“We expect this to last a long time,” Lustig said Wednesday. But “we don’t know what’s going to happen and we don’t know whether we can do a second dose. But, probably, I would guess, at some point that would have to be done.”

For now, the treatment is considered low-hanging fruit for the burgeoning field of gene therapy since it targets a severe condition caused by recessive mutations in a single gene. Otoferlin mutations lead to a very specific type of deafness called auditory neuropathy, in which the ear fails to send signals to the brain but works perfectly fine otherwise. This is an ultra-rare form of deafness affecting 1–8 percent of people with deafness globally. Only about 30 to 50 people in the US are born with this type of deafness each year.

However, Lustig calls it a “jumping point.” Now that researchers have shown that this gene therapy can work, “This is going to really spark, we hope, the development of gene therapy for more common types of deafness,” he said.

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