Publisher Health

The mucus in the airways is not as sticky, inflammation in the lungs significantly reduced: Triple combination therapy can achieve these positive, lasting effects in patients with cystic fibrosis (CF). Researchers from Charité — Universitätsmedizin Berlin and the Max Delbrück Center have just recently published their findings in the European Respiratory Journal.* According to their research, this form of medication improves the symptoms of CF in many patients.
Two years ago, a research group headed by Charité showed that combination therapy involving three drugs — elexacaftor, tezacaftor, and ivacaftor — is effective in a large portion of patients with cystic fibrosis, a hereditary disease, meaning that the treatment noticeably improves both lung function and quality of life. Now, the team headed by Prof. Marcus Mall, who has been the lead researcher in both studies, has investigated for the first time whether this form of treatment is also helpful in the long term, meaning over a period of 12 months or more. To examine this, the researchers took a closer look at the sputum, the secretions from patients’ respiratory tracts. “In patients with cystic fibrosis, the mucus in the airways is very sticky because it doesn’t contain enough water and the mucins, the molecules that form mucus, adhere too much due to their chemical properties. This results in thick, sticky mucus, which clogs the airways, making it harder for patients to breathe and leading to chronic bacterial infection and inflammation of the lungs,” explains Mall, Director of the Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and the Christiane Herzog Cystic Fibrosis Center at Charité.
In the current study, the researchers show that a combination of elexacaftor, tezacaftor, and ivacaftor results in less viscous respiratory secretions and decreasing inflammation and bacterial infection in the lungs of cystic fibrosis patients. “What’s more, the effects lasted over the entire one-year study period. This is really important because previous medications caused a rebound in the bacterial load in the airways,” explains Dr. Simon Gräber, who also works in the Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine at Charité and was one of the co-leaders of the study. 79 adolescents and adults with cystic fibrosis and chronic lung disease participated in the trial.
A major step in treating cystic fibrosis, further research important
“This is a major step forward in treating cystic fibrosis,” Mall says. “At the same time, it would be premature to say that patients have been normalized, let alone cured. Chronic lung changes arising over many years of living with the disease cannot be reversed, unfortunately.” This means patients with advanced lung disease will still need to rely on established treatments involving inhaling mucus-thinning medications, taking antibiotics, and physical therapy.
“We plan to forge ahead with our research on how to make treatments that address cystic fibrosis via the molecular defects that cause the disease — like the triple medication combination studied here — even more effective. This includes starting treatment in early childhood with the goal of preventing chronic lung changes wherever possible,” Mall notes. “Aside from that, this therapy is not available to about ten percent of our patients right now due to their genetic conditions,” Gräber adds. “That’s why we are also hard at work on research involving new molecular treatments so we can treat all people with cystic fibrosis effectively.”
The researchers are also working to advance their understanding of mucus defects in cystic fibrosis and develop new mucolytics, drugs that thin and loosen the mucus. This research could also benefit patients with common chronic inflammatory lung diseases such as asthma and COPD.
Cystic fibrosis
Cystic fibrosis is one of the most common fatal hereditary diseases worldwide. As many as 8,000 children, teens, and adults are living with the disease in Germany today. An imbalance in salt and water transport across mucosal surfaces of the body causes people with cystic fibrosis to produce thick, sticky secretions that harm organs such as the lungs, intestine and pancreas. This leads to progressive loss of lung function and shortness of breath, which still significantly lowers life expectancy despite advances in treatment. Some 150 to 200 children are born with this rare disease in Germany each year.
About the triple combination therapy
A combination of three drugs — elexacaftor, tezacaftor, and ivacaftor — became available in Europe in August 2020. The therapy noticeably improves lung function and quality of life in patients with the most common genetic defect involved in CF, F508del. This means the treatment is an option for nearly 90 percent of those living with cystic fibrosis. The combination therapy was approved for children starting at the age of six years in early 2022.

The primary drug used to treat the sexually transmitted infection could be scarce into next year, Pfizer warns.A new shortage of a type of penicillin crucial to the fight against syphilis is alarming infectious disease experts, who warn that a protracted scarcity of the drug could worsen the U.S. epidemic of the sexually transmitted infection.The shortage, announced by the drugmaker Pfizer in a letter last month, involves Bicillin L-A, a long-acting injectable antibiotic also known as penicillin G benzathine. The company cited significant increases in demand because of the rising rate of syphilis infections, as well as Bicillin’s recent use as an alternative to amoxicillin, another antibiotic that has periodically been scarce and is prescribed for more general infections like strep throat.Steven Danehy, a spokesman for Pfizer, said it would likely take about a year for the company to ramp up production by 50 percent at its plant in Rochester, Mich., and ultimately manufacture enough Bicillin to meet demand and shore up reserves.Syphilis has been on the rise in the United States since 2000, reaching 176,713 cases in 2021, which was an increase of nearly 75 percent since 2017, according to the Centers for Disease Control and Prevention.Congenital syphilis tripled during that four-year period, to 2,855 cases, including 220 stillbirths or infant deaths. Rates are highest among the infants of Native American, Native Hawaiian, Pacific Islander and Black mothers.Bicillin is the only recommended treatment for pregnant women who are infected, and is very effective at preventing transmission to the fetus if provided early enough. Congenital syphilis has a high fatality rate, and can otherwise cause preterm birth and severe birth defects.“It worries me that these moms may not have access to lifesaving medication,” Dr. Anita Henderson, a pediatrician in Hattiesburg, Miss., said. The state had seen large increases in the rate of congenital syphilis over the last five years, she said.Among adult syphilis cases, nearly one-fourth are in women; just under a third are in men who have sex only with men; and about one-fifth are in men who only have sex with women.The infection can cause sores and a rash and, if left untreated, can seriously damage the internal organs, nervous system, eyes and ears, and can be fatal.Pfizer also warned that its supply of a rarely used pediatric version of Bicillin would soon run out because the company had begun using that drug’s production line to increase the adult formula. Doctors turned to it in the last year in lieu of amoxicillin during an increase in the number of strep throat cases.Bicillin is also used to manage rheumatic heart disease and rheumatic fever, which are particular health risks, albeit uncommon, for children. Multiple antibiotic alternatives are available for these conditions, according to Dr. Meg Doherty, director of global H.I.V., hepatitis and sexually transmitted infections programs at the World Health Organization.Treponema pallidum, the bacteria that causes syphilis.NIAIDTo ward off bacterial infections, military recruits receive Bicillin during boot camp, where the drug is known as the “peanut butter shot” because of its color and consistency. According to Dr. Ryan C. Maves, a professor of infectious diseases at Wake Forest University School of Medicine, recruits otherwise face a high risk of invasive streptococcal infection.Alternatives to Bicillin for pregnant women are under development and review but are years away from becoming available to them, said Dr. Jeffrey Klausner, an infectious disease expert at the University of Southern California. He urged the Biden administration to pay Pfizer for some 500,000 doses to encourage production.The Bicillin shortfall is but one element of a widespread drug-shortage crisis that has left doctors and pharmacists scrambling for vital therapeutic staples and forced them to ration treatments like chemotherapy. A recent Senate report also characterized the supply problems as a threat to national security.Most drug companies have not been particularly keen on developing antibiotics, in part because the profit margin for this class of drugs is typically far lower than the next blockbuster drug that could be worth billions of dollars.A bipartisan group in Congress recently reintroduced the $6 billion Pasteur Act, a Netflix-like subscription model that would act as a financial incentive for research and development by pharmaceutical companies.While the legislation could address drug shortages, its main goal is to combat the global threat of drug-resistant pathogens.David Harvey, executive director of the National Coalition of S.T.D. Directors, a trade association for public health associations, said rates of syphilis, chlamydia and gonorrhea are all surging “in part due to a public health landscape that is stretched dangerously thin, resulting in a lack of S.T.I. prevention, testing, and treatment.”He and others criticized Pfizer for inadequate production of the drug given the decades-long rising trajectory of syphilis infections. But Pfizer’s spokesman, Mr. Danehy, said the company had invested $38 million in its Michigan plant to improve manufacturing after a previous shortage of Bicillin in 2017.Mr. Harvey also denounced the Biden administration for agreeing in the debt ceiling deal to slash $400 million from the C.D.C.’s budget for S.T.I. prevention.To stretch the Bicillin supply, the C.D.C. recommends that doctors give preference to pregnant patients and infected or exposed infants. Other patients should instead be prescribed doxycycline for two to four weeks, depending on the disease stage. But experts expressed worry that such individuals, including the partners of pregnant women, might have trouble sticking to the twice-daily pill regimen, potentially compromising its effectiveness.Eric Tichy, division chair of supply chain management at Mayo Clinic in Rochester, Minn., said Pfizer likely stands alone in producing Bicillin for the U.S. market because of the considerable complexity and expense of manufacturing the drug.But other experts objected to Pfizer’s pricing practices. “Here’s a prime example of why leaving public health to the free market can be disastrous,” Tim Horn, director of medication access at the National Alliance of State and Territorial AIDS Directors, an advocacy group, said in an email.“Since 2013, the price of Bicillin L-A has increased an astonishing 275 percent,” Mr. Horn said.Mr. Danehy said the list price for a 4-milliliter Bicillin L-A syringe is $470, and that the company adjusted prices to ensure proper, quality supply.While many health care organizations and clinics are able to secure discounts, some frontline independent clinics are paying top dollar for the antibiotic.Dr. Phyllis Ritchie, who runs a free S.T.I. clinic largely serving gay men in Palm Springs, Calif., said the cost of a 10-pack of shots of Bicillin had risen to $6,500 from $4,000 two years ago. With the clinic using about 15 to 20 of the 10-packs annually, its $225,000 yearly budget can no longer withstand the financial strain, she said.When she first began practicing medicine in the mid-1990s, Dr. Ritchie recalled, a 10-pack cost under $300.“It’s a crisis,” she said.

Unprocessed red meat and whole grains can be included or left out of a healthy diet, according to a study conducted in 80 countries across all inhabited continents and published today in European Heart Journal, a journal of the European Society of Cardiology (ESC).1 Diets emphasising fruit, vegetables, dairy (mainly whole-fat), nuts, legumes and fish were linked with a lower risk of cardiovascular disease (CVD) and premature death in all world regions. The addition of unprocessed red meat or whole grains had little impact on outcomes.
“Low-fat foods have taken centre stage with the public, food industry and policymakers, with nutrition labels focused on reducing fat and saturated fat,” said study author Dr. Andrew Mente of the Population Health Research Institute, McMaster University, Hamilton, Canada. “Our findings suggest that the priority should be increasing protective foods such as nuts (often avoided as too energy dense), fish and dairy, rather than restricting dairy (especially whole-fat) to very low amounts. Our results show that up to two servings a day of dairy, mainly whole-fat, can be included in a healthy diet. This is in keeping with modern nutrition science showing that dairy, particularly whole-fat, may protect against high blood pressure and metabolic syndrome.”
The study examined the relationships between a new diet score and health outcomes in a global population. A healthy diet score was created based on six foods that have each been linked with longevity. The PURE diet included 2-3 servings of fruit per day, 2-3 servings of vegetables per day, 3-4 servings of legumes per week, 7 servings of nuts per week, 2-3 servings of fish per week, and 14 servings of dairy products (mainly whole fat but not including butter or whipped cream) per week. A score of 1 (healthy) was assigned for intake above the median in the group and a score of 0 (unhealthy) for intake at or below the median, for a total of 0 to 6. Dr. Mente explained: “Participants in the top 50% of the population — an achievable level — on each of the six food components attained the maximum diet score of six.”
Associations of the score with mortality, myocardial infarction, stroke and total CVD (including fatal CVD and non-fatal myocardial infarction, stroke and heart failure) were tested in the PURE study which included 147,642 people from the general population in 21 countries. The analyses were adjusted for factors that could influence the relationships such as age, sex, waist-to-hip ratio, education level, income, urban or rural location, physical activity, smoking status, diabetes, use of statins or high blood pressure medications, and total energy intake.
The average diet score was 2.95. During a median follow-up of 9.3 years, there were 15,707 deaths and 40,764 cardiovascular events. Compared with the least healthy diet (score of 1 or less), the healthiest diet (score of 5 or more) was linked with a 30% lower risk of death, 18% lower likelihood of CVD, 14% lower risk of myocardial infarction and 19% lower risk of stroke. Associations between the healthy diet score and outcomes were confirmed in five independent studies including a total of 96,955 patients with CVD in 70 countries.
Dr. Mente said: “This was by far the most diverse study of nutrition and health outcomes in the world and the only one with sufficient representation from high-, middle- and low-income countries. The connection between the PURE diet and health outcomes was found in generally healthy people, patients with CVD, patients with diabetes, and across economies.”
“The associations were strongest in areas with the poorest quality diet, including South Asia, China and Africa, where calorie intake was low and dominated by refined carbohydrates. This suggests that a large proportion of deaths and CVD in adults around the world may be due to undernutrition, that is, low intakes of energy and protective foods, rather than overnutrition. This challenges current beliefs,” said Professor Salim Yusuf, senior author and principal investigator of PURE.
In an accompanying editorial, Dr. Dariush Mozaffarian of the Friedman School of Nutrition Science and Policy, Tufts University, Boston, US stated: “The new results in PURE, in combination with prior reports, call for a re-evaluation of unrelenting guidelines to avoid whole-fat dairy products. Investigations such as the one by Mente and colleagues remind us of the continuing and devastating rise in diet-related chronic diseases globally, and of the power of protective foods to help address these burdens. It is time for national nutrition guidelines, private sector innovations, government tax policy and agricultural incentives, food procurement policies, labelling and other regulatory priorities, and food-based healthcare interventions to catch up to the science. Millions of lives depend on it.”

A study led by McMaster University and Hamilton Health Sciences researchers at the Population Research Health Institute (PHRI) has found that not eating enough of six key foods in combination is associated with a higher risk of cardiovascular disease (CVD) in adults.
Consuming fruits, vegetables, legumes, nuts, fish and whole-fat dairy products is key to lowering the risk of CVD, including heart attacks and strokes. The study also found that a healthy diet can be achieved in various ways, such as including moderate amounts of whole grains or unprocessed meats.
Previous and similar research has focused on Western countries and diets that combined harmful, ultra-processed foods with nutrient-dense foods. This research was global in scope and focused on foods commonly considered to be healthy.
The World Health Organization estimates nearly 18 million people died from CVD in 2019, representing 32 per cent of all global deaths. Of these deaths, 85 per cent were due to heart attacks and strokes. PHRI researchers and their global collaborators analyzed data from 245,000 people in 80 countries from multiple studies. The results were published in the European Heart Journal on July 6.
Researchers derived a diet score from PHRI’s ongoing, large-scale global Prospective Urban and Rural Epidemiological (PURE) study, then replicated that in five independent studies to measure health outcomes in different world regions and in people with and without prior CVD.
“Previous diet scores — including the EAT-Lancet Planetary Diet and the Mediterranean Diet tested the relationship of diet to CVD and death mainly in Western countries. The PURE Healthy Diet Score included a good representation of high, middle, and low-income countries,” said Salim Yusuf, senior author and principal investigator of PURE.
As well as being truly global, the PURE Healthy Diet Score focused on exclusively protective, or natural, foods.
“We were unique in that focus. The other diet scores combined foods considered to be harmful — such as processed and ultra-processed foods — with foods and nutrients believed to be protective of one’s health,” said first author Andrew Mente, PHRI scientist and assistant professor at McMaster’s Department of Health Research Methods, Evidence, and Impact.
“There is a recent increased focus on higher consumption of protective foods for disease prevention. Outside of larger amounts of fruits, vegetables, nuts and legumes, the researchers showed that moderation is key in the consumption of natural foods,” he said.
“Moderate amounts of fish and whole-fat dairy are associated with a lower risk of CVD and mortality. The same health outcomes can be achieved with moderate consumption of grains and meats — as long as they are unrefined whole grains and unprocessed meats.”
The PURE Healthy Diet Score recommends an average daily intake of: Fruits at two to three servings; vegetables at two to three servings; nuts at one serving; and dairy at two servings. The score also includes three to four weekly servings of legumes and two to three weekly servings of fish. Possible substitutes included whole grains at one serving daily, and unprocessed red meat or poultry at one serving daily.
There was no specific funding for this analysis, although each study that contributed data was funded separately and conducted over a 25-year period.

Many at-risk forest tree species will probably need biotechnology along with traditional tree-breeding approaches to survive, according to insights published in the July issue of the journal New Forests.
Purdue University’s Douglass Jacobs and Kasten Dumroese of the U.S. Forest Service led a team of 19 co-authors, including scientists, land managers and regulators, in presenting their findings on biotechnological risk assessment and forest tree restoration. Their New Forests paper, published in a special issue on threatened tree species, presents key outcomes of a 2021 virtual international conference on the issues.
Among their conclusions: Society drives policy. If genetic engineering is the only way to save some species, its use will require public acceptance.
“Biotechnology is a diverse toolkit comprising different technologies that can be used to impart pest resistance — it could be bugs or pathogens — in our threatened forest trees,” said Jacobs, the Fred M. van Eck Professor of Forest Biology. But many people mistakenly equate biotechnology with genetic engineering.
“Traditional tree breeding, whether you’re breeding different species or different varieties within species, has been going on for thousands of years. And the regulations on planting trees that have been traditionally bred are wide open,” he said. “Genetic engineering, on the other hand, is highly regulated, but all biotechnology is certainly not genetic engineering.”
Scientists often use genomics, for example, which involves working with the complete set of an organism’s genetic material, to learn more about what causes disease. Genomics also can help identify the genes responsible for useful traits such as pest resistance.

Blight began afflicting the American chestnut in the 1900s, killing billions of trees. Despite being the target of decades-long tree-breeding efforts, the chestnut’s prospects remain in doubt. The list of at-risk species also includes ash, butternut, and bristlecone pine among other members of the five-needle white pine family.
“I feel a sense of urgency. We can’t take a hundred years like we’ve taken with chestnut to turn the page,” said Dumroese, a research plant physiologist at the Forest Service’s Rocky Mountain Research Station in Idaho.
“The species are becoming ecologically extinct,” Dumroese said. “They’re not able to provide their historic level of ecosystem function because often they don’t grow to maturity. And that’s happening at a faster and faster pace. Look at how rapidly we’ve lost ash trees from our forests and urban landscapes because of the introduced insect pest emerald ash borer.”
The western white pine is an example of how the Forest Service has, starting in the 1960s, effectively used traditional tree breeding to cope with white pine blister rust. The white pine population remains below its pre-blister-rust levels, however, and may never become fully restored.
“But we see a lot more western white pine on the landscape and being planted on the landscape every year because of those efforts,” Dumroese said. “That process only took a couple of decades where we come from a big problem to making improvements. We need that pace for all of the species that we’re calling at risk.”
Back in Indiana, the Hardwood Tree Improvement & Regeneration Center, a joint effort between Purdue and the Forest Service, for years has maintained a breeding program for pest resistance. Almost all of the center’s efforts to date have focused on traditional tree breeding and genomics.

“The chance to work with chestnut and help reintroduce it back to the landscape was a big reason I took the Purdue job in the first place back in December of 2001,” Jacobs said. “Watching species disappear from the landscape provides me personally with a lot of motivation to contribute whatever I can toward helping to save some of these at-risk species.”
In the last 10 years, Jacobs has seen striking advancements in novel biotechnologies that use genomics and genetic engineering.
“For some species, traditional tree breeding doesn’t appear to be a viable long-term option to get disease-resistant trees. In those cases, it’s probably going to have to be genetic engineering if we want to save the species,” he said.
That applies even to a species like the blight-afflicted American chestnut, the target of a breeding program for 50 years. “Introducing enough chestnut and ash trees to bring us back to the pre-disturbance level is likely not possible in anyone’s lifetime, but you have to start somewhere,” Dumroese noted.
The participants of the 2021 conference came to a consensus on the applicability of biotechnology toward reintroducing some threatened forest tree species. They came from academia, the Forest Service, and organizations such as the American Chestnut Foundation and the Nature Conservancy.
“Societal perception and policy remain the weakest links,” Jacobs said. “There’s been this consistent one-way flow of information from scientists to the public with the idea of, ‘Hey, we’re scientists, trust us.’ Or ‘We’re the government, trust us.’ But you need a much more interactive dialogue to be successful in changing public opinion.”
Support for the conference and related work was provided by the U.S. Department of Agriculture Forest Service and National Institute of Food and Agriculture.

The F.D.A. gave full approval to the drug, but added a black-box warning about safety risks. Medicare said it would cover most of the high cost.The Food and Drug Administration on Thursday gave full approval to the Alzheimer’s drug Leqembi, and Medicare said it would cover much of its high cost, laying the foundation for widespread use of a medication that can modestly slow cognitive decline in the early stages of the disease but also carries significant safety risks.The F.D.A.’s decision marks the first time in two decades that a drug for Alzheimer’s has received full approval, meaning that the agency concluded there is solid evidence of potential benefit. But the agency also added a so-called black-box warning — the most urgent level — on the drug’s label, stating that in rare cases the drug can cause “serious and life-threatening events” and that there have been cases of brain bleeding, “some of which have been fatal.”Leqembi cannot repair cognitive damage, reverse the course of the disease or stop it from getting worse. But data from a large clinical trial suggests that the drug — administered every two weeks as an intravenous infusion — may slow decline by about five months over about 18 months for people with mild symptoms.Still, some Alzheimer’s experts have said it is unclear from the medical evidence whether Leqembi’s ability to delay erosion of memory and cognition would be enough to be noticeable or meaningful for patients and their families. And while most cases of brain swelling and bleeding have been mild or moderate and have resolved, there have been some serious cases.“The risks are very vivid,” said Dr. Jason Karlawish, a co-director of the University of Pennsylvania’s Penn Memory Center, who said he will prescribe Leqembi after carefully evaluating patients and explaining the potential pros and cons. “Within the first few months, you may have small bleeds or swelling in your brain, which may or may not be symptomatic and if not detected in time can cause disability.”“In contrast,” Dr. Karlawish continued, “the benefits of slowing are subtle. You’re not going to experience the perception of changes in your cognition or function in the same amount of time.”Though Medicare will cover 80 percent of Leqembi’s $26,500 cost, patients could still shoulder thousands of dollars in co-payments.Eisai, a Japanese pharmaceutical company, led the development and testing of Leqembi (pronounced le-KEM-bee). Eisai is partnering and splitting profits with the American company Biogen, the maker of the controversial Alzheimer’s drug Aduhelm, for its commercialization and marketing.The F.D.A.’s approval of Aduhelm was severely criticized because the evidence of potential benefit was inconclusive, with one trial showing modest slowing of decline but another showing no slowing. Before that approval, a committee of independent advisers and an F.D.A. council of senior officials said there was not enough evidence that it worked. Many medical centers declined to prescribe Aduhelm, and Medicare has covered it only for clinical trial participants, sharply restricting its availability.Evidence supporting Leqembi is much clearer, Alzheimer’s experts said.Leqembi will be available for people with mild dementia or a pre-Alzheimer’s condition called mild cognitive impairment. The F.D.A. label instructs doctors not to treat patients without testing to confirm they have an accumulation of the protein amyloid, a hallmark of Alzheimer’s that Leqembi attacks.About 1.5 million people in the United States are estimated to be in the beginning phases of Alzheimer’s. Many more — about five million — have progressed too far to be eligible for Leqembi. Alex Scott, Eisai’s executive vice president of integrity, said the company recommends patients stop using Leqembi once they develop moderate Alzheimer’s disease.Alzheimer’s experts said they would inform some patients that they had greater risk for brain swelling and bleeding — including those taking blood thinners, those with more than four microscopic bleeds in the brain and those with an Alzheimer’s-linked gene mutation called APOE4.The risk to people with two copies of the APOE4 mutation — about 15 percent of people with Alzheimer’s — is so high that the F.D.A.’s black-box warning recommends that all patients be genetically tested to assess their safety risk and spells out that those with two APOE4 copies are more vulnerable to developing “symptomatic, serious and severe” brain bleeding or swelling.The black-box warning will apply to all drugs that, like Leqembi, are monoclonal antibodies that attack amyloid. Leqembi is the first to get full approval, but others are in various stages of development.The warning does not mention patients who are taking blood thinners, but Leqembi’s label says that “additional caution should be exercised” when considering whether to give blood thinners to Leqembi patients. The F.D.A. greenlighted Aduhelm under a program called “accelerated approval,” which can be given to drugs with uncertain benefit under specific criteria, including that the company conduct another clinical trial. Leqembi received accelerated approval in January, but that status meant Medicare would only cover the drug in limited circumstances.The F.D.A. decision granting full approval to Leqembi means that Medicare will cover it for eligible patients.Still, some patients will be unable to afford the 20 percent Medicare does not cover, possibly about $6,600 a year. Including costs of medical visits and required regular brain scans, some of which will receive Medicare reimbursement, the treatment could run to about $90,000 a year, some experts estimate.A recent study estimated that covering the drug and necessary services for about 85,000 patients would cost Medicare $2 billion a year and would climb to $5.1 billion if the number of patients reached about 216,000. That could lead to an increase in premiums for all Medicare beneficiaries, not just those receiving Leqembi, the study said.In interviews, Ivan Cheung, the chairman and chief executive of Eisai’s United States operations, estimated that in the first three years, about 100,000 patients would be receiving the drug.The Medicare agency is adding a requirement that doctors prescribing Leqembi submit medical information about each patient before and while they are being treated with the drug. The information will be kept in patient registries and evaluated to learn more about Leqembi’s benefits or harms, the agency said.“With F.D.A.’s decision, C.M.S. will cover this medication broadly while continuing to gather data that will help us understand how the drug works,” the administrator of the Centers for Medicare and Medicaid Services, Chiquita Brooks-LaSure, said in a statement.Some advocacy groups, like the Alzheimer’s Association, have criticized the registry requirement, calling it an unnecessary barrier to access. But medical experts say registry programs are common and easy to comply with. Their concern is that the registry won’t be comparing Leqembi patients with others, so it won’t be able to say if Leqembi slows cognitive decline.The F.D.A.’s approval on Thursday was based on a large trial indicating that patients receiving Leqembi declined 27 percent more slowly over 18 months than patients receiving a placebo. The difference between those receiving drug and placebo was small — less than half a point, on an 18-point cognitive scale that assesses functions like memory and problem-solving. Some Alzheimer’s experts say that for slowing of decline to be clinically meaningful, or noticeable to patients and families, the difference between the groups must be at least one point.Leqembi patients also declined more slowly on three secondary measures of cognition and daily function, and data on biological markers was generally stronger for Leqembi than for the placebo. All these measures moving in the same direction strengthens the idea that the drug can benefit patients, experts say.Still, a report on the data, published in The New England Journal of Medicine and co-written by scientists from Eisai, concluded that “longer trials are warranted to determine the efficacy and safety.”Concerns about safety have been stoked by reports of deaths of three clinical trial participants who experienced brain swelling and brain bleeding, two of whom were being treated with blood thinners. Eisai has said it is unclear if Leqembi contributed to their deaths because the patients had complex medical issues.“You’ve got small benefits and a certain risk for serious adverse events, and that has to be balanced,” said Dr. Lon Schneider, director of the California Alzheimer’s Disease Center at the University of Southern California, who said he will prescribe Leqembi to carefully evaluated patients.“If its efficacy were greater, we would not be talking about adverse events as much because we would see a clear benefit,” he said, adding, “I think many people will see this and say it’s not worth the effort, it’s not worth twice-a-month infusions.”Dr. Karlawish said the decisions facing patients and families will be complicated. Because eligible patients have only mild symptoms of cognitive decline, some might opt to take any medication that might prolong that relatively functional stage, while others might only consider the risks of the drug worthwhile if they were much more impaired.Dr. Karlawish said one recent patient declined to get evaluated for potential treatment, indicating that “‘I want more benefits, I don’t see the value.’” But, he said, “I have other patients, though, who would say, You mean you can give me a drug that could slow the disease?”In the trial, nearly 13 percent of patients receiving Leqembi experienced brain swelling, which was mostly mild or moderate, while less than 2 percent of patients receiving the placebo experienced such swelling. Most brain swelling did not cause any symptoms, generally emerged soon after use began and resolved within a few months. About 17 percent of Leqembi patients experienced brain bleeding, compared with 9 percent of patients receiving a placebo. The most common symptom from brain bleeds was dizziness.Overall, the results suggest the risk of brain bleeding and swelling was significantly lower than for patients in trials of Aduhelm.Dr. Jerry Avorn, a professor of medicine at Harvard Medical School who studies medication regulation and use, said doctors will feel pressure to prescribe Leqembi from patients, families and advocacy organizations. Medical institutions will also have an “enormous financial incentive” because of the Medicare reimbursement that “they could then spend on social workers and all the other things that Medicare will not reimburse,” he said, adding “any economically self-respecting memory center is going to see this as an economic windfall.”

AI (artificial intelligence) may sound like a cold robotic system, but Osaka Metropolitan University scientists have shown that it can deliver heartwarming — or, more to the point, “heart-warning” — support. They unveiled an innovative use of AI that classifies cardiac functions and pinpoints valvular heart disease with unprecedented accuracy, demonstrating continued progress in merging the fields of medicine and technology to advance patient care. The results will be published in The Lancet Digital Health.
Valvular heart disease, one cause of heart failure, is often diagnosed using echocardiography. This technique, however, requires specialized skills, so there is a corresponding shortage of qualified technicians. Meanwhile, chest radiography is one of the most common tests to identify diseases, primarily of the lungs. Even though the heart is also visible in chest radiographs, little was known heretofore about the ability of chest radiographs to detect cardiac function or disease. Chest radiographs, or chest X-Rays, are performed in many hospitals and very little time is required to conduct them, making them highly accessible and reproducible. Accordingly, the research team led by Dr. Daiju Ueda, from the Department of Diagnostic and Interventional Radiology at the Graduate School of Medicine of Osaka Metropolitan University, reckoned that if cardiac function and disease could be determined from chest radiographs, this test could serve as a supplement to echocardiography.
Dr. Ueda’s team successfully developed a model that utilizes AI to accurately classify cardiac functions and valvular heart diseases from chest radiographs. Since AI trained on a single dataset faces potential bias, leading to low accuracy, the team aimed for multi-institutional data. Accordingly, a total of 22,551 chest radiographs associated with 22,551 echocardiograms were collected from 16,946 patients at four facilities between 2013 and 2021. With the chest radiographs set as input data and the echocardiograms set as output data, the AI model was trained to learn features connecting both datasets.
The AI model was able to categorize precisely six selected types of valvular heart disease, with the Area Under the Curve, or AUC, ranging from 0.83 to 0.92. (AUC is a rating index that indicates the capability of an AI model and uses a value range from 0 to 1, with the closer to 1, the better.) The AUC was 0.92 at a 40% cut-off for detecting left ventricular ejection fraction — an important measure for monitoring cardiac function.
“It took us a very long time to get to these results, but I believe this is significant research,” stated Dr. Ueda. “In addition to improving the efficiency of doctors’ diagnoses, the system might also be used in areas where there are no specialists, in night-time emergencies, and for patients who have difficulty undergoing echocardiography.”

The NewsAn overwhelming majority of women were able to end unwanted pregnancies with abortion medications and without additional medical procedures, even if they were well beyond the first trimester, according to a report published on Thursday.The study was based on the experiences of 264 women who were nine to 16 weeks pregnant in Argentina, Nigeria and an unnamed country in Southeast Asia where abortion is illegal. Almost half of the women took only one drug, misoprostol, instead of the standard two-drug regimen, mifepristone and misoprostol.They were nonetheless able to terminate the pregnancies, according to the study, published in the journal Obstetrics & Gynecology. All of the participants received information from an abortion support group.The findings align with clinical data showing the efficacy and safety of medication abortions conducted under medical supervision throughout pregnancy, said Ruvani Jayaweera, an epidemiologist and research scientist at Ibis Reproductive Health and one of the study’s authors.Nearly one in four women sought medical care after the abortions, most frequently to confirm that the termination was complete. A smaller percentage wanted to address concerns about bleeding, pain, fever or discharge.Women who were pregnant for 12 weeks or longer were significantly more likely to seek medical care after a medication abortion, compared with those who were nine to 11 weeks pregnant.Almost half of the women with unwanted pregnancies who took abortion medication at nine weeks’ gestation or longer took only one drug, misoprostol, and not the standard two-drug regimen. The majority were still able to complete the termination.Adria Malcolm for The New York TimesWhy It MattersAs more than a dozen states banned abortion in the past year, women with unwanted pregnancies have turned in growing numbers to self-managed medication abortions.But the arduous and time-consuming methods needed to procure the drugs create delays, often meaning pregnancies are more advanced by the time the drugs arrive. The new study, one of the first to report on self-managed medication abortions carried out after the first trimester of pregnancy, offers these women some reassurance, researchers said.“This paper adds to previous research indicating that self-managed abortion with medications is safe and effective, including after 12 weeks of pregnancy,” said Dr. Daniel Grossman, a professor of obstetrics, gynecology and reproductive sciences at the University of California, San Francisco. “As clinic-based abortion care becomes less available in many parts of the country due to state-level bans, self-managed abortion will become more common, as we are already seeing.”The research also suggests an alternative path to medication abortion if access to mifepristone is severely curtailed. In April, the Supreme Court blocked a lower-court ruling that would have stopped the distribution and sale of mifepristone throughout the United States while the case wends its way through the legal system.Some 44 percent of the participants in the new study used only misoprostol, which is prescribed for many conditions and available in many countries without a prescription.BackgroundAbout 90 percent of the women in the study succeeded at ending pregnancies with self-managed medication abortions, without any additional intervention needed. Five percent had a procedure to complete the abortion, and 5 percent had an incomplete abortion.The two-drug regimen of mifepristone and misoprostol is approved by the Food and Drug Administration for use through only 10 weeks of pregnancy, under the supervision of a health care provider.But the W.H.O., taking into account shortages of health care providers in much of the developing world, endorses self-managed medical abortions in pregnancies of up to 12 weeks without medical supervision.What’s NextThe new report was a sub-analysis of a larger study that looked at 1,352 women who self-managed abortion at different stages of pregnancy, and the number with more advanced gestations was relatively small.Only three participants self-managed abortions with gestations of 17 weeks and longer, and the study’s authors called for more research into medication abortion and later pregnancies.Access to drugs that are used for these abortions, which are often ordered through the mail, continues to be a flashpoint in the ongoing debate over abortion in the United States.

Medicare will cover much of the cost for patients in the early stages of the disease, but Leqembi has safety risks and can only modestly slow cognitive decline.On Thursday, the Food and Drug Administration gave full approval to the drug Leqembi for patients who are in the early stages of Alzheimer’s disease, and Medicare said it would cover 80 percent of the cost of the $26,500-per-year medication. The decisions by the two federal agencies will vastly increase access to the drug but also present a dilemma for patients and their families.There are many factors, both financial and medical, to weigh. Here are answers to some crucial questions:How well does the drug work?Leqembi is not a cure for Alzheimer’s, and the drug doesn’t improve patients’ memories or cognitive abilities. It also does not stop the disease from getting worse. What Leqembi can do is modestly slow down cognitive decline in patients who are in the early stages of the disease. Data from a large clinical trial suggested that the drug may slow decline by about five months over a period of 18 months for those patients.How the drug might affect a patient’s daily life is likely to vary widely. For some people, Leqembi might mean several additional months of being able to follow a recipe, balance a checkbook or accomplish other activities without help. For others, the impact might be much more subtle and barely noticeable.Are there risks from taking it?Yes. The drug can cause swelling or bleeding in the brain that is often mild or moderate and resolves on its own but can be serious and in very rare cases can be fatal. The F.D.A. was so concerned about these side effects that it is requiring a “black-box warning” — the most urgent level — on the drug’s label, saying that the medication can cause “serious and life-threatening events.”Patients who are at higher risk include those on blood thinners, those who have had more than four microscopic bleeds in the brain and those with an Alzheimer’s-linked gene mutation called APOE4 — especially if they have two copies of the mutation. They, along with their doctors, should consider whether the increased safety risk outweighs their desire for a medication that might modestly slow cognitive decline.A large clinical trial of the drug found that nearly 13 percent of patients receiving Leqembi experienced brain swelling, but most of those cases were mild or moderate. Less than 2 percent of patients receiving the placebo experienced such swelling. Most brain swelling did not cause any symptoms and generally resolved within a few months.About 17 percent of the patients receiving Leqembi experienced brain bleeding, compared with 9 percent of patients receiving the placebo. The most common symptom from brain bleeds was dizziness, the study said.Who is eligible to take Leqembi?Leqembi — which is administered by intravenous infusions in a doctor’s office or clinic every two weeks — will be available for people diagnosed as having early-stage Alzheimer’s and for those with a pre-Alzheimer’s condition called mild cognitive impairment. About 1.5 million people in the United States fit that description. An additional 5 million who have Alzheimer’s will not qualify for Leqembi because their disease has progressed too far.The F.D.A.-required label on the drug instructs doctors not to treat patients without testing to confirm that they have one of the hallmarks of Alzheimer’s: a buildup in the brain of the protein amyloid, which Leqembi attacks. Amyloid levels can be assessed with PET scans, spinal taps or newly available blood tests.How much will we have to pay?Most patients will be old enough for Medicare, which has said it will pay for 80 percent of the $26,500 annual cost of the drug. Patients would be left with about $6,600 in co-payments, which may put the drug out of financial reach for many. Some or all of that co-payment might be covered by the supplemental private insurance policies that many Medicare patients have.There are potentially tens of thousands of dollars of additional costs, however — including medical visits for the infusions and regular brain scans. Some Alzheimer’s experts have estimated that the total cost of taking Leqembi could run to about $90,000 a year. With 80 percent coverage, treatment could potentially leave patients saddled with $18,000 per year in out-of-pocket costs.How should people and their families decide?Talk to your doctor. If your doctor is not well-versed in Alzheimer’s treatments, consider talking with a specialist. The most important thing is to discuss the decision with medical experts who will carefully explain the risks for your specific situation.To learn those risks, ask for genetic testing to determine if you have the APOE4 gene mutation. People with two copies of that mutation — about 15 percent of Alzheimer’s patients — are at especially high risk of brain swelling and bleeding.There are other factors to consider too. Would going to a clinic for a drug infusion every two weeks pose a burden?And, importantly, how do you and your family perceive your current cognitive condition and how it affects your life? Because Leqembi is for people with mild symptoms, some people might be less inclined to take safety risks, but others might consider it especially important to try a drug that might keep them at this mild stage a bit longer.

Oregon Health & Science University researchers showed that consuming THC while pregnant could potentially affect development of the fetus and lead to life-long health impacts for offspring.
The preclinical study was published today in the journal Clinical Epigenetics.
Delta-9-tetrahydrocannabinol, or THC, is the main psychoactive ingredient in cannabis, a substance growing in popularity and availability in the United States. The prevalence of cannabis use in pregnancy is also rapidly increasing, especially during the first trimester — a time when the fetus is most vulnerable to environmental exposures — to mitigate common symptoms like morning sickness. However, the potential effects of prenatal cannabis use on fetal development remain inconclusive, in part due to a lack of safety data. This study aimed to identify the potential long-term health impacts of THC use during pregnancy.
In a non-human primate model, OHSU researchers found that exposing a pregnant subject to THC altered the placental and fetal epigenome — including the chemical modifications to DNA responsible for gene regulation and expression, that is telling genes what, where and when to do something. Researchers also found that that these changes to gene regulation and expression are consistent with those seen with many common neurobehavioral conditions, including autism spectrum disorder.
“Cannabis is one of the most commonly used drugs and is widely available across the country, so there is a common perception that its completely safe to use,” said the study’s lead author Lyndsey Shorey-Kendrick, Ph.D., a computational biologist in the Division of Neurosciences at OHSU’s Oregon National Primate Research Center, or ONPRC. “The reality is that cannabis still carries many health risks for certain populations, including those who are pregnant. If we’re able to better understand the impacts, we can more effectively communicate the risks to patients and support safer habits during the vulnerable prenatal period.”
In a model using nonhuman primates, researchers administered THC in a daily edible and compared its effects to a group receiving a placebo. Specifically, researchers evaluated the epigenetic changes in several key areas that indicate healthy prenatal development: the placenta — the disc of tissue that connects the umbilical cord and uterus — and fetal lung, brain and heart.
When looking at these areas, analyses showed that THC exposure altered the epigenome, meaning a process in which the information encoded in a gene is turned into a function or observable trait. Genes — the segments which make up DNA — are all specifically coded to contribute to different functions of the body and brain, so any impact on epigenetic processes due to drug exposure is concerning, especially during a critical developmental window such as pregnancy.
Researchers found that significant changes involved genes associated with common neurobehavioral disorders, including autism spectrum disorder and attention deficit hyperactivity disorder. These conditions are linked to adverse health outcomes in childhood and adolescence, including poorer memory and verbal reasoning skills, and increased hyperactivity, impulsivity and inattention.
The research team, which includes Eliot Spindel, M.D., Ph.D., Elinor Sullivan, Ph.D., Owen McCarty, Ph.D., and Jason Hedges, M.D., Ph.D., hopes findings from this study will add to the limited existing literature on THC use during pregnancy, and help guide patient counseling and public health polices focused on cannabis in the future.
“It’s not common practice for providers to discuss cannabis use with patients who are pregnant or trying to conceive,” said the study’s corresponding author, Jamie Lo, M.D., M.C.R., associate professor of obstetrics and gynecology (maternal-fetal medicine), OHSU School of Medicine, and Division of Reproductive and Developmental Sciences at the ONPRC. “I hope our work can help open up a broader dialogue about the risks of cannabis use in the preconception and prenatal period, so we can improve children’s health in the long run.”