If the preliminary decision is finalized this spring, it would sharply limit the number of patients who use the expensive drug.Medicare officials have decided that the federal health insurance program should only cover the controversial new Alzheimer’s drug Aduhelm for patients who are participating in approved clinical trials. The preliminary decision, reached after lengthy deliberations, was released on Tuesday by the Center for Medicare and Medicaid Services, or C.M.S. If it is finalized later this year, it would significantly limit the number of patients who could use the expensive drug.The decision said that coverage should be provided for patients in “C.M.S. approved randomized controlled trials” and trials supported by the National Institutes of Health. The decision said “all trials must be conducted in a hospital-based outpatient setting.”The agency added that Aduhelm of other similar drugs for Alzheimer’s that are provided outside of these trials “are nationally non-covered.”“Alzheimer’s disease is a devastating illness that has touched the lives of millions of American families. Throughout this National Coverage Determination process, CMS has been and remains committed to providing the American public with a clear, trusted, evidence-based decision that is made only after a thorough analysis of public feedback on the benefits and risks of coverage for Medicare patients,” said the C.M.S. administrator, Chiquita Brooks-LaSure. “C.M.S. has proposed an evidence-based coverage policy after experts reviewed all relevant publicly available evidence and feedback received from stakeholders.”Whether Medicare ends up covering Aduhelm is considered pivotal to the future of the drug, which is made by Biogen and priced at $28,200 a year per patient. Roughly 80 percent of the 1.5 million Americans who have the type of condition the F.D.A. approved the drug to treat — mild Alzheimer’s-related cognitive decline — are old enough to receive coverage under Medicare.For the next 30 days, C.M.S. will have a public comment period on the preliminary decision, and the agency is expected to announce its final decision about covering the drug by mid-April.The fact that Medicare is conducting an extensive review of Aduhelm is itself unusual. The program almost always pays for F.D.A.-approved drugs, at least for the medical conditions designated on their label, health policy experts said.Biogen initially priced the drug at $56,000 a year, but slashed the price in half last month after months of weak sales. Before Biogen’s price cut, Medicare’s actuarial division, acting without knowing what the coverage decision would be, imposed one of the biggest-ever increases in Medicare Part B premiums for 2022, partly driven by the possibility of Aduhelm coverage.After Biogen’s price cut, advocacy groups for Alzheimer’s patients urged C.M.S. to lower the premium increase. On Monday, the secretary for health and human services, Xavier Becerra, said that he was instructing C.M.S. to re-examine the premium hike “given the dramatic price change of the Alzheimer’s drug, Aduhelm.”Aduhelm was approved by the Food and Drug Administration in June in a decision vigorously criticized by many doctors and Alzheimer’s experts because clinical trial results showed it had significant safety risks and unclear benefit to patients.Congress is investigating whether the F.D.A. worked too closely with Biogen and why Aduhelm was approved despite strong objections from some senior F.D.A. officials and the agency’s independent advisory committee.So far, only a small number of patients — a fraction of the number Biogen and industry analysts had initially expected — have used Aduhelm, a monoclonal antibody administered as a monthly infusion. Many large American health care systems have declined to offer the drug, citing questions about its benefits and risks. Medicare officials are supposed to determine coverage based on whether a drug is a “reasonable and necessary” treatment, a phrase that usually “means adequate evidence of improved health outcomes,” said Dr. Sean Tunis, a former official with C.M.S. who is now a senior fellow at the Center for the Evaluation of Value and Risk in Health at Tufts Medical Center.Medicare’s decision on Aduhelm will also establish standards for evaluating several similar Alzheimer’s drugs in the pipeline.The F.D.A. itself acknowledged in its approval of Aduhelm that there was insufficient evidence it would help patients. Instead, it greenlighted the medication — the first new treatment for Alzheimer’s in 18 years — under a program called “accelerated approval,” which allows authorization of unproven drugs for serious diseases with few treatment options if the drug affects a biological mechanism in a way considered “reasonably likely to predict clinical benefit.”The F.D.A. said it based accelerated approval on Aduhelm’s reduction of a protein, called amyloid, that clumps into plaques in the brains of people with Alzheimer’s. But many Alzheimer’s specialists say that extensive research has shown little evidence that reducing amyloid slows cognitive decline. The F.D.A. also required Biogen to conduct another clinical trial to determine if the drug provided any evidence of benefit. In the years it will take for that trial to be completed, Aduhelm will be available to patients.

A group of Alzheimer’s experts and health advocates called on the F.D.A. to withdraw its approval of the drug, the latest of several setbacks for the treatment.Biogen slashed the price of its controversial new Alzheimer’s drug Aduhelm on Monday as the drug faces weak sales and mounting criticism.The price was reduced to $28,200 a year from $56,000 on the same day that a group of Alzheimer’s experts and health advocates called on the Food and Drug Administration to pull the drug off the market and said they were supporting an effort to file a formal petition with the agency to withdraw it.“The F.D.A.’s decision to approve Aduhelm is indefensible in both scientific and clinical terms,” said a statement signed by 18 scientists, most of them doctors. “This drug should be withdrawn from the market immediately.”The agency approved Aduhelm in June, even though a council of senior F.D.A. officials, an advisory committee of outside experts and many Alzheimer’s specialists said the scientific evidence showed that the drug did not provide a clear benefit to patients and that it carried risks of dangerous side effects.Major health systems, including Cleveland Clinic, Mount Sinai Health System, Mass General Brigham and the Department of Veterans Affairs have declined to offer Aduhelm, citing questions about its benefits and risks. In October, Biogen reported that Aduhelm had brought in just $1.9 million in revenue through September, a strikingly small amount given that about 1.5 million Americans have the mild Alzheimer’s-related dementia that makes them eligible for the drug.In a statement about the price-cutting on Monday, Michel Vounatsos, Biogen’s chief executive officer, said the company had “listened to the feedback of our stakeholders” and believed that “too many patients are not being offered the choice of Aduhelm due to financial considerations.”But Brian Skorney, an analyst at Robert W. Baird & Company, said after the price announcement: “For the broad majority of people who are critical of Aduhelm, $56,000 and $28,000 are both exceptionally high prices for a drug that a lot of people perceive doesn’t work at all.”The statement from Alzheimer’s experts and health advocates calling on the F.D.A. to withdraw Aduhelm grew out of a three-hour video meeting among the scientists last week.“We’re not just saying the approval was probably the worst decision the F.D.A. ever made,” Dr. Peter Whitehouse, a neurologist and Alzheimer’s expert at Case Western Reserve University who led the Dec. 15 meeting, told attendees during the session. “It’s so bad that we should advocate for withdrawal.”The doctors and scientists who signed the statement also agreed to provide their expertise to support the filing of a citizen petition, a formal process to seek reversal of the F.D.A.’s decision. The petition will be filed by the Right Care Alliance, a coalition of clinicians, patients and community members, which is also circulating a pledge for physicians who promise not to prescribe Aduhelm and for patients and family members who say they will not request it.Dr. Vikas Saini, chairman of the Right Care Alliance and president of the Lown Institute, a health care think tank, said that while the citizen petition process can take months or years, it can prompt F.D.A. action.Dr. Saini, who helped organize last week’s meeting, said that out of 45 citizen petitions filed since 1971 by the group Public Citizen, in 27 cases the F.D.A. withdrew drugs from the market and in seven other cases the agency sharply restricted a drug’s use.In response to the call to withdraw approval of Aduhelm, also known by its scientific name, aducanumab, an F.D.A. spokeswoman said that “the data set for Aduhelm was very complex, and our review has been thorough.”The spokeswoman also said that “careful analyses of the Phase 2 and Phase 3 clinical trials support the conclusion that it is likely that Aduhelm provides clinical benefit — although the data currently available do not provide substantial evidence of effectiveness on clinical benefit.”Aduhelm has also been encountering resistance in other countries. On Friday, reviewers at the European Union’s drug regulator, the European Medicines Agency, recommended against approving Aduhelm, a decision that Biogen said it would ask to be re-examined.Aduhelm is a monoclonal antibody, given as a monthly infusion. In clinical trials, 41 percent of patients receiving the F.D.A.-approved higher dose experienced brain swelling or brain bleeding, often mild, but serious in some cases.Pool photo by Jessica RinaldiSeveral months ago, leading Canadian Alzheimer’s research organizations said that approving the drug in Canada “cannot be justified.”Dr. Howard Chertkow, scientific director of the Canadian Consortium on Neurodegeneration in Aging, was one of three Alzheimer’s experts from outside the United States who signed the statement calling on the F.D.A. to withdraw the drug. “We feel it’s an abrogation of our responsibility as physicians to allow a marginal medication with a very high cost associated with it to come into the country, so we’re quite active in trying to block what has happened in the states from occurring in Canada,” he said at last week’s meeting.Two nearly identical clinical trials of Aduhelm, a monoclonal antibody given as a monthly infusion, were stopped early because an independent data monitoring committee concluded that the drug didn’t appear to be beneficial. A later analysis by Biogen found that participants receiving the high dose of the drug in one trial had experienced a very slight slowing of cognitive decline but that participants in the other trial had not benefited at all.About 41 percent of patients receiving the high dose — the dose the F.D.A. approved — experienced brain swelling or brain bleeding, side effects that were often mild or asymptomatic, but were sometimes serious.Monday’s statement also objects to the F.D.A.’s justification for its approval. Acknowledging there was insufficient evidence that Aduhelm would help patients, the agency greenlighted it under a program called “accelerated approval,” which allows authorization of drugs without proof of benefit for serious diseases that have few treatment options if the drug affects part of the disease’s biology (known as a surrogate endpoint) in a way that is “reasonably likely to predict clinical benefit.”The F.D.A. based its approval on Aduhelm’s ability to reduce a protein called amyloid that forms plaques in the brains of people with Alzheimer’s. But experts say years of studies have not shown that reducing amyloid helps memory or thinking problems.Approving the drug because of amyloid reduction “will have huge and wide-ranging negative implications for patients, families” and dementia research, Dr. Kenneth Langa, a professor of medicine at the University of Michigan, said in last week’s meeting. The group’s statement, which includes a section for others to sign their names in support, plays on the F.D.A.’s language by calling for “accelerated withdrawal.”“Reading the justification of the F.D.A. was like watching a ‘Saturday Night Live’ skit for data nerds.” Dr. Saini said. “I mean, I had trouble believing it.”The agency’s approval requires that Biogen conduct another trial to see if Aduhelm works. In its response Monday, the F.D.A. spokeswoman said “we believe that the data support accelerated approval while holding the company accountable for conducting an additional study.” Last week, Biogen said that it had developed a protocol to get that trial completed in 2026, several years before the F.D.A.-imposed deadline.Before he signed Monday’s statement, Dr. Sam Gandy, director of Mount Sinai’s Center for Cognitive Health, who helped organize the meeting, said that with advocacy groups like the Alzheimer’s Association still supporting the drug’s approval, he had a “concern that calling for something may trigger a backlash that undoes where we really want to go.”But Dr. Jerry Avorn, a professor of medicine at Harvard Medical School who also signed the statement, said that while it was unlikely that calling for withdrawal would make F.D.A. officials say, “‘Yeah, they’re right, we goofed, we better undo this decision,’” the action was nonetheless important. “We’re taking a stand and saying the process was terrible and the outcome was terrible, and even if they don’t listen to it, it’ll be kind of a shot across the bow.”Rebecca Robbins contributed reporting.

Scientists who injected idle mice with blood from athletic mice found improvements in learning and memory. The findings could have implications for Alzheimer’s research and beyond.What if something in the blood of an athlete could boost the brainpower of someone who doesn’t or can’t exercise? Could a protein that gets amplified when people exercise help stave off symptoms of Alzheimer’s and other memory disorders?That’s the tantalizing prospect raised by a new study in which researchers injected sedentary mice with blood from mice that ran for miles on exercise wheels, and found that the sedentary mice then did better on tests of learning and memory.The study, published Wednesday in the journal Nature, also found that the type of brain inflammation involved in Alzheimer’s and other neurological disorders was reduced in sedentary mice after they received their athletic counterparts’ blood.Scientific results with mice don’t necessarily translate to humans. Still, experts said the study supports a growing body of research.“We’re seeing an increasing number of studies where proteins from outside the brain that are made when you exercise get into the brain and are helpful for improving brain health, or even improving cognition and disease,” said Rudolph Tanzi, a professor of neurology at Massachusetts General Hospital and Harvard Medical School. He led a 2018 study that found that exercise helped the brains of mice engineered to have a version of Alzheimer’s.The most promising outcome would be if exercise-generated proteins can become the basis for treatments, experts said.“The demonstration that there are transferable factors in the blood that seemed to convey beneficial effects on the brain that improve learning and memory is by far the most interesting aspect of the work,” said Dr. Madhav Thambisetty, a neurologist and senior investigator at the National Institute on Aging, who was not involved in the new research.The study, led by researchers at Stanford School of Medicine, found that one protein — clusterin, produced in the liver and in heart muscle cells — seemed to account for most of the anti-inflammatory effects. But several experts noted that recent studies have found benefits from other proteins. They also said more needs to be learned about clusterin, which plays a role in many diseases, including cancer, and may have negative effects in early stages of Alzheimer’s before brain inflammation becomes dominant.“It’s far too premature to conclude that higher or lower levels of clusterin might be either beneficial or not,” said Dr. Thambisetty, who has studied clusterin. “I don’t think we’re at the stage yet where people can trade in their treadmills or cancel their gym memberships for a clusterin pill or a clusterin injection.”The study was led by Tony Wyss-Coray, a professor of neurology and neurological sciences at Stanford, who had previously done research finding that the blood of young mice can reverse age-related cognitive impairment in old mice.Dr. Wyss-Coray said he wanted to see “if exercise produced factors that would also accumulate in the blood and that you could then transfer them.”The study involved mice that were about three months old — roughly the equivalent of 25-to-30-years-old for humans. Some of the mice, nocturnal animals that love to run, could freely use exercise wheels in their cages and logged about four to six miles on the wheels each night. The wheels were locked for other mice that could scoot around their cages but could not get an extended cardio workout.After 28 days, the researchers took a third group of mice that also did not exercise and injected them with blood plasma, the liquid that surrounds blood cells, from either the runner mice or the non-runner mice. Mice receiving runner blood did better on two tests of learning and memory than those receiving blood from the non-runner mice.In one test, which measures how long a mouse will freeze in fear when it is returned to a cage where it previously received an electric foot shock, mice with runner blood froze 25 percent longer, indicating they had better memory of the stressful event, Dr. Wyss-Coray said. In the other test, mice with runner blood were twice as fast at finding a platform submerged in opaque water, he said.The team also found that the brains of mice with runner blood produced more of several types of brain cells, including those that generate new neurons in the hippocampus, a region involved in memory and spatial learning.A genetic analysis showed that about 1,950 genes had changed in response to the infusion of runner blood, becoming either more or less activated. Most of the 250 genes with the greatest activation changes were involved in inflammation and their changes suggested that brain inflammation was reduced.The team tested whether removing any of the four most significant proteins in the runner blood would matter, and found that if clusterin was removed, anti-inflammatory effects disappeared. And when mice engineered to have a type of brain inflammation or a version of Alzheimer’s were injected with clusterin, it lessened their brain inflammation.In the only part of the study involving humans, 20 military veterans with a pre-dementia condition called mild cognitive impairment who had participated in a six-month exercise program were found to have high levels of clusterin in their blood.Kaci Fairchild, associate director of the Department of Veterans Affairs Sierra Pacific Mental Illness Research, Education and Clinical Center, and an author of the new study, said the veterans, ranging in age from 50 to 89, exercised three times a week, combining cardio with weight training.Dr. Fairchild said that in results that have not yet been published, besides having elevated clusterin, the veterans did better on tests involving word memory and story recall.“Across the board, veterans had improvements in cognitive function, largely related to learning and memory,” Dr. Fairchild said. Noting that some people have disabilities or limitations that prevent them from exercising, she said she hoped that “the implications from this clusterin is that we can develop a medication targeting this protein for persons who weren’t able to engage in physical activity.”In the brain, clusterin binds to cells that line the blood vessels, cells that become inflamed in Alzheimer’s disease, Dr. Wyss-Coray said, suggesting that a potential drug might bind to those cells and “mimic the anti-inflammatory effects.”Still, experts who study Alzheimer’s disease and neuroinflammation said much more research is needed before therapies can be developed.“Not everything that works in mice works in humans, and we don’t know if there are other unexpected side effects that could make it untenable in humans,” said Mark Gluck, a professor of neuroscience and public health at Rutgers University in Newark, N.J., who was not involved in the study.Dr. Michael Heneka, the incoming director of the Luxembourg Centre for Systems Biomedicine who was not involved in the study, said the role of inflammation in diseases processes can change over time, being protective early on and detrimental later, so it is important to target inflammation at the appropriate time.It’s also unclear if clusterin is the optimal protein for a therapy.Other proteins linked to physical exercise have been shown in recent studies to improve cognition in mice. One, irisin, released by muscles, was found to reduce neuroinflammation and help mice perform better on memory and learning tests. Another, called Gpld1, an enzyme produced in the liver, was shown to increase after exercise and to correlate with better cognitive function in elderly mice.Whichever proteins end up being promising, it would be safer to develop a medication than to try to transfuse blood, which would contain other things beside the proteins, said Dr. Tanzi, who was not involved in the new study. “The big question,” he added, “is which proteins are the winners and how do we take advantage of them to provide new therapies?”

Newly published safety data shows that 41 percent of patients in key clinical trials of the Alzheimer’s drug experienced brain bleeding or swelling, though many cases were asymptomatic.Concerns about safety risks of the controversial new Alzheimer’s drug Aduhelm have intensified in the wake of the death of a 75-year-old woman who experienced brain swelling after receiving infusions of the drug as a participant in a clinical trial.The death of the woman, who lived in Canada, occurred in late September and was reported by a doctor to the Food and Drug Administration’s adverse event reporting system this summer. It is being investigated by both the F.D.A. and Biogen, which makes the drug, also known by its scientific name, aducanumab.In a statement Biogen said: “The cause of death is unknown at this time. We know the 75-year-old clinical trial patient was admitted to the hospital with a seizure” and diagnosed with brain swelling.“Following a prolonged hospitalization, the patient was being prepared for discharge when she deteriorated and was transferred to another facility,” the statement continued. “We have requested missing information, including brain imaging, from the critical last nine days of hospitalization.”Last week, Brian Abrahams, a biotech analyst with RBC Capital Markets who has a medical degree, wrote to clients that he had obtained the woman’s case report through a public records request and had concluded that the brain swelling probably caused the woman’s death and “that this is likely to have been caused by aducanumab.”In its statement, Biogen said that “the RBC report only provides a partial view of the case,” adding, “We take this event very seriously and continue to work with the reporting investigator.”In a note earlier this month, Dr. Abrahams, whose assessments of the case were reported previously by Endpoints News, Fierce Pharma and other publications, wrote that the report suggested that the patient “did not appear to have any other contributing conditions listed.”Brain swelling and brain bleeding are known to be possible side effects of Aduhelm, a monoclonal antibody that is administered as a monthly infusion. The F.D.A. approved the drug in June even though a council of senior F.D.A. officials, an advisory committee of outside experts, and many Alzheimer’s specialists said it was unclear whether Aduhelm could benefit patients and that the drug carried serious risks of harm.On Aduhelm’s label, the F.D.A. warns about these brain side effects, known as amyloid related imaging abnormalities (ARIA), and advises physicians to monitor patients and obtain two M.R.I. brain scans during the first year of treatment. The label does not say that people with ARIA should necessarily be taken off the drug. Many cases of ARIA are mild or asymptomatic, but some can be serious.Between July and September, three other cases of ARIA were reported to the F.D.A.’s adverse event database, all requiring hospitalization. Biogen said it was also reviewing those cases.In a recent statement, the American Academy of Neurology noted that “the F.D.A. label calls for less frequent monitoring than was performed in clinical trials” and said that “additional MRIs will often be needed in response to changes in patients’ clinical condition.”The academy said that when talking with patients and families, “neurologists must communicate information about potential adverse effects and the burdens of monitoring.”Dr. Sam Gandy, an Alzheimer’s clinician who is director of the Mount Sinai Center for Cognitive Health, said that another major concern is that the patients in the Aduhelm clinical trials were healthier than many people with Alzheimer’s who might use the drug now that it is available. People were excluded from participating in the trials if they had medical issues that many older people experience, including previous cardiac problems, any indication of impaired liver or kidney function or if they were taking blood thinners.The F.D.A. label does not exclude any of these conditions. “Now if those common comorbidities are not excluded and it’s sort of all comers,” Dr. Gandy said, “I worry that things may look worse in the real world than they did under these very controlled conditions.” He said one of the patients in his private practice, a man in his 80s, participated in an Aduhelm clinical trial and experienced 10 microbleeds in his brain over about a year, causing him to be dismissed from the trial. Since the drug’s approval, Dr. Gandy said, several patients have sought his opinion and have decided against getting the drug in part because of safety concerns.Most data available about Aduhelm comes from two nearly identical Phase 3 clinical trials that Biogen conducted before applying for F.D.A. approval of the drug. Both trials were shut down in 2019 because an independent monitoring committee concluded that the drug did not appear to be helping patients. A later analysis by Biogen found that participants receiving the highest dose of the drug in one trial experienced a very slight slowing of cognitive decline, but participants in the other trial did not benefit at all.Safety data from those trials was published Monday in the journal JAMA Neurology in a study whose authors included eight Biogen employees.The data showed that 425 of 1,029 patients, or 41 percent, who received the high dose of the drug — the dose that the F.D.A. later approved — experienced either brain swelling or bleeding. Sixty-four patients had to stop participating in the trials because of swelling or bleeding.Most of the affected patients, 362, experienced swelling, and 94 of those reported symptoms, according to the study, which also said that most cases of brain swelling resolved within 16 weeks. In a statement, Biogen noted that most swelling emerged early in the treatment period, either while patients were being ramped up to the high dose or shortly after they reached that dose.The study, which reported on the same safety data Biogen presented to the F.D.A. during the drug review process, said that symptoms like headaches, confusion, dizziness or nausea occurred in 103 patients receiving the dose that was later approved. Less frequent symptoms included fatigue, visual impairment, blurred vision and gait disturbance.Biogen said that M.R.I.s showed that swelling or bleeding was mild or moderate in most patients with those side effects. Still, the study reported that scans showed severe effects in 12 percent of patients with swelling, 12 percent of patients with microbleeds and 22 percent of patients with a type of slow brain bleeding.The study said that people with moderate or severe swelling were taken off the drug until their episode resolved. Those with mild swelling and no symptoms could stay on the drug, and the study said their swelling did not get worse. There were no deaths as a result of brain swelling or bleeding in the two trials, the study said. In an earlier safety study, one participant died. The 75-year-old woman who died in September was participating in an extension trial of the drug, Biogen said.More of the patients with brain swelling or bleeding were carriers of a gene mutation, APOE4, which also increases a person’s risk of developing Alzheimer’s disease. While patients in the trials appeared more likely to experience a slowing of decline if they carried the APOE4 mutation, the data suggests they also face greater safety risks from the drug.

It’s the first study of individualized brain stimulation to treat severe depression. Sarah’s case raises the possibility the method may help people who don’t respond to other therapies.Driving home from work in Northern California five years ago, a young woman was so overwhelmed with depression that all she could think about was ending her life.“I couldn’t stop crying,” recalled Sarah, now 38. “The thought that consumed me the entire way on that road was just driving my car into the marshland so I can drown.”She made it home, but soon after, moved in with her parents because doctors considered it unsafe for her to live alone. No longer able to function at work, she quit her health technology job.She tried nearly every treatment: roughly 20 different medications, months in a hospital day program, electroconvulsive therapy, transcranial magnetic stimulation. But as with nearly a third of the more than 250 million people with depression worldwide, her symptoms persisted. Then Sarah became the first participant in an unusual study of an experimental therapy. Now, her depression is so manageable that she’s taking data analysis classes, has moved to her own place and helps care for her mother, who suffered a fall.“Within a few weeks, the suicidal thoughts just disappeared,” said Sarah, who asked to be identified by only her first name to protect her privacy. “Then it was just a gradual process where it was like my lens on the world changed.”Researchers at the University of California, San Francisco surgically implanted a battery-operated, matchbook-sized device in Sarah’s brain — a “pacemaker for the brain” some call it — calibrated to detect the neural activity pattern that occurs when she is becoming depressed. It then delivers pulses of electrical stimulation to stave off depression.Twelve days after Sarah’s device was fully operational in August 2020, her score on a standard depression scale dropped to 14 from 33, and several months later, it fell below 10, essentially signaling remission, the researchers reported.“The device has kept my depression at bay, allowing me to return to my best self and rebuild a life worth living,” Sarah said.Sarah’s is the first documented case of personalizing a technique called deep brain stimulation to successfully treat depression. Much more research is needed before it’s clear how effective the approach could be and for how many patients. But several teams of scientists are now working on ways to essentially match the electrical stimulation to what happens in an individual patient’s brain.Deep brain stimulation is used to treat Parkinson’s disease and several other disorders, but isn’t approved by federal regulators for depression because results have been inconsistent. While some previous studies suggested benefits, two trials sponsored by U.S. device companies were stopped in the last decade because stimulation seemed no better than the placebo effect of a “sham” implant that provided no stimulation.But those studies didn’t target individualized locations or patterns of electrical activity in people’s brains. It was “one size fits all,” said Dr. Darin Dougherty, director of neurotherapeutics at Massachusetts General Hospital, who worked on one of the halted trials. He called the personalized approach with Sarah, which he wasn’t involved in, “very exciting.”“One person’s depression might look very different from another person’s depression,” said Dr. Katherine Scangos, an assistant professor of psychiatry at U.C.S.F. and an author of a report about Sarah’s case, published Monday in the journal Nature Medicine. The senior authors were Dr. Andrew Krystal, an expert in neuro-modulation and mood disorders, and Dr. Edward Chang, whose work includes brain implants for paralyzed patients who cannot speak.To identify the specific brain activity pattern linked to Sarah’s depression, researchers conducted an intensive 10-day exploration of Sarah’s brain, placing multiple electrodes in it and asking about her feelings when they applied stimulation to different locations in varying doses.“One person’s depression might look very different from another person’s depression,” said Dr. Katherine Scangos, a researcher on a new study using deep brain stimulation as a personalized treatment.Mike Kai Chen for The New York TimesSarah remembers an “aha moment” when she felt like “the Pillsbury Doughboy,” emitting a “giant belly laugh,” which she said was “the first time I spontaneously laughed and smiled” in five years. Another feeling resembled “being in front of warm fire and reading a comforting book,” while a negative sensation felt like “nails on a chalkboard.”Eventually, the team identified a specific pattern of electrical activity that coincided with Sarah becoming depressed.The exploratory phase guided the researchers to place the stimulation device in Sarah’s right brain hemisphere linked to electrodes in two regions. One was the the ventral striatum, involved in emotion, motivation and reward, where stimulation “consistently eliminated her feelings of depression,” and the other the amygdala, where changes could “predict when her symptoms were most severe,” Dr. Scangos said.While deep brain stimulation is typically delivered continuously, Sarah’s device is set to supply only a six-second burst when it recognizes her depression-linked brain activity pattern. The goal, said Dr. Dougherty, is that stimulation will disrupt or shift the neural activity to produce a healthier pattern that will ease depressive symptoms.Sarah has continued taking psychiatric medications, and the stimulation hasn’t eliminated depression-causing activity in her brain. But she can manage her illness much better, she said, instead of being unable to make even the smallest decisions, like what to eat.Now, “you’re experiencing that whole negative, depressive, whatever the triggering thing is, and then it’s like suddenly the ultra-rational side of you comes on and those emotions can be separated,” she said in an interview, wearing a T-shirt that said “Take it easy lemon squeezy.”That separation helps her productively use tools from talk therapy, like staying calm and maintaining perspective.About 30 percent of people with depression don’t respond to standard treatments or find the side effects intolerable. Deep brain stimulation wouldn’t be appropriate for all because it costs tens of thousands of dollars and brain surgery to implant the device carries risks like infection. But if the new attempts work, it might help a significant number, experts said. Dr. Chang said the research may also lead to noninvasive approaches that would help more people.“Our job now is really to figure out what is it that identifies who needs this kind of intervention,” said Dr. Helen Mayberg, director of the Center for Advanced Circuit Therapeutics at the Icahn School of Medicine in New York City, who pioneered the concept of deep brain stimulation for depression nearly 20 years ago.Dr. Mayberg uses a different method of individualization. With imaging, she finds the location in each person’s brain where four white matter bundles intersect near a key depression-related region. After implanting electrodes and a stimulation device, “we pretty much set it and forget it,” delivering stimulation continuously, while also helping patients with conventional therapy.Dr. Scangos examined a graph of Sarah’s brain activity. Mike Kai Chen for The New York TimesNeural activity is monitored “to learn the brain signature that heralds an impending depressive relapse or need for a dose adjustment or just indicates that the person is just having a bad week,” Dr. Mayberg said. She led one of the halted trials, but her work has also allowed patients to experience improvements that continue for years if stimulation is sustained.In another approach, Dr. Sameer Sheth, an associate professor of neurosurgery at Baylor College of Medicine, and colleagues study a patient’s specific brain activity pattern to identify which of billions of combinations of stimulation characteristics, like frequency and amplitude, improve that patient’s depression.He then tunes electrodes in two regions and applies that specific combination as continuous stimulation.Dr. Sheth said the first patient, given the device in March 2020, “is remarkably well” now, maintaining a relationship and becoming a father. To test for a placebo effect, researchers gradually stopped stimulation to one brain region without the patient knowing when. His depression “got worse and worse” said Dr. Sheth, until he needed “rescue.” After stimulation restarted, he improved, suggesting the effect “is definitely stimulation-related.”Several months ago, Sarah needed a rescue too. Shortly after entering a study phase where the device is either turned off or left on for six weeks without the participant knowing which, “the suicidal thoughts were back,” Sarah said. Her family tried to get her hospitalized, but hospitals were full. “Things were really bad,” Sarah said.“She did have a very severe worsening of her depression,” said Dr. Scangos. She said she couldn’t disclose whether stimulation had been off or on, but said a device company technician was sent to Sarah’s home to “make a rescue change.”Afterward, Sarah said, she improved again.Over the year, the number of times a day that Sarah’s device has detected depression-linked brain activity and delivered stimulation has decreased somewhat, but is still substantial, Dr. Scangos said. Still, some days Sarah doesn’t need the maximum amount the device is set to provide: 300 times or 30 total minutes daily. (It automatically stops around 6 p.m. because evening stimulation made her too alert to sleep.)Longer-term and more detailed data on Sarah will be published later, said the researchers, who have two other participants so far. The device is intentionally tuned so Sarah cannot feel the stimulation, but she believes she knows that it’s occurred because she subsequently develops a sense of “emotional distance” that keeps negative feelings “compartmentalized,” she said.Also, “I feel alert,” she said. “I feel present.” That’s “a really good sign,” said Dr. Dougherty, who is considering using a similar approach for depression and possibly addiction. “The emotions are still there, but instead of sticking like mud, it’s running off like water.”To help researchers correlate brain activity with emotional states, two or three times a day, Sarah holds a doughnut-shaped magnet to her head, triggering the device to save the next 90 seconds of neural activity, and she completes a mental health survey. She’s been encouraged to pick moments “when she’s in a very good mood or a bad mood,” Dr. Scangos said. Also, twice daily, 12 minutes of neural data are automatically relayed to the device company and researchers.One question, experts said, is whether Sarah’s results support the theory that stimulating briefly whenever depression begins works because it keeps the brain from becoming accustomed to the treatment. Or, Dr. Sheth asked, does Sarah’s need for many daily doses after a year suggest continuous stimulation would be as or more effective?Another question is whether the therapy can prompt lasting brain changes to eventually avert depression with little or no continuing stimulation.Because of her implanted device that delivers deep brain stimulation, Sarah has been able to move to her own apartment and take classes in data analysis.Ruth Fremson/The New York TimesResearchers, several of whom consult for device companies or have patents related to deep brain stimulation, expect it will take years to learn if individualized approaches are effective enough to be approved. Different methods might work for different people’s depression, and individualized stimulation might eventually help other psychiatric disorders, researcher say. The most elemental things have improved for Sarah, who said she’s started to “relearn my life” and that “hobbies I used to distract myself from suicidal thoughts suddenly became pleasurable again.” When depressed, Sarah, a passionate cook and foodie, had such slow reflexes and trouble functioning that she’d cut or burn herself in the kitchen and doctors told her it wasn’t safe to cook anymore. Foods had little flavor. But after receiving the device, she ate Vietnamese pho in the hospital cafeteria and was thrilled she could taste “the brightness and the herbs,” she said. While being driven home from the hospital, she saw the marshes and exclaimed: “God, the color differentiation is gorgeous.” Now, she said, she’s “seeing things that are beautiful in the world, and when I was in the depths of depression, all I saw was what was ugly.”If you are having thoughts of suicide, call the National Suicide Prevention Lifeline at 1-800-273-8255 (TALK) or go to SpeakingOfSuicide.com/resources for a list of additional resources.

En un gran estudio reciente, los pacientes recuperados de COVID-19 tuvieron 35 por ciento más probabilidades de sufrir daños a largo plazo en los riñones o un deterioro de la función renal.Desde el principio de la pandemia, los médicos han descubierto que la gente que experimenta casos graves de COVID-19 a menudo tiene problemas renales y no solo el daño pulmonar característico de esta enfermedad.Ahora, un estudio muy grande señala que, después de que los pacientes se recuperan de la infección inicial, los problemas renales pueden durar meses y que en algunos pacientes las secuelas pueden originar una reducción considerable de la función renal.En este estudio, publicado el 1 de septiembre en la revista Journal of the American Society of Nephrology, se descubrió que cuanto más enfermos estuvieran los pacientes al principio, más probable era que sufrieran un daño renal prolongado.Pero incluso las personas que contraen el virus y presentan una infección menos grave podrían ser vulnerables.“De manera generalizada, en realidad vemos un mayor riesgo de que se presente una serie de eventos importantes vinculados con el riñón”, señaló F. Perry Wilson, nefrólogo y profesor adjunto de Medicina en la Universidad de Yale, quien no participó en el estudio. “Y lo que más me sorprendió es que estos perduraron”.Los riñones tienen una participación fundamental en el organismo para eliminar las toxinas y el exceso de líquido de la sangre, ayudar a mantener una presión arterial saludable y regular el equilibrio de electrolitos y de otras sustancias importantes. Cuando los riñones no funcionan bien o de manera eficiente, los líquidos se acumulan y provocan inflamación, presión sanguínea alta, debilidad en los huesos y otros problemas.El corazón, los pulmones, el sistema nervioso central y el sistema inmunitario pueden sufrir un deterioro. En la etapa terminal de la insuficiencia renal, quizás se necesite la diálisis o un trasplante de riñón. Esta enfermedad podría provocar la muerte.Este nuevo estudio, el cual se basó en los registros de los pacientes del sistema de salud del Departamento de Asuntos de los Veteranos, analizó la información de 89.216 personas que dieron positivo al coronavirus entre el 1 de marzo de 2020 y el 15 de marzo de 2021, así como la información de 1.637.467 personas que no tuvieron covid.Entre uno y seis meses después de haberse infectado, los sobrevivientes de covid tuvieron aproximadamente un 35 por ciento más de probabilidades de tener un daño renal o un deterioro considerable en la función renal que quienes no tuvieron covid, señaló Ziyad Al-Aly, director del servicio de investigación y desarrollo en el Sistema de Atención a la Salud de San Luis del Departamento de Asuntos de los Veteranos (VA, por su sigla en inglés) y autor sénior del estudio.“Las personas que han sobrevivido a los primeros 30 días de la covid están en riesgo de desarrollar insuficiencia renal”, mencionó Al-Aly, nefrólogo y profesor adjunto de Medicina en la Escuela de Medicina de la Universidad de Washington.Debido a que muchas personas que tienen una función renal disminuida no experimentan dolor ni otros síntomas, “lo que importa en realidad es que la gente sepa que existe un riesgo y que los médicos de los pacientes que tuvieron covid estén muy atentos a la función y a la insuficiencia renal”, explicó.Los dos grupos de pacientes del estudio diferían en que todos los miembros de un grupo se habían infectado con covid y los miembros del otro grupo podían haber tenido una variedad de otros padecimientos. Los especialistas advirtieron que las comparaciones tenían limitaciones.Los investigadores intentaron reducir al mínimo las diferencias a través de análisis detallados que ajustaron a partir de una larga lista de características demográficas, enfermedades preexistentes, uso de medicamentos y si las personas estaban en asilos.Otra limitación es que los pacientes en el estudio del VA eran en su mayoría varones blancos de una edad promedio de 68 años, así que no queda muy claro cuán generalizables son los resultados.Según los expertos, un aspecto sólido de la investigación es que contempla a más de 1,7 millones de pacientes con expedientes médicos electrónicos detallados, lo que la convierte en el estudio más grande hasta ahora sobre problemas renales vinculados a la covid.Aunque lo más probable es que los resultados no sean aplicables para todos los pacientes con covid, muestran que entre los participantes del estudio “existe una afectación muy notable a largo plazo para la salud renal de los sobrevivientes de COVID-19, sobre todo para quienes estuvieron muy enfermos durante la enfermedad aguda”, señaló C. John Sperati, nefrólogo y profesor adjunto de Medicina en la Universidad Johns Hopkins, quien no participó en el estudio.Otros investigadores han descubierto patrones parecidos, “así que este no es el único estudio que indica que estos eventos están ocurriendo después de una infección de COVID-19”, añadió.Sperati y otros especialistas han señalado que incluso si solo un pequeño porcentaje de los millones de sobrevivientes de COVID-19 en Estados Unidos desarrollasen problemas renales prolongados, el impacto para la atención sanitaria sería muy importante.Con el fin de evaluar la función renal, el equipo de investigación evaluó los niveles de creatinina, un producto de desecho que los riñones deben eliminar del cuerpo y también un indicador de la adecuada filtración de la sangre, el cual se denomina índice de filtración glomerular.Wilson explicó que, a lo largo de la vida, los adultos sanos poco a poco pierden la función renal a partir de los treinta y tantos o cuarenta y tantos años a razón de aproximadamente el uno por ciento o menos al año. Las enfermedades y las infecciones importantes pueden provocar una pérdida más significativa o permanente de esta función, la cual puede originar una insuficiencia renal crónica o una insuficiencia renal en etapa terminal.Según Al-Aly, en el nuevo estudio se descubrió que 4757 sobrevivientes de covid habían perdido al menos un 30 por ciento de la función renal en el año posterior a haber tenido la infección.Eso equivale a cerca de “30 años de deterioro en la función renal”, afirmó Wilson.En el estudio se descubrió que existía un 25 por ciento más de probabilidades de que los pacientes que tuvieron covid alcanzaran ese nivel de deterioro que las personas que no contrajeron la enfermedad.Un grupo más pequeño de sobrevivientes de covid presentó deterioro más acentuado. Pero había un 44 por ciento más de probabilidades de que los pacientes con covid perdieran al menos el 40 por ciento de la función renal y era un 62 por ciento más probable que perdieran al menos el 50 por ciento que los pacientes sin covid.Al-Aly informó que en 220 pacientes con covid se detectó insuficiencia renal en etapa terminal, la cual se presenta cuando se pierde al menos el 85 por ciento de la función renal. En el estudio se encontró que los sobrevivientes de covid tenían tres veces más probabilidades de recibir este diagnóstico que los pacientes sin covid.Al-Aly y sus colegas también investigaron un tipo de falla renal repentina llamada insuficiencia renal aguda, la cual otros estudios han encontrado en hasta la mitad de los pacientes hospitalizados con covid. Esta falla puede sanar sin provocar pérdida de la función renal a largo plazo.No obstante, en el estudio del veteranos, se descubrió que meses después de haber tenido la infección, 2812 sobrevivientes de covid sufrieron insuficiencia renal aguda, casi el doble que los pacientes sin covid, aseveró Al-Aly.Wilson señaló que los nuevos datos respaldaban los resultados de un estudio con 1612 pacientes que realizaron él y sus colegas en el cual descubrieron que los pacientes con covid que tenían insuficiencia renal aguda presentaron una función renal significativamente peor en los meses posteriores a su salida del hospital comparados con quienes presentaban daños renales agudos resultantes de otras enfermedades.En el nuevo estudio, los investigadores no compararon de manera directa a los sobrevivientes de covid con las personas infectadas por otros virus, como el de la influenza, lo cual dificultaba saber si “en realidad estás más enfermo que si hubieras tenido otra infección grave”, comentó Sperati.Sin embargo, en un estudio anterior realizado por el equipo de Al-Aly, en el que se analizaron muchos problemas de salud posteriores a la covid, incluidos los problemas renales, las personas hospitalizadas por COVID-19 tenían un riesgo significativamente mayor de desarrollar problemas de salud a largo plazo en prácticamente todas las categorías médicas, incluidas las afecciones cardiovasculares, metabólicas y gastrointestinales, que las personas hospitalizadas por la gripe.Todos los tipos de trastornos renales monitoreados en el nuevo estudio fueron mucho más frecuentes en los pacientes de covid que estuvieron más enfermos al principio, es decir, los que pasaron algún tiempo en cuidados intensivos o los que experimentaron una lesión renal aguda en el hospital.Las personas que estuvieron menos graves durante su hospitalización por covid tenían menos probabilidades de sufrir problemas renales persistentes, pero seguían siendo considerablemente más propensas que los pacientes que no habían tenido covid.“Las personas que corren mayor riesgo son las que realmente lo pasaron mal ya desde el inicio”, dijo Al-Aly. “Pero realmente, nadie se libra del riesgo”.El estudio también descubrió que incluso los pacientes de covid que nunca necesitaron hospitalización tenían un riesgo ligeramente mayor de sufrir problemas renales que la población general de pacientes del VA. Pero el riesgo parecía tan pequeño, dijo Sperati, que “no sé si confiaría” en esos resultados.Wilson observó que algunos pacientes de covid que no necesitaron hospitalización estaban, sin embargo, bastante enfermos y requirieron permanecer en cama durante días. Dijo que es posible que esos fueran los que desarrollaron una disfunción renal a largo plazo, en lugar de las personas en el extremo más leve del espectro de covid.Los médicos no saben por qué la covid puede provocar daño renal. Los expertos explicaron que es posible que los riñones sean especialmente sensibles al aumento de la inflamación o la activación del sistema inmunitario, o que los problemas de formación de coágulos sanguíneos que casi siempre se observan en los pacientes con covid alteren la función renal.Sperati dijo que los pacientes de covid en el hospital parecían tener mayor necesidad de diálisis, y más proteínas y sangre en la orina que los pacientes hospitalizados con otras enfermedades graves.“El coronavirus es probablemente un virus un poco más tóxico para los riñones”, dijo Wilson. “Creo que el síndrome por covid tiene algunos efectos adversos a largo plazo en el riñón”.Pam Belluck es una reportera de ciencia y salud cuyos galardones incluyen un Premio Pulitzer compartido en 2015 y el premio Nellie Bly a la mejor historia de primera plana. Es autora de Island Practice, un libro sobre un doctor peculiar. @PamBelluck

In a study of veterans, Covid survivors were 35 percent more likely than other patients to have long-term kidney damage or declines in kidney function.Since the beginning of the pandemic, doctors have found that people who become very ill with Covid-19 often experience kidney problems, not just the lung impairments that are the hallmark of the illness.Now, a large study suggests that kidney issues can last for months after patients recover from the initial infection, and may lead to a serious lifelong reduction of kidney function in some patients.The study, published Wednesday in the Journal of the American Society of Nephrology, found that the sicker Covid patients were initially, the more likely they were to experience lingering kidney damage.But even people with less severe initial infections could be vulnerable.“You see really, across the board, a higher risk of a bunch of important kidney-associated events,” said Dr. F. Perry Wilson, a nephrologist and associate professor of medicine at Yale, who was not involved in the study. “And what was particularly striking to me was that these persisted.”Kidneys play a vital role in the body, clearing toxins and excess fluid from the blood, helping maintain a healthy blood pressure, and keeping a balance of electrolytes and other important substances. When the kidneys are not working properly or efficiently, fluids build up, leading to swelling, high blood pressure, weakened bones and other problems.The heart, lungs, central nervous system and immune system can become impaired. In end-stage kidney disease, dialysis or an organ transplant may become necessary. The condition can be fatal.The new study, based on records of patients in the Department of Veterans Affairs health system, analyzed data from 89,216 people who tested positive for the coronavirus between March 1, 2020, and March 15, 2021, as well as data from 1,637,467 people who were not Covid patients.Between one and six months after becoming infected, Covid survivors were about 35 percent more likely than non-Covid patients to have kidney damage or substantial declines in kidney function, said Dr. Ziyad Al-Aly, chief of the research and development service at the V.A. St. Louis Health Care System and senior author of the study.“People who have survived the first 30 days of Covid are at risk of developing kidney disease,” Dr. Al-Aly, a nephrologist, said.Because many people with reduced kidney function do not experience pain or other symptoms, “what’s really important is that people realize that the risk is there and that physicians caring for post-Covid patients really pay attention to kidney function and disease,” he said.The two sets of patients in the study differed, in that members of one group had all been infected with Covid and members of the other group may have had a variety of other health conditions. Experts cautioned that there were limitations to the comparisons.The researchers tried to minimize the differences with detailed analyses that adjusted for a long list of demographic characteristics, pre-existing health conditions, medication usage and whether people were in nursing homes.Another limitation is that patients in the V.A. study were largely male and white, with a median age of 68, so it is unclear how generalizable the results are.One strength of the research, experts said, is that it involves over 1.7 million patients with detailed electronic medical records, making it the largest study so far on Covid-related kidney problems.While the results most likely would not apply to all Covid patients, they show that for those in the study, “there’s a pretty notable impact on kidney health in survivors of Covid-19 over the long term, particularly those who were very sick during their acute illness,” said Dr. C. John Sperati, a nephrologist and associate professor of medicine at Johns Hopkins, who was not involved in the study.Other researchers have found similar patterns, “so this is not the only study suggesting that these events are transpiring after Covid-19 infection,” he added.He and other experts said that if even a small percentage of the millions of Covid survivors in the United States developed lasting kidney problems, the impact on health care would be great.To assess kidney function, the research team evaluated levels of creatinine, a waste product that kidneys are supposed to clear from the body, as well as a measure of how well the kidneys filter the blood called the estimated glomerular filtration rate.Healthy adults gradually lose kidney function over time, about 1 percent or less a year, starting in their 30s or 40s, Dr. Wilson said. Serious illnesses and infections can cause more profound or permanent loss of function that may lead to chronic kidney disease or end-stage kidney disease.The new study found that 4,757 Covid survivors had lost at least 30 percent of kidney function in the year after their infection, Dr. Al-Aly said.That is equivalent to roughly “30 years of kidney function decline,” Dr. Wilson said.Covid patients were 25 percent more likely to reach that level of decline than people who had not had the illness, the study found.Smaller numbers of Covid survivors had steeper declines. But Covid patients were 44 percent more likely than non-Covid patients to lose at least 40 percent of kidney function and 62 percent more likely to lose at least 50 percent.End-stage kidney disease, which occurs when at least 85 percent of kidney function is lost, was detected in 220 Covid patients, Dr. Al-Aly said. Covid survivors were nearly three times as likely to receive the diagnosis as patients without Covid, the study found.Dr. Al-Aly and his colleagues also looked at a type of sudden renal failure called acute kidney injury, which other studies have found in up to half of hospitalized Covid patients. The condition can heal without causing long-term loss of kidney function.But the V.A. study found that months after their infection, 2,812 Covid survivors suffered acute kidney injury, nearly twice the rate in non-Covid patients, Dr. Al-Aly said.Dr. Wilson said the new data supported results of a study of 1,612 patients that he and colleagues conducted that found that Covid patients with acute kidney injury had significantly worse kidney function in the months after leaving the hospital than people with acute kidney injuries from other medical conditions.In the new study, researchers did not directly compare Covid survivors with people infected with other viruses, like the flu, making it hard to know “are you really any sicker than if you just had another bad infection,” Dr. Sperati said.In a previous study by Dr. Al-Aly’s team, however, which looked at many post-Covid health issues, including kidney problems, people hospitalized with Covid-19 were at significantly greater risk of developing long-term health problems in virtually every medical category, including cardiovascular, metabolic and gastrointestinal conditions, than were people hospitalized with the flu.Every type of kidney impairment measured in the new study was much more common in Covid patients who were sicker initially — those in intensive care or who experienced acute kidney injury in the hospital.People who were less ill during their Covid hospitalization were less likely to have lingering kidney problems, but still considerably more likely than non-Covid patients.“People who are at highest risk are the people who really had it bad to start with,” Dr. Al-Aly said. “But really, no one is spared the risk.”The study also found that even Covid patients who never needed hospitalization had slightly higher risk of kidney trouble than the general V.A. patient population. But the risk seemed so small, Dr. Sperati said, that “I don’t know that I would hang my hat on” those results.Dr. Wilson noted that some Covid patients who did not need hospitalization were nonetheless quite ill, needing to stay in bed for days. He said it’s possible that those were the ones who developed long-term kidney dysfunction, rather than people at the mildest end of the Covid spectrum.Doctors are unsure why Covid can cause kidney damage. Kidneys might be especially sensitive to surges of inflammation or immune system activation, or blood-clotting problems often seen in Covid patients may disturb kidney function, experts said.Dr. Sperati said Covid patients in the hospital seemed to have greater need for dialysis, and more protein and blood in their urine, than patients hospitalized with other severe illnesses.“Covid is probably a little more of a kidney-toxic virus,” Dr. Wilson said. “I do think that the Covid syndrome has some long-term adverse effects on the kidney.”

Dr. Anthony S. Fauci warned on Sunday that the coronavirus pandemic is now “going in the wrong direction” in the United States because too many Americans are still choosing not to get vaccinated.Asked on CNN’s “State of the Union” program about projections in recent statistical models that Covid-19 cases and deaths could surge in the coming months if vaccination rates don’t increase, Dr. Fauci said “it’s not going to be good.”With about half of Americans not yet vaccinated and the fast-spreading Delta variant circulating, Dr. Fauci and a range of current and former health officials expressed exasperation at the situation on Sunday and vigorously pressed the case that vaccination is the best and most effective way to stem the tide of Covid cases.“It is really a pandemic among the unvaccinated,” Dr. Fauci said, adding “It’s like you have two kinds of America. You have the very vulnerable unvaccinated part and you have the really relatively protected vaccinated part. If you are vaccinated, you are in a very different category than someone who is not vaccinated.”The situation is so dire that in recent days, even some Republican governors in low-vaccination states have been pointedly exhorting people to get a Covid vaccine.On Sunday on CNN, Gov. Asa Hutchinson of Arkansas said that, with the new school year on the horizon, “this is a pivotal moment in our race against the Covid virus,” adding that “what’s holding us back is a low vaccination rate.”Governor Hutchinson, a Republican, said he has been holding town halls recently, which he credited for a 40 percent increase in vaccination. Still he added that “certainly the resistance has hardened” among some people. “It’s simply false information,” he said. “It is myths.”On CBS’s “Face the Nation,” Dr. Jerome Adams, who was surgeon general in the Trump administration, also encouraged vaccination, casting the decision in patriotic terms. “Get vaccinated because it’s going to help every single American enjoy the freedoms that we want to return to,” he said.Dr. Adams said some people still have legitimate questions about getting vaccinated, including workers who worry post-vaccine side effects might cause them to miss a day of work or a paycheck. He predicted immunization rates would increase once the vaccines — currently available under emergency use authorization from the Food and Drug Administration — become fully licensed. That will likely prompt the military and some businesses to mandate vaccination for service members and employees, he said.In the meantime, Dr. Adams said the message should be “it is your choice, but choices come with consequences to you and other people,” including children not yet old enough for vaccination and people who are medically vulnerable..css-1xzcza9{list-style-type:disc;padding-inline-start:1em;}.css-3btd0c{font-family:nyt-franklin,helvetica,arial,sans-serif;font-size:1rem;line-height:1.375rem;color:#333;margin-bottom:0.78125rem;}@media (min-width:740px){.css-3btd0c{font-size:1.0625rem;line-height:1.5rem;margin-bottom:0.9375rem;}}.css-3btd0c strong{font-weight:600;}.css-3btd0c em{font-style:italic;}.css-w739ur{margin:0 auto 5px;font-family:nyt-franklin,helvetica,arial,sans-serif;font-weight:700;font-size:1.125rem;line-height:1.3125rem;color:#121212;}#NYT_BELOW_MAIN_CONTENT_REGION .css-w739ur{font-family:nyt-cheltenham,georgia,’times new roman’,times,serif;font-weight:700;font-size:1.375rem;line-height:1.625rem;}@media (min-width:740px){#NYT_BELOW_MAIN_CONTENT_REGION .css-w739ur{font-size:1.6875rem;line-height:1.875rem;}}@media (min-width:740px){.css-w739ur{font-size:1.25rem;line-height:1.4375rem;}}.css-9s9ecg{margin-bottom:15px;}.css-uf1ume{display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-box-pack:justify;-webkit-justify-content:space-between;-ms-flex-pack:justify;justify-content:space-between;}.css-wxi1cx{display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-flex-direction:column;-ms-flex-direction:column;flex-direction:column;-webkit-align-self:flex-end;-ms-flex-item-align:end;align-self:flex-end;}.css-12vbvwq{background-color:white;border:1px solid #e2e2e2;width:calc(100% – 40px);max-width:600px;margin:1.5rem auto 1.9rem;padding:15px;box-sizing:border-box;}@media (min-width:740px){.css-12vbvwq{padding:20px;width:100%;}}.css-12vbvwq:focus{outline:1px solid #e2e2e2;}#NYT_BELOW_MAIN_CONTENT_REGION .css-12vbvwq{border:none;padding:10px 0 0;border-top:2px solid #121212;}.css-12vbvwq[data-truncated] .css-rdoyk0{-webkit-transform:rotate(0deg);-ms-transform:rotate(0deg);transform:rotate(0deg);}.css-12vbvwq[data-truncated] .css-eb027h{max-height:300px;overflow:hidden;-webkit-transition:none;transition:none;}.css-12vbvwq[data-truncated] .css-5gimkt:after{content:’See more’;}.css-12vbvwq[data-truncated] .css-6mllg9{opacity:1;}.css-qjk116{margin:0 auto;overflow:hidden;}.css-qjk116 strong{font-weight:700;}.css-qjk116 em{font-style:italic;}.css-qjk116 a{color:#326891;-webkit-text-decoration:underline;text-decoration:underline;text-underline-offset:1px;-webkit-text-decoration-thickness:1px;text-decoration-thickness:1px;-webkit-text-decoration-color:#326891;text-decoration-color:#326891;}.css-qjk116 a:visited{color:#326891;-webkit-text-decoration-color:#326891;text-decoration-color:#326891;}.css-qjk116 a:hover{-webkit-text-decoration:none;text-decoration:none;}Several current and former officials discussed whether recommendations or mandates for wearing masks should be reinstated.Dr. Fauci said the Biden administration is considering reissuing stronger mask-wearing guidelines. In May, the Centers for Disease Control and Prevention relaxed its guidance, saying that people who are fully vaccinated do not need to wear a mask in most indoor settings.Dr. Adams said “that guidance, quite frankly, has confused citizens, it’s frustrated businesses and public health officials who I continue to hear from, and it’s been, by any qualification, a failure.”He said the C.D.C. should state clearly that even people who are vaccinated should wear masks if they are in public, around people whose vaccination status is unclear or in a community where Covid cases are increasing. “The CDC needs to give those businesses, those health officials a little bit of cover by clarifying the guidance that they have out there,” Dr. Adams said.

The major medical center’s rejection of the new Alzheimer’s drug is one of the starkest signs of concern over its effectiveness.In a striking reflection of concern over the approval of the controversial new Alzheimer’s drug Aduhelm, the Cleveland Clinic said Wednesday evening that it would not administer it to patients.The clinic, one of the largest and most respected medical centers in the country, said in a statement that a panel of its experts had “reviewed all available scientific evidence on this medication,” which is also called aducanumab.“Based on the current data regarding its safety and efficacy, we have decided not to carry aducanumab at this time,” the statement said.A spokeswoman for the clinic said that individual physicians there could prescribe Aduhelm to patients, but those patients would have to go elsewhere to receive the drug, which is administered as a monthly intravenous infusion.The stance by the major medical center is the latest fallout from the Food and Drug Administration’s approval of the drug on June 7, a decision that has also spurred congressional investigations.Many Alzheimer’s experts and other scientists have said that it is unclear that the drug works to help slow cognitive decline and that in the best-case scenario, the evidence suggested only a slight slowing while also showing that Aduhelm could cause brain swelling or brain bleeding.The F.D.A. recently approved Aduhelm despite scant evidence that it helps patients.Biogen, via Associated PressThe drug is also expensive. Biogen, the maker, has set its price at $56,000 a year.In a recent survey of nearly 200 neurologists and primary care doctors, most said they disagreed with the F.D.A. decision and did not plan to prescribe the drug to their patients.Last week, in response to growing criticism, Dr. Janet Woodcock, the acting F.D.A. commissioner, called for an independent federal investigation into the agency’s approval process, writing that “to the extent these concerns could undermine the public’s confidence in F.D.A.’s decision, I believe it is critical that the events at issue be reviewed by an independent body.”Two nearly identical clinical trials of Aduhelm were stopped early because an independent data monitoring committee concluded that the drug didn’t appear to be helping patients. A later analysis by Biogen found that participants receiving the high dose of the drug in one trial had experienced a very slight slowing of cognitive decline — 0.39 on an 18-point scale — but that participants in the other trial had not benefited at all.About 40 percent of trial participants developed brain bleeding or brain swelling, and while most of those cases were mild or manageable, about 6 percent of participants dropped out of the trials because of serious adverse effects from those conditions.After evaluating the data late last year, an F.D.A. advisory committee of outside experts strongly recommended against approval, and three of its members resigned in protest last month when the agency bucked the advisory committee’s advice. The American Geriatrics Society had also urged the agency not to approve the drug, saying it would be “premature given the lack of sufficient evidence.”Last week, in response to widespread criticism that it had approved Aduhelm for anyone with Alzheimer’s, the F.D.A. sharply narrowed the drug’s recommended use, saying it should be used only for people with mild memory or thinking problems because there was no data on Aduhelm’s use in later stages of Alzheimer’s.

Even those who supported the F.D.A.’s approval of the controversial new drug said authorizing it for anyone with Alzheimer’s disease was much too broad.A new drug for the treatment of Alzheimer’s disease should be given to a much narrower group of patients than the federal approval permits, Alzheimer’s experts — including those who strongly supported approval of the medication — said on Monday.Since the Food and Drug Administration approved the controversial and expensive drug, Aduhelm, made by Biogen, this month, much discussion has focused on the fact that many scientists, and the F.D.A.’s own independent advisory committee, say the evidence does not convincingly show that the drug works.But another major issue has received less attention: which patients should receive the drug and what doctors should do to prescribe it responsibly and safely.The F.D.A. has so far imposed strikingly few limitations on Aduhelm, a monthly intravenous infusion that requires patients to have regular M.R.I. scans because the drug can cause swelling or hemorrhaging in the brain.While the only patients who received the drug during clinical trials were those with very mild Alzheimer’s or an even milder pre-Alzheimer’s impairment, the F.D.A.’s label for Aduhelm says simply that the drug is “for the treatment of Alzheimer’s disease.” Under “contraindications,” the term for health conditions or other characteristics that should prevent patients from taking a drug, the label says “None.”The broadness of the label has surprised and concerned even the biggest champions of the drug.“Oy,” said one enthusiastic supporter of Aduhelm’s approval, Dr. Stephen Salloway, describing his reaction “when I saw from the label that there are no contraindications.”Dr. Salloway, director of neurology and the Memory and Aging Program at Butler Hospital in Providence, R.I., spoke on Monday in a forum sponsored by the Alzheimer’s Association, a large patient advocacy group that pushed for approval of the drug. He and the five other experts answering questions about the use of the drug emphasized that the use of Aduhelm should be limited to certain patients: those in early stages of the disease whose brains contain high levels of amyloid, a protein that clumps into plaques in people with Alzheimer’s disease.The panelists, who had varying opinions about whether Aduhelm should have been approved, agreed that the drug’s potential brain side effects must be monitored carefully and that doctors should disclose to interested patients that there are many unknowns about Aduhelm, including whether it can provide any benefit.Aduhelm was designed to slow the progression of memory and thinking problems in people with mild cognitive symptoms, but its approval has been contentious. A number of scientists objected because only one of two clinical trials showed any hint of benefit, and in that trial the high dose of the medication slowed cognitive decline only slightly — by about four months in an 18-month period.Dr. Salloway, a site principal investigator for trials of the drug, wasn’t paid for that work but has received research and consulting fees from Biogen. He said doctors should use the drug only for patients whose statuses match those in the clinical trials.“There’s no evidence that it could be beneficial for any other stage of Alzheimer’s,” he said.Mary Sano, director of the Mount Sinai Alzheimer’s Disease Research Center in New York City, said the criteria that she and other panelists outlined were “very important” and meant that “it’s going to be very restrictive and the ability to share this drug with a wide range of people will be significantly limited, at least at this time.”Treating people only with mild symptoms would mean that for dementia clinicians, “most of your people in your current practice are probably not eligible,” Dr. Sano said.In its decision, the F.D.A. acknowledged that there was not the level of evidence of benefit that the agency usually requires. As a result, it is making Aduhelm available under a program called accelerated approval, citing the drug’s ability to reduce levels of amyloid in the brain. But reducing amyloid is not the same thing as slowing symptoms of dementia. Many amyloid-reducing drugs have failed to slow decline in clinical trials, a history that makes some experts especially wary of placing confidence in Aduhelm based on the evidence produced so far.Given the agency’s emphasis on amyloid in its approval decision, and the fact that all of the clinical trial participants had to have high amyloid levels, experts have also been surprised that the F.D.A. label does not require patients to be screened for the protein. Doctors at the Alzheimer’s Association forum all said that high levels of amyloid, typically measured by PET scan or spinal tap, should be a condition of treatment.Several of the panelists said that, at least at the outset, relatively few doctors and clinics would have the ability to adequately diagnose, screen and treat patients.“This is not a simple medication to use,” said Dr. Paul Aisen, director of the Alzheimer’s Therapeutic Research Institute at the University of Southern California and a co-author of an article that urged the F.D.A. to approve the drug. “I think that establishing the appropriate individuals for treatment, and monitoring treatment, requires knowledge and benefits from experience, and there are very few clinicians who have this experience.”The panelists devoted considerable discussion to the possibility of brain swelling and hemorrhages, which occurred in about 40 percent of participants who received the high dose in the two large clinical trials. Many cases were mild or asymptomatic, but Dr. Alireza Atri, director of the Banner Sun Health Research Institute in Phoenix and another co-author of the article supporting approval of the drug, said that it was possible that “one out of 200 or 300 individuals can have a serious side effect and need to be in a hospital.”Dr. Salloway said that it would be “more challenging” for doctors to safely monitor for brain side effects than it was within the strict standards of the clinical trials. He said that people should not be given the drug if they have had a macro-hemorrhage in the brain; more than five micro-hemorrhages; a significant stroke; or “unstable medical conditions that could interfere with treatment.”Dr. David S. Knopman, a clinical neurologist at the Mayo Clinic and a site principal investigator for one of the trials, who did not support approval, said people who were taking blood thinners should also be excluded.“We know that this treatment carries considerable risks,” said Suzanne Craft, co-director of the Roena B. Kulynych Center for Memory and Cognition Research at the Wake Forest University School of Medicine. And assessing how and whether it helps patients could be tricky, Dr. Craft and others said.It will be important to have comprehensive discussions with patients and families about “how to weigh the inconvenience and cost and risk against the possible benefit,” Dr. Aisen said.“Managing expectations is a huge challenge here,” he said, adding that “our expectation is a modest slowing of the rate of decline. It is impossible to determine on an individual patient level whether someone is benefiting or not.”