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  • The Big COVID Question for Hospitals This Fall

    The Big COVID Question for Hospitals This Fall

    Back in the spring, around the end of the COVID-19 public-health emergency, hospitals around the country underwent a change in dress code. The masks that staff had been wearing at work for more than three years vanished, in some places overnight. At UChicago Medicine, where masking policies softened at the end of May, Emily Landon, the executive medical director of infection prevention and control, fielded hate mail from colleagues, some chiding her for waiting too long to lift the requirement, others accusing her of imperiling the immunocompromised. At Vanderbilt University Medical Center, which did away with masking in April, ahead of many institutions, Tom Talbot, the chief hospital epidemiologist, was inundated with thank-yous. “People were ready; they were tired,” he told me. “They’d been asking for several months before that, ‘Can we not stop?’”

    But across hospitals and policies, infection-prevention experts shared one sentiment: They felt almost certain that the masks would need to return, likely by the end of the calendar year. The big question was exactly when.

    For some hospitals, the answer is now. In recent weeks, as COVID-19 hospitalizations have been rising nationwide, stricter masking requirements have returned to a smattering of hospitals in Massachusetts, California, and New York. But what’s happening around the country is hardly uniform. The coming respiratory-virus season will be the country’s first after the end of the public-health emergency—its first, since the arrival of COVID, without crisis-caliber funding set aside, routine tracking of community spread, and health-care precautions already in place. After years of fighting COVID in concert, hospitals are back to going it alone.

    A return to masking has a clear logic in hospitals. Sick patients come into close contact; medical procedures produce aerosols. “It’s a perfect storm for potential transmission of microbes,” Costi David Sifri, the director of hospital epidemiology at UVA Health, told me. Hospitals are on the front lines of disease response: They, more than nearly any other place, must prioritize protecting society’s vulnerable. And with one more deadly respiratory virus now in winter’s repertoire, precautions should logically increase in lockstep. But “there is no clear answer on how to do this right,” says Cameron Wolfe, an infectious-disease physician at Duke. Americans have already staked out their stances on masks, and now hospitals have to operate within those confines.


    When hospitals moved away from masking this spring, they each did so at their own pace—and settled on very different baselines. Like many other hospitals in Massachusetts, Brigham and Women’s Hospital dropped its mask mandate on May 12, the day the public-health emergency expired; “it was a noticeable difference, just walking around the hospital” that day, Meghan Baker, a hospital epidemiologist for both Brigham and Women’s Hospital and Dana-Farber Cancer Institute, told me. UVA Health, meanwhile, weaned staff off of universal masking over the course of about 10 weeks.

    Most masks at the Brigham are now donned on only a case-by-case basis: when a patient has active respiratory symptoms, say, or when a health-care worker has been recently sick or exposed to the coronavirus. Staff also still mask around the same subset of vulnerable patients that received extra protection before the pandemic, including bone-marrow-transplant patients and others who are highly immunocompromised, says Chanu Rhee, an associate hospital epidemiologist at Brigham and Women’s Hospital. UVA Health, meanwhile, is requiring masks for everyone in the hospital’s highest-risk areas—among them, certain intensive-care units, as well as cancer, transplant, and infusion wards. And although Brigham patients can always request that their providers mask, at UVA, all patients are asked upon admission whether they’d like hospital staff to mask.

    Nearly every expert I spoke with told me they expected that masks would at some point come back. But unlike the early days of the pandemic, “there is basically no guidance from the top now,” Saskia Popescu, an epidemiologist and infection-prevention expert at the University of Maryland School of Medicine, said. The CDC still has a webpage with advice on when to mask. Those recommendations are tailored to the general public, though—and don’t advise covering up until COVID hospital admissions go “way high, when the horse has well and truly left the barn,” Landon, at UChicago, told me. “In health care, we need to do something before that”—tamping down transmission prior to wards filling up.

    More specific advice could still emerge from the CDC, or individual state health departments. But going forward, the assumption is that “each hospital is supposed to have its own general plan,” Rhee told me. (I reached out to the CDC repeatedly about whether it might update its infection-prevention-guidance webpage for COVID—last retooled in May—but didn’t receive a response.)

    Which leaves hospitals with one of two possible paths. They could schedule a start to masking season, based on when they estimate cases might rise—or they could react to data as they come in, tying masking policies to transmission bumps. With SARS-CoV-2 still so unpredictable, many hospitals are opting for the latter. That also means defining a true case rise—“what I think everybody is struggling with right now,” Rhee said. There is no universal definition, still, for what constitutes a surge. And with more immunity layered over the population, fewer infections are resulting in severe disease and death—even, to a limited extent, long COVID—making numbers that might have triggered mitigations just a year or two ago now less urgent catalysts.

    Further clouding the forecast is the fact that much of the data that experts once relied on to monitor COVID in the community have faded away. In most parts of the country, COVID cases are no longer regularly tallied; people are either not testing, or testing only at home. Wastewater surveillance and systems that track all influenza-like illnesses could provide some support. But that’s not a whole lot to go on, especially in parts of the country such as Tennessee, where sewage isn’t as closely tracked, Tom Talbot, of Vanderbilt, told me.

    Some hospitals have turned instead to in-house stats. At Duke—which has adopted a mitigation policy that’s very similar to UVA’s—Wolfe has mulled pulling the more-masking lever when respiratory viruses account for 2 to 4 percent of emergency and urgent-care visits; at UVA, Sifri has considered taking action once 1 or 2 percent of employees call out sick, with the aim of staunching sickness and preserving staff. “It really doesn’t take much to have an impact on our ability to maintain operations,” Sifri told me. But “I don’t know if those are the right numbers.” Plus, internal metrics are now tricky for the same reasons they’ve gotten shaky elsewhere, says Xiaoyan Song, the chief infection-control officer at Children’s National Hospital, in Washington, D.C. Screening is no longer routine for patients, skewing positivity stats; even sniffly health-care workers, several experts told me, are now less eager to test and report.

    For hospitals that have maintained a more masky baseline, scenarios in which universal masking returns are a little easier to envision and enact. At UChicago Medicine, Landon and her colleagues have developed a color-coded system that begins at teal—masking for high-risk patients, patients who request masked care, and anyone with symptoms, plus masking in high-risk areas—and goes through everyone-mask-up-everywhere red; their team plans to meet weekly to assess the situation, based on a variety of community and internal metrics, and march their masking up or down. Wolfe, of Duke, told me that his hospital “wanted to reserve a little bit of extra masking quite intentionally,” so that any shift back toward stricter standards would feel like less of a shock: Habits are hard to break and then reform.

    Other hospitals that have been living mostly maskless for months, though, have a longer road back to universal masking, and staff members who might not be game for the trek. Should masks need to return at the Brigham or Dana-Farber, for instance, “I suspect the reaction will be mixed,” Baker told me. “So we really are trying to be judicious.” The hospital might try to preserve some maskless zones in offices and waiting rooms, for instance, or lower-risk rooms. And at Children’s National, which has also largely done away with masks, Song plans to follow the local health department’s lead. “Once D.C. Health requires hospitals to reimplement the universal-masking policy,” she told me, “we will be implementing it too.”

    Other mitigations are on the table. Several hospital epidemiologists told me they expected to reimplement some degree of asymptomatic screening for various viruses around the same time they reinstate masks. But measures such as visiting restrictions are a tougher call. Wolfe is reluctant to pull that lever before he absolutely has to: Going through a hospital stay alone is one of the “harder things for patients to endure.”


    A bespoke approach to hospital masking isn’t impractical. COVID waves won’t happen synchronously across communities, and so perhaps neither should policies. But hospitals that lack the resources to keep tabs on viral spread will likely be at a disadvantage, and Popescu told me she worries that “we’re going to see significant transmission” in the very institutions least equipped to handle such influx. Even the best-resourced places may hit stumbling blocks: Many are still reeling from three-plus years of crisis and are dealing with nursing shortages and worker burnout.

    Coordination hasn’t entirely gone away. In North Carolina, Duke is working with the University of North Carolina at Chapel Hill and North Carolina State University to shift policies in tandem; in Washington State, several regional health-care organizations have pledged to align their masking policies. And the Veterans Health Administration—where masking remains required in high-risk units—has developed a playbook for augmenting mitigations across its many facilities, which together make up the country’s largest integrated health-care system, says Shereef Elnahal, the undersecretary of Veterans Affairs for health. Still, institutions can struggle to move in sync: Attitudes on masking aren’t exactly universal across health-care providers, even within a hospital.

    The country’s experience with COVID has made hospitals that much more attuned to the impacts of infectious disease. Before the pandemic began, Talbot said, masking was a rarity in his hospital, even around high-risk patients; many employees would go on shifts sick. “We were pretty complacent about influenza,” he told me. “People could come to work and spread it.” Now hospital workers hold themselves to a stricter standard. At the same time, they have become intimately attuned to the drawbacks of constant masking: Some have complained that masks interfere with communication, especially for patients who are young or hard of hearing, or who have a language barrier. “I do think you lose a little bit of that personal bonding,” Talbot said. And prior to the lifting of universal masking at Vanderbilt, he said, some staff were telling him that one out of 10 times they’d ask a patient or family to mask, the exchange would “get antagonistic.”

    When lifting mandates, many of the hospital epidemiologists I spoke with were careful to message to colleagues that the situation was fluid: “We’re suspending universal masking temporarily,” as Landon put it to her colleagues. Still, she admits that she felt uncomfortable returning to a low-mask norm at all. (When she informally polled nearly two dozen other hospital epidemiologists around the country in the spring, most of them told her that they felt the same.) Health-care settings aren’t meant to look like the rest of the world; they are places where precautions are expected to go above and beyond. COVID’s arrival had cemented masks’ ability to stop respiratory spread in close quarters; removing them felt to Landon like pushing those data aside, and putting the onus on patients—particularly those already less likely to advocate for themselves—to account for their own protection.

    She can still imagine a United States in which a pandemic-era response solidified, as it has in several other countries, into a peacetime norm: where wearing masks would have remained as routine as donning gloves while drawing blood, a tangible symbol of pandemic lessons learned. Instead, many American hospitals will be entering their fourth COVID winter looking a lot like they did in early 2020—when the virus surprised us, when our defenses were down.

    Katherine J. Wu

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  • Anti-Allergy Formula Is on the Rise. Milk Allergies Might Not Be.

    Anti-Allergy Formula Is on the Rise. Milk Allergies Might Not Be.

    This article was originally published by Undark Magazine.

    For Taylor Arnold, a registered dietitian nutritionist, feeding her second baby was not easy. At eight weeks old, he screamed when he ate and wouldn’t gain much weight. Arnold brought him to a gastroenterologist, who diagnosed him with allergic proctocolitis—an immune response to the proteins found in certain foods, which she narrowed down to cow’s milk.

    Cow’s-milk-protein allergies, or CMPA, might be on the rise—following a similar trend in other children’s food allergies—and they can upend a caregiver’s feeding plans: In many cases, a breastfeeding parent is told to eliminate dairy from their diet, or switch to a specialized hypoallergenic formula, which can be expensive.

    But although some evidence suggests that CMPA rates are climbing, the source and extent of that increase remain unclear. Some experts say that the uptick is partly because doctors are getting better at recognizing symptoms. Others claim that the condition is overdiagnosed. And among those who believe that milk-allergy rates are inflated, some suspect that the global formula industry, valued at $55 billion according to a 2022 report from the World Health Organization and UNICEF, may have an undue influence.

    Meanwhile, “no one has ever studied these kids in a systematic way,” Victoria Martin, a pediatric gastroenterologist and allergy researcher at Massachusetts General Hospital, told me. “It’s pretty unusual in disease that is this common, that has been going on for this long, that there hasn’t been more careful, controlled study.”

    This lack of clarity can leave doctors in the dark about how to diagnose the condition and leave parents with more questions than answers about how best to treat it.

    When Arnold’s son became sick with CMPA symptoms, it was “really, really stressful,” she told me. Plus, “I didn’t get a lot of support from the doctors, and that was frustrating.”

    Though the gastroenterologist recommended that she switch to formula, Arnold ultimately used a lactation consultant and gave up dairy so she could continue breastfeeding. But she said she can understand why others might not make the same choice: “A lot of moms go to formula because there’s not a lot of support for how to manage the diet.”


    Food allergies primarily come in two forms: One, called an IgE-mediated allergy, has symptoms that appear soon after ingesting a food—such as swelling, hives, or difficulty breathing—and may be confirmed by a skin-prick test. The second, which Arnold’s son was diagnosed with, is a non-IgE-mediated allergy, or food-protein-induced allergic proctocolitis, and is harder to diagnose.

    With non-IgE allergies, symptom onset doesn’t tend to happen immediately after a person eats a triggering food, and there is no definitive test to confirm a diagnosis. (Some specialists don’t like to call the condition an allergy, because it doesn’t present with classic allergy symptoms.) Instead, physicians often rely on past training, online resources, or published guidelines written by experts in the field, which list symptoms and help doctors make a treatment plan.

    Numerous such guidelines exist to help providers diagnose milk allergies, but the process is not always straightforward. “It’s a perfect storm” of vague and common symptoms and no diagnostic test, Adam Fox, a pediatric allergist and a professor at King’s College London, told me, noting that commercial interests such as formula-company marketing can also be misleading. “It’s not really a surprise that you’ve got confused patients and, frankly, a lot of very confused doctors.”

    Fox is the lead author of the International Milk Allergy in Primary Care, or iMAP, guidelines, one of many similar documents intended to help physicians diagnose CMPA. But some guidelines—including iMAP, which was known as the Milk Allergy in Primary Care Guideline until 2017—have been criticized for listing a broad range of symptoms, like colic, nonspecific rashes, and constipation, which can be common in healthy infants during the first year of their life.

    “Lots of babies cry, or they [regurgitate milk], or they get a little minor rash or something,” Michael Perkin, a pediatric allergist based in the U.K., told me. “But that doesn’t mean they’ve got a pathological process going on.”

    In a paper published online in December 2021, Perkin and colleagues found that in a food-allergy trial, nearly three-quarters of the infants’ parents reported at least two symptoms that matched the iMAP guidelines’ “mild-moderate” non-IgE-mediated cow’s-milk-allergy symptoms, such as vomiting. But another study, whose authors included Perkin and Robert Boyle, a children’s-allergy specialist at Imperial College London, reviewed available evidence and found estimated that only about 1 percent of babies have a milk allergy that has been proved by what’s called a “food challenge,” in which a person is exposed to the allergen and their reactions are monitored.

    That same study reported that as many as 14 percent of families believe their baby has a milk allergy. Another study by Boyle and colleagues showed that milk-allergy formula prescriptions increased 2.8-fold in England from 2007 to 2018. Researchers at the University of Rochester found similar trends stateside: Hypoallergenic-formula sales rose from 4.9 percent of formula sold in the U.S. in 2017 to 7.6 percent in 2019.

    Perkin and Boyle suspect that the formula industry has influenced diagnosis guidelines. In their 2020 report, published in JAMA Pediatrics, they found that 81 percent of authors who had worked on various physicians’ guidelines for the condition—including several for iMAP’s 2013 guidance—reported a financial conflict of interest with formula manufacturers.

    The formula industry also sends representatives and promotional materials to some pediatric clinics. One recent study found that about 85 percent of U.S. pediatricians surveyed reported a visit by a representative, some of whom sponsored meals with them.

    Formula companies “like people getting the idea that whenever a baby cries, or does a runny poo, or anything,” it might be a milk allergy, Boyle told me.

    In response to criticism that the guidelines have influenced the increase in specialized-formula sales, Fox, the lead author of the iMap guidelines, noted that the rise began in the early 2000s. One of the first diagnosis guidelines, meanwhile, was published in 2007. He also said that the symptoms listed in the iMAP guidelines are those outlined by the U.K.’s National Institute for Health and Care Excellence and the U.S.’s National Institute of Allergy and Infectious Diseases.

    As for the conflicts of interest, Fox said: “We never made any money from this; there was never any money for the development of it. We’ve done this with best intentions. We absolutely recognize where that may not have turned out the way that we intended it; we have tried our best to address that.”

    Following backlash over close ties between the formula industry and health-care professionals, including author conflicts of interest, iMAP updated its guidelines in 2019. The new version responded directly to criticism and said the guidelines received no direct industry funding, but it acknowledged “a potential risk of unconscious bias” related to research funding, educational grants, and consultant fees. The authors noted that the new guidelines had tried to mitigate such influence through independent patient input.

    Fox also said he cut all formula ties in 2018, and led the British Society for Allergy & Clinical Immunology to do the same when he was president.

    I reached out to the Infant Nutrition Council of America, an association of some of the largest U.S. manufacturers of infant formula, multiple times but did not receive any comment in response.


    Though the guidelines have issues, Nigel Rollins, a pediatrician and researcher at the World Health Organization, told me, he sees the rise in diagnoses as driven by formula-industry marketing to parents, which can fuel the idea that fussiness or colic might be signs of a milk allergy. Parents then go to their pediatrician to talk about milk allergy, Rollins said, and “the family doctor isn’t actually well positioned to argue otherwise.”

    Rollins led much of the research in the 2022 report from the WHO and UNICEF, which surveyed more than 8,500 pregnant and postpartum people in eight countries (not including the U.S.). Of those participants, 51 percent were exposed to aggressive formula-milk marketing, which the report states “represents one of the most underappreciated risks to infants and young children’s health.”

    Amy Burris, a pediatric allergist and immunologist at the University of Rochester Medical Center, told me that there are many likely causes of overdiagnosis: “I don’t know that there’s one particular thing that stands out in my head as the reason it’s overdiagnosed.”

    Some physicians rely on their own criteria, rather than the guidelines, to diagnose non-IgE milk allergy—for instance, conducting a test that detects microscopic blood in stool. But Burris and Rollins both pointed out that healthy infants, or infants who have recently had a virus or stomach bug, can have traces of blood in their stool too.

    Martin, the allergy researcher at Massachusetts General Hospital, said the better way to confirm an infant dairy allergy is to reintroduce milk about a month after it has been eliminated: If the symptoms reappear, then the baby most likely has the allergy. The guidelines say to do this, but both Martin and Perkin told me that this almost never happens; parents can be reluctant to reintroduce a food if their baby seems better without it.

    “I wish every physician followed the guidelines right now, until we write better guidelines, because, unequivocally, what folks are doing not following the guidelines is worse,” Martin said, adding that kids are on a restricted diet for a longer time than they should be.


    Giving up potentially allergenic foods, including dairy, isn’t without consequences. “I think there’s a lot of potential risk in having moms unnecessarily avoid cow’s milk or other foods,” Burris said. “Also, you’re putting the breastfeeding relationship at risk.”

    By the time Burris sees a baby, she said, the mother has in many cases already given up breastfeeding after a primary-care provider suggested a food allergy, and “at that point, it’s too late to restimulate the supply.” It also remains an open question whether allergens in breast milk actually trigger infant allergies. According to Perkin, the amount of cow’s-milk protein that enters breast milk is “tiny.”

    For babies, Martin said, dietary elimination may affect sensitivity to other foods. She pointed to research indicating that early introduction of food allergens such as peanuts can reduce the likelihood of developing allergies.

    Martin also said that some babies with a CMPA diagnosis may not have to give up milk entirely. She led a 2020 study suggesting that even when parents don’t elect to make any dietary changes for babies with a non-IgE-mediated food-allergy diagnosis, they later report an improvement in their baby’s symptoms by taking other steps, such as acid suppression. But when parents do make changes to their baby’s diet, in Martin’s experience, if they later reintroduce milk, “the vast majority of them do fine,” she said. “I think some people would argue that maybe you had the wrong diagnosis initially. But I think the other possibility is that it’s the right diagnosis; it just turns around pretty fast.”

    Still, many parents who give up dairy or switch to a hypoallergenic formula report an improvement in their baby’s symptoms. Arnold said her son’s symptoms improved when she eliminated dairy. But when he was about eight months old, they reintroduced the food group to his diet, and he had no issues.

    Whether that’s because the cow’s-milk-protein allergy was short-lived or because his symptoms were due to something else is unclear. But Arnold sees moms self-diagnosing their baby with food allergies on social media, and believes that many are experiencing a placebo effect when they say their baby improves. “Nobody’s immune to that. Even me,” she said. “There’s absolutely a chance that that was the case with my baby.”

    Christina Szalinski

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  • Adult ADHD Is the Wild West of Psychiatry

    Adult ADHD Is the Wild West of Psychiatry

    In October, when the FDA first announced a shortage of Adderall in America, the agency expected it to resolve quickly. But five months in, the effects of the shortage are still making life tough for people with attention-deficit hyperactivity disorder who rely on the drug. Stories abound of frustrated people going to dozens of pharmacies in search of medication each month, only to come up short every time. Without treatment, students have had a hard time in school, and adults have struggled to keep up at work and maintain relationships. The Adderall shortage has ended, but the widely used generic versions of the drug, known as amphetamine mixed salts, are still scarce.

    A “perfect storm” of factors—manufacturing delays, labor shortages, tight regulations—is to blame for the shortage, David Goodman, an ADHD expert and a psychiatry professor at the Johns Hopkins University School of Medicine, told me. And they have all been compounded by the fact that the pandemic produced a surge in Americans who want Adderall. The most dramatic changes occurred among adults, according to a recent CDC report on stimulant prescriptions, with increases in some age groups of more than 10 percent in just a single year, from 2020 to 2021. It’s the nature of the spike in demand for Adderall—among adults—that has some ADHD experts worried about “whether the demand is legitimate,” Goodman said. It’s possible that at least some of these new Adderall patients, he said, are getting prescriptions they do not need.

    The problem is that America has no standard clinical guidelines for how doctors should diagnose and treat adults with ADHD—a gap the CDC has called a “public health concern.” When people come in wanting help for ADHD, providers have “a lot of choices about what to use and when to use it, and those parameters have implications for good care or bad care,” Craig Surman, a psychiatry professor and an ADHD expert at Harvard and the scientific coordinator of adult-ADHD research at Massachusetts General Hospital, told me. The stimulant shortage will end, but even then, adults with ADHD may not get the care they need.

    For more than 200 years, symptoms related to ADHD—such as difficulty focusing, inability to sit still, and fidgeting—have largely been associated with children and teenagers. Doctors widely assumed that kids would grow out of it eventually. Although symptoms become “evident at a very early period of life,” one Scottish physician wrote in 1798, “what is very fortunate [is that] it is generally diminished with age.” For some people, ADHD symptoms really do get better as they enter adulthood, but for most, symptoms continue. The focus on children persists today in part because of parental pressure. Pediatricians have had to build a child-focused ADHD model, Surman said, because parents come in and say, “What are we going to do with our kid?” As a result, treating children ages 4 to 18 for ADHD is relatively straightforward: Clear-cut clinical guidelines from the American Academy of Pediatrics specify the need for rigorous psychiatric testing that rules out other causes and includes reports about the patient from parents and teachers. Treatment usually involves behavior management and, if necessary, medication.

    But there is no equivalent playbook for adults with ADHD in the U.S.—unlike in other developed nations, including the U.K. and Canada. In fact, the disorder was only recently acknowledged within the field of adult psychiatry. One reason it went overlooked for so long is because ADHD can sometimes look different in kids compared with adults: Physical hyperactivity tends to decrease with age as opposed to, say, emotional or organizational problems. “The recognition that ADHD is a life-span disorder that persists into adulthood in most people has really only happened in the last 20 years,” Margaret Sibley, a psychiatry professor at the University of Washington School of Medicine, told me. And the field of adult psychiatry has been slow to catch up. Adult ADHD was directly addressed for the first time in DSM-5—the American Psychiatric Association’s diagnostic bible—in 2013, but the criteria described there still haven’t been translated into practical instructions for clinicians.

    Addressing adult ADHD isn’t as simple as adapting children’s standards for grown-ups. A key distinction is that the disorder impairs different aspects of an adult’s life: Whereas a pediatrician would investigate ADHD’s impact at school or at home, a provider evaluating an adult might delve into its effects at work or in romantic relationships. Sources of information differ too: Parents and teachers can shed light on a child’s situation, but “you wouldn’t call the parent of a 40-year-old to get their take on whether the person has ADHD,” Sibley said. Providers usually rely instead on self-reporting—which isn’t always accurate. Complicating matters, the symptoms of ADHD tend to be masked by other cognitive issues that arise in adulthood, such as those caused by depression, drug use, thyroid problems, or hormonal shifts, Sibley said: “It’s a tough disorder to diagnose, because there’s no objective test.” The best option is to perform a lengthy psychiatric evaluation, which usually involves reviewing symptoms, performing a medical exam, taking the patient’s history, and assessing the patient using rating scales or checklists, according to the APA.

    Without clinical guidelines or an organizational body to enforce them, there is no pressure to uphold that standard. Virtual forms of ADHD care that proliferated during the pandemic, for example, were rarely conducive to lengthy evaluations. A major telehealth platform that dispensed ADHD prescriptions, Cerebral, has been investigated for sacrificing medical rigor for speedy treatment and customer satisfaction, potentially letting people without ADHD get Adderall for recreational use. In one survey, 97 percent of Cerebral users said they’d received a prescription of some kind. Initial consultations with providers lasted just half an hour, reported The Wall Street Journal; former employees feared that the company’s rampant stimulant-prescribing was fueling an addiction crisis. “It’s impossible to do a comprehensive psychiatric evaluation in 30 minutes,” Goodman said. (Cerebral previously denied wrongdoing and no longer prescribes Adderall or other stimulants.)

    The bigger problem is that too few providers are equipped to do those evaluations in the first place. Because adult ADHD was only recently recognized, most psychiatrists working today received no formal training in treating the disorder. “There’s a shortage of expertise,” Surman said. “It’s a confusing space where, at this point, consumers often are educating providers.” The dearth of trained professionals means that many adults seeking help for ADHD are seen by providers, including primary-care doctors, social workers, and nurse practitioners, who lack the experience to offer it. “It’s a systemic issue,” Sibley said, “not that they’re being negligent.”

    The lack of trained providers opens up the potential for inadequate or even dangerous care. Adderall is just one of many stimulants used to treat ADHD, and choosing the right one for a patient can be challenging—and not all people with ADHD need or want to take them. But even the most well-intentioned health-care professionals may be unprepared to evaluate patients properly. The federal government considers Adderall a highly addictive Schedule II drug, like oxycodone and fentanyl, and the risks of prescribing it unnecessarily are high: Apart from dependency, it can also cause issues such as heart problems, mood changes, anxiety, and depression. Some people with ADHD might be better off with behavioral therapy or drugs that aren’t stimulants. Unfortunately, it can be all too easy for inexperienced providers to start a patient on these drugs and continue treatment. “If I give stimulants to the average person, they’ll say their mood, their thinking, and their energy are better,” Goodman said. “It’s very important not to make a diagnosis based on the response to stimulant medication.” But the uptick in adults receiving prescriptions for those drugs since at least 2016 is a sign that this might be happening.

    The fact that adult ADHD is surging may soon lead to change. Last year, the American Professional Society of ADHD and Related Disorders began drafting the long-needed guidelines. The organization’s goal is to standardize care and treatment for adult ADHD across the country, said Goodman, who is APSARD’s treasurer. Establishing standards could have “broad, sweeping implications” beyond patient care, he added: Their existence could compel more medical schools to teach about adult ADHD, persuade insurance companies to cover treatment, and pressure lawmakers to include it in workplace policies.

    A way out of this mess, however long overdue, is only going to become even more necessary. Nearly 5 percent of adults are thought to have the disorder, but less than 20 percent of them have been diagnosed or have received treatment (compared with about 77 percent of children). “You have a much larger market of recognized and untreated adults, and that will continue to increase,” Goodman said. Women—who, like girls, are historically underdiagnosed—will likely make up a substantial share. Adults with ADHD may have suffered in silence in the past, but a growing awareness of the disorder, made possible by ongoing destigmatization, will continue to boost the ranks of people who want help. On social media, ADHD influencers abound, as do dedicated podcasts on Spotify.

    Until guidelines are published—and embedded into medical practice—the adult-ADHD landscape will remain chaotic. Some people will continue to get Adderall prescriptions they don’t need, and others may be unable to get an Adderall prescription they do need. Rules alone couldn’t have prevented the shortage, and they won’t stop it now. But in more ways than one, their absence means that many people who need help for ADHD are unable to receive it.

    Yasmin Tayag

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  • No One Can Decide If Grapefruit Is Dangerous

    No One Can Decide If Grapefruit Is Dangerous

    Roughly a century ago, a new fad diet began to sweep the United States. Hollywood starlets such as Ethel Barrymore supposedly swore by it; the citrus industry hopped on board. All a figure-conscious girl had to do was eat a lot of grapefruit for a week, or two, or three.

    The Grapefruit Diet, like pretty much all other fad diets, is mostly bunk. If people were losing weight with the regimen, that’s because the citrus was being recommended as part of a portion-controlled, low-calorie, low-carbohydrate diet—not because it had exceptional flab-blasting powers. And yet, the diet has survived through the decades, spawning a revival in the 1970s and ’80s, a dangerous juice-exclusive spin-off called the grapefruit fast, and even a shout-out from Weird Al; its hype still plagues nutritionists today.

    But for every grapefruit evangelist, there is a critic warning of its dangers—probably one with a background in pharmacology. The fruit, for all its tastiness and dietetic appeal, has another, more sinister trait: It raises the level of dozens of FDA-approved medications in the body, and for a select few drugs, the amplification can be potent enough to trigger a life-threatening overdose. For most people, chowing down on grapefruit is completely safe; it would take “a perfect storm” of factors—say, a vulnerable person taking an especially grapefruit-sensitive medication within a certain window of drinking a particular amount of grapefruit juice—for disaster to unfurl, says Emily Heil, an infectious-disease pharmacist at the University of Maryland. But that leaves grapefruit in a bit of a weird position. No one can agree on exactly how much the world should worry about this bittersweet treat whose chemical properties scientists still don’t fully understand.

    Grapefruit’s medication-concentrating powers were discovered only because of a culinary accident. Some three decades ago, the clinical pharmacologist David Bailey (who died earlier this year) was running a trial testing the effects of alcohol consumption on a blood-pressure medication called felodipine. Hoping to mask the distinctive taste of booze for his volunteers, Bailey mixed it with grapefruit juice, and was shocked to discover that blood levels of felodipine were suddenly skyrocketing in everyone—even those in the control group, who were drinking virgin grapefruit juice.

    After running experiments on himself, Bailey confirmed that the juice was to blame. Some chemical in grapefruit was messing with the body’s natural ability to break down felodipine in the hours after it was taken, causing the drug to accumulate in the blood. It’s the rough physiological equivalent of jamming a garbage disposal: Waste that normally gets flushed just builds, and builds, and builds. In this case, the garbage disposal is an enzyme called cytochrome P450 3A4—CYP3A4 for short—capable of breaking down a whole slate of potentially harmful chemicals found in foods and meds. And the jamming culprit is a compound found in the pulp and peel of grapefruit and related citrus, including pomelos and Seville oranges. It doesn’t take much: Even half a grapefruit can be enough to trigger a noticeable interaction, says George Dresser, a pharmacologist at Western University, in Ontario.

    The possible consequences of these molecular clogs can sometimes get intense. “On the list of concerning food-drug interactions,” Dresser told me, “arguably, this is the most important one.” When paired with certain heart medications, grapefruit could potentially cause arrhythmias; with some antidepressants, it might induce nausea, vomiting, and an elevated heart rate. Grapefruit can also raise blood levels of the cholesterol drugs atorvastatin and simvastatin, prompting muscle pain and, eventually, muscle breakdown. One of the fruit’s most worrying interactions occurs with an immunosuppressive drug called tacrolimus, frequently prescribed to organ-transplant patients, that may, when amped up by grapefruit, spark headaches, tremors, hypoglycemia, and kidney problems. The citrus even has the ability to lift blood levels of drugs of abuse, including fentanyl, oxycodone, and ketamine.

    The full list of potential interactions is long. “More than 50 percent of drugs on the market are metabolized by CYP3A4,” which inhabits both the liver and the gut, says Mary Paine, a pharmacologist at Washington State University. That said, grapefruit can really affect only intestinal CYP3A4, and will cause only a small fraction of those medications to reach notably higher concentrations in the blood (and sometimes only when fairly large quantities of juice are consumed—a quart or more). And only a small fraction of those medications will, when amassed, threaten true toxicity. Our bodies are always making more CYP3A4; stop eating grapefruit and, within a day or two, levels of the protein should more or less reset.

    Professionals disagree on how to characterize grapefruit’s risks. To Shirley Tsunoda, a pharmacist at UC San Diego, “it’s definitely a big deal,” especially for the organ-transplant patients to whom she prescribes tacrolimus. Her advice to them is to indulge in grapefruit exactly never—and ideally, tacrolimus-takers should skip related citrus too. Tsunoda even advises people to check the labels of mixed-fruit juices, just in case the makers sneaked some grapefruit in, and she thinks twice when considering noshing on it herself. Paul Watkins, a pharmacologist at the University of North Carolina at Chapel Hill, is much less worried; his bigger concern, he told me, is that the fruit’s reputation as a nemesis of oral medications has been way overblown. He used to study grapefruit-drug interaction but abandoned it years ago, after “I came to the conclusion that it wasn’t very important,” he told me. Some concern is absolutely warranted for certain people on certain meds, he noted. But “I think the actual incidence of patients who have gotten into any kind of trouble or had serious adverse reactions due to taking their drugs with grapefruit juice is very, very small.”

    Even the FDA seems a bit unsure of how it feels about the fruit. The agency has stamped the documentation of several grapefruit-sensitive medications with official warnings. But fact sheets for other drugs merely mention that they can interact with grapefruit, say to consult a health-care professional, or just counsel people to avoid drinking the juice in “large amounts.” And as Dan Nosowitz has reported for Atlas Obscura, several interacting drugs that bear warnings in Canada—among them, Viagra, oxycodone, the HIV antiviral Edurant, and the blood pressure medication verapamildon’t mention any issues with grapefruit in the United States. (When I asked the agency about these discrepancies, a spokesperson wrote, “The FDA is continuously reviewing new information about approved drugs, including studies and reports of adverse events. If the FDA determines there is a safety concern, the agency will take appropriate action.”)

    Very little solid data can precisely quantify grapefruit’s perils. Over the years, researchers have documented a number of isolated cases of citrus-drug interactions that prompted urgent medical care. But some of them involved truly exceptional amounts of juice. And citrus stans aren’t constantly dropping dead in clinical trials or nursing homes. Even when Bailey first presented his findings to the greater medical community, “people asked, ‘Where are all the bodies?’” Dresser, who was mentored by Bailey, told me. The paucity of data, Dresser contends, stems in part from health-care workers neglecting to check their patients for a history of juice-chugging.

    For now, the conversation has mostly stalled, while grapefruit has served up even more mysteries. In the years since Bailey’s discovery, researchers have found that the fruit might lower the concentration of certain drugs, such as the allergy med fexofenadine, perhaps by keeping the lining of the intestines from absorbing certain compounds. New drugs are a particularly murky area, especially because grapefruit interactions aren’t a typical first priority when a new medication hits the market. The popular COVID antiviral pill Paxlovid, for instance, contains the CYP3A4-susceptible ingredient ritonavir. A Pfizer representative told me that the company is not concerned about toxicity. But Heil wonders whether grapefruit could mildly aggravate some of Paxlovid’s irksome side effects: diarrhea, for instance, or maybe the sour, metallic taste that reminds many people of … well, grapefruit.

    That said, most grapefruit lovers need not despair. The fruit is still healthy—chock-full of vitamins and flavor—and yet is often overlooked, says Heidi Silver, a nutrition scientist at Vanderbilt University. Silver and researchers have shown that consuming grapefruit flesh or juice might be able to slightly lower levels of triglycerides and cholesterol. Technically, it can even play a role in weight loss: Snacking on a small portion before a meal can help people feel full faster. Then again, a glass of water will too. Just as grapefruit is not a miraculous vanquisher of fat, it isn’t a ubiquitous killer.

    Even people on certain medications may be able to enjoy it if they consult an expert first. Heil’s own father absolutely adores grapefruit, and also happens to take an oral medication that can interact. Swallow them too close together, and he risks dizziness and fatigue. But he and Heil have found a compromise: He can have small portions of grapefruit or its juice in the morning, spaced about 12 hours out from when he takes his meds at bedtime. A few weeks ago, Heil (who thinks grapefruit is disgusting) even gave her dad the green light to enjoy a dinnertime cocktail that contained a small splash of the juice. Maybe the smidge of fruit affected his meds that day. But “it wasn’t going to be the end of the world,” Heil told me. To say that, after all, would have been an exaggeration.

    Katherine J. Wu

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