But the scope of the outbreak among cattle remains uncertain, and little human testing has been done.Additional testing of retail dairy products from across the country has turned up no signs of live bird flu virus, strengthening the consensus that pasteurization is protecting consumers from the threat, federal health and agriculture officials said at a news briefing on Wednesday.But the scope of the bird flu outbreak in cattle remains unclear, as dairy herds are not routinely tested for the infection, scientists and other experts have noted.Just one human infection, which was mild, has been reported, in a dairy worker in Texas who had direct contact with sick cows. But scientists fear there may be many more undetected infections, particularly among farm workers.Barely two dozen people have been tested for bird flu, federal officials said at the briefing. There have been no unusual increases in flu cases around the country, even in areas with infected cows, they added.But Dr. Keith Poulsen, director of the Wisconsin Veterinary Diagnostic Laboratory, said that farms are not required to test employees, many of whom are migrant workers who are reluctant to work with state health officials.“How much are we ignoring because of anxiety and fear of what happens if you don’t get an answer that you like?” Dr. Poulsen said.Until last week, potentially tainted dairy products had seemed to be the most immediate threat to the public. Federal regulators last week announced early test results of around 95 retail milk samples: Roughly one in five was found to contain genetic fragments of the virus, a fact that health officials said did not present a threat to consumers.More advanced testing later in the week turned up no live virus in the samples, a relief to federal regulators.On Wednesday, Dr. Donald A. Prater, the acting director of the Center for Food Safety and Applied Nutrition at the Food and Drug Administration, said federal scientists had examined an additional 201 commercial dairy samples, including milk, cottage cheese and sour cream.So far the scientists have not found evidence of potentially infectious virus. “Findings from the U.S. government partners, as well as academic researchers, do not change our assessment of the safety of the milk,” Dr. Prater said.Dr. Prater said that the F.D.A. still strongly advised against consuming raw, unpasteurized dairy products. Federal scientists are still reviewing data on whether the virus in raw milk could be infectious, he added.As of Wednesday, the outbreak had spread to 36 herds in nine states, according to the Department of Agriculture. Scientists have criticized the Biden administration for not conducting more testing of animals in order to determine the scope of the outbreak.Some dairy farms have been difficult to gain access to, and owners are at times reluctant to grant government workers entry to production facilities, federal officials have said.“There’s a lot of farms out there that are not reporting,” Dr. Poulsen, the Wisconsin expert, said. “They’re not reporting because they’re really afraid of what would happen if they’re not negative.”The Department of Agriculture has ruled that lactating cows must test negative for influenza A viruses, a class that includes bird flu, before they are transported across state lines. The rule also requires owners of herds with positive tests to provide data on the whereabouts of cattle to help investigators trace the disease.But further guidance released last week revealed that farmers need to test only 30 cows in a group, potentially allowing infected cows in larger herds to move between states undetected.Dr. Rosemary Sifford, a senior U.S.D.A. official, defended the scope of the order, saying that 30 cows were a “statistically significant number to be able to determine the status of the lot.” The department now requires laboratories and state veterinarians to report any positive tests from cattle to the agency.The U.S.D.A. also has turned its attention to meat. Colombia last week become the first country to ban beef and beef products from certain U.S. states because of the bird flu outbreak.Dr. José Emilio Esteban, a senior food safety official at the U.S.D.A., said at the briefing that beef was safe to eat, but that the agency was conducting three studies to “enhance our scientific knowledge to make sure we have additional data points.”The department is testing ground beef from grocery stores, as well as the remnants of slaughtered animals, in states known to have infected dairy cattle, Dr. Esteban said. The agency is also examining the effectiveness of cooking at killing the virus by heating beef patties to three different temperatures.Officials are also considering possible ways to compensate dairy farmers for “their cooperation and taking up of additional biosecurity practices,” Dr. Sifford said.Underlying much of the concern about the cattle outbreak is a fear among scientists that the bird flu virus is adapting to mammals. Dr. Sifford said at the briefing that federal scientists had not detected any changes in the virus that would allow it to spread more easily between humans.Dr. Demetre Daskalakis, a senior official at the Centers for Disease Control and Prevention, conceded that only around 25 people had been tested for infection, about the same number reported last week.More than 100 people are being monitored for symptoms. Dr. Daskalakis said that the numbers of people who were being tested and monitored were “dynamic,” in part because the monitoring period for people goes away as infected herds recover.Emily Anthes contributed reporting.

A meta-analysis of psilocybin trials confirmed its possible benefit as a depression treatment, but raised questions about its safety and use in clinical practice.
Seven of nine studies included in the analysis showed a significant benefit with psilocybin for adults with depression, favoring it over a comparator treatment (Hedges’ g 1.64, 95% CI 0.55-2.73, P

The Arizona Legislature approved a repeal of a long-dormant ban on nearly all abortions Wednesday, advancing the bill to Democratic Gov. Katie Hobbs, who is expected to sign it.
Two Republicans joined with Democrats in the Senate on the 16-14 vote in favor of repealing a Civil War-era ban on abortions that the state’s highest court recently allowed to take effect. The repeal bill narrowly cleared the Arizona House last week.
Hobbs said in a statement that she looks forward to quickly signing the repeal into law.
“The devastating consequences of this archaic ban are why I’ve called for it to be repealed since day one of my administration,” she said.
“Arizona women should not have to live in a state where politicians make decisions that should be between a woman and her doctor,” Hobbs continued. “While this repeal is essential for protecting women’s lives, it is just the beginning of our fight to protect reproductive healthcare in Arizona.”
The near-total ban, which predates Arizona’s statehood, permits abortions only to save the patient’s life — and provides no exceptions for survivors of rape or incest. In a ruling last month, the Arizona Supreme Court suggested doctors could be prosecuted under the 1864 law, which says that anyone who assists in an abortion can be sentenced to 2 to 5 years in prison.
If the repeal bill is signed, a 2022 statute banning the procedure after 15 weeks of pregnancy would become Arizona’s prevailing abortion law. Still, there would likely be a period when nearly all abortions would be outlawed, because the repeal won’t take effect until 90 days after the end of the legislative session, likely in June or July.
Several senators spoke about their motivations for voting as numbers were tallied on the repeal bill.
“This is a clear statement that the Legislature does not want the territorial ban to be enforceable,” said Democratic state Sen. Priya Sundareshan, who voted yes to repeal.
Arizona state Attorney General Kris Mayes called the vote “a win for freedom in our state,” but expressed concern that without an emergency clause, Arizonans would still be subject to the near total-abortion ban for some time.
“Rest assured, my office is exploring every option available to prevent this outrageous 160-year-old law from ever taking effect,” she said.
There were numerous disruptions from people in the Senate gallery as Republican state Sen. Shawnna Bolick explained her vote in favor of repeal, joining with Democrats.
GOP state Sen. Jake Hoffman denounced Republican colleagues for joining with Democratic colleagues, calling it an affront to his party’s principles.
“It is disgusting that this is the state of the Republican Party today,” Hoffman said.
Advocates on both sides of the abortion issue arrived outside the Arizona Senate on Wednesday to emphasize their views. They included people affiliated with Planned Parenthood and faith-based groups opposed to abortion.
A school-age girl knelt in prayer in front of a table holding a large statue of the Virgin Mary, while a man with a megaphone shouted at passersby to repent.
“I am expecting it will be repealed, but I am praying it won’t be,” said Karen Frigon, who was handing out brochures from the Arizona Right to Life.
Arizona is one of a handful of battleground states that will decide the next president. Former President Donald Trump, who has warned that the issue could lead to Republican losses, has avoided endorsing a national abortion ban but said he’s proud to have appointed the Supreme Court justices who allowed states to outlaw it.
The law had been blocked since the U.S. Supreme Court’s 1973 Roe v. Wade decision guaranteed the constitutional right to an abortion nationwide.
When Roe v. Wade was overturned in June 2022 though, then-Arizona Attorney General Mark Brnovich, a Republican, persuaded a state judge that the 1864 ban could again be enforced. Still, the law hasn’t actually been enforced while the case was making its way through the courts. Mayes, who succeeded Brnovich, urged the state’s high court against reviving the law.
Planned Parenthood officials vowed to continue providing abortions for the short time they are still legal and said they will reinforce networks that help patients travel out of state to places like New Mexico and California to access abortion.
Advocates are collecting signatures for a ballot measure allowing abortions until a fetus could survive outside the womb, typically around 24 weeks, with exceptions — to save the parent’s life, or to protect her physical or mental health.
Republican lawmakers, in turn, are considering putting one or more competing abortion proposals on the November ballot.
A leaked planning document outlined the approaches being considered by House Republicans, such as codifying existing abortion regulations, proposing a 14-week ban that would be “disguised as a 15-week law” because it would allow abortions until the beginning of the 15th week, and a measure that would prohibit abortions after 6 weeks of pregnancy, before many people know they’re pregnant.
House Republicans have not yet publicly released any such proposed ballot measures.

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The investigational combination xanomeline-trospium (KarXT) was effective and well tolerated in individuals with schizophrenia who were experiencing acute psychosis, according to the randomized controlled phase III EMERGENT-3 trial.
Participants randomized to the novel combination therapy had significantly reduced Positive and Negative Syndrome Scale (PANSS) total scores over 5 weeks compared with those on placebo (−20.6 vs −12.2), according to Steven Paul, MD, of Karuna Therapeutics in Boston, and colleagues.
The comparative reduction in PANSS total scores corresponded with a least squares mean difference of −8.4 between the combination therapy and placebo (95% CI −12.4 to −4.3, P

Kentucky has become the first state to decriminalize medical errors — a move many medical associations support.
HB 159 was signed by Kentucky’s Democratic Gov. Andy Beshear on March 26 after passing the state legislature earlier that week. The bill states that “a health care provider providing health services shall be immune from criminal liability for any harm or damages alleged to arise from an act or omission relating to the provision of health services.” It does not apply to “gross negligence or wanton, willful, malicious, or intentional misconduct.”
The bill is popular among some medical associations. Last month, the Kentucky Nurses Association urged members to ask their Senators to support the bill, citing that fear of criminal charges could contribute to the ongoing nursing shortage in the state. They also said voluntary reporting and cooperation are vital for updating systems and processes when earnest mistakes happen — which the possibility of criminal charges could discourage.
Nancy Galvagni, president and chief executive officer of the Kentucky Hospital Association, told MedPage Today in an email that HB 159 was a good piece of legislation the group has been happy to support. “Our nurses should not be held criminally liable for a mere mistake and the legal system already has ample means available to address any true negligence,” she said.
Similarly, Chris Dellinger, BSN, RN, president of the Emergency Nurses Association (ENA), told MedPage Today in an email that ENA “is supportive of this bill for decriminalizing honest mistakes that might occur during the delivery of care” and that this law “provides everyone with clarity as to the legal threshold prosecutors must consider when assessing medical errors in Kentucky.”
“Emergency nurses, and all members of the emergency care team, hold themselves to the highest standards for delivering care to patients in their moment of need, but they will always be humans working in a fast-paced, oft-challenging, environment,” Dellinger said. “Although every effort is made through training, best practices, and evidence-based guidelines to prevent mistakes, they do happen.”
The Kentucky law takes effect in the aftermath of the high profile case of RaDonda Vaught, a former nurse at Vanderbilt University Medical Center in Nashville, Tennessee. In 2017, a 75-year-old woman died after Vaught gave her the paralytic vecuronium rather than the sedative midazolam (Versed) by mistake.
Court documents have shown that Vaught reported her mistake to doctors and Vanderbilt as soon as she realized it. Still, Vaught was charged with reckless homicide and impaired adult abuse, of which she was then convicted in 2022. She was sentenced to 3 years of probation, though she evaded any prison time. Last December, Tennessee courts rejected Vaught’s bid to get her nursing license back.
While Vaught’s case happened in neighboring Tennessee, HB 159 in Kentucky addresses concerns nurses and other healthcare professionals have raised about how criminal punishment for honest mistakes can discourage transparent reporting and potentially put patients at higher risk.

Rachael Robertson is a writer on the MedPage Today enterprise and investigative team, also covering OB/GYN news. Her print, data, and audio stories have appeared in Everyday Health, Gizmodo, the Bronx Times, and multiple podcasts. Follow

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A peer-to-peer support intervention did not improve the well-being of healthcare workers overall during the COVID-19 pandemic, but the program did have a positive effect for those ages 30 and younger, a cluster randomized trial showed.
In an intention-to-treat analysis of over 2,000 healthcare workers from 28 hospitals and federally qualified health centers (FQHCs), there was no overall treatment effect for psychological distress score or post-traumatic stress disorder (PTSD) symptom score among those who participated in Stress First Aid, an evidence-informed peer-to-peer support intervention, compared with usual care, reported Lisa S. Meredith, PhD, of the RAND Corporation in Santa Monica, California, and colleagues.
However, in a post-hoc analysis that looked at treatment effects of the intervention by age group, healthcare workers at FQHCs who were 30 or younger had significantly less psychological distress and PTSD after participation in the intervention. In this age group, the psychological distress score decreased by 4.52 points (P=0.01) and the mean PTSD score decreased by 6.77 points (P=0.04) compared with usual care, they noted in JAMA Network Open.
This study highlighted “the importance of collegiality and mutual support in a cataclysmic crisis,” wrote Jason H. Wasfy, MD, MPhil, of Massachusetts General Hospital and Harvard Medical School in Boston, and colleagues in an accompanying editorial. “On the basis of the results of their study, this may be especially meaningful for young healthcare workers who have yet to develop the most personally meaningful coping strategies, clinical confidence, and workplace community and networks that a longer career in healthcare may afford.”
Co-author Courtney Gidengil, MD, MPH, of the RAND Corporation in Boston, told MedPage Today that she and her team had “hoped to see an intervention effect, given how desperately it is needed with all that healthcare workers have suffered through. But on the other hand, it’s really hard to learn to swim when you’re already drowning — healthcare workers had an impossible burden on their plates.”
Meredith told MedPage Today that “alleviating stress and burnout among healthcare workers is a bigger concern than can be solved by this study. While there is potential for SFA [Stress First Aid] trainees to gain coping skills by using the SFA tools, what we really need are bigger systemic solutions to these problems.”
Wasfy and colleagues also noted that “burnout is a problem not only because of the suffering of our colleagues and their families, but also because of the repercussions for the healthcare system.”
“For instance, clinicians who are burned out are more likely to consider leaving the practice of medicine,” they wrote. “In a national survey [from] December 2020, 1 in 5 physicians and 2 in 5 nurses reported intending to leave medical practice within 2 years, and 1 in 3 healthcare workers reported intending to reduce their work hours.”
“With the growing concern over healthcare worker shortages, the burnout crisis for healthcare clinicians is already likely contributing to a lack of availability of care for patients,” they added.
At the beginning of the study, approximately 36% to 40% of all participants at FQHCs reported burnout, 15% to 18% reported serious psychological distress, and 13% to 20% met PTSD diagnostic criteria. Among workers at hospitals, about 50% reported burnout, 10% to 12% reported serious psychological distress, and 17% to 19% met PTSD diagnostic criteria.
The Stress First Aid intervention was originally developed by the U.S. Navy and Marine Corps to help individuals without any mental health training manage stressful circumstances among themselves and peers. It promotes five key elements of safety, calm, connectedness, self- and community-efficacy, and hope. To attain these goals, the intervention encourages seven core actions: check, coordinate, cover, calm, connect, competence, and confidence.
The trial took place from March 2021 to late July 2022. A total of 28 sites were recruited in pairs — eight hospital pairs and six FQHCs pairs — so that they were matched based on size, type, and COVID-19 burden. Each site within a pair was randomized to the Stress First Aid intervention or to usual care.
Among enrolled facilities, 2,077 healthcare workers participated in the study and completed a pre-intervention and post-intervention survey. Of the 1,649 healthcare workers from hospitals and 428 from FQHCs, 862 individuals were randomly assigned to the intervention arm and 1,215 were assigned to the usual care arm. Approximately 80% of all participants were women, and most were ages 31 to 50.
The authors noted that at site-level randomization, baseline characteristics were not balanced among individual healthcare workers. For example, healthcare workers at FQHCs were younger and more likely to have been working in healthcare for at least 5 years compared with their counterparts at hospitals. Healthcare workers at FQHCs were also more likely to be Black or Hispanic or Latino/Latina than those at hospitals. Also, across all the sites, more healthcare workers participating in the intervention were administrators, assistants, or technicians, rather than physicians, nurses or nurse practitioners, or physician assistants.
The researchers identified at least one site champion for every 50 healthcare workers, who watched 4 hours of video training and participated in a 2-hour virtual peer-to-peer support training session. The champions then trained their peers at their own organizations. Sites that were randomized to usual care continued to provide any healthcare worker support programs that were already in place.
General psychological distress was measured with the Kessler 6 instrument (range 0-24, with the highest scores indicating higher distress), and PTSD was measured with the PTSD Checklist (possible range 0-80, with the highest scores indicating greater symptom severity). Baseline mean psychological distress score was 5.86, and the baseline mean PTSD score was 16.11.
In addition to the primary outcome of psychological distress and PTSD, secondary outcomes included sleep problems, workplace stress, burnout, resilience, and moral distress. There were no statistically significant differences between the intervention group and the usual care group for these outcomes.
The authors noted several limitations to the study. Implementation of the intervention was occasionally paused due to “enormous clinical demands” on participating healthcare facilities during the pandemic. Training in the intervention may not have been intensive enough, and the follow-up period may have been too short. Also, participants who had an improvement in mental health may have been less likely to complete follow-up surveys.

Katherine Kahn is a staff writer at MedPage Today, covering the infectious diseases beat. She has been a medical writer for over 15 years.

Disclosures
The study was funded by the Patient-Centered Outcomes Research Institute.Meredith and Gidengil reported no relevant financial disclosures; one study co-author reported multiple ties to industry.The editorialists reported no relevant financial disclosures.

Primary Source
JAMA Network Open
Source Reference: Meredith LS, et al “Testing an intervention to improve health care worker well-being during the COVID-19 pandemic: a cluster randomized clinical trial” JAMA Netw Open 2024; DOI: 10.1001/jamanetworkopen.2024.4192.

Secondary Source
JAMA Network Open
Source Reference: O’Kelly AC, et al “Learning how to protect the health system by protecting caregivers” JAMA Netw Open 2024; DOI: 10.1001/jamanetworkopen.2024.4167.

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Additional preliminary testing by the FDA has found that retail milk products such as cottage cheese and sour cream don’t contain any viable H5N1 avian influenza virus, officials said during a press briefing.
Results announced last week from 96 products found retail milk samples didn’t have any viable virus, and these additional results from 201 retail milk products showed no viable virus, either, Donald Prater, DVM, acting director of FDA’s Center for Food Safety and Applied Nutrition, said during the briefing.
The agency also tested retail powdered infant formula and powdered milk products marketed as toddler formula, and there were no viral fragments on PCR testing, so additional testing for culturable virus weren’t necessary, Prater said.
“These additional preliminary results further affirm the safety of the U.S. commercial milk supply,” Prater said, adding that the agency is “continuing to identify additional products that we may test.”
He reiterated the agency’s stark warning against consuming raw milk and raw milk products: “We continue to strongly advise against the consumption of … milk that has not been pasteurized, and recommend that industry does not manufacture or sell raw milk or raw milk products made with milk from cows showing symptoms of illness, including those infected with avian influenza viruses or exposed to those infected with avian influenza viruses,” he said.
Last week, the agency announced on a symposium held by the Association of State and Territorial Health Officials that preliminary results from analysis of the 96 retail milk samples found one in five had viral fragments of H5N1, and the preponderance of these samples came from areas with known infections among dairy cattle herds.
The agency also previously reported that there was no culturable virus in that batch of samples.
Demetre Daskalakis, MD, MPH, director of CDC’s National Center for Immunization and Respiratory Diseases, said more than 100 people have been monitored for symptoms and about 25 have been tested. Still only one person has tested positive for H5N1 during this outbreak among dairy cattle.
Daskalakis did not know how many people exposed to infected cattle reported having conjunctivitis.
He added that the agency developed updated interim guidance for various groups of workers, which was recently expanded to people who work in slaughterhouses.
The agency also developed interim guidance for veterinarians handling cats potentially exposed to the virus, as well as for prevention, monitoring, and public health investigations.
Two existing H5 candidate vaccine viruses tailored to the strain involved in the current outbreak, 2.3.4.4b, are available to manufacturers and can be used to make vaccine if needed, Daskalakis said. A representative from the HHS Administration for Strategic Preparedness and Response said one of those candidate vaccines is now in early clinical trials, being evaluated for safety and immunogenicity by two manufacturers.
Available influenza antivirals also appear to work against the virus picked up from the Texas human case, Daskalakis said.
CDC plans to conduct serologic studies in farm workers but the agency is “waiting for the appropriate time and place to be able to launch them,” he added.
Rosemary Sifford, DVM, chief veterinary officer at the U.S. Department of Agriculture (USDA), said there’s no evidence of virus in any beef herds at this time.
José Emilio Esteban, PhD, under secretary for food safety at the USDA, said the agency is “confident the meat supply is safe,” but is conducting three sampling efforts to be sure. Those include analysis of retail samples of ground beef; beef muscle samples from culled dairy cows; and cooking studies to ensure cooking would kill the virus should it exist in the meat.
“We’re pretty sure that the meat supply is safe,” he said. “We’re doing this to enhance our scientific knowledge.”
Sifford said evidence points to a single spillover event in the Texas panhandle, from wild birds into dairy cattle. Animals from those herds moving to herds in other states led to the initial movement of the virus, she said, adding that these animals being moved were asymptomatic.
Also, spread occurred through movement of equipment or other items between herds, she said.
The virus also moved from those cattle herds into other poultry flocks, Sifford said.
In the affected dairy herds, about 10% of the cows had symptoms, she said. These animals return to their previous levels of production after they recover, which takes about 2 weeks, she said. There’s been little or no associated mortality, she added.
As of press time, 36 dairy cattle herds in nine states have tested positive for H5N1.
“At this time, our focus is on identifying the currently affected herds and being able to work with them to eradicate the virus from the herd,” Sifford said. “But we do have plans to do some serologic testing to try to understand the overall scope, including previously infected herds.”

Kristina Fiore leads MedPage’s enterprise & investigative reporting team. She’s been a medical journalist for more than a decade and her work has been recognized by Barlett & Steele, AHCJ, SABEW, and others. Send story tips to k.fiore@medpagetoday.com. Follow

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The appearance of virology researcher Peter Daszak, PhD, whose organization worked with the Wuhan Institute of Virology (WIV) to study bat coronaviruses, drew the expected tough questions from House Republicans at a hearing Wednesday, but Democrats weren’t letting Daszak off the hook either.
“Today we’ll hear from both sides that there are serious concerns about EcoHealth Alliance’s failure to comply with reporting requirements for federal grantees — concerns that draw into question whether you, Dr. Daszak, sought to deliberately mislead regulators at NIH and NIAID [the National Institute of Allergy and Infectious Diseases],” Rep. Raul Ruiz, MD, (D-Calif.) ranking member of the House Oversight and Accountability Select Subcommittee on the Coronavirus Pandemic, said at a hearing featuring Daszak as the lone witness. “We will also examine whether Dr. Daszak, beyond his obligations as an employee of a federally funded grantee, acted with integrity in his engagement with the possibility that COVID-19 resulted from a research-related incident.”
Rep. Debbie Dingell (D-Mich.) asked Daszak, who is president of the EcoHealth Alliance, about why he appeared to mislead the Defense Advanced Research Projects Agency (DARPA) in relation to the Wuhan lab’s potential participation when his organization submitted a grant application — which was never funded — for proposed coronavirus research to be done in cooperation with the University of North Carolina. “That kind of raises some questions for me,” she said. “Why did you even entertain the thought of minimizing and apparently omitting the extent of Wuhan’s involvement?”
Daszak denied he had done that. “I talked to the DARPA staff right at the beginning … and asked them straight up in an email chain, ‘Is it OK to propose this, to work with colleagues in China on coronaviruses from China?'” he said. “They said, ‘Yes.’ So there was no intent to hide any China involvement. They’re in the proposal.”
Dingell remained unconvinced. “My Democratic colleagues and I want to emphasize the importance of transparency,” she said. “We believe in a full accounting of facts, and I believe we have been very fair with you … But to the extent you’ve considered misrepresenting facts, or done so, we will consider that a very serious mistake.”
Subcommittee chair Rep. Brad Wenstrup, DPM (R-Ohio), highlighted some of the conclusions of an interim report published Wednesday on the issue by the subcommittee’s majority members. “We have found that EcoHealth was nearly 2 years late in submitting a routine progress report to NIH, that EcoHealth failed to report, as required, a potentially dangerous experiment conducted at the Wuhan Institute of Virology, that EcoHealth used taxpayer dollars to facilitate risky gain-of-function research, and that Dr. Daszak omitted a material fact regarding his access to unanalyzed virus samples and sequences at the WIV in his successful effort to have his grant reinstated by NIH,” he said in his opening statement.
In addition, he said, “Dr. Daszak has been less than cooperative with the Select Subcommittee, he has been slow to produce requested documents, and has regularly played semantics with the definition of gain-of-function research, even in his previous testimony.” Generally, “gain-of-function” refers to research involving a genetic mutation in an organism — such as a virus — that confers a new or enhanced ability upon it.
Gain-of-function research was the focus of questions from Rep. Nicole Malliotakis (R-N.Y.) “EcoHealth Alliance never has, and did not do, gain-of-function research, by definition,” Daszak said in response to her question.
“Are you aware of the Wuhan lab conducting that type of research?” Malliotakis said. “No,” Daszak replied. When she asked him why his organization decided to work with the Wuhan lab, he replied, “If you want to work with a foreign country to find the next potential risk of a pandemic, you have to work with labs in those countries. We looked at labs across China; the [Wuhan lab] is the premier viral research [lab] in China” and has a “very good biosafety level.” He estimated that in total, his organization has received about $60-$64 million in government funding since the start of the pandemic.
Several subcommittee members tried to focus on the future. “It’s critical we understand what went wrong at NIAID and EcoHealth’s relationship with Wuhan,” said Rep. Morgan Griffith (R-Va.). “My hope is that when we’re finished we have a package of legislative proposals and other recommendations on biosafety and biosecurity. I increasingly think that means taking final approval authority for these experiments away from NIAID … in favor of an independent entity.”
“In my opinion [NIAID and EcoHealth] were grossly negligent,” Griffith said, adding that NIAID continues to fund EcoHealth’s research “to this very day. Even after COVID-19, at NIAID, it’s business as usual. It’s absurd and it’s got to change.”
Dingell had a different take. She urged her colleagues to focus on how to protect Americans from future pandemics. “Sowing distrust in the scientific community is not the best way to accomplish this goal,” Dingell said. “While I agree that the EcoHealth Alliance proved to be careless and imprecise with federal funding … this does not mean we should throw out the baby with the bathwater. NIH and NIAID serve important functions in medical and scientific research … They’ve done good work in the past and we want that good work to continue in the future.”
“Throughout this investigation, my Republican colleagues have been trying to cast blame for the COVID-19 pandemic on [former NIH director Francis] Collins and [former NIAID director Anthony] Fauci … contrary to the evidence,” she added. “We should be holding today’s witness accountable … but this should not distract us from our ultimate goal: future pandemic preparedness.”

Joyce Frieden oversees MedPage Today’s Washington coverage, including stories about Congress, the White House, the Supreme Court, healthcare trade associations, and federal agencies. She has 35 years of experience covering health policy. Follow

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A recombinant replacement for the ADAMTS13 protein (Adzynma) missing in congenital thrombotic thrombocytopenic purpura (TTP) restored levels and reduced acute TTP events, according to interim trial data that led to FDA approval.
For the primary endpoint, no acute TTP events occurred among patients getting prophylactic ADAMTS13 compared with one case on standard therapy with plasma-derived products (mean annualized event rate 0.05) over 6 months, reported Marie Scully, MD, of University College London Hospitals, and colleagues in the New England Journal of Medicine.
Thrombocytopenia, the most common disease manifestation, was also less common with recombinant ADAMTS13 (annualized event rate 0.74 vs 1.73).
With just 30 of the randomized 48 patients having finished the trial by the time of the interim analysis and given the rarity of congenital TTP, the trial did not have sufficient power to enable statistical hypothesis testing, the researchers cautioned. They could only calculate 95% confidence intervals unadjusted for multiplicity, the width of which “should not be used to infer definitive treatment effects,” they wrote.
Nevertheless, these data led to FDA approval in November 2023 for recombinant ADAMTS13 as prophylactic or on-demand enzyme replacement therapy for the extremely rare, chronic disorder that causes clotting in the small blood vessels throughout the body and can lead to severe bleeding episodes, strokes, and organ damage.
Scully’s group suggested that “prophylaxis with recombinant ADAMTS13 may allow the treatment landscape for congenital TTP to evolve toward preventing long-term organ damage by minimizing the formation of platelet-rich microthrombi.”
Its apparently more acceptable side-effect profile and higher average ADAMTS13 activity levels (mean 101% vs 19% with standard therapy) seen in the trial “may, in clinical practice, help expand patient access to long-term prophylaxis,” they added.
ADAMTS13 replacement through prophylactic or on-demand infusions of fresh-frozen plasma, plasma treated with a solvent-detergent process, or ADAMTS13-containing plasma-derived factor VIII/von Willebrand factor concentrates relies on donor plasma given as lengthy in-hospital infusions and carries the potential for severe and treatment-limiting allergic reactions to plasma.

“Patients appreciate it — it’s much much easier for them,” Spero R. Cataland, MD, of the Ohio State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research Institute in Columbus, told MedPage Today. “You’re talking 30 minutes [for an infusion] as opposed to 4 or 5 hours, and side effects are much better on this recombinant.”
Severe adverse events occurred in 7% of patients receiving recombinant ADAMTS13 compared with 14% on standard therapy. The most common adverse events of any severity were headache, migraine, nasopharyngitis, and diarrhea.

Their phase III trial enrolled patients in two cohorts. A total of 48 patients were randomized in a crossover design to thromboprophylaxis with weekly or every-other-week IV recombinant ADAMTS13 (40 IU/kg) or investigator’s choice of standard therapy with plasma-derived products. After 6 months, they switched to the other treatment for another 6 months, followed by 6 months when everyone received recombinant ADAMTS13.
An on-demand cohort of five patients who enrolled during an acute congenital TTP event were eligible to join the prophylactic cohort after resolution of the initial event, which three did.
At the interim analysis, 32 patients had completed the trial in the prophylactic cohort (all adults and adolescents) and another 14 patients (including eight younger than 12 years of age) were still underway in the trial. One adult discontinued due to a severe allergic reaction to prophylaxis with standard therapy; a second stopped after their diagnosis was confirmed as immune-mediated TTP. The trial protocol called for enrollment of only congenital TTP as confirmed by molecular genetic testing and ADAMTS13 activity of less than 10%.

Given that the disease affects only one or two persons per million, “those numbers are actually pretty good, all things considered,” Cataland noted.

For the primary outcome endpoint, acute TTP events were defined as a drop in platelets by at least 50% from baseline or to a level less than 100,000 platelets/mL and either a doubling in lactate dehydrogenase or rise to more than two times the upper limit of normal. While an objective and laboratory-based definition, it was “probably conservative as compared with clinical practice and existing literature,” Scully’s group noted.
Among the secondary endpoints, two subacute TTP events occurred in patients while on recombinant ADAMTS13 compared with five occurring in four patients on standard therapy (raw mean annualized event rate 0.07 vs 0.25).

“When these patients have episodes, their platelet counts are dropping because they are consuming their platelets to form clots throughout the body,” Cataland said. “So when you see a high platelet count, that’s a good thing.”

The researchers acknowledged the risk of immunogenicity with the enzyme replacement but noted no neutralizing antibodies in any patient during 12 months of prophylactic use.
“Historically, an important consideration with recombinant hematologic products has been the development of inhibitors against the product, such as factor VIII,” they wrote. “Given these findings and the results reported here, the overall immunogenic potential for ADAMTS13 replacement in patients with congenital TTP appears to be low.”
No other safety concerns emerged with recombinant ADAMTS13.
The trial’s open-label design was a limitation, albeit “necessary because the substantial differences in volume between recombinant ADAMTS13 and standard therapy could not be masked,” the researchers wrote. Another limitation was the lack of data on pediatric patients, for whom limited data were available because of age-staggered enrollment.
Importantly, “owing to the rarity of congenital TTP, limited available data on the natural history of the disorder, and lack of data from controlled clinical trials, our trial did not have sufficient power to detect differences between comparator groups,” Scully and team wrote.
In announcing approval, drugmaker Takeda had noted that a continuation study of both the prophylactic and on-demand cohorts supported approval, although these data have not yet been published. Follow-up is planned for a total duration of approximately 6 years for a maximum of approximately 77 participants.

Disclosures
The trial was supported by Takeda Development Center Americas and Baxalta Innovations, a Takeda company.Scully disclosed relationships with Alexion Pharmaceuticals, Octapharma USA, Sanofi US Services, and Takeda Oncology.Cataland disclosed consulting for Takeda.

Primary Source
New England Journal of Medicine
Source Reference: Scully M, et al “Recombinant ADAMTS13 in congenital thrombotic thrombocytopenic purpura” N Engl J Med 2024; DOI: 10.1056/NEJMoa2314793.

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Screening for hepatocellular carcinoma (HCC) in liver disease patients with cirrhosis may indeed lead to a survival benefit, a retrospective analysis of data from two large U.S. health systems suggested.
Among more than 1,300 patients diagnosed with HCC, the median survival reached 37 months for those with screening-detected tumors compared with 19 months for those whose tumors were found incidentally or due to symptoms (unadjusted HR 0.65, 95% CI 0.56-0.75).
And this difference persisted in adjusted models that accounted for lead-time bias (HR 0.77 for a mean sojourn time of 6 months, 95% CI 0.67-0.89), Amit Singal, MD, of the University of Texas Southwestern Medical Center in Dallas, and colleagues detailed in JAMA Network Open.
Guidelines from the American Association for the Study of Liver Diseases recommend screening high-risk patients for HCC using ultrasound, with or without α-fetoprotein (AFP). And the recommendations extend to liver disease patients with cirrhosis.
But “the efficacy of HCC screening in patients with cirrhosis is controversial because of the lack of randomized data and the inherent biases of cohort studies, including lead-time and length-time biases,” noted Singal and colleagues.
The controversy over whether to screen patients with cirrhosis was further fueled by a study in veterans that found no association between screening and reduced HCC-related mortality, though Singal and co-authors posited that this could have been due to downstream failures in care, including the underuse of curative therapies for early tumors.
In the current study, crude estimates showed 3- and 5-year survival rates of 46% and 32%, respectively, for the patients with screening-detected HCCs versus 25% and 8% for the group with non-screening cancers.
Analyses that corrected for both lead-time and length-time biases (using a mean sojourn time of 6 months) showed 3- and 5-year survival rates of 37% and 25% in the screening-detected group. “Lead-time bias occurs when screening leads to earlier cancer detection, so the time from diagnosis to death appears longer without an actual difference in mortality,” the researchers explained, while “length-time bias results from screening being more likely to detect slow-growing indolent tumors that are less likely to be fatal, which confers an artificial perception of improved survival.”
Overall, 42.3% of the cancers in the study were detected by screening. Tumor doubling time was similar for screening- and non-screening-detected HCCs (median 3.8 vs 5.6 months, respectively, P=0.40), numbers in line with a meta-analysis on the matter, and a similar proportion of patients in the two groups had indolent tumors (35.4% vs 38.1%; risk ratio 0.93, 95% CI 0.60-1.43).
“Overall, these data highlight the importance of promoting HCC screening implementation in practice,” the authors wrote in conclusion, noting that the underuse of screening has been reported in several studies.
The retrospective cohort study from Singal and colleagues included 1,313 patients diagnosed with HCC at UT Southwestern Medical Center and Parkland Health, both in Dallas, from January 2008 to December 2022, including 556 whose tumors were detected via screening.
Patients had an average age of 62 years, and three-fourths were men. A little more than a third of patients were white (36%), 30% were Black, and 29% were Hispanic. Most (62.5%) had Child Pugh class A cirrhosis and the rest class B. (Patients with class C cirrhosis were excluded from the analysis, as screening is not indicated in this group due to the high competing risk of mortality.)
HCC in the screening group was detected by imaging alone in 44.6%, AFP alone in 10.6%, and by both methods in 44.7%. Most tumors in the non-screening group (75.3%) were found incidentally, with the rest detected following symptoms.
At the time of cancer diagnosis, a majority (56%) had Barcelona Clinic Liver Cancer stage 0/A disease, 20% had stage B disease, and 24% had stage C disease. Hepatitis C or B viruses were considered the cause in 60% and 7%, with alcohol responsible for 14% and metabolic dysfunction-associated steatotic liver disease for 12% of cases.
Patients with tumors detected by screening were more likely to have early-stage HCC (70.7% vs 45.7% in the non-screening group) and receive curative treatment (51.1% vs 33.5%). Exploratory analyses, however, showed similar responses to curative-intent treatment regardless of whether tumors were screen-detected, found incidentally, or found due to symptoms, with response rates exceeding 80% in each group. Response rates after embolic treatments were similar for patients with screen-detected or incidental HCCs (54.8% vs 59.9%), but lower among those whose tumors were detected due to symptoms (38.9%).
Study limitations included that some imaging may have been performed in other health systems, though outside clinical records were reviewed; potential misclassification bias; the risk for residual confounding; and that a higher proportion of patients with indolent tumors may have been used to estimate tumor doubling time.

Ian Ingram is Managing Editor at MedPage Today and helps cover oncology for the site.

Disclosures
The study was funded in part by grants from the Cancer Intervention and Prevention Discoveries Program, the Singapore Ministry of Health’s National Medical Research Council, the National Cancer Institute, and Cancer Prevention & Research Institute of Texas.Singal disclosed relationships with Genentech, AstraZeneca, Eisai, Bayer, Exelixis, Fujifilm Medical, Exact Sciences, Roche, Glycotest, Freenome, GRAIL, Boston Scientific, Sirtex, HistoSonics, and Merck. Co-authors reported relationships with AstraZeneca, Eisai, Exact Sciences, Exelixis, Fujifilm Medical, Gilead, Glycotest, Madrigal, and Sirtex.

Primary Source
JAMA Network Open
Source Reference: Daher D, et al “Hepatocellular carcinoma screening in a contemporary cohort of at-risk patients” JAMA Netw Open 2024; DOI: 10.1001/jamanetworkopen.2024.8755.

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