MDedge Pediatrics

INDIANAPOLIS – When adolescents present with acne that is not responding to isotretinoin, make sure to ask if they’re taking the medication when eating fatty food – which is known to increase the drug’s bioavailability, advises James R. Treat, MD, a pediatric dermatologist at Children’s Hospital of Philadelphia.

“We see lots of teenagers who are on a restrictive diet,” which is “certainly one reason they could be failing isotretinoin,” Dr. Treat said at the annual meeting of the Society for Pediatric Dermatology.

Often, patients say that they have been referred to him because they had no response to 20 mg or 30 mg per day of isotretinoin. But after a dose escalation to 60 mg per day, their acne worsened.

If the patient’s acne is worsening with a cystic flare, “tripling the dose of isotretinoin is not something that you should do,” Dr. Treat said. “You should lower the dose and consider adding steroids.” For evidence-based recommendations on managing acne fulminans, he recommended an article published in the Journal of the American Academy of Dermatology in 2017.

Skin picking is another common reason for failure of isotretinoin, as well as with other acne therapies. These patients may have associated anxiety, which “might be a contraindication or at least something to consider before you put them on isotretinoin,” he noted.

In his experience, off-label use of N-acetylcysteine, an antioxidant and cysteine prodrug, has been “extremely effective” for patients with excoriation disorder. In a randomized trial of adults 18-60 years of age, 47% patients who took 1,200-3,000 mg per day doses of N-acetylcysteine for 12 weeks reported that their skin picking was much or very much improved, compared to 19% of those who took placebo (P = .03). The authors wrote that N-acetylcysteine “increases extracellular levels of glutamate in the nucleus accumbens,” and that these results support the hypothesis that “pharmacologic manipulation of the glutamate system may target core symptoms of compulsive behaviors.”

The tumor necrosis factor (TNF)-alpha blocker adalimumab is a reasonable option for patients with severe cystic inflammatory acne who fail isotretinoin, Dr. Treat said. In one published case, clinicians administered adalimumab 40 mg every other week for a 16-year-old male patient who received isotretinoin for moderate acne vulgaris, which caused sudden development of acne fulminans and incapacitating acute sacroiliitis with bilateral hip arthritis. Inflammatory lesions started to clear in 1 month and comedones improved by 3 months of treatment. Adalimumab was discontinued after 1 year and the patient remained clear.

“There are now multiple reports as well as some case series showing TNF-alpha agents causing clearance of acne,” said Dr. Treat, who directs the hospital’s pediatric dermatology fellowship program. A literature review of adalimumab, etanercept, and infliximab for treatment-resistant acne found that all agents had similar efficacy after 3-6 months of therapy. “We see this in our GI population, where TNF-alpha agents are helping their acne also,” he said. “We just have to augment it with some topical medications.”

Certain medications can drive the development of acne, including phenytoin, phenobarbital, lithium, MEK inhibitors, EGFR inhibitors, systemic steroids, and unopposed progesterone contraceptives. Some genetic conditions also predispose patients to acne, including mutations in the NCSTN gene and trisomy 13.

Dr. Treat discussed one of his patients with severe acne who had trisomy 13. The patient failed 12 months of doxycycline and amoxicillin in combination with a topical retinoid. He also failed low- and high-dose isotretinoin in combination with prednisone, as well as oral dapsone at a dose of 1 mg/kg per day for 3 months. He was started on adalimumab, but that was stopped after he flared. The patient is now maintained on ustekinumab monthly at a dose of 45 mg.

“I’ve only had a few patients where isotretinoin truly has failed,” Dr. Treat said. He described one patient with severe acne who had a hidradenitis-like appearance in his axilla and groin. “I treated with isotretinoin very gingerly in the beginning, [but] he flared significantly. I had given him concomitant steroids from the very beginning and transitioned to multiple different therapies – all of which failed.”

Next, Dr. Treat tried a course of systemic dapsone, and the patient responded nicely. “As an anti-inflammatory agent, dapsone is very reasonable” to consider, he said. “It’s something to add to your armamentarium.”

Dr. Treat disclosed that he is a consultant for Palvella and Regeneron. He has ownership interests in Matinas Biopharma Holdings, Axsome, Sorrento, and Amarin.

INDIANAPOLIS – When adolescents present with acne that is not responding to isotretinoin, make sure to ask if they’re taking the medication when eating fatty food – which is known to increase the drug’s bioavailability, advises James R. Treat, MD, a pediatric dermatologist at Children’s Hospital of Philadelphia.

“We see lots of teenagers who are on a restrictive diet,” which is “certainly one reason they could be failing isotretinoin,” Dr. Treat said at the annual meeting of the Society for Pediatric Dermatology.

Often, patients say that they have been referred to him because they had no response to 20 mg or 30 mg per day of isotretinoin. But after a dose escalation to 60 mg per day, their acne worsened.

If the patient’s acne is worsening with a cystic flare, “tripling the dose of isotretinoin is not something that you should do,” Dr. Treat said. “You should lower the dose and consider adding steroids.” For evidence-based recommendations on managing acne fulminans, he recommended an article published in the Journal of the American Academy of Dermatology in 2017.

Skin picking is another common reason for failure of isotretinoin, as well as with other acne therapies. These patients may have associated anxiety, which “might be a contraindication or at least something to consider before you put them on isotretinoin,” he noted.

In his experience, off-label use of N-acetylcysteine, an antioxidant and cysteine prodrug, has been “extremely effective” for patients with excoriation disorder. In a randomized trial of adults 18-60 years of age, 47% patients who took 1,200-3,000 mg per day doses of N-acetylcysteine for 12 weeks reported that their skin picking was much or very much improved, compared to 19% of those who took placebo (P = .03). The authors wrote that N-acetylcysteine “increases extracellular levels of glutamate in the nucleus accumbens,” and that these results support the hypothesis that “pharmacologic manipulation of the glutamate system may target core symptoms of compulsive behaviors.”

The tumor necrosis factor (TNF)-alpha blocker adalimumab is a reasonable option for patients with severe cystic inflammatory acne who fail isotretinoin, Dr. Treat said. In one published case, clinicians administered adalimumab 40 mg every other week for a 16-year-old male patient who received isotretinoin for moderate acne vulgaris, which caused sudden development of acne fulminans and incapacitating acute sacroiliitis with bilateral hip arthritis. Inflammatory lesions started to clear in 1 month and comedones improved by 3 months of treatment. Adalimumab was discontinued after 1 year and the patient remained clear.

“There are now multiple reports as well as some case series showing TNF-alpha agents causing clearance of acne,” said Dr. Treat, who directs the hospital’s pediatric dermatology fellowship program. A literature review of adalimumab, etanercept, and infliximab for treatment-resistant acne found that all agents had similar efficacy after 3-6 months of therapy. “We see this in our GI population, where TNF-alpha agents are helping their acne also,” he said. “We just have to augment it with some topical medications.”

Certain medications can drive the development of acne, including phenytoin, phenobarbital, lithium, MEK inhibitors, EGFR inhibitors, systemic steroids, and unopposed progesterone contraceptives. Some genetic conditions also predispose patients to acne, including mutations in the NCSTN gene and trisomy 13.

Dr. Treat discussed one of his patients with severe acne who had trisomy 13. The patient failed 12 months of doxycycline and amoxicillin in combination with a topical retinoid. He also failed low- and high-dose isotretinoin in combination with prednisone, as well as oral dapsone at a dose of 1 mg/kg per day for 3 months. He was started on adalimumab, but that was stopped after he flared. The patient is now maintained on ustekinumab monthly at a dose of 45 mg.

“I’ve only had a few patients where isotretinoin truly has failed,” Dr. Treat said. He described one patient with severe acne who had a hidradenitis-like appearance in his axilla and groin. “I treated with isotretinoin very gingerly in the beginning, [but] he flared significantly. I had given him concomitant steroids from the very beginning and transitioned to multiple different therapies – all of which failed.”

Next, Dr. Treat tried a course of systemic dapsone, and the patient responded nicely. “As an anti-inflammatory agent, dapsone is very reasonable” to consider, he said. “It’s something to add to your armamentarium.”

Dr. Treat disclosed that he is a consultant for Palvella and Regeneron. He has ownership interests in Matinas Biopharma Holdings, Axsome, Sorrento, and Amarin.

INDIANAPOLIS – When adolescents present with acne that is not responding to isotretinoin, make sure to ask if they’re taking the medication when eating fatty food – which is known to increase the drug’s bioavailability, advises James R. Treat, MD, a pediatric dermatologist at Children’s Hospital of Philadelphia.

“We see lots of teenagers who are on a restrictive diet,” which is “certainly one reason they could be failing isotretinoin,” Dr. Treat said at the annual meeting of the Society for Pediatric Dermatology.

Often, patients say that they have been referred to him because they had no response to 20 mg or 30 mg per day of isotretinoin. But after a dose escalation to 60 mg per day, their acne worsened.

If the patient’s acne is worsening with a cystic flare, “tripling the dose of isotretinoin is not something that you should do,” Dr. Treat said. “You should lower the dose and consider adding steroids.” For evidence-based recommendations on managing acne fulminans, he recommended an article published in the Journal of the American Academy of Dermatology in 2017.

Skin picking is another common reason for failure of isotretinoin, as well as with other acne therapies. These patients may have associated anxiety, which “might be a contraindication or at least something to consider before you put them on isotretinoin,” he noted.

In his experience, off-label use of N-acetylcysteine, an antioxidant and cysteine prodrug, has been “extremely effective” for patients with excoriation disorder. In a randomized trial of adults 18-60 years of age, 47% patients who took 1,200-3,000 mg per day doses of N-acetylcysteine for 12 weeks reported that their skin picking was much or very much improved, compared to 19% of those who took placebo (P = .03). The authors wrote that N-acetylcysteine “increases extracellular levels of glutamate in the nucleus accumbens,” and that these results support the hypothesis that “pharmacologic manipulation of the glutamate system may target core symptoms of compulsive behaviors.”

The tumor necrosis factor (TNF)-alpha blocker adalimumab is a reasonable option for patients with severe cystic inflammatory acne who fail isotretinoin, Dr. Treat said. In one published case, clinicians administered adalimumab 40 mg every other week for a 16-year-old male patient who received isotretinoin for moderate acne vulgaris, which caused sudden development of acne fulminans and incapacitating acute sacroiliitis with bilateral hip arthritis. Inflammatory lesions started to clear in 1 month and comedones improved by 3 months of treatment. Adalimumab was discontinued after 1 year and the patient remained clear.

“There are now multiple reports as well as some case series showing TNF-alpha agents causing clearance of acne,” said Dr. Treat, who directs the hospital’s pediatric dermatology fellowship program. A literature review of adalimumab, etanercept, and infliximab for treatment-resistant acne found that all agents had similar efficacy after 3-6 months of therapy. “We see this in our GI population, where TNF-alpha agents are helping their acne also,” he said. “We just have to augment it with some topical medications.”

Certain medications can drive the development of acne, including phenytoin, phenobarbital, lithium, MEK inhibitors, EGFR inhibitors, systemic steroids, and unopposed progesterone contraceptives. Some genetic conditions also predispose patients to acne, including mutations in the NCSTN gene and trisomy 13.

Dr. Treat discussed one of his patients with severe acne who had trisomy 13. The patient failed 12 months of doxycycline and amoxicillin in combination with a topical retinoid. He also failed low- and high-dose isotretinoin in combination with prednisone, as well as oral dapsone at a dose of 1 mg/kg per day for 3 months. He was started on adalimumab, but that was stopped after he flared. The patient is now maintained on ustekinumab monthly at a dose of 45 mg.

“I’ve only had a few patients where isotretinoin truly has failed,” Dr. Treat said. He described one patient with severe acne who had a hidradenitis-like appearance in his axilla and groin. “I treated with isotretinoin very gingerly in the beginning, [but] he flared significantly. I had given him concomitant steroids from the very beginning and transitioned to multiple different therapies – all of which failed.”

Next, Dr. Treat tried a course of systemic dapsone, and the patient responded nicely. “As an anti-inflammatory agent, dapsone is very reasonable” to consider, he said. “It’s something to add to your armamentarium.”

Dr. Treat disclosed that he is a consultant for Palvella and Regeneron. He has ownership interests in Matinas Biopharma Holdings, Axsome, Sorrento, and Amarin.

Scientists seeking to stay ahead of an evolving SARS-Cov-2 virus are looking at new strategies, including developing intranasal vaccines, according to speakers at a conference on July 26.

The Biden administration held a summit on the future of COVID-19 vaccines, inviting researchers to provide a public update on efforts to try to keep ahead of SARS-CoV-2.

Scientists and federal officials are looking to build on the successes seen in developing the original crop of COVID vaccines, which were authorized for use in the United States less than a year after the pandemic took hold.

But emerging variants are eroding these gains. For months now, officials at the Centers for Disease Control and Prevention and Food and Drug Administration have been keeping an eye on how the level of effectiveness of COVID vaccines has waned during the rise of the Omicron strain. And there’s continual concern about how SARS-CoV-2 might evolve over time.

“Our vaccines are terrific,” Ashish K. Jha, MD, the White House’s COVID-19 response coordinator, said at the summit. “[But] we have to do better.”

Among the approaches being considered are vaccines that would be applied intranasally, with the idea that this might be able to boost the immune response to SARS-CoV-2.

At the summit, Akiko Iwasaki, PhD, of Yale University, New Haven, Conn., said the intranasal approach might be helpful in preventing transmission as well as reducing the burden of illness for those who are infected with SARS-CoV-2.

“We’re stopping the virus from spreading right at the border,” Dr. Iwasaki said at the summit. “This is akin to putting a guard outside of the house in order to patrol for invaders compared to putting the guards in the hallway of the building in the hope that they capture the invader.”

Dr. Iwasaki is one of the founders of Xanadu Bio, a private company created last year to focus on ways to kill SARS-CoV-2 in the nasosinus before it spreads deeper into the respiratory tract. In an editorial in Science Immunology, Dr. Iwasaki and Eric J. Topol, MD, director of the Scripps Research Translational Institute, urged greater federal investment in this approach to fighting SARS-CoV-2. (Dr. Topol is editor-in-chief of Medscape.)

Titled “Operation Nasal Vaccine – Lightning speed to counter COVID-19,” their editorial noted the “unprecedented success” seen in the rapid development of the first two mRNA shots. Dr. Iwasaki and Dr. Topol noted that these victories had been “fueled by the $10 billion governmental investment in Operation Warp Speed.

“During the first year of the pandemic, meaningful evolution of the virus was slow-paced, without any functional consequences, but since that time we have seen a succession of important variants of concern, with increasing transmissibility and immune evasion, culminating in the Omicron lineages,”  wrote Dr. Iwasaki and Dr. Topol.

Recent developments have “spotlighted the possibility of nasal vaccines, with their allure for achieving mucosal immunity, complementing, and likely bolstering the circulating immunity achieved via intramuscular shots,” they added.
 

An early setback

Scientists at the National Institutes of Health and the Biomedical Advanced Research and Development Authority (BARDA) have for some time been looking to vet an array of next-generation vaccine concepts, including ones that trigger mucosal immunity, the Washington Post reported in April.

At the summit on July 26, several participants, including Dr. Jha, stressed the role that public-private partnerships were key to the rapid development of the initial COVID vaccines. They said continued U.S. government support will be needed to make advances in this field.

One of the presenters, Biao He, PhD, founder and president of CyanVac and Blue Lake Biotechnology, spoke of the federal support that his efforts have received over the years to develop intranasal vaccines. His Georgia-based firm already has an experimental intranasal vaccine candidate, CVXGA1-001, in phase 1 testing (NCT04954287).

The CVXGA-001 builds on technology already used in a veterinary product, an intranasal vaccine long used to prevent kennel cough in dogs, he said at the summit.

The emerging field of experimental intranasal COVID vaccines already has had at least one setback.

The biotech firm Altimmune in June 2021 announced that it would discontinue development of its experimental intranasal AdCOVID vaccine following disappointing phase 1 results. The vaccine appeared to be well tolerated in the test, but the immunogenicity data demonstrated lower than expected results in healthy volunteers, especially in light of the responses seen to already cleared vaccines, Altimmune said in a release. 

In the statement, Scot Roberts, PhD, chief scientific officer at Altimmune, noted that the study participants lacked immunity from prior infection or vaccination. “We believe that prior immunity in humans may be important for a robust immune response to intranasal dosing with AdCOVID,” he said.

At the summit, Marty Moore, PhD, cofounder and chief scientific officer for Redwood City, Calif.–based Meissa Vaccines, noted the challenges that remain ahead for intranasal COVID vaccines, while also highlighting what he sees as the potential of this approach.

Meissa also has advanced an experimental intranasal COVID vaccine as far as phase 1 testing (NCT04798001).

“No one here today can tell you that mucosal COVID vaccines work. We’re not there yet. We need clinical efficacy data to answer that question,” Dr. Moore said.

But there’s a potential for a “knockout blow to COVID, a transmission-blocking vaccine” from the intranasal approach, he said.

“The virus is mutating faster than our ability to manage vaccines and not enough people are getting boosters. These injectable vaccines do a great job of preventing severe disease, but they do little to prevent infection” from spreading, Dr. Moore said.

A version of this article first appeared on Medscape.com.

Scientists seeking to stay ahead of an evolving SARS-Cov-2 virus are looking at new strategies, including developing intranasal vaccines, according to speakers at a conference on July 26.

The Biden administration held a summit on the future of COVID-19 vaccines, inviting researchers to provide a public update on efforts to try to keep ahead of SARS-CoV-2.

Scientists and federal officials are looking to build on the successes seen in developing the original crop of COVID vaccines, which were authorized for use in the United States less than a year after the pandemic took hold.

But emerging variants are eroding these gains. For months now, officials at the Centers for Disease Control and Prevention and Food and Drug Administration have been keeping an eye on how the level of effectiveness of COVID vaccines has waned during the rise of the Omicron strain. And there’s continual concern about how SARS-CoV-2 might evolve over time.

“Our vaccines are terrific,” Ashish K. Jha, MD, the White House’s COVID-19 response coordinator, said at the summit. “[But] we have to do better.”

Among the approaches being considered are vaccines that would be applied intranasally, with the idea that this might be able to boost the immune response to SARS-CoV-2.

At the summit, Akiko Iwasaki, PhD, of Yale University, New Haven, Conn., said the intranasal approach might be helpful in preventing transmission as well as reducing the burden of illness for those who are infected with SARS-CoV-2.

“We’re stopping the virus from spreading right at the border,” Dr. Iwasaki said at the summit. “This is akin to putting a guard outside of the house in order to patrol for invaders compared to putting the guards in the hallway of the building in the hope that they capture the invader.”

Dr. Iwasaki is one of the founders of Xanadu Bio, a private company created last year to focus on ways to kill SARS-CoV-2 in the nasosinus before it spreads deeper into the respiratory tract. In an editorial in Science Immunology, Dr. Iwasaki and Eric J. Topol, MD, director of the Scripps Research Translational Institute, urged greater federal investment in this approach to fighting SARS-CoV-2. (Dr. Topol is editor-in-chief of Medscape.)

Titled “Operation Nasal Vaccine – Lightning speed to counter COVID-19,” their editorial noted the “unprecedented success” seen in the rapid development of the first two mRNA shots. Dr. Iwasaki and Dr. Topol noted that these victories had been “fueled by the $10 billion governmental investment in Operation Warp Speed.

“During the first year of the pandemic, meaningful evolution of the virus was slow-paced, without any functional consequences, but since that time we have seen a succession of important variants of concern, with increasing transmissibility and immune evasion, culminating in the Omicron lineages,”  wrote Dr. Iwasaki and Dr. Topol.

Recent developments have “spotlighted the possibility of nasal vaccines, with their allure for achieving mucosal immunity, complementing, and likely bolstering the circulating immunity achieved via intramuscular shots,” they added.
 

An early setback

Scientists at the National Institutes of Health and the Biomedical Advanced Research and Development Authority (BARDA) have for some time been looking to vet an array of next-generation vaccine concepts, including ones that trigger mucosal immunity, the Washington Post reported in April.

At the summit on July 26, several participants, including Dr. Jha, stressed the role that public-private partnerships were key to the rapid development of the initial COVID vaccines. They said continued U.S. government support will be needed to make advances in this field.

One of the presenters, Biao He, PhD, founder and president of CyanVac and Blue Lake Biotechnology, spoke of the federal support that his efforts have received over the years to develop intranasal vaccines. His Georgia-based firm already has an experimental intranasal vaccine candidate, CVXGA1-001, in phase 1 testing (NCT04954287).

The CVXGA-001 builds on technology already used in a veterinary product, an intranasal vaccine long used to prevent kennel cough in dogs, he said at the summit.

The emerging field of experimental intranasal COVID vaccines already has had at least one setback.

The biotech firm Altimmune in June 2021 announced that it would discontinue development of its experimental intranasal AdCOVID vaccine following disappointing phase 1 results. The vaccine appeared to be well tolerated in the test, but the immunogenicity data demonstrated lower than expected results in healthy volunteers, especially in light of the responses seen to already cleared vaccines, Altimmune said in a release. 

In the statement, Scot Roberts, PhD, chief scientific officer at Altimmune, noted that the study participants lacked immunity from prior infection or vaccination. “We believe that prior immunity in humans may be important for a robust immune response to intranasal dosing with AdCOVID,” he said.

At the summit, Marty Moore, PhD, cofounder and chief scientific officer for Redwood City, Calif.–based Meissa Vaccines, noted the challenges that remain ahead for intranasal COVID vaccines, while also highlighting what he sees as the potential of this approach.

Meissa also has advanced an experimental intranasal COVID vaccine as far as phase 1 testing (NCT04798001).

“No one here today can tell you that mucosal COVID vaccines work. We’re not there yet. We need clinical efficacy data to answer that question,” Dr. Moore said.

But there’s a potential for a “knockout blow to COVID, a transmission-blocking vaccine” from the intranasal approach, he said.

“The virus is mutating faster than our ability to manage vaccines and not enough people are getting boosters. These injectable vaccines do a great job of preventing severe disease, but they do little to prevent infection” from spreading, Dr. Moore said.

A version of this article first appeared on Medscape.com.

Scientists seeking to stay ahead of an evolving SARS-Cov-2 virus are looking at new strategies, including developing intranasal vaccines, according to speakers at a conference on July 26.

The Biden administration held a summit on the future of COVID-19 vaccines, inviting researchers to provide a public update on efforts to try to keep ahead of SARS-CoV-2.

Scientists and federal officials are looking to build on the successes seen in developing the original crop of COVID vaccines, which were authorized for use in the United States less than a year after the pandemic took hold.

But emerging variants are eroding these gains. For months now, officials at the Centers for Disease Control and Prevention and Food and Drug Administration have been keeping an eye on how the level of effectiveness of COVID vaccines has waned during the rise of the Omicron strain. And there’s continual concern about how SARS-CoV-2 might evolve over time.

“Our vaccines are terrific,” Ashish K. Jha, MD, the White House’s COVID-19 response coordinator, said at the summit. “[But] we have to do better.”

Among the approaches being considered are vaccines that would be applied intranasally, with the idea that this might be able to boost the immune response to SARS-CoV-2.

At the summit, Akiko Iwasaki, PhD, of Yale University, New Haven, Conn., said the intranasal approach might be helpful in preventing transmission as well as reducing the burden of illness for those who are infected with SARS-CoV-2.

“We’re stopping the virus from spreading right at the border,” Dr. Iwasaki said at the summit. “This is akin to putting a guard outside of the house in order to patrol for invaders compared to putting the guards in the hallway of the building in the hope that they capture the invader.”

Dr. Iwasaki is one of the founders of Xanadu Bio, a private company created last year to focus on ways to kill SARS-CoV-2 in the nasosinus before it spreads deeper into the respiratory tract. In an editorial in Science Immunology, Dr. Iwasaki and Eric J. Topol, MD, director of the Scripps Research Translational Institute, urged greater federal investment in this approach to fighting SARS-CoV-2. (Dr. Topol is editor-in-chief of Medscape.)

Titled “Operation Nasal Vaccine – Lightning speed to counter COVID-19,” their editorial noted the “unprecedented success” seen in the rapid development of the first two mRNA shots. Dr. Iwasaki and Dr. Topol noted that these victories had been “fueled by the $10 billion governmental investment in Operation Warp Speed.

“During the first year of the pandemic, meaningful evolution of the virus was slow-paced, without any functional consequences, but since that time we have seen a succession of important variants of concern, with increasing transmissibility and immune evasion, culminating in the Omicron lineages,”  wrote Dr. Iwasaki and Dr. Topol.

Recent developments have “spotlighted the possibility of nasal vaccines, with their allure for achieving mucosal immunity, complementing, and likely bolstering the circulating immunity achieved via intramuscular shots,” they added.
 

An early setback

Scientists at the National Institutes of Health and the Biomedical Advanced Research and Development Authority (BARDA) have for some time been looking to vet an array of next-generation vaccine concepts, including ones that trigger mucosal immunity, the Washington Post reported in April.

At the summit on July 26, several participants, including Dr. Jha, stressed the role that public-private partnerships were key to the rapid development of the initial COVID vaccines. They said continued U.S. government support will be needed to make advances in this field.

One of the presenters, Biao He, PhD, founder and president of CyanVac and Blue Lake Biotechnology, spoke of the federal support that his efforts have received over the years to develop intranasal vaccines. His Georgia-based firm already has an experimental intranasal vaccine candidate, CVXGA1-001, in phase 1 testing (NCT04954287).

The CVXGA-001 builds on technology already used in a veterinary product, an intranasal vaccine long used to prevent kennel cough in dogs, he said at the summit.

The emerging field of experimental intranasal COVID vaccines already has had at least one setback.

The biotech firm Altimmune in June 2021 announced that it would discontinue development of its experimental intranasal AdCOVID vaccine following disappointing phase 1 results. The vaccine appeared to be well tolerated in the test, but the immunogenicity data demonstrated lower than expected results in healthy volunteers, especially in light of the responses seen to already cleared vaccines, Altimmune said in a release. 

In the statement, Scot Roberts, PhD, chief scientific officer at Altimmune, noted that the study participants lacked immunity from prior infection or vaccination. “We believe that prior immunity in humans may be important for a robust immune response to intranasal dosing with AdCOVID,” he said.

At the summit, Marty Moore, PhD, cofounder and chief scientific officer for Redwood City, Calif.–based Meissa Vaccines, noted the challenges that remain ahead for intranasal COVID vaccines, while also highlighting what he sees as the potential of this approach.

Meissa also has advanced an experimental intranasal COVID vaccine as far as phase 1 testing (NCT04798001).

“No one here today can tell you that mucosal COVID vaccines work. We’re not there yet. We need clinical efficacy data to answer that question,” Dr. Moore said.

But there’s a potential for a “knockout blow to COVID, a transmission-blocking vaccine” from the intranasal approach, he said.

“The virus is mutating faster than our ability to manage vaccines and not enough people are getting boosters. These injectable vaccines do a great job of preventing severe disease, but they do little to prevent infection” from spreading, Dr. Moore said.

A version of this article first appeared on Medscape.com.

A new study suggests that going beyond current guidance on moderate and vigorous physical activity levels may add years to one’s life.

Americans are advised to do a minimum of 150-300 minutes a week of moderate exercise or 75-150 minutes a week of vigorous exercise, or an equivalent combination of both, according to U.S. Department of Health and Human Services Physical Activity Guidelines.

Results from more than 100,000 U.S. adults followed for 30 years showed that individuals who performed double the currently recommended range of either moderate or vigorous physical activity weekly had the lowest long-term risk of mortality.

Adults who reported completing four times the minimum recommended activity levels saw no clear incremental mortality benefit but also no harm, according to the study, published in the journal Circulation.

“I think we’re worried more about the lower end and people that are not even doing the minimum, but this should be reassuring to people who like to do a lot of exercise,” senior author Edward Giovannucci, MD, ScD, with the Harvard T.H. Chan School of Public Health, Boston, told this news organization.

Some studies have suggested that long-term, high-intensity exercise (e.g., marathons, triathlons, and long-distance cycling) may be associated with increased risks of atrial fibrillation, coronary artery calcification, and sudden cardiac death.

A recent analysis from the Copenhagen City Heart Study showed a U-shaped association between long-term all-cause mortality and 0 to 2.5 hours and more than 10 hours of weekly, leisure-time sports activities.

Most studies suggesting harm, however, have used only one measurement of physical activity capturing a mix of people who chronically exercise at high levels and those who do it sporadically, which possibly can be harmful, Dr. Giovannucci said. “We were better able to look at consistent long-term activity and saw there was no harm.”

The study included 116,221 participants in the Nurses’ Health Study and the Health Professionals Follow-up Study between 1988 and 2018, who completed up to 15 (median, 11) questionnaires on their health and leisure-time physical activity that were updated every 2 years.

Most were White (96%), 63% were female, and the average age and body mass index over follow-up was 66 years and 26 kg/m². During 30 years of follow-up, there were 47,596 deaths.
 

‘Any effort is worthwhile’

The analysis found that individuals who met the guideline for long-term vigorous physical activity (75-150 min/week) cut their adjusted risk of death from cardiovascular disease (CVD) by a whopping 31%, from non-CVD causes by 15%, and all-causes by 19%, compared with those with no long-term vigorous activity.

Those completing two to four times the recommended minimum (150-299 min/week) had a 27%-33% lower risk of CVD mortality, 19% lower risk of non-CVD mortality, and 21%-23% lower risk of all-cause mortality.

Higher levels did not appear to further lower mortality risk. For example, 300-374 min/week of vigorous physical activity was associated with a 32% lower risk of CVD death, 18% lower risk of non-CVD death, and 22% lower risk of dying from any cause.

The analysis also found that individuals who met the guidelines for moderate physical activity had lower CVD, non-CVD, and all-cause mortality risks whether they were active 150-244 min/week (22%, 19%, and 20%, respectively) or 225-299 min/week (21%, 25%, and 20%, respectively), compared with those with almost no long-term moderate activity.

Those fitting in two to four times the recommended minimum (300-599 min/week) had a 28%-38% lower risk of CVD mortality, 25%-27% lower risk of non-CVD mortality, and 26%-31% lower risk of all-cause mortality.

The mortality benefit appeared to plateau, with 600 min/week of moderate physical activity showing associations similar to 300-599 min/week.

“The sweet spot seems to be two to four times the recommended levels but for people who are sedentary, I think one of the key messages that I give my patients is that any effort is worthwhile; that any physical activity, even less than the recommended, has some mortality reduction,” Erin Michos, MD, MHS, associate director of preventive cardiology at Johns Hopkins University, Baltimore, said in an interview.

Indeed, individuals who reported doing just 20-74 minutes of moderate exercise per week had a 19% lower risk of dying from any cause and a 13% lower risk of dying from CVD compared with those doing less.

Current American Heart Association (AHA) recommendations are for at least 150 minutes per week of moderate-intensity aerobic exercise or 75 minutes per week of vigorous aerobic exercise, or a combination of both.

“This suggests that even more is probably better, in the range of two to four times that, so maybe we should move our targets a little bit higher, which is kind of what the Department of Health and Human Services has already done,” said Dr. Michos, who was not involved in the study.

Former AHA president Donna K. Arnett, PhD, who was not involved in the study, said in a statement that “we’ve known for a long time that moderate or intense levels of physical exercise can reduce a person’s risk of both atherosclerotic cardiovascular disease and mortality.

“We have also seen that getting more than 300 minutes of moderate-intensity aerobic physical activity or more than 150 minutes of vigorous-intensity aerobic physical exercise each week may reduce a person’s risk of atherosclerotic cardiovascular disease even further, so it makes sense that getting those extra minutes of exercise may also decrease mortality,” she added.
 

Mix and match

Dr. Giovannucci noted that the joint effects of the two types of exercise on mortality have not been studied and “there are some questions, for example, about whether doing a lot of moderate activity is sufficient or can you get more benefits by doing vigorous activity also.”

Joint analyses of both exercise intensities found that additional vigorous physical activity was associated with lower mortality among participants with insufficient (less than 300 min/week) levels of moderate exercise but not among those with at least 300 min/week of moderate exercise.

“The main message is that you can get essentially all of the benefit by just doing moderate exercise,” Dr. Giovannucci said. “There’s no magic benefit of doing vigorous [exercise]. But if someone wants to do vigorous, they can get the benefit in about half the time. So if you only have 2-3 hours a week to exercise and can do, say 2 or 3 hours of running, you can get pretty much the maximum benefit.”

Sensitivity analyses showed a consistent association between long-term leisure physical activity and mortality without adjustment for body mass index/calorie intake.

“Some people think the effect of exercise is to lower your body weight or keep it down, which could be one of the benefits, but even independent of that, you get benefits even if it has no effect on your weight,” he said. “So, definitely, that’s important.”

Dr. Michos pointed out that vigorous physical activity may seem daunting for many individuals but that moderate exercise can include activities such as brisk walking, ballroom dancing, active yoga, and recreational swimming.

“The nice thing is that you can really combine or substitute both and get just as similar mortality reductions with moderate physical activity, because a lot of patients may not want to do vigorous activity,” she said. “They don’t want to get on the treadmill; that’s too intimidating or stressful.”

The study was supported by the National Institutes of Health. The authors and Dr. Michos report no relevant financial relationships.

A version of this article first appeared on Medscape.com.


A new study suggests that going beyond current guidance on moderate and vigorous physical activity levels may add years to one’s life.

Americans are advised to do a minimum of 150-300 minutes a week of moderate exercise or 75-150 minutes a week of vigorous exercise, or an equivalent combination of both, according to U.S. Department of Health and Human Services Physical Activity Guidelines.

Results from more than 100,000 U.S. adults followed for 30 years showed that individuals who performed double the currently recommended range of either moderate or vigorous physical activity weekly had the lowest long-term risk of mortality.

Adults who reported completing four times the minimum recommended activity levels saw no clear incremental mortality benefit but also no harm, according to the study, published in the journal Circulation.

“I think we’re worried more about the lower end and people that are not even doing the minimum, but this should be reassuring to people who like to do a lot of exercise,” senior author Edward Giovannucci, MD, ScD, with the Harvard T.H. Chan School of Public Health, Boston, told this news organization.

Some studies have suggested that long-term, high-intensity exercise (e.g., marathons, triathlons, and long-distance cycling) may be associated with increased risks of atrial fibrillation, coronary artery calcification, and sudden cardiac death.

A recent analysis from the Copenhagen City Heart Study showed a U-shaped association between long-term all-cause mortality and 0 to 2.5 hours and more than 10 hours of weekly, leisure-time sports activities.

Most studies suggesting harm, however, have used only one measurement of physical activity capturing a mix of people who chronically exercise at high levels and those who do it sporadically, which possibly can be harmful, Dr. Giovannucci said. “We were better able to look at consistent long-term activity and saw there was no harm.”

The study included 116,221 participants in the Nurses’ Health Study and the Health Professionals Follow-up Study between 1988 and 2018, who completed up to 15 (median, 11) questionnaires on their health and leisure-time physical activity that were updated every 2 years.

Most were White (96%), 63% were female, and the average age and body mass index over follow-up was 66 years and 26 kg/m². During 30 years of follow-up, there were 47,596 deaths.
 

‘Any effort is worthwhile’

The analysis found that individuals who met the guideline for long-term vigorous physical activity (75-150 min/week) cut their adjusted risk of death from cardiovascular disease (CVD) by a whopping 31%, from non-CVD causes by 15%, and all-causes by 19%, compared with those with no long-term vigorous activity.

Those completing two to four times the recommended minimum (150-299 min/week) had a 27%-33% lower risk of CVD mortality, 19% lower risk of non-CVD mortality, and 21%-23% lower risk of all-cause mortality.

Higher levels did not appear to further lower mortality risk. For example, 300-374 min/week of vigorous physical activity was associated with a 32% lower risk of CVD death, 18% lower risk of non-CVD death, and 22% lower risk of dying from any cause.

The analysis also found that individuals who met the guidelines for moderate physical activity had lower CVD, non-CVD, and all-cause mortality risks whether they were active 150-244 min/week (22%, 19%, and 20%, respectively) or 225-299 min/week (21%, 25%, and 20%, respectively), compared with those with almost no long-term moderate activity.

Those fitting in two to four times the recommended minimum (300-599 min/week) had a 28%-38% lower risk of CVD mortality, 25%-27% lower risk of non-CVD mortality, and 26%-31% lower risk of all-cause mortality.

The mortality benefit appeared to plateau, with 600 min/week of moderate physical activity showing associations similar to 300-599 min/week.

“The sweet spot seems to be two to four times the recommended levels but for people who are sedentary, I think one of the key messages that I give my patients is that any effort is worthwhile; that any physical activity, even less than the recommended, has some mortality reduction,” Erin Michos, MD, MHS, associate director of preventive cardiology at Johns Hopkins University, Baltimore, said in an interview.

Indeed, individuals who reported doing just 20-74 minutes of moderate exercise per week had a 19% lower risk of dying from any cause and a 13% lower risk of dying from CVD compared with those doing less.

Current American Heart Association (AHA) recommendations are for at least 150 minutes per week of moderate-intensity aerobic exercise or 75 minutes per week of vigorous aerobic exercise, or a combination of both.

“This suggests that even more is probably better, in the range of two to four times that, so maybe we should move our targets a little bit higher, which is kind of what the Department of Health and Human Services has already done,” said Dr. Michos, who was not involved in the study.

Former AHA president Donna K. Arnett, PhD, who was not involved in the study, said in a statement that “we’ve known for a long time that moderate or intense levels of physical exercise can reduce a person’s risk of both atherosclerotic cardiovascular disease and mortality.

“We have also seen that getting more than 300 minutes of moderate-intensity aerobic physical activity or more than 150 minutes of vigorous-intensity aerobic physical exercise each week may reduce a person’s risk of atherosclerotic cardiovascular disease even further, so it makes sense that getting those extra minutes of exercise may also decrease mortality,” she added.
 

Mix and match

Dr. Giovannucci noted that the joint effects of the two types of exercise on mortality have not been studied and “there are some questions, for example, about whether doing a lot of moderate activity is sufficient or can you get more benefits by doing vigorous activity also.”

Joint analyses of both exercise intensities found that additional vigorous physical activity was associated with lower mortality among participants with insufficient (less than 300 min/week) levels of moderate exercise but not among those with at least 300 min/week of moderate exercise.

“The main message is that you can get essentially all of the benefit by just doing moderate exercise,” Dr. Giovannucci said. “There’s no magic benefit of doing vigorous [exercise]. But if someone wants to do vigorous, they can get the benefit in about half the time. So if you only have 2-3 hours a week to exercise and can do, say 2 or 3 hours of running, you can get pretty much the maximum benefit.”

Sensitivity analyses showed a consistent association between long-term leisure physical activity and mortality without adjustment for body mass index/calorie intake.

“Some people think the effect of exercise is to lower your body weight or keep it down, which could be one of the benefits, but even independent of that, you get benefits even if it has no effect on your weight,” he said. “So, definitely, that’s important.”

Dr. Michos pointed out that vigorous physical activity may seem daunting for many individuals but that moderate exercise can include activities such as brisk walking, ballroom dancing, active yoga, and recreational swimming.

“The nice thing is that you can really combine or substitute both and get just as similar mortality reductions with moderate physical activity, because a lot of patients may not want to do vigorous activity,” she said. “They don’t want to get on the treadmill; that’s too intimidating or stressful.”

The study was supported by the National Institutes of Health. The authors and Dr. Michos report no relevant financial relationships.

A version of this article first appeared on Medscape.com.


A new study suggests that going beyond current guidance on moderate and vigorous physical activity levels may add years to one’s life.

Americans are advised to do a minimum of 150-300 minutes a week of moderate exercise or 75-150 minutes a week of vigorous exercise, or an equivalent combination of both, according to U.S. Department of Health and Human Services Physical Activity Guidelines.

Results from more than 100,000 U.S. adults followed for 30 years showed that individuals who performed double the currently recommended range of either moderate or vigorous physical activity weekly had the lowest long-term risk of mortality.

Adults who reported completing four times the minimum recommended activity levels saw no clear incremental mortality benefit but also no harm, according to the study, published in the journal Circulation.

“I think we’re worried more about the lower end and people that are not even doing the minimum, but this should be reassuring to people who like to do a lot of exercise,” senior author Edward Giovannucci, MD, ScD, with the Harvard T.H. Chan School of Public Health, Boston, told this news organization.

Some studies have suggested that long-term, high-intensity exercise (e.g., marathons, triathlons, and long-distance cycling) may be associated with increased risks of atrial fibrillation, coronary artery calcification, and sudden cardiac death.

A recent analysis from the Copenhagen City Heart Study showed a U-shaped association between long-term all-cause mortality and 0 to 2.5 hours and more than 10 hours of weekly, leisure-time sports activities.

Most studies suggesting harm, however, have used only one measurement of physical activity capturing a mix of people who chronically exercise at high levels and those who do it sporadically, which possibly can be harmful, Dr. Giovannucci said. “We were better able to look at consistent long-term activity and saw there was no harm.”

The study included 116,221 participants in the Nurses’ Health Study and the Health Professionals Follow-up Study between 1988 and 2018, who completed up to 15 (median, 11) questionnaires on their health and leisure-time physical activity that were updated every 2 years.

Most were White (96%), 63% were female, and the average age and body mass index over follow-up was 66 years and 26 kg/m². During 30 years of follow-up, there were 47,596 deaths.
 

‘Any effort is worthwhile’

The analysis found that individuals who met the guideline for long-term vigorous physical activity (75-150 min/week) cut their adjusted risk of death from cardiovascular disease (CVD) by a whopping 31%, from non-CVD causes by 15%, and all-causes by 19%, compared with those with no long-term vigorous activity.

Those completing two to four times the recommended minimum (150-299 min/week) had a 27%-33% lower risk of CVD mortality, 19% lower risk of non-CVD mortality, and 21%-23% lower risk of all-cause mortality.

Higher levels did not appear to further lower mortality risk. For example, 300-374 min/week of vigorous physical activity was associated with a 32% lower risk of CVD death, 18% lower risk of non-CVD death, and 22% lower risk of dying from any cause.

The analysis also found that individuals who met the guidelines for moderate physical activity had lower CVD, non-CVD, and all-cause mortality risks whether they were active 150-244 min/week (22%, 19%, and 20%, respectively) or 225-299 min/week (21%, 25%, and 20%, respectively), compared with those with almost no long-term moderate activity.

Those fitting in two to four times the recommended minimum (300-599 min/week) had a 28%-38% lower risk of CVD mortality, 25%-27% lower risk of non-CVD mortality, and 26%-31% lower risk of all-cause mortality.

The mortality benefit appeared to plateau, with 600 min/week of moderate physical activity showing associations similar to 300-599 min/week.

“The sweet spot seems to be two to four times the recommended levels but for people who are sedentary, I think one of the key messages that I give my patients is that any effort is worthwhile; that any physical activity, even less than the recommended, has some mortality reduction,” Erin Michos, MD, MHS, associate director of preventive cardiology at Johns Hopkins University, Baltimore, said in an interview.

Indeed, individuals who reported doing just 20-74 minutes of moderate exercise per week had a 19% lower risk of dying from any cause and a 13% lower risk of dying from CVD compared with those doing less.

Current American Heart Association (AHA) recommendations are for at least 150 minutes per week of moderate-intensity aerobic exercise or 75 minutes per week of vigorous aerobic exercise, or a combination of both.

“This suggests that even more is probably better, in the range of two to four times that, so maybe we should move our targets a little bit higher, which is kind of what the Department of Health and Human Services has already done,” said Dr. Michos, who was not involved in the study.

Former AHA president Donna K. Arnett, PhD, who was not involved in the study, said in a statement that “we’ve known for a long time that moderate or intense levels of physical exercise can reduce a person’s risk of both atherosclerotic cardiovascular disease and mortality.

“We have also seen that getting more than 300 minutes of moderate-intensity aerobic physical activity or more than 150 minutes of vigorous-intensity aerobic physical exercise each week may reduce a person’s risk of atherosclerotic cardiovascular disease even further, so it makes sense that getting those extra minutes of exercise may also decrease mortality,” she added.
 

Mix and match

Dr. Giovannucci noted that the joint effects of the two types of exercise on mortality have not been studied and “there are some questions, for example, about whether doing a lot of moderate activity is sufficient or can you get more benefits by doing vigorous activity also.”

Joint analyses of both exercise intensities found that additional vigorous physical activity was associated with lower mortality among participants with insufficient (less than 300 min/week) levels of moderate exercise but not among those with at least 300 min/week of moderate exercise.

“The main message is that you can get essentially all of the benefit by just doing moderate exercise,” Dr. Giovannucci said. “There’s no magic benefit of doing vigorous [exercise]. But if someone wants to do vigorous, they can get the benefit in about half the time. So if you only have 2-3 hours a week to exercise and can do, say 2 or 3 hours of running, you can get pretty much the maximum benefit.”

Sensitivity analyses showed a consistent association between long-term leisure physical activity and mortality without adjustment for body mass index/calorie intake.

“Some people think the effect of exercise is to lower your body weight or keep it down, which could be one of the benefits, but even independent of that, you get benefits even if it has no effect on your weight,” he said. “So, definitely, that’s important.”

Dr. Michos pointed out that vigorous physical activity may seem daunting for many individuals but that moderate exercise can include activities such as brisk walking, ballroom dancing, active yoga, and recreational swimming.

“The nice thing is that you can really combine or substitute both and get just as similar mortality reductions with moderate physical activity, because a lot of patients may not want to do vigorous activity,” she said. “They don’t want to get on the treadmill; that’s too intimidating or stressful.”

The study was supported by the National Institutes of Health. The authors and Dr. Michos report no relevant financial relationships.

A version of this article first appeared on Medscape.com.


“Children’s hospitals saw a more than 25% decline in injury-related emergency room visits during the first year of the pandemic.” There’s a headline that should soothe a nation starved for some good news. It was based on a study published in Pediatrics that reports on data collected in the Pediatric Health Information System between March 2020 and March 2021 using a 3-year period between 2017 and 2020 as a control. How could this not be good news? First, let’s not be too hasty in celebrating the good fortune of all those millions of children spared the pain and anxiety of an emergency department visit.

If you were an administrator of an emergency department attempting to match revenues with expenses, a 25% drop in visits may have hit your bottom line. Office-based pediatricians experienced a similar phenomenon when many parents quickly learned that they could ignore or self-manage minor illnesses and complaints.

A decrease in visits doesn’t necessarily mean that the conditions that drive the traffic flow in your facility have gone away. It may simply be that they are being managed somewhere else. However, it is equally likely that for some reason the pandemic created situations that made the usual illnesses and injuries that flood into emergency departments less likely to occur. And, here, other anecdotal evidence about weight gain and a decline in fitness point to the conclusion that when children are no longer in school, they settle into more sedentary and less injury-generating activities. Injuries from falling off the couch watching television or playing video games alone do occur but certainly with less frequency than the random collisions that are inevitable when scores of classmates are running around on the playground.

So while it may be tempting to view a decline in emergency department visits as a positive statistic, this pandemic should remind us to be careful about how we choose our metrics to measure the health of the community. A decline in injuries in the short term may be masking a more serious erosion in the health of the pediatric population over the long term. At times I worry that as a specialty we are so focused on injury prevention that we lose sight of the fact that being physically active comes with a risk. A risk that we may wish to minimize, but a risk we must accept if we want to encourage the physical activity that we know is so important in the bigger health picture. For example, emergency department visits caused by pedal cycles initially rose 60%, eventually settling into the 25%-30% range leading one to suspect there was a learning or relearning curve.

However, while visits for minor injuries declined 25%, those associated with firearms rose initially 22%, and then 42%, and finally over 35%. These numbers combined with significant increases in visits from suffocation, nonpedal transportation, and suicide intent make it clear that, for most children, being in school is significantly less dangerous than staying at home.

As the pandemic continues to tumble on and we are presented with future questions about whether to keep schools open or closed, I hope the results of this study and others will help school officials and their advisers step back and look beyond the simple metric of case numbers and appreciate that there are benefits to being in school that go far beyond what can be learned in class.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

“Children’s hospitals saw a more than 25% decline in injury-related emergency room visits during the first year of the pandemic.” There’s a headline that should soothe a nation starved for some good news. It was based on a study published in Pediatrics that reports on data collected in the Pediatric Health Information System between March 2020 and March 2021 using a 3-year period between 2017 and 2020 as a control. How could this not be good news? First, let’s not be too hasty in celebrating the good fortune of all those millions of children spared the pain and anxiety of an emergency department visit.

If you were an administrator of an emergency department attempting to match revenues with expenses, a 25% drop in visits may have hit your bottom line. Office-based pediatricians experienced a similar phenomenon when many parents quickly learned that they could ignore or self-manage minor illnesses and complaints.

A decrease in visits doesn’t necessarily mean that the conditions that drive the traffic flow in your facility have gone away. It may simply be that they are being managed somewhere else. However, it is equally likely that for some reason the pandemic created situations that made the usual illnesses and injuries that flood into emergency departments less likely to occur. And, here, other anecdotal evidence about weight gain and a decline in fitness point to the conclusion that when children are no longer in school, they settle into more sedentary and less injury-generating activities. Injuries from falling off the couch watching television or playing video games alone do occur but certainly with less frequency than the random collisions that are inevitable when scores of classmates are running around on the playground.

So while it may be tempting to view a decline in emergency department visits as a positive statistic, this pandemic should remind us to be careful about how we choose our metrics to measure the health of the community. A decline in injuries in the short term may be masking a more serious erosion in the health of the pediatric population over the long term. At times I worry that as a specialty we are so focused on injury prevention that we lose sight of the fact that being physically active comes with a risk. A risk that we may wish to minimize, but a risk we must accept if we want to encourage the physical activity that we know is so important in the bigger health picture. For example, emergency department visits caused by pedal cycles initially rose 60%, eventually settling into the 25%-30% range leading one to suspect there was a learning or relearning curve.

However, while visits for minor injuries declined 25%, those associated with firearms rose initially 22%, and then 42%, and finally over 35%. These numbers combined with significant increases in visits from suffocation, nonpedal transportation, and suicide intent make it clear that, for most children, being in school is significantly less dangerous than staying at home.

As the pandemic continues to tumble on and we are presented with future questions about whether to keep schools open or closed, I hope the results of this study and others will help school officials and their advisers step back and look beyond the simple metric of case numbers and appreciate that there are benefits to being in school that go far beyond what can be learned in class.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

“Children’s hospitals saw a more than 25% decline in injury-related emergency room visits during the first year of the pandemic.” There’s a headline that should soothe a nation starved for some good news. It was based on a study published in Pediatrics that reports on data collected in the Pediatric Health Information System between March 2020 and March 2021 using a 3-year period between 2017 and 2020 as a control. How could this not be good news? First, let’s not be too hasty in celebrating the good fortune of all those millions of children spared the pain and anxiety of an emergency department visit.

If you were an administrator of an emergency department attempting to match revenues with expenses, a 25% drop in visits may have hit your bottom line. Office-based pediatricians experienced a similar phenomenon when many parents quickly learned that they could ignore or self-manage minor illnesses and complaints.

A decrease in visits doesn’t necessarily mean that the conditions that drive the traffic flow in your facility have gone away. It may simply be that they are being managed somewhere else. However, it is equally likely that for some reason the pandemic created situations that made the usual illnesses and injuries that flood into emergency departments less likely to occur. And, here, other anecdotal evidence about weight gain and a decline in fitness point to the conclusion that when children are no longer in school, they settle into more sedentary and less injury-generating activities. Injuries from falling off the couch watching television or playing video games alone do occur but certainly with less frequency than the random collisions that are inevitable when scores of classmates are running around on the playground.

So while it may be tempting to view a decline in emergency department visits as a positive statistic, this pandemic should remind us to be careful about how we choose our metrics to measure the health of the community. A decline in injuries in the short term may be masking a more serious erosion in the health of the pediatric population over the long term. At times I worry that as a specialty we are so focused on injury prevention that we lose sight of the fact that being physically active comes with a risk. A risk that we may wish to minimize, but a risk we must accept if we want to encourage the physical activity that we know is so important in the bigger health picture. For example, emergency department visits caused by pedal cycles initially rose 60%, eventually settling into the 25%-30% range leading one to suspect there was a learning or relearning curve.

However, while visits for minor injuries declined 25%, those associated with firearms rose initially 22%, and then 42%, and finally over 35%. These numbers combined with significant increases in visits from suffocation, nonpedal transportation, and suicide intent make it clear that, for most children, being in school is significantly less dangerous than staying at home.

As the pandemic continues to tumble on and we are presented with future questions about whether to keep schools open or closed, I hope the results of this study and others will help school officials and their advisers step back and look beyond the simple metric of case numbers and appreciate that there are benefits to being in school that go far beyond what can be learned in class.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

New COVID-19 cases rose for the second week in a row as cumulative cases among U.S. children passed the 14-million mark, but a recent survey shows that more than half of parents believe that the vaccine is a greater risk to children under age 5 years than the virus.

In a Kaiser Family Foundation survey conducted July 7-17, 53% of parents with children aged 6 months to 5 years said that the vaccine is “a bigger risk to their child’s health than getting infected with COVID-19, compared to 44% who say getting infected is the bigger risk,” KFF reported July 26.

More than 4 out of 10 of respondents (43%) said that they will “definitely not” get their eligible children vaccinated, while only 7% said that their children had already received it and 10% said their children would get it as soon as possible, according to the KFF survey, which had an overall sample size of 1,847 adults, including an oversample of 471 parents of children under age 5.

Vaccine initiation has been slow in the first month since it was approved for the youngest children. Just 2.8% of all eligible children under age 5 had received an initial dose as of July 19, compared with first-month uptake figures of more than 18% for the 5- to 11-year-olds and 27% for those aged 12-15, based on data from the Centers for Disease Control and Prevention.

The current rates for vaccination in those aged 5 and older look like this: 70.2% of 12- to 17-year-olds have received at least one dose, versus 37.1% of those aged 5-11. Just over 60% of the older children were fully vaccinated as of July 19, as were 30.2% of the 5- to 11-year-olds, the CDC reported on its COVID Data Tracker.
 

Number of new cases hits 2-month high

Despite the vaccine, SARS-CoV-2 and its various mutations have continued with their summer travels. With 92,000 newly infected children added for the week of July 15-21, there have now been a total of 14,003,497 pediatric cases reported since the start of the pandemic, which works out to 18.6% of cases in all ages, the American Academy of Pediatrics and the Children’s Hospital Association said in their weekly COVID-19 report.

The 92,000 new cases represent an increase of almost 22% over the previous week and mark the highest 1-week count since May, when the total passed 100,000 for 2 consecutive weeks. More recently the trend had seemed more stable as weekly cases dropped twice and rose twice as the total hovered around 70,000, based on the data collected by the AAP and CHA from state and territorial health departments.

A different scenario has played out for emergency department visits and hospital admissions, which have risen steadily since the beginning of April. The admission rate for children aged 0-17, which was just 0.13 new patients per 100,000 population on April 11, was up to 0.44 per 100,000 on July 21. By comparison, the highest rate reached last year during the Delta surge was 0.47 per 100,000, based on CDC data.

The 7-day average of emergency dept. visits among the youngest age group, 0-11 years, shows the same general increase as hospital admissions, but the older children have diverged form that path (see graph). For those aged 12-15 and 16-17, hospitalizations started dropping in late May and into mid-June before climbing again, although more slowly than for the youngest group, the CDC data show.

The ED visit rate with diagnosed COVID among those aged 0-11, measured at 6.1% of all visits on July 19, is, in fact, considerably higher than at any time during the Delta surge last year, when it never passed 4.0%, although much lower than peak Omicron (14.1%). That 6.1% was also higher than any other age group on that day, adults included, the CDC said.

[email protected]

New COVID-19 cases rose for the second week in a row as cumulative cases among U.S. children passed the 14-million mark, but a recent survey shows that more than half of parents believe that the vaccine is a greater risk to children under age 5 years than the virus.

In a Kaiser Family Foundation survey conducted July 7-17, 53% of parents with children aged 6 months to 5 years said that the vaccine is “a bigger risk to their child’s health than getting infected with COVID-19, compared to 44% who say getting infected is the bigger risk,” KFF reported July 26.

More than 4 out of 10 of respondents (43%) said that they will “definitely not” get their eligible children vaccinated, while only 7% said that their children had already received it and 10% said their children would get it as soon as possible, according to the KFF survey, which had an overall sample size of 1,847 adults, including an oversample of 471 parents of children under age 5.

Vaccine initiation has been slow in the first month since it was approved for the youngest children. Just 2.8% of all eligible children under age 5 had received an initial dose as of July 19, compared with first-month uptake figures of more than 18% for the 5- to 11-year-olds and 27% for those aged 12-15, based on data from the Centers for Disease Control and Prevention.

The current rates for vaccination in those aged 5 and older look like this: 70.2% of 12- to 17-year-olds have received at least one dose, versus 37.1% of those aged 5-11. Just over 60% of the older children were fully vaccinated as of July 19, as were 30.2% of the 5- to 11-year-olds, the CDC reported on its COVID Data Tracker.
 

Number of new cases hits 2-month high

Despite the vaccine, SARS-CoV-2 and its various mutations have continued with their summer travels. With 92,000 newly infected children added for the week of July 15-21, there have now been a total of 14,003,497 pediatric cases reported since the start of the pandemic, which works out to 18.6% of cases in all ages, the American Academy of Pediatrics and the Children’s Hospital Association said in their weekly COVID-19 report.

The 92,000 new cases represent an increase of almost 22% over the previous week and mark the highest 1-week count since May, when the total passed 100,000 for 2 consecutive weeks. More recently the trend had seemed more stable as weekly cases dropped twice and rose twice as the total hovered around 70,000, based on the data collected by the AAP and CHA from state and territorial health departments.

A different scenario has played out for emergency department visits and hospital admissions, which have risen steadily since the beginning of April. The admission rate for children aged 0-17, which was just 0.13 new patients per 100,000 population on April 11, was up to 0.44 per 100,000 on July 21. By comparison, the highest rate reached last year during the Delta surge was 0.47 per 100,000, based on CDC data.

The 7-day average of emergency dept. visits among the youngest age group, 0-11 years, shows the same general increase as hospital admissions, but the older children have diverged form that path (see graph). For those aged 12-15 and 16-17, hospitalizations started dropping in late May and into mid-June before climbing again, although more slowly than for the youngest group, the CDC data show.

The ED visit rate with diagnosed COVID among those aged 0-11, measured at 6.1% of all visits on July 19, is, in fact, considerably higher than at any time during the Delta surge last year, when it never passed 4.0%, although much lower than peak Omicron (14.1%). That 6.1% was also higher than any other age group on that day, adults included, the CDC said.

[email protected]

New COVID-19 cases rose for the second week in a row as cumulative cases among U.S. children passed the 14-million mark, but a recent survey shows that more than half of parents believe that the vaccine is a greater risk to children under age 5 years than the virus.

In a Kaiser Family Foundation survey conducted July 7-17, 53% of parents with children aged 6 months to 5 years said that the vaccine is “a bigger risk to their child’s health than getting infected with COVID-19, compared to 44% who say getting infected is the bigger risk,” KFF reported July 26.

More than 4 out of 10 of respondents (43%) said that they will “definitely not” get their eligible children vaccinated, while only 7% said that their children had already received it and 10% said their children would get it as soon as possible, according to the KFF survey, which had an overall sample size of 1,847 adults, including an oversample of 471 parents of children under age 5.

Vaccine initiation has been slow in the first month since it was approved for the youngest children. Just 2.8% of all eligible children under age 5 had received an initial dose as of July 19, compared with first-month uptake figures of more than 18% for the 5- to 11-year-olds and 27% for those aged 12-15, based on data from the Centers for Disease Control and Prevention.

The current rates for vaccination in those aged 5 and older look like this: 70.2% of 12- to 17-year-olds have received at least one dose, versus 37.1% of those aged 5-11. Just over 60% of the older children were fully vaccinated as of July 19, as were 30.2% of the 5- to 11-year-olds, the CDC reported on its COVID Data Tracker.
 

Number of new cases hits 2-month high

Despite the vaccine, SARS-CoV-2 and its various mutations have continued with their summer travels. With 92,000 newly infected children added for the week of July 15-21, there have now been a total of 14,003,497 pediatric cases reported since the start of the pandemic, which works out to 18.6% of cases in all ages, the American Academy of Pediatrics and the Children’s Hospital Association said in their weekly COVID-19 report.

The 92,000 new cases represent an increase of almost 22% over the previous week and mark the highest 1-week count since May, when the total passed 100,000 for 2 consecutive weeks. More recently the trend had seemed more stable as weekly cases dropped twice and rose twice as the total hovered around 70,000, based on the data collected by the AAP and CHA from state and territorial health departments.

A different scenario has played out for emergency department visits and hospital admissions, which have risen steadily since the beginning of April. The admission rate for children aged 0-17, which was just 0.13 new patients per 100,000 population on April 11, was up to 0.44 per 100,000 on July 21. By comparison, the highest rate reached last year during the Delta surge was 0.47 per 100,000, based on CDC data.

The 7-day average of emergency dept. visits among the youngest age group, 0-11 years, shows the same general increase as hospital admissions, but the older children have diverged form that path (see graph). For those aged 12-15 and 16-17, hospitalizations started dropping in late May and into mid-June before climbing again, although more slowly than for the youngest group, the CDC data show.

The ED visit rate with diagnosed COVID among those aged 0-11, measured at 6.1% of all visits on July 19, is, in fact, considerably higher than at any time during the Delta surge last year, when it never passed 4.0%, although much lower than peak Omicron (14.1%). That 6.1% was also higher than any other age group on that day, adults included, the CDC said.

[email protected]

For the seventh consecutive year, the Mayo Clinic in Rochester, Minn., took the top spot in the annual honor roll of best hospitals, published July 26 by U.S. News & World Report.

The 2022 rankings, which marks the 33rd edition, showcase several methodology changes, including new ratings for ovarian, prostate, and uterine cancer surgeries that “provide patients ... with previously unavailable information to assist them in making a critical health care decision,” a news release from the publication explains.

Additional expanded health equity measures assess “which hospitals provide more care to low-income patients and which have racial disparities in certain surgical outcomes,” said the release. Finally, a new metric called “home time” determines how successfully each hospital helps patients return home.
 

Mayo Clinic remains No. 1

For the 2022-2023 rankings and ratings, U.S. News compared more than 4,500 medical centers across the country in 15 specialties and 20 procedures and conditions. Of these, 493 were recognized as Best Regional Hospitals as a result of their overall strong performance.

The list was then narrowed to the top 20 hospitals, outlined in the honor roll below, that deliver “exceptional treatment across multiple areas of care.”

Following Mayo Clinic in the annual ranking’s top spot, Cedars-Sinai Medical Center in Los Angeles rises from No. 6 to No. 2, and New York University Langone Hospitals finish third, up from eighth in 2021.

Cleveland Clinic in Ohio holds the No. 4 spot, down two from 2021, while Johns Hopkins Hospital in Baltimore and UCLA Medical Center in Los Angeles tie for fifth place. Rounding out the top 10, in order, are: New York–Presbyterian Hospital–Columbia and Cornell, New York; Massachusetts General Hospital, Boston; Northwestern Memorial Hospital, Chicago; Stanford (Calif.) Health Care–Stanford Hospital.

The following hospitals complete the top 20 in the United States:

• 11. Barnes-Jewish Hospital, St. Louis
• 12. UCSF Medical Center, San Francisco
• 13. Hospitals of the University of Pennsylvania–Penn Presbyterian, Philadelphia
• 14. Brigham and Women’s Hospital, Boston
• 15. Houston Methodist Hospital
• 16. Mount Sinai Hospital, New York
• 17. University of Michigan Health–Michigan Medicine, Ann Arbor
• 18. Mayo Clinic–Phoenix
• 19. Vanderbilt University Medical Center, Nashville, Tenn.
• 20. Rush University Medical Center, Chicago

For the specialty rankings, the University of Texas MD Anderson Cancer Center, Houston, remains No. 1 in cancer care, the Cleveland Clinic is No. 1 in cardiology and heart surgery, and the Hospital for Special Surgery in New York is No. 1 in orthopedics.
 

Top five for cancer

• 1. University of Texas MD Anderson Cancer Center, Houston
• 2. Memorial Sloan Kettering Cancer Center, New York
• 3. Mayo Clinic, Rochester, Minn.
• 4. Dana-Farber/Brigham and Women’s Cancer Center, Boston
• 5. UCLA Medical Center, Los Angeles

Top five for cardiology and heart surgery

• 1. Cleveland Clinic
• 2. Mayo Clinic, Rochester, Minn.
• 3. Cedars-Sinai Medical Center, Los Angeles
• 4. New York–Presbyterian Hospital–Columbia and Cornell, New York
• 5. New York University Langone Hospitals

Top five for orthopedics

• 1. Hospital for Special Surgery, New York
• 2. Mayo Clinic, Rochester, Minn.
• 3. Cedars-Sinai Medical Center, Los Angeles
• 4. New York University Langone Hospitals
• 5. (tie) Rush University Medical Center, Chicago
• 5. (tie) UCLA Medical Center, Los Angeles

According to the news release, the procedures and conditions ratings are based entirely on objective patient care measures like survival rates, patient experience, home time, and level of nursing care. The Best Hospitals rankings consider a variety of data provided by the Centers for Medicare & Medicaid Services, American Hospital Association, professional organizations, and medical specialists.

The full report is available online.

A version of this article first appeared on Medscape.com.

For the seventh consecutive year, the Mayo Clinic in Rochester, Minn., took the top spot in the annual honor roll of best hospitals, published July 26 by U.S. News & World Report.

The 2022 rankings, which marks the 33rd edition, showcase several methodology changes, including new ratings for ovarian, prostate, and uterine cancer surgeries that “provide patients ... with previously unavailable information to assist them in making a critical health care decision,” a news release from the publication explains.

Additional expanded health equity measures assess “which hospitals provide more care to low-income patients and which have racial disparities in certain surgical outcomes,” said the release. Finally, a new metric called “home time” determines how successfully each hospital helps patients return home.
 

Mayo Clinic remains No. 1

For the 2022-2023 rankings and ratings, U.S. News compared more than 4,500 medical centers across the country in 15 specialties and 20 procedures and conditions. Of these, 493 were recognized as Best Regional Hospitals as a result of their overall strong performance.

The list was then narrowed to the top 20 hospitals, outlined in the honor roll below, that deliver “exceptional treatment across multiple areas of care.”

Following Mayo Clinic in the annual ranking’s top spot, Cedars-Sinai Medical Center in Los Angeles rises from No. 6 to No. 2, and New York University Langone Hospitals finish third, up from eighth in 2021.

Cleveland Clinic in Ohio holds the No. 4 spot, down two from 2021, while Johns Hopkins Hospital in Baltimore and UCLA Medical Center in Los Angeles tie for fifth place. Rounding out the top 10, in order, are: New York–Presbyterian Hospital–Columbia and Cornell, New York; Massachusetts General Hospital, Boston; Northwestern Memorial Hospital, Chicago; Stanford (Calif.) Health Care–Stanford Hospital.

The following hospitals complete the top 20 in the United States:

• 11. Barnes-Jewish Hospital, St. Louis
• 12. UCSF Medical Center, San Francisco
• 13. Hospitals of the University of Pennsylvania–Penn Presbyterian, Philadelphia
• 14. Brigham and Women’s Hospital, Boston
• 15. Houston Methodist Hospital
• 16. Mount Sinai Hospital, New York
• 17. University of Michigan Health–Michigan Medicine, Ann Arbor
• 18. Mayo Clinic–Phoenix
• 19. Vanderbilt University Medical Center, Nashville, Tenn.
• 20. Rush University Medical Center, Chicago

For the specialty rankings, the University of Texas MD Anderson Cancer Center, Houston, remains No. 1 in cancer care, the Cleveland Clinic is No. 1 in cardiology and heart surgery, and the Hospital for Special Surgery in New York is No. 1 in orthopedics.
 

Top five for cancer

• 1. University of Texas MD Anderson Cancer Center, Houston
• 2. Memorial Sloan Kettering Cancer Center, New York
• 3. Mayo Clinic, Rochester, Minn.
• 4. Dana-Farber/Brigham and Women’s Cancer Center, Boston
• 5. UCLA Medical Center, Los Angeles

Top five for cardiology and heart surgery

• 1. Cleveland Clinic
• 2. Mayo Clinic, Rochester, Minn.
• 3. Cedars-Sinai Medical Center, Los Angeles
• 4. New York–Presbyterian Hospital–Columbia and Cornell, New York
• 5. New York University Langone Hospitals

Top five for orthopedics

• 1. Hospital for Special Surgery, New York
• 2. Mayo Clinic, Rochester, Minn.
• 3. Cedars-Sinai Medical Center, Los Angeles
• 4. New York University Langone Hospitals
• 5. (tie) Rush University Medical Center, Chicago
• 5. (tie) UCLA Medical Center, Los Angeles

According to the news release, the procedures and conditions ratings are based entirely on objective patient care measures like survival rates, patient experience, home time, and level of nursing care. The Best Hospitals rankings consider a variety of data provided by the Centers for Medicare & Medicaid Services, American Hospital Association, professional organizations, and medical specialists.

The full report is available online.

A version of this article first appeared on Medscape.com.

For the seventh consecutive year, the Mayo Clinic in Rochester, Minn., took the top spot in the annual honor roll of best hospitals, published July 26 by U.S. News & World Report.

The 2022 rankings, which marks the 33rd edition, showcase several methodology changes, including new ratings for ovarian, prostate, and uterine cancer surgeries that “provide patients ... with previously unavailable information to assist them in making a critical health care decision,” a news release from the publication explains.

Additional expanded health equity measures assess “which hospitals provide more care to low-income patients and which have racial disparities in certain surgical outcomes,” said the release. Finally, a new metric called “home time” determines how successfully each hospital helps patients return home.
 

Mayo Clinic remains No. 1

For the 2022-2023 rankings and ratings, U.S. News compared more than 4,500 medical centers across the country in 15 specialties and 20 procedures and conditions. Of these, 493 were recognized as Best Regional Hospitals as a result of their overall strong performance.

The list was then narrowed to the top 20 hospitals, outlined in the honor roll below, that deliver “exceptional treatment across multiple areas of care.”

Following Mayo Clinic in the annual ranking’s top spot, Cedars-Sinai Medical Center in Los Angeles rises from No. 6 to No. 2, and New York University Langone Hospitals finish third, up from eighth in 2021.

Cleveland Clinic in Ohio holds the No. 4 spot, down two from 2021, while Johns Hopkins Hospital in Baltimore and UCLA Medical Center in Los Angeles tie for fifth place. Rounding out the top 10, in order, are: New York–Presbyterian Hospital–Columbia and Cornell, New York; Massachusetts General Hospital, Boston; Northwestern Memorial Hospital, Chicago; Stanford (Calif.) Health Care–Stanford Hospital.

The following hospitals complete the top 20 in the United States:

• 11. Barnes-Jewish Hospital, St. Louis
• 12. UCSF Medical Center, San Francisco
• 13. Hospitals of the University of Pennsylvania–Penn Presbyterian, Philadelphia
• 14. Brigham and Women’s Hospital, Boston
• 15. Houston Methodist Hospital
• 16. Mount Sinai Hospital, New York
• 17. University of Michigan Health–Michigan Medicine, Ann Arbor
• 18. Mayo Clinic–Phoenix
• 19. Vanderbilt University Medical Center, Nashville, Tenn.
• 20. Rush University Medical Center, Chicago

For the specialty rankings, the University of Texas MD Anderson Cancer Center, Houston, remains No. 1 in cancer care, the Cleveland Clinic is No. 1 in cardiology and heart surgery, and the Hospital for Special Surgery in New York is No. 1 in orthopedics.
 

Top five for cancer

• 1. University of Texas MD Anderson Cancer Center, Houston
• 2. Memorial Sloan Kettering Cancer Center, New York
• 3. Mayo Clinic, Rochester, Minn.
• 4. Dana-Farber/Brigham and Women’s Cancer Center, Boston
• 5. UCLA Medical Center, Los Angeles

Top five for cardiology and heart surgery

• 1. Cleveland Clinic
• 2. Mayo Clinic, Rochester, Minn.
• 3. Cedars-Sinai Medical Center, Los Angeles
• 4. New York–Presbyterian Hospital–Columbia and Cornell, New York
• 5. New York University Langone Hospitals

Top five for orthopedics

• 1. Hospital for Special Surgery, New York
• 2. Mayo Clinic, Rochester, Minn.
• 3. Cedars-Sinai Medical Center, Los Angeles
• 4. New York University Langone Hospitals
• 5. (tie) Rush University Medical Center, Chicago
• 5. (tie) UCLA Medical Center, Los Angeles

According to the news release, the procedures and conditions ratings are based entirely on objective patient care measures like survival rates, patient experience, home time, and level of nursing care. The Best Hospitals rankings consider a variety of data provided by the Centers for Medicare & Medicaid Services, American Hospital Association, professional organizations, and medical specialists.

The full report is available online.

A version of this article first appeared on Medscape.com.

More than half of studies testing anticancer drugs against each other have rules with regard to dose modification and growth support that favor the experimental drug arm, a new analysis suggests.

“We found it sobering that this practice is so common,” Timothée Olivier, MD, with Geneva University Hospital and the University of California, San Francisco, said in an interview.

Trials may be “rigged” in a way where the new therapy appears more effective than if the trial would have been designed with fairer rules, he explained.

This leaves open the question of whether new drugs are truly superior to older ones or if instead different outcomes are caused by more aggressive dosing or growth factor support, the investigators said.

Dr. Olivier, with UCSF coinvestigators Alyson Haslam, PhD, and Vinay Prasad, MD, reported their findings online in the European Journal of Cancer.

‘Highly concerning’

Different drug modification rules or growth factor support guidance may affect the results of randomized controlled trials (RCTs) of testing new cancer agents.

For their study, Dr. Olivier and colleagues did a cross-sectional analysis of all 62 head-to-head registration RCTs that led to Food and Drug Administration approval between 2009 and 2021.

All of the trials examined anticancer drugs in the advanced or metastatic setting where a comparison was made between arms regarding either dose modification rules or myeloid growth factors recommendations.

The researchers assessed imbalance in drug modification rules, myeloid growth factor recommendations, or both, according to prespecified rules.

They discovered that 40 of the 62 trials (65%) had unequal rules for dose medication, granulocyte colony-stimulating factor (G-CSF) use, or both.

Six trials (10%) had rules favoring the control arm, while 34 (55%) had rules favoring the experimental arm. Among these, 50% had unequal drug modification rules, 41% had unequal G-CSF rules, and 9% had both.

Dr. Olivier said in an interview the results are “highly concerning because when you are investigating the effect of a new drug, you don’t want to have a false sense of a drug’s effect because of other factors not directly related to the drug’s efficacy.”

“If you introduce unfair rules about dose modification or supporting medication that favors the new drug, then you don’t know if a positive trial is due to the effect of the new drug or to the effect of differential dosing or supporting medication,” he added.
 

Blame industry?

Dr. Olivier said the fact that most registration trials are industry-sponsored is likely the primary explanation of the findings.

“Industry-sponsored trials may be designed so that the new drug has the best chance to get the largest ‘win,’ because this means more market share and more profit for the company that manufactures the drug. This is not a criticism of the industry, which runs on a business model that naturally aims to gain more market share and more profit,” Dr. Olivier said.

“However, it is the role and duty of regulators to reconcile industry incentives with the patients’ best interests, and there is accumulating data showing the regulators are failing to do so,” he added.

Addressing this problem will likely take buy-in from multiple stakeholders.

Awareness of the problem is a first step and understanding the influence of commercial incentives in drug development is also key, Dr. Olivier said.

Institutional review boards and drug regulators could also systematically evaluate drug dosing modification and supportive medication rules before a trial gets underway.

Regulators could also incentivize companies to implement balanced rules between arms by not granting drug approval based on trials suffering from such flaws.

“However, financial conflict of interest is present at many levels of drug development, including in drug regulation,” Dr. Olivier noted.

He pointed to a recent study that found when hematology-oncology medical reviewers working at the FDA leave the agency, more than half end up working or consulting for the pharmaceutical industry.

Dr. Olivier wondered: “How can one fairly and independently appraise a medical intervention if one’s current or future revenue depends on its source?”

The study was funded by Arnold Ventures, through a grant paid to UCSF. Dr. Olivier and Dr. Haslam had no relevant disclosures. Dr. Prasad reported receiving royalties from Arnold Ventures.

A version of this article first appeared on Medscape.com.

More than half of studies testing anticancer drugs against each other have rules with regard to dose modification and growth support that favor the experimental drug arm, a new analysis suggests.

“We found it sobering that this practice is so common,” Timothée Olivier, MD, with Geneva University Hospital and the University of California, San Francisco, said in an interview.

Trials may be “rigged” in a way where the new therapy appears more effective than if the trial would have been designed with fairer rules, he explained.

This leaves open the question of whether new drugs are truly superior to older ones or if instead different outcomes are caused by more aggressive dosing or growth factor support, the investigators said.

Dr. Olivier, with UCSF coinvestigators Alyson Haslam, PhD, and Vinay Prasad, MD, reported their findings online in the European Journal of Cancer.

‘Highly concerning’

Different drug modification rules or growth factor support guidance may affect the results of randomized controlled trials (RCTs) of testing new cancer agents.

For their study, Dr. Olivier and colleagues did a cross-sectional analysis of all 62 head-to-head registration RCTs that led to Food and Drug Administration approval between 2009 and 2021.

All of the trials examined anticancer drugs in the advanced or metastatic setting where a comparison was made between arms regarding either dose modification rules or myeloid growth factors recommendations.

The researchers assessed imbalance in drug modification rules, myeloid growth factor recommendations, or both, according to prespecified rules.

They discovered that 40 of the 62 trials (65%) had unequal rules for dose medication, granulocyte colony-stimulating factor (G-CSF) use, or both.

Six trials (10%) had rules favoring the control arm, while 34 (55%) had rules favoring the experimental arm. Among these, 50% had unequal drug modification rules, 41% had unequal G-CSF rules, and 9% had both.

Dr. Olivier said in an interview the results are “highly concerning because when you are investigating the effect of a new drug, you don’t want to have a false sense of a drug’s effect because of other factors not directly related to the drug’s efficacy.”

“If you introduce unfair rules about dose modification or supporting medication that favors the new drug, then you don’t know if a positive trial is due to the effect of the new drug or to the effect of differential dosing or supporting medication,” he added.
 

Blame industry?

Dr. Olivier said the fact that most registration trials are industry-sponsored is likely the primary explanation of the findings.

“Industry-sponsored trials may be designed so that the new drug has the best chance to get the largest ‘win,’ because this means more market share and more profit for the company that manufactures the drug. This is not a criticism of the industry, which runs on a business model that naturally aims to gain more market share and more profit,” Dr. Olivier said.

“However, it is the role and duty of regulators to reconcile industry incentives with the patients’ best interests, and there is accumulating data showing the regulators are failing to do so,” he added.

Addressing this problem will likely take buy-in from multiple stakeholders.

Awareness of the problem is a first step and understanding the influence of commercial incentives in drug development is also key, Dr. Olivier said.

Institutional review boards and drug regulators could also systematically evaluate drug dosing modification and supportive medication rules before a trial gets underway.

Regulators could also incentivize companies to implement balanced rules between arms by not granting drug approval based on trials suffering from such flaws.

“However, financial conflict of interest is present at many levels of drug development, including in drug regulation,” Dr. Olivier noted.

He pointed to a recent study that found when hematology-oncology medical reviewers working at the FDA leave the agency, more than half end up working or consulting for the pharmaceutical industry.

Dr. Olivier wondered: “How can one fairly and independently appraise a medical intervention if one’s current or future revenue depends on its source?”

The study was funded by Arnold Ventures, through a grant paid to UCSF. Dr. Olivier and Dr. Haslam had no relevant disclosures. Dr. Prasad reported receiving royalties from Arnold Ventures.

A version of this article first appeared on Medscape.com.

More than half of studies testing anticancer drugs against each other have rules with regard to dose modification and growth support that favor the experimental drug arm, a new analysis suggests.

“We found it sobering that this practice is so common,” Timothée Olivier, MD, with Geneva University Hospital and the University of California, San Francisco, said in an interview.

Trials may be “rigged” in a way where the new therapy appears more effective than if the trial would have been designed with fairer rules, he explained.

This leaves open the question of whether new drugs are truly superior to older ones or if instead different outcomes are caused by more aggressive dosing or growth factor support, the investigators said.

Dr. Olivier, with UCSF coinvestigators Alyson Haslam, PhD, and Vinay Prasad, MD, reported their findings online in the European Journal of Cancer.

‘Highly concerning’

Different drug modification rules or growth factor support guidance may affect the results of randomized controlled trials (RCTs) of testing new cancer agents.

For their study, Dr. Olivier and colleagues did a cross-sectional analysis of all 62 head-to-head registration RCTs that led to Food and Drug Administration approval between 2009 and 2021.

All of the trials examined anticancer drugs in the advanced or metastatic setting where a comparison was made between arms regarding either dose modification rules or myeloid growth factors recommendations.

The researchers assessed imbalance in drug modification rules, myeloid growth factor recommendations, or both, according to prespecified rules.

They discovered that 40 of the 62 trials (65%) had unequal rules for dose medication, granulocyte colony-stimulating factor (G-CSF) use, or both.

Six trials (10%) had rules favoring the control arm, while 34 (55%) had rules favoring the experimental arm. Among these, 50% had unequal drug modification rules, 41% had unequal G-CSF rules, and 9% had both.

Dr. Olivier said in an interview the results are “highly concerning because when you are investigating the effect of a new drug, you don’t want to have a false sense of a drug’s effect because of other factors not directly related to the drug’s efficacy.”

“If you introduce unfair rules about dose modification or supporting medication that favors the new drug, then you don’t know if a positive trial is due to the effect of the new drug or to the effect of differential dosing or supporting medication,” he added.
 

Blame industry?

Dr. Olivier said the fact that most registration trials are industry-sponsored is likely the primary explanation of the findings.

“Industry-sponsored trials may be designed so that the new drug has the best chance to get the largest ‘win,’ because this means more market share and more profit for the company that manufactures the drug. This is not a criticism of the industry, which runs on a business model that naturally aims to gain more market share and more profit,” Dr. Olivier said.

“However, it is the role and duty of regulators to reconcile industry incentives with the patients’ best interests, and there is accumulating data showing the regulators are failing to do so,” he added.

Addressing this problem will likely take buy-in from multiple stakeholders.

Awareness of the problem is a first step and understanding the influence of commercial incentives in drug development is also key, Dr. Olivier said.

Institutional review boards and drug regulators could also systematically evaluate drug dosing modification and supportive medication rules before a trial gets underway.

Regulators could also incentivize companies to implement balanced rules between arms by not granting drug approval based on trials suffering from such flaws.

“However, financial conflict of interest is present at many levels of drug development, including in drug regulation,” Dr. Olivier noted.

He pointed to a recent study that found when hematology-oncology medical reviewers working at the FDA leave the agency, more than half end up working or consulting for the pharmaceutical industry.

Dr. Olivier wondered: “How can one fairly and independently appraise a medical intervention if one’s current or future revenue depends on its source?”

The study was funded by Arnold Ventures, through a grant paid to UCSF. Dr. Olivier and Dr. Haslam had no relevant disclosures. Dr. Prasad reported receiving royalties from Arnold Ventures.

A version of this article first appeared on Medscape.com.

Researchers from France have identified two distinct phenotypes of fulminant COVID-19–related myocarditis in adults, with different clinical presentations, immunologic profiles, and outcomes.

Differentiation between the two bioclinical entities is important to understand for patient management and further pathophysiological studies, they said.

The first phenotype occurs early (within a few days) in acute SARS-CoV-2 infection, with active viral replication (polymerase chain reaction positive) in adults who meet criteria for multisystem inflammatory syndrome (MIS-A+).

Floaria Bicher/iStock/Getty Images Plus

In this early phenotype, there is “limited systemic inflammation without skin and mucosal involvement, but myocardial dysfunction is fulminant and frequently associated with large pericardial effusions. These cases more often require extracorporeal membrane oxygenation [ECMO],” Guy Gorochov, MD, PhD, Sorbonne University, Paris, said in an interview.

The second is a delayed, postinfectious, immune-driven phenotype that occurs in adults who fail to meet the criteria for MIS-A (MIS-A–).

This phenotype occurs weeks after SARS-CoV-2 infection, usually beyond detectable active viral replication (PCR–) in the context of specific immune response and severe systemic inflammation with skin and mucosal involvement. Myocardial dysfunction is more progressive and rarely associated with large pericardial effusions, Dr. Gorochov explained.

The study was published in the Journal of the American College of Cardiology.
 

Evolving understanding

The findings are based on a retrospective analysis of 38 patients without a history of COVID-19 vaccination who were admitted to the intensive care unit from March 2020 to June 2021 for suspected fulminant COVID-19 myocarditis.

Patients were confirmed to have SARS-CoV-2 infection by PCR and/or by serologic testing. As noted in other studies, the patients were predominantly young men (66%; median age, 27.5 years). Twenty-five (66%) patients were MIS-A+ and 13 (34%) were MIS-A–.

In general, the MIS-A– patients were sicker and had worse outcomes.

Specifically, compared with the MIS-A+ patients, MIS-A– patients had a shorter time between the onset of COVID-19 symptoms and the development of myocarditis, a shorter time to ICU admission, and more severe presentations assessed using lower left ventricular ejection fraction and sequential organ failure assessment scores.

MIS-A– patients also had higher lactate levels, were more likely to need venoarterial ECMO (92% vs 16%), had higher ICU mortality (31% vs. 4%), and a had lower probability of survival at 3 months (68% vs. 96%), compared with their MIS-A+ peers.

Immunologic differences

The immunologic profiles of these two distinct clinical phenotypes also differed.

In MIS-A– early-type COVID-19 myocarditis, RNA polymerase III autoantibodies are frequently positive and serum levels of antiviral interferon-alpha and granulocyte-attracting interleukin-8 are elevated.

In contrast, in MIS-A+ delayed-type COVID-19 myocarditis, RNA polymerase III autoantibodies are negative and serum levels of IL-17 and IL-22 are highly elevated.

“We suggest that IL-17 and IL-22 are novel criteria that should help to assess in adults the recently recognized MIS-A,” Dr. Gorochov told this news organization. “It should be tested whether IL-17 and IL-22 are also elevated in children with MIS-C.”

The researchers also observed “extremely” high serum IL-10 levels in both patient groups. This has been previously associated with severe myocardial injury and an increase in the risk for death in severe COVID-19 patients.

The researchers said the phenotypic clustering of patients with fulminant COVID-19–related myocarditis “seems relevant” for their management.

MIS-A– cases, owing to the high risk for evolution toward refractory cardiogenic shock, should be “urgently” referred to a center with venoarterial ECMO and closely monitored to prevent a “too-late” cannulation, especially under cardiopulmonary resuscitation, known to be associated with poor outcomes, they advised.

They noted that the five patients who died in their series had late venoarterial ECMO implantation, while undergoing multiple organ failures or resuscitation.

Conversely, the risk for evolution to refractory cardiogenic shock is lower in MIS-A+ cases. However, identifying MIS-A+ cases is “all the more important given that numerous data support the efficacy of corticosteroids and/or intravenous immunoglobulins in MIS-C,” Dr. Gorochov and colleagues wrote.

The authors of a linked editorial said the French team should be “commended on their work in furthering our understanding of fulminant myocarditis related to COVID-19 infection.”

Ajith Nair, MD, Baylor College of Medicine, and Anita Deswal, MD, MPH, University of Texas M.D. Anderson Cancer Center, both in Houston, noted that fulminant myocarditis is rare and can result from either of two mechanisms: viral tropism or an immune-mediated mechanism.

“It remains to be seen whether using antiviral therapy versus immunomodulatory therapy on the basis of clinical and cytokine profiles will yield benefits,” they wrote.

“Fulminant myocarditis invariably requires hemodynamic support and carries a high mortality risk if it is recognized late. However, the long-term prognosis in patients who survive the critical period is favorable, with recovery of myocardial function,” they added.

“This study highlights the ever-shifting understanding of the pathophysiology and therapeutic approaches to fulminant myocarditis,” Dr. Nair and Dr. Deswal concluded.

This research was supported in part by the Foundation of France, French National Research Agency, Sorbonne University, and Clinical Research Hospital. The researchers have filed a patent application based on these results. Dr. Nair and Dr. Deswal have no relevant disclosures.

A version of this article first appeared on Medscape.com.

Researchers from France have identified two distinct phenotypes of fulminant COVID-19–related myocarditis in adults, with different clinical presentations, immunologic profiles, and outcomes.

Differentiation between the two bioclinical entities is important to understand for patient management and further pathophysiological studies, they said.

The first phenotype occurs early (within a few days) in acute SARS-CoV-2 infection, with active viral replication (polymerase chain reaction positive) in adults who meet criteria for multisystem inflammatory syndrome (MIS-A+).

Floaria Bicher/iStock/Getty Images Plus

In this early phenotype, there is “limited systemic inflammation without skin and mucosal involvement, but myocardial dysfunction is fulminant and frequently associated with large pericardial effusions. These cases more often require extracorporeal membrane oxygenation [ECMO],” Guy Gorochov, MD, PhD, Sorbonne University, Paris, said in an interview.

The second is a delayed, postinfectious, immune-driven phenotype that occurs in adults who fail to meet the criteria for MIS-A (MIS-A–).

This phenotype occurs weeks after SARS-CoV-2 infection, usually beyond detectable active viral replication (PCR–) in the context of specific immune response and severe systemic inflammation with skin and mucosal involvement. Myocardial dysfunction is more progressive and rarely associated with large pericardial effusions, Dr. Gorochov explained.

The study was published in the Journal of the American College of Cardiology.
 

Evolving understanding

The findings are based on a retrospective analysis of 38 patients without a history of COVID-19 vaccination who were admitted to the intensive care unit from March 2020 to June 2021 for suspected fulminant COVID-19 myocarditis.

Patients were confirmed to have SARS-CoV-2 infection by PCR and/or by serologic testing. As noted in other studies, the patients were predominantly young men (66%; median age, 27.5 years). Twenty-five (66%) patients were MIS-A+ and 13 (34%) were MIS-A–.

In general, the MIS-A– patients were sicker and had worse outcomes.

Specifically, compared with the MIS-A+ patients, MIS-A– patients had a shorter time between the onset of COVID-19 symptoms and the development of myocarditis, a shorter time to ICU admission, and more severe presentations assessed using lower left ventricular ejection fraction and sequential organ failure assessment scores.

MIS-A– patients also had higher lactate levels, were more likely to need venoarterial ECMO (92% vs 16%), had higher ICU mortality (31% vs. 4%), and a had lower probability of survival at 3 months (68% vs. 96%), compared with their MIS-A+ peers.

Immunologic differences

The immunologic profiles of these two distinct clinical phenotypes also differed.

In MIS-A– early-type COVID-19 myocarditis, RNA polymerase III autoantibodies are frequently positive and serum levels of antiviral interferon-alpha and granulocyte-attracting interleukin-8 are elevated.

In contrast, in MIS-A+ delayed-type COVID-19 myocarditis, RNA polymerase III autoantibodies are negative and serum levels of IL-17 and IL-22 are highly elevated.

“We suggest that IL-17 and IL-22 are novel criteria that should help to assess in adults the recently recognized MIS-A,” Dr. Gorochov told this news organization. “It should be tested whether IL-17 and IL-22 are also elevated in children with MIS-C.”

The researchers also observed “extremely” high serum IL-10 levels in both patient groups. This has been previously associated with severe myocardial injury and an increase in the risk for death in severe COVID-19 patients.

The researchers said the phenotypic clustering of patients with fulminant COVID-19–related myocarditis “seems relevant” for their management.

MIS-A– cases, owing to the high risk for evolution toward refractory cardiogenic shock, should be “urgently” referred to a center with venoarterial ECMO and closely monitored to prevent a “too-late” cannulation, especially under cardiopulmonary resuscitation, known to be associated with poor outcomes, they advised.

They noted that the five patients who died in their series had late venoarterial ECMO implantation, while undergoing multiple organ failures or resuscitation.

Conversely, the risk for evolution to refractory cardiogenic shock is lower in MIS-A+ cases. However, identifying MIS-A+ cases is “all the more important given that numerous data support the efficacy of corticosteroids and/or intravenous immunoglobulins in MIS-C,” Dr. Gorochov and colleagues wrote.

The authors of a linked editorial said the French team should be “commended on their work in furthering our understanding of fulminant myocarditis related to COVID-19 infection.”

Ajith Nair, MD, Baylor College of Medicine, and Anita Deswal, MD, MPH, University of Texas M.D. Anderson Cancer Center, both in Houston, noted that fulminant myocarditis is rare and can result from either of two mechanisms: viral tropism or an immune-mediated mechanism.

“It remains to be seen whether using antiviral therapy versus immunomodulatory therapy on the basis of clinical and cytokine profiles will yield benefits,” they wrote.

“Fulminant myocarditis invariably requires hemodynamic support and carries a high mortality risk if it is recognized late. However, the long-term prognosis in patients who survive the critical period is favorable, with recovery of myocardial function,” they added.

“This study highlights the ever-shifting understanding of the pathophysiology and therapeutic approaches to fulminant myocarditis,” Dr. Nair and Dr. Deswal concluded.

This research was supported in part by the Foundation of France, French National Research Agency, Sorbonne University, and Clinical Research Hospital. The researchers have filed a patent application based on these results. Dr. Nair and Dr. Deswal have no relevant disclosures.

A version of this article first appeared on Medscape.com.

Researchers from France have identified two distinct phenotypes of fulminant COVID-19–related myocarditis in adults, with different clinical presentations, immunologic profiles, and outcomes.

Differentiation between the two bioclinical entities is important to understand for patient management and further pathophysiological studies, they said.

The first phenotype occurs early (within a few days) in acute SARS-CoV-2 infection, with active viral replication (polymerase chain reaction positive) in adults who meet criteria for multisystem inflammatory syndrome (MIS-A+).

Floaria Bicher/iStock/Getty Images Plus

In this early phenotype, there is “limited systemic inflammation without skin and mucosal involvement, but myocardial dysfunction is fulminant and frequently associated with large pericardial effusions. These cases more often require extracorporeal membrane oxygenation [ECMO],” Guy Gorochov, MD, PhD, Sorbonne University, Paris, said in an interview.

The second is a delayed, postinfectious, immune-driven phenotype that occurs in adults who fail to meet the criteria for MIS-A (MIS-A–).

This phenotype occurs weeks after SARS-CoV-2 infection, usually beyond detectable active viral replication (PCR–) in the context of specific immune response and severe systemic inflammation with skin and mucosal involvement. Myocardial dysfunction is more progressive and rarely associated with large pericardial effusions, Dr. Gorochov explained.

The study was published in the Journal of the American College of Cardiology.
 

Evolving understanding

The findings are based on a retrospective analysis of 38 patients without a history of COVID-19 vaccination who were admitted to the intensive care unit from March 2020 to June 2021 for suspected fulminant COVID-19 myocarditis.

Patients were confirmed to have SARS-CoV-2 infection by PCR and/or by serologic testing. As noted in other studies, the patients were predominantly young men (66%; median age, 27.5 years). Twenty-five (66%) patients were MIS-A+ and 13 (34%) were MIS-A–.

In general, the MIS-A– patients were sicker and had worse outcomes.

Specifically, compared with the MIS-A+ patients, MIS-A– patients had a shorter time between the onset of COVID-19 symptoms and the development of myocarditis, a shorter time to ICU admission, and more severe presentations assessed using lower left ventricular ejection fraction and sequential organ failure assessment scores.

MIS-A– patients also had higher lactate levels, were more likely to need venoarterial ECMO (92% vs 16%), had higher ICU mortality (31% vs. 4%), and a had lower probability of survival at 3 months (68% vs. 96%), compared with their MIS-A+ peers.

Immunologic differences

The immunologic profiles of these two distinct clinical phenotypes also differed.

In MIS-A– early-type COVID-19 myocarditis, RNA polymerase III autoantibodies are frequently positive and serum levels of antiviral interferon-alpha and granulocyte-attracting interleukin-8 are elevated.

In contrast, in MIS-A+ delayed-type COVID-19 myocarditis, RNA polymerase III autoantibodies are negative and serum levels of IL-17 and IL-22 are highly elevated.

“We suggest that IL-17 and IL-22 are novel criteria that should help to assess in adults the recently recognized MIS-A,” Dr. Gorochov told this news organization. “It should be tested whether IL-17 and IL-22 are also elevated in children with MIS-C.”

The researchers also observed “extremely” high serum IL-10 levels in both patient groups. This has been previously associated with severe myocardial injury and an increase in the risk for death in severe COVID-19 patients.

The researchers said the phenotypic clustering of patients with fulminant COVID-19–related myocarditis “seems relevant” for their management.

MIS-A– cases, owing to the high risk for evolution toward refractory cardiogenic shock, should be “urgently” referred to a center with venoarterial ECMO and closely monitored to prevent a “too-late” cannulation, especially under cardiopulmonary resuscitation, known to be associated with poor outcomes, they advised.

They noted that the five patients who died in their series had late venoarterial ECMO implantation, while undergoing multiple organ failures or resuscitation.

Conversely, the risk for evolution to refractory cardiogenic shock is lower in MIS-A+ cases. However, identifying MIS-A+ cases is “all the more important given that numerous data support the efficacy of corticosteroids and/or intravenous immunoglobulins in MIS-C,” Dr. Gorochov and colleagues wrote.

The authors of a linked editorial said the French team should be “commended on their work in furthering our understanding of fulminant myocarditis related to COVID-19 infection.”

Ajith Nair, MD, Baylor College of Medicine, and Anita Deswal, MD, MPH, University of Texas M.D. Anderson Cancer Center, both in Houston, noted that fulminant myocarditis is rare and can result from either of two mechanisms: viral tropism or an immune-mediated mechanism.

“It remains to be seen whether using antiviral therapy versus immunomodulatory therapy on the basis of clinical and cytokine profiles will yield benefits,” they wrote.

“Fulminant myocarditis invariably requires hemodynamic support and carries a high mortality risk if it is recognized late. However, the long-term prognosis in patients who survive the critical period is favorable, with recovery of myocardial function,” they added.

“This study highlights the ever-shifting understanding of the pathophysiology and therapeutic approaches to fulminant myocarditis,” Dr. Nair and Dr. Deswal concluded.

This research was supported in part by the Foundation of France, French National Research Agency, Sorbonne University, and Clinical Research Hospital. The researchers have filed a patent application based on these results. Dr. Nair and Dr. Deswal have no relevant disclosures.

A version of this article first appeared on Medscape.com.

Emma Sherman, a 13-year-old girl in Ascot, England, woke up to a dizzying aura of blind spots and flashing lights in her field of vision. It was May 2020, and she also had crippling nausea and headaches. By August, her dizziness was so overwhelming, she couldn’t hold her head up, lying in her mother’s lap for hours, too fatigued to attend school.

The former competitive gymnast, who had hoped to try out for the cheerleading squad, now used a wheelchair and was a shadow of her former self. She had been diagnosed with COVID-induced postural orthostatic tachycardia syndrome, a condition often caused by an infection that results in a higher heart rate, extreme nausea, dizziness, and fatigue.

“I was so into sports before I got long COVID, and afterwards I could barely walk,” Emma said.

Even minor movements sent her heart rate sky-high. Her long chestnut hair turned gray and fell out in clumps. In the hospital, she was pricked and prodded, her blood tested for numerous conditions.

“They ran every scan known to man and took an MRI of her brain,” said Emma’s mother, Marie Sherman. “All was clear.”

Emma’s pediatrician determined that the teen had long COVID after having had a mild case of the virus in March, about 2 months before her puzzling symptoms began. But beyond a positive antibody test, doctors have found little evidence of what was causing Emma’s symptoms.

For Emma and others with long COVID, there are no medications shown to directly target the condition. Instead, caregivers target their symptoms, which include nausea, dizziness, fatigue, headaches, and a racing heart, said Laura Malone, MD, codirector of the Johns Hopkins Kennedy Krieger Pediatric Post–COVID-19 Rehabilitation Clinic in Baltimore.

“Right now, it’s a rehabilitation-based approach focused on improving symptoms and functioning so that kids can go back to their usual activities as much as possible,” she says.

Depression and anxiety are common, although doctors are struggling to figure out whether COVID is changing the brain or whether mental health symptoms result from all the life disruptions. There’s little research to show how may kids have depression because of long COVID. Dr. Malone said about half of her patients at the Kennedy Krieger Institute›s long COVID clinic are also dealing with mental health issues.

Patients with headaches, dizziness, and nausea are given pain and nausea medications and recommendations for a healthy diet with added fruits and vegetables, monounsaturated fats, lower sodium, unprocessed foods, and whole grains. Kids with irregular or racing heart rates are referred to cardiologists and potentially prescribed beta-blockers to treat their heart arrhythmias, while children with breathing problems may be referred to pulmonologists and those with depression to a psychiatrist.

Still, many patients like Emma go to their doctors with phantom symptoms that don’t show up on scans or blood tests.

“We’re not seeing any evidence of structural damage to the brain, for example,” said Dr. Malone. “When we do MRIs, they often come out normal.”

It’s possible that the virus lingers in some patients, said Rajeev Fernando, MD, an infectious disease specialist and a fellow at Harvard Medical School, Boston. Kids’ strong immune systems often fend off problems that can be noticed. But on the inside, dead fragments of the virus persist, floating in hidden parts of the body and activating the immune system long after the threat has passed.

The virus can be in the gut and in the brain, which may help explain why symptoms like brain fog and nausea can linger in children.

“The immune system doesn’t recognize whether fragments of the virus are dead or alive. It continues to think it’s fighting active COVID,” said Dr. Fernando.

There is little data on how long symptoms last, Dr. Fernando said, as well as how many kids get them and why some are more vulnerable than others. Some research has found that about 5%-15% of children with COVID may get long COVID, but the statistics vary globally.

“Children with long COVID have largely been ignored. And while we’re talking about it now, we’ve got some work to do,” said Dr. Fernando.

As for Emma, she recovered in January of 2021, heading back to school and her friends, although her cardiologist advised her to skip gym classes.

“For the first time in months, I was feeling like myself again,” she said.

But the coronavirus found its way to Emma again. Although she was fully vaccinated in the fall of 2021, when the Omicron variant swept the world late that year, she was infected again.

“When the wave of Omicron descended, Emma was like a sitting duck,” her mother said.

She was bedridden with a high fever and cough. The cold-like symptoms eventually went away, but the issues in her gut stuck around. Since then, Emma has had extreme nausea, losing most of the weight she had gained back.

For her part, Ms. Sherman has found solace in a group called Long COVID Kids, a nonprofit in Europe and the United States. The group is raising awareness about the condition in kids to increase funding, boost understanding, and improve treatment and outcomes.

“There’s nothing worse than watching your child suffer and not being able to do anything about it,” she said. “I tell Emma all the time: If I could just crawl in your body and take it, I would do it in a second.”

Emma is hoping for a fresh start with her family’s move in the coming weeks to Sotogrande in southern Spain.

“I miss the simplest things like going for a run, going to the fair with my friends, and just feeling well,” she said. “I have a long list of things I’ll do once this is all done.”

A version of this article first appeared on WebMD.com.

Emma Sherman, a 13-year-old girl in Ascot, England, woke up to a dizzying aura of blind spots and flashing lights in her field of vision. It was May 2020, and she also had crippling nausea and headaches. By August, her dizziness was so overwhelming, she couldn’t hold her head up, lying in her mother’s lap for hours, too fatigued to attend school.

The former competitive gymnast, who had hoped to try out for the cheerleading squad, now used a wheelchair and was a shadow of her former self. She had been diagnosed with COVID-induced postural orthostatic tachycardia syndrome, a condition often caused by an infection that results in a higher heart rate, extreme nausea, dizziness, and fatigue.

“I was so into sports before I got long COVID, and afterwards I could barely walk,” Emma said.

Even minor movements sent her heart rate sky-high. Her long chestnut hair turned gray and fell out in clumps. In the hospital, she was pricked and prodded, her blood tested for numerous conditions.

“They ran every scan known to man and took an MRI of her brain,” said Emma’s mother, Marie Sherman. “All was clear.”

Emma’s pediatrician determined that the teen had long COVID after having had a mild case of the virus in March, about 2 months before her puzzling symptoms began. But beyond a positive antibody test, doctors have found little evidence of what was causing Emma’s symptoms.

For Emma and others with long COVID, there are no medications shown to directly target the condition. Instead, caregivers target their symptoms, which include nausea, dizziness, fatigue, headaches, and a racing heart, said Laura Malone, MD, codirector of the Johns Hopkins Kennedy Krieger Pediatric Post–COVID-19 Rehabilitation Clinic in Baltimore.

“Right now, it’s a rehabilitation-based approach focused on improving symptoms and functioning so that kids can go back to their usual activities as much as possible,” she says.

Depression and anxiety are common, although doctors are struggling to figure out whether COVID is changing the brain or whether mental health symptoms result from all the life disruptions. There’s little research to show how may kids have depression because of long COVID. Dr. Malone said about half of her patients at the Kennedy Krieger Institute›s long COVID clinic are also dealing with mental health issues.

Patients with headaches, dizziness, and nausea are given pain and nausea medications and recommendations for a healthy diet with added fruits and vegetables, monounsaturated fats, lower sodium, unprocessed foods, and whole grains. Kids with irregular or racing heart rates are referred to cardiologists and potentially prescribed beta-blockers to treat their heart arrhythmias, while children with breathing problems may be referred to pulmonologists and those with depression to a psychiatrist.

Still, many patients like Emma go to their doctors with phantom symptoms that don’t show up on scans or blood tests.

“We’re not seeing any evidence of structural damage to the brain, for example,” said Dr. Malone. “When we do MRIs, they often come out normal.”

It’s possible that the virus lingers in some patients, said Rajeev Fernando, MD, an infectious disease specialist and a fellow at Harvard Medical School, Boston. Kids’ strong immune systems often fend off problems that can be noticed. But on the inside, dead fragments of the virus persist, floating in hidden parts of the body and activating the immune system long after the threat has passed.

The virus can be in the gut and in the brain, which may help explain why symptoms like brain fog and nausea can linger in children.

“The immune system doesn’t recognize whether fragments of the virus are dead or alive. It continues to think it’s fighting active COVID,” said Dr. Fernando.

There is little data on how long symptoms last, Dr. Fernando said, as well as how many kids get them and why some are more vulnerable than others. Some research has found that about 5%-15% of children with COVID may get long COVID, but the statistics vary globally.

“Children with long COVID have largely been ignored. And while we’re talking about it now, we’ve got some work to do,” said Dr. Fernando.

As for Emma, she recovered in January of 2021, heading back to school and her friends, although her cardiologist advised her to skip gym classes.

“For the first time in months, I was feeling like myself again,” she said.

But the coronavirus found its way to Emma again. Although she was fully vaccinated in the fall of 2021, when the Omicron variant swept the world late that year, she was infected again.

“When the wave of Omicron descended, Emma was like a sitting duck,” her mother said.

She was bedridden with a high fever and cough. The cold-like symptoms eventually went away, but the issues in her gut stuck around. Since then, Emma has had extreme nausea, losing most of the weight she had gained back.

For her part, Ms. Sherman has found solace in a group called Long COVID Kids, a nonprofit in Europe and the United States. The group is raising awareness about the condition in kids to increase funding, boost understanding, and improve treatment and outcomes.

“There’s nothing worse than watching your child suffer and not being able to do anything about it,” she said. “I tell Emma all the time: If I could just crawl in your body and take it, I would do it in a second.”

Emma is hoping for a fresh start with her family’s move in the coming weeks to Sotogrande in southern Spain.

“I miss the simplest things like going for a run, going to the fair with my friends, and just feeling well,” she said. “I have a long list of things I’ll do once this is all done.”

A version of this article first appeared on WebMD.com.

Emma Sherman, a 13-year-old girl in Ascot, England, woke up to a dizzying aura of blind spots and flashing lights in her field of vision. It was May 2020, and she also had crippling nausea and headaches. By August, her dizziness was so overwhelming, she couldn’t hold her head up, lying in her mother’s lap for hours, too fatigued to attend school.

The former competitive gymnast, who had hoped to try out for the cheerleading squad, now used a wheelchair and was a shadow of her former self. She had been diagnosed with COVID-induced postural orthostatic tachycardia syndrome, a condition often caused by an infection that results in a higher heart rate, extreme nausea, dizziness, and fatigue.

“I was so into sports before I got long COVID, and afterwards I could barely walk,” Emma said.

Even minor movements sent her heart rate sky-high. Her long chestnut hair turned gray and fell out in clumps. In the hospital, she was pricked and prodded, her blood tested for numerous conditions.

“They ran every scan known to man and took an MRI of her brain,” said Emma’s mother, Marie Sherman. “All was clear.”

Emma’s pediatrician determined that the teen had long COVID after having had a mild case of the virus in March, about 2 months before her puzzling symptoms began. But beyond a positive antibody test, doctors have found little evidence of what was causing Emma’s symptoms.

For Emma and others with long COVID, there are no medications shown to directly target the condition. Instead, caregivers target their symptoms, which include nausea, dizziness, fatigue, headaches, and a racing heart, said Laura Malone, MD, codirector of the Johns Hopkins Kennedy Krieger Pediatric Post–COVID-19 Rehabilitation Clinic in Baltimore.

“Right now, it’s a rehabilitation-based approach focused on improving symptoms and functioning so that kids can go back to their usual activities as much as possible,” she says.

Depression and anxiety are common, although doctors are struggling to figure out whether COVID is changing the brain or whether mental health symptoms result from all the life disruptions. There’s little research to show how may kids have depression because of long COVID. Dr. Malone said about half of her patients at the Kennedy Krieger Institute›s long COVID clinic are also dealing with mental health issues.

Patients with headaches, dizziness, and nausea are given pain and nausea medications and recommendations for a healthy diet with added fruits and vegetables, monounsaturated fats, lower sodium, unprocessed foods, and whole grains. Kids with irregular or racing heart rates are referred to cardiologists and potentially prescribed beta-blockers to treat their heart arrhythmias, while children with breathing problems may be referred to pulmonologists and those with depression to a psychiatrist.

Still, many patients like Emma go to their doctors with phantom symptoms that don’t show up on scans or blood tests.

“We’re not seeing any evidence of structural damage to the brain, for example,” said Dr. Malone. “When we do MRIs, they often come out normal.”

It’s possible that the virus lingers in some patients, said Rajeev Fernando, MD, an infectious disease specialist and a fellow at Harvard Medical School, Boston. Kids’ strong immune systems often fend off problems that can be noticed. But on the inside, dead fragments of the virus persist, floating in hidden parts of the body and activating the immune system long after the threat has passed.

The virus can be in the gut and in the brain, which may help explain why symptoms like brain fog and nausea can linger in children.

“The immune system doesn’t recognize whether fragments of the virus are dead or alive. It continues to think it’s fighting active COVID,” said Dr. Fernando.

There is little data on how long symptoms last, Dr. Fernando said, as well as how many kids get them and why some are more vulnerable than others. Some research has found that about 5%-15% of children with COVID may get long COVID, but the statistics vary globally.

“Children with long COVID have largely been ignored. And while we’re talking about it now, we’ve got some work to do,” said Dr. Fernando.

As for Emma, she recovered in January of 2021, heading back to school and her friends, although her cardiologist advised her to skip gym classes.

“For the first time in months, I was feeling like myself again,” she said.

But the coronavirus found its way to Emma again. Although she was fully vaccinated in the fall of 2021, when the Omicron variant swept the world late that year, she was infected again.

“When the wave of Omicron descended, Emma was like a sitting duck,” her mother said.

She was bedridden with a high fever and cough. The cold-like symptoms eventually went away, but the issues in her gut stuck around. Since then, Emma has had extreme nausea, losing most of the weight she had gained back.

For her part, Ms. Sherman has found solace in a group called Long COVID Kids, a nonprofit in Europe and the United States. The group is raising awareness about the condition in kids to increase funding, boost understanding, and improve treatment and outcomes.

“There’s nothing worse than watching your child suffer and not being able to do anything about it,” she said. “I tell Emma all the time: If I could just crawl in your body and take it, I would do it in a second.”

Emma is hoping for a fresh start with her family’s move in the coming weeks to Sotogrande in southern Spain.

“I miss the simplest things like going for a run, going to the fair with my friends, and just feeling well,” she said. “I have a long list of things I’ll do once this is all done.”

A version of this article first appeared on WebMD.com.

INDIANAPOLIS – An investigational topical treatment for dystrophic epidermolysis bullosa (DEB) known as beremagene geperpavec (B-VEC) showed durable and statistically significant improvement in complete wound healing at 3 and 6 months compared with placebo, according to results from a small phase 3 study.

DEB is a serious, ultra-rare genetic blistering disease caused by mutations in the COL7A1 gene, encoding for type VII collagen and leading to skin fragility and wounds. No approved therapies are currently available. In the study, treatment was generally well tolerated.

Doug Brunk/MDedge News

“B-VEC is the first treatment that has not only been shown to be effective, but the first to directly target the defect through topical application,” the study’s principal investigator, Shireen V. Guide, MD, said in an interview during a poster session at the annual meeting of the Society for Pediatric Dermatology. “It delivers type VII collagen gene therapy to these patients, which allows healing in areas that they may have had open since birth. It’s been life-changing for them.”

B-VEC is a herpes simplex virus (HSV-1)-based topical, redosable gene therapy being developed by Krystal Biotech that is designed to restore functional COL7 protein by delivering the COL7A1 gene. For the phase 3, multicenter, double-blind, placebo-controlled study known GEM-3, Dr. Guide, who practices dermatology in Rancho Santa Margarita, Calif., and her colleagues, including Peter Marinkovich, MD, from Stanford (Calif.) University, and Mercedes Gonzalez, MD, from the University of Miami, enrolled 31 patients aged 6 months and older with genetically confirmed DEB. Each patient had one wound treated randomized 1:1 to treatment with B-VEC once a week or placebo for 6 months. The mean age of the 31 study participants was 17 years, 65% were male, 65% were White, and 19% were Asian.

The primary endpoint was complete wound healing (defined as 100% wound closure from exact wound area at baseline, specified as skin re-epithelialization without drainage) at 6 months. Additional endpoints included complete wound healing at 3 months and change in pain associated with wound dressing changes.

At 3 months, 70% of wounds treated with B-VEC met the endpoint of complete wound healing, compared with 20% of wounds treated with placebo (P < .005). At 6 months, 67% of wounds treated with B-VEC met the endpoint of complete wound healing compared with 22% of those treated with placebo (P < .005).

Of the total wounds that closed at 3 months, 67% of wounds treated with B-VEC were also closed at 6 months, compared with 33% of those treated with placebo (P = .02). In other findings, a trend toward decreased pain was observed in wounds treated with B-VEC vs. those treated with placebo.

B-VEC was well tolerated with no treatment-related serious adverse events or discontinuations. Three patients experienced a total of five serious adverse events during the study: anemia (two events), and cellulitis, diarrhea, and positive blood culture (one event each). None were considered related to the study drug.

Dr. Guide, who is on staff at Children’s Health of Orange County, Orange, Calif., characterized B-VEC as “very novel because it’s very practical.”

To date, all treatments for DEB “have been extremely labor intensive, including skin grafting and hospitalizations. It’s a topical application that can be done in the office and potentially applied at home in the future. It’s also durable. Not only are the [treated] areas closing, but they are staying closed.”

Kalyani S. Marathe, MD, MPH, director of the dermatology division at Cincinnati Children’s Hospital, who was asked to comment on the study, said that topical application of B-VEC “allows the side effect profile to be very favorable. The results are remarkable in the amount of wound healing and reduction in pain.”

The tolerability of this medication “is crucial,” she added. “EB patients have a lot of pain from their wounds and so any treatment needs to be as painless as possible for it to be usable. I’m very excited about the next phase of studies for this medication and hopeful that it heralds new treatments for our EB patients.”

In June 2022, the manufacturer announced that it had submitted a biologics license application to the Food and Drug Administration for approval of B-VEC for the treatment of DEB, and that it anticipates submitting an application for marketing authorization with the European Medical Agency (EMA) in the second half of 2022.

Dr. Guide disclosed that she has served as an investigator for Krystal Biotech, Innovaderm Research, Arcutis, Premier Research, Paidion, and Castle Biosciences. Dr. Marathe disclosed that she has served as an adviser for Verrica, and that Cincinnati Children’s Hospital is a site for the next phase studies for B-VEC.

*This story was updated on July 25. 

INDIANAPOLIS – An investigational topical treatment for dystrophic epidermolysis bullosa (DEB) known as beremagene geperpavec (B-VEC) showed durable and statistically significant improvement in complete wound healing at 3 and 6 months compared with placebo, according to results from a small phase 3 study.

DEB is a serious, ultra-rare genetic blistering disease caused by mutations in the COL7A1 gene, encoding for type VII collagen and leading to skin fragility and wounds. No approved therapies are currently available. In the study, treatment was generally well tolerated.

Doug Brunk/MDedge News

“B-VEC is the first treatment that has not only been shown to be effective, but the first to directly target the defect through topical application,” the study’s principal investigator, Shireen V. Guide, MD, said in an interview during a poster session at the annual meeting of the Society for Pediatric Dermatology. “It delivers type VII collagen gene therapy to these patients, which allows healing in areas that they may have had open since birth. It’s been life-changing for them.”

B-VEC is a herpes simplex virus (HSV-1)-based topical, redosable gene therapy being developed by Krystal Biotech that is designed to restore functional COL7 protein by delivering the COL7A1 gene. For the phase 3, multicenter, double-blind, placebo-controlled study known GEM-3, Dr. Guide, who practices dermatology in Rancho Santa Margarita, Calif., and her colleagues, including Peter Marinkovich, MD, from Stanford (Calif.) University, and Mercedes Gonzalez, MD, from the University of Miami, enrolled 31 patients aged 6 months and older with genetically confirmed DEB. Each patient had one wound treated randomized 1:1 to treatment with B-VEC once a week or placebo for 6 months. The mean age of the 31 study participants was 17 years, 65% were male, 65% were White, and 19% were Asian.

The primary endpoint was complete wound healing (defined as 100% wound closure from exact wound area at baseline, specified as skin re-epithelialization without drainage) at 6 months. Additional endpoints included complete wound healing at 3 months and change in pain associated with wound dressing changes.

At 3 months, 70% of wounds treated with B-VEC met the endpoint of complete wound healing, compared with 20% of wounds treated with placebo (P < .005). At 6 months, 67% of wounds treated with B-VEC met the endpoint of complete wound healing compared with 22% of those treated with placebo (P < .005).

Of the total wounds that closed at 3 months, 67% of wounds treated with B-VEC were also closed at 6 months, compared with 33% of those treated with placebo (P = .02). In other findings, a trend toward decreased pain was observed in wounds treated with B-VEC vs. those treated with placebo.

B-VEC was well tolerated with no treatment-related serious adverse events or discontinuations. Three patients experienced a total of five serious adverse events during the study: anemia (two events), and cellulitis, diarrhea, and positive blood culture (one event each). None were considered related to the study drug.

Dr. Guide, who is on staff at Children’s Health of Orange County, Orange, Calif., characterized B-VEC as “very novel because it’s very practical.”

To date, all treatments for DEB “have been extremely labor intensive, including skin grafting and hospitalizations. It’s a topical application that can be done in the office and potentially applied at home in the future. It’s also durable. Not only are the [treated] areas closing, but they are staying closed.”

Kalyani S. Marathe, MD, MPH, director of the dermatology division at Cincinnati Children’s Hospital, who was asked to comment on the study, said that topical application of B-VEC “allows the side effect profile to be very favorable. The results are remarkable in the amount of wound healing and reduction in pain.”

The tolerability of this medication “is crucial,” she added. “EB patients have a lot of pain from their wounds and so any treatment needs to be as painless as possible for it to be usable. I’m very excited about the next phase of studies for this medication and hopeful that it heralds new treatments for our EB patients.”

In June 2022, the manufacturer announced that it had submitted a biologics license application to the Food and Drug Administration for approval of B-VEC for the treatment of DEB, and that it anticipates submitting an application for marketing authorization with the European Medical Agency (EMA) in the second half of 2022.

Dr. Guide disclosed that she has served as an investigator for Krystal Biotech, Innovaderm Research, Arcutis, Premier Research, Paidion, and Castle Biosciences. Dr. Marathe disclosed that she has served as an adviser for Verrica, and that Cincinnati Children’s Hospital is a site for the next phase studies for B-VEC.

*This story was updated on July 25. 

INDIANAPOLIS – An investigational topical treatment for dystrophic epidermolysis bullosa (DEB) known as beremagene geperpavec (B-VEC) showed durable and statistically significant improvement in complete wound healing at 3 and 6 months compared with placebo, according to results from a small phase 3 study.

DEB is a serious, ultra-rare genetic blistering disease caused by mutations in the COL7A1 gene, encoding for type VII collagen and leading to skin fragility and wounds. No approved therapies are currently available. In the study, treatment was generally well tolerated.

Doug Brunk/MDedge News

“B-VEC is the first treatment that has not only been shown to be effective, but the first to directly target the defect through topical application,” the study’s principal investigator, Shireen V. Guide, MD, said in an interview during a poster session at the annual meeting of the Society for Pediatric Dermatology. “It delivers type VII collagen gene therapy to these patients, which allows healing in areas that they may have had open since birth. It’s been life-changing for them.”

B-VEC is a herpes simplex virus (HSV-1)-based topical, redosable gene therapy being developed by Krystal Biotech that is designed to restore functional COL7 protein by delivering the COL7A1 gene. For the phase 3, multicenter, double-blind, placebo-controlled study known GEM-3, Dr. Guide, who practices dermatology in Rancho Santa Margarita, Calif., and her colleagues, including Peter Marinkovich, MD, from Stanford (Calif.) University, and Mercedes Gonzalez, MD, from the University of Miami, enrolled 31 patients aged 6 months and older with genetically confirmed DEB. Each patient had one wound treated randomized 1:1 to treatment with B-VEC once a week or placebo for 6 months. The mean age of the 31 study participants was 17 years, 65% were male, 65% were White, and 19% were Asian.

The primary endpoint was complete wound healing (defined as 100% wound closure from exact wound area at baseline, specified as skin re-epithelialization without drainage) at 6 months. Additional endpoints included complete wound healing at 3 months and change in pain associated with wound dressing changes.

At 3 months, 70% of wounds treated with B-VEC met the endpoint of complete wound healing, compared with 20% of wounds treated with placebo (P < .005). At 6 months, 67% of wounds treated with B-VEC met the endpoint of complete wound healing compared with 22% of those treated with placebo (P < .005).

Of the total wounds that closed at 3 months, 67% of wounds treated with B-VEC were also closed at 6 months, compared with 33% of those treated with placebo (P = .02). In other findings, a trend toward decreased pain was observed in wounds treated with B-VEC vs. those treated with placebo.

B-VEC was well tolerated with no treatment-related serious adverse events or discontinuations. Three patients experienced a total of five serious adverse events during the study: anemia (two events), and cellulitis, diarrhea, and positive blood culture (one event each). None were considered related to the study drug.

Dr. Guide, who is on staff at Children’s Health of Orange County, Orange, Calif., characterized B-VEC as “very novel because it’s very practical.”

To date, all treatments for DEB “have been extremely labor intensive, including skin grafting and hospitalizations. It’s a topical application that can be done in the office and potentially applied at home in the future. It’s also durable. Not only are the [treated] areas closing, but they are staying closed.”

Kalyani S. Marathe, MD, MPH, director of the dermatology division at Cincinnati Children’s Hospital, who was asked to comment on the study, said that topical application of B-VEC “allows the side effect profile to be very favorable. The results are remarkable in the amount of wound healing and reduction in pain.”

The tolerability of this medication “is crucial,” she added. “EB patients have a lot of pain from their wounds and so any treatment needs to be as painless as possible for it to be usable. I’m very excited about the next phase of studies for this medication and hopeful that it heralds new treatments for our EB patients.”

In June 2022, the manufacturer announced that it had submitted a biologics license application to the Food and Drug Administration for approval of B-VEC for the treatment of DEB, and that it anticipates submitting an application for marketing authorization with the European Medical Agency (EMA) in the second half of 2022.

Dr. Guide disclosed that she has served as an investigator for Krystal Biotech, Innovaderm Research, Arcutis, Premier Research, Paidion, and Castle Biosciences. Dr. Marathe disclosed that she has served as an adviser for Verrica, and that Cincinnati Children’s Hospital is a site for the next phase studies for B-VEC.

*This story was updated on July 25.