MDedge Dermatology

Key clinical point: Disease burden of atopic dermatitis (AD) is associated with multiple factors, with the strongest association being with disease severity, time spent managing AD symptoms, and comorbid depression.

Major finding: Disease burden was strongly associated with AD severity (moderate: odds ratio [OR] 4.13; 95% CI 2.94-5.79 or severe: OR 13.63; 95% CI 8.65-21.5 vs mild AD), time spent managing AD symptoms (11-20 hours/week: OR 2.67; 95% CI 1.77-4.03 or ≥21 hours/week: OR 5.34; 95% CI 3.22-8.85 vs 0-4 hours/week), and comorbid depression (OR 1.44; 95% CI 1.04-2.00).

Study details: Findings are from a survey study that analyzed the responses of 1065 adults with mostly moderate or severe AD.

Disclosures: This study was partly supported by National Eczema Association. The authors declared serving as fiscal agents or receiving grants, sponsorships, honoraria, or other compensation from several sources, including the National Eczema Association.

Source: Elsawi R et al. The multidimensional burden of atopic dermatitis among adults: Results from a large national survey. JAMA Dermatol. 2022 (Jun 29). Doi: 10.1001/jamadermatol.2022.1906

Key clinical point: Disease burden of atopic dermatitis (AD) is associated with multiple factors, with the strongest association being with disease severity, time spent managing AD symptoms, and comorbid depression.

Major finding: Disease burden was strongly associated with AD severity (moderate: odds ratio [OR] 4.13; 95% CI 2.94-5.79 or severe: OR 13.63; 95% CI 8.65-21.5 vs mild AD), time spent managing AD symptoms (11-20 hours/week: OR 2.67; 95% CI 1.77-4.03 or ≥21 hours/week: OR 5.34; 95% CI 3.22-8.85 vs 0-4 hours/week), and comorbid depression (OR 1.44; 95% CI 1.04-2.00).

Study details: Findings are from a survey study that analyzed the responses of 1065 adults with mostly moderate or severe AD.

Disclosures: This study was partly supported by National Eczema Association. The authors declared serving as fiscal agents or receiving grants, sponsorships, honoraria, or other compensation from several sources, including the National Eczema Association.

Source: Elsawi R et al. The multidimensional burden of atopic dermatitis among adults: Results from a large national survey. JAMA Dermatol. 2022 (Jun 29). Doi: 10.1001/jamadermatol.2022.1906

Key clinical point: Disease burden of atopic dermatitis (AD) is associated with multiple factors, with the strongest association being with disease severity, time spent managing AD symptoms, and comorbid depression.

Major finding: Disease burden was strongly associated with AD severity (moderate: odds ratio [OR] 4.13; 95% CI 2.94-5.79 or severe: OR 13.63; 95% CI 8.65-21.5 vs mild AD), time spent managing AD symptoms (11-20 hours/week: OR 2.67; 95% CI 1.77-4.03 or ≥21 hours/week: OR 5.34; 95% CI 3.22-8.85 vs 0-4 hours/week), and comorbid depression (OR 1.44; 95% CI 1.04-2.00).

Study details: Findings are from a survey study that analyzed the responses of 1065 adults with mostly moderate or severe AD.

Disclosures: This study was partly supported by National Eczema Association. The authors declared serving as fiscal agents or receiving grants, sponsorships, honoraria, or other compensation from several sources, including the National Eczema Association.

Source: Elsawi R et al. The multidimensional burden of atopic dermatitis among adults: Results from a large national survey. JAMA Dermatol. 2022 (Jun 29). Doi: 10.1001/jamadermatol.2022.1906

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.

To the Editor:

There is increasing demand for medical care in the United States due to expanded health care coverage; an aging population; and advancements in diagnostics, treatment, and technology.¹ It is predicted that by 2050 the number of dermatologists will be 24.4% short of the expected estimate of demand.²

Accordingly, dermatologists are increasingly practicing in team-based care delivery models that incorporate nonphysician clinicians (NPCs), including nurse practitioners and physician assistants.¹ Despite recognition that NPCs are taking a larger role in medical teams, there is, to our knowledge, limited training for dermatologists and dermatologists in-training to optimize this professional alliance.

The objectives of this study included (1) determining whether residency programs adequately prepare residents to work with or supervise NPCs and (2) understanding the relationship between NPCs and dermatology residents across residency programs in the United States.

An anonymous cross-sectional, Internet-based survey designed using Google Forms survey creation and administration software was distributed to 117 dermatology residency program directors through email, with a request for further dissemination to residents through self-maintained listserves. Four email reminders about completing and disseminating the survey were sent to program directors between August and November 2020. The study was approved by the Emory University institutional review board. All respondents consented to participate in this survey prior to completing it.

The survey included questions pertaining to demographic information, residents’ experiences working with NPCs, residency program training specific to working with NPCs, and residents’ and residency program directors’ opinions on NPCs’ impact on education and patient care. Program directors were asked to respond N/A to 6 questions on the survey because data from those questions represented residents’ opinions only. Questions relating to residents’ and residency program directors’ opinions were based on a 5-point scale of impact (1=strongly impact in a negative way; 5=strongly impact in a positive way) or importance (1=not at all important; 5=extremely important). The survey was not previously validated.

Descriptive analysis and a paired t test were conducted when appropriate. Missing data were excluded.

There were 81 respondents to the survey. Demographic information is shown Table 1. Thirty-five dermatology residency program directors (29.9% of 117 programs) responded. Of the 45 residents or recent graduates, 29 (64.4%) reported that they foresaw the need to work with or supervise NPCs in the future (Table 2). Currently, 29 (64.4%) residents also reported that (1) they do not feel adequately trained to provide supervision of or to work with NPCs or (2) were uncertain whether they could do so. Sixty-five (80.2%) respondents stated that there was no formalized training in their program for supervising or working with NPCs; 45 (55.6%) respondents noted that they do not think that their program provided adequate training in supervising NPCs.

Regarding NPCs impact on care, residency program directors who completed the survey were more likely to rank NPCs as having a more significant positive impact on patient care than residents (mean score, 3.43 vs 2.78; P=.043; 95% CI, –1.28 to –0.20)(Table 3).

This study demonstrated a lack of dermatology training related to working with NPCs in a professional setting and highlighted residents’ perception that formal education in working with and supervising NPCs could be of benefit to their education. Furthermore, residency directors perceived NPCs as having a greater positive impact on patient care than residents did, underscoring the importance of the continued need to educate residents on working synergistically with NPCs to optimize patient care. Ultimately, these results suggest a potential area for further development of residency curricula.

There are approximately 360,000 NPCs serving as integral members of interdisciplinary medical teams across the United States.^3,4 In a 2014 survey, 46% of 2001 dermatologists noted that they already employed 1 or more NPCs, a number that has increased over time and is likely to continue to do so.⁵ Although the number of NPCs in dermatology has increased, there remain limited formal training and certificate programs for these providers.^1,6

Furthermore, the American Academy of Dermatology recommends that “[w]hen practicing in a dermatological setting, non-dermatologist physicians and non-physician clinicians . . . should be directly supervised by a board-certified dermatologist.”⁷ Therefore, the responsibility for a dermatology-specific education can fall on the dermatologist, necessitating adequate supervision and training of NPCs.

The findings of this study were limited by a small sample size; response bias because distribution of the survey relied on program directors disseminating the instrument to their residents, thereby limiting generalizability; and a lack of predissemination validation of the survey. Additional research in this area should focus on survey validation and distribution directly to dermatology residents, instead of relying on dermatology program directors to disseminate the survey.

To the Editor:

There is increasing demand for medical care in the United States due to expanded health care coverage; an aging population; and advancements in diagnostics, treatment, and technology.¹ It is predicted that by 2050 the number of dermatologists will be 24.4% short of the expected estimate of demand.²

Accordingly, dermatologists are increasingly practicing in team-based care delivery models that incorporate nonphysician clinicians (NPCs), including nurse practitioners and physician assistants.¹ Despite recognition that NPCs are taking a larger role in medical teams, there is, to our knowledge, limited training for dermatologists and dermatologists in-training to optimize this professional alliance.

The objectives of this study included (1) determining whether residency programs adequately prepare residents to work with or supervise NPCs and (2) understanding the relationship between NPCs and dermatology residents across residency programs in the United States.

An anonymous cross-sectional, Internet-based survey designed using Google Forms survey creation and administration software was distributed to 117 dermatology residency program directors through email, with a request for further dissemination to residents through self-maintained listserves. Four email reminders about completing and disseminating the survey were sent to program directors between August and November 2020. The study was approved by the Emory University institutional review board. All respondents consented to participate in this survey prior to completing it.

The survey included questions pertaining to demographic information, residents’ experiences working with NPCs, residency program training specific to working with NPCs, and residents’ and residency program directors’ opinions on NPCs’ impact on education and patient care. Program directors were asked to respond N/A to 6 questions on the survey because data from those questions represented residents’ opinions only. Questions relating to residents’ and residency program directors’ opinions were based on a 5-point scale of impact (1=strongly impact in a negative way; 5=strongly impact in a positive way) or importance (1=not at all important; 5=extremely important). The survey was not previously validated.

Descriptive analysis and a paired t test were conducted when appropriate. Missing data were excluded.

There were 81 respondents to the survey. Demographic information is shown Table 1. Thirty-five dermatology residency program directors (29.9% of 117 programs) responded. Of the 45 residents or recent graduates, 29 (64.4%) reported that they foresaw the need to work with or supervise NPCs in the future (Table 2). Currently, 29 (64.4%) residents also reported that (1) they do not feel adequately trained to provide supervision of or to work with NPCs or (2) were uncertain whether they could do so. Sixty-five (80.2%) respondents stated that there was no formalized training in their program for supervising or working with NPCs; 45 (55.6%) respondents noted that they do not think that their program provided adequate training in supervising NPCs.

Regarding NPCs impact on care, residency program directors who completed the survey were more likely to rank NPCs as having a more significant positive impact on patient care than residents (mean score, 3.43 vs 2.78; P=.043; 95% CI, –1.28 to –0.20)(Table 3).

This study demonstrated a lack of dermatology training related to working with NPCs in a professional setting and highlighted residents’ perception that formal education in working with and supervising NPCs could be of benefit to their education. Furthermore, residency directors perceived NPCs as having a greater positive impact on patient care than residents did, underscoring the importance of the continued need to educate residents on working synergistically with NPCs to optimize patient care. Ultimately, these results suggest a potential area for further development of residency curricula.

There are approximately 360,000 NPCs serving as integral members of interdisciplinary medical teams across the United States.^3,4 In a 2014 survey, 46% of 2001 dermatologists noted that they already employed 1 or more NPCs, a number that has increased over time and is likely to continue to do so.⁵ Although the number of NPCs in dermatology has increased, there remain limited formal training and certificate programs for these providers.^1,6

Furthermore, the American Academy of Dermatology recommends that “[w]hen practicing in a dermatological setting, non-dermatologist physicians and non-physician clinicians . . . should be directly supervised by a board-certified dermatologist.”⁷ Therefore, the responsibility for a dermatology-specific education can fall on the dermatologist, necessitating adequate supervision and training of NPCs.

The findings of this study were limited by a small sample size; response bias because distribution of the survey relied on program directors disseminating the instrument to their residents, thereby limiting generalizability; and a lack of predissemination validation of the survey. Additional research in this area should focus on survey validation and distribution directly to dermatology residents, instead of relying on dermatology program directors to disseminate the survey.

To the Editor:

There is increasing demand for medical care in the United States due to expanded health care coverage; an aging population; and advancements in diagnostics, treatment, and technology.¹ It is predicted that by 2050 the number of dermatologists will be 24.4% short of the expected estimate of demand.²

Accordingly, dermatologists are increasingly practicing in team-based care delivery models that incorporate nonphysician clinicians (NPCs), including nurse practitioners and physician assistants.¹ Despite recognition that NPCs are taking a larger role in medical teams, there is, to our knowledge, limited training for dermatologists and dermatologists in-training to optimize this professional alliance.

The objectives of this study included (1) determining whether residency programs adequately prepare residents to work with or supervise NPCs and (2) understanding the relationship between NPCs and dermatology residents across residency programs in the United States.

An anonymous cross-sectional, Internet-based survey designed using Google Forms survey creation and administration software was distributed to 117 dermatology residency program directors through email, with a request for further dissemination to residents through self-maintained listserves. Four email reminders about completing and disseminating the survey were sent to program directors between August and November 2020. The study was approved by the Emory University institutional review board. All respondents consented to participate in this survey prior to completing it.

The survey included questions pertaining to demographic information, residents’ experiences working with NPCs, residency program training specific to working with NPCs, and residents’ and residency program directors’ opinions on NPCs’ impact on education and patient care. Program directors were asked to respond N/A to 6 questions on the survey because data from those questions represented residents’ opinions only. Questions relating to residents’ and residency program directors’ opinions were based on a 5-point scale of impact (1=strongly impact in a negative way; 5=strongly impact in a positive way) or importance (1=not at all important; 5=extremely important). The survey was not previously validated.

Descriptive analysis and a paired t test were conducted when appropriate. Missing data were excluded.

There were 81 respondents to the survey. Demographic information is shown Table 1. Thirty-five dermatology residency program directors (29.9% of 117 programs) responded. Of the 45 residents or recent graduates, 29 (64.4%) reported that they foresaw the need to work with or supervise NPCs in the future (Table 2). Currently, 29 (64.4%) residents also reported that (1) they do not feel adequately trained to provide supervision of or to work with NPCs or (2) were uncertain whether they could do so. Sixty-five (80.2%) respondents stated that there was no formalized training in their program for supervising or working with NPCs; 45 (55.6%) respondents noted that they do not think that their program provided adequate training in supervising NPCs.

Regarding NPCs impact on care, residency program directors who completed the survey were more likely to rank NPCs as having a more significant positive impact on patient care than residents (mean score, 3.43 vs 2.78; P=.043; 95% CI, –1.28 to –0.20)(Table 3).

This study demonstrated a lack of dermatology training related to working with NPCs in a professional setting and highlighted residents’ perception that formal education in working with and supervising NPCs could be of benefit to their education. Furthermore, residency directors perceived NPCs as having a greater positive impact on patient care than residents did, underscoring the importance of the continued need to educate residents on working synergistically with NPCs to optimize patient care. Ultimately, these results suggest a potential area for further development of residency curricula.

There are approximately 360,000 NPCs serving as integral members of interdisciplinary medical teams across the United States.^3,4 In a 2014 survey, 46% of 2001 dermatologists noted that they already employed 1 or more NPCs, a number that has increased over time and is likely to continue to do so.⁵ Although the number of NPCs in dermatology has increased, there remain limited formal training and certificate programs for these providers.^1,6

Furthermore, the American Academy of Dermatology recommends that “[w]hen practicing in a dermatological setting, non-dermatologist physicians and non-physician clinicians . . . should be directly supervised by a board-certified dermatologist.”⁷ Therefore, the responsibility for a dermatology-specific education can fall on the dermatologist, necessitating adequate supervision and training of NPCs.

The findings of this study were limited by a small sample size; response bias because distribution of the survey relied on program directors disseminating the instrument to their residents, thereby limiting generalizability; and a lack of predissemination validation of the survey. Additional research in this area should focus on survey validation and distribution directly to dermatology residents, instead of relying on dermatology program directors to disseminate the survey.

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.

The Diagnosis: Elephantiasis Nostras Verrucosa

Histopathology revealed a benign fibroepithelial polyp demonstrating areas of hyperkeratosis, acanthosis, and focal papillomatosis (Figure, A). Increased superficial vessels with dilated lymphatics, stellate fibroblasts, edematous stroma, and plasmolymphocytosis also were noted (Figure, B). Clinical and histopathological findings led to a diagnosis of lymphedema papules in the setting of elephantiasis nostra verrucosa (ENV).

Elephantiasis nostras verrucosa is a complication of long-standing nonfilarial obstruction of lymphatic drainage leading to grotesque enlargement of the affected areas. Common cutaneous manifestations of ENV include nonpitting edema, dermal fibrosis, and extensive hyperkeratosis with verrucous and papillomatous lesions.¹ In the beginning stages of ENV, the skin has a cobblestonelike appearance. As the disease progresses, the verrucous lesions continue to enlarge, giving the affected area a mossy appearance. Although less common, groupings of large papillomas similar to our patient’s presentation also can form.² Ulcer formation is more likely to occur in advanced disease states, increasing the risk for bacterial and fungal colonization. Elephantiasis nostras verrucosa classically affects the legs; however, this condition can develop in any area with chronic lymphedema. Cases of ENV involving the arms, abdomen, scrotum, and ear have been documented.^3-5

The pathogenesis of ENV involves the proliferation of fibroblasts and fibrosis secondary to lymphostasis and inflammation.⁶ When interstitial fluid builds up in the affected region, the protein-rich fluid is believed to trigger fibrogenesis and increase macrophage, keratinocyte, and adipocyte activity.⁷ Because of this inflammatory process, dilation and fibrosis of the lymphatic channels develop. Lymphatic obstruction can have several etiologies, most notably infection and malignancy. Staphylococcal lymphangitis and erysipelas create fibrosis of the lymphatic system and are the main infectious causes of ENV.⁶ Large tumors or lymphomas are insidious causes of lymphatic obstruction and should be ruled out when investigating for ENV. Other risk factors include obesity, chronic venous insufficiency, surgery, trauma, radiation, and uncontrolled congestive heart failure.^1,6,8

An ENV diagnosis is clinicopathologic, involving a comprehensive metabolic panel and complete blood cell count with differential. A biopsy is needed for pathologic confirmation and to rule out malignancy. Histologically, ENV is characterized by pseudoepitheliomatous hyperplasia, dermal fibrosis, hyperkeratosis of the epidermis, and dilated lymphatic vessels.^6,8 Additional studies for diagnosis include wound and lymph node culture, Wood lamp examination, and lymphoscintigraphy.

Given the chronic and progressive nature of the disease, ENV is difficult to treat. There currently is no standard of treatment, but the mainstay of management involves reducing peripheral edema. Lifestyle changes including weight loss, extremity elevation, and increased ambulation are helpful first-line therapies.³ Compression of the affected extremity using stockings or intermittent pneumatic compression devices has proven to be beneficial with long-term use.⁷ Patients should be followed for wound care to prevent the infection of ulcers.² Pharmacologic treatments include systemic retinoids, which have been shown to reduce the appearance of hyperkeratosis, verrucous lesions, and papillomatous nodules.⁶ Prophylactic antibiotics are reserved for advanced stages of disease or in patients with recurrent infections.^2,7 In severe cases of ENV that are unresponsive to medical management, surgical intervention such as lymphatic anastomosis and debulking may be considered.^9,10

Other diagnoses to consider for ENV include pretibial myxedema, lymphatic filariasis, Stewart-Treves syndrome, and papillomatosis cutis carcinoides. Pretibial myxedema is an uncommon dermatologic manifestation of Graves disease. It is a local autoimmune reaction in the cutaneous tissue characterized by hyperpigmentation, nonpitting edema, and nodules on the anterior leg. Histopathology shows increased hyaluronic acid and chondroitin as well as compression of dermal lymphatics.¹¹

Filariasis is a parasitic infection caused by Wuchereria bancrofti, Brugia malayi or Brugia timori, and Onchocerca volvulus.⁶ This condition presents with elephantiasis of the affected extremities but should be considered in areas endemic for filarial parasites such as tropical and subtropical countries.¹² Eosinophilia and identification of microfilaria in a peripheral blood smear would indicate parasitic infection. Stewart-Treves syndrome is a rare angiosarcoma that arises in areas of chronic lymphedema. This condition classically is seen on the upper extremities following a mastectomy with lymphadenectomy, lymph node irradiation, or both.

Stewart-Treves syndrome presents with coalescing purpuric macules and nodules that eventually coalesce into cutaneous masses. Histopathology reveals proliferating vascular channels that split apart dermal collagen with hyperchromatism and pleomorphism in the tumor endothelial cells that line these channels.¹³

Papillomatosis cutis carcinoides is a low-grade squamous cell carcinoma that occurs secondary to human papillomavirus commonly affecting the mouth, anogenital area, and the plantar surfaces of the feet. It presents with exophytic growths and ulcerated tumors that are unilateral and asymmetrical. The presence of blunt-shaped tumor projections extending deep into the dermis to form sinuses and keratin-filled cysts is characteristic of papillomatosis cutis carcinoides.¹⁴

The Diagnosis: Elephantiasis Nostras Verrucosa

Histopathology revealed a benign fibroepithelial polyp demonstrating areas of hyperkeratosis, acanthosis, and focal papillomatosis (Figure, A). Increased superficial vessels with dilated lymphatics, stellate fibroblasts, edematous stroma, and plasmolymphocytosis also were noted (Figure, B). Clinical and histopathological findings led to a diagnosis of lymphedema papules in the setting of elephantiasis nostra verrucosa (ENV).

Elephantiasis nostras verrucosa is a complication of long-standing nonfilarial obstruction of lymphatic drainage leading to grotesque enlargement of the affected areas. Common cutaneous manifestations of ENV include nonpitting edema, dermal fibrosis, and extensive hyperkeratosis with verrucous and papillomatous lesions.¹ In the beginning stages of ENV, the skin has a cobblestonelike appearance. As the disease progresses, the verrucous lesions continue to enlarge, giving the affected area a mossy appearance. Although less common, groupings of large papillomas similar to our patient’s presentation also can form.² Ulcer formation is more likely to occur in advanced disease states, increasing the risk for bacterial and fungal colonization. Elephantiasis nostras verrucosa classically affects the legs; however, this condition can develop in any area with chronic lymphedema. Cases of ENV involving the arms, abdomen, scrotum, and ear have been documented.^3-5

The pathogenesis of ENV involves the proliferation of fibroblasts and fibrosis secondary to lymphostasis and inflammation.⁶ When interstitial fluid builds up in the affected region, the protein-rich fluid is believed to trigger fibrogenesis and increase macrophage, keratinocyte, and adipocyte activity.⁷ Because of this inflammatory process, dilation and fibrosis of the lymphatic channels develop. Lymphatic obstruction can have several etiologies, most notably infection and malignancy. Staphylococcal lymphangitis and erysipelas create fibrosis of the lymphatic system and are the main infectious causes of ENV.⁶ Large tumors or lymphomas are insidious causes of lymphatic obstruction and should be ruled out when investigating for ENV. Other risk factors include obesity, chronic venous insufficiency, surgery, trauma, radiation, and uncontrolled congestive heart failure.^1,6,8

An ENV diagnosis is clinicopathologic, involving a comprehensive metabolic panel and complete blood cell count with differential. A biopsy is needed for pathologic confirmation and to rule out malignancy. Histologically, ENV is characterized by pseudoepitheliomatous hyperplasia, dermal fibrosis, hyperkeratosis of the epidermis, and dilated lymphatic vessels.^6,8 Additional studies for diagnosis include wound and lymph node culture, Wood lamp examination, and lymphoscintigraphy.

Given the chronic and progressive nature of the disease, ENV is difficult to treat. There currently is no standard of treatment, but the mainstay of management involves reducing peripheral edema. Lifestyle changes including weight loss, extremity elevation, and increased ambulation are helpful first-line therapies.³ Compression of the affected extremity using stockings or intermittent pneumatic compression devices has proven to be beneficial with long-term use.⁷ Patients should be followed for wound care to prevent the infection of ulcers.² Pharmacologic treatments include systemic retinoids, which have been shown to reduce the appearance of hyperkeratosis, verrucous lesions, and papillomatous nodules.⁶ Prophylactic antibiotics are reserved for advanced stages of disease or in patients with recurrent infections.^2,7 In severe cases of ENV that are unresponsive to medical management, surgical intervention such as lymphatic anastomosis and debulking may be considered.^9,10

Other diagnoses to consider for ENV include pretibial myxedema, lymphatic filariasis, Stewart-Treves syndrome, and papillomatosis cutis carcinoides. Pretibial myxedema is an uncommon dermatologic manifestation of Graves disease. It is a local autoimmune reaction in the cutaneous tissue characterized by hyperpigmentation, nonpitting edema, and nodules on the anterior leg. Histopathology shows increased hyaluronic acid and chondroitin as well as compression of dermal lymphatics.¹¹

Filariasis is a parasitic infection caused by Wuchereria bancrofti, Brugia malayi or Brugia timori, and Onchocerca volvulus.⁶ This condition presents with elephantiasis of the affected extremities but should be considered in areas endemic for filarial parasites such as tropical and subtropical countries.¹² Eosinophilia and identification of microfilaria in a peripheral blood smear would indicate parasitic infection. Stewart-Treves syndrome is a rare angiosarcoma that arises in areas of chronic lymphedema. This condition classically is seen on the upper extremities following a mastectomy with lymphadenectomy, lymph node irradiation, or both.

Stewart-Treves syndrome presents with coalescing purpuric macules and nodules that eventually coalesce into cutaneous masses. Histopathology reveals proliferating vascular channels that split apart dermal collagen with hyperchromatism and pleomorphism in the tumor endothelial cells that line these channels.¹³

Papillomatosis cutis carcinoides is a low-grade squamous cell carcinoma that occurs secondary to human papillomavirus commonly affecting the mouth, anogenital area, and the plantar surfaces of the feet. It presents with exophytic growths and ulcerated tumors that are unilateral and asymmetrical. The presence of blunt-shaped tumor projections extending deep into the dermis to form sinuses and keratin-filled cysts is characteristic of papillomatosis cutis carcinoides.¹⁴

The Diagnosis: Elephantiasis Nostras Verrucosa

Histopathology revealed a benign fibroepithelial polyp demonstrating areas of hyperkeratosis, acanthosis, and focal papillomatosis (Figure, A). Increased superficial vessels with dilated lymphatics, stellate fibroblasts, edematous stroma, and plasmolymphocytosis also were noted (Figure, B). Clinical and histopathological findings led to a diagnosis of lymphedema papules in the setting of elephantiasis nostra verrucosa (ENV).

Elephantiasis nostras verrucosa is a complication of long-standing nonfilarial obstruction of lymphatic drainage leading to grotesque enlargement of the affected areas. Common cutaneous manifestations of ENV include nonpitting edema, dermal fibrosis, and extensive hyperkeratosis with verrucous and papillomatous lesions.¹ In the beginning stages of ENV, the skin has a cobblestonelike appearance. As the disease progresses, the verrucous lesions continue to enlarge, giving the affected area a mossy appearance. Although less common, groupings of large papillomas similar to our patient’s presentation also can form.² Ulcer formation is more likely to occur in advanced disease states, increasing the risk for bacterial and fungal colonization. Elephantiasis nostras verrucosa classically affects the legs; however, this condition can develop in any area with chronic lymphedema. Cases of ENV involving the arms, abdomen, scrotum, and ear have been documented.^3-5

The pathogenesis of ENV involves the proliferation of fibroblasts and fibrosis secondary to lymphostasis and inflammation.⁶ When interstitial fluid builds up in the affected region, the protein-rich fluid is believed to trigger fibrogenesis and increase macrophage, keratinocyte, and adipocyte activity.⁷ Because of this inflammatory process, dilation and fibrosis of the lymphatic channels develop. Lymphatic obstruction can have several etiologies, most notably infection and malignancy. Staphylococcal lymphangitis and erysipelas create fibrosis of the lymphatic system and are the main infectious causes of ENV.⁶ Large tumors or lymphomas are insidious causes of lymphatic obstruction and should be ruled out when investigating for ENV. Other risk factors include obesity, chronic venous insufficiency, surgery, trauma, radiation, and uncontrolled congestive heart failure.^1,6,8

An ENV diagnosis is clinicopathologic, involving a comprehensive metabolic panel and complete blood cell count with differential. A biopsy is needed for pathologic confirmation and to rule out malignancy. Histologically, ENV is characterized by pseudoepitheliomatous hyperplasia, dermal fibrosis, hyperkeratosis of the epidermis, and dilated lymphatic vessels.^6,8 Additional studies for diagnosis include wound and lymph node culture, Wood lamp examination, and lymphoscintigraphy.

Given the chronic and progressive nature of the disease, ENV is difficult to treat. There currently is no standard of treatment, but the mainstay of management involves reducing peripheral edema. Lifestyle changes including weight loss, extremity elevation, and increased ambulation are helpful first-line therapies.³ Compression of the affected extremity using stockings or intermittent pneumatic compression devices has proven to be beneficial with long-term use.⁷ Patients should be followed for wound care to prevent the infection of ulcers.² Pharmacologic treatments include systemic retinoids, which have been shown to reduce the appearance of hyperkeratosis, verrucous lesions, and papillomatous nodules.⁶ Prophylactic antibiotics are reserved for advanced stages of disease or in patients with recurrent infections.^2,7 In severe cases of ENV that are unresponsive to medical management, surgical intervention such as lymphatic anastomosis and debulking may be considered.^9,10

Other diagnoses to consider for ENV include pretibial myxedema, lymphatic filariasis, Stewart-Treves syndrome, and papillomatosis cutis carcinoides. Pretibial myxedema is an uncommon dermatologic manifestation of Graves disease. It is a local autoimmune reaction in the cutaneous tissue characterized by hyperpigmentation, nonpitting edema, and nodules on the anterior leg. Histopathology shows increased hyaluronic acid and chondroitin as well as compression of dermal lymphatics.¹¹

Filariasis is a parasitic infection caused by Wuchereria bancrofti, Brugia malayi or Brugia timori, and Onchocerca volvulus.⁶ This condition presents with elephantiasis of the affected extremities but should be considered in areas endemic for filarial parasites such as tropical and subtropical countries.¹² Eosinophilia and identification of microfilaria in a peripheral blood smear would indicate parasitic infection. Stewart-Treves syndrome is a rare angiosarcoma that arises in areas of chronic lymphedema. This condition classically is seen on the upper extremities following a mastectomy with lymphadenectomy, lymph node irradiation, or both.

Stewart-Treves syndrome presents with coalescing purpuric macules and nodules that eventually coalesce into cutaneous masses. Histopathology reveals proliferating vascular channels that split apart dermal collagen with hyperchromatism and pleomorphism in the tumor endothelial cells that line these channels.¹³

Papillomatosis cutis carcinoides is a low-grade squamous cell carcinoma that occurs secondary to human papillomavirus commonly affecting the mouth, anogenital area, and the plantar surfaces of the feet. It presents with exophytic growths and ulcerated tumors that are unilateral and asymmetrical. The presence of blunt-shaped tumor projections extending deep into the dermis to form sinuses and keratin-filled cysts is characteristic of papillomatosis cutis carcinoides.¹⁴

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.

NEW YORK – A questionnaire-based screening tool appears to accelerate the time to diagnosis of axial involvement in patients presenting with psoriasis but no clinical signs of joint pain, according to a study called ATTRACT that was presented at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

The risk of a delayed diagnosis of an axial component in patients with psoriasis, meaning a delay in the underlying diagnosis of psoriatic arthritis (PsA), is substantial, according to Devis Benfaremo, MD, of the department of clinical and molecular science at Marche Polytechnic University, Ancona, Italy.

Ted Bosworth/MDedge News

There is “no consensus for the best strategy to achieve early detection of joint disease” in patients presenting with psoriasis, but Dr. Benfaremo pointed out that missing axial involvement is a particular problem because it is far more likely than swollen joints to be missed on clinical examination.

While about one in three patients with psoriasis have or will develop psoriatic arthritis, according to the National Psoriasis Foundation, delays in diagnosis are common, according to Dr. Benfaremo. In patients with undiagnosed PsA characterized by axial involvement alone, subtle symptoms can be overlooked or attributed to other causes.

There are several screening questionnaires to detect joint symptoms in patients presenting with psoriasis, such as the five-question Psoriasis Epidemiology Screening Tool, but the questionnaire tested in the ATTRACT trial is focused on detecting axial involvement specifically. It was characterized as the first to do so.

In the ongoing ATTRACT study, 253 patients with psoriasis but no history of PsA or axial disease have been enrolled so far. In the study, patients are screened for PsA based on a patient-completed yes-or-no questionnaire, which takes only a few minutes to complete.

“It is a validated questionnaire for axial [spondyloarthritis], but we have adopted it for detection of psoriasis patients with PsA,” Dr. Benfaremo explained.

The questionnaire for axial spondyloarthritis (axSpA) was initially evaluated and validated by Fabian Proft, MD, head of the clinical trials unit at Charité Hospital, Berlin. In addition to a patient self-completed questionnaire, Dr. Proft and coinvestigators have also created a related questionnaire to be administered by physicians.

In the ATTRACT study, patients completed the questionnaire on an electronic device in the waiting room. Positive answers to specific questions about symptoms, which addressed back pain and joint function as well as joint symptoms, divided patients into three groups:

• Group A patients did not respond positively to any of the symptom questions that would prompt suspicion of axial disease. These represented about one-third of those screened so far.
• Group B patients were those who answered positively to at least two questions that related to a high suspicion of axial involvement. These represented 45% of patients.
• The remaining patients were placed in Group C, a category of intermediate risk based on positive responses to some, but not all, questions relating to axial symptoms.

Those in group B are being referred to rheumatology. Patients in group C are given “conditional” eligibility based on the presence of additional risk factors.
 

AxSpA screening tool ‘makes sense’ for potential use in PsA

The primary outcome of the ATTRACT trial is early identification of axial PsA. Correctly identifying patients with or without peripheral joint involvement is one of several secondary outcomes. The identification of patients who fulfill Assessment Spondyloarthritis International Society (ASAS) criteria for axSpA is another secondary outcome.

Of the 114 patients placed in group B and analyzed so far, 87 have completed an assessment by a rheumatologist with laboratory analyses and imaging, as well as a clinical examination.

Of those 87 assessed by a rheumatologist, 17 did not have either axial or peripheral inflammation. Another 19 were diagnosed with axial disease, including 14 who met ASAS criteria. A total of 10 were classified as having PsA with peripheral inflammation, according to Classification for Psoriatic Arthritis criteria, and 41 are still being considered for a diagnosis of axial or peripheral PsA on the basis of further workup.

“Among the patients with axial PsA, only 10% had elevated C-reactive protein levels,” according to Dr. Benfaremo, echoing previous evidence that inflammatory biomarkers by themselves have limited value for identifying psoriasis patients at high risk of joint involvement.

The findings are preliminary, but Dr. Benfaremo reported that the questionnaire is showing promise for the routine stratification of patients who should be considered for a rheumatology consultation.

If further analyses validate the clinical utility of these stratifications, there is the potential for a substantial acceleration to the diagnosis of PsA.

When contacted to comment about this work, Dr. Proft said that there is an important need for new strategies reduce delay in the diagnosis of PsA among patients presenting with psoriasis. He thinks the screening tool he developed for axSpA “makes sense” as a potential tool in PsA.

“If validated, this could be a very useful for earlier identification of PsA,” Dr. Proft said. He reiterated the importance of focusing on axial involvement.

“Previous screening tools have focused on symptoms of PsA more generally, but inflammation in the peripheral joints is something that you can easily see in most patients,” he said.

In addition to the patient-completed questionnaire and the physician-administered questionnaire, Dr. Proft has also evaluated an online self-referral tool for patients.

“If we can diagnose PsA earlier in the course of disease, we can start treatment earlier, prevent or delay joint damage, and potentially improve outcomes for patients,” Dr. Proft said. He considers this an important direction of research.

Dr. Benfaremo and Dr. Proft reported no potential conflicts of interest.

NEW YORK – A questionnaire-based screening tool appears to accelerate the time to diagnosis of axial involvement in patients presenting with psoriasis but no clinical signs of joint pain, according to a study called ATTRACT that was presented at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

The risk of a delayed diagnosis of an axial component in patients with psoriasis, meaning a delay in the underlying diagnosis of psoriatic arthritis (PsA), is substantial, according to Devis Benfaremo, MD, of the department of clinical and molecular science at Marche Polytechnic University, Ancona, Italy.

Ted Bosworth/MDedge News

There is “no consensus for the best strategy to achieve early detection of joint disease” in patients presenting with psoriasis, but Dr. Benfaremo pointed out that missing axial involvement is a particular problem because it is far more likely than swollen joints to be missed on clinical examination.

While about one in three patients with psoriasis have or will develop psoriatic arthritis, according to the National Psoriasis Foundation, delays in diagnosis are common, according to Dr. Benfaremo. In patients with undiagnosed PsA characterized by axial involvement alone, subtle symptoms can be overlooked or attributed to other causes.

There are several screening questionnaires to detect joint symptoms in patients presenting with psoriasis, such as the five-question Psoriasis Epidemiology Screening Tool, but the questionnaire tested in the ATTRACT trial is focused on detecting axial involvement specifically. It was characterized as the first to do so.

In the ongoing ATTRACT study, 253 patients with psoriasis but no history of PsA or axial disease have been enrolled so far. In the study, patients are screened for PsA based on a patient-completed yes-or-no questionnaire, which takes only a few minutes to complete.

“It is a validated questionnaire for axial [spondyloarthritis], but we have adopted it for detection of psoriasis patients with PsA,” Dr. Benfaremo explained.

The questionnaire for axial spondyloarthritis (axSpA) was initially evaluated and validated by Fabian Proft, MD, head of the clinical trials unit at Charité Hospital, Berlin. In addition to a patient self-completed questionnaire, Dr. Proft and coinvestigators have also created a related questionnaire to be administered by physicians.

In the ATTRACT study, patients completed the questionnaire on an electronic device in the waiting room. Positive answers to specific questions about symptoms, which addressed back pain and joint function as well as joint symptoms, divided patients into three groups:

• Group A patients did not respond positively to any of the symptom questions that would prompt suspicion of axial disease. These represented about one-third of those screened so far.
• Group B patients were those who answered positively to at least two questions that related to a high suspicion of axial involvement. These represented 45% of patients.
• The remaining patients were placed in Group C, a category of intermediate risk based on positive responses to some, but not all, questions relating to axial symptoms.

Those in group B are being referred to rheumatology. Patients in group C are given “conditional” eligibility based on the presence of additional risk factors.
 

AxSpA screening tool ‘makes sense’ for potential use in PsA

The primary outcome of the ATTRACT trial is early identification of axial PsA. Correctly identifying patients with or without peripheral joint involvement is one of several secondary outcomes. The identification of patients who fulfill Assessment Spondyloarthritis International Society (ASAS) criteria for axSpA is another secondary outcome.

Of the 114 patients placed in group B and analyzed so far, 87 have completed an assessment by a rheumatologist with laboratory analyses and imaging, as well as a clinical examination.

Of those 87 assessed by a rheumatologist, 17 did not have either axial or peripheral inflammation. Another 19 were diagnosed with axial disease, including 14 who met ASAS criteria. A total of 10 were classified as having PsA with peripheral inflammation, according to Classification for Psoriatic Arthritis criteria, and 41 are still being considered for a diagnosis of axial or peripheral PsA on the basis of further workup.

“Among the patients with axial PsA, only 10% had elevated C-reactive protein levels,” according to Dr. Benfaremo, echoing previous evidence that inflammatory biomarkers by themselves have limited value for identifying psoriasis patients at high risk of joint involvement.

The findings are preliminary, but Dr. Benfaremo reported that the questionnaire is showing promise for the routine stratification of patients who should be considered for a rheumatology consultation.

If further analyses validate the clinical utility of these stratifications, there is the potential for a substantial acceleration to the diagnosis of PsA.

When contacted to comment about this work, Dr. Proft said that there is an important need for new strategies reduce delay in the diagnosis of PsA among patients presenting with psoriasis. He thinks the screening tool he developed for axSpA “makes sense” as a potential tool in PsA.

“If validated, this could be a very useful for earlier identification of PsA,” Dr. Proft said. He reiterated the importance of focusing on axial involvement.

“Previous screening tools have focused on symptoms of PsA more generally, but inflammation in the peripheral joints is something that you can easily see in most patients,” he said.

In addition to the patient-completed questionnaire and the physician-administered questionnaire, Dr. Proft has also evaluated an online self-referral tool for patients.

“If we can diagnose PsA earlier in the course of disease, we can start treatment earlier, prevent or delay joint damage, and potentially improve outcomes for patients,” Dr. Proft said. He considers this an important direction of research.

Dr. Benfaremo and Dr. Proft reported no potential conflicts of interest.

NEW YORK – A questionnaire-based screening tool appears to accelerate the time to diagnosis of axial involvement in patients presenting with psoriasis but no clinical signs of joint pain, according to a study called ATTRACT that was presented at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

The risk of a delayed diagnosis of an axial component in patients with psoriasis, meaning a delay in the underlying diagnosis of psoriatic arthritis (PsA), is substantial, according to Devis Benfaremo, MD, of the department of clinical and molecular science at Marche Polytechnic University, Ancona, Italy.

Ted Bosworth/MDedge News

There is “no consensus for the best strategy to achieve early detection of joint disease” in patients presenting with psoriasis, but Dr. Benfaremo pointed out that missing axial involvement is a particular problem because it is far more likely than swollen joints to be missed on clinical examination.

While about one in three patients with psoriasis have or will develop psoriatic arthritis, according to the National Psoriasis Foundation, delays in diagnosis are common, according to Dr. Benfaremo. In patients with undiagnosed PsA characterized by axial involvement alone, subtle symptoms can be overlooked or attributed to other causes.

There are several screening questionnaires to detect joint symptoms in patients presenting with psoriasis, such as the five-question Psoriasis Epidemiology Screening Tool, but the questionnaire tested in the ATTRACT trial is focused on detecting axial involvement specifically. It was characterized as the first to do so.

In the ongoing ATTRACT study, 253 patients with psoriasis but no history of PsA or axial disease have been enrolled so far. In the study, patients are screened for PsA based on a patient-completed yes-or-no questionnaire, which takes only a few minutes to complete.

“It is a validated questionnaire for axial [spondyloarthritis], but we have adopted it for detection of psoriasis patients with PsA,” Dr. Benfaremo explained.

The questionnaire for axial spondyloarthritis (axSpA) was initially evaluated and validated by Fabian Proft, MD, head of the clinical trials unit at Charité Hospital, Berlin. In addition to a patient self-completed questionnaire, Dr. Proft and coinvestigators have also created a related questionnaire to be administered by physicians.

In the ATTRACT study, patients completed the questionnaire on an electronic device in the waiting room. Positive answers to specific questions about symptoms, which addressed back pain and joint function as well as joint symptoms, divided patients into three groups:

• Group A patients did not respond positively to any of the symptom questions that would prompt suspicion of axial disease. These represented about one-third of those screened so far.
• Group B patients were those who answered positively to at least two questions that related to a high suspicion of axial involvement. These represented 45% of patients.
• The remaining patients were placed in Group C, a category of intermediate risk based on positive responses to some, but not all, questions relating to axial symptoms.

Those in group B are being referred to rheumatology. Patients in group C are given “conditional” eligibility based on the presence of additional risk factors.
 

AxSpA screening tool ‘makes sense’ for potential use in PsA

The primary outcome of the ATTRACT trial is early identification of axial PsA. Correctly identifying patients with or without peripheral joint involvement is one of several secondary outcomes. The identification of patients who fulfill Assessment Spondyloarthritis International Society (ASAS) criteria for axSpA is another secondary outcome.

Of the 114 patients placed in group B and analyzed so far, 87 have completed an assessment by a rheumatologist with laboratory analyses and imaging, as well as a clinical examination.

Of those 87 assessed by a rheumatologist, 17 did not have either axial or peripheral inflammation. Another 19 were diagnosed with axial disease, including 14 who met ASAS criteria. A total of 10 were classified as having PsA with peripheral inflammation, according to Classification for Psoriatic Arthritis criteria, and 41 are still being considered for a diagnosis of axial or peripheral PsA on the basis of further workup.

“Among the patients with axial PsA, only 10% had elevated C-reactive protein levels,” according to Dr. Benfaremo, echoing previous evidence that inflammatory biomarkers by themselves have limited value for identifying psoriasis patients at high risk of joint involvement.

The findings are preliminary, but Dr. Benfaremo reported that the questionnaire is showing promise for the routine stratification of patients who should be considered for a rheumatology consultation.

If further analyses validate the clinical utility of these stratifications, there is the potential for a substantial acceleration to the diagnosis of PsA.

When contacted to comment about this work, Dr. Proft said that there is an important need for new strategies reduce delay in the diagnosis of PsA among patients presenting with psoriasis. He thinks the screening tool he developed for axSpA “makes sense” as a potential tool in PsA.

“If validated, this could be a very useful for earlier identification of PsA,” Dr. Proft said. He reiterated the importance of focusing on axial involvement.

“Previous screening tools have focused on symptoms of PsA more generally, but inflammation in the peripheral joints is something that you can easily see in most patients,” he said.

In addition to the patient-completed questionnaire and the physician-administered questionnaire, Dr. Proft has also evaluated an online self-referral tool for patients.

“If we can diagnose PsA earlier in the course of disease, we can start treatment earlier, prevent or delay joint damage, and potentially improve outcomes for patients,” Dr. Proft said. He considers this an important direction of research.

Dr. Benfaremo and Dr. Proft reported no potential conflicts of interest.

Single ulcers, anal lesions, and mouth sores are all unique symptoms of the current monkeypox outbreak, according to the largest international monkeypox case series to date. These findings underscore the need to broaden case definitions for the disease, researchers say.

“While we expected various skin problems and rashes, we also found that 1 in 10 people had only a single skin lesion in the genital area, and 15% had anal and/or rectal pain,” John Thornhill, MD, PhD, the lead author of the research, said in a press release. Dr. Thornhill is a consultant physician in sexual health and HIV and a clinical senior lecturer at Barts NHS Health Trust and Queen Mary University of London. “These different presentations highlight that monkeypox infections could be missed or easily confused with common sexually transmitted infections such as syphilis or herpes,” he said.

Since April 2022, more than 15,000 cases of monkeypox have been reported in 66 countries where the virus was previously not known to be present. The virus, a less severe cousin of smallpox, is endemic to areas of central and west Africa. In the current outbreak, infections have overwhelmingly been found in men who have sex with men.

In a study published in the New England Journal of Medicine, researchers reported clinical details and outcomes of 528 monkeypox infections across 16 countries. All the cases were diagnosed between April 27 and June 24, 2022. Ninety-five percent of the cases were suspected to have been transmitted through sexual activity, 98% of patients identified as gay or bisexual men, and 75% of the patients were White. The median age of patients in this case series was 38 years, and 90% of infections occurred in Europe. Forty-one percent of patients were HIV-positive, and 96% of these individuals were receiving antiretroviral therapy. Among patients whose HIV status was negative or unknown, 57% reported using preexposure prophylaxis against HIV. About 3 in 10 (29%) individuals tested positive for concurrent sexually transmitted infections.

Nearly three out of four patients (73%) had anogenital lesions, and 41% had mucosal lesions. Fifty-four patients had one genital lesion, and 64% had fewer than 10 lesions in total. Fever (62%), swollen lymph nodes (56%), lethargy (41%), and myalgia (31%) were commonly reported symptoms prior to the development of the rash. Seventy patients (13%) required hospitalization, most commonly for severe anorectal pain and soft-tissue superinfection. Just 5% of patients received monkeypox-specific treatment: intravenous or topical cidofovir (2%), tecovirimat (2%), and vaccinia immune globulin (<1%).

The study “importantly reinforces our current understanding that the overwhelming majority of cases have been sexually associated, predominantly in men who have sex with men,” Jeffrey Klausner, MD, PhD, an infectious disease specialist at the University of Southern California, Los Angeles, said in an interview with this news organization. He was not involved with the research. “Anyone can get monkeypox, but it is most effectively spread through what we call dense networks – where there is a frequent, close personal contact,” he said. “It just happens that gay men and other men who have sex with men have some of those networks.”

The fact that most lesions are present in the genital and anal region – which is unique to this outbreak – points to transmission of the infection during intimate contact, he noted. Still, there is not enough evidence to suggest that monkeypox is spread through sexual transmission. While most semen samples in the study tested positive for monkeypox viral DNA, it is not known whether there is enough virus present to cause transmission, Dr. Thornhill said. He noted that more research is needed.

Dr. Klausner also emphasized the importance of developing new tests to diagnose monkeypox earlier to prevent spread. The lab test for monkeypox requires a swab from a lesion, but this study showed that most patients had notable symptoms prior to developing the standard rash or lesions, he said. Reliable tests using saliva or throat swabs could help detect infections faster, he noted. Patients are thought to be most contagious when they develop lesions, Dr. Klausner said, so diagnosing patients before this stage would allow them to be isolated sooner.

The California-based lab company Flow Health announced a saliva-based PCR test for monkeypox on July 9, although the Food and Drug Administration cautioned that test results from other sample types beside lesion swabs may be inaccurate. “The FDA is not aware of clinical data supporting the use of other sample types, such as blood or saliva, for monkeypox virus testing,” the agency said in a statement on July 15. “Testing samples not taken from a lesion may lead to false test results.”

Dr. Klausner reports no relevant financial relationships.

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

Single ulcers, anal lesions, and mouth sores are all unique symptoms of the current monkeypox outbreak, according to the largest international monkeypox case series to date. These findings underscore the need to broaden case definitions for the disease, researchers say.

“While we expected various skin problems and rashes, we also found that 1 in 10 people had only a single skin lesion in the genital area, and 15% had anal and/or rectal pain,” John Thornhill, MD, PhD, the lead author of the research, said in a press release. Dr. Thornhill is a consultant physician in sexual health and HIV and a clinical senior lecturer at Barts NHS Health Trust and Queen Mary University of London. “These different presentations highlight that monkeypox infections could be missed or easily confused with common sexually transmitted infections such as syphilis or herpes,” he said.

Since April 2022, more than 15,000 cases of monkeypox have been reported in 66 countries where the virus was previously not known to be present. The virus, a less severe cousin of smallpox, is endemic to areas of central and west Africa. In the current outbreak, infections have overwhelmingly been found in men who have sex with men.

In a study published in the New England Journal of Medicine, researchers reported clinical details and outcomes of 528 monkeypox infections across 16 countries. All the cases were diagnosed between April 27 and June 24, 2022. Ninety-five percent of the cases were suspected to have been transmitted through sexual activity, 98% of patients identified as gay or bisexual men, and 75% of the patients were White. The median age of patients in this case series was 38 years, and 90% of infections occurred in Europe. Forty-one percent of patients were HIV-positive, and 96% of these individuals were receiving antiretroviral therapy. Among patients whose HIV status was negative or unknown, 57% reported using preexposure prophylaxis against HIV. About 3 in 10 (29%) individuals tested positive for concurrent sexually transmitted infections.

Nearly three out of four patients (73%) had anogenital lesions, and 41% had mucosal lesions. Fifty-four patients had one genital lesion, and 64% had fewer than 10 lesions in total. Fever (62%), swollen lymph nodes (56%), lethargy (41%), and myalgia (31%) were commonly reported symptoms prior to the development of the rash. Seventy patients (13%) required hospitalization, most commonly for severe anorectal pain and soft-tissue superinfection. Just 5% of patients received monkeypox-specific treatment: intravenous or topical cidofovir (2%), tecovirimat (2%), and vaccinia immune globulin (<1%).

The study “importantly reinforces our current understanding that the overwhelming majority of cases have been sexually associated, predominantly in men who have sex with men,” Jeffrey Klausner, MD, PhD, an infectious disease specialist at the University of Southern California, Los Angeles, said in an interview with this news organization. He was not involved with the research. “Anyone can get monkeypox, but it is most effectively spread through what we call dense networks – where there is a frequent, close personal contact,” he said. “It just happens that gay men and other men who have sex with men have some of those networks.”

The fact that most lesions are present in the genital and anal region – which is unique to this outbreak – points to transmission of the infection during intimate contact, he noted. Still, there is not enough evidence to suggest that monkeypox is spread through sexual transmission. While most semen samples in the study tested positive for monkeypox viral DNA, it is not known whether there is enough virus present to cause transmission, Dr. Thornhill said. He noted that more research is needed.

Dr. Klausner also emphasized the importance of developing new tests to diagnose monkeypox earlier to prevent spread. The lab test for monkeypox requires a swab from a lesion, but this study showed that most patients had notable symptoms prior to developing the standard rash or lesions, he said. Reliable tests using saliva or throat swabs could help detect infections faster, he noted. Patients are thought to be most contagious when they develop lesions, Dr. Klausner said, so diagnosing patients before this stage would allow them to be isolated sooner.

The California-based lab company Flow Health announced a saliva-based PCR test for monkeypox on July 9, although the Food and Drug Administration cautioned that test results from other sample types beside lesion swabs may be inaccurate. “The FDA is not aware of clinical data supporting the use of other sample types, such as blood or saliva, for monkeypox virus testing,” the agency said in a statement on July 15. “Testing samples not taken from a lesion may lead to false test results.”

Dr. Klausner reports no relevant financial relationships.

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

Single ulcers, anal lesions, and mouth sores are all unique symptoms of the current monkeypox outbreak, according to the largest international monkeypox case series to date. These findings underscore the need to broaden case definitions for the disease, researchers say.

“While we expected various skin problems and rashes, we also found that 1 in 10 people had only a single skin lesion in the genital area, and 15% had anal and/or rectal pain,” John Thornhill, MD, PhD, the lead author of the research, said in a press release. Dr. Thornhill is a consultant physician in sexual health and HIV and a clinical senior lecturer at Barts NHS Health Trust and Queen Mary University of London. “These different presentations highlight that monkeypox infections could be missed or easily confused with common sexually transmitted infections such as syphilis or herpes,” he said.

Since April 2022, more than 15,000 cases of monkeypox have been reported in 66 countries where the virus was previously not known to be present. The virus, a less severe cousin of smallpox, is endemic to areas of central and west Africa. In the current outbreak, infections have overwhelmingly been found in men who have sex with men.

In a study published in the New England Journal of Medicine, researchers reported clinical details and outcomes of 528 monkeypox infections across 16 countries. All the cases were diagnosed between April 27 and June 24, 2022. Ninety-five percent of the cases were suspected to have been transmitted through sexual activity, 98% of patients identified as gay or bisexual men, and 75% of the patients were White. The median age of patients in this case series was 38 years, and 90% of infections occurred in Europe. Forty-one percent of patients were HIV-positive, and 96% of these individuals were receiving antiretroviral therapy. Among patients whose HIV status was negative or unknown, 57% reported using preexposure prophylaxis against HIV. About 3 in 10 (29%) individuals tested positive for concurrent sexually transmitted infections.

Nearly three out of four patients (73%) had anogenital lesions, and 41% had mucosal lesions. Fifty-four patients had one genital lesion, and 64% had fewer than 10 lesions in total. Fever (62%), swollen lymph nodes (56%), lethargy (41%), and myalgia (31%) were commonly reported symptoms prior to the development of the rash. Seventy patients (13%) required hospitalization, most commonly for severe anorectal pain and soft-tissue superinfection. Just 5% of patients received monkeypox-specific treatment: intravenous or topical cidofovir (2%), tecovirimat (2%), and vaccinia immune globulin (<1%).

The study “importantly reinforces our current understanding that the overwhelming majority of cases have been sexually associated, predominantly in men who have sex with men,” Jeffrey Klausner, MD, PhD, an infectious disease specialist at the University of Southern California, Los Angeles, said in an interview with this news organization. He was not involved with the research. “Anyone can get monkeypox, but it is most effectively spread through what we call dense networks – where there is a frequent, close personal contact,” he said. “It just happens that gay men and other men who have sex with men have some of those networks.”

The fact that most lesions are present in the genital and anal region – which is unique to this outbreak – points to transmission of the infection during intimate contact, he noted. Still, there is not enough evidence to suggest that monkeypox is spread through sexual transmission. While most semen samples in the study tested positive for monkeypox viral DNA, it is not known whether there is enough virus present to cause transmission, Dr. Thornhill said. He noted that more research is needed.

Dr. Klausner also emphasized the importance of developing new tests to diagnose monkeypox earlier to prevent spread. The lab test for monkeypox requires a swab from a lesion, but this study showed that most patients had notable symptoms prior to developing the standard rash or lesions, he said. Reliable tests using saliva or throat swabs could help detect infections faster, he noted. Patients are thought to be most contagious when they develop lesions, Dr. Klausner said, so diagnosing patients before this stage would allow them to be isolated sooner.

The California-based lab company Flow Health announced a saliva-based PCR test for monkeypox on July 9, although the Food and Drug Administration cautioned that test results from other sample types beside lesion swabs may be inaccurate. “The FDA is not aware of clinical data supporting the use of other sample types, such as blood or saliva, for monkeypox virus testing,” the agency said in a statement on July 15. “Testing samples not taken from a lesion may lead to false test results.”

Dr. Klausner reports no relevant financial relationships.

A version of this article first appeared on Medscape.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.