CARLSBAD, CALIF. – For the estimated 10 million wounds that clinicians treat in the United States each year resulting from surgical procedures, trauma, burns, and other causes, the best outcome is a scar, a fibrotic dermis with a flattened epidermis that contains no sweat glands, no pilosebaceous units, and impaired nerve function.

But what if the outcome was skin regeneration instead of scar formation? At the annual symposium of the California Society of Dermatology & Dermatologic Surgery, Philip O. Scumpia, MD, PhD, described the development of a biomaterial known as microporous annealed particle (MAP) hydrogel, which in preclinical studies has been shown to trigger the immune system leading to improved tissue repair and healthier, stronger skin.

“We’re preprogrammed to undergo scarring,” said Dr. Scumpia, associate professor of dermatology at the University of California, Los Angeles. “Tissue fibrosis is an evolutionary process” where a fibrotic matrix is deposited “as quickly as possible to close the gap caused by an injury,” he noted. “All of the cues in the normal wound healing process result in fibrosis, but we want to move from scarring to tissue regeneration. The goal is to make something that can shift from this evolutionary process, and it’s proven to be inherently difficult.”

Dr. Scumpia

Common approaches to wound treatment include simple and advanced dressings, negative pressure, and hyperbaric oxygen. For wounds that persist beyond 30 days, advanced treatment options include decellularized grafts such as placental membranes, amniotic membranes, and acellular dermal matrices. “There are also cellularized grafts such as dressings that contain neonatal dermal fibroblasts,” which are expensive, said Dr. Scumpia, director of dermatopathology at the West Los Angeles VA Medical Center. “There are also semi-synthetic grafts such as single or double layer dermal replacement templates and synthetic dermal substitutes in the form of sheets or foam. All of these can help with wound coverage and help chronic wounds close on their own.”

Meanwhile, tissue regeneration – or efforts to restore tissue to its original functionality – include growth factors, stem cells, or replacement extracellular matrix (skin substitutes), or a combination. “Bioengineered dressings and bioengineered skin substitutes have shown modest improvement in wound healing but not tissue regeneration,” Dr. Scumpia said. “At best, we can accelerate scar formation and close the wound quicker, but nothing has been shown to regenerate tissue.”

Approaches to skin regeneration

Studies from the embryology literature have helped researchers develop better approaches to skin regeneration. For example, fetal skin heals without scarring when injured. “Hairs form from placodes, then sebaceous glands form, and fibroblasts that are part of the papillary mesenchymal body expressing special factors such as engrailed or CRABP1 drive hair follicle formation,” he said. “Many studies have shown that sonic hedgehog signaling, and Wnt/beta-catenin signaling can play a role in the development of new hair follicles. Also, fibroblasts in the dermis can drive hair follicle formation.”

Researchers are also learning about tissue regeneration from mouse models. For example, African spiny mice have been shown to heal regeneratively. “If you make wounds large enough on lab mice, the center heals regeneratively,” Dr. Scumpia said. “What’s interesting is that these same signals are present in embryonic hair follicle development. Why is this important? Who wants a hairy scar? It’s an organized structure that develops in the wound. That can help us understand what we need to put in so that our body regenerates on its own. In mouse models, the immune system has been shown to play a role in regeneration.”

Expanding on initial work conducted at UCLA, Dr. Scumpia and his colleagues founded San Diego-based Tempo Therapeutics, which is commercializing the MAP hydrogel to mimic the natural porosity and stiffness of skin. They sought to develop a new biomaterial, he said, noting that “the skin is porous on a microscale level, allowing cells to infiltrate different areas.” And the problem with existing biomaterials “is that they don’t incorporate into the skin very well,” he explained. “They’re usually stiff and rubbery and can cause a foreign body reaction, which can result in fibrous encapsulation and inflammation.”

The MAP hydrogel is composed of randomly packed “microsphere building blocks,” including an amino acid that promotes an immune response. When injected into a wound, the hydrogel forms a porous matrix in the tissue. Surface annealing locks in porosity and tissue grows into porous spaces, which avoids scar formation pathways and enables critical organs to regain function.

During in vivo tests, researchers observed decreases in inflammation compared with traditional hydrogels in the first 48 hours. “In mouse models, we found that if you inject in a hydrogel that has no porosity, the body tries to spit it out, and you have an immune reaction,” Dr. Scumpia said. “But when we used the MAP hydrogel, we found that cells can migrate through it, which allows wounds to heal quicker. When we added an antigen in the hydrogel trying to allow the hydrogel to degrade slower, it actually degraded more rapidly, but we found that new hair follicles formed in the center of these wounds, a hallmark of skin regeneration. My lab has been studying why this occurs and trying to use this to our advantage in other models.”

In an unpublished mouse burn wound model study, he and his colleagues excised a wound, but it never healed with regeneration in the center. “We don’t understand why,” he said. But when the researchers used the MAP gel in wounds of hairless mice, they observed the formation of sebaceous glands and hair follicles over the wound beds. “It’s an exciting finding to see hair follicles develop in the center of a wound,” Dr. Scumpia said. He noted that to date, use of the MAP hydrogel has demonstrated tissue regeneration in some of the 27 veterinary cases that have been performed, including for wounds following traumatic injuries or following tumor resections on paws that allowed the pets to avoid amputation.

Clinical trials planned

The first clinical trials of the MAP hydrogel are planned for treating complex diabetic wounds in early 2024 but will likely expand to other difficult-to-treat wounds, including venous stasis ulcers, decubitus ulcers, and use following large surgical resections. Dr. Scumpia and colleagues will also examine the regenerative biomaterial for tissue aesthetics, including dermal and deep tissue filler applications. The next steps in his laboratory, he said, are to combine biomaterials with stem cells, immune factors, or small molecular activators/inhibitors to improve sweat gland, nerve, or hair follicle regeneration.

Dr. Scumpia disclosed that he is a cofounder and shareholder in Tempo Therapeutics. He has also received grant support from the National Institutes of Health, Department of Veteran Affairs, and the LEO Foundation.

CARLSBAD, CALIF. – For the estimated 10 million wounds that clinicians treat in the United States each year resulting from surgical procedures, trauma, burns, and other causes, the best outcome is a scar, a fibrotic dermis with a flattened epidermis that contains no sweat glands, no pilosebaceous units, and impaired nerve function.

But what if the outcome was skin regeneration instead of scar formation? At the annual symposium of the California Society of Dermatology & Dermatologic Surgery, Philip O. Scumpia, MD, PhD, described the development of a biomaterial known as microporous annealed particle (MAP) hydrogel, which in preclinical studies has been shown to trigger the immune system leading to improved tissue repair and healthier, stronger skin.

“We’re preprogrammed to undergo scarring,” said Dr. Scumpia, associate professor of dermatology at the University of California, Los Angeles. “Tissue fibrosis is an evolutionary process” where a fibrotic matrix is deposited “as quickly as possible to close the gap caused by an injury,” he noted. “All of the cues in the normal wound healing process result in fibrosis, but we want to move from scarring to tissue regeneration. The goal is to make something that can shift from this evolutionary process, and it’s proven to be inherently difficult.”

Dr. Scumpia

Common approaches to wound treatment include simple and advanced dressings, negative pressure, and hyperbaric oxygen. For wounds that persist beyond 30 days, advanced treatment options include decellularized grafts such as placental membranes, amniotic membranes, and acellular dermal matrices. “There are also cellularized grafts such as dressings that contain neonatal dermal fibroblasts,” which are expensive, said Dr. Scumpia, director of dermatopathology at the West Los Angeles VA Medical Center. “There are also semi-synthetic grafts such as single or double layer dermal replacement templates and synthetic dermal substitutes in the form of sheets or foam. All of these can help with wound coverage and help chronic wounds close on their own.”

Meanwhile, tissue regeneration – or efforts to restore tissue to its original functionality – include growth factors, stem cells, or replacement extracellular matrix (skin substitutes), or a combination. “Bioengineered dressings and bioengineered skin substitutes have shown modest improvement in wound healing but not tissue regeneration,” Dr. Scumpia said. “At best, we can accelerate scar formation and close the wound quicker, but nothing has been shown to regenerate tissue.”

Approaches to skin regeneration

Studies from the embryology literature have helped researchers develop better approaches to skin regeneration. For example, fetal skin heals without scarring when injured. “Hairs form from placodes, then sebaceous glands form, and fibroblasts that are part of the papillary mesenchymal body expressing special factors such as engrailed or CRABP1 drive hair follicle formation,” he said. “Many studies have shown that sonic hedgehog signaling, and Wnt/beta-catenin signaling can play a role in the development of new hair follicles. Also, fibroblasts in the dermis can drive hair follicle formation.”

Researchers are also learning about tissue regeneration from mouse models. For example, African spiny mice have been shown to heal regeneratively. “If you make wounds large enough on lab mice, the center heals regeneratively,” Dr. Scumpia said. “What’s interesting is that these same signals are present in embryonic hair follicle development. Why is this important? Who wants a hairy scar? It’s an organized structure that develops in the wound. That can help us understand what we need to put in so that our body regenerates on its own. In mouse models, the immune system has been shown to play a role in regeneration.”

Expanding on initial work conducted at UCLA, Dr. Scumpia and his colleagues founded San Diego-based Tempo Therapeutics, which is commercializing the MAP hydrogel to mimic the natural porosity and stiffness of skin. They sought to develop a new biomaterial, he said, noting that “the skin is porous on a microscale level, allowing cells to infiltrate different areas.” And the problem with existing biomaterials “is that they don’t incorporate into the skin very well,” he explained. “They’re usually stiff and rubbery and can cause a foreign body reaction, which can result in fibrous encapsulation and inflammation.”

The MAP hydrogel is composed of randomly packed “microsphere building blocks,” including an amino acid that promotes an immune response. When injected into a wound, the hydrogel forms a porous matrix in the tissue. Surface annealing locks in porosity and tissue grows into porous spaces, which avoids scar formation pathways and enables critical organs to regain function.

During in vivo tests, researchers observed decreases in inflammation compared with traditional hydrogels in the first 48 hours. “In mouse models, we found that if you inject in a hydrogel that has no porosity, the body tries to spit it out, and you have an immune reaction,” Dr. Scumpia said. “But when we used the MAP hydrogel, we found that cells can migrate through it, which allows wounds to heal quicker. When we added an antigen in the hydrogel trying to allow the hydrogel to degrade slower, it actually degraded more rapidly, but we found that new hair follicles formed in the center of these wounds, a hallmark of skin regeneration. My lab has been studying why this occurs and trying to use this to our advantage in other models.”

In an unpublished mouse burn wound model study, he and his colleagues excised a wound, but it never healed with regeneration in the center. “We don’t understand why,” he said. But when the researchers used the MAP gel in wounds of hairless mice, they observed the formation of sebaceous glands and hair follicles over the wound beds. “It’s an exciting finding to see hair follicles develop in the center of a wound,” Dr. Scumpia said. He noted that to date, use of the MAP hydrogel has demonstrated tissue regeneration in some of the 27 veterinary cases that have been performed, including for wounds following traumatic injuries or following tumor resections on paws that allowed the pets to avoid amputation.

Clinical trials planned

The first clinical trials of the MAP hydrogel are planned for treating complex diabetic wounds in early 2024 but will likely expand to other difficult-to-treat wounds, including venous stasis ulcers, decubitus ulcers, and use following large surgical resections. Dr. Scumpia and colleagues will also examine the regenerative biomaterial for tissue aesthetics, including dermal and deep tissue filler applications. The next steps in his laboratory, he said, are to combine biomaterials with stem cells, immune factors, or small molecular activators/inhibitors to improve sweat gland, nerve, or hair follicle regeneration.

Dr. Scumpia disclosed that he is a cofounder and shareholder in Tempo Therapeutics. He has also received grant support from the National Institutes of Health, Department of Veteran Affairs, and the LEO Foundation.

CARLSBAD, CALIF. – For the estimated 10 million wounds that clinicians treat in the United States each year resulting from surgical procedures, trauma, burns, and other causes, the best outcome is a scar, a fibrotic dermis with a flattened epidermis that contains no sweat glands, no pilosebaceous units, and impaired nerve function.

But what if the outcome was skin regeneration instead of scar formation? At the annual symposium of the California Society of Dermatology & Dermatologic Surgery, Philip O. Scumpia, MD, PhD, described the development of a biomaterial known as microporous annealed particle (MAP) hydrogel, which in preclinical studies has been shown to trigger the immune system leading to improved tissue repair and healthier, stronger skin.

“We’re preprogrammed to undergo scarring,” said Dr. Scumpia, associate professor of dermatology at the University of California, Los Angeles. “Tissue fibrosis is an evolutionary process” where a fibrotic matrix is deposited “as quickly as possible to close the gap caused by an injury,” he noted. “All of the cues in the normal wound healing process result in fibrosis, but we want to move from scarring to tissue regeneration. The goal is to make something that can shift from this evolutionary process, and it’s proven to be inherently difficult.”

Dr. Scumpia

Common approaches to wound treatment include simple and advanced dressings, negative pressure, and hyperbaric oxygen. For wounds that persist beyond 30 days, advanced treatment options include decellularized grafts such as placental membranes, amniotic membranes, and acellular dermal matrices. “There are also cellularized grafts such as dressings that contain neonatal dermal fibroblasts,” which are expensive, said Dr. Scumpia, director of dermatopathology at the West Los Angeles VA Medical Center. “There are also semi-synthetic grafts such as single or double layer dermal replacement templates and synthetic dermal substitutes in the form of sheets or foam. All of these can help with wound coverage and help chronic wounds close on their own.”

Meanwhile, tissue regeneration – or efforts to restore tissue to its original functionality – include growth factors, stem cells, or replacement extracellular matrix (skin substitutes), or a combination. “Bioengineered dressings and bioengineered skin substitutes have shown modest improvement in wound healing but not tissue regeneration,” Dr. Scumpia said. “At best, we can accelerate scar formation and close the wound quicker, but nothing has been shown to regenerate tissue.”

Approaches to skin regeneration

Studies from the embryology literature have helped researchers develop better approaches to skin regeneration. For example, fetal skin heals without scarring when injured. “Hairs form from placodes, then sebaceous glands form, and fibroblasts that are part of the papillary mesenchymal body expressing special factors such as engrailed or CRABP1 drive hair follicle formation,” he said. “Many studies have shown that sonic hedgehog signaling, and Wnt/beta-catenin signaling can play a role in the development of new hair follicles. Also, fibroblasts in the dermis can drive hair follicle formation.”

Researchers are also learning about tissue regeneration from mouse models. For example, African spiny mice have been shown to heal regeneratively. “If you make wounds large enough on lab mice, the center heals regeneratively,” Dr. Scumpia said. “What’s interesting is that these same signals are present in embryonic hair follicle development. Why is this important? Who wants a hairy scar? It’s an organized structure that develops in the wound. That can help us understand what we need to put in so that our body regenerates on its own. In mouse models, the immune system has been shown to play a role in regeneration.”

Expanding on initial work conducted at UCLA, Dr. Scumpia and his colleagues founded San Diego-based Tempo Therapeutics, which is commercializing the MAP hydrogel to mimic the natural porosity and stiffness of skin. They sought to develop a new biomaterial, he said, noting that “the skin is porous on a microscale level, allowing cells to infiltrate different areas.” And the problem with existing biomaterials “is that they don’t incorporate into the skin very well,” he explained. “They’re usually stiff and rubbery and can cause a foreign body reaction, which can result in fibrous encapsulation and inflammation.”

The MAP hydrogel is composed of randomly packed “microsphere building blocks,” including an amino acid that promotes an immune response. When injected into a wound, the hydrogel forms a porous matrix in the tissue. Surface annealing locks in porosity and tissue grows into porous spaces, which avoids scar formation pathways and enables critical organs to regain function.

During in vivo tests, researchers observed decreases in inflammation compared with traditional hydrogels in the first 48 hours. “In mouse models, we found that if you inject in a hydrogel that has no porosity, the body tries to spit it out, and you have an immune reaction,” Dr. Scumpia said. “But when we used the MAP hydrogel, we found that cells can migrate through it, which allows wounds to heal quicker. When we added an antigen in the hydrogel trying to allow the hydrogel to degrade slower, it actually degraded more rapidly, but we found that new hair follicles formed in the center of these wounds, a hallmark of skin regeneration. My lab has been studying why this occurs and trying to use this to our advantage in other models.”

In an unpublished mouse burn wound model study, he and his colleagues excised a wound, but it never healed with regeneration in the center. “We don’t understand why,” he said. But when the researchers used the MAP gel in wounds of hairless mice, they observed the formation of sebaceous glands and hair follicles over the wound beds. “It’s an exciting finding to see hair follicles develop in the center of a wound,” Dr. Scumpia said. He noted that to date, use of the MAP hydrogel has demonstrated tissue regeneration in some of the 27 veterinary cases that have been performed, including for wounds following traumatic injuries or following tumor resections on paws that allowed the pets to avoid amputation.

Clinical trials planned

The first clinical trials of the MAP hydrogel are planned for treating complex diabetic wounds in early 2024 but will likely expand to other difficult-to-treat wounds, including venous stasis ulcers, decubitus ulcers, and use following large surgical resections. Dr. Scumpia and colleagues will also examine the regenerative biomaterial for tissue aesthetics, including dermal and deep tissue filler applications. The next steps in his laboratory, he said, are to combine biomaterials with stem cells, immune factors, or small molecular activators/inhibitors to improve sweat gland, nerve, or hair follicle regeneration.

Dr. Scumpia disclosed that he is a cofounder and shareholder in Tempo Therapeutics. He has also received grant support from the National Institutes of Health, Department of Veteran Affairs, and the LEO Foundation.

TOPLINE:

Detection rates of mild cognitive impairment (MCI) in primary care are extremely low, with only about 8% of expected cases diagnosed on average, a finding that points to an urgent need to improve early detection in primary care.

METHODOLOGY:

• Researchers estimated MCI detection rates among 226,756 primary care clinicians and 54,597 practices that had at least 25 patients enrolled in Medicare between 2017 and 2019. 
• They compared the expected number of MCI cases, based on a predictive model, to actual diagnosed cases as documented in claims and encounter data.
• They accounted for uncertainty in these estimates to determine whether detection rates are within the expected range or significantly higher or lower.

TAKEAWAY:

• More than 25% of clinicians and practices did not have a single patient with diagnosed MCI; the average detection rate was 0.01 for both clinicians and practices.
• The modeled expected MCI detection rate, however, was much higher (average 0.19 for clinicians and 0.20 for practices).
• Average detection rates for clinicians and practices was 0.08, with more than 99% of clinicians and practices underdiagnosing MCI; clinicians practicing geriatric medicine had higher detection rates than others.

IN PRACTICE:

The findings are “concerning not only because patients might not get identified for a disease-modifying AD treatment in time, but also because numerous causes of MCI – such as hypothyroidism and medication side effects – are reversible, and the condition itself can be stabilized by lifestyle modification interventions,” the authors write.

SOURCE:

The study was published online in the Journal of Prevention of Alzheimer’s Disease. The first author was Ying Liu, PhD, of the University of Southern California, Los Angeles.

LIMITATIONS:

The predictive model based on demographic information has only moderate accuracy. Expected prevalence of MCI was based on cognitive test scores, which is not the same as a true clinical diagnosis.

DISCLOSURES:

The study was partially funded by a contract from Genentech to the University of Southern California. Coauthors Soeren Mattke and Christopher Wallick have disclosed relationships with Genentech.

A version of this article appeared on Medscape.com.

TOPLINE:

Detection rates of mild cognitive impairment (MCI) in primary care are extremely low, with only about 8% of expected cases diagnosed on average, a finding that points to an urgent need to improve early detection in primary care.

METHODOLOGY:

• Researchers estimated MCI detection rates among 226,756 primary care clinicians and 54,597 practices that had at least 25 patients enrolled in Medicare between 2017 and 2019. 
• They compared the expected number of MCI cases, based on a predictive model, to actual diagnosed cases as documented in claims and encounter data.
• They accounted for uncertainty in these estimates to determine whether detection rates are within the expected range or significantly higher or lower.

TAKEAWAY:

• More than 25% of clinicians and practices did not have a single patient with diagnosed MCI; the average detection rate was 0.01 for both clinicians and practices.
• The modeled expected MCI detection rate, however, was much higher (average 0.19 for clinicians and 0.20 for practices).
• Average detection rates for clinicians and practices was 0.08, with more than 99% of clinicians and practices underdiagnosing MCI; clinicians practicing geriatric medicine had higher detection rates than others.

IN PRACTICE:

The findings are “concerning not only because patients might not get identified for a disease-modifying AD treatment in time, but also because numerous causes of MCI – such as hypothyroidism and medication side effects – are reversible, and the condition itself can be stabilized by lifestyle modification interventions,” the authors write.

SOURCE:

The study was published online in the Journal of Prevention of Alzheimer’s Disease. The first author was Ying Liu, PhD, of the University of Southern California, Los Angeles.

LIMITATIONS:

The predictive model based on demographic information has only moderate accuracy. Expected prevalence of MCI was based on cognitive test scores, which is not the same as a true clinical diagnosis.

DISCLOSURES:

The study was partially funded by a contract from Genentech to the University of Southern California. Coauthors Soeren Mattke and Christopher Wallick have disclosed relationships with Genentech.

A version of this article appeared on Medscape.com.

TOPLINE:

Detection rates of mild cognitive impairment (MCI) in primary care are extremely low, with only about 8% of expected cases diagnosed on average, a finding that points to an urgent need to improve early detection in primary care.

METHODOLOGY:

• Researchers estimated MCI detection rates among 226,756 primary care clinicians and 54,597 practices that had at least 25 patients enrolled in Medicare between 2017 and 2019. 
• They compared the expected number of MCI cases, based on a predictive model, to actual diagnosed cases as documented in claims and encounter data.
• They accounted for uncertainty in these estimates to determine whether detection rates are within the expected range or significantly higher or lower.

TAKEAWAY:

• More than 25% of clinicians and practices did not have a single patient with diagnosed MCI; the average detection rate was 0.01 for both clinicians and practices.
• The modeled expected MCI detection rate, however, was much higher (average 0.19 for clinicians and 0.20 for practices).
• Average detection rates for clinicians and practices was 0.08, with more than 99% of clinicians and practices underdiagnosing MCI; clinicians practicing geriatric medicine had higher detection rates than others.

IN PRACTICE:

The findings are “concerning not only because patients might not get identified for a disease-modifying AD treatment in time, but also because numerous causes of MCI – such as hypothyroidism and medication side effects – are reversible, and the condition itself can be stabilized by lifestyle modification interventions,” the authors write.

SOURCE:

The study was published online in the Journal of Prevention of Alzheimer’s Disease. The first author was Ying Liu, PhD, of the University of Southern California, Los Angeles.

LIMITATIONS:

The predictive model based on demographic information has only moderate accuracy. Expected prevalence of MCI was based on cognitive test scores, which is not the same as a true clinical diagnosis.

DISCLOSURES:

The study was partially funded by a contract from Genentech to the University of Southern California. Coauthors Soeren Mattke and Christopher Wallick have disclosed relationships with Genentech.

A version of this article appeared on Medscape.com.

WASHINGTON – Half of youth broadcasting live streams on the online platform Twitch revealed their real-world location, and nearly half provided their name to viewers, according to research presented at the annual meeting of the American Academy of Pediatrics. It took researchers less than 5 minutes – and sometimes as little as 12 seconds – to find minors in different video game categories, suggesting the environment offers opportunities to predators to gain sensitive information about minors, reported Fiona Dubrosa, BS, BA, a visiting scholar at Cohen Children’s Medical Center, New York, and colleagues.

A ‘clandestine, threatening digital environment’

“Twitch represents a clandestine, threatening digital environment where minors are interacting with adult strangers without parental supervision,” the authors concluded. “The nature of live streaming makes it particularly dangerous, as there is no way to take back information that has been revealed or regulate content or viewers. Parents and pediatricians should be aware of the dangers presented by Twitch and other live-streaming platforms and counsel children on best practices for Internet safety.”

Twitch is an online streaming platform where people can watch creator’s live content, such as music performances or narrating real-time video game playing. The platform requires live streamers to be 13 years old with a valid email address or phone number to create an account, but no age restrictions or identification requirements exist for viewers, “potentially putting minors in danger of being watched, followed, and groomed by predators,” the researchers noted. They added that people following different streamers receive notifications when those streamers are live. Further, “viewers can donate money to streamers, which can make it easier for predators to manipulate, track, and encourage risky behaviors from minors.”

To better understand the risks the platform might pose to minors, the researchers searched for and analyzed popular video game live streams that appeared to be streamed by minors who had their cameras on and their faces visible. Then the researchers noted the name of the video game, the topics discussed by the streamers, the time it took to find minors under each game, and each streamer’s age, name, follower count, location, streaming schedule, and social media links for money donations.

The researchers analyzed 100 Twitch streamers who were minors, who had a combined 1,755,452 million followers. Nearly half the streamers (47%) provided their presumably real names, and half (50%) gave out their location. Nearly two-thirds (64%) linked other social media accounts they had and encouraged viewers to follow them. Detailed schedules of when they would be live were available for 38% of the streamers, and 37% of the minor streamers were accepting money donations.

Only 11% of the discussion on the streams revealed personal details, most often related to trying on different outfits for viewers and talking about real-world locations they liked to visit. The researchers needed anywhere from 12 seconds to 5 minutes to find a minor in each game category.

”Young users clearly feel a false sense of safety on the platform; a significant proportion were willing to reveal personal information despite having no knowledge of who might be listening,” the researchers said. “The donation system provides a menacing avenue for manipulation and continued exploitation of minors. Our findings reveal the need for stricter age limitations for streamers and more stringent identity verification of audience members on Twitch.”
 

Open-minded parental guidance is warranted

Jenny Radesky, MD, a developmental behavioral pediatrician and media researcher at University of Michigan Medicine, Ann Arbor, was not surprised that many teens live stream on Twitch since it’s a popular platform for video gaming, but she was surprised at how many revealed their locations and other personal details.

courtesy University of Michigan Medicine

“I suspect that they do this to build closeness with their viewers, by seeming more authentic,” said Dr. Radesky, who was not involved in the study. “It is this type of parasocial relationship with influencers and gamers that keeps an audience engaged, and encourages future viewing and purchases.”

Their willingness to share personal details suggests it’s important to conduct qualitative research to find out how teen live streamers think about privacy risks, what privacy settings they can use and choose to use, and how they handle inappropriate contact from adults, Dr. Radesky said.

Meanwhile, parents should talk with their kids in an open-minded way about what platforms they use and what they like and dislike about them. She recommended parents read the Common Sense Media guide about different social platforms ”to understand what attracts kids to content on specific sites, what their pitfalls are, and what types of privacy and safety settings are available.”

“A child or teen is much more likely to be honest about negative experiences online if they think their parent will hear them out – not judge them or take away their tech. No teen wants to talk with a panicky parent,” Dr. Radesky said.

David Hill, MD, a hospitalist pediatrician for Goldsboro Pediatrics in Wayne County, North Carolina, who also specializes in media communication, said that Twitch is just one example of a social media platform where children can encounter a variety of dangers, including sometimes adult predators.

courtesy Goldsboro Pediatrics

“This just highlights the importance of parents having an ongoing conversation with their children about how they use their social media platforms and ensuring, just as we do with learning to ride a bicycle or learning to drive a car, that they apply some basic rules of safety,” Dr. Hill said. Then it’s important to keep coming back to that conversation “again and again as they grow and change and as those platforms change to ensure that those kids are continuing to apply those rules consistently.

“The best way for parents to keep up is ask your kids,” he said. “They love to share. They love to teach. They love to be in a position to show you something, especially if it’s something that interests them.”

An example of a rule would be setting personal accounts to private, not public, by default, Dr. Radesky said. “When interviewed, teens often say that they feel intruded upon by older people ‘stalking’ them or trying to connect with them on social platforms,” so making an account private can reduce those opportunities.

For teens who specifically want to create content on social platforms, parent oversight is needed, she said, but she acknowledged it can be a lot of work. “This might take the form of talking about what a teen plans to post before they do, expectations for positive behaviors or language, plans for privacy settings (such as public vs. private accounts), and what to do with trolls or hateful comment,” she said. “Parents may want to follow their child’s account to check in on it.”
 

Useful advice

Dr. Radesky also provided a handful of talking points that pediatricians can use in talking with patients who use these platforms:

• Keep your account private to just your friends and people you want to interact with. There are a lot of people on the Internet that you don’t want intruding upon your social life.
• Maintain your feed and the accounts you follow to keep it positive, entertaining, and not a source of stress or self-doubt. Content creators are always trying to grab your attention in new ways, some of which are rude or dehumanizing, so don’t waste your time on things that bring you down.
• Talk about why you want to post or live stream. Is it to get reactions or feel validated? If so, can you find other ways to feel validated that don’t require performing for other people? Is it to share a special skill? If so, how do you keep your posts creative and community building rather than attention grabbing? And how can you keep your parents involved so that they can help you navigate challenges?”

Ms. Dubrosa and Dr. Hill had no disclosures. Dr. Radesky is a consultant for Melissa & Doug. No information on external funding was provided.

WASHINGTON – Half of youth broadcasting live streams on the online platform Twitch revealed their real-world location, and nearly half provided their name to viewers, according to research presented at the annual meeting of the American Academy of Pediatrics. It took researchers less than 5 minutes – and sometimes as little as 12 seconds – to find minors in different video game categories, suggesting the environment offers opportunities to predators to gain sensitive information about minors, reported Fiona Dubrosa, BS, BA, a visiting scholar at Cohen Children’s Medical Center, New York, and colleagues.

A ‘clandestine, threatening digital environment’

“Twitch represents a clandestine, threatening digital environment where minors are interacting with adult strangers without parental supervision,” the authors concluded. “The nature of live streaming makes it particularly dangerous, as there is no way to take back information that has been revealed or regulate content or viewers. Parents and pediatricians should be aware of the dangers presented by Twitch and other live-streaming platforms and counsel children on best practices for Internet safety.”

Twitch is an online streaming platform where people can watch creator’s live content, such as music performances or narrating real-time video game playing. The platform requires live streamers to be 13 years old with a valid email address or phone number to create an account, but no age restrictions or identification requirements exist for viewers, “potentially putting minors in danger of being watched, followed, and groomed by predators,” the researchers noted. They added that people following different streamers receive notifications when those streamers are live. Further, “viewers can donate money to streamers, which can make it easier for predators to manipulate, track, and encourage risky behaviors from minors.”

To better understand the risks the platform might pose to minors, the researchers searched for and analyzed popular video game live streams that appeared to be streamed by minors who had their cameras on and their faces visible. Then the researchers noted the name of the video game, the topics discussed by the streamers, the time it took to find minors under each game, and each streamer’s age, name, follower count, location, streaming schedule, and social media links for money donations.

The researchers analyzed 100 Twitch streamers who were minors, who had a combined 1,755,452 million followers. Nearly half the streamers (47%) provided their presumably real names, and half (50%) gave out their location. Nearly two-thirds (64%) linked other social media accounts they had and encouraged viewers to follow them. Detailed schedules of when they would be live were available for 38% of the streamers, and 37% of the minor streamers were accepting money donations.

Only 11% of the discussion on the streams revealed personal details, most often related to trying on different outfits for viewers and talking about real-world locations they liked to visit. The researchers needed anywhere from 12 seconds to 5 minutes to find a minor in each game category.

”Young users clearly feel a false sense of safety on the platform; a significant proportion were willing to reveal personal information despite having no knowledge of who might be listening,” the researchers said. “The donation system provides a menacing avenue for manipulation and continued exploitation of minors. Our findings reveal the need for stricter age limitations for streamers and more stringent identity verification of audience members on Twitch.”
 

Open-minded parental guidance is warranted

Jenny Radesky, MD, a developmental behavioral pediatrician and media researcher at University of Michigan Medicine, Ann Arbor, was not surprised that many teens live stream on Twitch since it’s a popular platform for video gaming, but she was surprised at how many revealed their locations and other personal details.

courtesy University of Michigan Medicine

“I suspect that they do this to build closeness with their viewers, by seeming more authentic,” said Dr. Radesky, who was not involved in the study. “It is this type of parasocial relationship with influencers and gamers that keeps an audience engaged, and encourages future viewing and purchases.”

Their willingness to share personal details suggests it’s important to conduct qualitative research to find out how teen live streamers think about privacy risks, what privacy settings they can use and choose to use, and how they handle inappropriate contact from adults, Dr. Radesky said.

Meanwhile, parents should talk with their kids in an open-minded way about what platforms they use and what they like and dislike about them. She recommended parents read the Common Sense Media guide about different social platforms ”to understand what attracts kids to content on specific sites, what their pitfalls are, and what types of privacy and safety settings are available.”

“A child or teen is much more likely to be honest about negative experiences online if they think their parent will hear them out – not judge them or take away their tech. No teen wants to talk with a panicky parent,” Dr. Radesky said.

David Hill, MD, a hospitalist pediatrician for Goldsboro Pediatrics in Wayne County, North Carolina, who also specializes in media communication, said that Twitch is just one example of a social media platform where children can encounter a variety of dangers, including sometimes adult predators.

courtesy Goldsboro Pediatrics

“This just highlights the importance of parents having an ongoing conversation with their children about how they use their social media platforms and ensuring, just as we do with learning to ride a bicycle or learning to drive a car, that they apply some basic rules of safety,” Dr. Hill said. Then it’s important to keep coming back to that conversation “again and again as they grow and change and as those platforms change to ensure that those kids are continuing to apply those rules consistently.

“The best way for parents to keep up is ask your kids,” he said. “They love to share. They love to teach. They love to be in a position to show you something, especially if it’s something that interests them.”

An example of a rule would be setting personal accounts to private, not public, by default, Dr. Radesky said. “When interviewed, teens often say that they feel intruded upon by older people ‘stalking’ them or trying to connect with them on social platforms,” so making an account private can reduce those opportunities.

For teens who specifically want to create content on social platforms, parent oversight is needed, she said, but she acknowledged it can be a lot of work. “This might take the form of talking about what a teen plans to post before they do, expectations for positive behaviors or language, plans for privacy settings (such as public vs. private accounts), and what to do with trolls or hateful comment,” she said. “Parents may want to follow their child’s account to check in on it.”
 

Useful advice

Dr. Radesky also provided a handful of talking points that pediatricians can use in talking with patients who use these platforms:

• Keep your account private to just your friends and people you want to interact with. There are a lot of people on the Internet that you don’t want intruding upon your social life.
• Maintain your feed and the accounts you follow to keep it positive, entertaining, and not a source of stress or self-doubt. Content creators are always trying to grab your attention in new ways, some of which are rude or dehumanizing, so don’t waste your time on things that bring you down.
• Talk about why you want to post or live stream. Is it to get reactions or feel validated? If so, can you find other ways to feel validated that don’t require performing for other people? Is it to share a special skill? If so, how do you keep your posts creative and community building rather than attention grabbing? And how can you keep your parents involved so that they can help you navigate challenges?”

Ms. Dubrosa and Dr. Hill had no disclosures. Dr. Radesky is a consultant for Melissa & Doug. No information on external funding was provided.

WASHINGTON – Half of youth broadcasting live streams on the online platform Twitch revealed their real-world location, and nearly half provided their name to viewers, according to research presented at the annual meeting of the American Academy of Pediatrics. It took researchers less than 5 minutes – and sometimes as little as 12 seconds – to find minors in different video game categories, suggesting the environment offers opportunities to predators to gain sensitive information about minors, reported Fiona Dubrosa, BS, BA, a visiting scholar at Cohen Children’s Medical Center, New York, and colleagues.

A ‘clandestine, threatening digital environment’

“Twitch represents a clandestine, threatening digital environment where minors are interacting with adult strangers without parental supervision,” the authors concluded. “The nature of live streaming makes it particularly dangerous, as there is no way to take back information that has been revealed or regulate content or viewers. Parents and pediatricians should be aware of the dangers presented by Twitch and other live-streaming platforms and counsel children on best practices for Internet safety.”

Twitch is an online streaming platform where people can watch creator’s live content, such as music performances or narrating real-time video game playing. The platform requires live streamers to be 13 years old with a valid email address or phone number to create an account, but no age restrictions or identification requirements exist for viewers, “potentially putting minors in danger of being watched, followed, and groomed by predators,” the researchers noted. They added that people following different streamers receive notifications when those streamers are live. Further, “viewers can donate money to streamers, which can make it easier for predators to manipulate, track, and encourage risky behaviors from minors.”

To better understand the risks the platform might pose to minors, the researchers searched for and analyzed popular video game live streams that appeared to be streamed by minors who had their cameras on and their faces visible. Then the researchers noted the name of the video game, the topics discussed by the streamers, the time it took to find minors under each game, and each streamer’s age, name, follower count, location, streaming schedule, and social media links for money donations.

The researchers analyzed 100 Twitch streamers who were minors, who had a combined 1,755,452 million followers. Nearly half the streamers (47%) provided their presumably real names, and half (50%) gave out their location. Nearly two-thirds (64%) linked other social media accounts they had and encouraged viewers to follow them. Detailed schedules of when they would be live were available for 38% of the streamers, and 37% of the minor streamers were accepting money donations.

Only 11% of the discussion on the streams revealed personal details, most often related to trying on different outfits for viewers and talking about real-world locations they liked to visit. The researchers needed anywhere from 12 seconds to 5 minutes to find a minor in each game category.

”Young users clearly feel a false sense of safety on the platform; a significant proportion were willing to reveal personal information despite having no knowledge of who might be listening,” the researchers said. “The donation system provides a menacing avenue for manipulation and continued exploitation of minors. Our findings reveal the need for stricter age limitations for streamers and more stringent identity verification of audience members on Twitch.”
 

Open-minded parental guidance is warranted

Jenny Radesky, MD, a developmental behavioral pediatrician and media researcher at University of Michigan Medicine, Ann Arbor, was not surprised that many teens live stream on Twitch since it’s a popular platform for video gaming, but she was surprised at how many revealed their locations and other personal details.

courtesy University of Michigan Medicine

“I suspect that they do this to build closeness with their viewers, by seeming more authentic,” said Dr. Radesky, who was not involved in the study. “It is this type of parasocial relationship with influencers and gamers that keeps an audience engaged, and encourages future viewing and purchases.”

Their willingness to share personal details suggests it’s important to conduct qualitative research to find out how teen live streamers think about privacy risks, what privacy settings they can use and choose to use, and how they handle inappropriate contact from adults, Dr. Radesky said.

Meanwhile, parents should talk with their kids in an open-minded way about what platforms they use and what they like and dislike about them. She recommended parents read the Common Sense Media guide about different social platforms ”to understand what attracts kids to content on specific sites, what their pitfalls are, and what types of privacy and safety settings are available.”

“A child or teen is much more likely to be honest about negative experiences online if they think their parent will hear them out – not judge them or take away their tech. No teen wants to talk with a panicky parent,” Dr. Radesky said.

David Hill, MD, a hospitalist pediatrician for Goldsboro Pediatrics in Wayne County, North Carolina, who also specializes in media communication, said that Twitch is just one example of a social media platform where children can encounter a variety of dangers, including sometimes adult predators.

courtesy Goldsboro Pediatrics

“This just highlights the importance of parents having an ongoing conversation with their children about how they use their social media platforms and ensuring, just as we do with learning to ride a bicycle or learning to drive a car, that they apply some basic rules of safety,” Dr. Hill said. Then it’s important to keep coming back to that conversation “again and again as they grow and change and as those platforms change to ensure that those kids are continuing to apply those rules consistently.

“The best way for parents to keep up is ask your kids,” he said. “They love to share. They love to teach. They love to be in a position to show you something, especially if it’s something that interests them.”

An example of a rule would be setting personal accounts to private, not public, by default, Dr. Radesky said. “When interviewed, teens often say that they feel intruded upon by older people ‘stalking’ them or trying to connect with them on social platforms,” so making an account private can reduce those opportunities.

For teens who specifically want to create content on social platforms, parent oversight is needed, she said, but she acknowledged it can be a lot of work. “This might take the form of talking about what a teen plans to post before they do, expectations for positive behaviors or language, plans for privacy settings (such as public vs. private accounts), and what to do with trolls or hateful comment,” she said. “Parents may want to follow their child’s account to check in on it.”
 

Useful advice

Dr. Radesky also provided a handful of talking points that pediatricians can use in talking with patients who use these platforms:

• Keep your account private to just your friends and people you want to interact with. There are a lot of people on the Internet that you don’t want intruding upon your social life.
• Maintain your feed and the accounts you follow to keep it positive, entertaining, and not a source of stress or self-doubt. Content creators are always trying to grab your attention in new ways, some of which are rude or dehumanizing, so don’t waste your time on things that bring you down.
• Talk about why you want to post or live stream. Is it to get reactions or feel validated? If so, can you find other ways to feel validated that don’t require performing for other people? Is it to share a special skill? If so, how do you keep your posts creative and community building rather than attention grabbing? And how can you keep your parents involved so that they can help you navigate challenges?”

Ms. Dubrosa and Dr. Hill had no disclosures. Dr. Radesky is a consultant for Melissa & Doug. No information on external funding was provided.

Studies have shown links between statin use and type 2 diabetes (T2D) for more than a decade. A U.S. Food and Drug Administration label change for the drugs warned in 2012 about reports of increased risks of high blood glucose and glycosylated hemoglobin (A1c) levels. However, in the same warning, the FDA said it “continues to believe that the cardiovascular benefits of statins outweigh these small increased risks.”

Indeed, although the warning triggered much discussion at the time and a number of meta-analyses and other observational studies in more recent years, that conclusion seems to hold among clinicians and society guidelines.

For example, in a recent practice pointer on the risk of diabetes with statins published in the BMJ, Ishak Mansi, MD, of the Orlando VA Health Care System, and colleagues write, “This potential adverse effect of diabetes with statin use should not be a barrier to starting statin treatment when indicated.”

They also called for further research to answer such questions as, “Is statin-associated diabetes reversible upon statin discontinuation? Would intermittent use minimize this risk while maintaining cardiovascular benefits?”

An earlier study among individuals at high risk for diabetes found significantly higher rates of incident diabetes at 10 years among patients on placebo, metformin, or lifestyle intervention who also initiated statin therapy. Jill Crandall, MD, Albert Einstein College of Medicine, New York, and colleagues conclude, “For individual patients, a potential modest increase in diabetes risk clearly needs to be balanced against the consistent and highly significant reductions in myocardial infarction, stroke, and cardiovascular death associated with statin treatment.”

In the same vein, a recent review by Byron Hoogwerf, MD, Emeritus, department of endocrinology, diabetes, and metabolism, Cleveland Clinic, is titled, “Statins may increase diabetes, but benefit still outweighs risk.”
 

Rosuvastatin versus Atorvastatin

The latest study in this arena is an analysis of the LODESTAR randomized controlled trial of 4,400 patients with coronary artery disease in 12 hospitals in Korea which compares the risks associated with individual statins.

Senior author Myeong-Ki Hong, MD, PhD, Yonsei University College of Medicine, Severance Cardiovascular Hospital, Seoul, South Korea, said in an interview that the study was prompted by the “limited” studies evaluating clinical outcomes, including diabetes risk, according to statin type.

Dr. Hong and colleagues compared the risk of developing diabetes among those taking rosuvastatin (mean daily dose, 17.1 mg) or atorvastatin (mean daily dose 36 mg) for 3 years. While both statins effectively prevented myocardial infarction, stroke, and death, those taking rosuvastatin had a higher incidence of new-onset T2D requiring initiation of antidiabetic drugs (7.2% vs. 5.3%; hazard ratio, 1.39) and cataract surgery (2.5% vs. 1.5%; HR, 1.66).

Overall, the HR of new-onset T2D was 1.29 (95% confidence interval, 1.01-1.63; P = .04).

“The percentages of new-onset diabetes and cataract are in line with previous studies regarding statin therapy in patients with atherosclerotic cardiovascular disease,” Dr. Hong said. “Additional research specifically focusing on these outcomes is required, with more frequent measurement of glucose and A1c levels to detect new-onset diabetes and regular ophthalmologic examinations to detect cataracts.”

“However,” he added, “when using rosuvastatin over atorvastatin, we ... emphasize the importance of meticulous monitoring and appropriate lifestyle interventions to mitigate the risk of new-onset diabetes or cataracts.”

Steven Nissen, MD, chief academic officer of Cleveland Clinic’s Heart and Vascular Institute, was not convinced, and said the study “does not provide useful insights into the use of these drugs.”

The investigators used whatever dose they wanted, “and the authors report only the median dose after 3 years,” he said in an interview. “Because there was a slightly greater reduction in low-density lipoprotein (LDL) cholesterol with rosuvastatin, the relative dose was actually higher.”

“We know that new-onset diabetes with statins is dose-dependent,” he said. “The P-values for diabetes incidence were marginal (very close to P = .05). Accordingly, the diabetes data are unconvincing. ... The similar efficacy is not surprising given the open-label dosing with relatively similar effects on lipids.”

Seth Shay Martin, MD, MHS, director of the Advanced Lipid Disorders Program and Digital Health Lab, Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins Medicine, Baltimore, also commented on the results. The findings are “in line with existing knowledge and current guidelines,” he said. “Therefore, the study should not influence prescribing.”

“Although the study suggests that rosuvastatin was associated with a higher risk of new-onset diabetes mellitus requiring antidiabetics and cataract surgery, compared with atorvastatin, these findings should be interpreted with caution given the open-label nature of the study and require further investigation,” he said.

“The mean daily doses of statins were somewhat below target for secondary prevention,” he noted. “Ideally, patients with coronary artery disease (CAD) take 20-40 mg daily of rosuvastatin or 40-80 mg daily of atorvastatin.”

“Furthermore, the LDL cholesterol levels were not optimized in the patients,” he said. “The mean LDL-C was 1.8-1.9 mmol/L, which is equivalent to 70-73 mg/dL. In the current treatment era, we generally treat to LDL-C levels less than 70 mg/dL and often less than 55 mg/dL in CAD patients.”

“The cataracts finding is particularly odd,” he added. “There was historic concern for cataracts with statin therapy, initially because of studies in beagle dogs. However, high-quality evidence from statin trials has not shown a risk for cataracts.” 

So which statin has the lowest risk of triggering new-onset diabetes? As Dr. Hong noted, the literature is sparse when it comes to comparing the risk among specific statins. Some studies suggest that the risk may depend on the individual and their specific risk factors, as well as the dose and intensity of the prescribed statin.

One recent study suggests that while the overall chance of developing diabetes is small, when looking at risk by years of exposure, atorvastatin, rosuvastatin, and lovastatin carried the largest risk, whereas the risk was lower with pravastatin and simvastatin.

Risks also seemed lower with fluvastatin and pitavastatin, but there were too few study patients taking those drugs long-term to include in the subanalysis.

With input from the latest guidelines from the American Heart Association and the American Diabetes Association, as well as findings from a clinical guide on statin-associated diabetes, Dr. Hoogwerf suggests in his review that shared decision-making before starting statin therapy of any type include the following considerations/discussion points:

• For all patients: Screening to determine baseline glycemic status; nonstatin therapies to lower cholesterol; and variables associated with an increased risk of diabetes, including antihypertensive drugs.
• For patients without T2D: The possibility of developing T2D, types and doses of statins, and the fact that statin benefits “generally far outweigh” risks of developing diabetes.
• For patients with T2D: Possible small adverse effects on glycemic control; statin benefits in reducing risk for atherosclerotic cardiovascular disease, which “significantly outweigh” the small increase in A1c; and mitigation of adverse glycemic effects of statins with glucose-lowering therapies.

It’s worth noting that the AHA and ADA guidelines, among others, also emphasize that such discussions should include the importance of weight loss, regular exercise, and adhering to a healthy lifestyle to mitigate risks of both diabetes and heart disease, with or without statins.

Dr. Hong, Dr. Nissen, and Dr. Martin report no relevant financial relationships. Dr. Hoogwerf has disclosed ownership interest in Eli Lilly and consulting for MannKind and Zealand Pharmaceuticals.

A version of this article appeared on Medscape.com.

Studies have shown links between statin use and type 2 diabetes (T2D) for more than a decade. A U.S. Food and Drug Administration label change for the drugs warned in 2012 about reports of increased risks of high blood glucose and glycosylated hemoglobin (A1c) levels. However, in the same warning, the FDA said it “continues to believe that the cardiovascular benefits of statins outweigh these small increased risks.”

Indeed, although the warning triggered much discussion at the time and a number of meta-analyses and other observational studies in more recent years, that conclusion seems to hold among clinicians and society guidelines.

For example, in a recent practice pointer on the risk of diabetes with statins published in the BMJ, Ishak Mansi, MD, of the Orlando VA Health Care System, and colleagues write, “This potential adverse effect of diabetes with statin use should not be a barrier to starting statin treatment when indicated.”

They also called for further research to answer such questions as, “Is statin-associated diabetes reversible upon statin discontinuation? Would intermittent use minimize this risk while maintaining cardiovascular benefits?”

An earlier study among individuals at high risk for diabetes found significantly higher rates of incident diabetes at 10 years among patients on placebo, metformin, or lifestyle intervention who also initiated statin therapy. Jill Crandall, MD, Albert Einstein College of Medicine, New York, and colleagues conclude, “For individual patients, a potential modest increase in diabetes risk clearly needs to be balanced against the consistent and highly significant reductions in myocardial infarction, stroke, and cardiovascular death associated with statin treatment.”

In the same vein, a recent review by Byron Hoogwerf, MD, Emeritus, department of endocrinology, diabetes, and metabolism, Cleveland Clinic, is titled, “Statins may increase diabetes, but benefit still outweighs risk.”
 

Rosuvastatin versus Atorvastatin

The latest study in this arena is an analysis of the LODESTAR randomized controlled trial of 4,400 patients with coronary artery disease in 12 hospitals in Korea which compares the risks associated with individual statins.

Senior author Myeong-Ki Hong, MD, PhD, Yonsei University College of Medicine, Severance Cardiovascular Hospital, Seoul, South Korea, said in an interview that the study was prompted by the “limited” studies evaluating clinical outcomes, including diabetes risk, according to statin type.

Dr. Hong and colleagues compared the risk of developing diabetes among those taking rosuvastatin (mean daily dose, 17.1 mg) or atorvastatin (mean daily dose 36 mg) for 3 years. While both statins effectively prevented myocardial infarction, stroke, and death, those taking rosuvastatin had a higher incidence of new-onset T2D requiring initiation of antidiabetic drugs (7.2% vs. 5.3%; hazard ratio, 1.39) and cataract surgery (2.5% vs. 1.5%; HR, 1.66).

Overall, the HR of new-onset T2D was 1.29 (95% confidence interval, 1.01-1.63; P = .04).

“The percentages of new-onset diabetes and cataract are in line with previous studies regarding statin therapy in patients with atherosclerotic cardiovascular disease,” Dr. Hong said. “Additional research specifically focusing on these outcomes is required, with more frequent measurement of glucose and A1c levels to detect new-onset diabetes and regular ophthalmologic examinations to detect cataracts.”

“However,” he added, “when using rosuvastatin over atorvastatin, we ... emphasize the importance of meticulous monitoring and appropriate lifestyle interventions to mitigate the risk of new-onset diabetes or cataracts.”

Steven Nissen, MD, chief academic officer of Cleveland Clinic’s Heart and Vascular Institute, was not convinced, and said the study “does not provide useful insights into the use of these drugs.”

The investigators used whatever dose they wanted, “and the authors report only the median dose after 3 years,” he said in an interview. “Because there was a slightly greater reduction in low-density lipoprotein (LDL) cholesterol with rosuvastatin, the relative dose was actually higher.”

“We know that new-onset diabetes with statins is dose-dependent,” he said. “The P-values for diabetes incidence were marginal (very close to P = .05). Accordingly, the diabetes data are unconvincing. ... The similar efficacy is not surprising given the open-label dosing with relatively similar effects on lipids.”

Seth Shay Martin, MD, MHS, director of the Advanced Lipid Disorders Program and Digital Health Lab, Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins Medicine, Baltimore, also commented on the results. The findings are “in line with existing knowledge and current guidelines,” he said. “Therefore, the study should not influence prescribing.”

“Although the study suggests that rosuvastatin was associated with a higher risk of new-onset diabetes mellitus requiring antidiabetics and cataract surgery, compared with atorvastatin, these findings should be interpreted with caution given the open-label nature of the study and require further investigation,” he said.

“The mean daily doses of statins were somewhat below target for secondary prevention,” he noted. “Ideally, patients with coronary artery disease (CAD) take 20-40 mg daily of rosuvastatin or 40-80 mg daily of atorvastatin.”

“Furthermore, the LDL cholesterol levels were not optimized in the patients,” he said. “The mean LDL-C was 1.8-1.9 mmol/L, which is equivalent to 70-73 mg/dL. In the current treatment era, we generally treat to LDL-C levels less than 70 mg/dL and often less than 55 mg/dL in CAD patients.”

“The cataracts finding is particularly odd,” he added. “There was historic concern for cataracts with statin therapy, initially because of studies in beagle dogs. However, high-quality evidence from statin trials has not shown a risk for cataracts.” 

So which statin has the lowest risk of triggering new-onset diabetes? As Dr. Hong noted, the literature is sparse when it comes to comparing the risk among specific statins. Some studies suggest that the risk may depend on the individual and their specific risk factors, as well as the dose and intensity of the prescribed statin.

One recent study suggests that while the overall chance of developing diabetes is small, when looking at risk by years of exposure, atorvastatin, rosuvastatin, and lovastatin carried the largest risk, whereas the risk was lower with pravastatin and simvastatin.

Risks also seemed lower with fluvastatin and pitavastatin, but there were too few study patients taking those drugs long-term to include in the subanalysis.

With input from the latest guidelines from the American Heart Association and the American Diabetes Association, as well as findings from a clinical guide on statin-associated diabetes, Dr. Hoogwerf suggests in his review that shared decision-making before starting statin therapy of any type include the following considerations/discussion points:

• For all patients: Screening to determine baseline glycemic status; nonstatin therapies to lower cholesterol; and variables associated with an increased risk of diabetes, including antihypertensive drugs.
• For patients without T2D: The possibility of developing T2D, types and doses of statins, and the fact that statin benefits “generally far outweigh” risks of developing diabetes.
• For patients with T2D: Possible small adverse effects on glycemic control; statin benefits in reducing risk for atherosclerotic cardiovascular disease, which “significantly outweigh” the small increase in A1c; and mitigation of adverse glycemic effects of statins with glucose-lowering therapies.

It’s worth noting that the AHA and ADA guidelines, among others, also emphasize that such discussions should include the importance of weight loss, regular exercise, and adhering to a healthy lifestyle to mitigate risks of both diabetes and heart disease, with or without statins.

Dr. Hong, Dr. Nissen, and Dr. Martin report no relevant financial relationships. Dr. Hoogwerf has disclosed ownership interest in Eli Lilly and consulting for MannKind and Zealand Pharmaceuticals.

A version of this article appeared on Medscape.com.

Studies have shown links between statin use and type 2 diabetes (T2D) for more than a decade. A U.S. Food and Drug Administration label change for the drugs warned in 2012 about reports of increased risks of high blood glucose and glycosylated hemoglobin (A1c) levels. However, in the same warning, the FDA said it “continues to believe that the cardiovascular benefits of statins outweigh these small increased risks.”

Indeed, although the warning triggered much discussion at the time and a number of meta-analyses and other observational studies in more recent years, that conclusion seems to hold among clinicians and society guidelines.

For example, in a recent practice pointer on the risk of diabetes with statins published in the BMJ, Ishak Mansi, MD, of the Orlando VA Health Care System, and colleagues write, “This potential adverse effect of diabetes with statin use should not be a barrier to starting statin treatment when indicated.”

They also called for further research to answer such questions as, “Is statin-associated diabetes reversible upon statin discontinuation? Would intermittent use minimize this risk while maintaining cardiovascular benefits?”

An earlier study among individuals at high risk for diabetes found significantly higher rates of incident diabetes at 10 years among patients on placebo, metformin, or lifestyle intervention who also initiated statin therapy. Jill Crandall, MD, Albert Einstein College of Medicine, New York, and colleagues conclude, “For individual patients, a potential modest increase in diabetes risk clearly needs to be balanced against the consistent and highly significant reductions in myocardial infarction, stroke, and cardiovascular death associated with statin treatment.”

In the same vein, a recent review by Byron Hoogwerf, MD, Emeritus, department of endocrinology, diabetes, and metabolism, Cleveland Clinic, is titled, “Statins may increase diabetes, but benefit still outweighs risk.”
 

Rosuvastatin versus Atorvastatin

The latest study in this arena is an analysis of the LODESTAR randomized controlled trial of 4,400 patients with coronary artery disease in 12 hospitals in Korea which compares the risks associated with individual statins.

Senior author Myeong-Ki Hong, MD, PhD, Yonsei University College of Medicine, Severance Cardiovascular Hospital, Seoul, South Korea, said in an interview that the study was prompted by the “limited” studies evaluating clinical outcomes, including diabetes risk, according to statin type.

Dr. Hong and colleagues compared the risk of developing diabetes among those taking rosuvastatin (mean daily dose, 17.1 mg) or atorvastatin (mean daily dose 36 mg) for 3 years. While both statins effectively prevented myocardial infarction, stroke, and death, those taking rosuvastatin had a higher incidence of new-onset T2D requiring initiation of antidiabetic drugs (7.2% vs. 5.3%; hazard ratio, 1.39) and cataract surgery (2.5% vs. 1.5%; HR, 1.66).

Overall, the HR of new-onset T2D was 1.29 (95% confidence interval, 1.01-1.63; P = .04).

“The percentages of new-onset diabetes and cataract are in line with previous studies regarding statin therapy in patients with atherosclerotic cardiovascular disease,” Dr. Hong said. “Additional research specifically focusing on these outcomes is required, with more frequent measurement of glucose and A1c levels to detect new-onset diabetes and regular ophthalmologic examinations to detect cataracts.”

“However,” he added, “when using rosuvastatin over atorvastatin, we ... emphasize the importance of meticulous monitoring and appropriate lifestyle interventions to mitigate the risk of new-onset diabetes or cataracts.”

Steven Nissen, MD, chief academic officer of Cleveland Clinic’s Heart and Vascular Institute, was not convinced, and said the study “does not provide useful insights into the use of these drugs.”

The investigators used whatever dose they wanted, “and the authors report only the median dose after 3 years,” he said in an interview. “Because there was a slightly greater reduction in low-density lipoprotein (LDL) cholesterol with rosuvastatin, the relative dose was actually higher.”

“We know that new-onset diabetes with statins is dose-dependent,” he said. “The P-values for diabetes incidence were marginal (very close to P = .05). Accordingly, the diabetes data are unconvincing. ... The similar efficacy is not surprising given the open-label dosing with relatively similar effects on lipids.”

Seth Shay Martin, MD, MHS, director of the Advanced Lipid Disorders Program and Digital Health Lab, Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins Medicine, Baltimore, also commented on the results. The findings are “in line with existing knowledge and current guidelines,” he said. “Therefore, the study should not influence prescribing.”

“Although the study suggests that rosuvastatin was associated with a higher risk of new-onset diabetes mellitus requiring antidiabetics and cataract surgery, compared with atorvastatin, these findings should be interpreted with caution given the open-label nature of the study and require further investigation,” he said.

“The mean daily doses of statins were somewhat below target for secondary prevention,” he noted. “Ideally, patients with coronary artery disease (CAD) take 20-40 mg daily of rosuvastatin or 40-80 mg daily of atorvastatin.”

“Furthermore, the LDL cholesterol levels were not optimized in the patients,” he said. “The mean LDL-C was 1.8-1.9 mmol/L, which is equivalent to 70-73 mg/dL. In the current treatment era, we generally treat to LDL-C levels less than 70 mg/dL and often less than 55 mg/dL in CAD patients.”

“The cataracts finding is particularly odd,” he added. “There was historic concern for cataracts with statin therapy, initially because of studies in beagle dogs. However, high-quality evidence from statin trials has not shown a risk for cataracts.” 

So which statin has the lowest risk of triggering new-onset diabetes? As Dr. Hong noted, the literature is sparse when it comes to comparing the risk among specific statins. Some studies suggest that the risk may depend on the individual and their specific risk factors, as well as the dose and intensity of the prescribed statin.

One recent study suggests that while the overall chance of developing diabetes is small, when looking at risk by years of exposure, atorvastatin, rosuvastatin, and lovastatin carried the largest risk, whereas the risk was lower with pravastatin and simvastatin.

Risks also seemed lower with fluvastatin and pitavastatin, but there were too few study patients taking those drugs long-term to include in the subanalysis.

With input from the latest guidelines from the American Heart Association and the American Diabetes Association, as well as findings from a clinical guide on statin-associated diabetes, Dr. Hoogwerf suggests in his review that shared decision-making before starting statin therapy of any type include the following considerations/discussion points:

• For all patients: Screening to determine baseline glycemic status; nonstatin therapies to lower cholesterol; and variables associated with an increased risk of diabetes, including antihypertensive drugs.
• For patients without T2D: The possibility of developing T2D, types and doses of statins, and the fact that statin benefits “generally far outweigh” risks of developing diabetes.
• For patients with T2D: Possible small adverse effects on glycemic control; statin benefits in reducing risk for atherosclerotic cardiovascular disease, which “significantly outweigh” the small increase in A1c; and mitigation of adverse glycemic effects of statins with glucose-lowering therapies.

It’s worth noting that the AHA and ADA guidelines, among others, also emphasize that such discussions should include the importance of weight loss, regular exercise, and adhering to a healthy lifestyle to mitigate risks of both diabetes and heart disease, with or without statins.

Dr. Hong, Dr. Nissen, and Dr. Martin report no relevant financial relationships. Dr. Hoogwerf has disclosed ownership interest in Eli Lilly and consulting for MannKind and Zealand Pharmaceuticals.

A version of this article appeared on Medscape.com.

TOPLINE:

Nirmatrelvir-ritonavir doesn’t reduce the incidence of most post-COVID conditions, according to a new study. Thromboembolic events are the exception.
 

METHODOLOGY:

• A retrospective study of 9,593 veterans older than 65 years examined the impact of nirmatrelvir-ritonavir in comparison with no treatment on post–COVID-19 conditions (PCCs).
• Researchers coded 31 conditions, including those that fell into cardiac, pulmonary, renal, thromboembolic, gastrointestinal, neurologic, mental health, musculoskeletal, and endocrine categories.
• The incidence of PCCs was analyzed 31-180 days after treatment.

TAKEAWAY:

• The combined incidence of venous thromboembolism and pulmonary embolism was reduced among patients given nirmatrelvir-ritonavir.
• No statistically significant reduction of other conditions was found.
• Results differ from the conclusions of a smaller study that found that the incidence of 10 of 13 PCCs was lower.

IN PRACTICE:

“Our results suggest that considerations about PCCs may not be an important factor in COVID-19 treatment decisions,” the authors write.

SOURCE:

The study was funded by the Department of Veterans Affairs and was published online in Annals of Internal Medicine. George Ioannou, MD, director of hepatology at the VA Puget Sound Health Care System in Seattle, led the study.

LIMITATIONS:

A large number of outcomes were observed, so it’s possible that the association between treatment with nirmatrelvir-ritonavir and reduced incidence of thromboembolic events occurred by chance.

Data on COVID-19 treatments and PCCs may be incomplete. The long-term effects of PCCs may not have been fully captured by the ICD-10, which was used for diagnosis codes.

Electronic health records did not accurately capture the symptom burden or the date symptoms began. Patients in the treatment arm may have had more symptoms than matched control persons who were not treated.
 

DISCLOSURES:

The authors reported relationships with the Korean Diabetes Association, the American Diabetes Association, the International Society for the Diabetic Foot, Quality Insights, Brown University, and the Society for Women in Urology, among others.

A version of this article appeared on Medscape.com.

TOPLINE:

Nirmatrelvir-ritonavir doesn’t reduce the incidence of most post-COVID conditions, according to a new study. Thromboembolic events are the exception.
 

METHODOLOGY:

• A retrospective study of 9,593 veterans older than 65 years examined the impact of nirmatrelvir-ritonavir in comparison with no treatment on post–COVID-19 conditions (PCCs).
• Researchers coded 31 conditions, including those that fell into cardiac, pulmonary, renal, thromboembolic, gastrointestinal, neurologic, mental health, musculoskeletal, and endocrine categories.
• The incidence of PCCs was analyzed 31-180 days after treatment.

TAKEAWAY:

• The combined incidence of venous thromboembolism and pulmonary embolism was reduced among patients given nirmatrelvir-ritonavir.
• No statistically significant reduction of other conditions was found.
• Results differ from the conclusions of a smaller study that found that the incidence of 10 of 13 PCCs was lower.

IN PRACTICE:

“Our results suggest that considerations about PCCs may not be an important factor in COVID-19 treatment decisions,” the authors write.

SOURCE:

The study was funded by the Department of Veterans Affairs and was published online in Annals of Internal Medicine. George Ioannou, MD, director of hepatology at the VA Puget Sound Health Care System in Seattle, led the study.

LIMITATIONS:

A large number of outcomes were observed, so it’s possible that the association between treatment with nirmatrelvir-ritonavir and reduced incidence of thromboembolic events occurred by chance.

Data on COVID-19 treatments and PCCs may be incomplete. The long-term effects of PCCs may not have been fully captured by the ICD-10, which was used for diagnosis codes.

Electronic health records did not accurately capture the symptom burden or the date symptoms began. Patients in the treatment arm may have had more symptoms than matched control persons who were not treated.
 

DISCLOSURES:

The authors reported relationships with the Korean Diabetes Association, the American Diabetes Association, the International Society for the Diabetic Foot, Quality Insights, Brown University, and the Society for Women in Urology, among others.

A version of this article appeared on Medscape.com.

TOPLINE:

Nirmatrelvir-ritonavir doesn’t reduce the incidence of most post-COVID conditions, according to a new study. Thromboembolic events are the exception.
 

METHODOLOGY:

• A retrospective study of 9,593 veterans older than 65 years examined the impact of nirmatrelvir-ritonavir in comparison with no treatment on post–COVID-19 conditions (PCCs).
• Researchers coded 31 conditions, including those that fell into cardiac, pulmonary, renal, thromboembolic, gastrointestinal, neurologic, mental health, musculoskeletal, and endocrine categories.
• The incidence of PCCs was analyzed 31-180 days after treatment.

TAKEAWAY:

• The combined incidence of venous thromboembolism and pulmonary embolism was reduced among patients given nirmatrelvir-ritonavir.
• No statistically significant reduction of other conditions was found.
• Results differ from the conclusions of a smaller study that found that the incidence of 10 of 13 PCCs was lower.

IN PRACTICE:

“Our results suggest that considerations about PCCs may not be an important factor in COVID-19 treatment decisions,” the authors write.

SOURCE:

The study was funded by the Department of Veterans Affairs and was published online in Annals of Internal Medicine. George Ioannou, MD, director of hepatology at the VA Puget Sound Health Care System in Seattle, led the study.

LIMITATIONS:

A large number of outcomes were observed, so it’s possible that the association between treatment with nirmatrelvir-ritonavir and reduced incidence of thromboembolic events occurred by chance.

Data on COVID-19 treatments and PCCs may be incomplete. The long-term effects of PCCs may not have been fully captured by the ICD-10, which was used for diagnosis codes.

Electronic health records did not accurately capture the symptom burden or the date symptoms began. Patients in the treatment arm may have had more symptoms than matched control persons who were not treated.
 

DISCLOSURES:

The authors reported relationships with the Korean Diabetes Association, the American Diabetes Association, the International Society for the Diabetic Foot, Quality Insights, Brown University, and the Society for Women in Urology, among others.

A version of this article appeared on Medscape.com.

Flohr and colleagues present the results of a controlled trial of cyclosporine vs methotrexate for severe atopic dermatitis ("Efficacy and Safety of Ciclosporin Versus Methotrexate in the Treatment of Severe Atopic Dermatitis in Children and Young People"). Cyclosporine worked faster, yet methotrexate was a bit more effective in the long run. Both treatments had considerable side effects; 10% and 14% had serious events with cyclosporine and methotrexate, respectively. My only quibble is with the first word of the abstract background section; the authors call cyclosporine and methotrexate "conventional" systemic drugs for atopic dermatitis. At this point, considering safety and efficacy, I would consider drugs like dupilumab to be the "conventional" systemic treatment for atopic dermatitis.

Wan and colleagues ("Neuropsychiatric Disorders in Adults With Atopic Dermatitis") present an exceptionally well-done study with a huge patient population. The study compared about 600,000 adults with atopic dermatitis vs over 2,000,000 adults without the disease. A sample size like that offers a lot of power to detect very small differences between groups. The researchers report higher rates of anxiety and depression in patients with atopic dermatitis compared to those without. Are those differences clinically meaningfully different? The rates of depression were 14 and 17 cases per 1000 patient-years for those without and those with severe atopic dermatitis, respectively. That's a difference of 3 per 1000 patient-years. So maybe roughly 300 patients with atopic dermatitis would need to be seen to observe one patient with depression due to atopic dermatitis (assuming that the observed differences in rates between those with and those without atopic dermatitis were due to the dermatitis). The authors conclude, "Clinicians should inquire about mental health in patients with AD." I don't think their data support such a conclusion. We'd need to see a cost-effectiveness study to know if that's an intervention that we should do. Given the very small difference between the rates in those with and those without atopic dermatitis, it might be reasonable to conclude that we should inquire about mental health in patients with atopic dermatitis about as much as we should in patients without atopic dermatitis.

Some years ago, there was an over-the-counter topical product for psoriasis based on a banana peel extract. I think it was marketed as "FDA approved" for psoriasis (which was legal to say because the product also contained tar) and as being as effective as topical calcipotriene as published in the Journal of Investigational Dermatology (JID). I went to look for the article; the "publication" was the abstract of a poster presentation. The study followed a very small study population for a short period of time. The study was, I believe, underpowered to detect differences between the banana peel extract and the vitamin D analog. Those data were presented as a poster, the poster abstracts were printed in JID, and, voilà, the product was marketed as being as effective as topical calcipotriene as published in JID.

Sowlati and colleagues ("Efficacy and Tolerability of a Novel Topical Treatment Containing Pea Protein and Xyloglucan in the Management of Atopic Dermatitis in Children") randomly assigned 42 patients to receive either a xyloglucan/pea protein topical therapy or hydrocortisone. The participants were followed for 2 weeks. Both groups improved. We don't know whether they improved more than they would have with moisturizer. This study doesn't make me excited about prescribing the xyloglucan/pea protein topical.

The study by Mohamed and colleagues comparing tacrolimus and hydrocortisone reminds me that we have an effective generic topical anti-inflammatory for our patients with atopic dermatitis. Given the safety of topical tacrolimus, I prefer prescribing the 0.1% ointment for all my patients, though I give the lower concentration, approved for children, if the insurer makes me.

Simpson and colleagues' post hoc analysis of tralokinumab tells us that, with continued use, some patients who don't respond well initially will have greater improvement. But what I'd really like to see is a head-to-head study comparing tralokinumab vs dupilumab. Dupilumab seems to have stronger efficacy based on their reported trial numbers, but a head-to-head trial would give us greater confidence in their relative benefits.

I have trouble getting excited about this study by Cork and colleagues ("Dupilumab Safety and Efficacy in a Phase III Open-Label Extension Trial in Children 6-11 Years of Age With Severe Atopic Dermatitis"). I feel very comfortable with dupilumab already.

Flohr and colleagues present the results of a controlled trial of cyclosporine vs methotrexate for severe atopic dermatitis ("Efficacy and Safety of Ciclosporin Versus Methotrexate in the Treatment of Severe Atopic Dermatitis in Children and Young People"). Cyclosporine worked faster, yet methotrexate was a bit more effective in the long run. Both treatments had considerable side effects; 10% and 14% had serious events with cyclosporine and methotrexate, respectively. My only quibble is with the first word of the abstract background section; the authors call cyclosporine and methotrexate "conventional" systemic drugs for atopic dermatitis. At this point, considering safety and efficacy, I would consider drugs like dupilumab to be the "conventional" systemic treatment for atopic dermatitis.

Wan and colleagues ("Neuropsychiatric Disorders in Adults With Atopic Dermatitis") present an exceptionally well-done study with a huge patient population. The study compared about 600,000 adults with atopic dermatitis vs over 2,000,000 adults without the disease. A sample size like that offers a lot of power to detect very small differences between groups. The researchers report higher rates of anxiety and depression in patients with atopic dermatitis compared to those without. Are those differences clinically meaningfully different? The rates of depression were 14 and 17 cases per 1000 patient-years for those without and those with severe atopic dermatitis, respectively. That's a difference of 3 per 1000 patient-years. So maybe roughly 300 patients with atopic dermatitis would need to be seen to observe one patient with depression due to atopic dermatitis (assuming that the observed differences in rates between those with and those without atopic dermatitis were due to the dermatitis). The authors conclude, "Clinicians should inquire about mental health in patients with AD." I don't think their data support such a conclusion. We'd need to see a cost-effectiveness study to know if that's an intervention that we should do. Given the very small difference between the rates in those with and those without atopic dermatitis, it might be reasonable to conclude that we should inquire about mental health in patients with atopic dermatitis about as much as we should in patients without atopic dermatitis.

Some years ago, there was an over-the-counter topical product for psoriasis based on a banana peel extract. I think it was marketed as "FDA approved" for psoriasis (which was legal to say because the product also contained tar) and as being as effective as topical calcipotriene as published in the Journal of Investigational Dermatology (JID). I went to look for the article; the "publication" was the abstract of a poster presentation. The study followed a very small study population for a short period of time. The study was, I believe, underpowered to detect differences between the banana peel extract and the vitamin D analog. Those data were presented as a poster, the poster abstracts were printed in JID, and, voilà, the product was marketed as being as effective as topical calcipotriene as published in JID.

Sowlati and colleagues ("Efficacy and Tolerability of a Novel Topical Treatment Containing Pea Protein and Xyloglucan in the Management of Atopic Dermatitis in Children") randomly assigned 42 patients to receive either a xyloglucan/pea protein topical therapy or hydrocortisone. The participants were followed for 2 weeks. Both groups improved. We don't know whether they improved more than they would have with moisturizer. This study doesn't make me excited about prescribing the xyloglucan/pea protein topical.

The study by Mohamed and colleagues comparing tacrolimus and hydrocortisone reminds me that we have an effective generic topical anti-inflammatory for our patients with atopic dermatitis. Given the safety of topical tacrolimus, I prefer prescribing the 0.1% ointment for all my patients, though I give the lower concentration, approved for children, if the insurer makes me.

Simpson and colleagues' post hoc analysis of tralokinumab tells us that, with continued use, some patients who don't respond well initially will have greater improvement. But what I'd really like to see is a head-to-head study comparing tralokinumab vs dupilumab. Dupilumab seems to have stronger efficacy based on their reported trial numbers, but a head-to-head trial would give us greater confidence in their relative benefits.

I have trouble getting excited about this study by Cork and colleagues ("Dupilumab Safety and Efficacy in a Phase III Open-Label Extension Trial in Children 6-11 Years of Age With Severe Atopic Dermatitis"). I feel very comfortable with dupilumab already.

Flohr and colleagues present the results of a controlled trial of cyclosporine vs methotrexate for severe atopic dermatitis ("Efficacy and Safety of Ciclosporin Versus Methotrexate in the Treatment of Severe Atopic Dermatitis in Children and Young People"). Cyclosporine worked faster, yet methotrexate was a bit more effective in the long run. Both treatments had considerable side effects; 10% and 14% had serious events with cyclosporine and methotrexate, respectively. My only quibble is with the first word of the abstract background section; the authors call cyclosporine and methotrexate "conventional" systemic drugs for atopic dermatitis. At this point, considering safety and efficacy, I would consider drugs like dupilumab to be the "conventional" systemic treatment for atopic dermatitis.

Wan and colleagues ("Neuropsychiatric Disorders in Adults With Atopic Dermatitis") present an exceptionally well-done study with a huge patient population. The study compared about 600,000 adults with atopic dermatitis vs over 2,000,000 adults without the disease. A sample size like that offers a lot of power to detect very small differences between groups. The researchers report higher rates of anxiety and depression in patients with atopic dermatitis compared to those without. Are those differences clinically meaningfully different? The rates of depression were 14 and 17 cases per 1000 patient-years for those without and those with severe atopic dermatitis, respectively. That's a difference of 3 per 1000 patient-years. So maybe roughly 300 patients with atopic dermatitis would need to be seen to observe one patient with depression due to atopic dermatitis (assuming that the observed differences in rates between those with and those without atopic dermatitis were due to the dermatitis). The authors conclude, "Clinicians should inquire about mental health in patients with AD." I don't think their data support such a conclusion. We'd need to see a cost-effectiveness study to know if that's an intervention that we should do. Given the very small difference between the rates in those with and those without atopic dermatitis, it might be reasonable to conclude that we should inquire about mental health in patients with atopic dermatitis about as much as we should in patients without atopic dermatitis.

Some years ago, there was an over-the-counter topical product for psoriasis based on a banana peel extract. I think it was marketed as "FDA approved" for psoriasis (which was legal to say because the product also contained tar) and as being as effective as topical calcipotriene as published in the Journal of Investigational Dermatology (JID). I went to look for the article; the "publication" was the abstract of a poster presentation. The study followed a very small study population for a short period of time. The study was, I believe, underpowered to detect differences between the banana peel extract and the vitamin D analog. Those data were presented as a poster, the poster abstracts were printed in JID, and, voilà, the product was marketed as being as effective as topical calcipotriene as published in JID.

Sowlati and colleagues ("Efficacy and Tolerability of a Novel Topical Treatment Containing Pea Protein and Xyloglucan in the Management of Atopic Dermatitis in Children") randomly assigned 42 patients to receive either a xyloglucan/pea protein topical therapy or hydrocortisone. The participants were followed for 2 weeks. Both groups improved. We don't know whether they improved more than they would have with moisturizer. This study doesn't make me excited about prescribing the xyloglucan/pea protein topical.

The study by Mohamed and colleagues comparing tacrolimus and hydrocortisone reminds me that we have an effective generic topical anti-inflammatory for our patients with atopic dermatitis. Given the safety of topical tacrolimus, I prefer prescribing the 0.1% ointment for all my patients, though I give the lower concentration, approved for children, if the insurer makes me.

Simpson and colleagues' post hoc analysis of tralokinumab tells us that, with continued use, some patients who don't respond well initially will have greater improvement. But what I'd really like to see is a head-to-head study comparing tralokinumab vs dupilumab. Dupilumab seems to have stronger efficacy based on their reported trial numbers, but a head-to-head trial would give us greater confidence in their relative benefits.

I have trouble getting excited about this study by Cork and colleagues ("Dupilumab Safety and Efficacy in a Phase III Open-Label Extension Trial in Children 6-11 Years of Age With Severe Atopic Dermatitis"). I feel very comfortable with dupilumab already.

Patients with hand osteoarthritis (OA) and MRI-detected synovitis who took methotrexate (MTX) 20 mg weekly over a 6-month period had a significant and potentially clinically meaningful reduction in pain and stiffness over those who received placebo in the first randomized controlled trial of its kind to show positive results with the drug.

Patients who were randomly assigned to MTX took 10 mg orally for the first 4 weeks then increased to 20 mg for the rest of the trial, with differences in the primary outcome of pain measured by visual analog scale (VAS) first becoming significant over placebo at 3 months.

Senior author of the METHODS study (Methotrexate to Treat Hand Osteoarthritis with Synovitis), Flavia Cicuttini, PhD, MSc, head of the musculoskeletal unit at Monash University and head of rheumatology at Alfred Hospital, Melbourne, Australia, noted that the effect of MTX was higher than effect sizes that have been reported for NSAIDs on pain in hip or knee OA.

Astrid Gast/Thinkstock

The study was published online October 12 in The Lancet.

METHODS makes improvements on past studies

While OA is traditionally categorized as a noninflammatory process, it’s known that there are some patients who have a clinical phenotype characterized by joint swelling (synovitis) and others develop erosive disease. MTX is one of the most common therapies for inflammatory arthritis and standard of care for rheumatoid arthritis (RA) management. Previous studies of methotrexate showed lack of efficacy in hand OA but may have been because of the use of a low dose, poor power due to moderate sample size, and failure to target the specific inflammatory OA phenotype.

Dr. Cicuttini

In an interview, Dr. Cicuttini noted the selection of methotrexate for this trial was intentional. “We considered the evidence and decided to test methotrexate because we know it is effective in inflammatory arthritis, and its mode of action is broader than the more selective anti-TNF [tumor necrosis factor] agents,” which she noted have failed in prior hand OA trials. She also noted that the only previous randomized controlled trial of MTX tested a dose of 10 mg/week, rather than the 20 mg/week dose used in METHODS. 
 

Study details and results

METHODS was a randomized, double-blind, placebo-controlled trial at multiple sites within Australia. Patients were recruited from 2017 to 2022, with a temporary pause in 2020 during the COVID-19 pandemic because of safety concerns regarding MTX use. Participants included in this study were aged 40-75 years, had pain in hand joints for most days in the past 3 months, and a pain score of at least 40 mm on a 100-mm VAS in the past 7 days.

The participants’ hand OA fulfilled American College of Rheumatology criteria, radiographic osteoarthritis (Kellgren and Lawrence grade 2 or more) in at least one joint, and MRI-detected synovitis of grade 1 or more in at least one joint. They excluded patients with concomitant rheumatic disease, gout, psoriasis, positive rheumatoid factor or anti-cyclic citrullinated peptides, or elevated inflammatory markers (erythrocyte sedimentation rate or C-reactive protein), as well as those with contraindication to methotrexate or MRI.

The trials’ 97 participants were assigned 1:1 to MTX or placebo using block randomization. The MTX group started on oral MTX 10 mg weekly for the first 4 weeks, followed by 20 mg weekly for the remainder of the study. Participants took folic acid 5 mg once a day to reduce risk of MTX-related side effects.

The mean age of the participants was 61 years, with 70% female. Baseline characteristics were generally well-balanced, except for higher mean BMI in the MTX group. At 6 months, the MTX group had a greater reduction in mean VAS pain than the placebo group (–15.2 mm vs. –7.7 mm; adjusted between-group difference, –9.9 mm). The minimally clinically important difference for OA trials is a 15-mm change (out of 100) in VAS pain.

The MTX group also had greater reduction in mean Australian Canadian OA Hand Index (AUSCAN) score for pain and stiffness at 6 months, compared with placebo, but there were no differences in other secondary outcomes (mean AUSCAN, Functional Index for Hand Osteoarthritis, Health Assessment Questionnaire, Michigan Hand Outcomes Questionnaire, or grip strength).

MTX was well-tolerated with no serious adverse events related to treatment; only 5 of 50 participants in the MTX group and 4 of 47 in the placebo group discontinued study medication. Incidence of adverse events was similar in the two groups throughout the trial, including mild leukopenia, elevated liver enzymes, mild reduction of hemoglobin, and raised creatinine. None of the laboratory abnormalities required change in medication dosage or affected ability to continue in the study. 
 

Qualifications and considerations for MTX use

Commenting on the study, OA researcher Amanda E. Nelson, MD, MSCR, associate professor of medicine at the University of North Carolina at Chapel Hill’s Thurston Arthritis Research Center, said that its overall design was “excellent,” including appropriate masking, controls, randomization, and power and sample size calculations, contributing to “the trial’s relatively positive, although still modest, results.” Dr. Nelson was not involved with the METHODS study.

Dr. Nelson

Several factors may have contributed to the study’s success, including the broader mechanism of action of methotrexate and higher dose used, Ida K. Haugen, MD, PhD, senior researcher at Diakonhjemmet Hospital’s Center for Treatment of Rheumatic and Musculoskeletal Diseases in Oslo, Norway, told this news organization.

She noted that the MTX 20 mg/week dosage is similar to what is used in treatment of RA and may be key to better targeting inflammation.

Nicolas Tourrenc

“Furthermore, the study included individuals with hand OA and synovitis by MRI, and thus may have found the right patient population in comparison to prior studies,” Dr. Haugen said.

Dr. Cicuttini agreed, noting that “previous trials [of MTX] did not target the inflammatory phenotype of hand osteoarthritis that would be expected to respond.” In the previous randomized controlled trial of MTX in hand OA, only 29 of a total 1024 joints had synovitis, she explained. “Their inclusion criteria were individuals with severe erosive hand osteoarthritis, suggesting that this later-stage disease is less likely to respond.”

Dr. Cicuttini said that she saw no specific issues in regard to potential use of MTX in the OA population in the clinic. “The data we have, together with the large experience we have with using methotrexate and the fact that treatments for hand OA are not very effective, means that it would be reasonable to offer this to patients with hand OA and inflammation,” she said. “The level of evidence for an effect of methotrexate would need to be discussed with the patient. The discussion around the use of methotrexate would then need to proceed in the same way we discuss the use of methotrexate with patients when used for other inflammatory joint diseases, and the decision is then made with the patient.”

In contrast, Dr. Nelson expressed some concerns regarding the immediate use of MTX for this population. “Many individuals with hand OA have multiple medical comorbidities and polypharmacy, which are important when considering additional treatments, particularly those with modest benefit and potential adverse effects over the long term,” she said. “I do not think this single study provides enough evidence to suggest that all such patients should be treated with methotrexate, and more data, particularly about long-term use and optimal risk stratification, is needed.” 

While MTX use in refractory inflammatory hand OA is not yet recommended in international guidelines, Dr. Haugen believes this study supports use of MTX in this patient population. Given that MRI and ultrasound may not always be available to identify synovitis, Dr. Nelson and Dr. Haugen suggested identifying patients who may benefit through careful history and clinical examination for evidence of swollen joints. In addition, Dr. Cicuttini explained that she would not necessarily use MTX in patients with erosive OA radiographically because it may be a later stage of disease that is less likely to respond.

The authors highlighted potential limitations of the METHODS trial. They initially planned to study whether MTX reduced pain and improved radiographic progression at 2 years, but since they paused the study for 7 months during the COVID-19 pandemic, they amended the trial protocol and focused on pain reduction at 6 months as the primary endpoint instead.

Tender and swollen joint counts were initially going to be included, but this was modified given the use of virtual telemedicine visits during the pandemic. Dr. Cicuttini said that further studies are underway to identify potential subpopulations who may benefit from immunosuppression, and others are needed to determine whether MTX reduces joint damage and slows disease progression in hand OA with inflammation.

Dr. Cicuttini said her research group is interested to see whether women who develop hand OA around the time of menopause (“menopausal OA”) are a group that could benefit. Dr. Haugen noted that she is involved in a study testing MTX in erosive hand OA (the MERINO trial). 

The study was funded by a project grant from the National Health and Medical Research Council of Australia. The authors reported no relevant financial relationships.
 

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

Patients with hand osteoarthritis (OA) and MRI-detected synovitis who took methotrexate (MTX) 20 mg weekly over a 6-month period had a significant and potentially clinically meaningful reduction in pain and stiffness over those who received placebo in the first randomized controlled trial of its kind to show positive results with the drug.

Patients who were randomly assigned to MTX took 10 mg orally for the first 4 weeks then increased to 20 mg for the rest of the trial, with differences in the primary outcome of pain measured by visual analog scale (VAS) first becoming significant over placebo at 3 months.

Senior author of the METHODS study (Methotrexate to Treat Hand Osteoarthritis with Synovitis), Flavia Cicuttini, PhD, MSc, head of the musculoskeletal unit at Monash University and head of rheumatology at Alfred Hospital, Melbourne, Australia, noted that the effect of MTX was higher than effect sizes that have been reported for NSAIDs on pain in hip or knee OA.

Astrid Gast/Thinkstock

The study was published online October 12 in The Lancet.

METHODS makes improvements on past studies

While OA is traditionally categorized as a noninflammatory process, it’s known that there are some patients who have a clinical phenotype characterized by joint swelling (synovitis) and others develop erosive disease. MTX is one of the most common therapies for inflammatory arthritis and standard of care for rheumatoid arthritis (RA) management. Previous studies of methotrexate showed lack of efficacy in hand OA but may have been because of the use of a low dose, poor power due to moderate sample size, and failure to target the specific inflammatory OA phenotype.

Dr. Cicuttini

In an interview, Dr. Cicuttini noted the selection of methotrexate for this trial was intentional. “We considered the evidence and decided to test methotrexate because we know it is effective in inflammatory arthritis, and its mode of action is broader than the more selective anti-TNF [tumor necrosis factor] agents,” which she noted have failed in prior hand OA trials. She also noted that the only previous randomized controlled trial of MTX tested a dose of 10 mg/week, rather than the 20 mg/week dose used in METHODS. 
 

Study details and results

METHODS was a randomized, double-blind, placebo-controlled trial at multiple sites within Australia. Patients were recruited from 2017 to 2022, with a temporary pause in 2020 during the COVID-19 pandemic because of safety concerns regarding MTX use. Participants included in this study were aged 40-75 years, had pain in hand joints for most days in the past 3 months, and a pain score of at least 40 mm on a 100-mm VAS in the past 7 days.

The participants’ hand OA fulfilled American College of Rheumatology criteria, radiographic osteoarthritis (Kellgren and Lawrence grade 2 or more) in at least one joint, and MRI-detected synovitis of grade 1 or more in at least one joint. They excluded patients with concomitant rheumatic disease, gout, psoriasis, positive rheumatoid factor or anti-cyclic citrullinated peptides, or elevated inflammatory markers (erythrocyte sedimentation rate or C-reactive protein), as well as those with contraindication to methotrexate or MRI.

The trials’ 97 participants were assigned 1:1 to MTX or placebo using block randomization. The MTX group started on oral MTX 10 mg weekly for the first 4 weeks, followed by 20 mg weekly for the remainder of the study. Participants took folic acid 5 mg once a day to reduce risk of MTX-related side effects.

The mean age of the participants was 61 years, with 70% female. Baseline characteristics were generally well-balanced, except for higher mean BMI in the MTX group. At 6 months, the MTX group had a greater reduction in mean VAS pain than the placebo group (–15.2 mm vs. –7.7 mm; adjusted between-group difference, –9.9 mm). The minimally clinically important difference for OA trials is a 15-mm change (out of 100) in VAS pain.

The MTX group also had greater reduction in mean Australian Canadian OA Hand Index (AUSCAN) score for pain and stiffness at 6 months, compared with placebo, but there were no differences in other secondary outcomes (mean AUSCAN, Functional Index for Hand Osteoarthritis, Health Assessment Questionnaire, Michigan Hand Outcomes Questionnaire, or grip strength).

MTX was well-tolerated with no serious adverse events related to treatment; only 5 of 50 participants in the MTX group and 4 of 47 in the placebo group discontinued study medication. Incidence of adverse events was similar in the two groups throughout the trial, including mild leukopenia, elevated liver enzymes, mild reduction of hemoglobin, and raised creatinine. None of the laboratory abnormalities required change in medication dosage or affected ability to continue in the study. 
 

Qualifications and considerations for MTX use

Commenting on the study, OA researcher Amanda E. Nelson, MD, MSCR, associate professor of medicine at the University of North Carolina at Chapel Hill’s Thurston Arthritis Research Center, said that its overall design was “excellent,” including appropriate masking, controls, randomization, and power and sample size calculations, contributing to “the trial’s relatively positive, although still modest, results.” Dr. Nelson was not involved with the METHODS study.

Dr. Nelson

Several factors may have contributed to the study’s success, including the broader mechanism of action of methotrexate and higher dose used, Ida K. Haugen, MD, PhD, senior researcher at Diakonhjemmet Hospital’s Center for Treatment of Rheumatic and Musculoskeletal Diseases in Oslo, Norway, told this news organization.

She noted that the MTX 20 mg/week dosage is similar to what is used in treatment of RA and may be key to better targeting inflammation.

Nicolas Tourrenc

“Furthermore, the study included individuals with hand OA and synovitis by MRI, and thus may have found the right patient population in comparison to prior studies,” Dr. Haugen said.

Dr. Cicuttini agreed, noting that “previous trials [of MTX] did not target the inflammatory phenotype of hand osteoarthritis that would be expected to respond.” In the previous randomized controlled trial of MTX in hand OA, only 29 of a total 1024 joints had synovitis, she explained. “Their inclusion criteria were individuals with severe erosive hand osteoarthritis, suggesting that this later-stage disease is less likely to respond.”

Dr. Cicuttini said that she saw no specific issues in regard to potential use of MTX in the OA population in the clinic. “The data we have, together with the large experience we have with using methotrexate and the fact that treatments for hand OA are not very effective, means that it would be reasonable to offer this to patients with hand OA and inflammation,” she said. “The level of evidence for an effect of methotrexate would need to be discussed with the patient. The discussion around the use of methotrexate would then need to proceed in the same way we discuss the use of methotrexate with patients when used for other inflammatory joint diseases, and the decision is then made with the patient.”

In contrast, Dr. Nelson expressed some concerns regarding the immediate use of MTX for this population. “Many individuals with hand OA have multiple medical comorbidities and polypharmacy, which are important when considering additional treatments, particularly those with modest benefit and potential adverse effects over the long term,” she said. “I do not think this single study provides enough evidence to suggest that all such patients should be treated with methotrexate, and more data, particularly about long-term use and optimal risk stratification, is needed.” 

While MTX use in refractory inflammatory hand OA is not yet recommended in international guidelines, Dr. Haugen believes this study supports use of MTX in this patient population. Given that MRI and ultrasound may not always be available to identify synovitis, Dr. Nelson and Dr. Haugen suggested identifying patients who may benefit through careful history and clinical examination for evidence of swollen joints. In addition, Dr. Cicuttini explained that she would not necessarily use MTX in patients with erosive OA radiographically because it may be a later stage of disease that is less likely to respond.

The authors highlighted potential limitations of the METHODS trial. They initially planned to study whether MTX reduced pain and improved radiographic progression at 2 years, but since they paused the study for 7 months during the COVID-19 pandemic, they amended the trial protocol and focused on pain reduction at 6 months as the primary endpoint instead.

Tender and swollen joint counts were initially going to be included, but this was modified given the use of virtual telemedicine visits during the pandemic. Dr. Cicuttini said that further studies are underway to identify potential subpopulations who may benefit from immunosuppression, and others are needed to determine whether MTX reduces joint damage and slows disease progression in hand OA with inflammation.

Dr. Cicuttini said her research group is interested to see whether women who develop hand OA around the time of menopause (“menopausal OA”) are a group that could benefit. Dr. Haugen noted that she is involved in a study testing MTX in erosive hand OA (the MERINO trial). 

The study was funded by a project grant from the National Health and Medical Research Council of Australia. The authors reported no relevant financial relationships.
 

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

Patients with hand osteoarthritis (OA) and MRI-detected synovitis who took methotrexate (MTX) 20 mg weekly over a 6-month period had a significant and potentially clinically meaningful reduction in pain and stiffness over those who received placebo in the first randomized controlled trial of its kind to show positive results with the drug.

Patients who were randomly assigned to MTX took 10 mg orally for the first 4 weeks then increased to 20 mg for the rest of the trial, with differences in the primary outcome of pain measured by visual analog scale (VAS) first becoming significant over placebo at 3 months.

Senior author of the METHODS study (Methotrexate to Treat Hand Osteoarthritis with Synovitis), Flavia Cicuttini, PhD, MSc, head of the musculoskeletal unit at Monash University and head of rheumatology at Alfred Hospital, Melbourne, Australia, noted that the effect of MTX was higher than effect sizes that have been reported for NSAIDs on pain in hip or knee OA.

Astrid Gast/Thinkstock

The study was published online October 12 in The Lancet.

METHODS makes improvements on past studies

While OA is traditionally categorized as a noninflammatory process, it’s known that there are some patients who have a clinical phenotype characterized by joint swelling (synovitis) and others develop erosive disease. MTX is one of the most common therapies for inflammatory arthritis and standard of care for rheumatoid arthritis (RA) management. Previous studies of methotrexate showed lack of efficacy in hand OA but may have been because of the use of a low dose, poor power due to moderate sample size, and failure to target the specific inflammatory OA phenotype.

Dr. Cicuttini

In an interview, Dr. Cicuttini noted the selection of methotrexate for this trial was intentional. “We considered the evidence and decided to test methotrexate because we know it is effective in inflammatory arthritis, and its mode of action is broader than the more selective anti-TNF [tumor necrosis factor] agents,” which she noted have failed in prior hand OA trials. She also noted that the only previous randomized controlled trial of MTX tested a dose of 10 mg/week, rather than the 20 mg/week dose used in METHODS. 
 

Study details and results

METHODS was a randomized, double-blind, placebo-controlled trial at multiple sites within Australia. Patients were recruited from 2017 to 2022, with a temporary pause in 2020 during the COVID-19 pandemic because of safety concerns regarding MTX use. Participants included in this study were aged 40-75 years, had pain in hand joints for most days in the past 3 months, and a pain score of at least 40 mm on a 100-mm VAS in the past 7 days.

The participants’ hand OA fulfilled American College of Rheumatology criteria, radiographic osteoarthritis (Kellgren and Lawrence grade 2 or more) in at least one joint, and MRI-detected synovitis of grade 1 or more in at least one joint. They excluded patients with concomitant rheumatic disease, gout, psoriasis, positive rheumatoid factor or anti-cyclic citrullinated peptides, or elevated inflammatory markers (erythrocyte sedimentation rate or C-reactive protein), as well as those with contraindication to methotrexate or MRI.

The trials’ 97 participants were assigned 1:1 to MTX or placebo using block randomization. The MTX group started on oral MTX 10 mg weekly for the first 4 weeks, followed by 20 mg weekly for the remainder of the study. Participants took folic acid 5 mg once a day to reduce risk of MTX-related side effects.

The mean age of the participants was 61 years, with 70% female. Baseline characteristics were generally well-balanced, except for higher mean BMI in the MTX group. At 6 months, the MTX group had a greater reduction in mean VAS pain than the placebo group (–15.2 mm vs. –7.7 mm; adjusted between-group difference, –9.9 mm). The minimally clinically important difference for OA trials is a 15-mm change (out of 100) in VAS pain.

The MTX group also had greater reduction in mean Australian Canadian OA Hand Index (AUSCAN) score for pain and stiffness at 6 months, compared with placebo, but there were no differences in other secondary outcomes (mean AUSCAN, Functional Index for Hand Osteoarthritis, Health Assessment Questionnaire, Michigan Hand Outcomes Questionnaire, or grip strength).

MTX was well-tolerated with no serious adverse events related to treatment; only 5 of 50 participants in the MTX group and 4 of 47 in the placebo group discontinued study medication. Incidence of adverse events was similar in the two groups throughout the trial, including mild leukopenia, elevated liver enzymes, mild reduction of hemoglobin, and raised creatinine. None of the laboratory abnormalities required change in medication dosage or affected ability to continue in the study. 
 

Qualifications and considerations for MTX use

Commenting on the study, OA researcher Amanda E. Nelson, MD, MSCR, associate professor of medicine at the University of North Carolina at Chapel Hill’s Thurston Arthritis Research Center, said that its overall design was “excellent,” including appropriate masking, controls, randomization, and power and sample size calculations, contributing to “the trial’s relatively positive, although still modest, results.” Dr. Nelson was not involved with the METHODS study.

Dr. Nelson

Several factors may have contributed to the study’s success, including the broader mechanism of action of methotrexate and higher dose used, Ida K. Haugen, MD, PhD, senior researcher at Diakonhjemmet Hospital’s Center for Treatment of Rheumatic and Musculoskeletal Diseases in Oslo, Norway, told this news organization.

She noted that the MTX 20 mg/week dosage is similar to what is used in treatment of RA and may be key to better targeting inflammation.

Nicolas Tourrenc

“Furthermore, the study included individuals with hand OA and synovitis by MRI, and thus may have found the right patient population in comparison to prior studies,” Dr. Haugen said.

Dr. Cicuttini agreed, noting that “previous trials [of MTX] did not target the inflammatory phenotype of hand osteoarthritis that would be expected to respond.” In the previous randomized controlled trial of MTX in hand OA, only 29 of a total 1024 joints had synovitis, she explained. “Their inclusion criteria were individuals with severe erosive hand osteoarthritis, suggesting that this later-stage disease is less likely to respond.”

Dr. Cicuttini said that she saw no specific issues in regard to potential use of MTX in the OA population in the clinic. “The data we have, together with the large experience we have with using methotrexate and the fact that treatments for hand OA are not very effective, means that it would be reasonable to offer this to patients with hand OA and inflammation,” she said. “The level of evidence for an effect of methotrexate would need to be discussed with the patient. The discussion around the use of methotrexate would then need to proceed in the same way we discuss the use of methotrexate with patients when used for other inflammatory joint diseases, and the decision is then made with the patient.”

In contrast, Dr. Nelson expressed some concerns regarding the immediate use of MTX for this population. “Many individuals with hand OA have multiple medical comorbidities and polypharmacy, which are important when considering additional treatments, particularly those with modest benefit and potential adverse effects over the long term,” she said. “I do not think this single study provides enough evidence to suggest that all such patients should be treated with methotrexate, and more data, particularly about long-term use and optimal risk stratification, is needed.” 

While MTX use in refractory inflammatory hand OA is not yet recommended in international guidelines, Dr. Haugen believes this study supports use of MTX in this patient population. Given that MRI and ultrasound may not always be available to identify synovitis, Dr. Nelson and Dr. Haugen suggested identifying patients who may benefit through careful history and clinical examination for evidence of swollen joints. In addition, Dr. Cicuttini explained that she would not necessarily use MTX in patients with erosive OA radiographically because it may be a later stage of disease that is less likely to respond.

The authors highlighted potential limitations of the METHODS trial. They initially planned to study whether MTX reduced pain and improved radiographic progression at 2 years, but since they paused the study for 7 months during the COVID-19 pandemic, they amended the trial protocol and focused on pain reduction at 6 months as the primary endpoint instead.

Tender and swollen joint counts were initially going to be included, but this was modified given the use of virtual telemedicine visits during the pandemic. Dr. Cicuttini said that further studies are underway to identify potential subpopulations who may benefit from immunosuppression, and others are needed to determine whether MTX reduces joint damage and slows disease progression in hand OA with inflammation.

Dr. Cicuttini said her research group is interested to see whether women who develop hand OA around the time of menopause (“menopausal OA”) are a group that could benefit. Dr. Haugen noted that she is involved in a study testing MTX in erosive hand OA (the MERINO trial). 

The study was funded by a project grant from the National Health and Medical Research Council of Australia. The authors reported no relevant financial relationships.
 

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

Key abstracts on multiple sclerosis treatment from the 2023 European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) meeting are reported by Dr Ellen Mowry of Johns Hopkins University.

Dr Mowry begins with a convenient alternative method of drug administration in patients with multiple sclerosis (MS). The phase 3 OCARINA II randomized trial showed promising results in safety and efficacy of subcutaneous ocrelizumab vs traditional longer intravenous infusion. Ocrelizumab is pending US Food and Drug Administration approval.

Next, Dr Mowry highlights two studies that examined known increased risks associated with anti-CD20 therapies. Dr Mowry discusses the importance of continued research into monitoring immunoglobin levels to determine dose escalation or extended interval dosing in patients with MS.

She then discusses the NEXT MS trial that looked at personalized dosing of natalizumab. The interim data indicate a dosing schedule that aims to maintain blood levels of the drug above a certain threshold appears as effective in controlling disease activity in relapsing-remitting MS (RRMS) as the approved 4-week dosing schedule.

Finally, Dr Mowry discusses a phase 2 randomized trial of the gold nanoparticle CNM-Au8, which has been used to treat other autoimmune diseases, to determine its potential benefits in RRMS.

--

Ellen Mowry, MD, MCR, Professor of Neurology & Epidemiology, Johns Hopkins University, Baltimore, Maryland

Ellen Mowry, MD, MCR, has disclosed the following relevant financial relationships:

Serve(d) as a consultant for: BeCareLink, LLC

Received research grant from: Biogen; Genentech

Received royalties from: UpToDate

Key abstracts on multiple sclerosis treatment from the 2023 European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) meeting are reported by Dr Ellen Mowry of Johns Hopkins University.

Dr Mowry begins with a convenient alternative method of drug administration in patients with multiple sclerosis (MS). The phase 3 OCARINA II randomized trial showed promising results in safety and efficacy of subcutaneous ocrelizumab vs traditional longer intravenous infusion. Ocrelizumab is pending US Food and Drug Administration approval.

Next, Dr Mowry highlights two studies that examined known increased risks associated with anti-CD20 therapies. Dr Mowry discusses the importance of continued research into monitoring immunoglobin levels to determine dose escalation or extended interval dosing in patients with MS.

She then discusses the NEXT MS trial that looked at personalized dosing of natalizumab. The interim data indicate a dosing schedule that aims to maintain blood levels of the drug above a certain threshold appears as effective in controlling disease activity in relapsing-remitting MS (RRMS) as the approved 4-week dosing schedule.

Finally, Dr Mowry discusses a phase 2 randomized trial of the gold nanoparticle CNM-Au8, which has been used to treat other autoimmune diseases, to determine its potential benefits in RRMS.

--

Ellen Mowry, MD, MCR, Professor of Neurology & Epidemiology, Johns Hopkins University, Baltimore, Maryland

Ellen Mowry, MD, MCR, has disclosed the following relevant financial relationships:

Serve(d) as a consultant for: BeCareLink, LLC

Received research grant from: Biogen; Genentech

Received royalties from: UpToDate

Key abstracts on multiple sclerosis treatment from the 2023 European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) meeting are reported by Dr Ellen Mowry of Johns Hopkins University.

Dr Mowry begins with a convenient alternative method of drug administration in patients with multiple sclerosis (MS). The phase 3 OCARINA II randomized trial showed promising results in safety and efficacy of subcutaneous ocrelizumab vs traditional longer intravenous infusion. Ocrelizumab is pending US Food and Drug Administration approval.

Next, Dr Mowry highlights two studies that examined known increased risks associated with anti-CD20 therapies. Dr Mowry discusses the importance of continued research into monitoring immunoglobin levels to determine dose escalation or extended interval dosing in patients with MS.

She then discusses the NEXT MS trial that looked at personalized dosing of natalizumab. The interim data indicate a dosing schedule that aims to maintain blood levels of the drug above a certain threshold appears as effective in controlling disease activity in relapsing-remitting MS (RRMS) as the approved 4-week dosing schedule.

Finally, Dr Mowry discusses a phase 2 randomized trial of the gold nanoparticle CNM-Au8, which has been used to treat other autoimmune diseases, to determine its potential benefits in RRMS.

--

Ellen Mowry, MD, MCR, Professor of Neurology & Epidemiology, Johns Hopkins University, Baltimore, Maryland

Ellen Mowry, MD, MCR, has disclosed the following relevant financial relationships:

Serve(d) as a consultant for: BeCareLink, LLC

Received research grant from: Biogen; Genentech

Received royalties from: UpToDate

TOPLINE:

Treatment with two naturally occurring psychedelics was associated with reduced depressive and anxiety symptoms in trauma-exposed U.S. Special Operations Forces Veterans (SOFVs), according to a new study. Perhaps most surprising to investigators, however, was that treatment was also associated with improved cognitive scores in the veterans, many of whom had traumatic brain injuries.

METHODOLOGY:

• Investigators reviewed clinical charts of 86 SOFVs who received psychedelic-assisted treatment at a therapeutic program in Mexico, 86% of whom sustained head injuries during deployment.
• On the first day of the study, participants received a single oral dose (10 mg/kg) of ibogaine hydrochloride in a group setting with two to five other attendees and spent the next day reflecting on their experience with program staff.
• On the third day, participants inhaled 5-MeO-DMT in three incremental doses for a total of 50 mg and were then invited to reflect on their experience both individually and with the group of peers who shared the experience.
• Follow-up surveys at 1, 3, and 6 months posttreatment between September 2019 to March 2021 measured symptoms of posttraumatic stress disorder, cognitive functioning, generalized anxiety disorder, depression, and quality of life.

TAKEAWAY:

• There were significant improvements in self-reported PTSD symptoms, depression, anxiety, insomnia severity, anger, and a large improvement in self-reported satisfaction with life (P < .001 for all).
• Participants reported significant increases in psychological flexibility (P < .001), cognitive functioning (P < .001), and postconcussive symptoms (P < .001).
• Treatment was also associated with a significant reduction in suicidal ideation from pretreatment to 1-month follow-up (P < .01).

IN PRACTICE:

“If consistently replicated, this could have major implications for the landscape of mental health care if people are able to experience significant and sustained healing with 3 days of intensive treatment, relative to our traditionally available interventions that require 8-12 weeks of weekly therapy (for example, gold standard talk therapies such as [prolonged exposure] or [cognitive processing therapy]), or daily use of a pharmacotherapy such as [a selective serotonin reuptake inhibitor] for months to years,” study authors write.

SOURCE:

Alan Kooi Davis, PhD, of the Center for Psychedelic Drug Research and Education at Ohio State University, led the study, which was published online  in the American Journal of Drug and Alcohol Abuse.

LIMITATIONS:

Study assessments are based solely on self-report measures. Future research should implement carefully designed batteries that include both self-report and gold-standard clinician-administered measures to better capture symptom improvement and other information. The sample also lacked diversity with regard to race, religion, and socioeconomic status.

DISCLOSURES:

The study was funded by Veterans Exploring Treatment Solutions. Dr. Davis is a board member at Source Resource Foundation and a lead trainer at Fluence. Full disclosures are included in the original article.

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

TOPLINE:

Treatment with two naturally occurring psychedelics was associated with reduced depressive and anxiety symptoms in trauma-exposed U.S. Special Operations Forces Veterans (SOFVs), according to a new study. Perhaps most surprising to investigators, however, was that treatment was also associated with improved cognitive scores in the veterans, many of whom had traumatic brain injuries.

METHODOLOGY:

• Investigators reviewed clinical charts of 86 SOFVs who received psychedelic-assisted treatment at a therapeutic program in Mexico, 86% of whom sustained head injuries during deployment.
• On the first day of the study, participants received a single oral dose (10 mg/kg) of ibogaine hydrochloride in a group setting with two to five other attendees and spent the next day reflecting on their experience with program staff.
• On the third day, participants inhaled 5-MeO-DMT in three incremental doses for a total of 50 mg and were then invited to reflect on their experience both individually and with the group of peers who shared the experience.
• Follow-up surveys at 1, 3, and 6 months posttreatment between September 2019 to March 2021 measured symptoms of posttraumatic stress disorder, cognitive functioning, generalized anxiety disorder, depression, and quality of life.

TAKEAWAY:

• There were significant improvements in self-reported PTSD symptoms, depression, anxiety, insomnia severity, anger, and a large improvement in self-reported satisfaction with life (P < .001 for all).
• Participants reported significant increases in psychological flexibility (P < .001), cognitive functioning (P < .001), and postconcussive symptoms (P < .001).
• Treatment was also associated with a significant reduction in suicidal ideation from pretreatment to 1-month follow-up (P < .01).

IN PRACTICE:

“If consistently replicated, this could have major implications for the landscape of mental health care if people are able to experience significant and sustained healing with 3 days of intensive treatment, relative to our traditionally available interventions that require 8-12 weeks of weekly therapy (for example, gold standard talk therapies such as [prolonged exposure] or [cognitive processing therapy]), or daily use of a pharmacotherapy such as [a selective serotonin reuptake inhibitor] for months to years,” study authors write.

SOURCE:

Alan Kooi Davis, PhD, of the Center for Psychedelic Drug Research and Education at Ohio State University, led the study, which was published online  in the American Journal of Drug and Alcohol Abuse.

LIMITATIONS:

Study assessments are based solely on self-report measures. Future research should implement carefully designed batteries that include both self-report and gold-standard clinician-administered measures to better capture symptom improvement and other information. The sample also lacked diversity with regard to race, religion, and socioeconomic status.

DISCLOSURES:

The study was funded by Veterans Exploring Treatment Solutions. Dr. Davis is a board member at Source Resource Foundation and a lead trainer at Fluence. Full disclosures are included in the original article.

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

TOPLINE:

Treatment with two naturally occurring psychedelics was associated with reduced depressive and anxiety symptoms in trauma-exposed U.S. Special Operations Forces Veterans (SOFVs), according to a new study. Perhaps most surprising to investigators, however, was that treatment was also associated with improved cognitive scores in the veterans, many of whom had traumatic brain injuries.

METHODOLOGY:

• Investigators reviewed clinical charts of 86 SOFVs who received psychedelic-assisted treatment at a therapeutic program in Mexico, 86% of whom sustained head injuries during deployment.
• On the first day of the study, participants received a single oral dose (10 mg/kg) of ibogaine hydrochloride in a group setting with two to five other attendees and spent the next day reflecting on their experience with program staff.
• On the third day, participants inhaled 5-MeO-DMT in three incremental doses for a total of 50 mg and were then invited to reflect on their experience both individually and with the group of peers who shared the experience.
• Follow-up surveys at 1, 3, and 6 months posttreatment between September 2019 to March 2021 measured symptoms of posttraumatic stress disorder, cognitive functioning, generalized anxiety disorder, depression, and quality of life.

TAKEAWAY:

• There were significant improvements in self-reported PTSD symptoms, depression, anxiety, insomnia severity, anger, and a large improvement in self-reported satisfaction with life (P < .001 for all).
• Participants reported significant increases in psychological flexibility (P < .001), cognitive functioning (P < .001), and postconcussive symptoms (P < .001).
• Treatment was also associated with a significant reduction in suicidal ideation from pretreatment to 1-month follow-up (P < .01).

IN PRACTICE:

“If consistently replicated, this could have major implications for the landscape of mental health care if people are able to experience significant and sustained healing with 3 days of intensive treatment, relative to our traditionally available interventions that require 8-12 weeks of weekly therapy (for example, gold standard talk therapies such as [prolonged exposure] or [cognitive processing therapy]), or daily use of a pharmacotherapy such as [a selective serotonin reuptake inhibitor] for months to years,” study authors write.

SOURCE:

Alan Kooi Davis, PhD, of the Center for Psychedelic Drug Research and Education at Ohio State University, led the study, which was published online  in the American Journal of Drug and Alcohol Abuse.

LIMITATIONS:

Study assessments are based solely on self-report measures. Future research should implement carefully designed batteries that include both self-report and gold-standard clinician-administered measures to better capture symptom improvement and other information. The sample also lacked diversity with regard to race, religion, and socioeconomic status.

DISCLOSURES:

The study was funded by Veterans Exploring Treatment Solutions. Dr. Davis is a board member at Source Resource Foundation and a lead trainer at Fluence. Full disclosures are included in the original article.

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

TOPLINE:

New research suggests that long-term exposure to air pollution during and after pregnancy increases the risk of postpartum depression (PPD), adding to prior research linking air pollution to mental health issues.

METHODOLOGY:

• Researchers analyzed data on 340,679 women who had singleton live births at Kaiser Permanente Southern California facilities between 2008 and 2016.
• Ambient air pollution exposures were assessed based on maternal residential addresses using monthly averages of particulate matter ≤ 2.5 mcm (PM_2.5), PM ≤ 10 mcm (PM₁₀), nitrogen dioxide, and ozone from Environmental Protection Agency monitoring stations.
• Constituents of PM_2.5 (sulfate, nitrate, ammonium, organic matter, and black carbon) were obtained from models based on satellite, ground-based monitor, and chemical transport modeling data.
• Women with an Edinburgh Postnatal Depression Scale score of at least 10 during the first 6 months postpartum were referred for further assessment, including diagnosis and treatment.

TAKEAWAY:

• A total of 25,674 women had PPD (7.5%).
• Positive associations were observed between PPD ozone (adjusted odds ratio, 1.09), PM₁₀ (aOR, 1.02), and PM_2.5 (aOR, 1.02), with no statistically significant association with nitrogen dioxide.
• Among PM_2.5 constituents, black carbon had the strongest association with PPD (OR 1.04).
• Overall, a higher risk of PPD was associated with ozone exposure during the entire pregnancy and postpartum periods and with PM exposure during the late pregnancy and postpartum periods.

IN PRACTICE:

“These findings suggest that long-term antepartum and postpartum air pollution exposure is a potentially modifiable environmental risk factor for PPD and an important public health issue to address for improved maternal mental health,” the authors wrote.

SOURCE:

The study, with first author Yi Sun, PhD, Chinese Academy of Medical Sciences and Peking Medical College, Beijing, was published online in JAMA Network Open.

LIMITATIONS:

Postpartum exposures were estimated using only maternal address at delivery, which may have led to exposure misclassification. Potential exposure misclassifications may also exist since indoor and personal exposure levels could not be estimated. Although several covariates were adjusted for, some residual or unmeasured covariates were inevitable due to data unavailability, such as psychiatric history, adverse life events, and marital status, which may affect mental health.

DISCLOSURES:

This study was supported by a grant from the National Institute of Environmental Health Sciences. The authors report no relevant financial relationships.

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

TOPLINE:

New research suggests that long-term exposure to air pollution during and after pregnancy increases the risk of postpartum depression (PPD), adding to prior research linking air pollution to mental health issues.

METHODOLOGY:

• Researchers analyzed data on 340,679 women who had singleton live births at Kaiser Permanente Southern California facilities between 2008 and 2016.
• Ambient air pollution exposures were assessed based on maternal residential addresses using monthly averages of particulate matter ≤ 2.5 mcm (PM_2.5), PM ≤ 10 mcm (PM₁₀), nitrogen dioxide, and ozone from Environmental Protection Agency monitoring stations.
• Constituents of PM_2.5 (sulfate, nitrate, ammonium, organic matter, and black carbon) were obtained from models based on satellite, ground-based monitor, and chemical transport modeling data.
• Women with an Edinburgh Postnatal Depression Scale score of at least 10 during the first 6 months postpartum were referred for further assessment, including diagnosis and treatment.

TAKEAWAY:

• A total of 25,674 women had PPD (7.5%).
• Positive associations were observed between PPD ozone (adjusted odds ratio, 1.09), PM₁₀ (aOR, 1.02), and PM_2.5 (aOR, 1.02), with no statistically significant association with nitrogen dioxide.
• Among PM_2.5 constituents, black carbon had the strongest association with PPD (OR 1.04).
• Overall, a higher risk of PPD was associated with ozone exposure during the entire pregnancy and postpartum periods and with PM exposure during the late pregnancy and postpartum periods.

IN PRACTICE:

“These findings suggest that long-term antepartum and postpartum air pollution exposure is a potentially modifiable environmental risk factor for PPD and an important public health issue to address for improved maternal mental health,” the authors wrote.

SOURCE:

The study, with first author Yi Sun, PhD, Chinese Academy of Medical Sciences and Peking Medical College, Beijing, was published online in JAMA Network Open.

LIMITATIONS:

Postpartum exposures were estimated using only maternal address at delivery, which may have led to exposure misclassification. Potential exposure misclassifications may also exist since indoor and personal exposure levels could not be estimated. Although several covariates were adjusted for, some residual or unmeasured covariates were inevitable due to data unavailability, such as psychiatric history, adverse life events, and marital status, which may affect mental health.

DISCLOSURES:

This study was supported by a grant from the National Institute of Environmental Health Sciences. The authors report no relevant financial relationships.

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

TOPLINE:

New research suggests that long-term exposure to air pollution during and after pregnancy increases the risk of postpartum depression (PPD), adding to prior research linking air pollution to mental health issues.

METHODOLOGY:

• Researchers analyzed data on 340,679 women who had singleton live births at Kaiser Permanente Southern California facilities between 2008 and 2016.
• Ambient air pollution exposures were assessed based on maternal residential addresses using monthly averages of particulate matter ≤ 2.5 mcm (PM_2.5), PM ≤ 10 mcm (PM₁₀), nitrogen dioxide, and ozone from Environmental Protection Agency monitoring stations.
• Constituents of PM_2.5 (sulfate, nitrate, ammonium, organic matter, and black carbon) were obtained from models based on satellite, ground-based monitor, and chemical transport modeling data.
• Women with an Edinburgh Postnatal Depression Scale score of at least 10 during the first 6 months postpartum were referred for further assessment, including diagnosis and treatment.

TAKEAWAY:

• A total of 25,674 women had PPD (7.5%).
• Positive associations were observed between PPD ozone (adjusted odds ratio, 1.09), PM₁₀ (aOR, 1.02), and PM_2.5 (aOR, 1.02), with no statistically significant association with nitrogen dioxide.
• Among PM_2.5 constituents, black carbon had the strongest association with PPD (OR 1.04).
• Overall, a higher risk of PPD was associated with ozone exposure during the entire pregnancy and postpartum periods and with PM exposure during the late pregnancy and postpartum periods.

IN PRACTICE:

“These findings suggest that long-term antepartum and postpartum air pollution exposure is a potentially modifiable environmental risk factor for PPD and an important public health issue to address for improved maternal mental health,” the authors wrote.

SOURCE:

The study, with first author Yi Sun, PhD, Chinese Academy of Medical Sciences and Peking Medical College, Beijing, was published online in JAMA Network Open.

LIMITATIONS:

Postpartum exposures were estimated using only maternal address at delivery, which may have led to exposure misclassification. Potential exposure misclassifications may also exist since indoor and personal exposure levels could not be estimated. Although several covariates were adjusted for, some residual or unmeasured covariates were inevitable due to data unavailability, such as psychiatric history, adverse life events, and marital status, which may affect mental health.

DISCLOSURES:

This study was supported by a grant from the National Institute of Environmental Health Sciences. The authors report no relevant financial relationships.

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