News

If Miley Cyrus has planted “Flowers” in your head, rest assured you’re not alone.

An earworm – a bit of music you can’t shake from your brain – happens to almost everyone. 

The culprit is typically a song you’ve heard repeatedly with a strong rhythm and melody (like Miley’s No. 1 hit this year).

It pops into your head and stays there, unbidden and often unwanted. As you fish for something new on Spotify, there’s always a chance that a catchy hook holds an earworm.

“A catchy tune or melody is the part of a song most likely to get stuck in a person’s head, often a bit from the chorus,” said Elizabeth H. Margulis, PhD, a professor at Princeton (N.J.) University and director of its music cognition lab. The phenomenon, which has been studied since 1885 (way before earbuds), goes by such names as stuck song syndrome, sticky music, musical imagery repetition, intrusive musical imagery, or the semi-official term, involuntary musical imagery, or INMI.

Research confirms how common it is. A 2020 study of American college students found that 97% had experienced an earworm in the past month, similar to findings from a larger Finnish survey done more than 10 years ago.

One in five people had experienced an earworm more than once a day, the study found. The typical length was 10-30 minutes, though 8.5% said theirs lasted more than 3 hours. Levels of “distress and interference” that earworms caused was mostly “mild to moderate.” 

Some 86% said they tried to stop it – most frequently by distraction, like talking to a friend or listening to another song.

If music is important to you, your earworms are more likely to last longer and be harder to control, earlier research found. And women are thought to be more likely to have them.

“Very musical people may have more earworms because it’s easy for them to conjure up a certain tune,” says David Silbersweig, MD, chairman of the department of psychiatry and codirector of the Institute for the Neurosciences at Brigham and Women’s Hospital in Boston.

Moreover, people who lack “psychological flexibility” may find earworms more bothersome. The more they try to avoid or control intrusive thoughts (or songs), the more persistent those thoughts become. 

“This is consistent with OCD (obsessive-compulsive disorder) research on the paradoxical effect of thought suppression,” the authors of the 2020 study wrote. In fact, people who report very annoying or stressful earworms are more likely to have obsessive-compulsive symptoms.

Earworms have been linked to other medical conditions as well, and even harmless earworms can be intrusive and time-consuming. That makes them worth a closer look.

Digging for the source of earworms

Scientists trace earworms to the auditory cortex in the temporal lobe of the brain, which controls how you perceive music, as well as deep temporal lobe areas that are responsible for retrieving memories. Your amygdala and ventral striatum, parts of your brain that involve emotion, also tie into the making of an earworm.

MRI experiments found that “INMI is a common internal experience recruiting brain networks involved in perception, emotions, memory and spontaneous thoughts,” a 2015 paper in  Consciousness and Cognition  reported.

These brain networks work in tandem if you connect a song to an emotional memory – that’s when you’re more likely to experience it as an earworm. The “loop” of music you’ll hear in your head is usually a 20-second snippet.

Think of it as a “cognitive itch,” as researchers from the Netherlands put it. An earworm can be triggered by associating a song with a specific situation or emotion. Trying to suppress it just reminds you it’s there, “scratching” the itch and making it worse. “The more one tries to suppress the songs, the more their impetus increases, a mental process known as ironic process theory,” they wrote. 

“It’s also worth pointing out that earworms don’t always occur right after a song ends,” said Michael K. Scullin, PhD, an associate professor of psychology and neuroscience at Baylor University in Waco, Tex. “Sometimes they only occur many hours later, and sometimes the earworm isn’t the song you were most recently listening to.”

These processes aren’t fully understood, he said, “but they likely represent memory consolidation mechanisms; that is, the brain trying to reactivate and stabilize musical memories.” Kind of like switching “radio stations” in your head. 

When to worry

Earworms are most often harmless. “They’re part of a healthy brain,” said Dr. Silbersweig. But in rare cases, they indicate certain medical conditions. People with OCD, for example, have been shown to have earworms during times of stress. If this is the case, cognitive-behavioral therapy as well as some antidepressants may help.

Take an earworm seriously if it’s linked to other symptoms, said Elaine Jones, MD, a neurologist in Hilton Head, S.C., and a fellow of the American Academy of Neurology. Those symptoms could include “loss of consciousness or confusion, visual loss or changes, speech arrest, tremors of arms or legs,” she said.

“Most worrisome would be a seizure, but other causes could include a migraine aura. In a younger person, less than 20 years old, this kind of earworm could indicate a psychiatric condition like schizophrenia.” Drug toxicity or brain damage can also present with earworms.

Her bottom line: “If an earworm is persistent for more than 24 hours, or if it is associated with the other symptoms mentioned above, it would be important to reach out to your primary care doctor to ensure that nothing more serious is going on,” said Dr. Jones. With no other symptoms, “it is more likely to be just an earworm.”

Japanese research also indicates that an earworm that lasts for several hours in a day can be linked to depression. If a person has symptoms such as low mood, insomnia, and loss of appetite, along with earworms that last several hours a day, treatment may help. 

There’s another category called “musical hallucinations” – where the person thinks they are actually hearing music, which could be a symptom of depression, although scientists don’t know for sure. The drug vortioxetine, which may help boost serotonin in the brain, has shown some promise in reducing earworms. 

Some research has shown that diseases that damage the auditory pathway in the brain have a link to musical hallucinations. 

How to stop a simple earworm

Here are six easy ways to make it stop:

• Mix up your playlist. “Listening to songs repeatedly does increase the likelihood that they’ll get stuck,” said Dr. Margulis. 
• Take breaks from your tunes throughout the day. “Longer listening durations are more likely to lead to earworms,” Dr. Scullin said.
• Use your feet. than the beat of your earworm. This will interrupt your memory of the tempo and can help chase away the earworm.
• Stick with that song. “Listen to a song all the way through,” said Dr. Silbersweig. If you only listen to snippets of a song, the  can take hold. That’s the brain’s tendency to remember things that are interrupted more easily than completed things.
• Distract yourself. Lose yourself in a book, a movie, your work, or a hobby that requires concentration. “Redirecting attention to an absorbing task can be an effective way to dislodge an earworm,” said Dr. Margulis. 
• Chew gum.  shows that the action of doing so interferes with repetitive memories and stops your mind from “scanning” a song. Then enjoy the sound of silence!

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

If Miley Cyrus has planted “Flowers” in your head, rest assured you’re not alone.

An earworm – a bit of music you can’t shake from your brain – happens to almost everyone. 

The culprit is typically a song you’ve heard repeatedly with a strong rhythm and melody (like Miley’s No. 1 hit this year).

It pops into your head and stays there, unbidden and often unwanted. As you fish for something new on Spotify, there’s always a chance that a catchy hook holds an earworm.

“A catchy tune or melody is the part of a song most likely to get stuck in a person’s head, often a bit from the chorus,” said Elizabeth H. Margulis, PhD, a professor at Princeton (N.J.) University and director of its music cognition lab. The phenomenon, which has been studied since 1885 (way before earbuds), goes by such names as stuck song syndrome, sticky music, musical imagery repetition, intrusive musical imagery, or the semi-official term, involuntary musical imagery, or INMI.

Research confirms how common it is. A 2020 study of American college students found that 97% had experienced an earworm in the past month, similar to findings from a larger Finnish survey done more than 10 years ago.

One in five people had experienced an earworm more than once a day, the study found. The typical length was 10-30 minutes, though 8.5% said theirs lasted more than 3 hours. Levels of “distress and interference” that earworms caused was mostly “mild to moderate.” 

Some 86% said they tried to stop it – most frequently by distraction, like talking to a friend or listening to another song.

If music is important to you, your earworms are more likely to last longer and be harder to control, earlier research found. And women are thought to be more likely to have them.

“Very musical people may have more earworms because it’s easy for them to conjure up a certain tune,” says David Silbersweig, MD, chairman of the department of psychiatry and codirector of the Institute for the Neurosciences at Brigham and Women’s Hospital in Boston.

Moreover, people who lack “psychological flexibility” may find earworms more bothersome. The more they try to avoid or control intrusive thoughts (or songs), the more persistent those thoughts become. 

“This is consistent with OCD (obsessive-compulsive disorder) research on the paradoxical effect of thought suppression,” the authors of the 2020 study wrote. In fact, people who report very annoying or stressful earworms are more likely to have obsessive-compulsive symptoms.

Earworms have been linked to other medical conditions as well, and even harmless earworms can be intrusive and time-consuming. That makes them worth a closer look.

Digging for the source of earworms

Scientists trace earworms to the auditory cortex in the temporal lobe of the brain, which controls how you perceive music, as well as deep temporal lobe areas that are responsible for retrieving memories. Your amygdala and ventral striatum, parts of your brain that involve emotion, also tie into the making of an earworm.

MRI experiments found that “INMI is a common internal experience recruiting brain networks involved in perception, emotions, memory and spontaneous thoughts,” a 2015 paper in  Consciousness and Cognition  reported.

These brain networks work in tandem if you connect a song to an emotional memory – that’s when you’re more likely to experience it as an earworm. The “loop” of music you’ll hear in your head is usually a 20-second snippet.

Think of it as a “cognitive itch,” as researchers from the Netherlands put it. An earworm can be triggered by associating a song with a specific situation or emotion. Trying to suppress it just reminds you it’s there, “scratching” the itch and making it worse. “The more one tries to suppress the songs, the more their impetus increases, a mental process known as ironic process theory,” they wrote. 

“It’s also worth pointing out that earworms don’t always occur right after a song ends,” said Michael K. Scullin, PhD, an associate professor of psychology and neuroscience at Baylor University in Waco, Tex. “Sometimes they only occur many hours later, and sometimes the earworm isn’t the song you were most recently listening to.”

These processes aren’t fully understood, he said, “but they likely represent memory consolidation mechanisms; that is, the brain trying to reactivate and stabilize musical memories.” Kind of like switching “radio stations” in your head. 

When to worry

Earworms are most often harmless. “They’re part of a healthy brain,” said Dr. Silbersweig. But in rare cases, they indicate certain medical conditions. People with OCD, for example, have been shown to have earworms during times of stress. If this is the case, cognitive-behavioral therapy as well as some antidepressants may help.

Take an earworm seriously if it’s linked to other symptoms, said Elaine Jones, MD, a neurologist in Hilton Head, S.C., and a fellow of the American Academy of Neurology. Those symptoms could include “loss of consciousness or confusion, visual loss or changes, speech arrest, tremors of arms or legs,” she said.

“Most worrisome would be a seizure, but other causes could include a migraine aura. In a younger person, less than 20 years old, this kind of earworm could indicate a psychiatric condition like schizophrenia.” Drug toxicity or brain damage can also present with earworms.

Her bottom line: “If an earworm is persistent for more than 24 hours, or if it is associated with the other symptoms mentioned above, it would be important to reach out to your primary care doctor to ensure that nothing more serious is going on,” said Dr. Jones. With no other symptoms, “it is more likely to be just an earworm.”

Japanese research also indicates that an earworm that lasts for several hours in a day can be linked to depression. If a person has symptoms such as low mood, insomnia, and loss of appetite, along with earworms that last several hours a day, treatment may help. 

There’s another category called “musical hallucinations” – where the person thinks they are actually hearing music, which could be a symptom of depression, although scientists don’t know for sure. The drug vortioxetine, which may help boost serotonin in the brain, has shown some promise in reducing earworms. 

Some research has shown that diseases that damage the auditory pathway in the brain have a link to musical hallucinations. 

How to stop a simple earworm

Here are six easy ways to make it stop:

• Mix up your playlist. “Listening to songs repeatedly does increase the likelihood that they’ll get stuck,” said Dr. Margulis. 
• Take breaks from your tunes throughout the day. “Longer listening durations are more likely to lead to earworms,” Dr. Scullin said.
• Use your feet. than the beat of your earworm. This will interrupt your memory of the tempo and can help chase away the earworm.
• Stick with that song. “Listen to a song all the way through,” said Dr. Silbersweig. If you only listen to snippets of a song, the  can take hold. That’s the brain’s tendency to remember things that are interrupted more easily than completed things.
• Distract yourself. Lose yourself in a book, a movie, your work, or a hobby that requires concentration. “Redirecting attention to an absorbing task can be an effective way to dislodge an earworm,” said Dr. Margulis. 
• Chew gum.  shows that the action of doing so interferes with repetitive memories and stops your mind from “scanning” a song. Then enjoy the sound of silence!

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

If Miley Cyrus has planted “Flowers” in your head, rest assured you’re not alone.

An earworm – a bit of music you can’t shake from your brain – happens to almost everyone. 

The culprit is typically a song you’ve heard repeatedly with a strong rhythm and melody (like Miley’s No. 1 hit this year).

It pops into your head and stays there, unbidden and often unwanted. As you fish for something new on Spotify, there’s always a chance that a catchy hook holds an earworm.

“A catchy tune or melody is the part of a song most likely to get stuck in a person’s head, often a bit from the chorus,” said Elizabeth H. Margulis, PhD, a professor at Princeton (N.J.) University and director of its music cognition lab. The phenomenon, which has been studied since 1885 (way before earbuds), goes by such names as stuck song syndrome, sticky music, musical imagery repetition, intrusive musical imagery, or the semi-official term, involuntary musical imagery, or INMI.

Research confirms how common it is. A 2020 study of American college students found that 97% had experienced an earworm in the past month, similar to findings from a larger Finnish survey done more than 10 years ago.

One in five people had experienced an earworm more than once a day, the study found. The typical length was 10-30 minutes, though 8.5% said theirs lasted more than 3 hours. Levels of “distress and interference” that earworms caused was mostly “mild to moderate.” 

Some 86% said they tried to stop it – most frequently by distraction, like talking to a friend or listening to another song.

If music is important to you, your earworms are more likely to last longer and be harder to control, earlier research found. And women are thought to be more likely to have them.

“Very musical people may have more earworms because it’s easy for them to conjure up a certain tune,” says David Silbersweig, MD, chairman of the department of psychiatry and codirector of the Institute for the Neurosciences at Brigham and Women’s Hospital in Boston.

Moreover, people who lack “psychological flexibility” may find earworms more bothersome. The more they try to avoid or control intrusive thoughts (or songs), the more persistent those thoughts become. 

“This is consistent with OCD (obsessive-compulsive disorder) research on the paradoxical effect of thought suppression,” the authors of the 2020 study wrote. In fact, people who report very annoying or stressful earworms are more likely to have obsessive-compulsive symptoms.

Earworms have been linked to other medical conditions as well, and even harmless earworms can be intrusive and time-consuming. That makes them worth a closer look.

Digging for the source of earworms

Scientists trace earworms to the auditory cortex in the temporal lobe of the brain, which controls how you perceive music, as well as deep temporal lobe areas that are responsible for retrieving memories. Your amygdala and ventral striatum, parts of your brain that involve emotion, also tie into the making of an earworm.

MRI experiments found that “INMI is a common internal experience recruiting brain networks involved in perception, emotions, memory and spontaneous thoughts,” a 2015 paper in  Consciousness and Cognition  reported.

These brain networks work in tandem if you connect a song to an emotional memory – that’s when you’re more likely to experience it as an earworm. The “loop” of music you’ll hear in your head is usually a 20-second snippet.

Think of it as a “cognitive itch,” as researchers from the Netherlands put it. An earworm can be triggered by associating a song with a specific situation or emotion. Trying to suppress it just reminds you it’s there, “scratching” the itch and making it worse. “The more one tries to suppress the songs, the more their impetus increases, a mental process known as ironic process theory,” they wrote. 

“It’s also worth pointing out that earworms don’t always occur right after a song ends,” said Michael K. Scullin, PhD, an associate professor of psychology and neuroscience at Baylor University in Waco, Tex. “Sometimes they only occur many hours later, and sometimes the earworm isn’t the song you were most recently listening to.”

These processes aren’t fully understood, he said, “but they likely represent memory consolidation mechanisms; that is, the brain trying to reactivate and stabilize musical memories.” Kind of like switching “radio stations” in your head. 

When to worry

Earworms are most often harmless. “They’re part of a healthy brain,” said Dr. Silbersweig. But in rare cases, they indicate certain medical conditions. People with OCD, for example, have been shown to have earworms during times of stress. If this is the case, cognitive-behavioral therapy as well as some antidepressants may help.

Take an earworm seriously if it’s linked to other symptoms, said Elaine Jones, MD, a neurologist in Hilton Head, S.C., and a fellow of the American Academy of Neurology. Those symptoms could include “loss of consciousness or confusion, visual loss or changes, speech arrest, tremors of arms or legs,” she said.

“Most worrisome would be a seizure, but other causes could include a migraine aura. In a younger person, less than 20 years old, this kind of earworm could indicate a psychiatric condition like schizophrenia.” Drug toxicity or brain damage can also present with earworms.

Her bottom line: “If an earworm is persistent for more than 24 hours, or if it is associated with the other symptoms mentioned above, it would be important to reach out to your primary care doctor to ensure that nothing more serious is going on,” said Dr. Jones. With no other symptoms, “it is more likely to be just an earworm.”

Japanese research also indicates that an earworm that lasts for several hours in a day can be linked to depression. If a person has symptoms such as low mood, insomnia, and loss of appetite, along with earworms that last several hours a day, treatment may help. 

There’s another category called “musical hallucinations” – where the person thinks they are actually hearing music, which could be a symptom of depression, although scientists don’t know for sure. The drug vortioxetine, which may help boost serotonin in the brain, has shown some promise in reducing earworms. 

Some research has shown that diseases that damage the auditory pathway in the brain have a link to musical hallucinations. 

How to stop a simple earworm

Here are six easy ways to make it stop:

• Mix up your playlist. “Listening to songs repeatedly does increase the likelihood that they’ll get stuck,” said Dr. Margulis. 
• Take breaks from your tunes throughout the day. “Longer listening durations are more likely to lead to earworms,” Dr. Scullin said.
• Use your feet. than the beat of your earworm. This will interrupt your memory of the tempo and can help chase away the earworm.
• Stick with that song. “Listen to a song all the way through,” said Dr. Silbersweig. If you only listen to snippets of a song, the  can take hold. That’s the brain’s tendency to remember things that are interrupted more easily than completed things.
• Distract yourself. Lose yourself in a book, a movie, your work, or a hobby that requires concentration. “Redirecting attention to an absorbing task can be an effective way to dislodge an earworm,” said Dr. Margulis. 
• Chew gum.  shows that the action of doing so interferes with repetitive memories and stops your mind from “scanning” a song. Then enjoy the sound of silence!

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

Just 16% of psoriasis-related visits to dermatology providers in the United States involve screening for cardiovascular (CV) risk factors, with screening lowest in the region with the highest CV disease burden, according to an analysis of 10 years of national survey data.

From 2007 to 2016, national screening rates for four CV risk factors at 14.8 million psoriasis-related visits to dermatology providers were 11% (body-mass index), 7.4% (blood pressure), 2.9% (cholesterol), and 1.7% (glucose). Data from the National Ambulatory Medical Care Survey showed that at least one of the four factors was screened at 16% of dermatology visits, said William B. Song, BS, of the department of dermatology, University of Pennsylvania, Philadelphia, and associates.

The main focus of their study, however, was regional differences. “CV risk factor screening by dermatology providers for patients with psoriasis is low across all regions of the United States and lowest in the South, the region that experiences the highest CVD burden in the United States,” they wrote in a letter to the editor.

Compared with the South, the adjusted odds of any CV screening were 0.98 in the West, 1.25 in the Northeast, and 1.92 in the Midwest. Blood pressure screening was significantly higher in all three regions, compared with the South, while BMI screening was actually lower in the West (0.74), the investigators reported. Odds ratios were not available for cholesterol and glucose screening because of sample size limitations.

The regional variation in screening rates “is not explained by patient demographics or disease severity,” they noted, adding that 2.8 million visits with BP screening would have been added over the 10-year study period “if providers in the South screened patients with psoriasis for high blood pressure at the same rate as providers in the Northeast.”

Guidelines published in 2019 by the American Academy of Dermatology and the National Psoriasis Foundation – which were cowritten by Joel M. Gelfand, MD, senior author of the current study – noted that dermatologists “play an important role in evidence-based screening of CV risk factors in patients with psoriasis,” the investigators wrote. But the regional variations suggest “that some regions experience barriers to appropriate screening or challenges in adhering to guidelines for managing psoriasis and CV risk.”

While the lack of data from after 2016 is one of the study limitations, they added, “continued efforts to develop effective interventions to improve CV screening and care for people with psoriasis in all regions of the U.S. are needed to more effectively address the burden of CV disease experienced by people with psoriasis.”

The study was partly funded by the National Psoriasis Foundation. Three of the seven investigators disclosed earnings from private companies in the form of consultant fees, research support, and honoraria. Dr. Gelfand is a deputy editor for the Journal of Investigative Dermatology.

Just 16% of psoriasis-related visits to dermatology providers in the United States involve screening for cardiovascular (CV) risk factors, with screening lowest in the region with the highest CV disease burden, according to an analysis of 10 years of national survey data.

From 2007 to 2016, national screening rates for four CV risk factors at 14.8 million psoriasis-related visits to dermatology providers were 11% (body-mass index), 7.4% (blood pressure), 2.9% (cholesterol), and 1.7% (glucose). Data from the National Ambulatory Medical Care Survey showed that at least one of the four factors was screened at 16% of dermatology visits, said William B. Song, BS, of the department of dermatology, University of Pennsylvania, Philadelphia, and associates.

The main focus of their study, however, was regional differences. “CV risk factor screening by dermatology providers for patients with psoriasis is low across all regions of the United States and lowest in the South, the region that experiences the highest CVD burden in the United States,” they wrote in a letter to the editor.

Compared with the South, the adjusted odds of any CV screening were 0.98 in the West, 1.25 in the Northeast, and 1.92 in the Midwest. Blood pressure screening was significantly higher in all three regions, compared with the South, while BMI screening was actually lower in the West (0.74), the investigators reported. Odds ratios were not available for cholesterol and glucose screening because of sample size limitations.

The regional variation in screening rates “is not explained by patient demographics or disease severity,” they noted, adding that 2.8 million visits with BP screening would have been added over the 10-year study period “if providers in the South screened patients with psoriasis for high blood pressure at the same rate as providers in the Northeast.”

Guidelines published in 2019 by the American Academy of Dermatology and the National Psoriasis Foundation – which were cowritten by Joel M. Gelfand, MD, senior author of the current study – noted that dermatologists “play an important role in evidence-based screening of CV risk factors in patients with psoriasis,” the investigators wrote. But the regional variations suggest “that some regions experience barriers to appropriate screening or challenges in adhering to guidelines for managing psoriasis and CV risk.”

While the lack of data from after 2016 is one of the study limitations, they added, “continued efforts to develop effective interventions to improve CV screening and care for people with psoriasis in all regions of the U.S. are needed to more effectively address the burden of CV disease experienced by people with psoriasis.”

The study was partly funded by the National Psoriasis Foundation. Three of the seven investigators disclosed earnings from private companies in the form of consultant fees, research support, and honoraria. Dr. Gelfand is a deputy editor for the Journal of Investigative Dermatology.

Just 16% of psoriasis-related visits to dermatology providers in the United States involve screening for cardiovascular (CV) risk factors, with screening lowest in the region with the highest CV disease burden, according to an analysis of 10 years of national survey data.

From 2007 to 2016, national screening rates for four CV risk factors at 14.8 million psoriasis-related visits to dermatology providers were 11% (body-mass index), 7.4% (blood pressure), 2.9% (cholesterol), and 1.7% (glucose). Data from the National Ambulatory Medical Care Survey showed that at least one of the four factors was screened at 16% of dermatology visits, said William B. Song, BS, of the department of dermatology, University of Pennsylvania, Philadelphia, and associates.

The main focus of their study, however, was regional differences. “CV risk factor screening by dermatology providers for patients with psoriasis is low across all regions of the United States and lowest in the South, the region that experiences the highest CVD burden in the United States,” they wrote in a letter to the editor.

Compared with the South, the adjusted odds of any CV screening were 0.98 in the West, 1.25 in the Northeast, and 1.92 in the Midwest. Blood pressure screening was significantly higher in all three regions, compared with the South, while BMI screening was actually lower in the West (0.74), the investigators reported. Odds ratios were not available for cholesterol and glucose screening because of sample size limitations.

The regional variation in screening rates “is not explained by patient demographics or disease severity,” they noted, adding that 2.8 million visits with BP screening would have been added over the 10-year study period “if providers in the South screened patients with psoriasis for high blood pressure at the same rate as providers in the Northeast.”

Guidelines published in 2019 by the American Academy of Dermatology and the National Psoriasis Foundation – which were cowritten by Joel M. Gelfand, MD, senior author of the current study – noted that dermatologists “play an important role in evidence-based screening of CV risk factors in patients with psoriasis,” the investigators wrote. But the regional variations suggest “that some regions experience barriers to appropriate screening or challenges in adhering to guidelines for managing psoriasis and CV risk.”

While the lack of data from after 2016 is one of the study limitations, they added, “continued efforts to develop effective interventions to improve CV screening and care for people with psoriasis in all regions of the U.S. are needed to more effectively address the burden of CV disease experienced by people with psoriasis.”

The study was partly funded by the National Psoriasis Foundation. Three of the seven investigators disclosed earnings from private companies in the form of consultant fees, research support, and honoraria. Dr. Gelfand is a deputy editor for the Journal of Investigative Dermatology.

Over-the-scope clips (OTSC) may prevent further bleeding more so than standard endoscopic treatment when used as primary treatment in patients with high-risk nonvariceal upper gastrointestinal lesions, shows a randomized controlled trial (RCT).

However, noted the investigators, writing in Annals of Internal Medicine, and physicians who wrote an accompanying editorial, reservations remain about first-line use of OTSCs, but mostly relate to method, technique, and cost.

“The absolute difference in the rate of further bleeding was 11.4 percentage points. We should however be cautious in our recommendation of using OTSC as first-line treatment,” wrote researchers who were led by James Y.W. Lau, MD, from Prince of Wales Hospital, Chinese University of Hong Kong.

“The primary use of OTSCs may find a role in the treatment of ulcers predicted to fail standard endoscopic treatment,” the authors wrote.  However, they emphasized that, “We are not advocating routine primary use of OTSCs. These clips are costly, and a formal cost analysis is not available in the literature. The use of OTSCs involves scope withdrawal, mounting of the OTSCs, and scope reinsertion, which increase the procedure time. Endoscopists also require training before using OTSCs.”

Alan N. Barkun, MD, gastroenterologist and professor of medicine with McGill University, Montreal, who cowrote the editorial accompanying the research paper, said the study investigators were highly experienced surgeon-scientists, pointing out that, overall, first-line use of OTSC in this patient group improved patient outcomes.

“The main message here is that if you can position the clip properly, then it is likely to stay in place, better than standard approaches,” he said, adding that, “I support it fully for second-line use but there currently still exists uncertainty for routine first-line adoption in nonvariceal bleeding. Clinicians fail to position the clip properly in around 5% of patients which is higher than standard endoscopic approaches, and nobody has yet clearly defined the lesions that are difficult to clip with the OTSC.

“If you’re going to tell people to use it, then you need to tell them with which particular lesions OTSC works best as first-line approach,” he added.

Lesions of concern include upon leaving the stomach and entering the duodenum, and in passing from the first to the second stage of the duodenum. “These are tight areas, and these larger full-thickness bite OTSC may create pseudo-polyps, even possibly causing obstruction. Perforation is also a risk.” One of each of these complications were noted in this study.

The study included 190 adult patients with active bleeding or a nonbleeding visible vessel from a nonvariceal cause on upper gastrointestinal endoscopy. Of these, 97 patients received standard hemostatic treatment and 93 received OTSC. The primary endpoint of a 30-day probability of further bleeding was 14.6% in the standard treatment and 3.2% in the OTSC group (risk difference, 11.4 percentage points [95% confidence interval (CI), 3.3-20.0 percentage points]; P = .006). Failure to control bleeding after assigned endoscopic treatment in the standard treatment and OTSC groups was 6 versus 1 in the standard treatment and OTSC groups, respectively. Thirty-day recurrent bleeding was 8 versus 2 in the standard treatment and OTSC groups, respectively. Eight patients in the standard treatment group needed further intervention compared with two in the OTSC group. Thirty-day mortality was four versus two, respectively.

“First-line OTSC has a role to play but whether it is the best approach is hard to say due to methodological limitations that were seen in this and earlier studies, however if you can position the clip properly it likely does well,” Dr. Barkun said.

Dr. Lau declares that he received honorarium for a lecture from OVESCO. Dr. Li has no disclosures. Dr. Barkun has no relevant disclosures.  

Over-the-scope clips (OTSC) may prevent further bleeding more so than standard endoscopic treatment when used as primary treatment in patients with high-risk nonvariceal upper gastrointestinal lesions, shows a randomized controlled trial (RCT).

However, noted the investigators, writing in Annals of Internal Medicine, and physicians who wrote an accompanying editorial, reservations remain about first-line use of OTSCs, but mostly relate to method, technique, and cost.

“The absolute difference in the rate of further bleeding was 11.4 percentage points. We should however be cautious in our recommendation of using OTSC as first-line treatment,” wrote researchers who were led by James Y.W. Lau, MD, from Prince of Wales Hospital, Chinese University of Hong Kong.

“The primary use of OTSCs may find a role in the treatment of ulcers predicted to fail standard endoscopic treatment,” the authors wrote.  However, they emphasized that, “We are not advocating routine primary use of OTSCs. These clips are costly, and a formal cost analysis is not available in the literature. The use of OTSCs involves scope withdrawal, mounting of the OTSCs, and scope reinsertion, which increase the procedure time. Endoscopists also require training before using OTSCs.”

Alan N. Barkun, MD, gastroenterologist and professor of medicine with McGill University, Montreal, who cowrote the editorial accompanying the research paper, said the study investigators were highly experienced surgeon-scientists, pointing out that, overall, first-line use of OTSC in this patient group improved patient outcomes.

“The main message here is that if you can position the clip properly, then it is likely to stay in place, better than standard approaches,” he said, adding that, “I support it fully for second-line use but there currently still exists uncertainty for routine first-line adoption in nonvariceal bleeding. Clinicians fail to position the clip properly in around 5% of patients which is higher than standard endoscopic approaches, and nobody has yet clearly defined the lesions that are difficult to clip with the OTSC.

“If you’re going to tell people to use it, then you need to tell them with which particular lesions OTSC works best as first-line approach,” he added.

Lesions of concern include upon leaving the stomach and entering the duodenum, and in passing from the first to the second stage of the duodenum. “These are tight areas, and these larger full-thickness bite OTSC may create pseudo-polyps, even possibly causing obstruction. Perforation is also a risk.” One of each of these complications were noted in this study.

The study included 190 adult patients with active bleeding or a nonbleeding visible vessel from a nonvariceal cause on upper gastrointestinal endoscopy. Of these, 97 patients received standard hemostatic treatment and 93 received OTSC. The primary endpoint of a 30-day probability of further bleeding was 14.6% in the standard treatment and 3.2% in the OTSC group (risk difference, 11.4 percentage points [95% confidence interval (CI), 3.3-20.0 percentage points]; P = .006). Failure to control bleeding after assigned endoscopic treatment in the standard treatment and OTSC groups was 6 versus 1 in the standard treatment and OTSC groups, respectively. Thirty-day recurrent bleeding was 8 versus 2 in the standard treatment and OTSC groups, respectively. Eight patients in the standard treatment group needed further intervention compared with two in the OTSC group. Thirty-day mortality was four versus two, respectively.

“First-line OTSC has a role to play but whether it is the best approach is hard to say due to methodological limitations that were seen in this and earlier studies, however if you can position the clip properly it likely does well,” Dr. Barkun said.

Dr. Lau declares that he received honorarium for a lecture from OVESCO. Dr. Li has no disclosures. Dr. Barkun has no relevant disclosures.  

Over-the-scope clips (OTSC) may prevent further bleeding more so than standard endoscopic treatment when used as primary treatment in patients with high-risk nonvariceal upper gastrointestinal lesions, shows a randomized controlled trial (RCT).

However, noted the investigators, writing in Annals of Internal Medicine, and physicians who wrote an accompanying editorial, reservations remain about first-line use of OTSCs, but mostly relate to method, technique, and cost.

“The absolute difference in the rate of further bleeding was 11.4 percentage points. We should however be cautious in our recommendation of using OTSC as first-line treatment,” wrote researchers who were led by James Y.W. Lau, MD, from Prince of Wales Hospital, Chinese University of Hong Kong.

“The primary use of OTSCs may find a role in the treatment of ulcers predicted to fail standard endoscopic treatment,” the authors wrote.  However, they emphasized that, “We are not advocating routine primary use of OTSCs. These clips are costly, and a formal cost analysis is not available in the literature. The use of OTSCs involves scope withdrawal, mounting of the OTSCs, and scope reinsertion, which increase the procedure time. Endoscopists also require training before using OTSCs.”

Alan N. Barkun, MD, gastroenterologist and professor of medicine with McGill University, Montreal, who cowrote the editorial accompanying the research paper, said the study investigators were highly experienced surgeon-scientists, pointing out that, overall, first-line use of OTSC in this patient group improved patient outcomes.

“The main message here is that if you can position the clip properly, then it is likely to stay in place, better than standard approaches,” he said, adding that, “I support it fully for second-line use but there currently still exists uncertainty for routine first-line adoption in nonvariceal bleeding. Clinicians fail to position the clip properly in around 5% of patients which is higher than standard endoscopic approaches, and nobody has yet clearly defined the lesions that are difficult to clip with the OTSC.

“If you’re going to tell people to use it, then you need to tell them with which particular lesions OTSC works best as first-line approach,” he added.

Lesions of concern include upon leaving the stomach and entering the duodenum, and in passing from the first to the second stage of the duodenum. “These are tight areas, and these larger full-thickness bite OTSC may create pseudo-polyps, even possibly causing obstruction. Perforation is also a risk.” One of each of these complications were noted in this study.

The study included 190 adult patients with active bleeding or a nonbleeding visible vessel from a nonvariceal cause on upper gastrointestinal endoscopy. Of these, 97 patients received standard hemostatic treatment and 93 received OTSC. The primary endpoint of a 30-day probability of further bleeding was 14.6% in the standard treatment and 3.2% in the OTSC group (risk difference, 11.4 percentage points [95% confidence interval (CI), 3.3-20.0 percentage points]; P = .006). Failure to control bleeding after assigned endoscopic treatment in the standard treatment and OTSC groups was 6 versus 1 in the standard treatment and OTSC groups, respectively. Thirty-day recurrent bleeding was 8 versus 2 in the standard treatment and OTSC groups, respectively. Eight patients in the standard treatment group needed further intervention compared with two in the OTSC group. Thirty-day mortality was four versus two, respectively.

“First-line OTSC has a role to play but whether it is the best approach is hard to say due to methodological limitations that were seen in this and earlier studies, however if you can position the clip properly it likely does well,” Dr. Barkun said.

Dr. Lau declares that he received honorarium for a lecture from OVESCO. Dr. Li has no disclosures. Dr. Barkun has no relevant disclosures.  

High-dose prophylactic anticoagulation or therapeutic anticoagulation reduced de novo thrombosis in patients with hypoxemic COVID-19 pneumonia, based on data from 334 adults.

Patients with hypoxemic COVID-19 pneumonia are at increased risk of thrombosis and anticoagulation-related bleeding, therefore data to identify the lowest effective anticoagulant dose are needed, wrote Vincent Labbé, MD, of Sorbonne University, Paris, and colleagues.

Previous studies of different anticoagulation strategies for noncritically ill and critically ill patients with COVID-19 pneumonia have shown contrasting results, but some institutions recommend a high-dose regimen in the wake of data showing macrovascular thrombosis in patients with COVID-19 who were treated with standard anticoagulation, the authors wrote.

However, no previously published studies have compared the effectiveness of the three anticoagulation strategies: high-dose prophylactic anticoagulation (HD-PA), standard dose prophylactic anticoagulation (SD-PA), and therapeutic anticoagulation (TA), they said.

In the open-label Anticoagulation COVID-19 (ANTICOVID) trial, published in JAMA Internal Medicine, the researchers identified consecutively hospitalized adults aged 18 years and older being treated for hypoxemic COVID-19 pneumonia in 23 centers in France between April 2021 and December 2021.

The patients were randomly assigned to SD-PA (116 patients), HD-PA (111 patients), and TA (112 patients) using low-molecular-weight heparin for 14 days, or until either hospital discharge or weaning from supplemental oxygen for 48 consecutive hours, whichever outcome occurred first.  The HD-PA patients received two times the SD-PA dose. The mean age of the patients was 58.3 years, and approximately two-thirds were men; race and ethnicity data were not collected. Participants had no macrovascular thrombosis at the start of the study.

The primary outcomes were all-cause mortality and time to clinical improvement (defined as the time from randomization to a 2-point improvement on a 7-category respiratory function scale).

The secondary outcome was a combination of safety and efficacy at day 28 that included a composite of thrombosis (ischemic stroke, noncerebrovascular arterial thrombosis, deep venous thrombosis, pulmonary artery thrombosis, and central venous catheter–related deep venous thrombosis), major bleeding, or all-cause death.

For the primary outcome, results were similar among the groups; HD-PA had no significant benefit over SD-PA or TA. All-cause death rates for SD-PA, HD-PA, and TA patients were 14%, 12%, and 13%, respectively. The time to clinical improvement for the three groups was approximately 8 days, 9 days, and 8 days, respectively. Results for the primary outcome were consistent across all prespecified subgroups.

However, HD-PA was associated with a significant fourfold reduced risk of de novo thrombosis compared with SD-PA (5.5% vs. 20.2%) with no observed increase in major bleeding. TA was not associated with any significant improvement in primary or secondary outcomes compared with HD-PA or SD-PA.

The current study findings of no improvement in survival or disease resolution in patients with a higher anticoagulant dose reflects data from previous studies, the researchers wrote in their discussion. “Our study results together with those of previous RCTs support the premise that the role of microvascular thrombosis in worsening organ dysfunction may be narrower than estimated,” they said.

The findings were limited by several factors including the open-label design and the relatively small sample size, the lack of data on microvascular (vs. macrovascular) thrombosis at baseline, and the predominance of the Delta variant of COVID-19 among the study participants, which may have contributed to a lower mortality rate, the researchers noted.

However, given the significant reduction in de novo thrombosis, the results support the routine use of HD-PA in patients with severe hypoxemic COVID-19 pneumonia, they concluded.
 

Results inform current clinical practice

Over the course of the COVID-19 pandemic, “Patients hospitalized with COVID-19 manifested the highest risk for thromboembolic complications, especially patients in the intensive care setting,” and early reports suggested that standard prophylactic doses of anticoagulant therapy might be insufficient to prevent thrombotic events, Richard C. Becker, MD, of the University of Cincinnati, and Thomas L. Ortel, MD, of Duke University, Durham, N.C., wrote in an accompanying editorial.

“Although there have been several studies that have investigated the role of anticoagulant therapy in hospitalized patients with COVID-19, this is the first study that specifically compared a standard, prophylactic dose of low-molecular-weight heparin to a ‘high-dose’ prophylactic regimen and to a full therapeutic dose regimen,” Dr. Ortel said in an interview.

“Given the concerns about an increased thrombotic risk with prophylactic dose anticoagulation, and the potential bleeding risk associated with a full therapeutic dose of anticoagulation, this approach enabled the investigators to explore the efficacy and safety of an intermediate dose between these two extremes,” he said.

In the current study, “It was notable that the primary driver of the improved outcomes with the ‘high-dose’ prophylactic regimen reflected the fourfold reduction in macrovascular thrombosis, a finding that was not observed in other studies investigating anticoagulant therapy in hospitalized patients with severe COVID-19,” Dr. Ortel told this news organization. “Much initial concern about progression of disease in patients hospitalized with severe COVID-19 focused on the role of microvascular thrombosis, which appears to be less important in this process, or, alternatively, less responsive to anticoagulant therapy.”

The clinical takeaway from the study, Dr. Ortel said, is the decreased risk for venous thromboembolism with a high-dose prophylactic anticoagulation strategy compared with a standard-dose prophylactic regimen for patients hospitalized with hypoxemic COVID-19 pneumonia, “leading to an improved net clinical outcome.”

Looking ahead, “Additional research is needed to determine whether a higher dose of prophylactic anticoagulation would be beneficial for patients hospitalized with COVID-19 pneumonia who are not in an intensive care unit setting,” Dr. Ortel said. Studies are needed to determine whether therapeutic interventions are equally beneficial in patients with different coronavirus variants, since most patients in the current study were infected with the Delta variant, he added.

The study was supported by LEO Pharma. Dr. Labbé disclosed grants from LEO Pharma during the study and fees from AOP Health unrelated to the current study.

Dr. Becker disclosed personal fees from Novartis Data Safety Monitoring Board, Ionis Data Safety Monitoring Board, and Basking Biosciences Scientific Advisory Board unrelated to the current study. Dr. Ortel disclosed grants from the National Institutes of Health, Instrumentation Laboratory, Stago, and Siemens; contract fees from the Centers for Disease Control and Prevention; and honoraria from UpToDate unrelated to the current study.
 

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

High-dose prophylactic anticoagulation or therapeutic anticoagulation reduced de novo thrombosis in patients with hypoxemic COVID-19 pneumonia, based on data from 334 adults.

Patients with hypoxemic COVID-19 pneumonia are at increased risk of thrombosis and anticoagulation-related bleeding, therefore data to identify the lowest effective anticoagulant dose are needed, wrote Vincent Labbé, MD, of Sorbonne University, Paris, and colleagues.

Previous studies of different anticoagulation strategies for noncritically ill and critically ill patients with COVID-19 pneumonia have shown contrasting results, but some institutions recommend a high-dose regimen in the wake of data showing macrovascular thrombosis in patients with COVID-19 who were treated with standard anticoagulation, the authors wrote.

However, no previously published studies have compared the effectiveness of the three anticoagulation strategies: high-dose prophylactic anticoagulation (HD-PA), standard dose prophylactic anticoagulation (SD-PA), and therapeutic anticoagulation (TA), they said.

In the open-label Anticoagulation COVID-19 (ANTICOVID) trial, published in JAMA Internal Medicine, the researchers identified consecutively hospitalized adults aged 18 years and older being treated for hypoxemic COVID-19 pneumonia in 23 centers in France between April 2021 and December 2021.

The patients were randomly assigned to SD-PA (116 patients), HD-PA (111 patients), and TA (112 patients) using low-molecular-weight heparin for 14 days, or until either hospital discharge or weaning from supplemental oxygen for 48 consecutive hours, whichever outcome occurred first.  The HD-PA patients received two times the SD-PA dose. The mean age of the patients was 58.3 years, and approximately two-thirds were men; race and ethnicity data were not collected. Participants had no macrovascular thrombosis at the start of the study.

The primary outcomes were all-cause mortality and time to clinical improvement (defined as the time from randomization to a 2-point improvement on a 7-category respiratory function scale).

The secondary outcome was a combination of safety and efficacy at day 28 that included a composite of thrombosis (ischemic stroke, noncerebrovascular arterial thrombosis, deep venous thrombosis, pulmonary artery thrombosis, and central venous catheter–related deep venous thrombosis), major bleeding, or all-cause death.

For the primary outcome, results were similar among the groups; HD-PA had no significant benefit over SD-PA or TA. All-cause death rates for SD-PA, HD-PA, and TA patients were 14%, 12%, and 13%, respectively. The time to clinical improvement for the three groups was approximately 8 days, 9 days, and 8 days, respectively. Results for the primary outcome were consistent across all prespecified subgroups.

However, HD-PA was associated with a significant fourfold reduced risk of de novo thrombosis compared with SD-PA (5.5% vs. 20.2%) with no observed increase in major bleeding. TA was not associated with any significant improvement in primary or secondary outcomes compared with HD-PA or SD-PA.

The current study findings of no improvement in survival or disease resolution in patients with a higher anticoagulant dose reflects data from previous studies, the researchers wrote in their discussion. “Our study results together with those of previous RCTs support the premise that the role of microvascular thrombosis in worsening organ dysfunction may be narrower than estimated,” they said.

The findings were limited by several factors including the open-label design and the relatively small sample size, the lack of data on microvascular (vs. macrovascular) thrombosis at baseline, and the predominance of the Delta variant of COVID-19 among the study participants, which may have contributed to a lower mortality rate, the researchers noted.

However, given the significant reduction in de novo thrombosis, the results support the routine use of HD-PA in patients with severe hypoxemic COVID-19 pneumonia, they concluded.
 

Results inform current clinical practice

Over the course of the COVID-19 pandemic, “Patients hospitalized with COVID-19 manifested the highest risk for thromboembolic complications, especially patients in the intensive care setting,” and early reports suggested that standard prophylactic doses of anticoagulant therapy might be insufficient to prevent thrombotic events, Richard C. Becker, MD, of the University of Cincinnati, and Thomas L. Ortel, MD, of Duke University, Durham, N.C., wrote in an accompanying editorial.

“Although there have been several studies that have investigated the role of anticoagulant therapy in hospitalized patients with COVID-19, this is the first study that specifically compared a standard, prophylactic dose of low-molecular-weight heparin to a ‘high-dose’ prophylactic regimen and to a full therapeutic dose regimen,” Dr. Ortel said in an interview.

“Given the concerns about an increased thrombotic risk with prophylactic dose anticoagulation, and the potential bleeding risk associated with a full therapeutic dose of anticoagulation, this approach enabled the investigators to explore the efficacy and safety of an intermediate dose between these two extremes,” he said.

In the current study, “It was notable that the primary driver of the improved outcomes with the ‘high-dose’ prophylactic regimen reflected the fourfold reduction in macrovascular thrombosis, a finding that was not observed in other studies investigating anticoagulant therapy in hospitalized patients with severe COVID-19,” Dr. Ortel told this news organization. “Much initial concern about progression of disease in patients hospitalized with severe COVID-19 focused on the role of microvascular thrombosis, which appears to be less important in this process, or, alternatively, less responsive to anticoagulant therapy.”

The clinical takeaway from the study, Dr. Ortel said, is the decreased risk for venous thromboembolism with a high-dose prophylactic anticoagulation strategy compared with a standard-dose prophylactic regimen for patients hospitalized with hypoxemic COVID-19 pneumonia, “leading to an improved net clinical outcome.”

Looking ahead, “Additional research is needed to determine whether a higher dose of prophylactic anticoagulation would be beneficial for patients hospitalized with COVID-19 pneumonia who are not in an intensive care unit setting,” Dr. Ortel said. Studies are needed to determine whether therapeutic interventions are equally beneficial in patients with different coronavirus variants, since most patients in the current study were infected with the Delta variant, he added.

The study was supported by LEO Pharma. Dr. Labbé disclosed grants from LEO Pharma during the study and fees from AOP Health unrelated to the current study.

Dr. Becker disclosed personal fees from Novartis Data Safety Monitoring Board, Ionis Data Safety Monitoring Board, and Basking Biosciences Scientific Advisory Board unrelated to the current study. Dr. Ortel disclosed grants from the National Institutes of Health, Instrumentation Laboratory, Stago, and Siemens; contract fees from the Centers for Disease Control and Prevention; and honoraria from UpToDate unrelated to the current study.
 

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

High-dose prophylactic anticoagulation or therapeutic anticoagulation reduced de novo thrombosis in patients with hypoxemic COVID-19 pneumonia, based on data from 334 adults.

Patients with hypoxemic COVID-19 pneumonia are at increased risk of thrombosis and anticoagulation-related bleeding, therefore data to identify the lowest effective anticoagulant dose are needed, wrote Vincent Labbé, MD, of Sorbonne University, Paris, and colleagues.

Previous studies of different anticoagulation strategies for noncritically ill and critically ill patients with COVID-19 pneumonia have shown contrasting results, but some institutions recommend a high-dose regimen in the wake of data showing macrovascular thrombosis in patients with COVID-19 who were treated with standard anticoagulation, the authors wrote.

However, no previously published studies have compared the effectiveness of the three anticoagulation strategies: high-dose prophylactic anticoagulation (HD-PA), standard dose prophylactic anticoagulation (SD-PA), and therapeutic anticoagulation (TA), they said.

In the open-label Anticoagulation COVID-19 (ANTICOVID) trial, published in JAMA Internal Medicine, the researchers identified consecutively hospitalized adults aged 18 years and older being treated for hypoxemic COVID-19 pneumonia in 23 centers in France between April 2021 and December 2021.

The patients were randomly assigned to SD-PA (116 patients), HD-PA (111 patients), and TA (112 patients) using low-molecular-weight heparin for 14 days, or until either hospital discharge or weaning from supplemental oxygen for 48 consecutive hours, whichever outcome occurred first.  The HD-PA patients received two times the SD-PA dose. The mean age of the patients was 58.3 years, and approximately two-thirds were men; race and ethnicity data were not collected. Participants had no macrovascular thrombosis at the start of the study.

The primary outcomes were all-cause mortality and time to clinical improvement (defined as the time from randomization to a 2-point improvement on a 7-category respiratory function scale).

The secondary outcome was a combination of safety and efficacy at day 28 that included a composite of thrombosis (ischemic stroke, noncerebrovascular arterial thrombosis, deep venous thrombosis, pulmonary artery thrombosis, and central venous catheter–related deep venous thrombosis), major bleeding, or all-cause death.

For the primary outcome, results were similar among the groups; HD-PA had no significant benefit over SD-PA or TA. All-cause death rates for SD-PA, HD-PA, and TA patients were 14%, 12%, and 13%, respectively. The time to clinical improvement for the three groups was approximately 8 days, 9 days, and 8 days, respectively. Results for the primary outcome were consistent across all prespecified subgroups.

However, HD-PA was associated with a significant fourfold reduced risk of de novo thrombosis compared with SD-PA (5.5% vs. 20.2%) with no observed increase in major bleeding. TA was not associated with any significant improvement in primary or secondary outcomes compared with HD-PA or SD-PA.

The current study findings of no improvement in survival or disease resolution in patients with a higher anticoagulant dose reflects data from previous studies, the researchers wrote in their discussion. “Our study results together with those of previous RCTs support the premise that the role of microvascular thrombosis in worsening organ dysfunction may be narrower than estimated,” they said.

The findings were limited by several factors including the open-label design and the relatively small sample size, the lack of data on microvascular (vs. macrovascular) thrombosis at baseline, and the predominance of the Delta variant of COVID-19 among the study participants, which may have contributed to a lower mortality rate, the researchers noted.

However, given the significant reduction in de novo thrombosis, the results support the routine use of HD-PA in patients with severe hypoxemic COVID-19 pneumonia, they concluded.
 

Results inform current clinical practice

Over the course of the COVID-19 pandemic, “Patients hospitalized with COVID-19 manifested the highest risk for thromboembolic complications, especially patients in the intensive care setting,” and early reports suggested that standard prophylactic doses of anticoagulant therapy might be insufficient to prevent thrombotic events, Richard C. Becker, MD, of the University of Cincinnati, and Thomas L. Ortel, MD, of Duke University, Durham, N.C., wrote in an accompanying editorial.

“Although there have been several studies that have investigated the role of anticoagulant therapy in hospitalized patients with COVID-19, this is the first study that specifically compared a standard, prophylactic dose of low-molecular-weight heparin to a ‘high-dose’ prophylactic regimen and to a full therapeutic dose regimen,” Dr. Ortel said in an interview.

“Given the concerns about an increased thrombotic risk with prophylactic dose anticoagulation, and the potential bleeding risk associated with a full therapeutic dose of anticoagulation, this approach enabled the investigators to explore the efficacy and safety of an intermediate dose between these two extremes,” he said.

In the current study, “It was notable that the primary driver of the improved outcomes with the ‘high-dose’ prophylactic regimen reflected the fourfold reduction in macrovascular thrombosis, a finding that was not observed in other studies investigating anticoagulant therapy in hospitalized patients with severe COVID-19,” Dr. Ortel told this news organization. “Much initial concern about progression of disease in patients hospitalized with severe COVID-19 focused on the role of microvascular thrombosis, which appears to be less important in this process, or, alternatively, less responsive to anticoagulant therapy.”

The clinical takeaway from the study, Dr. Ortel said, is the decreased risk for venous thromboembolism with a high-dose prophylactic anticoagulation strategy compared with a standard-dose prophylactic regimen for patients hospitalized with hypoxemic COVID-19 pneumonia, “leading to an improved net clinical outcome.”

Looking ahead, “Additional research is needed to determine whether a higher dose of prophylactic anticoagulation would be beneficial for patients hospitalized with COVID-19 pneumonia who are not in an intensive care unit setting,” Dr. Ortel said. Studies are needed to determine whether therapeutic interventions are equally beneficial in patients with different coronavirus variants, since most patients in the current study were infected with the Delta variant, he added.

The study was supported by LEO Pharma. Dr. Labbé disclosed grants from LEO Pharma during the study and fees from AOP Health unrelated to the current study.

Dr. Becker disclosed personal fees from Novartis Data Safety Monitoring Board, Ionis Data Safety Monitoring Board, and Basking Biosciences Scientific Advisory Board unrelated to the current study. Dr. Ortel disclosed grants from the National Institutes of Health, Instrumentation Laboratory, Stago, and Siemens; contract fees from the Centers for Disease Control and Prevention; and honoraria from UpToDate unrelated to the current study.
 

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

Complex polypharmacy in patients with bipolar disorder was associated with sociodemographic and clinical features, including older age, single status, and psychiatric comorbidities, based on data from more than 500 individuals.

Patients with bipolar disorder (BD) often receive prescriptions for multiple medications to manage a range of medical and psychiatric symptoms, but the definition of polypharmacy in these patients is inconsistent, and characteristics associated with complex polypharmacy have not been well studied, wrote Andrea Aguglia, MD, of the University of Genoa, Italy, and colleagues.

Previous studies have shown an increased risk for comorbid medical and psychiatric illnesses in BD patients, the researchers noted, and changes in prescribing trends have prompted greater use of combination therapies such as mood stabilizers with or without antipsychotics.

In a study published in Psychiatry Research, the investigators reviewed data from 556 adults with BD. Participants were aged 18 and older with a primary diagnosis of BD type I or II based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria. The mean age of the participants was 49.17 years, 43.7% were male, and 34.2% were employed. A total of 327 patients (58.8%) had a medical comorbidity, and 193 (34.7%) used an illicit substance.

A total of 225 patients (40.5%) met the criteria for complex polypharmacy by taking at least 4 medications.

BD patients with complex polypharmacy were significantly more likely than those without complex polypharmacy to be single (50.7% vs. 37.8%, P = .025) and unemployed (25.3% vs. 40.2%, P < .001).

On the clinical side, complex polypharmacy in BD patients was significantly associated with a higher prevalence of both medical and psychiatric comorbidities (65.3% vs. 54.4%, P = .010; and 50.7% vs. 34.1%, P < .001, respectively). The association with medical comorbidities and complex polypharmacy in BD was unexpected, the researchers said, “as psychotropic medications should be used with cautiousness in patients suffering from medical conditions.”

BD patients with complex polypharmacy also had a significantly earlier age of onset, longer duration of illness, and increased number of hospitalizations than those without complex polypharmacy.

Rates of at least one substance including alcohol, cannabinoids, and cocaine/amphetamines were significantly higher among BD patients with complex polypharmacy, compared with those without, but no differences in heroin use were noted between the groups.

In a logistic regression analysis, single status, older age, number of hospitalizations, and the presence of psychiatric comorbidities were significantly associated with complex polypharmacy.

The study findings were limited by several factors including the focus on an inpatient population, inability to consider clinical factors such as type of mood episode and bipolar cycle, and the cross-sectional design that prevented conclusions of causality, the researchers noted.

However, the study is the first known to focus on both sociodemographic and clinical factors associated with polypharmacy in BD, and the results suggest that implementing complementary psychosocial strategies might help reduce medication use in these patients, they concluded. Data from further longitudinal studies may help guide long-term management of BD, “especially when pharmacological discontinuation is needed,” they said.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Complex polypharmacy in patients with bipolar disorder was associated with sociodemographic and clinical features, including older age, single status, and psychiatric comorbidities, based on data from more than 500 individuals.

Patients with bipolar disorder (BD) often receive prescriptions for multiple medications to manage a range of medical and psychiatric symptoms, but the definition of polypharmacy in these patients is inconsistent, and characteristics associated with complex polypharmacy have not been well studied, wrote Andrea Aguglia, MD, of the University of Genoa, Italy, and colleagues.

Previous studies have shown an increased risk for comorbid medical and psychiatric illnesses in BD patients, the researchers noted, and changes in prescribing trends have prompted greater use of combination therapies such as mood stabilizers with or without antipsychotics.

In a study published in Psychiatry Research, the investigators reviewed data from 556 adults with BD. Participants were aged 18 and older with a primary diagnosis of BD type I or II based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria. The mean age of the participants was 49.17 years, 43.7% were male, and 34.2% were employed. A total of 327 patients (58.8%) had a medical comorbidity, and 193 (34.7%) used an illicit substance.

A total of 225 patients (40.5%) met the criteria for complex polypharmacy by taking at least 4 medications.

BD patients with complex polypharmacy were significantly more likely than those without complex polypharmacy to be single (50.7% vs. 37.8%, P = .025) and unemployed (25.3% vs. 40.2%, P < .001).

On the clinical side, complex polypharmacy in BD patients was significantly associated with a higher prevalence of both medical and psychiatric comorbidities (65.3% vs. 54.4%, P = .010; and 50.7% vs. 34.1%, P < .001, respectively). The association with medical comorbidities and complex polypharmacy in BD was unexpected, the researchers said, “as psychotropic medications should be used with cautiousness in patients suffering from medical conditions.”

BD patients with complex polypharmacy also had a significantly earlier age of onset, longer duration of illness, and increased number of hospitalizations than those without complex polypharmacy.

Rates of at least one substance including alcohol, cannabinoids, and cocaine/amphetamines were significantly higher among BD patients with complex polypharmacy, compared with those without, but no differences in heroin use were noted between the groups.

In a logistic regression analysis, single status, older age, number of hospitalizations, and the presence of psychiatric comorbidities were significantly associated with complex polypharmacy.

The study findings were limited by several factors including the focus on an inpatient population, inability to consider clinical factors such as type of mood episode and bipolar cycle, and the cross-sectional design that prevented conclusions of causality, the researchers noted.

However, the study is the first known to focus on both sociodemographic and clinical factors associated with polypharmacy in BD, and the results suggest that implementing complementary psychosocial strategies might help reduce medication use in these patients, they concluded. Data from further longitudinal studies may help guide long-term management of BD, “especially when pharmacological discontinuation is needed,” they said.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Complex polypharmacy in patients with bipolar disorder was associated with sociodemographic and clinical features, including older age, single status, and psychiatric comorbidities, based on data from more than 500 individuals.

Patients with bipolar disorder (BD) often receive prescriptions for multiple medications to manage a range of medical and psychiatric symptoms, but the definition of polypharmacy in these patients is inconsistent, and characteristics associated with complex polypharmacy have not been well studied, wrote Andrea Aguglia, MD, of the University of Genoa, Italy, and colleagues.

Previous studies have shown an increased risk for comorbid medical and psychiatric illnesses in BD patients, the researchers noted, and changes in prescribing trends have prompted greater use of combination therapies such as mood stabilizers with or without antipsychotics.

In a study published in Psychiatry Research, the investigators reviewed data from 556 adults with BD. Participants were aged 18 and older with a primary diagnosis of BD type I or II based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria. The mean age of the participants was 49.17 years, 43.7% were male, and 34.2% were employed. A total of 327 patients (58.8%) had a medical comorbidity, and 193 (34.7%) used an illicit substance.

A total of 225 patients (40.5%) met the criteria for complex polypharmacy by taking at least 4 medications.

BD patients with complex polypharmacy were significantly more likely than those without complex polypharmacy to be single (50.7% vs. 37.8%, P = .025) and unemployed (25.3% vs. 40.2%, P < .001).

On the clinical side, complex polypharmacy in BD patients was significantly associated with a higher prevalence of both medical and psychiatric comorbidities (65.3% vs. 54.4%, P = .010; and 50.7% vs. 34.1%, P < .001, respectively). The association with medical comorbidities and complex polypharmacy in BD was unexpected, the researchers said, “as psychotropic medications should be used with cautiousness in patients suffering from medical conditions.”

BD patients with complex polypharmacy also had a significantly earlier age of onset, longer duration of illness, and increased number of hospitalizations than those without complex polypharmacy.

Rates of at least one substance including alcohol, cannabinoids, and cocaine/amphetamines were significantly higher among BD patients with complex polypharmacy, compared with those without, but no differences in heroin use were noted between the groups.

In a logistic regression analysis, single status, older age, number of hospitalizations, and the presence of psychiatric comorbidities were significantly associated with complex polypharmacy.

The study findings were limited by several factors including the focus on an inpatient population, inability to consider clinical factors such as type of mood episode and bipolar cycle, and the cross-sectional design that prevented conclusions of causality, the researchers noted.

However, the study is the first known to focus on both sociodemographic and clinical factors associated with polypharmacy in BD, and the results suggest that implementing complementary psychosocial strategies might help reduce medication use in these patients, they concluded. Data from further longitudinal studies may help guide long-term management of BD, “especially when pharmacological discontinuation is needed,” they said.

The study received no outside funding. The researchers had no financial conflicts to disclose.

During 2 days of hearings on potential modifications to the isotretinoin iPLEDGE Risk Evaluation and Mitigation Strategy (REMS), there was much agreement among dermatologists, industry representatives, and Food and Drug Administration representatives that provider and patient burdens persist after the chaotic rollout of the new REMS platform at the end of 2021.

On March 29, at the end of the FDA’s joint meeting of two advisory committees that addressed ways to improve the iPLEDGE program, most panelists voted to change the 19-day lockout period for patients who can become pregnant, and the requirement that every month, providers must document counseling of those who cannot get pregnant and are taking the drug for acne.

However, there was no consensus on whether there should be a lockout at all or for how long, and what an appropriate interval for counseling those who cannot get pregnant would be, if not monthly. Those voting on the questions repeatedly cited a lack of data to make well-informed decisions.

The meeting of the two panels, the FDA’s Drug Safety and Risk Management Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee, was held March 28-29, to discuss proposed changes to iPLEDGE requirements, to minimize the program’s burden on patients, prescribers, and pharmacies – while maintaining safe use of the highly teratogenic drug.

Lockout based on outdated reasoning

John S. Barbieri, MD, a dermatologist and epidemiologist, and director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital in Boston, speaking as deputy chair of the American Academy of Dermatology Association (AADA) iPLEDGE work group, described the burden of getting the drug to patients. He was not on the panel, but spoke during the open public hearing.

“Compared to other acne medications, the time it takes to successfully go from prescribed (isotretinoin) to when the patient actually has it in their hands is 5- to 10-fold higher,” he said.

Many don’t have a monthly cycle

But Dr. Barbieri said that reasoning is outdated.

“The current program’s focus on the menstrual cycle is really an antiquated approach,” he said. “Many patients do not have a monthly cycle due to medical conditions like polycystic ovarian syndrome, or due to [certain kinds of] contraception.”

He added, “By removing this 19-day lockout and, really, the archaic timing around the menstrual cycle in general in this program, we can simplify the program, improve it, and better align it with the real-world biology of our patients.” He added that patients are often missing the 7-day window for picking up their prescriptions through no fault of their own. Speakers at the hearing also mentioned insurance hassles and ordering delays.


 

Communication with IPMG

Ilona Frieden, MD, professor of dermatology and pediatrics at the University of California, San Francisco, and outgoing chair of the AADA iPLEDGE work group, cited difficulty in working with IPMG on modifications as another barrier. She also spoke during the open public hearing.

UCSF

“Despite many, many attempts to work with the IPMG, we are not aware of any organizational structure or key leaders to communicate with. Instead we have been given repeatedly a generic email address for trying to establish a working relationship and we believe this may explain the inaction of the IPMG since our proposals 4 years ago in 2019.”

Among those proposals, she said, were allowing telemedicine visits as part of the iPLEDGE REMS program and reducing counseling attestation to every 6 months instead of monthly for those who cannot become pregnant.

She pointed to the chaotic rollout of modifications to the iPLEDGE program on a new website at the end of 2021.

In 2021, she said, “despite 6 months of notification, no prescriber input was solicited before revamping the website. This lack of transparency and accountability has been a major hurdle in improving iPLEDGE.”

Dr. Barbieri called the rollout “a debacle” that could have been mitigated with communication with IPMG. “We warned about every issue that happened and talked about ways to mitigate it and were largely ignored,” he said.

“By including dermatologists and key stakeholders in these discussions, as we move forward with changes to improve this program, we can make sure that it’s patient-centered.”

IPMG did not address the specific complaints about the working relationship with the AADA workgroup at the meeting.
 

Monthly attestation for counseling patients who cannot get pregnant

Dr. Barbieri said the monthly requirement to counsel patients who cannot get pregnant and document that counseling unfairly burdens clinicians and patients. “We’re essentially asking patients to come in monthly just to tell them not to share their drugs [or] donate blood,” he said.

Ken Katz, MD, MSc, a dermatologist at Kaiser Permanente in San Francisco, was among the panel members voting not to continue the 19-day lockout.

“I think this places an unduly high burden physically and psychologically on our patients. It seems arbitrary,” he said. “Likely we will miss some pregnancies; we are missing some already. But the burden is not matched by the benefit.”

IPMG representative Dr. Wedin, said, “while we cannot support eliminating or extending the confirmation interval to a year, the [iPLEDGE] sponsors are agreeable [to] a 120-day confirmation interval.”

He said that while an extension to 120 days would reduce burden on prescribers, it comes with the risk in reducing oversight by a certified iPLEDGE prescriber and potentially increasing the risk for drug sharing.

“A patient may be more likely to share their drug with another person the further along with therapy they get as their condition improves,” Dr. Wedin said.
 

Home pregnancy testing

The advisory groups were also tasked with discussing whether home pregnancy tests, allowed during the COVID-19 public health emergency, should continue to be allowed. Most committee members and those in the public hearing who spoke on the issue agreed that home tests should continue in an effort to increase access and decrease burden.

During the pandemic, iPLEDGE rules have been relaxed from having a pregnancy test done only at a Clinical Laboratory Improvement Amendments–certified laboratory.

Lindsey Crist, PharmD, a risk management analyst at the FDA, who presented the FDA review committee’s analysis, said that the FDA’s review committee recommends ending the allowance of home tests, citing insufficient data on use and the discovery of instances of falsification of pregnancy tests.

“One study at an academic medical center reviewed the medical records of 89 patients who used home pregnancy tests while taking isotretinoin during the public health emergency. It found that 15.7% submitted falsified pregnancy test results,” Dr. Crist said.

Dr. Crist added, however, that the review committee recommends allowing the tests to be done in a provider’s office as an alternative.
 

Workaround to avoid falsification

Advisory committee member Brian P. Green, DO, associate professor of dermatology at Penn State University, Hershey, Pa., spoke in support of home pregnancy tests.

“What we have people do for telemedicine is take the stick, write their name, write the date on it, and send a picture of that the same day as their visit,” he said. “That way we have the pregnancy test the same day. Allowing this to continue to happen at home is important. Bringing people in is burdensome and costly.”

Emmy Graber, MD, a dermatologist who practices in Boston, and a director of the American Acne and Rosacea Society (AARS), relayed an example of the burden for a patient using isotretinoin who lives 1.5 hours away from the dermatology office. She is able to meet the requirements of iPLEDGE only through telehealth.

Suggestions for improvement

At the end of the hearing, advisory committee members were asked to propose improvements to the iPLEDGE REMS program.

Dr. Green advocated for the addition of an iPLEDGE mobile app.

“Most people go to their phones rather than their computers, particularly teenagers and younger people,” he noted.

Advisory committee member Megha M. Tollefson, MD, professor of dermatology and pediatric and adolescent medicine at Mayo Clinic in Rochester, Minn., echoed the need for an iPLEDGE app.

The young patients getting isotretinoin “don’t respond to email, they don’t necessarily go onto web pages. If we’re going to be as effective as possible, it’s going to have to be through an app-based system.”

Dr. Tollefson said she would like to see patient counseling standardized through the app. “I think there’s a lot of variability in what counseling is given when it’s left to the individual prescriber or practice,” she said.
 

Exceptions for long-acting contraceptives?

Advisory committee member Abbey B. Berenson, MD, PhD, professor of obstetrics and gynecology at University of Texas Medical Branch in Galveston, said that patients taking long-acting reversible contraceptives (LARCs) may need to be considered differently when deciding the intervals for attestation or whether to have a lockout period.

“LARC methods’ rate of failure is extremely low,” she said. “While it is true, as it has been pointed out, that all methods can fail, when they’re over 99% effective, I think that we can treat those methods differently than we treat methods such as birth control pills or abstinence that fail far more often. That is one way we could minimize burden on the providers and the patients.”

She also suggested using members of the health care team other than physicians to complete counseling, such as a nurse or pharmacist.
 

Prescriptions for emergency contraception

Advisory committee member Sascha Dublin, MD, PhD, senior scientific investigator for Kaiser Permanente Washington Health Research Institute in Seattle, said most patients taking the drug who can get pregnant should get a prescription for emergency contraception at the time of the first isotretinoin prescription.

“They don’t have to buy it, but to make it available at the very beginning sets the expectation that it would be good to have in your medicine cabinet, particularly if the [contraception] choice is abstinence or birth control pills.”

Dr. Dublin also called for better transparency surrounding the role of IPMG.

She said IPMG should be expected to collect data in a way that allows examination of health disparities, including by race and ethnicity and insurance status. Dr. Dublin added that she was concerned about the poor communication between dermatological societies and IPMG.

“The FDA should really require that IPMG hold periodic, regularly scheduled stakeholder forums,” she said. “There has to be a mechanism in place for IPMG to listen to those concerns in real time and respond.”

The advisory committees’ recommendations to the FDA are nonbinding, but the FDA generally follows the recommendations of advisory panels.

During 2 days of hearings on potential modifications to the isotretinoin iPLEDGE Risk Evaluation and Mitigation Strategy (REMS), there was much agreement among dermatologists, industry representatives, and Food and Drug Administration representatives that provider and patient burdens persist after the chaotic rollout of the new REMS platform at the end of 2021.

On March 29, at the end of the FDA’s joint meeting of two advisory committees that addressed ways to improve the iPLEDGE program, most panelists voted to change the 19-day lockout period for patients who can become pregnant, and the requirement that every month, providers must document counseling of those who cannot get pregnant and are taking the drug for acne.

However, there was no consensus on whether there should be a lockout at all or for how long, and what an appropriate interval for counseling those who cannot get pregnant would be, if not monthly. Those voting on the questions repeatedly cited a lack of data to make well-informed decisions.

The meeting of the two panels, the FDA’s Drug Safety and Risk Management Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee, was held March 28-29, to discuss proposed changes to iPLEDGE requirements, to minimize the program’s burden on patients, prescribers, and pharmacies – while maintaining safe use of the highly teratogenic drug.

Lockout based on outdated reasoning

John S. Barbieri, MD, a dermatologist and epidemiologist, and director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital in Boston, speaking as deputy chair of the American Academy of Dermatology Association (AADA) iPLEDGE work group, described the burden of getting the drug to patients. He was not on the panel, but spoke during the open public hearing.

“Compared to other acne medications, the time it takes to successfully go from prescribed (isotretinoin) to when the patient actually has it in their hands is 5- to 10-fold higher,” he said.

Many don’t have a monthly cycle

But Dr. Barbieri said that reasoning is outdated.

“The current program’s focus on the menstrual cycle is really an antiquated approach,” he said. “Many patients do not have a monthly cycle due to medical conditions like polycystic ovarian syndrome, or due to [certain kinds of] contraception.”

He added, “By removing this 19-day lockout and, really, the archaic timing around the menstrual cycle in general in this program, we can simplify the program, improve it, and better align it with the real-world biology of our patients.” He added that patients are often missing the 7-day window for picking up their prescriptions through no fault of their own. Speakers at the hearing also mentioned insurance hassles and ordering delays.


 

Communication with IPMG

Ilona Frieden, MD, professor of dermatology and pediatrics at the University of California, San Francisco, and outgoing chair of the AADA iPLEDGE work group, cited difficulty in working with IPMG on modifications as another barrier. She also spoke during the open public hearing.

UCSF

“Despite many, many attempts to work with the IPMG, we are not aware of any organizational structure or key leaders to communicate with. Instead we have been given repeatedly a generic email address for trying to establish a working relationship and we believe this may explain the inaction of the IPMG since our proposals 4 years ago in 2019.”

Among those proposals, she said, were allowing telemedicine visits as part of the iPLEDGE REMS program and reducing counseling attestation to every 6 months instead of monthly for those who cannot become pregnant.

She pointed to the chaotic rollout of modifications to the iPLEDGE program on a new website at the end of 2021.

In 2021, she said, “despite 6 months of notification, no prescriber input was solicited before revamping the website. This lack of transparency and accountability has been a major hurdle in improving iPLEDGE.”

Dr. Barbieri called the rollout “a debacle” that could have been mitigated with communication with IPMG. “We warned about every issue that happened and talked about ways to mitigate it and were largely ignored,” he said.

“By including dermatologists and key stakeholders in these discussions, as we move forward with changes to improve this program, we can make sure that it’s patient-centered.”

IPMG did not address the specific complaints about the working relationship with the AADA workgroup at the meeting.
 

Monthly attestation for counseling patients who cannot get pregnant

Dr. Barbieri said the monthly requirement to counsel patients who cannot get pregnant and document that counseling unfairly burdens clinicians and patients. “We’re essentially asking patients to come in monthly just to tell them not to share their drugs [or] donate blood,” he said.

Ken Katz, MD, MSc, a dermatologist at Kaiser Permanente in San Francisco, was among the panel members voting not to continue the 19-day lockout.

“I think this places an unduly high burden physically and psychologically on our patients. It seems arbitrary,” he said. “Likely we will miss some pregnancies; we are missing some already. But the burden is not matched by the benefit.”

IPMG representative Dr. Wedin, said, “while we cannot support eliminating or extending the confirmation interval to a year, the [iPLEDGE] sponsors are agreeable [to] a 120-day confirmation interval.”

He said that while an extension to 120 days would reduce burden on prescribers, it comes with the risk in reducing oversight by a certified iPLEDGE prescriber and potentially increasing the risk for drug sharing.

“A patient may be more likely to share their drug with another person the further along with therapy they get as their condition improves,” Dr. Wedin said.
 

Home pregnancy testing

The advisory groups were also tasked with discussing whether home pregnancy tests, allowed during the COVID-19 public health emergency, should continue to be allowed. Most committee members and those in the public hearing who spoke on the issue agreed that home tests should continue in an effort to increase access and decrease burden.

During the pandemic, iPLEDGE rules have been relaxed from having a pregnancy test done only at a Clinical Laboratory Improvement Amendments–certified laboratory.

Lindsey Crist, PharmD, a risk management analyst at the FDA, who presented the FDA review committee’s analysis, said that the FDA’s review committee recommends ending the allowance of home tests, citing insufficient data on use and the discovery of instances of falsification of pregnancy tests.

“One study at an academic medical center reviewed the medical records of 89 patients who used home pregnancy tests while taking isotretinoin during the public health emergency. It found that 15.7% submitted falsified pregnancy test results,” Dr. Crist said.

Dr. Crist added, however, that the review committee recommends allowing the tests to be done in a provider’s office as an alternative.
 

Workaround to avoid falsification

Advisory committee member Brian P. Green, DO, associate professor of dermatology at Penn State University, Hershey, Pa., spoke in support of home pregnancy tests.

“What we have people do for telemedicine is take the stick, write their name, write the date on it, and send a picture of that the same day as their visit,” he said. “That way we have the pregnancy test the same day. Allowing this to continue to happen at home is important. Bringing people in is burdensome and costly.”

Emmy Graber, MD, a dermatologist who practices in Boston, and a director of the American Acne and Rosacea Society (AARS), relayed an example of the burden for a patient using isotretinoin who lives 1.5 hours away from the dermatology office. She is able to meet the requirements of iPLEDGE only through telehealth.

Suggestions for improvement

At the end of the hearing, advisory committee members were asked to propose improvements to the iPLEDGE REMS program.

Dr. Green advocated for the addition of an iPLEDGE mobile app.

“Most people go to their phones rather than their computers, particularly teenagers and younger people,” he noted.

Advisory committee member Megha M. Tollefson, MD, professor of dermatology and pediatric and adolescent medicine at Mayo Clinic in Rochester, Minn., echoed the need for an iPLEDGE app.

The young patients getting isotretinoin “don’t respond to email, they don’t necessarily go onto web pages. If we’re going to be as effective as possible, it’s going to have to be through an app-based system.”

Dr. Tollefson said she would like to see patient counseling standardized through the app. “I think there’s a lot of variability in what counseling is given when it’s left to the individual prescriber or practice,” she said.
 

Exceptions for long-acting contraceptives?

Advisory committee member Abbey B. Berenson, MD, PhD, professor of obstetrics and gynecology at University of Texas Medical Branch in Galveston, said that patients taking long-acting reversible contraceptives (LARCs) may need to be considered differently when deciding the intervals for attestation or whether to have a lockout period.

“LARC methods’ rate of failure is extremely low,” she said. “While it is true, as it has been pointed out, that all methods can fail, when they’re over 99% effective, I think that we can treat those methods differently than we treat methods such as birth control pills or abstinence that fail far more often. That is one way we could minimize burden on the providers and the patients.”

She also suggested using members of the health care team other than physicians to complete counseling, such as a nurse or pharmacist.
 

Prescriptions for emergency contraception

Advisory committee member Sascha Dublin, MD, PhD, senior scientific investigator for Kaiser Permanente Washington Health Research Institute in Seattle, said most patients taking the drug who can get pregnant should get a prescription for emergency contraception at the time of the first isotretinoin prescription.

“They don’t have to buy it, but to make it available at the very beginning sets the expectation that it would be good to have in your medicine cabinet, particularly if the [contraception] choice is abstinence or birth control pills.”

Dr. Dublin also called for better transparency surrounding the role of IPMG.

She said IPMG should be expected to collect data in a way that allows examination of health disparities, including by race and ethnicity and insurance status. Dr. Dublin added that she was concerned about the poor communication between dermatological societies and IPMG.

“The FDA should really require that IPMG hold periodic, regularly scheduled stakeholder forums,” she said. “There has to be a mechanism in place for IPMG to listen to those concerns in real time and respond.”

The advisory committees’ recommendations to the FDA are nonbinding, but the FDA generally follows the recommendations of advisory panels.

During 2 days of hearings on potential modifications to the isotretinoin iPLEDGE Risk Evaluation and Mitigation Strategy (REMS), there was much agreement among dermatologists, industry representatives, and Food and Drug Administration representatives that provider and patient burdens persist after the chaotic rollout of the new REMS platform at the end of 2021.

On March 29, at the end of the FDA’s joint meeting of two advisory committees that addressed ways to improve the iPLEDGE program, most panelists voted to change the 19-day lockout period for patients who can become pregnant, and the requirement that every month, providers must document counseling of those who cannot get pregnant and are taking the drug for acne.

However, there was no consensus on whether there should be a lockout at all or for how long, and what an appropriate interval for counseling those who cannot get pregnant would be, if not monthly. Those voting on the questions repeatedly cited a lack of data to make well-informed decisions.

The meeting of the two panels, the FDA’s Drug Safety and Risk Management Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee, was held March 28-29, to discuss proposed changes to iPLEDGE requirements, to minimize the program’s burden on patients, prescribers, and pharmacies – while maintaining safe use of the highly teratogenic drug.

Lockout based on outdated reasoning

John S. Barbieri, MD, a dermatologist and epidemiologist, and director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital in Boston, speaking as deputy chair of the American Academy of Dermatology Association (AADA) iPLEDGE work group, described the burden of getting the drug to patients. He was not on the panel, but spoke during the open public hearing.

“Compared to other acne medications, the time it takes to successfully go from prescribed (isotretinoin) to when the patient actually has it in their hands is 5- to 10-fold higher,” he said.

Many don’t have a monthly cycle

But Dr. Barbieri said that reasoning is outdated.

“The current program’s focus on the menstrual cycle is really an antiquated approach,” he said. “Many patients do not have a monthly cycle due to medical conditions like polycystic ovarian syndrome, or due to [certain kinds of] contraception.”

He added, “By removing this 19-day lockout and, really, the archaic timing around the menstrual cycle in general in this program, we can simplify the program, improve it, and better align it with the real-world biology of our patients.” He added that patients are often missing the 7-day window for picking up their prescriptions through no fault of their own. Speakers at the hearing also mentioned insurance hassles and ordering delays.


 

Communication with IPMG

Ilona Frieden, MD, professor of dermatology and pediatrics at the University of California, San Francisco, and outgoing chair of the AADA iPLEDGE work group, cited difficulty in working with IPMG on modifications as another barrier. She also spoke during the open public hearing.

UCSF

“Despite many, many attempts to work with the IPMG, we are not aware of any organizational structure or key leaders to communicate with. Instead we have been given repeatedly a generic email address for trying to establish a working relationship and we believe this may explain the inaction of the IPMG since our proposals 4 years ago in 2019.”

Among those proposals, she said, were allowing telemedicine visits as part of the iPLEDGE REMS program and reducing counseling attestation to every 6 months instead of monthly for those who cannot become pregnant.

She pointed to the chaotic rollout of modifications to the iPLEDGE program on a new website at the end of 2021.

In 2021, she said, “despite 6 months of notification, no prescriber input was solicited before revamping the website. This lack of transparency and accountability has been a major hurdle in improving iPLEDGE.”

Dr. Barbieri called the rollout “a debacle” that could have been mitigated with communication with IPMG. “We warned about every issue that happened and talked about ways to mitigate it and were largely ignored,” he said.

“By including dermatologists and key stakeholders in these discussions, as we move forward with changes to improve this program, we can make sure that it’s patient-centered.”

IPMG did not address the specific complaints about the working relationship with the AADA workgroup at the meeting.
 

Monthly attestation for counseling patients who cannot get pregnant

Dr. Barbieri said the monthly requirement to counsel patients who cannot get pregnant and document that counseling unfairly burdens clinicians and patients. “We’re essentially asking patients to come in monthly just to tell them not to share their drugs [or] donate blood,” he said.

Ken Katz, MD, MSc, a dermatologist at Kaiser Permanente in San Francisco, was among the panel members voting not to continue the 19-day lockout.

“I think this places an unduly high burden physically and psychologically on our patients. It seems arbitrary,” he said. “Likely we will miss some pregnancies; we are missing some already. But the burden is not matched by the benefit.”

IPMG representative Dr. Wedin, said, “while we cannot support eliminating or extending the confirmation interval to a year, the [iPLEDGE] sponsors are agreeable [to] a 120-day confirmation interval.”

He said that while an extension to 120 days would reduce burden on prescribers, it comes with the risk in reducing oversight by a certified iPLEDGE prescriber and potentially increasing the risk for drug sharing.

“A patient may be more likely to share their drug with another person the further along with therapy they get as their condition improves,” Dr. Wedin said.
 

Home pregnancy testing

The advisory groups were also tasked with discussing whether home pregnancy tests, allowed during the COVID-19 public health emergency, should continue to be allowed. Most committee members and those in the public hearing who spoke on the issue agreed that home tests should continue in an effort to increase access and decrease burden.

During the pandemic, iPLEDGE rules have been relaxed from having a pregnancy test done only at a Clinical Laboratory Improvement Amendments–certified laboratory.

Lindsey Crist, PharmD, a risk management analyst at the FDA, who presented the FDA review committee’s analysis, said that the FDA’s review committee recommends ending the allowance of home tests, citing insufficient data on use and the discovery of instances of falsification of pregnancy tests.

“One study at an academic medical center reviewed the medical records of 89 patients who used home pregnancy tests while taking isotretinoin during the public health emergency. It found that 15.7% submitted falsified pregnancy test results,” Dr. Crist said.

Dr. Crist added, however, that the review committee recommends allowing the tests to be done in a provider’s office as an alternative.
 

Workaround to avoid falsification

Advisory committee member Brian P. Green, DO, associate professor of dermatology at Penn State University, Hershey, Pa., spoke in support of home pregnancy tests.

“What we have people do for telemedicine is take the stick, write their name, write the date on it, and send a picture of that the same day as their visit,” he said. “That way we have the pregnancy test the same day. Allowing this to continue to happen at home is important. Bringing people in is burdensome and costly.”

Emmy Graber, MD, a dermatologist who practices in Boston, and a director of the American Acne and Rosacea Society (AARS), relayed an example of the burden for a patient using isotretinoin who lives 1.5 hours away from the dermatology office. She is able to meet the requirements of iPLEDGE only through telehealth.

Suggestions for improvement

At the end of the hearing, advisory committee members were asked to propose improvements to the iPLEDGE REMS program.

Dr. Green advocated for the addition of an iPLEDGE mobile app.

“Most people go to their phones rather than their computers, particularly teenagers and younger people,” he noted.

Advisory committee member Megha M. Tollefson, MD, professor of dermatology and pediatric and adolescent medicine at Mayo Clinic in Rochester, Minn., echoed the need for an iPLEDGE app.

The young patients getting isotretinoin “don’t respond to email, they don’t necessarily go onto web pages. If we’re going to be as effective as possible, it’s going to have to be through an app-based system.”

Dr. Tollefson said she would like to see patient counseling standardized through the app. “I think there’s a lot of variability in what counseling is given when it’s left to the individual prescriber or practice,” she said.
 

Exceptions for long-acting contraceptives?

Advisory committee member Abbey B. Berenson, MD, PhD, professor of obstetrics and gynecology at University of Texas Medical Branch in Galveston, said that patients taking long-acting reversible contraceptives (LARCs) may need to be considered differently when deciding the intervals for attestation or whether to have a lockout period.

“LARC methods’ rate of failure is extremely low,” she said. “While it is true, as it has been pointed out, that all methods can fail, when they’re over 99% effective, I think that we can treat those methods differently than we treat methods such as birth control pills or abstinence that fail far more often. That is one way we could minimize burden on the providers and the patients.”

She also suggested using members of the health care team other than physicians to complete counseling, such as a nurse or pharmacist.
 

Prescriptions for emergency contraception

Advisory committee member Sascha Dublin, MD, PhD, senior scientific investigator for Kaiser Permanente Washington Health Research Institute in Seattle, said most patients taking the drug who can get pregnant should get a prescription for emergency contraception at the time of the first isotretinoin prescription.

“They don’t have to buy it, but to make it available at the very beginning sets the expectation that it would be good to have in your medicine cabinet, particularly if the [contraception] choice is abstinence or birth control pills.”

Dr. Dublin also called for better transparency surrounding the role of IPMG.

She said IPMG should be expected to collect data in a way that allows examination of health disparities, including by race and ethnicity and insurance status. Dr. Dublin added that she was concerned about the poor communication between dermatological societies and IPMG.

“The FDA should really require that IPMG hold periodic, regularly scheduled stakeholder forums,” she said. “There has to be a mechanism in place for IPMG to listen to those concerns in real time and respond.”

The advisory committees’ recommendations to the FDA are nonbinding, but the FDA generally follows the recommendations of advisory panels.

Despite federal legislation doing away with cost-sharing for initial breast cancer screening, out-of-pocket costs for needed follow-up tests remain significant financial barriers for many women.

An analysis of claims data found that women with higher cost-sharing undergo fewer subsequent breast diagnostic tests after an abnormal screening mammogram, compared with peers with lower cost-sharing.

“The chief clinical implication is that women with abnormal mammograms – that is, potentially at risk for cancer – are deciding not to follow-up on diagnostic imaging because of high out-of-pocket costs,” Danny Hughes, PhD, professor, College of Health Solutions, Arizona State University in Phoenix, told this news organization.

One course of action for radiologists is to “strongly communicate the importance of adhering to recommended follow-on testing,” Dr. Hughes said.

Another is to “work to pass national and state legislation, such as recently passed [legislation] in Connecticut, that removes out-of-pocket costs for follow-on diagnostic breast imaging and biopsy in the same way that these patient costs are prohibited for screening mammography,” he suggested.

The study was published online in JAMA Network Open.


 

‘Worrisome’ findings

The Affordable Care Act removed out-of-pocket costs for preventive health care, such as screening mammograms in women aged 40 and over.

However, lingering cost barriers remain for some individuals who have a positive initial screening mammogram and need follow-up tests. For instance, research shows that women in high-deductible plans, which often have higher out-of-pocket costs than other plans, may experience delays in follow-on care, including diagnostic breast imaging.

Dr. Hughes and colleagues examined the association between the degree of patient cost-sharing across different health plans – those dominated by copays, coinsurance, or deductibles as well as those classified as balanced across the three categories – and the use of diagnostic breast cancer imaging after a screening mammogram.

The data came from Optum’s database of administrative health claims for members of large commercial and Medicare Advantage health plans. The team used a machine learning algorithm to rank patient insurance plans by type of cost-sharing.

The sample included 230,845 mostly White (71%) women 40 years and older with no prior history of breast cancer who underwent screening mammography. These women were covered by 22,828 distinct insurance plans associated with roughly 6 million enrollees and nearly 45 million distinct medical claims.

Plans dominated by coinsurance had the lowest average out-of-pocket costs ($945), followed by plans balanced across the three cost-sharing categories ($1,017), plans dominated by copays ($1,020), and plans dominated by deductibles ($1,186).

Compared with women with coinsurance plans, those with copay- and deductible-dominated plans underwent significantly fewer subsequent breast-imaging procedures – 24 and 16 fewer procedures per 1,000 women, respectively.

Use of follow-on breast MRI was nearly 24% lower among women in plans with the highest cost-sharing versus those in plans with the lowest cost-sharing.

The team found no statistically significant difference in breast biopsy use between plan types.

Considering the risks posed by an unconfirmed positive mammogram result, these findings are “startling” and question the efficacy of legislation that eliminated cost-sharing from many preventive services, including screening mammograms, Dr. Hughes and colleagues write.

“Additional policy changes, such as removing cost-sharing for subsequent tests after abnormal screening results or bundling all breast cancer diagnostic testing into a single reimbursement, may provide avenues to mitigate these financial barriers to care,” the authors add.

The authors of an accompanying editorial found the study’s main finding – that some women who have an abnormal result on a mammogram may not get appropriate follow-up because of cost – is “worrisome.” 

“From a population health perspective, failure to complete the screening process limits the program’s effectiveness and likely exacerbates health disparities,” write Ilana Richman, MD, with Yale University, New Haven, Conn., and A. Mark Fendrick, MD, with the University of Michigan, Ann Arbor.

“On an individual level, high out-of-pocket costs may directly contribute to worse health outcomes or require individuals to use scarce financial resources that may otherwise be used for critical items such as food or rent,” Dr. Richman and Dr. Fendrick add. And “the removal of financial barriers for the entire breast cancer screening process has potential to improve total screening uptake and follow-up rates.”

Support for the study was provided by the Harvey L. Neiman Health Policy Institute. Dr. Hughes has reported no relevant financial relationships. Dr. Richman has reported receiving salary support from the Centers for Medicare & Medicaid Services to develop health care quality measures outside the submitted work. Dr. Fendrick has reported serving as a consultant for AbbVie, Amgen, Bayer, CareFirst, BlueCross BlueShield, Centivo, Community Oncology Association, Covered California, EmblemHealth, Exact Sciences, GRAIL, Harvard University, HealthCorum, Hygieia, Johnson & Johnson, MedZed, Merck, Mercer, Montana Health Cooperative, Phathom Pharmaceuticals, Proton Intelligence, RA Capital, Teladoc Health, U.S. Department of Defense, Virginia Center for Health Innovation, Washington Health Benefit Exchange, Wildflower Health, and Yale-New Haven Health System; and serving as a consultant for and holding equity in Health at Scale Technologies, Pair Team, Sempre Health, Silver Fern Health, and Wellth.

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

Despite federal legislation doing away with cost-sharing for initial breast cancer screening, out-of-pocket costs for needed follow-up tests remain significant financial barriers for many women.

An analysis of claims data found that women with higher cost-sharing undergo fewer subsequent breast diagnostic tests after an abnormal screening mammogram, compared with peers with lower cost-sharing.

“The chief clinical implication is that women with abnormal mammograms – that is, potentially at risk for cancer – are deciding not to follow-up on diagnostic imaging because of high out-of-pocket costs,” Danny Hughes, PhD, professor, College of Health Solutions, Arizona State University in Phoenix, told this news organization.

One course of action for radiologists is to “strongly communicate the importance of adhering to recommended follow-on testing,” Dr. Hughes said.

Another is to “work to pass national and state legislation, such as recently passed [legislation] in Connecticut, that removes out-of-pocket costs for follow-on diagnostic breast imaging and biopsy in the same way that these patient costs are prohibited for screening mammography,” he suggested.

The study was published online in JAMA Network Open.


 

‘Worrisome’ findings

The Affordable Care Act removed out-of-pocket costs for preventive health care, such as screening mammograms in women aged 40 and over.

However, lingering cost barriers remain for some individuals who have a positive initial screening mammogram and need follow-up tests. For instance, research shows that women in high-deductible plans, which often have higher out-of-pocket costs than other plans, may experience delays in follow-on care, including diagnostic breast imaging.

Dr. Hughes and colleagues examined the association between the degree of patient cost-sharing across different health plans – those dominated by copays, coinsurance, or deductibles as well as those classified as balanced across the three categories – and the use of diagnostic breast cancer imaging after a screening mammogram.

The data came from Optum’s database of administrative health claims for members of large commercial and Medicare Advantage health plans. The team used a machine learning algorithm to rank patient insurance plans by type of cost-sharing.

The sample included 230,845 mostly White (71%) women 40 years and older with no prior history of breast cancer who underwent screening mammography. These women were covered by 22,828 distinct insurance plans associated with roughly 6 million enrollees and nearly 45 million distinct medical claims.

Plans dominated by coinsurance had the lowest average out-of-pocket costs ($945), followed by plans balanced across the three cost-sharing categories ($1,017), plans dominated by copays ($1,020), and plans dominated by deductibles ($1,186).

Compared with women with coinsurance plans, those with copay- and deductible-dominated plans underwent significantly fewer subsequent breast-imaging procedures – 24 and 16 fewer procedures per 1,000 women, respectively.

Use of follow-on breast MRI was nearly 24% lower among women in plans with the highest cost-sharing versus those in plans with the lowest cost-sharing.

The team found no statistically significant difference in breast biopsy use between plan types.

Considering the risks posed by an unconfirmed positive mammogram result, these findings are “startling” and question the efficacy of legislation that eliminated cost-sharing from many preventive services, including screening mammograms, Dr. Hughes and colleagues write.

“Additional policy changes, such as removing cost-sharing for subsequent tests after abnormal screening results or bundling all breast cancer diagnostic testing into a single reimbursement, may provide avenues to mitigate these financial barriers to care,” the authors add.

The authors of an accompanying editorial found the study’s main finding – that some women who have an abnormal result on a mammogram may not get appropriate follow-up because of cost – is “worrisome.” 

“From a population health perspective, failure to complete the screening process limits the program’s effectiveness and likely exacerbates health disparities,” write Ilana Richman, MD, with Yale University, New Haven, Conn., and A. Mark Fendrick, MD, with the University of Michigan, Ann Arbor.

“On an individual level, high out-of-pocket costs may directly contribute to worse health outcomes or require individuals to use scarce financial resources that may otherwise be used for critical items such as food or rent,” Dr. Richman and Dr. Fendrick add. And “the removal of financial barriers for the entire breast cancer screening process has potential to improve total screening uptake and follow-up rates.”

Support for the study was provided by the Harvey L. Neiman Health Policy Institute. Dr. Hughes has reported no relevant financial relationships. Dr. Richman has reported receiving salary support from the Centers for Medicare & Medicaid Services to develop health care quality measures outside the submitted work. Dr. Fendrick has reported serving as a consultant for AbbVie, Amgen, Bayer, CareFirst, BlueCross BlueShield, Centivo, Community Oncology Association, Covered California, EmblemHealth, Exact Sciences, GRAIL, Harvard University, HealthCorum, Hygieia, Johnson & Johnson, MedZed, Merck, Mercer, Montana Health Cooperative, Phathom Pharmaceuticals, Proton Intelligence, RA Capital, Teladoc Health, U.S. Department of Defense, Virginia Center for Health Innovation, Washington Health Benefit Exchange, Wildflower Health, and Yale-New Haven Health System; and serving as a consultant for and holding equity in Health at Scale Technologies, Pair Team, Sempre Health, Silver Fern Health, and Wellth.

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

Despite federal legislation doing away with cost-sharing for initial breast cancer screening, out-of-pocket costs for needed follow-up tests remain significant financial barriers for many women.

An analysis of claims data found that women with higher cost-sharing undergo fewer subsequent breast diagnostic tests after an abnormal screening mammogram, compared with peers with lower cost-sharing.

“The chief clinical implication is that women with abnormal mammograms – that is, potentially at risk for cancer – are deciding not to follow-up on diagnostic imaging because of high out-of-pocket costs,” Danny Hughes, PhD, professor, College of Health Solutions, Arizona State University in Phoenix, told this news organization.

One course of action for radiologists is to “strongly communicate the importance of adhering to recommended follow-on testing,” Dr. Hughes said.

Another is to “work to pass national and state legislation, such as recently passed [legislation] in Connecticut, that removes out-of-pocket costs for follow-on diagnostic breast imaging and biopsy in the same way that these patient costs are prohibited for screening mammography,” he suggested.

The study was published online in JAMA Network Open.


 

‘Worrisome’ findings

The Affordable Care Act removed out-of-pocket costs for preventive health care, such as screening mammograms in women aged 40 and over.

However, lingering cost barriers remain for some individuals who have a positive initial screening mammogram and need follow-up tests. For instance, research shows that women in high-deductible plans, which often have higher out-of-pocket costs than other plans, may experience delays in follow-on care, including diagnostic breast imaging.

Dr. Hughes and colleagues examined the association between the degree of patient cost-sharing across different health plans – those dominated by copays, coinsurance, or deductibles as well as those classified as balanced across the three categories – and the use of diagnostic breast cancer imaging after a screening mammogram.

The data came from Optum’s database of administrative health claims for members of large commercial and Medicare Advantage health plans. The team used a machine learning algorithm to rank patient insurance plans by type of cost-sharing.

The sample included 230,845 mostly White (71%) women 40 years and older with no prior history of breast cancer who underwent screening mammography. These women were covered by 22,828 distinct insurance plans associated with roughly 6 million enrollees and nearly 45 million distinct medical claims.

Plans dominated by coinsurance had the lowest average out-of-pocket costs ($945), followed by plans balanced across the three cost-sharing categories ($1,017), plans dominated by copays ($1,020), and plans dominated by deductibles ($1,186).

Compared with women with coinsurance plans, those with copay- and deductible-dominated plans underwent significantly fewer subsequent breast-imaging procedures – 24 and 16 fewer procedures per 1,000 women, respectively.

Use of follow-on breast MRI was nearly 24% lower among women in plans with the highest cost-sharing versus those in plans with the lowest cost-sharing.

The team found no statistically significant difference in breast biopsy use between plan types.

Considering the risks posed by an unconfirmed positive mammogram result, these findings are “startling” and question the efficacy of legislation that eliminated cost-sharing from many preventive services, including screening mammograms, Dr. Hughes and colleagues write.

“Additional policy changes, such as removing cost-sharing for subsequent tests after abnormal screening results or bundling all breast cancer diagnostic testing into a single reimbursement, may provide avenues to mitigate these financial barriers to care,” the authors add.

The authors of an accompanying editorial found the study’s main finding – that some women who have an abnormal result on a mammogram may not get appropriate follow-up because of cost – is “worrisome.” 

“From a population health perspective, failure to complete the screening process limits the program’s effectiveness and likely exacerbates health disparities,” write Ilana Richman, MD, with Yale University, New Haven, Conn., and A. Mark Fendrick, MD, with the University of Michigan, Ann Arbor.

“On an individual level, high out-of-pocket costs may directly contribute to worse health outcomes or require individuals to use scarce financial resources that may otherwise be used for critical items such as food or rent,” Dr. Richman and Dr. Fendrick add. And “the removal of financial barriers for the entire breast cancer screening process has potential to improve total screening uptake and follow-up rates.”

Support for the study was provided by the Harvey L. Neiman Health Policy Institute. Dr. Hughes has reported no relevant financial relationships. Dr. Richman has reported receiving salary support from the Centers for Medicare & Medicaid Services to develop health care quality measures outside the submitted work. Dr. Fendrick has reported serving as a consultant for AbbVie, Amgen, Bayer, CareFirst, BlueCross BlueShield, Centivo, Community Oncology Association, Covered California, EmblemHealth, Exact Sciences, GRAIL, Harvard University, HealthCorum, Hygieia, Johnson & Johnson, MedZed, Merck, Mercer, Montana Health Cooperative, Phathom Pharmaceuticals, Proton Intelligence, RA Capital, Teladoc Health, U.S. Department of Defense, Virginia Center for Health Innovation, Washington Health Benefit Exchange, Wildflower Health, and Yale-New Haven Health System; and serving as a consultant for and holding equity in Health at Scale Technologies, Pair Team, Sempre Health, Silver Fern Health, and Wellth.

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

In an analysis of randomized trials, the Mediterranean diet and low-fat diets were linked to reduced risks of all-cause mortality and nonfatal MI over 3 years in adults at increased risk for cardiovascular disease (CVD), while the Mediterranean diet also showed lower risk of stroke.

Five other popular diets appeared to have little or no benefit with regard to these outcomes.

“These findings with data presentations are extremely important for patients who are skeptical about the desirability of diet change,” wrote the authors, led by Giorgio Karam, a medical student at the University of Manitoba, Winnipeg.

The results were published online in The BMJ.

Dietary guidelines recommend various diets along with physical activity or other cointerventions for adults at increased CVD risk, but they are often based on low-certainty evidence from nonrandomized studies and on surrogate outcomes.

Several meta-analyses of randomized controlled trials with mortality and major CV outcomes have reported benefits of some dietary programs, but those studies did not use network meta-analysis to give absolute estimates and certainty of estimates for adults at intermediate and high risk, the authors noted.

For this study, Mr. Karam and colleagues conducted a comprehensive systematic review and network meta-analysis in which they compared the effects of seven popular structured diets on mortality and CVD events for adults with CVD or CVD risk factors.

The seven diet plans were the Mediterranean, low fat, very low fat, modified fat, combined low fat and low sodium, Ornish, and Pritikin diets. Data for the analysis came from 40 randomized controlled trials that involved 35,548 participants who were followed for an average of 3 years.

There was evidence of “moderate” certainty that the Mediterranean diet was superior to minimal intervention for all-cause mortality (odds ratio [OR], 0.72), CV mortality (OR, 0.55), stroke (OR, 0.65), and nonfatal MI (OR, 0.48).

On an absolute basis (per 1,000 over 5 years), the Mediterranean diet let to 17 fewer deaths from any cause, 13 fewer CV deaths, seven fewer strokes, and 17 fewer nonfatal MIs.

There was evidence of moderate certainty that a low-fat diet was superior to minimal intervention for prevention of all-cause mortality (OR, 0.84; nine fewer deaths per 1,000) and nonfatal MI (OR, 0.77; seven fewer deaths per 1,000). The low-fat diet had little to no benefit with regard to stroke reduction.

The Mediterranean diet was not “convincingly” superior to a low-fat diet for mortality or nonfatal MI, the authors noted.

The absolute effects for the Mediterranean and low-fat diets were more pronounced in adults at high CVD risk. With the Mediterranean diet, there were 36 fewer all-cause deaths and 39 fewer CV deaths per 1,000 over 5 years.

The five other dietary programs generally had “little or no benefit” compared with minimal intervention. The evidence was of low to moderate certainty.

The studies did not provide enough data to gauge the impact of the diets on angina, heart failure, peripheral vascular events, and atrial fibrillation.

The researchers say that strengths of their analysis include a comprehensive review and thorough literature search and a rigorous assessment of study bias. In addition, the researchers adhered to recognized GRADE methods for assessing the certainty of estimates.

Limitations of their work include not being able to measure adherence to dietary programs and the possibility that some of the benefits may have been due to other factors, such as drug treatment and support for quitting smoking.

The study had no specific funding. The authors have disclosed no relevant financial relationships.

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

In an analysis of randomized trials, the Mediterranean diet and low-fat diets were linked to reduced risks of all-cause mortality and nonfatal MI over 3 years in adults at increased risk for cardiovascular disease (CVD), while the Mediterranean diet also showed lower risk of stroke.

Five other popular diets appeared to have little or no benefit with regard to these outcomes.

“These findings with data presentations are extremely important for patients who are skeptical about the desirability of diet change,” wrote the authors, led by Giorgio Karam, a medical student at the University of Manitoba, Winnipeg.

The results were published online in The BMJ.

Dietary guidelines recommend various diets along with physical activity or other cointerventions for adults at increased CVD risk, but they are often based on low-certainty evidence from nonrandomized studies and on surrogate outcomes.

Several meta-analyses of randomized controlled trials with mortality and major CV outcomes have reported benefits of some dietary programs, but those studies did not use network meta-analysis to give absolute estimates and certainty of estimates for adults at intermediate and high risk, the authors noted.

For this study, Mr. Karam and colleagues conducted a comprehensive systematic review and network meta-analysis in which they compared the effects of seven popular structured diets on mortality and CVD events for adults with CVD or CVD risk factors.

The seven diet plans were the Mediterranean, low fat, very low fat, modified fat, combined low fat and low sodium, Ornish, and Pritikin diets. Data for the analysis came from 40 randomized controlled trials that involved 35,548 participants who were followed for an average of 3 years.

There was evidence of “moderate” certainty that the Mediterranean diet was superior to minimal intervention for all-cause mortality (odds ratio [OR], 0.72), CV mortality (OR, 0.55), stroke (OR, 0.65), and nonfatal MI (OR, 0.48).

On an absolute basis (per 1,000 over 5 years), the Mediterranean diet let to 17 fewer deaths from any cause, 13 fewer CV deaths, seven fewer strokes, and 17 fewer nonfatal MIs.

There was evidence of moderate certainty that a low-fat diet was superior to minimal intervention for prevention of all-cause mortality (OR, 0.84; nine fewer deaths per 1,000) and nonfatal MI (OR, 0.77; seven fewer deaths per 1,000). The low-fat diet had little to no benefit with regard to stroke reduction.

The Mediterranean diet was not “convincingly” superior to a low-fat diet for mortality or nonfatal MI, the authors noted.

The absolute effects for the Mediterranean and low-fat diets were more pronounced in adults at high CVD risk. With the Mediterranean diet, there were 36 fewer all-cause deaths and 39 fewer CV deaths per 1,000 over 5 years.

The five other dietary programs generally had “little or no benefit” compared with minimal intervention. The evidence was of low to moderate certainty.

The studies did not provide enough data to gauge the impact of the diets on angina, heart failure, peripheral vascular events, and atrial fibrillation.

The researchers say that strengths of their analysis include a comprehensive review and thorough literature search and a rigorous assessment of study bias. In addition, the researchers adhered to recognized GRADE methods for assessing the certainty of estimates.

Limitations of their work include not being able to measure adherence to dietary programs and the possibility that some of the benefits may have been due to other factors, such as drug treatment and support for quitting smoking.

The study had no specific funding. The authors have disclosed no relevant financial relationships.

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

In an analysis of randomized trials, the Mediterranean diet and low-fat diets were linked to reduced risks of all-cause mortality and nonfatal MI over 3 years in adults at increased risk for cardiovascular disease (CVD), while the Mediterranean diet also showed lower risk of stroke.

Five other popular diets appeared to have little or no benefit with regard to these outcomes.

“These findings with data presentations are extremely important for patients who are skeptical about the desirability of diet change,” wrote the authors, led by Giorgio Karam, a medical student at the University of Manitoba, Winnipeg.

The results were published online in The BMJ.

Dietary guidelines recommend various diets along with physical activity or other cointerventions for adults at increased CVD risk, but they are often based on low-certainty evidence from nonrandomized studies and on surrogate outcomes.

Several meta-analyses of randomized controlled trials with mortality and major CV outcomes have reported benefits of some dietary programs, but those studies did not use network meta-analysis to give absolute estimates and certainty of estimates for adults at intermediate and high risk, the authors noted.

For this study, Mr. Karam and colleagues conducted a comprehensive systematic review and network meta-analysis in which they compared the effects of seven popular structured diets on mortality and CVD events for adults with CVD or CVD risk factors.

The seven diet plans were the Mediterranean, low fat, very low fat, modified fat, combined low fat and low sodium, Ornish, and Pritikin diets. Data for the analysis came from 40 randomized controlled trials that involved 35,548 participants who were followed for an average of 3 years.

There was evidence of “moderate” certainty that the Mediterranean diet was superior to minimal intervention for all-cause mortality (odds ratio [OR], 0.72), CV mortality (OR, 0.55), stroke (OR, 0.65), and nonfatal MI (OR, 0.48).

On an absolute basis (per 1,000 over 5 years), the Mediterranean diet let to 17 fewer deaths from any cause, 13 fewer CV deaths, seven fewer strokes, and 17 fewer nonfatal MIs.

There was evidence of moderate certainty that a low-fat diet was superior to minimal intervention for prevention of all-cause mortality (OR, 0.84; nine fewer deaths per 1,000) and nonfatal MI (OR, 0.77; seven fewer deaths per 1,000). The low-fat diet had little to no benefit with regard to stroke reduction.

The Mediterranean diet was not “convincingly” superior to a low-fat diet for mortality or nonfatal MI, the authors noted.

The absolute effects for the Mediterranean and low-fat diets were more pronounced in adults at high CVD risk. With the Mediterranean diet, there were 36 fewer all-cause deaths and 39 fewer CV deaths per 1,000 over 5 years.

The five other dietary programs generally had “little or no benefit” compared with minimal intervention. The evidence was of low to moderate certainty.

The studies did not provide enough data to gauge the impact of the diets on angina, heart failure, peripheral vascular events, and atrial fibrillation.

The researchers say that strengths of their analysis include a comprehensive review and thorough literature search and a rigorous assessment of study bias. In addition, the researchers adhered to recognized GRADE methods for assessing the certainty of estimates.

Limitations of their work include not being able to measure adherence to dietary programs and the possibility that some of the benefits may have been due to other factors, such as drug treatment and support for quitting smoking.

The study had no specific funding. The authors have disclosed no relevant financial relationships.

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

PARIS – Childhood trauma affects women and men equally in terms of its impact on subsequent psychopathology, but trauma type has subsequent differential effects depending on gender, new research shows.

Investigators found childhood emotional and sexual abuse had a greater effect on women than men, whereas men were more adversely affected by emotional and physical neglect.

“Our findings indicate that exposure to childhood maltreatment increases the risk of having psychiatric symptoms in both men and women,” lead researcher Thanavadee Prachason, PhD, department of psychiatry and neuropsychology, Maastricht (the Netherlands) University Medical Center, said in a press release.

“Exposure to emotionally or sexually abusive experiences during childhood increases the risk of a variety of psychiatric symptoms, particularly in women. In contrast, a history of emotional or physical neglect in childhood increases the risk of having psychiatric symptoms more in men,” Dr. Prachason added.

The findings were presented at the European Psychiatric Association 2023 Congress.

A leading mental illness risk factor

Study presenter Laura Fusar-Poli, MD, PhD, from the department of brain and behavioral sciences, University of Pavia (Italy), said that the differential impact of trauma subtypes in men and women indicate that both gender and the type of childhood adversity experienced need to be taken into account in future studies.

Dr. Fusar-Poli began by highlighting that 13%-36% of individuals have experienced some kind of childhood trauma, with 30% exposed to at least two types of trauma.

Trauma has been identified as a risk factor for a range of mental health problems.

“It is estimated that, worldwide, around one third of all psychiatric disorders are related to childhood trauma,” senior researcher Sinan Gülöksüz, MD, PhD, also from Maastricht University Medical Center, said in the release.

Consequently, “childhood trauma is a leading preventable risk factor for mental illness,” he added.

Previous research suggests the subtype of trauma has an impact on subsequent biological changes and clinical outcomes, and that there are gender differences in the effects of childhood trauma.

To investigate, the researchers examined data from TwinssCan, a Belgian cohort of twins and siblings aged 15-35 years without a diagnosis of pervasive mental disorders.

The study included 477 females and 314 males who had completed the Childhood Trauma Questionnaire–Short Form (CTQ) and the Symptom Checklist-90 SR (SCL-90) to determine exposure to childhood adversity and levels of psychopathology, respectively.

Results showed that total CTQ scores were significantly associated with total SCL-90 scores in both men and women, as well as with each of the nine symptom domains of the SCL-90 (P < .001 for all assessments). These included psychoticism, paranoid ideation, anxiety, depression, somatization, obsessive-compulsive, interpersonal sensitivity, hostility, and phobic anxiety.

There were no significant differences in the associations with total CTQ scores between men and women.

However, when the researchers examined trauma subtypes and psychopathology, clear gender differences emerged.

Investigators found a significant association between emotional abuse on the CTQ and total SCL-90 scores in both men (P < .023) and women (P < .001), but that the association was significantly stronger in women (P = .043).

Sexual abuse was significantly associated with total SCL-90 scores in women (P < .001), while emotional neglect and physical neglect were significantly associated with psychopathology scores in men (P = .026 and P < .001, respectively).

“Physical neglect may include experiences of not having enough to eat, wearing dirty clothes, not being taken care of, and not getting taken to the doctor when the person was growing up,” said Dr. Prachason.

“Emotional neglect may include childhood experiences like not feeling loved or important, and not feeling close to the family.”

In women, emotional abuse was significantly associated with all nine symptom domains of the SCL-90, while sexual abuse was associated with seven: psychoticism, paranoid ideation, anxiety, depression, somatization, obsessive-compulsive, and hostility.

Physical neglect, in men, was significantly associated with eight of the symptom domains (all but somatization), but emotional neglect was linked only to depression, Dr. Fusar-Poli reported.

“This study showed a very important consequence of childhood trauma, and not only in people with mental disorders. I would like to underline that this is a general population, composed of adolescents and young adults, which is the age in which the majority of mental disorders starts, Dr. Fusar-Poli said in an interview.

She emphasized that psychotic disorders are only a part of the “broad range” of conditions that may be related to childhood trauma, which “can have an impact on sub-threshold symptoms that can affect functioning and quality of life in the general population.”

Addressing the differential findings in men and women, Dr. Gülöksüz noted women may be more “vulnerable to childhood trauma than men” simply because “they are exposed to more sexual and emotional abuse.”

However, he said, this is “something that we really need understand,” as there is likely an underlying mechanism, “and not only a biological mechanism but probably a societal one.”

Dr. Gülöksüz noted there could also be differences between societies in terms of the impact of childhood trauma. “Our sample was from Belgium, but what would happen if we conducted this study in Italy, or in India,” he said.

Compromised cognitive, emotional function

Commenting on the findings for this news organization, Elaine F. Walker, PhD, professor of psychology and neuroscience at Emory University in Atlanta, said stress exposure in general, including childhood trauma, “has transdiagnostic effects on vulnerability to mental disorders.”

“The effects are primarily mediated by the hypothalamic-pituitary-adrenal axis, which triggers the release of cortisol. When persistently elevated, this can result in neurobiological processes that have adverse effects on brain structure and circuitry which, in turn, compromises cognitive and emotional functioning,” said Dr. Walker, who was not associated with the study.

She noted that, “while it is possible that there are sex differences in biological sensitivity to certain subtypes of childhood trauma, it may also be the case that sex differences in the likelihood of exposure to trauma subtypes is actually the key factor.”

“At the present time, there are not specific treatment protocols aimed at addressing childhood trauma subtypes, but most experienced therapists will incorporate information about the individual’s trauma history in their treatment,” Dr. Walker added.

Also commenting on the research, Philip Gorwood, MD, PhD, head of the Clinique des Maladies Mentales et de l’Encéphale at Centre Hospitalier Sainte Anne in Paris, said the results are “important … as childhood trauma has been clearly recognized as a major risk factor for the vast majority of psychiatric disorders, but with poor knowledge of gender specificities.”

“Understanding which aspects of trauma are more damaging according to gender will facilitate research on the resilience process. Many intervention strategies will indeed benefit from a more personalized approach,” he said in a statement. Dr. Gorwood was not involved with this study.

The study authors, Dr. Gorwood, and Dr. Walker report no relevant financial relationships.

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

PARIS – Childhood trauma affects women and men equally in terms of its impact on subsequent psychopathology, but trauma type has subsequent differential effects depending on gender, new research shows.

Investigators found childhood emotional and sexual abuse had a greater effect on women than men, whereas men were more adversely affected by emotional and physical neglect.

“Our findings indicate that exposure to childhood maltreatment increases the risk of having psychiatric symptoms in both men and women,” lead researcher Thanavadee Prachason, PhD, department of psychiatry and neuropsychology, Maastricht (the Netherlands) University Medical Center, said in a press release.

“Exposure to emotionally or sexually abusive experiences during childhood increases the risk of a variety of psychiatric symptoms, particularly in women. In contrast, a history of emotional or physical neglect in childhood increases the risk of having psychiatric symptoms more in men,” Dr. Prachason added.

The findings were presented at the European Psychiatric Association 2023 Congress.

A leading mental illness risk factor

Study presenter Laura Fusar-Poli, MD, PhD, from the department of brain and behavioral sciences, University of Pavia (Italy), said that the differential impact of trauma subtypes in men and women indicate that both gender and the type of childhood adversity experienced need to be taken into account in future studies.

Dr. Fusar-Poli began by highlighting that 13%-36% of individuals have experienced some kind of childhood trauma, with 30% exposed to at least two types of trauma.

Trauma has been identified as a risk factor for a range of mental health problems.

“It is estimated that, worldwide, around one third of all psychiatric disorders are related to childhood trauma,” senior researcher Sinan Gülöksüz, MD, PhD, also from Maastricht University Medical Center, said in the release.

Consequently, “childhood trauma is a leading preventable risk factor for mental illness,” he added.

Previous research suggests the subtype of trauma has an impact on subsequent biological changes and clinical outcomes, and that there are gender differences in the effects of childhood trauma.

To investigate, the researchers examined data from TwinssCan, a Belgian cohort of twins and siblings aged 15-35 years without a diagnosis of pervasive mental disorders.

The study included 477 females and 314 males who had completed the Childhood Trauma Questionnaire–Short Form (CTQ) and the Symptom Checklist-90 SR (SCL-90) to determine exposure to childhood adversity and levels of psychopathology, respectively.

Results showed that total CTQ scores were significantly associated with total SCL-90 scores in both men and women, as well as with each of the nine symptom domains of the SCL-90 (P < .001 for all assessments). These included psychoticism, paranoid ideation, anxiety, depression, somatization, obsessive-compulsive, interpersonal sensitivity, hostility, and phobic anxiety.

There were no significant differences in the associations with total CTQ scores between men and women.

However, when the researchers examined trauma subtypes and psychopathology, clear gender differences emerged.

Investigators found a significant association between emotional abuse on the CTQ and total SCL-90 scores in both men (P < .023) and women (P < .001), but that the association was significantly stronger in women (P = .043).

Sexual abuse was significantly associated with total SCL-90 scores in women (P < .001), while emotional neglect and physical neglect were significantly associated with psychopathology scores in men (P = .026 and P < .001, respectively).

“Physical neglect may include experiences of not having enough to eat, wearing dirty clothes, not being taken care of, and not getting taken to the doctor when the person was growing up,” said Dr. Prachason.

“Emotional neglect may include childhood experiences like not feeling loved or important, and not feeling close to the family.”

In women, emotional abuse was significantly associated with all nine symptom domains of the SCL-90, while sexual abuse was associated with seven: psychoticism, paranoid ideation, anxiety, depression, somatization, obsessive-compulsive, and hostility.

Physical neglect, in men, was significantly associated with eight of the symptom domains (all but somatization), but emotional neglect was linked only to depression, Dr. Fusar-Poli reported.

“This study showed a very important consequence of childhood trauma, and not only in people with mental disorders. I would like to underline that this is a general population, composed of adolescents and young adults, which is the age in which the majority of mental disorders starts, Dr. Fusar-Poli said in an interview.

She emphasized that psychotic disorders are only a part of the “broad range” of conditions that may be related to childhood trauma, which “can have an impact on sub-threshold symptoms that can affect functioning and quality of life in the general population.”

Addressing the differential findings in men and women, Dr. Gülöksüz noted women may be more “vulnerable to childhood trauma than men” simply because “they are exposed to more sexual and emotional abuse.”

However, he said, this is “something that we really need understand,” as there is likely an underlying mechanism, “and not only a biological mechanism but probably a societal one.”

Dr. Gülöksüz noted there could also be differences between societies in terms of the impact of childhood trauma. “Our sample was from Belgium, but what would happen if we conducted this study in Italy, or in India,” he said.

Compromised cognitive, emotional function

Commenting on the findings for this news organization, Elaine F. Walker, PhD, professor of psychology and neuroscience at Emory University in Atlanta, said stress exposure in general, including childhood trauma, “has transdiagnostic effects on vulnerability to mental disorders.”

“The effects are primarily mediated by the hypothalamic-pituitary-adrenal axis, which triggers the release of cortisol. When persistently elevated, this can result in neurobiological processes that have adverse effects on brain structure and circuitry which, in turn, compromises cognitive and emotional functioning,” said Dr. Walker, who was not associated with the study.

She noted that, “while it is possible that there are sex differences in biological sensitivity to certain subtypes of childhood trauma, it may also be the case that sex differences in the likelihood of exposure to trauma subtypes is actually the key factor.”

“At the present time, there are not specific treatment protocols aimed at addressing childhood trauma subtypes, but most experienced therapists will incorporate information about the individual’s trauma history in their treatment,” Dr. Walker added.

Also commenting on the research, Philip Gorwood, MD, PhD, head of the Clinique des Maladies Mentales et de l’Encéphale at Centre Hospitalier Sainte Anne in Paris, said the results are “important … as childhood trauma has been clearly recognized as a major risk factor for the vast majority of psychiatric disorders, but with poor knowledge of gender specificities.”

“Understanding which aspects of trauma are more damaging according to gender will facilitate research on the resilience process. Many intervention strategies will indeed benefit from a more personalized approach,” he said in a statement. Dr. Gorwood was not involved with this study.

The study authors, Dr. Gorwood, and Dr. Walker report no relevant financial relationships.

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

PARIS – Childhood trauma affects women and men equally in terms of its impact on subsequent psychopathology, but trauma type has subsequent differential effects depending on gender, new research shows.

Investigators found childhood emotional and sexual abuse had a greater effect on women than men, whereas men were more adversely affected by emotional and physical neglect.

“Our findings indicate that exposure to childhood maltreatment increases the risk of having psychiatric symptoms in both men and women,” lead researcher Thanavadee Prachason, PhD, department of psychiatry and neuropsychology, Maastricht (the Netherlands) University Medical Center, said in a press release.

“Exposure to emotionally or sexually abusive experiences during childhood increases the risk of a variety of psychiatric symptoms, particularly in women. In contrast, a history of emotional or physical neglect in childhood increases the risk of having psychiatric symptoms more in men,” Dr. Prachason added.

The findings were presented at the European Psychiatric Association 2023 Congress.

A leading mental illness risk factor

Study presenter Laura Fusar-Poli, MD, PhD, from the department of brain and behavioral sciences, University of Pavia (Italy), said that the differential impact of trauma subtypes in men and women indicate that both gender and the type of childhood adversity experienced need to be taken into account in future studies.

Dr. Fusar-Poli began by highlighting that 13%-36% of individuals have experienced some kind of childhood trauma, with 30% exposed to at least two types of trauma.

Trauma has been identified as a risk factor for a range of mental health problems.

“It is estimated that, worldwide, around one third of all psychiatric disorders are related to childhood trauma,” senior researcher Sinan Gülöksüz, MD, PhD, also from Maastricht University Medical Center, said in the release.

Consequently, “childhood trauma is a leading preventable risk factor for mental illness,” he added.

Previous research suggests the subtype of trauma has an impact on subsequent biological changes and clinical outcomes, and that there are gender differences in the effects of childhood trauma.

To investigate, the researchers examined data from TwinssCan, a Belgian cohort of twins and siblings aged 15-35 years without a diagnosis of pervasive mental disorders.

The study included 477 females and 314 males who had completed the Childhood Trauma Questionnaire–Short Form (CTQ) and the Symptom Checklist-90 SR (SCL-90) to determine exposure to childhood adversity and levels of psychopathology, respectively.

Results showed that total CTQ scores were significantly associated with total SCL-90 scores in both men and women, as well as with each of the nine symptom domains of the SCL-90 (P < .001 for all assessments). These included psychoticism, paranoid ideation, anxiety, depression, somatization, obsessive-compulsive, interpersonal sensitivity, hostility, and phobic anxiety.

There were no significant differences in the associations with total CTQ scores between men and women.

However, when the researchers examined trauma subtypes and psychopathology, clear gender differences emerged.

Investigators found a significant association between emotional abuse on the CTQ and total SCL-90 scores in both men (P < .023) and women (P < .001), but that the association was significantly stronger in women (P = .043).

Sexual abuse was significantly associated with total SCL-90 scores in women (P < .001), while emotional neglect and physical neglect were significantly associated with psychopathology scores in men (P = .026 and P < .001, respectively).

“Physical neglect may include experiences of not having enough to eat, wearing dirty clothes, not being taken care of, and not getting taken to the doctor when the person was growing up,” said Dr. Prachason.

“Emotional neglect may include childhood experiences like not feeling loved or important, and not feeling close to the family.”

In women, emotional abuse was significantly associated with all nine symptom domains of the SCL-90, while sexual abuse was associated with seven: psychoticism, paranoid ideation, anxiety, depression, somatization, obsessive-compulsive, and hostility.

Physical neglect, in men, was significantly associated with eight of the symptom domains (all but somatization), but emotional neglect was linked only to depression, Dr. Fusar-Poli reported.

“This study showed a very important consequence of childhood trauma, and not only in people with mental disorders. I would like to underline that this is a general population, composed of adolescents and young adults, which is the age in which the majority of mental disorders starts, Dr. Fusar-Poli said in an interview.

She emphasized that psychotic disorders are only a part of the “broad range” of conditions that may be related to childhood trauma, which “can have an impact on sub-threshold symptoms that can affect functioning and quality of life in the general population.”

Addressing the differential findings in men and women, Dr. Gülöksüz noted women may be more “vulnerable to childhood trauma than men” simply because “they are exposed to more sexual and emotional abuse.”

However, he said, this is “something that we really need understand,” as there is likely an underlying mechanism, “and not only a biological mechanism but probably a societal one.”

Dr. Gülöksüz noted there could also be differences between societies in terms of the impact of childhood trauma. “Our sample was from Belgium, but what would happen if we conducted this study in Italy, or in India,” he said.

Compromised cognitive, emotional function

Commenting on the findings for this news organization, Elaine F. Walker, PhD, professor of psychology and neuroscience at Emory University in Atlanta, said stress exposure in general, including childhood trauma, “has transdiagnostic effects on vulnerability to mental disorders.”

“The effects are primarily mediated by the hypothalamic-pituitary-adrenal axis, which triggers the release of cortisol. When persistently elevated, this can result in neurobiological processes that have adverse effects on brain structure and circuitry which, in turn, compromises cognitive and emotional functioning,” said Dr. Walker, who was not associated with the study.

She noted that, “while it is possible that there are sex differences in biological sensitivity to certain subtypes of childhood trauma, it may also be the case that sex differences in the likelihood of exposure to trauma subtypes is actually the key factor.”

“At the present time, there are not specific treatment protocols aimed at addressing childhood trauma subtypes, but most experienced therapists will incorporate information about the individual’s trauma history in their treatment,” Dr. Walker added.

Also commenting on the research, Philip Gorwood, MD, PhD, head of the Clinique des Maladies Mentales et de l’Encéphale at Centre Hospitalier Sainte Anne in Paris, said the results are “important … as childhood trauma has been clearly recognized as a major risk factor for the vast majority of psychiatric disorders, but with poor knowledge of gender specificities.”

“Understanding which aspects of trauma are more damaging according to gender will facilitate research on the resilience process. Many intervention strategies will indeed benefit from a more personalized approach,” he said in a statement. Dr. Gorwood was not involved with this study.

The study authors, Dr. Gorwood, and Dr. Walker report no relevant financial relationships.

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

Increasing intake of folate and vitamin B6 beyond recommended daily levels offers no protective benefit against Parkinson’s disease (PD), a new study shows.

Though there was some evidence that vitamin B12 early in life was associated with decreased PD risk, the findings were inconsistent and were observed only in people whose daily intake was 10 times the recommended level.

“The results of this large prospective study do not support the hypothesis that increasing folate or vitamin B6 intakes above the current levels would reduce PD risk in this population of mostly White U.S. health professionals,” lead investigator Mario H. Flores-Torres, MD, PhD, a research scientist in the department of nutrition at the Harvard T.H. Chan School of Public Health, Boston, said in an interview.

However, he added, the study “leaves open the possibility that in some individuals the intake of vitamin B12 contributes to PD risk – a finding that warrants further research.”

The findings were published online  in Movement Disorders.
 

Mixed findings

Previous studies have suggested B vitamins – including folate, B6 and B12 – might affect PD risk, but results have been mixed.

The new study included 80,965 women from the Nurses’ Health Study (1984-2016) and 48,837 men from the Health Professionals Follow-up Study (1986-2016). The average age at baseline was 50 years in women and 54 years in men, and participants were followed for about 30 years.

Participants completed questionnaires about diet at the beginning of the study and again every 4 years.

To account for the possibility of reverse causation due to the long prodromal phase of PD, investigators conducted lagged analyses at 8, 12, 16, and 20 years.

During the follow-up period, 1,426 incident cases of PD were diagnosed (687 in women and 739 in men).

Researchers found no link between reduced PD risk and intake of vitamin B6 or folate.

Though the total cumulative average intake of vitamin B12 was not associated with PD risk, investigators noted a modest decrease in risk between those with highest baseline of B12 and participants with the lowest baseline levels (hazard ratio, 0.80; P = .01).

Individuals in the highest quintile of B12 intake at baseline had an average intake of 21-22 mcg/d, close to 10 times the recommended daily intake of 2.4 mcg/d.

“Although some of our results suggest that a higher intake of vitamin B12 may decrease the risk of PD in a population of U.S. health professionals, the associations we observed were modest and not entirely consistent,” Dr. Flores-Torres said.

“Additional studies need to confirm our findings to better understand whether people who take higher amounts of B12 younger in life may have a protective benefit against PD,” he added.
 

The whole picture?

Commenting on the findings for this article, Rebecca Gilbert, MD, PhD, chief scientific officer of the American Parkinson Disease Association, New York, noted that checking B vitamin levels is a fairly standard practice for most clinicians. In that regard, this study highlights why this is important.

“Neurologists will often test B12 levels and recommend a supplement if your level is below the normal range,” she said. “No one is questioning the value of B12 for nerves and recommend that B12 is in the normal to high normal range.”

But understanding how B vitamins may or may not affect PD risk might require a different kind of study.

“This analysis, much like many others, is trying so hard to figure out what is it in diets that affects Parkinson’s disease risk,” Dr. Gilbert said. “But we have yet to say these are the nutrients that prevent Parkinson’s or increase the risk.”

One reason for the conflicting results in studies such as this could be that the explanation for the link between diet and PD risk may not be in specific minerals consumed but rather in the diet as a whole.

“Focusing on specific elements of a diet may not give us the answer,” Dr. Gilbert said. “We should be analyzing diet as a complete holistic picture because it’s not just the elements but how everything in what we eat works together.”

The study was funded by the National Institutes of Health and the Parkinson’s Foundation. Dr. Flores-Torres and Dr. Gilbert report no relevant conflicts.
 

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

Increasing intake of folate and vitamin B6 beyond recommended daily levels offers no protective benefit against Parkinson’s disease (PD), a new study shows.

Though there was some evidence that vitamin B12 early in life was associated with decreased PD risk, the findings were inconsistent and were observed only in people whose daily intake was 10 times the recommended level.

“The results of this large prospective study do not support the hypothesis that increasing folate or vitamin B6 intakes above the current levels would reduce PD risk in this population of mostly White U.S. health professionals,” lead investigator Mario H. Flores-Torres, MD, PhD, a research scientist in the department of nutrition at the Harvard T.H. Chan School of Public Health, Boston, said in an interview.

However, he added, the study “leaves open the possibility that in some individuals the intake of vitamin B12 contributes to PD risk – a finding that warrants further research.”

The findings were published online  in Movement Disorders.
 

Mixed findings

Previous studies have suggested B vitamins – including folate, B6 and B12 – might affect PD risk, but results have been mixed.

The new study included 80,965 women from the Nurses’ Health Study (1984-2016) and 48,837 men from the Health Professionals Follow-up Study (1986-2016). The average age at baseline was 50 years in women and 54 years in men, and participants were followed for about 30 years.

Participants completed questionnaires about diet at the beginning of the study and again every 4 years.

To account for the possibility of reverse causation due to the long prodromal phase of PD, investigators conducted lagged analyses at 8, 12, 16, and 20 years.

During the follow-up period, 1,426 incident cases of PD were diagnosed (687 in women and 739 in men).

Researchers found no link between reduced PD risk and intake of vitamin B6 or folate.

Though the total cumulative average intake of vitamin B12 was not associated with PD risk, investigators noted a modest decrease in risk between those with highest baseline of B12 and participants with the lowest baseline levels (hazard ratio, 0.80; P = .01).

Individuals in the highest quintile of B12 intake at baseline had an average intake of 21-22 mcg/d, close to 10 times the recommended daily intake of 2.4 mcg/d.

“Although some of our results suggest that a higher intake of vitamin B12 may decrease the risk of PD in a population of U.S. health professionals, the associations we observed were modest and not entirely consistent,” Dr. Flores-Torres said.

“Additional studies need to confirm our findings to better understand whether people who take higher amounts of B12 younger in life may have a protective benefit against PD,” he added.
 

The whole picture?

Commenting on the findings for this article, Rebecca Gilbert, MD, PhD, chief scientific officer of the American Parkinson Disease Association, New York, noted that checking B vitamin levels is a fairly standard practice for most clinicians. In that regard, this study highlights why this is important.

“Neurologists will often test B12 levels and recommend a supplement if your level is below the normal range,” she said. “No one is questioning the value of B12 for nerves and recommend that B12 is in the normal to high normal range.”

But understanding how B vitamins may or may not affect PD risk might require a different kind of study.

“This analysis, much like many others, is trying so hard to figure out what is it in diets that affects Parkinson’s disease risk,” Dr. Gilbert said. “But we have yet to say these are the nutrients that prevent Parkinson’s or increase the risk.”

One reason for the conflicting results in studies such as this could be that the explanation for the link between diet and PD risk may not be in specific minerals consumed but rather in the diet as a whole.

“Focusing on specific elements of a diet may not give us the answer,” Dr. Gilbert said. “We should be analyzing diet as a complete holistic picture because it’s not just the elements but how everything in what we eat works together.”

The study was funded by the National Institutes of Health and the Parkinson’s Foundation. Dr. Flores-Torres and Dr. Gilbert report no relevant conflicts.
 

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

Increasing intake of folate and vitamin B6 beyond recommended daily levels offers no protective benefit against Parkinson’s disease (PD), a new study shows.

Though there was some evidence that vitamin B12 early in life was associated with decreased PD risk, the findings were inconsistent and were observed only in people whose daily intake was 10 times the recommended level.

“The results of this large prospective study do not support the hypothesis that increasing folate or vitamin B6 intakes above the current levels would reduce PD risk in this population of mostly White U.S. health professionals,” lead investigator Mario H. Flores-Torres, MD, PhD, a research scientist in the department of nutrition at the Harvard T.H. Chan School of Public Health, Boston, said in an interview.

However, he added, the study “leaves open the possibility that in some individuals the intake of vitamin B12 contributes to PD risk – a finding that warrants further research.”

The findings were published online  in Movement Disorders.
 

Mixed findings

Previous studies have suggested B vitamins – including folate, B6 and B12 – might affect PD risk, but results have been mixed.

The new study included 80,965 women from the Nurses’ Health Study (1984-2016) and 48,837 men from the Health Professionals Follow-up Study (1986-2016). The average age at baseline was 50 years in women and 54 years in men, and participants were followed for about 30 years.

Participants completed questionnaires about diet at the beginning of the study and again every 4 years.

To account for the possibility of reverse causation due to the long prodromal phase of PD, investigators conducted lagged analyses at 8, 12, 16, and 20 years.

During the follow-up period, 1,426 incident cases of PD were diagnosed (687 in women and 739 in men).

Researchers found no link between reduced PD risk and intake of vitamin B6 or folate.

Though the total cumulative average intake of vitamin B12 was not associated with PD risk, investigators noted a modest decrease in risk between those with highest baseline of B12 and participants with the lowest baseline levels (hazard ratio, 0.80; P = .01).

Individuals in the highest quintile of B12 intake at baseline had an average intake of 21-22 mcg/d, close to 10 times the recommended daily intake of 2.4 mcg/d.

“Although some of our results suggest that a higher intake of vitamin B12 may decrease the risk of PD in a population of U.S. health professionals, the associations we observed were modest and not entirely consistent,” Dr. Flores-Torres said.

“Additional studies need to confirm our findings to better understand whether people who take higher amounts of B12 younger in life may have a protective benefit against PD,” he added.
 

The whole picture?

Commenting on the findings for this article, Rebecca Gilbert, MD, PhD, chief scientific officer of the American Parkinson Disease Association, New York, noted that checking B vitamin levels is a fairly standard practice for most clinicians. In that regard, this study highlights why this is important.

“Neurologists will often test B12 levels and recommend a supplement if your level is below the normal range,” she said. “No one is questioning the value of B12 for nerves and recommend that B12 is in the normal to high normal range.”

But understanding how B vitamins may or may not affect PD risk might require a different kind of study.

“This analysis, much like many others, is trying so hard to figure out what is it in diets that affects Parkinson’s disease risk,” Dr. Gilbert said. “But we have yet to say these are the nutrients that prevent Parkinson’s or increase the risk.”

One reason for the conflicting results in studies such as this could be that the explanation for the link between diet and PD risk may not be in specific minerals consumed but rather in the diet as a whole.

“Focusing on specific elements of a diet may not give us the answer,” Dr. Gilbert said. “We should be analyzing diet as a complete holistic picture because it’s not just the elements but how everything in what we eat works together.”

The study was funded by the National Institutes of Health and the Parkinson’s Foundation. Dr. Flores-Torres and Dr. Gilbert report no relevant conflicts.
 

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