Neurology Reviews

We recently shared a clinical case drawn from a family medicine practice about the effect of adverse childhood experiences (ACEs) on health. The widespread epidemiology and significant health consequences require a focus on the prevention and management of ACEs. 
 

The Centers for Disease Control and Prevention published an important monograph on ACEs in 2019. Although it is evidence based, most of the interventions recommended to reduce ACEs and their sequelae are larger policy and public health efforts that go well beyond the clinician’s office. Important highlights from these recommended strategies to reduce ACEs include:

• Strengthen economic support for families through policies such as the earned income tax credit and child tax credit.
• Establish routine parental work/shift times to optimize cognitive outcomes in children.
• Promote social norms for healthy families through public health campaigns and legislative efforts to reduce corporal punishment of children. Bystander training that targets boys and men has also proven effective in reducing sexual violence.
• Facilitate early in-home visitation for at-risk families as well as high-quality childcare.
• Employ social-emotional learning approaches for children and adolescents, which can improve aggressive or violent behavior, rates of substance use, and academic success.
• Connect youth to after-school programs featuring caring adults.

But clinicians still play a vital role in the prevention and management of ACEs among their patients. Akin to gathering a patient’s past medical history or family history is initiating universal ACE screening in practice and exploring related topics in conversation.

The ACEs Aware initiative in California provides a comprehensive ACE screening clinical workflow to help implement these conversations in practice, including the assessment of associated health conditions and their appropriate clinical follow-up. While it is encouraged to universally screen patients, the key screenings to prioritize for the pediatric population are “parental depression, severe stress, unhealthy drug use, domestic violence, harsh punishment, [and] food insecurity.” Moreover, a systematic review by Steen and colleagues shared insight into newer interpretations of ACE screening which relate trauma to “[...] community violence, poverty, housing instability, structural racism, environmental blight, and climate change.” 

These exposures are now being investigated for a connection to the toxic stress response. In the long term, this genetic regulatory mechanism can be affected by “high doses of cumulative adversity experienced during critical and sensitive periods of early life development — without the buffering protections of trusted, nurturing caregivers and safe, stable environments.” This micro and macro lens fosters a deeper clinician understanding of a patient’s trauma origin and can better guide appropriate clinical follow-up. 

ACE-associated health conditions can be neurologic, endocrine, metabolic, or immune system–related. Early diagnosis and treatment of these conditions can help prevent long-term health care complications, costly for both patient and the health care system. 

After the initial clinical assessment, physicians can educate patients about the ways that ACE-associated health conditions are a consequence of toxic stress exposure. From there, physicians should rely on a broader integrated health team, within the health system and the community, to offer clinical interventions and services to mitigate patients’ toxic stress. The ACEs Aware Stress Buster wheel highlights seven targets to strategize stress regulation. This wheel can be used to identify existing protective factors for patients and track treatment progress, which may buffer the negative impact of stressors and contribute to health and resilience. 

The burden of universal screenings in primary care is high. Without ACE screening, however, the opportunity to address downstream health effects from toxic stress may be lost. Dubowitz and colleagues suggest ways to successfully incorporate ACE screenings in clinical workflow:

• Utilize technology to implement a streamlined referral processing/tracking system.
• Train clinicians to respond competently to positive ACE screens.
• Gather in-network and community-based resources for patients.

In addition, prioritize screening for families with children younger than 6 years of age to begin interventions as early as possible. Primary care clinicians have the unique opportunity to provide appropriate intervention over continual care. An intervention as simple as encouraging pediatric patient involvement in after-school programs may mitigate toxic stress and prevent the development of an ACE-associated health condition. 

Dr. Vega, Health Sciences Clinical Professor, Family Medicine, University of California, Irvine, disclosed ties with McNeil Pharmaceuticals. Alejandra Hurtado, MD candidate, University of California, Irvine School of Medicine, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

We recently shared a clinical case drawn from a family medicine practice about the effect of adverse childhood experiences (ACEs) on health. The widespread epidemiology and significant health consequences require a focus on the prevention and management of ACEs. 
 

The Centers for Disease Control and Prevention published an important monograph on ACEs in 2019. Although it is evidence based, most of the interventions recommended to reduce ACEs and their sequelae are larger policy and public health efforts that go well beyond the clinician’s office. Important highlights from these recommended strategies to reduce ACEs include:

• Strengthen economic support for families through policies such as the earned income tax credit and child tax credit.
• Establish routine parental work/shift times to optimize cognitive outcomes in children.
• Promote social norms for healthy families through public health campaigns and legislative efforts to reduce corporal punishment of children. Bystander training that targets boys and men has also proven effective in reducing sexual violence.
• Facilitate early in-home visitation for at-risk families as well as high-quality childcare.
• Employ social-emotional learning approaches for children and adolescents, which can improve aggressive or violent behavior, rates of substance use, and academic success.
• Connect youth to after-school programs featuring caring adults.

But clinicians still play a vital role in the prevention and management of ACEs among their patients. Akin to gathering a patient’s past medical history or family history is initiating universal ACE screening in practice and exploring related topics in conversation.

The ACEs Aware initiative in California provides a comprehensive ACE screening clinical workflow to help implement these conversations in practice, including the assessment of associated health conditions and their appropriate clinical follow-up. While it is encouraged to universally screen patients, the key screenings to prioritize for the pediatric population are “parental depression, severe stress, unhealthy drug use, domestic violence, harsh punishment, [and] food insecurity.” Moreover, a systematic review by Steen and colleagues shared insight into newer interpretations of ACE screening which relate trauma to “[...] community violence, poverty, housing instability, structural racism, environmental blight, and climate change.” 

These exposures are now being investigated for a connection to the toxic stress response. In the long term, this genetic regulatory mechanism can be affected by “high doses of cumulative adversity experienced during critical and sensitive periods of early life development — without the buffering protections of trusted, nurturing caregivers and safe, stable environments.” This micro and macro lens fosters a deeper clinician understanding of a patient’s trauma origin and can better guide appropriate clinical follow-up. 

ACE-associated health conditions can be neurologic, endocrine, metabolic, or immune system–related. Early diagnosis and treatment of these conditions can help prevent long-term health care complications, costly for both patient and the health care system. 

After the initial clinical assessment, physicians can educate patients about the ways that ACE-associated health conditions are a consequence of toxic stress exposure. From there, physicians should rely on a broader integrated health team, within the health system and the community, to offer clinical interventions and services to mitigate patients’ toxic stress. The ACEs Aware Stress Buster wheel highlights seven targets to strategize stress regulation. This wheel can be used to identify existing protective factors for patients and track treatment progress, which may buffer the negative impact of stressors and contribute to health and resilience. 

The burden of universal screenings in primary care is high. Without ACE screening, however, the opportunity to address downstream health effects from toxic stress may be lost. Dubowitz and colleagues suggest ways to successfully incorporate ACE screenings in clinical workflow:

• Utilize technology to implement a streamlined referral processing/tracking system.
• Train clinicians to respond competently to positive ACE screens.
• Gather in-network and community-based resources for patients.

In addition, prioritize screening for families with children younger than 6 years of age to begin interventions as early as possible. Primary care clinicians have the unique opportunity to provide appropriate intervention over continual care. An intervention as simple as encouraging pediatric patient involvement in after-school programs may mitigate toxic stress and prevent the development of an ACE-associated health condition. 

Dr. Vega, Health Sciences Clinical Professor, Family Medicine, University of California, Irvine, disclosed ties with McNeil Pharmaceuticals. Alejandra Hurtado, MD candidate, University of California, Irvine School of Medicine, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

We recently shared a clinical case drawn from a family medicine practice about the effect of adverse childhood experiences (ACEs) on health. The widespread epidemiology and significant health consequences require a focus on the prevention and management of ACEs. 
 

The Centers for Disease Control and Prevention published an important monograph on ACEs in 2019. Although it is evidence based, most of the interventions recommended to reduce ACEs and their sequelae are larger policy and public health efforts that go well beyond the clinician’s office. Important highlights from these recommended strategies to reduce ACEs include:

• Strengthen economic support for families through policies such as the earned income tax credit and child tax credit.
• Establish routine parental work/shift times to optimize cognitive outcomes in children.
• Promote social norms for healthy families through public health campaigns and legislative efforts to reduce corporal punishment of children. Bystander training that targets boys and men has also proven effective in reducing sexual violence.
• Facilitate early in-home visitation for at-risk families as well as high-quality childcare.
• Employ social-emotional learning approaches for children and adolescents, which can improve aggressive or violent behavior, rates of substance use, and academic success.
• Connect youth to after-school programs featuring caring adults.

But clinicians still play a vital role in the prevention and management of ACEs among their patients. Akin to gathering a patient’s past medical history or family history is initiating universal ACE screening in practice and exploring related topics in conversation.

The ACEs Aware initiative in California provides a comprehensive ACE screening clinical workflow to help implement these conversations in practice, including the assessment of associated health conditions and their appropriate clinical follow-up. While it is encouraged to universally screen patients, the key screenings to prioritize for the pediatric population are “parental depression, severe stress, unhealthy drug use, domestic violence, harsh punishment, [and] food insecurity.” Moreover, a systematic review by Steen and colleagues shared insight into newer interpretations of ACE screening which relate trauma to “[...] community violence, poverty, housing instability, structural racism, environmental blight, and climate change.” 

These exposures are now being investigated for a connection to the toxic stress response. In the long term, this genetic regulatory mechanism can be affected by “high doses of cumulative adversity experienced during critical and sensitive periods of early life development — without the buffering protections of trusted, nurturing caregivers and safe, stable environments.” This micro and macro lens fosters a deeper clinician understanding of a patient’s trauma origin and can better guide appropriate clinical follow-up. 

ACE-associated health conditions can be neurologic, endocrine, metabolic, or immune system–related. Early diagnosis and treatment of these conditions can help prevent long-term health care complications, costly for both patient and the health care system. 

After the initial clinical assessment, physicians can educate patients about the ways that ACE-associated health conditions are a consequence of toxic stress exposure. From there, physicians should rely on a broader integrated health team, within the health system and the community, to offer clinical interventions and services to mitigate patients’ toxic stress. The ACEs Aware Stress Buster wheel highlights seven targets to strategize stress regulation. This wheel can be used to identify existing protective factors for patients and track treatment progress, which may buffer the negative impact of stressors and contribute to health and resilience. 

The burden of universal screenings in primary care is high. Without ACE screening, however, the opportunity to address downstream health effects from toxic stress may be lost. Dubowitz and colleagues suggest ways to successfully incorporate ACE screenings in clinical workflow:

• Utilize technology to implement a streamlined referral processing/tracking system.
• Train clinicians to respond competently to positive ACE screens.
• Gather in-network and community-based resources for patients.

In addition, prioritize screening for families with children younger than 6 years of age to begin interventions as early as possible. Primary care clinicians have the unique opportunity to provide appropriate intervention over continual care. An intervention as simple as encouraging pediatric patient involvement in after-school programs may mitigate toxic stress and prevent the development of an ACE-associated health condition. 

Dr. Vega, Health Sciences Clinical Professor, Family Medicine, University of California, Irvine, disclosed ties with McNeil Pharmaceuticals. Alejandra Hurtado, MD candidate, University of California, Irvine School of Medicine, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

BOSTON — Patients who have had a stroke are thought to be at a higher risk for another one, but oral anticoagulation with edoxaban led to no discernible reduction in the risk for a second stroke, and the risk for major bleeding was more than quadruple the risk with no anticoagulation, a subanalysis of a major European trial has shown.

“There is no interaction between prior stroke or TIA [transient ischemic attack] and the treatment effect, and this is true for the primary outcome and the safety outcome,” Paulus Kirchoff, MD, director of cardiology at the University Heart and Vascular Center in Hamburg, Germany, said during his presentation of a subanalysis of the NOAH-AFNET 6 trial at the annual meeting of the Heart Rhythm Society (HRS) 2024. However, “there is a signal for more safety events in patients randomized to anticoagulation with a prior stroke.”

The subanalysis involved 253 patients who had had a stroke or TIA and who had device-detected atrial fibrillation (AF) from the overall NOAH-AFNET 6 population of 2536 patients, which enrolled patients 65 years and older with at least one additional CHA2DS-VASc risk factor and patients 75 years and older with device-detected subclinical AF episodes of at least 6 minutes. Patients were randomized to either edoxaban or no anticoagulation, but 53.9% of the no-anticoagulation group was taking aspirin at trial enrollment. Anticoagulation with edoxaban was shown to have no significant impact on stroke rates or other cardiovascular outcomes.
 

Subanalysis Results

In the subanalysis, a composite of stroke, systemic embolism, and cardiovascular death — the primary outcome — was similar in the edoxaban and no-anticoagulation groups (14/122 patients [11.5%] vs 16/131 patients [12.2%]; 5.7% vs 6.3% per patient-year).

The rate of recurrent stroke was also similar in the edoxaban and no-anticoagulation groups (4 of 122 patients [3.3%] vs 6 of 131 patients [4.6%]; 1.6% vs 2.3% per patient-year). And there were eight cardiovascular deaths in each group.

However, edoxaban patients had significantly higher rates of major bleeding.

“This is a subanalysis, so what we see in terms of the number of patients with events is not powered for a definitive answer, but we do see that there were 10 major bleeds in the group of patients with a prior stroke or TIA in NOAH,” Dr. Kirchoff reported. “Eight of those 10 major bleeds occurred in patients randomized to edoxaban.”

Results from the NOAH-AFNET 6 trial have been compared with those from the ARTESiA trial, which compared apixaban anticoagulation with aspirin in patients with subclinical AF and was also presented at HRS 2024. ARTESiA showed that apixaban significantly lowered the risk for stroke and systemic embolism.

“In ARTESiA, everyone was on aspirin when they were randomized to no anticoagulation; in NOAH, only about half were on aspirin,” Dr. Kirchoff said.

Both studies had similar outcomes for cardiovascular death in the anticoagulation and no-anticoagulation groups. “It’s not significant; it may be chance, but it’s definitely not the reduction in death that we have seen in the anticoagulant trials,” Dr. Kirchoff said. “When you look at the meta-analyses of the early anticoagulation trials, there’s a one third reduction in death, and here we’re talking about a smaller reduction.”

This research points to a need for a better way to evaluate stroke risk. “We need new markers,” Dr. Kirchoff said. “Some of them may be in the blood or imaging, genetics maybe, and one thing that really emerges from my perspective is that we now have the first evidence to suggest that patients with a very low atrial fibrillation burden have a low stroke rate.”

More research is needed to better understand AF characteristics and stroke risk, he said.
 

AF Care Enters a ‘Gray Zone’

The NOAH-AFNET 6 results, coupled with those from ARTESiA, are changing the paradigm for anticoagulation in patients with stroke, said Taya Glotzer, MD, an electrophysiologist at the Hackensack University Medical Center in Hackensack, New Jersey, who compiled her own analysis of the studies’ outcomes.

“In ARTESiA, the stroke reduction was only 0.44% a year, with a number needed to treat of 250,” she said. “In the NOAH-AFNET 6 main trial, the stroke reduction was 0.2%, with the number needed to treat of 500, and in the NOAH prior stroke patients, there was a 0.7% reduction, with a number needed to treat of 143.”

None of these trials would meet the standard for a class 1 recommendation for anticoagulation with a reduction of even 1%-2% per year, she noted, but they do show that the stroke rate “is very, very low” in prior patients with stroke.

“Prior to 2024, we knew what was black and white; we knew who to anticoagulate and who not to anticoagulate. And now we are in a gray zone, trying to balance the risk of stroke and bleeding. We have to individualize or hope for substudies, perhaps using the CHA2DS-VASc score or other information about the left atrium, to help us make decisions in these patients. It’s not just going to be black and white,” she said.

Dr. Kirchoff had no relevant financial relationships to disclose. Dr. Glotzer disclosed financial relationships with Medtronic, Abbott, Boston Scientific, and MediaSphere Medical.

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

BOSTON — Patients who have had a stroke are thought to be at a higher risk for another one, but oral anticoagulation with edoxaban led to no discernible reduction in the risk for a second stroke, and the risk for major bleeding was more than quadruple the risk with no anticoagulation, a subanalysis of a major European trial has shown.

“There is no interaction between prior stroke or TIA [transient ischemic attack] and the treatment effect, and this is true for the primary outcome and the safety outcome,” Paulus Kirchoff, MD, director of cardiology at the University Heart and Vascular Center in Hamburg, Germany, said during his presentation of a subanalysis of the NOAH-AFNET 6 trial at the annual meeting of the Heart Rhythm Society (HRS) 2024. However, “there is a signal for more safety events in patients randomized to anticoagulation with a prior stroke.”

The subanalysis involved 253 patients who had had a stroke or TIA and who had device-detected atrial fibrillation (AF) from the overall NOAH-AFNET 6 population of 2536 patients, which enrolled patients 65 years and older with at least one additional CHA2DS-VASc risk factor and patients 75 years and older with device-detected subclinical AF episodes of at least 6 minutes. Patients were randomized to either edoxaban or no anticoagulation, but 53.9% of the no-anticoagulation group was taking aspirin at trial enrollment. Anticoagulation with edoxaban was shown to have no significant impact on stroke rates or other cardiovascular outcomes.
 

Subanalysis Results

In the subanalysis, a composite of stroke, systemic embolism, and cardiovascular death — the primary outcome — was similar in the edoxaban and no-anticoagulation groups (14/122 patients [11.5%] vs 16/131 patients [12.2%]; 5.7% vs 6.3% per patient-year).

The rate of recurrent stroke was also similar in the edoxaban and no-anticoagulation groups (4 of 122 patients [3.3%] vs 6 of 131 patients [4.6%]; 1.6% vs 2.3% per patient-year). And there were eight cardiovascular deaths in each group.

However, edoxaban patients had significantly higher rates of major bleeding.

“This is a subanalysis, so what we see in terms of the number of patients with events is not powered for a definitive answer, but we do see that there were 10 major bleeds in the group of patients with a prior stroke or TIA in NOAH,” Dr. Kirchoff reported. “Eight of those 10 major bleeds occurred in patients randomized to edoxaban.”

Results from the NOAH-AFNET 6 trial have been compared with those from the ARTESiA trial, which compared apixaban anticoagulation with aspirin in patients with subclinical AF and was also presented at HRS 2024. ARTESiA showed that apixaban significantly lowered the risk for stroke and systemic embolism.

“In ARTESiA, everyone was on aspirin when they were randomized to no anticoagulation; in NOAH, only about half were on aspirin,” Dr. Kirchoff said.

Both studies had similar outcomes for cardiovascular death in the anticoagulation and no-anticoagulation groups. “It’s not significant; it may be chance, but it’s definitely not the reduction in death that we have seen in the anticoagulant trials,” Dr. Kirchoff said. “When you look at the meta-analyses of the early anticoagulation trials, there’s a one third reduction in death, and here we’re talking about a smaller reduction.”

This research points to a need for a better way to evaluate stroke risk. “We need new markers,” Dr. Kirchoff said. “Some of them may be in the blood or imaging, genetics maybe, and one thing that really emerges from my perspective is that we now have the first evidence to suggest that patients with a very low atrial fibrillation burden have a low stroke rate.”

More research is needed to better understand AF characteristics and stroke risk, he said.
 

AF Care Enters a ‘Gray Zone’

The NOAH-AFNET 6 results, coupled with those from ARTESiA, are changing the paradigm for anticoagulation in patients with stroke, said Taya Glotzer, MD, an electrophysiologist at the Hackensack University Medical Center in Hackensack, New Jersey, who compiled her own analysis of the studies’ outcomes.

“In ARTESiA, the stroke reduction was only 0.44% a year, with a number needed to treat of 250,” she said. “In the NOAH-AFNET 6 main trial, the stroke reduction was 0.2%, with the number needed to treat of 500, and in the NOAH prior stroke patients, there was a 0.7% reduction, with a number needed to treat of 143.”

None of these trials would meet the standard for a class 1 recommendation for anticoagulation with a reduction of even 1%-2% per year, she noted, but they do show that the stroke rate “is very, very low” in prior patients with stroke.

“Prior to 2024, we knew what was black and white; we knew who to anticoagulate and who not to anticoagulate. And now we are in a gray zone, trying to balance the risk of stroke and bleeding. We have to individualize or hope for substudies, perhaps using the CHA2DS-VASc score or other information about the left atrium, to help us make decisions in these patients. It’s not just going to be black and white,” she said.

Dr. Kirchoff had no relevant financial relationships to disclose. Dr. Glotzer disclosed financial relationships with Medtronic, Abbott, Boston Scientific, and MediaSphere Medical.

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

BOSTON — Patients who have had a stroke are thought to be at a higher risk for another one, but oral anticoagulation with edoxaban led to no discernible reduction in the risk for a second stroke, and the risk for major bleeding was more than quadruple the risk with no anticoagulation, a subanalysis of a major European trial has shown.

“There is no interaction between prior stroke or TIA [transient ischemic attack] and the treatment effect, and this is true for the primary outcome and the safety outcome,” Paulus Kirchoff, MD, director of cardiology at the University Heart and Vascular Center in Hamburg, Germany, said during his presentation of a subanalysis of the NOAH-AFNET 6 trial at the annual meeting of the Heart Rhythm Society (HRS) 2024. However, “there is a signal for more safety events in patients randomized to anticoagulation with a prior stroke.”

The subanalysis involved 253 patients who had had a stroke or TIA and who had device-detected atrial fibrillation (AF) from the overall NOAH-AFNET 6 population of 2536 patients, which enrolled patients 65 years and older with at least one additional CHA2DS-VASc risk factor and patients 75 years and older with device-detected subclinical AF episodes of at least 6 minutes. Patients were randomized to either edoxaban or no anticoagulation, but 53.9% of the no-anticoagulation group was taking aspirin at trial enrollment. Anticoagulation with edoxaban was shown to have no significant impact on stroke rates or other cardiovascular outcomes.
 

Subanalysis Results

In the subanalysis, a composite of stroke, systemic embolism, and cardiovascular death — the primary outcome — was similar in the edoxaban and no-anticoagulation groups (14/122 patients [11.5%] vs 16/131 patients [12.2%]; 5.7% vs 6.3% per patient-year).

The rate of recurrent stroke was also similar in the edoxaban and no-anticoagulation groups (4 of 122 patients [3.3%] vs 6 of 131 patients [4.6%]; 1.6% vs 2.3% per patient-year). And there were eight cardiovascular deaths in each group.

However, edoxaban patients had significantly higher rates of major bleeding.

“This is a subanalysis, so what we see in terms of the number of patients with events is not powered for a definitive answer, but we do see that there were 10 major bleeds in the group of patients with a prior stroke or TIA in NOAH,” Dr. Kirchoff reported. “Eight of those 10 major bleeds occurred in patients randomized to edoxaban.”

Results from the NOAH-AFNET 6 trial have been compared with those from the ARTESiA trial, which compared apixaban anticoagulation with aspirin in patients with subclinical AF and was also presented at HRS 2024. ARTESiA showed that apixaban significantly lowered the risk for stroke and systemic embolism.

“In ARTESiA, everyone was on aspirin when they were randomized to no anticoagulation; in NOAH, only about half were on aspirin,” Dr. Kirchoff said.

Both studies had similar outcomes for cardiovascular death in the anticoagulation and no-anticoagulation groups. “It’s not significant; it may be chance, but it’s definitely not the reduction in death that we have seen in the anticoagulant trials,” Dr. Kirchoff said. “When you look at the meta-analyses of the early anticoagulation trials, there’s a one third reduction in death, and here we’re talking about a smaller reduction.”

This research points to a need for a better way to evaluate stroke risk. “We need new markers,” Dr. Kirchoff said. “Some of them may be in the blood or imaging, genetics maybe, and one thing that really emerges from my perspective is that we now have the first evidence to suggest that patients with a very low atrial fibrillation burden have a low stroke rate.”

More research is needed to better understand AF characteristics and stroke risk, he said.
 

AF Care Enters a ‘Gray Zone’

The NOAH-AFNET 6 results, coupled with those from ARTESiA, are changing the paradigm for anticoagulation in patients with stroke, said Taya Glotzer, MD, an electrophysiologist at the Hackensack University Medical Center in Hackensack, New Jersey, who compiled her own analysis of the studies’ outcomes.

“In ARTESiA, the stroke reduction was only 0.44% a year, with a number needed to treat of 250,” she said. “In the NOAH-AFNET 6 main trial, the stroke reduction was 0.2%, with the number needed to treat of 500, and in the NOAH prior stroke patients, there was a 0.7% reduction, with a number needed to treat of 143.”

None of these trials would meet the standard for a class 1 recommendation for anticoagulation with a reduction of even 1%-2% per year, she noted, but they do show that the stroke rate “is very, very low” in prior patients with stroke.

“Prior to 2024, we knew what was black and white; we knew who to anticoagulate and who not to anticoagulate. And now we are in a gray zone, trying to balance the risk of stroke and bleeding. We have to individualize or hope for substudies, perhaps using the CHA2DS-VASc score or other information about the left atrium, to help us make decisions in these patients. It’s not just going to be black and white,” she said.

Dr. Kirchoff had no relevant financial relationships to disclose. Dr. Glotzer disclosed financial relationships with Medtronic, Abbott, Boston Scientific, and MediaSphere Medical.

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

After 26 years in practice, there are still things about the brain that amaze me, often that I first notice on myself.

Filtering (I guess “selective attention” sounds better) is one of them. We don’t notice it, but it’s definitely there.

Working at a jigsaw puzzle, I find myself looking for a specific piece, say, a white tab with a dark background and yellow stripe in the center. There may be several hundred pieces spread around me at the table, but the brain quickly starts filtering them out. In a fraction of a second I only notice ones with a white tab, then mentally those are broken down by the other characteristics. If it looks promising, I’ll look back at the space I’m trying to fit it in, mentally rotate the piece (another tricky thing if you think about it) and, if that seems to match, will pick up the piece to try. If it doesn’t fit the process repeats.

It’s a remarkable ability to see a relationship between two separate objects that isn’t always apparent.

But it’s not just sight. Although I’ve always loved music, it wasn’t until my own kids were in a band that I found the ability to break it down, removing the other instruments. It brings a remarkable clarity to suddenly hearing my daughter on the marimba, or son on the flute. Even with 70 other instrument playing around them.

You can try it yourself, listening to Keith Moon’s amazing drums on The Who’s “5:15.” Or in Bob Seger’s “Fire Lake.” Take out Seger and the instruments and you suddenly realize it’s the Eagles doing the background singing.

In Carly Simon’s “You’re So Vain,” a song you generally don’t attribute to the Rolling Stones, a little bit of focus will reveal Mick Jagger’s distinctive voice in the background chorus of “Don’t you, don’t you, don’t you?”

The ability isn’t something we created. It was there from our ancestors in the trees and caves. They used this ability to identify friend from foe, find the right path home, and pick out what was edible from what was poisonous. Like with so many other things, and without realizing it, our brains have retooled it for the world we now face, even if it’s just to find our car in the parking lot.

Sodium, calcium, potassium, and other ions flow in and out of nerve cells, an electrical impulse propagates though a network, matching incoming sounds and images to ones previously stored. That’s all it is, but the results are remarkable.

We take the everyday for granted, but should stop and think how amazing it really is.
 

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

After 26 years in practice, there are still things about the brain that amaze me, often that I first notice on myself.

Filtering (I guess “selective attention” sounds better) is one of them. We don’t notice it, but it’s definitely there.

Working at a jigsaw puzzle, I find myself looking for a specific piece, say, a white tab with a dark background and yellow stripe in the center. There may be several hundred pieces spread around me at the table, but the brain quickly starts filtering them out. In a fraction of a second I only notice ones with a white tab, then mentally those are broken down by the other characteristics. If it looks promising, I’ll look back at the space I’m trying to fit it in, mentally rotate the piece (another tricky thing if you think about it) and, if that seems to match, will pick up the piece to try. If it doesn’t fit the process repeats.

It’s a remarkable ability to see a relationship between two separate objects that isn’t always apparent.

But it’s not just sight. Although I’ve always loved music, it wasn’t until my own kids were in a band that I found the ability to break it down, removing the other instruments. It brings a remarkable clarity to suddenly hearing my daughter on the marimba, or son on the flute. Even with 70 other instrument playing around them.

You can try it yourself, listening to Keith Moon’s amazing drums on The Who’s “5:15.” Or in Bob Seger’s “Fire Lake.” Take out Seger and the instruments and you suddenly realize it’s the Eagles doing the background singing.

In Carly Simon’s “You’re So Vain,” a song you generally don’t attribute to the Rolling Stones, a little bit of focus will reveal Mick Jagger’s distinctive voice in the background chorus of “Don’t you, don’t you, don’t you?”

The ability isn’t something we created. It was there from our ancestors in the trees and caves. They used this ability to identify friend from foe, find the right path home, and pick out what was edible from what was poisonous. Like with so many other things, and without realizing it, our brains have retooled it for the world we now face, even if it’s just to find our car in the parking lot.

Sodium, calcium, potassium, and other ions flow in and out of nerve cells, an electrical impulse propagates though a network, matching incoming sounds and images to ones previously stored. That’s all it is, but the results are remarkable.

We take the everyday for granted, but should stop and think how amazing it really is.
 

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

After 26 years in practice, there are still things about the brain that amaze me, often that I first notice on myself.

Filtering (I guess “selective attention” sounds better) is one of them. We don’t notice it, but it’s definitely there.

Working at a jigsaw puzzle, I find myself looking for a specific piece, say, a white tab with a dark background and yellow stripe in the center. There may be several hundred pieces spread around me at the table, but the brain quickly starts filtering them out. In a fraction of a second I only notice ones with a white tab, then mentally those are broken down by the other characteristics. If it looks promising, I’ll look back at the space I’m trying to fit it in, mentally rotate the piece (another tricky thing if you think about it) and, if that seems to match, will pick up the piece to try. If it doesn’t fit the process repeats.

It’s a remarkable ability to see a relationship between two separate objects that isn’t always apparent.

But it’s not just sight. Although I’ve always loved music, it wasn’t until my own kids were in a band that I found the ability to break it down, removing the other instruments. It brings a remarkable clarity to suddenly hearing my daughter on the marimba, or son on the flute. Even with 70 other instrument playing around them.

You can try it yourself, listening to Keith Moon’s amazing drums on The Who’s “5:15.” Or in Bob Seger’s “Fire Lake.” Take out Seger and the instruments and you suddenly realize it’s the Eagles doing the background singing.

In Carly Simon’s “You’re So Vain,” a song you generally don’t attribute to the Rolling Stones, a little bit of focus will reveal Mick Jagger’s distinctive voice in the background chorus of “Don’t you, don’t you, don’t you?”

The ability isn’t something we created. It was there from our ancestors in the trees and caves. They used this ability to identify friend from foe, find the right path home, and pick out what was edible from what was poisonous. Like with so many other things, and without realizing it, our brains have retooled it for the world we now face, even if it’s just to find our car in the parking lot.

Sodium, calcium, potassium, and other ions flow in and out of nerve cells, an electrical impulse propagates though a network, matching incoming sounds and images to ones previously stored. That’s all it is, but the results are remarkable.

We take the everyday for granted, but should stop and think how amazing it really is.
 

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

SAN DIEGO — Susceptibility to post-traumatic headache could be linked to mutations in ion channel and ion transporter genes, according to results from a preliminary study.

Post-traumatic headache is a common symptom of traumatic brain injury (TBI).

There is evidence that genetic mutations could play a role in both TBI development and response. In particular, the S213L mutation for familial hemiplegic migraine-1 (FHM1), found in the CACNA1A gene, can cause individuals carrying it to be highly sensitive to otherwise trivial head impacts, according to Lyn Griffiths, PhD.

The consequences can be post-traumatic headache, but also seizures, cerebral edema, coma, or worse. Another form of FHM is associated with mutations in ATP1A2.

“This stimulated our interest in looking at genes that relate to TBI with a particular focus on ion channel genes,” said Dr. Griffiths, during a presentation of the study at the annual meeting of the American Headache Society.

The researchers analyzed data from 117 participants who had at least one concussion with a post-traumatic headache, and recruited family members when possible. There were 15 participants who developed severe reactions to trivial head trauma, 13 who had been diagnosed with concussion and underwent imaging related to TBI-associated symptoms, 54 who had been recruited through local sporting groups campuses, and 35 recruited through a medical research foundation. Blood or saliva samples were used to perform whole exome sequencing.

The researchers looked for gene candidates within different tiers. Tier 1 included genes that had already been implicated in severe migraine. The second tier included 353 ion channel and iron transporter genes. Tier 3 comprised neurotransmission-related genes.

After sequencing, the researchers filtered genetic mutations to include only those that affected amino acid composition of the protein, were predicted by two or more in silico analysis tools to be damaging, and were identified in multiple, unrelated patients.

In tier 2, the greatest number of potential damaging variants were found in the SCN9A gene, which is involved in pain perception and processing. There were six variants found in eight cases. Of these eight individuals, three had suffered severe reactions to relatively minor head trauma.

In tier 3, the researchers identified mutations in eight neurotransmitter-related genes.

Through comparison with a general population control group, the researchers identified 43 different rare, amino acid–changing variants that occurred within 16 ion channel and ion channel transporter genes. These mutations were found in 53 individuals, at an approximately fivefold higher frequency than the control group (odds ratio, 5.6; P < .0001).

“We identified a number of rare genetic variants implicated in migraine — ion channel and other neurologically associated genes — in those suffering from post-traumatic headache,” said Dr. Griffiths. She also noted that the whole genomes they collected will allow for further analysis of other gene candidates in the future.

During the Q&A period, Dr. Griffiths was asked if the research group tracked the severity of the TBIs suffered by participants. She responded that they had not, and this was a limitation of the study.

Another questioner asked if parents should consider genetic testing for susceptibility mutations when considering whether to allow a child to participate in sports or activities with elevated risk of TBI. “I don’t necessarily think this is a bad thing,” she said, though she conceded that the work is still immature. “It’s probably a bit early because we haven’t identified all the genes that are involved or all the specific mutations ... but I think down the track, that makes perfect sense. Why would you not do some sensible preventive screening to aid with things like maybe you wear more headgear or you consider what’s the appropriate sport for that person?”

Laine Green, MD, assistant professor of neurology at Mayo Clinic Arizona, Phoenix, who moderated the session, was asked for comment. “I think the idea of potentially identifying people that have more genetic susceptibility to injuries is very intriguing, because post-traumatic headache and symptoms is always a difficult area to treat, potentially identifying those that with more genetic susceptibility might be helpful. It may also potentially allow us to target specific treatments, especially in this case, looking at different ion channels. There are medications that may work better at ion channel targets than other targets,” said Dr. Green.

He also endorsed the potential value of screening. “Speaking as a parent, I might like to know my child is at higher risk if they’re going to participate in contact sports or other high risk activities,” he said.

Dr. Griffiths and Dr. Green have no relevant financial disclosures.

SAN DIEGO — Susceptibility to post-traumatic headache could be linked to mutations in ion channel and ion transporter genes, according to results from a preliminary study.

Post-traumatic headache is a common symptom of traumatic brain injury (TBI).

There is evidence that genetic mutations could play a role in both TBI development and response. In particular, the S213L mutation for familial hemiplegic migraine-1 (FHM1), found in the CACNA1A gene, can cause individuals carrying it to be highly sensitive to otherwise trivial head impacts, according to Lyn Griffiths, PhD.

The consequences can be post-traumatic headache, but also seizures, cerebral edema, coma, or worse. Another form of FHM is associated with mutations in ATP1A2.

“This stimulated our interest in looking at genes that relate to TBI with a particular focus on ion channel genes,” said Dr. Griffiths, during a presentation of the study at the annual meeting of the American Headache Society.

The researchers analyzed data from 117 participants who had at least one concussion with a post-traumatic headache, and recruited family members when possible. There were 15 participants who developed severe reactions to trivial head trauma, 13 who had been diagnosed with concussion and underwent imaging related to TBI-associated symptoms, 54 who had been recruited through local sporting groups campuses, and 35 recruited through a medical research foundation. Blood or saliva samples were used to perform whole exome sequencing.

The researchers looked for gene candidates within different tiers. Tier 1 included genes that had already been implicated in severe migraine. The second tier included 353 ion channel and iron transporter genes. Tier 3 comprised neurotransmission-related genes.

After sequencing, the researchers filtered genetic mutations to include only those that affected amino acid composition of the protein, were predicted by two or more in silico analysis tools to be damaging, and were identified in multiple, unrelated patients.

In tier 2, the greatest number of potential damaging variants were found in the SCN9A gene, which is involved in pain perception and processing. There were six variants found in eight cases. Of these eight individuals, three had suffered severe reactions to relatively minor head trauma.

In tier 3, the researchers identified mutations in eight neurotransmitter-related genes.

Through comparison with a general population control group, the researchers identified 43 different rare, amino acid–changing variants that occurred within 16 ion channel and ion channel transporter genes. These mutations were found in 53 individuals, at an approximately fivefold higher frequency than the control group (odds ratio, 5.6; P < .0001).

“We identified a number of rare genetic variants implicated in migraine — ion channel and other neurologically associated genes — in those suffering from post-traumatic headache,” said Dr. Griffiths. She also noted that the whole genomes they collected will allow for further analysis of other gene candidates in the future.

During the Q&A period, Dr. Griffiths was asked if the research group tracked the severity of the TBIs suffered by participants. She responded that they had not, and this was a limitation of the study.

Another questioner asked if parents should consider genetic testing for susceptibility mutations when considering whether to allow a child to participate in sports or activities with elevated risk of TBI. “I don’t necessarily think this is a bad thing,” she said, though she conceded that the work is still immature. “It’s probably a bit early because we haven’t identified all the genes that are involved or all the specific mutations ... but I think down the track, that makes perfect sense. Why would you not do some sensible preventive screening to aid with things like maybe you wear more headgear or you consider what’s the appropriate sport for that person?”

Laine Green, MD, assistant professor of neurology at Mayo Clinic Arizona, Phoenix, who moderated the session, was asked for comment. “I think the idea of potentially identifying people that have more genetic susceptibility to injuries is very intriguing, because post-traumatic headache and symptoms is always a difficult area to treat, potentially identifying those that with more genetic susceptibility might be helpful. It may also potentially allow us to target specific treatments, especially in this case, looking at different ion channels. There are medications that may work better at ion channel targets than other targets,” said Dr. Green.

He also endorsed the potential value of screening. “Speaking as a parent, I might like to know my child is at higher risk if they’re going to participate in contact sports or other high risk activities,” he said.

Dr. Griffiths and Dr. Green have no relevant financial disclosures.

SAN DIEGO — Susceptibility to post-traumatic headache could be linked to mutations in ion channel and ion transporter genes, according to results from a preliminary study.

Post-traumatic headache is a common symptom of traumatic brain injury (TBI).

There is evidence that genetic mutations could play a role in both TBI development and response. In particular, the S213L mutation for familial hemiplegic migraine-1 (FHM1), found in the CACNA1A gene, can cause individuals carrying it to be highly sensitive to otherwise trivial head impacts, according to Lyn Griffiths, PhD.

The consequences can be post-traumatic headache, but also seizures, cerebral edema, coma, or worse. Another form of FHM is associated with mutations in ATP1A2.

“This stimulated our interest in looking at genes that relate to TBI with a particular focus on ion channel genes,” said Dr. Griffiths, during a presentation of the study at the annual meeting of the American Headache Society.

The researchers analyzed data from 117 participants who had at least one concussion with a post-traumatic headache, and recruited family members when possible. There were 15 participants who developed severe reactions to trivial head trauma, 13 who had been diagnosed with concussion and underwent imaging related to TBI-associated symptoms, 54 who had been recruited through local sporting groups campuses, and 35 recruited through a medical research foundation. Blood or saliva samples were used to perform whole exome sequencing.

The researchers looked for gene candidates within different tiers. Tier 1 included genes that had already been implicated in severe migraine. The second tier included 353 ion channel and iron transporter genes. Tier 3 comprised neurotransmission-related genes.

After sequencing, the researchers filtered genetic mutations to include only those that affected amino acid composition of the protein, were predicted by two or more in silico analysis tools to be damaging, and were identified in multiple, unrelated patients.

In tier 2, the greatest number of potential damaging variants were found in the SCN9A gene, which is involved in pain perception and processing. There were six variants found in eight cases. Of these eight individuals, three had suffered severe reactions to relatively minor head trauma.

In tier 3, the researchers identified mutations in eight neurotransmitter-related genes.

Through comparison with a general population control group, the researchers identified 43 different rare, amino acid–changing variants that occurred within 16 ion channel and ion channel transporter genes. These mutations were found in 53 individuals, at an approximately fivefold higher frequency than the control group (odds ratio, 5.6; P < .0001).

“We identified a number of rare genetic variants implicated in migraine — ion channel and other neurologically associated genes — in those suffering from post-traumatic headache,” said Dr. Griffiths. She also noted that the whole genomes they collected will allow for further analysis of other gene candidates in the future.

During the Q&A period, Dr. Griffiths was asked if the research group tracked the severity of the TBIs suffered by participants. She responded that they had not, and this was a limitation of the study.

Another questioner asked if parents should consider genetic testing for susceptibility mutations when considering whether to allow a child to participate in sports or activities with elevated risk of TBI. “I don’t necessarily think this is a bad thing,” she said, though she conceded that the work is still immature. “It’s probably a bit early because we haven’t identified all the genes that are involved or all the specific mutations ... but I think down the track, that makes perfect sense. Why would you not do some sensible preventive screening to aid with things like maybe you wear more headgear or you consider what’s the appropriate sport for that person?”

Laine Green, MD, assistant professor of neurology at Mayo Clinic Arizona, Phoenix, who moderated the session, was asked for comment. “I think the idea of potentially identifying people that have more genetic susceptibility to injuries is very intriguing, because post-traumatic headache and symptoms is always a difficult area to treat, potentially identifying those that with more genetic susceptibility might be helpful. It may also potentially allow us to target specific treatments, especially in this case, looking at different ion channels. There are medications that may work better at ion channel targets than other targets,” said Dr. Green.

He also endorsed the potential value of screening. “Speaking as a parent, I might like to know my child is at higher risk if they’re going to participate in contact sports or other high risk activities,” he said.

Dr. Griffiths and Dr. Green have no relevant financial disclosures.

SAN DIEGO — Cognitive impairment, or “brain fog,” is a well-known effect of active migraines, but evidence is mounting that it is also common during interictal periods.

In fact, these effects may appear in the prodromal phase and carry through the headache and into the post-headache period, according to Richard Lipton, MD, who spoke about cognition and migraine at the annual meeting of the American Headache Society.

He pointed out existing evidence that migraine patients have cognitive impairment relative to the general population even during the interictal period. Such studies suggest that migraine, especially with aura, could be a risk factor for later dementia.

One important limitation of studies that compare people with migraines with controls is that a range of factors could explain an association between lower cognitive function and migraines, including socioeconomic factors, education, severe headaches requiring specialty care, and comorbidities, among others. Acute and preventative treatments could also affect cognition.

However, longitudinal studies of cognitive function in individual patients have been sparse. Questions remain, like whether cognitive performance differs between the headache period and the interictal period, as well as similar questions about the premonitory and post-drome phases. “And then there’s a long-term question: Do people with migraine show more interictal or ictal decline in cognitive performance relative to migraine-free controls?” said Dr. Lipton, professor of neurology at Albert Einstein College of Medicine in the Bronx, New York.

He showed evidence from a retrospective study by Lundbeck conducted at four sites that asked patients with chronic migraine about bothersome symptoms both before and after treatment. More than three-fourths (77.7%) rated “difficulty concentrating or thinking clearly” as a bothersome symptom.

Following treatment, 5.0% said their cognitive issues had completely improved, 32.0% that they were “very much” improved, 26.0% moderately improved, 23.0% slightly improved, and 14.0% not at all improved.

“I am not saying this is a rigorous study, but I am saying that it illustrates two points that are important for us today: One is that brain fog is very common in a subspecialty care sample of headache patients like the ones many of us treat, and it also suggests that there’s hope that treatment can improve cognitive impairment as migraine gets better,” said Dr. Lipton.

Cognition has received less attention than other migraine symptoms, and treatment can be a two-edged sword: “There’s some evidence that some treatments can reduce cognitive impairment, and obvious evidence that some treatments, topiramate and tricyclics, can induce cognitive impairment,” said Dr. Lipton.

Studies that compare cognition within the same patient at different time periods can get around some of the limitations of comparisons between populations, but face their own challenges. “Single shot” cognitive measures may not be reliably repeatable and differences seen on “good” versus “bad” days or proximity to recent headaches.

The solution, Dr. Lipton believes, is intensive repeated measures that avoid the practice effect, in which a participant improves at a test due to repetition.

He summarized a study that was presented later in the day at a poster session, which used smartphones or other devices to test 19 participants five times per day, over 5 days, in natural environments. Devices gathered both subjective and objective assessments of cognition, along with information on mood, stress, and status and fluctuations in pain, and have the potential to go further by measuring things like physical exertion, heart rate, pollution levels, and other variables.

“It clearly improves the reliability and the validity of cognitive assessment and makes it possible to link cognition to the stage of the headache cycle,” said Dr. Lipton.

The researchers found worse cognitive performance during the headache phase as compared with the interictal phase. “Objective cognitive performance measurably declines during the headache phase, and the next step is to fully control for acute medications that people may take during the headache phase,” said Dr. Lipton.

He expressed hope that improved measurements can improve outcomes, if it’s possible to identify therapies that don’t impact cognition. “We think it’s very likely that certain classes of acute and preventive medications may not cause cognitive impairment, and there is a strong hope that they may actually reduce the cognitive burden of disease and potentially even reduce cognitive decline. Those are areas that I’m very excited to explore in the future,” said Dr. Lipton.

The results emphasize the need to treat patients early, according to Nada Hindiyeh, MD, who attended the session and was asked for comment. “Generally, patients are going to come to you with episodic migraines. When migraines start to increase in frequency and severity, that means all of these other symptoms are going to come along with it and be increased in frequency and severity, so it’s important to recognize this early so you can get patients on the right treatments and preventives to really prevent these episodes from happening and prevent that cognitive decline,” said Dr. Hindiyeh, director of headache neurology at Metrodora Institute, West Valley City, Utah.

Dr. Lipton has financial relationships with Aeon, AbbVie/Allergan, Amgen, Biohaven, Dr. Reddy’s Laboratories, electroCore, Eli Lilly, GlaxoSmithKline, Lundbeck, Merck, Novartis, Pfizer, Teva, Axon, CoolTech, and Manistee. Dr. Hindiyeh has no relevant financial disclosures.

SAN DIEGO — Cognitive impairment, or “brain fog,” is a well-known effect of active migraines, but evidence is mounting that it is also common during interictal periods.

In fact, these effects may appear in the prodromal phase and carry through the headache and into the post-headache period, according to Richard Lipton, MD, who spoke about cognition and migraine at the annual meeting of the American Headache Society.

He pointed out existing evidence that migraine patients have cognitive impairment relative to the general population even during the interictal period. Such studies suggest that migraine, especially with aura, could be a risk factor for later dementia.

One important limitation of studies that compare people with migraines with controls is that a range of factors could explain an association between lower cognitive function and migraines, including socioeconomic factors, education, severe headaches requiring specialty care, and comorbidities, among others. Acute and preventative treatments could also affect cognition.

However, longitudinal studies of cognitive function in individual patients have been sparse. Questions remain, like whether cognitive performance differs between the headache period and the interictal period, as well as similar questions about the premonitory and post-drome phases. “And then there’s a long-term question: Do people with migraine show more interictal or ictal decline in cognitive performance relative to migraine-free controls?” said Dr. Lipton, professor of neurology at Albert Einstein College of Medicine in the Bronx, New York.

He showed evidence from a retrospective study by Lundbeck conducted at four sites that asked patients with chronic migraine about bothersome symptoms both before and after treatment. More than three-fourths (77.7%) rated “difficulty concentrating or thinking clearly” as a bothersome symptom.

Following treatment, 5.0% said their cognitive issues had completely improved, 32.0% that they were “very much” improved, 26.0% moderately improved, 23.0% slightly improved, and 14.0% not at all improved.

“I am not saying this is a rigorous study, but I am saying that it illustrates two points that are important for us today: One is that brain fog is very common in a subspecialty care sample of headache patients like the ones many of us treat, and it also suggests that there’s hope that treatment can improve cognitive impairment as migraine gets better,” said Dr. Lipton.

Cognition has received less attention than other migraine symptoms, and treatment can be a two-edged sword: “There’s some evidence that some treatments can reduce cognitive impairment, and obvious evidence that some treatments, topiramate and tricyclics, can induce cognitive impairment,” said Dr. Lipton.

Studies that compare cognition within the same patient at different time periods can get around some of the limitations of comparisons between populations, but face their own challenges. “Single shot” cognitive measures may not be reliably repeatable and differences seen on “good” versus “bad” days or proximity to recent headaches.

The solution, Dr. Lipton believes, is intensive repeated measures that avoid the practice effect, in which a participant improves at a test due to repetition.

He summarized a study that was presented later in the day at a poster session, which used smartphones or other devices to test 19 participants five times per day, over 5 days, in natural environments. Devices gathered both subjective and objective assessments of cognition, along with information on mood, stress, and status and fluctuations in pain, and have the potential to go further by measuring things like physical exertion, heart rate, pollution levels, and other variables.

“It clearly improves the reliability and the validity of cognitive assessment and makes it possible to link cognition to the stage of the headache cycle,” said Dr. Lipton.

The researchers found worse cognitive performance during the headache phase as compared with the interictal phase. “Objective cognitive performance measurably declines during the headache phase, and the next step is to fully control for acute medications that people may take during the headache phase,” said Dr. Lipton.

He expressed hope that improved measurements can improve outcomes, if it’s possible to identify therapies that don’t impact cognition. “We think it’s very likely that certain classes of acute and preventive medications may not cause cognitive impairment, and there is a strong hope that they may actually reduce the cognitive burden of disease and potentially even reduce cognitive decline. Those are areas that I’m very excited to explore in the future,” said Dr. Lipton.

The results emphasize the need to treat patients early, according to Nada Hindiyeh, MD, who attended the session and was asked for comment. “Generally, patients are going to come to you with episodic migraines. When migraines start to increase in frequency and severity, that means all of these other symptoms are going to come along with it and be increased in frequency and severity, so it’s important to recognize this early so you can get patients on the right treatments and preventives to really prevent these episodes from happening and prevent that cognitive decline,” said Dr. Hindiyeh, director of headache neurology at Metrodora Institute, West Valley City, Utah.

Dr. Lipton has financial relationships with Aeon, AbbVie/Allergan, Amgen, Biohaven, Dr. Reddy’s Laboratories, electroCore, Eli Lilly, GlaxoSmithKline, Lundbeck, Merck, Novartis, Pfizer, Teva, Axon, CoolTech, and Manistee. Dr. Hindiyeh has no relevant financial disclosures.

SAN DIEGO — Cognitive impairment, or “brain fog,” is a well-known effect of active migraines, but evidence is mounting that it is also common during interictal periods.

In fact, these effects may appear in the prodromal phase and carry through the headache and into the post-headache period, according to Richard Lipton, MD, who spoke about cognition and migraine at the annual meeting of the American Headache Society.

He pointed out existing evidence that migraine patients have cognitive impairment relative to the general population even during the interictal period. Such studies suggest that migraine, especially with aura, could be a risk factor for later dementia.

One important limitation of studies that compare people with migraines with controls is that a range of factors could explain an association between lower cognitive function and migraines, including socioeconomic factors, education, severe headaches requiring specialty care, and comorbidities, among others. Acute and preventative treatments could also affect cognition.

However, longitudinal studies of cognitive function in individual patients have been sparse. Questions remain, like whether cognitive performance differs between the headache period and the interictal period, as well as similar questions about the premonitory and post-drome phases. “And then there’s a long-term question: Do people with migraine show more interictal or ictal decline in cognitive performance relative to migraine-free controls?” said Dr. Lipton, professor of neurology at Albert Einstein College of Medicine in the Bronx, New York.

He showed evidence from a retrospective study by Lundbeck conducted at four sites that asked patients with chronic migraine about bothersome symptoms both before and after treatment. More than three-fourths (77.7%) rated “difficulty concentrating or thinking clearly” as a bothersome symptom.

Following treatment, 5.0% said their cognitive issues had completely improved, 32.0% that they were “very much” improved, 26.0% moderately improved, 23.0% slightly improved, and 14.0% not at all improved.

“I am not saying this is a rigorous study, but I am saying that it illustrates two points that are important for us today: One is that brain fog is very common in a subspecialty care sample of headache patients like the ones many of us treat, and it also suggests that there’s hope that treatment can improve cognitive impairment as migraine gets better,” said Dr. Lipton.

Cognition has received less attention than other migraine symptoms, and treatment can be a two-edged sword: “There’s some evidence that some treatments can reduce cognitive impairment, and obvious evidence that some treatments, topiramate and tricyclics, can induce cognitive impairment,” said Dr. Lipton.

Studies that compare cognition within the same patient at different time periods can get around some of the limitations of comparisons between populations, but face their own challenges. “Single shot” cognitive measures may not be reliably repeatable and differences seen on “good” versus “bad” days or proximity to recent headaches.

The solution, Dr. Lipton believes, is intensive repeated measures that avoid the practice effect, in which a participant improves at a test due to repetition.

He summarized a study that was presented later in the day at a poster session, which used smartphones or other devices to test 19 participants five times per day, over 5 days, in natural environments. Devices gathered both subjective and objective assessments of cognition, along with information on mood, stress, and status and fluctuations in pain, and have the potential to go further by measuring things like physical exertion, heart rate, pollution levels, and other variables.

“It clearly improves the reliability and the validity of cognitive assessment and makes it possible to link cognition to the stage of the headache cycle,” said Dr. Lipton.

The researchers found worse cognitive performance during the headache phase as compared with the interictal phase. “Objective cognitive performance measurably declines during the headache phase, and the next step is to fully control for acute medications that people may take during the headache phase,” said Dr. Lipton.

He expressed hope that improved measurements can improve outcomes, if it’s possible to identify therapies that don’t impact cognition. “We think it’s very likely that certain classes of acute and preventive medications may not cause cognitive impairment, and there is a strong hope that they may actually reduce the cognitive burden of disease and potentially even reduce cognitive decline. Those are areas that I’m very excited to explore in the future,” said Dr. Lipton.

The results emphasize the need to treat patients early, according to Nada Hindiyeh, MD, who attended the session and was asked for comment. “Generally, patients are going to come to you with episodic migraines. When migraines start to increase in frequency and severity, that means all of these other symptoms are going to come along with it and be increased in frequency and severity, so it’s important to recognize this early so you can get patients on the right treatments and preventives to really prevent these episodes from happening and prevent that cognitive decline,” said Dr. Hindiyeh, director of headache neurology at Metrodora Institute, West Valley City, Utah.

Dr. Lipton has financial relationships with Aeon, AbbVie/Allergan, Amgen, Biohaven, Dr. Reddy’s Laboratories, electroCore, Eli Lilly, GlaxoSmithKline, Lundbeck, Merck, Novartis, Pfizer, Teva, Axon, CoolTech, and Manistee. Dr. Hindiyeh has no relevant financial disclosures.

Among stroke survivors with diabetes or obesity, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduced secondary stroke risk by up to 16%, according to authors of a recent meta-analysis. With benefits across administration routes, dosing regimens, type 2 diabetes status, and total and nonfatal strokes, the findings could improve GLP-1 RA implementation by stroke specialists in patients with stroke history and concurrent type 2 diabetes or obesity, authors said. The study was published online in the International Journal of Stoke.

Extending Longevity

Agents including GLP-1 RAs that have been found to reduce cardiovascular events among patients with type 2 diabetes and patients who are overweight or obese also reduce risk of recurrent stroke among patients with a history of stroke who are overweight, obese, or have metabolic disease, said American Heart Association (AHA) Chief Clinical Science Officer Mitchell S. V. Elkind, MD, who was not involved with the study but was asked to comment.

“Stroke is a leading cause of mortality and the leading cause of serious long-term disability,” he added, “so medications that help to reduce that risk can play an important role in improving overall health and well-being and hopefully reducing premature mortality.”

Investigators Anastasia Adamou, MD, an internal medicine resident at AHEPA University Hospital in Thessaloniki, Greece, and colleagues searched MEDLINE and Scopus for cardiovascular outcome trials involving adults randomly assigned to GLP-1 RAs or placebo through November 2023, ultimately analyzing 11 randomized controlled trials (RCTs).

Among 60,380 participants in the nine studies that assessed total strokes, 2.5% of the GLP-1 RA group experienced strokes during follow-up, versus 3% in the placebo group (relative risk [RR] 0.85, 95% confidence interval [CI] 0.77-0.93). Regarding secondary outcomes, the GLP-1 RA group showed a significantly lower rate of nonfatal strokes versus patients on placebo (RR 0.87, 95% CI 0.79-0.95). Conversely, investigators observed no significant risk difference among the groups regarding fatal strokes, probably due to the low rate of events — 0.3% and 0.4% for treated and untreated patients, respectively.

Subgroup analyses revealed no interaction between dosing frequency and total, nonfatal, or fatal strokes. The investigators observed no difference in nonfatal strokes among participants by type 2 diabetes status and medication administration route (oral versus subcutaneous).

“The oral administration route could provide the advantage of lower local ecchymoses and allergic reactions due to subcutaneous infusions,” Dr. Adamou said in an interview. But because oral administration demands daily intake, she added, treatment adherence might be affected. “For this reason, our team performed another subgroup analysis to compare the once-a-day to the once-a-month administration. No interaction effect was again presented between the two subgroups. This outcome allows for personalization of the administration method for each patient.”

Addressing Underutilization

Despite more than 2 decades of widespread use and well-established effects on body weight, HbA1c, and cardiovascular risk, GLP-1 RAs remain underutilized, authors wrote. This is especially true in primary care, noted one study published in Clinical Diabetes.

“GLP-1 RAs have been used for many years to treat diabetic patients,” said Dr. Adamou. But because their impact on cardiovascular health regardless of diabetic status is only recently known, she said, physicians are exercising caution when prescribing this medication to patients without diabetes. “This is why more studies need to be available, especially RCTs.”

Most neurologists traditionally have left management of type 2 diabetes and other metabolic disorders to primary care doctors, said Dr. Elkind. “However, these medications are increasingly important to vascular risk reduction and should be considered part of the stroke specialist’s armamentarium.”

Vascular neurologists can play an important role in managing metabolic disease and obesity by recommending GLP-1 RAs for patients with a history of stroke, or by initiating these medications themselves, Dr. Elkind said. “These drugs are likely to become an important part of stroke patients’ medication regimens, along with antithrombotic agents, blood pressure control, and statins. Neurologists are well-positioned to educate other physicians about the important connections among brain, heart, and metabolic health.”

To that end, he said, the AHA will update guidelines for both primary and secondary stroke prevention as warranted by evidence supporting GLP-1 RAs and other medications that could impact stroke risk in type 2 diabetes and related metabolic disorders. However, no guidelines concerning use of GLP-1 RAs for secondary stroke prevention in obesity exist. Here, said Dr. Elkind, the AHA will continue building on its innovative Cardiovascular-Kidney Metabolic Health program, which includes clinical suggestions and may include more formal clinical practice guidelines as the evidence evolves.

Among the main drivers of the initiative, he said, is the recognition that cardiovascular disease — including stroke — is the major cause of death and morbidity among patients with obesity, type 2 diabetes, and metabolic disorders. “Stroke should be considered an important part of overall cardiovascular risk, and the findings that these drugs can help to reduce the risk of stroke specifically is an important additional reason for their use.”

Dr. Elkind and Dr. Adamou reported no conflicting interests. The authors received no financial support for the study.

Among stroke survivors with diabetes or obesity, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduced secondary stroke risk by up to 16%, according to authors of a recent meta-analysis. With benefits across administration routes, dosing regimens, type 2 diabetes status, and total and nonfatal strokes, the findings could improve GLP-1 RA implementation by stroke specialists in patients with stroke history and concurrent type 2 diabetes or obesity, authors said. The study was published online in the International Journal of Stoke.

Extending Longevity

Agents including GLP-1 RAs that have been found to reduce cardiovascular events among patients with type 2 diabetes and patients who are overweight or obese also reduce risk of recurrent stroke among patients with a history of stroke who are overweight, obese, or have metabolic disease, said American Heart Association (AHA) Chief Clinical Science Officer Mitchell S. V. Elkind, MD, who was not involved with the study but was asked to comment.

“Stroke is a leading cause of mortality and the leading cause of serious long-term disability,” he added, “so medications that help to reduce that risk can play an important role in improving overall health and well-being and hopefully reducing premature mortality.”

Investigators Anastasia Adamou, MD, an internal medicine resident at AHEPA University Hospital in Thessaloniki, Greece, and colleagues searched MEDLINE and Scopus for cardiovascular outcome trials involving adults randomly assigned to GLP-1 RAs or placebo through November 2023, ultimately analyzing 11 randomized controlled trials (RCTs).

Among 60,380 participants in the nine studies that assessed total strokes, 2.5% of the GLP-1 RA group experienced strokes during follow-up, versus 3% in the placebo group (relative risk [RR] 0.85, 95% confidence interval [CI] 0.77-0.93). Regarding secondary outcomes, the GLP-1 RA group showed a significantly lower rate of nonfatal strokes versus patients on placebo (RR 0.87, 95% CI 0.79-0.95). Conversely, investigators observed no significant risk difference among the groups regarding fatal strokes, probably due to the low rate of events — 0.3% and 0.4% for treated and untreated patients, respectively.

Subgroup analyses revealed no interaction between dosing frequency and total, nonfatal, or fatal strokes. The investigators observed no difference in nonfatal strokes among participants by type 2 diabetes status and medication administration route (oral versus subcutaneous).

“The oral administration route could provide the advantage of lower local ecchymoses and allergic reactions due to subcutaneous infusions,” Dr. Adamou said in an interview. But because oral administration demands daily intake, she added, treatment adherence might be affected. “For this reason, our team performed another subgroup analysis to compare the once-a-day to the once-a-month administration. No interaction effect was again presented between the two subgroups. This outcome allows for personalization of the administration method for each patient.”

Addressing Underutilization

Despite more than 2 decades of widespread use and well-established effects on body weight, HbA1c, and cardiovascular risk, GLP-1 RAs remain underutilized, authors wrote. This is especially true in primary care, noted one study published in Clinical Diabetes.

“GLP-1 RAs have been used for many years to treat diabetic patients,” said Dr. Adamou. But because their impact on cardiovascular health regardless of diabetic status is only recently known, she said, physicians are exercising caution when prescribing this medication to patients without diabetes. “This is why more studies need to be available, especially RCTs.”

Most neurologists traditionally have left management of type 2 diabetes and other metabolic disorders to primary care doctors, said Dr. Elkind. “However, these medications are increasingly important to vascular risk reduction and should be considered part of the stroke specialist’s armamentarium.”

Vascular neurologists can play an important role in managing metabolic disease and obesity by recommending GLP-1 RAs for patients with a history of stroke, or by initiating these medications themselves, Dr. Elkind said. “These drugs are likely to become an important part of stroke patients’ medication regimens, along with antithrombotic agents, blood pressure control, and statins. Neurologists are well-positioned to educate other physicians about the important connections among brain, heart, and metabolic health.”

To that end, he said, the AHA will update guidelines for both primary and secondary stroke prevention as warranted by evidence supporting GLP-1 RAs and other medications that could impact stroke risk in type 2 diabetes and related metabolic disorders. However, no guidelines concerning use of GLP-1 RAs for secondary stroke prevention in obesity exist. Here, said Dr. Elkind, the AHA will continue building on its innovative Cardiovascular-Kidney Metabolic Health program, which includes clinical suggestions and may include more formal clinical practice guidelines as the evidence evolves.

Among the main drivers of the initiative, he said, is the recognition that cardiovascular disease — including stroke — is the major cause of death and morbidity among patients with obesity, type 2 diabetes, and metabolic disorders. “Stroke should be considered an important part of overall cardiovascular risk, and the findings that these drugs can help to reduce the risk of stroke specifically is an important additional reason for their use.”

Dr. Elkind and Dr. Adamou reported no conflicting interests. The authors received no financial support for the study.

Among stroke survivors with diabetes or obesity, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduced secondary stroke risk by up to 16%, according to authors of a recent meta-analysis. With benefits across administration routes, dosing regimens, type 2 diabetes status, and total and nonfatal strokes, the findings could improve GLP-1 RA implementation by stroke specialists in patients with stroke history and concurrent type 2 diabetes or obesity, authors said. The study was published online in the International Journal of Stoke.

Extending Longevity

Agents including GLP-1 RAs that have been found to reduce cardiovascular events among patients with type 2 diabetes and patients who are overweight or obese also reduce risk of recurrent stroke among patients with a history of stroke who are overweight, obese, or have metabolic disease, said American Heart Association (AHA) Chief Clinical Science Officer Mitchell S. V. Elkind, MD, who was not involved with the study but was asked to comment.

“Stroke is a leading cause of mortality and the leading cause of serious long-term disability,” he added, “so medications that help to reduce that risk can play an important role in improving overall health and well-being and hopefully reducing premature mortality.”

Investigators Anastasia Adamou, MD, an internal medicine resident at AHEPA University Hospital in Thessaloniki, Greece, and colleagues searched MEDLINE and Scopus for cardiovascular outcome trials involving adults randomly assigned to GLP-1 RAs or placebo through November 2023, ultimately analyzing 11 randomized controlled trials (RCTs).

Among 60,380 participants in the nine studies that assessed total strokes, 2.5% of the GLP-1 RA group experienced strokes during follow-up, versus 3% in the placebo group (relative risk [RR] 0.85, 95% confidence interval [CI] 0.77-0.93). Regarding secondary outcomes, the GLP-1 RA group showed a significantly lower rate of nonfatal strokes versus patients on placebo (RR 0.87, 95% CI 0.79-0.95). Conversely, investigators observed no significant risk difference among the groups regarding fatal strokes, probably due to the low rate of events — 0.3% and 0.4% for treated and untreated patients, respectively.

Subgroup analyses revealed no interaction between dosing frequency and total, nonfatal, or fatal strokes. The investigators observed no difference in nonfatal strokes among participants by type 2 diabetes status and medication administration route (oral versus subcutaneous).

“The oral administration route could provide the advantage of lower local ecchymoses and allergic reactions due to subcutaneous infusions,” Dr. Adamou said in an interview. But because oral administration demands daily intake, she added, treatment adherence might be affected. “For this reason, our team performed another subgroup analysis to compare the once-a-day to the once-a-month administration. No interaction effect was again presented between the two subgroups. This outcome allows for personalization of the administration method for each patient.”

Addressing Underutilization

Despite more than 2 decades of widespread use and well-established effects on body weight, HbA1c, and cardiovascular risk, GLP-1 RAs remain underutilized, authors wrote. This is especially true in primary care, noted one study published in Clinical Diabetes.

“GLP-1 RAs have been used for many years to treat diabetic patients,” said Dr. Adamou. But because their impact on cardiovascular health regardless of diabetic status is only recently known, she said, physicians are exercising caution when prescribing this medication to patients without diabetes. “This is why more studies need to be available, especially RCTs.”

Most neurologists traditionally have left management of type 2 diabetes and other metabolic disorders to primary care doctors, said Dr. Elkind. “However, these medications are increasingly important to vascular risk reduction and should be considered part of the stroke specialist’s armamentarium.”

Vascular neurologists can play an important role in managing metabolic disease and obesity by recommending GLP-1 RAs for patients with a history of stroke, or by initiating these medications themselves, Dr. Elkind said. “These drugs are likely to become an important part of stroke patients’ medication regimens, along with antithrombotic agents, blood pressure control, and statins. Neurologists are well-positioned to educate other physicians about the important connections among brain, heart, and metabolic health.”

To that end, he said, the AHA will update guidelines for both primary and secondary stroke prevention as warranted by evidence supporting GLP-1 RAs and other medications that could impact stroke risk in type 2 diabetes and related metabolic disorders. However, no guidelines concerning use of GLP-1 RAs for secondary stroke prevention in obesity exist. Here, said Dr. Elkind, the AHA will continue building on its innovative Cardiovascular-Kidney Metabolic Health program, which includes clinical suggestions and may include more formal clinical practice guidelines as the evidence evolves.

Among the main drivers of the initiative, he said, is the recognition that cardiovascular disease — including stroke — is the major cause of death and morbidity among patients with obesity, type 2 diabetes, and metabolic disorders. “Stroke should be considered an important part of overall cardiovascular risk, and the findings that these drugs can help to reduce the risk of stroke specifically is an important additional reason for their use.”

Dr. Elkind and Dr. Adamou reported no conflicting interests. The authors received no financial support for the study.

It’s time to renew two of my three narcotic prescribing licenses. For the first time in my career, I’ve waffled on whether the financial outlay to the US Drug Enforcement Agency (DEA) is worth it. 

At $888 each, I’ve considered letting two licenses lapse because I only work part-time in Montana. But several friends advised me to keep a “spare” in case I transfer to a new location. 

I thought about just paying the fees until I could do a little more research, but there is no mechanism for a refund unless I die within the first year of the 3-year cycle, provide incorrect credit card digits, or accidentally duplicate payments.

The renewal fee is just part of the issue.
 

Mandatory 8-Hour Training

I also received an alert about the requirement for more “narcotics prescribing education” thanks to the Medication Access and Training Expansion Act (MATE). 

The requirement seems counterintuitive because opioid prescribing has decreased for the 10th consecutive year, according to the AMA Overdose Epidemic Report. The continuing rise in overdose deaths is largely due to illegitimate manufacturing of synthetic opioids. 

I’ve written zero outpatient narcotics prescriptions in the past 6 years, and I’ve written very few in my 33 years of practice. My use is limited to intravenous morphine for flash pulmonary edema or refractory angina, but unless you graduated from a training program within 5 years of the June 2023 mandate or are boarded in addiction medicine, there is no way to escape the 8-hour education requirement.

The problem is that these courses are never just 8 hours in duration. After signing up for one such CME course that cost $150, I was still dying of boredom and at risk for DVT 4 days later. That’s how long it took to sit through.

Instead of the 30 seconds it should have taken to review the simple instructions to deliver Narcan, there were scores of screens followed by juvenile quizlets and cartoons. All but about 2 hours out of the 4 days is now relegated to that category of “hours of my life that I can never get back.” Additionally, none of that mandatory “education” will change my prescribing habits one whit. 

And beware the penalty. 

Changes Needed

The only good thing that came of those 4 long days of opioid education was a motivation to drive change in our current licensing and educational experience. Why not use this opportunity to reform the DEA-physician/prescriber relationship? 

The educational requirements should be curtailed for those of us who do not provide outpatient narcotic prescriptions even if we use inpatient opioids. Meds with low abuse potential should be rescheduled to minimize who gets caught in the broad net of the education requirement. 

We should reduce overregulation of the legitimate prescribers by lowering, instead of increasing, licensing fees. We should change to a single license number that covers every state. In this digital age, there is no legitimate excuse to prevent this from happening. 

After all, the settlements from opioid manufacturers and distributors will in time total $50 billion. It seems that at least some of the responsibilities of the DEA could shift to states, cities, and towns. 

My friend Siamak Karimian, MD, who provides locum services in multiple states, pays for seven active DEA licenses every 3 years. He pointed out the hypocrisy in the current regulatory system: “It’s funny that you can have only one DEA or state license and work for the government in all other states or territories with no limits, including the VA, Indian healthcare systems, or prison systems.”

All other prescribers require a separate DEA number for every state. Ultimately, you’d think tracking prescriptions for a single DEA number should be far simpler than tracking someone with seven. 

Competent physicians not guilty of criminal overprescribing seem to be the last to be considered in nearly every healthcare endeavor these days. It would be refreshing if they would reduce our fees and prevent this waste of our time. 

And while we are at it, perhaps a more fitting punishment is due for Richard Sackler and all the Purdue Pharma–affiliated family members. The Sacklers will pay out $6 billion in exchange for immunity against civil litigation. That doesn’t seem like much when they are worth $11 billion. 

Perhaps they should be made to take an 8-hour course on opioid prescribing, annually and in perpetuity. Let’s see them complete a few quizlets and sit through screens of instruction on how to administer Naloxone. Of course, that would be a mild punishment for those who manufactured a drug that killed hundreds of thousands. But it would be a start. 
 

Dr. Walton-Shirley, a clinical cardiologist in Nashville, Tennessee, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

It’s time to renew two of my three narcotic prescribing licenses. For the first time in my career, I’ve waffled on whether the financial outlay to the US Drug Enforcement Agency (DEA) is worth it. 

At $888 each, I’ve considered letting two licenses lapse because I only work part-time in Montana. But several friends advised me to keep a “spare” in case I transfer to a new location. 

I thought about just paying the fees until I could do a little more research, but there is no mechanism for a refund unless I die within the first year of the 3-year cycle, provide incorrect credit card digits, or accidentally duplicate payments.

The renewal fee is just part of the issue.
 

Mandatory 8-Hour Training

I also received an alert about the requirement for more “narcotics prescribing education” thanks to the Medication Access and Training Expansion Act (MATE). 

The requirement seems counterintuitive because opioid prescribing has decreased for the 10th consecutive year, according to the AMA Overdose Epidemic Report. The continuing rise in overdose deaths is largely due to illegitimate manufacturing of synthetic opioids. 

I’ve written zero outpatient narcotics prescriptions in the past 6 years, and I’ve written very few in my 33 years of practice. My use is limited to intravenous morphine for flash pulmonary edema or refractory angina, but unless you graduated from a training program within 5 years of the June 2023 mandate or are boarded in addiction medicine, there is no way to escape the 8-hour education requirement.

The problem is that these courses are never just 8 hours in duration. After signing up for one such CME course that cost $150, I was still dying of boredom and at risk for DVT 4 days later. That’s how long it took to sit through.

Instead of the 30 seconds it should have taken to review the simple instructions to deliver Narcan, there were scores of screens followed by juvenile quizlets and cartoons. All but about 2 hours out of the 4 days is now relegated to that category of “hours of my life that I can never get back.” Additionally, none of that mandatory “education” will change my prescribing habits one whit. 

And beware the penalty. 

Changes Needed

The only good thing that came of those 4 long days of opioid education was a motivation to drive change in our current licensing and educational experience. Why not use this opportunity to reform the DEA-physician/prescriber relationship? 

The educational requirements should be curtailed for those of us who do not provide outpatient narcotic prescriptions even if we use inpatient opioids. Meds with low abuse potential should be rescheduled to minimize who gets caught in the broad net of the education requirement. 

We should reduce overregulation of the legitimate prescribers by lowering, instead of increasing, licensing fees. We should change to a single license number that covers every state. In this digital age, there is no legitimate excuse to prevent this from happening. 

After all, the settlements from opioid manufacturers and distributors will in time total $50 billion. It seems that at least some of the responsibilities of the DEA could shift to states, cities, and towns. 

My friend Siamak Karimian, MD, who provides locum services in multiple states, pays for seven active DEA licenses every 3 years. He pointed out the hypocrisy in the current regulatory system: “It’s funny that you can have only one DEA or state license and work for the government in all other states or territories with no limits, including the VA, Indian healthcare systems, or prison systems.”

All other prescribers require a separate DEA number for every state. Ultimately, you’d think tracking prescriptions for a single DEA number should be far simpler than tracking someone with seven. 

Competent physicians not guilty of criminal overprescribing seem to be the last to be considered in nearly every healthcare endeavor these days. It would be refreshing if they would reduce our fees and prevent this waste of our time. 

And while we are at it, perhaps a more fitting punishment is due for Richard Sackler and all the Purdue Pharma–affiliated family members. The Sacklers will pay out $6 billion in exchange for immunity against civil litigation. That doesn’t seem like much when they are worth $11 billion. 

Perhaps they should be made to take an 8-hour course on opioid prescribing, annually and in perpetuity. Let’s see them complete a few quizlets and sit through screens of instruction on how to administer Naloxone. Of course, that would be a mild punishment for those who manufactured a drug that killed hundreds of thousands. But it would be a start. 
 

Dr. Walton-Shirley, a clinical cardiologist in Nashville, Tennessee, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

It’s time to renew two of my three narcotic prescribing licenses. For the first time in my career, I’ve waffled on whether the financial outlay to the US Drug Enforcement Agency (DEA) is worth it. 

At $888 each, I’ve considered letting two licenses lapse because I only work part-time in Montana. But several friends advised me to keep a “spare” in case I transfer to a new location. 

I thought about just paying the fees until I could do a little more research, but there is no mechanism for a refund unless I die within the first year of the 3-year cycle, provide incorrect credit card digits, or accidentally duplicate payments.

The renewal fee is just part of the issue.
 

Mandatory 8-Hour Training

I also received an alert about the requirement for more “narcotics prescribing education” thanks to the Medication Access and Training Expansion Act (MATE). 

The requirement seems counterintuitive because opioid prescribing has decreased for the 10th consecutive year, according to the AMA Overdose Epidemic Report. The continuing rise in overdose deaths is largely due to illegitimate manufacturing of synthetic opioids. 

I’ve written zero outpatient narcotics prescriptions in the past 6 years, and I’ve written very few in my 33 years of practice. My use is limited to intravenous morphine for flash pulmonary edema or refractory angina, but unless you graduated from a training program within 5 years of the June 2023 mandate or are boarded in addiction medicine, there is no way to escape the 8-hour education requirement.

The problem is that these courses are never just 8 hours in duration. After signing up for one such CME course that cost $150, I was still dying of boredom and at risk for DVT 4 days later. That’s how long it took to sit through.

Instead of the 30 seconds it should have taken to review the simple instructions to deliver Narcan, there were scores of screens followed by juvenile quizlets and cartoons. All but about 2 hours out of the 4 days is now relegated to that category of “hours of my life that I can never get back.” Additionally, none of that mandatory “education” will change my prescribing habits one whit. 

And beware the penalty. 

Changes Needed

The only good thing that came of those 4 long days of opioid education was a motivation to drive change in our current licensing and educational experience. Why not use this opportunity to reform the DEA-physician/prescriber relationship? 

The educational requirements should be curtailed for those of us who do not provide outpatient narcotic prescriptions even if we use inpatient opioids. Meds with low abuse potential should be rescheduled to minimize who gets caught in the broad net of the education requirement. 

We should reduce overregulation of the legitimate prescribers by lowering, instead of increasing, licensing fees. We should change to a single license number that covers every state. In this digital age, there is no legitimate excuse to prevent this from happening. 

After all, the settlements from opioid manufacturers and distributors will in time total $50 billion. It seems that at least some of the responsibilities of the DEA could shift to states, cities, and towns. 

My friend Siamak Karimian, MD, who provides locum services in multiple states, pays for seven active DEA licenses every 3 years. He pointed out the hypocrisy in the current regulatory system: “It’s funny that you can have only one DEA or state license and work for the government in all other states or territories with no limits, including the VA, Indian healthcare systems, or prison systems.”

All other prescribers require a separate DEA number for every state. Ultimately, you’d think tracking prescriptions for a single DEA number should be far simpler than tracking someone with seven. 

Competent physicians not guilty of criminal overprescribing seem to be the last to be considered in nearly every healthcare endeavor these days. It would be refreshing if they would reduce our fees and prevent this waste of our time. 

And while we are at it, perhaps a more fitting punishment is due for Richard Sackler and all the Purdue Pharma–affiliated family members. The Sacklers will pay out $6 billion in exchange for immunity against civil litigation. That doesn’t seem like much when they are worth $11 billion. 

Perhaps they should be made to take an 8-hour course on opioid prescribing, annually and in perpetuity. Let’s see them complete a few quizlets and sit through screens of instruction on how to administer Naloxone. Of course, that would be a mild punishment for those who manufactured a drug that killed hundreds of thousands. But it would be a start. 
 

Dr. Walton-Shirley, a clinical cardiologist in Nashville, Tennessee, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

For decades, scientists have been trying to unravel the mysteries of restless legs syndrome (RLS), a poorly understood and underdiagnosed neurological disorder causing itching, crawling, and aching sensations in the limbs that can only be relieved with movement.

A sweeping new genetic study, coauthored by an international team of 70 — including the world’s leading RLS experts — marks a significant advance in that pursuit. Published in Nature Genetics, it is the largest genetic study of the disease to date.

“It’s a huge step forward for patients as well as the scientific community,” said lead author Juliane Winkelmann, MD, a neurologist and geneticist with the Technical University of Munich, Munich, Germany, who’s been studying and treating patients with RLS for 30 years. “We believe it will allow us to better predict the likelihood of developing RLS and investigate new ways to prevent and modify it.”

The common condition, affecting about 1 in 10 adults, was first described centuries ago — by English physician Thomas Willis in the late 1600s. And while we know a lot more about it today — it’s familial in about half of all patients and has been linked to iron deficiency, among other conditions — its exact cause remains unknown.

With preferred drugs long prescribed to quell symptoms shown in recent years to actually worsen the disorder over time, doctors and patients are hungry for alternatives to treat or prevent the sleep-sabotaging condition.

“The main treatments that everybody continues to use are actually making people worse,” said Andrew Berkowski, MD, a Michigan-based neurologist and RLS specialist not involved in the study. These drugs — dopamine agonists such as levodopa and pramipexole — can also potentially cause drug dependence, Dr. Berkowski said.
 

How This Could Lead to New Treatments

In the new study, the group analyzed three genome-wide association studies, collectively including genetic information from 116,647 patients with RLS and more than 1.5 million people without it.

They identified 161 gene regions believed to contribute to RLS, about a dozen of which are already targets for existing drugs for other conditions. Previously, scientists knew of only 22 associated genes.

“It’s useful in that it identifies new genes we haven’t looked at yet and reinforces the science behind some of the older genes,” said Dr. Berkowski. “It’s given us some ideas for different things we should look into more closely.”

Among the top candidates are genes that influence glutamate — a key chemical messenger that helps move signals between nerve cells in the brain.

Several anticonvulsant and antiseizure drugs, including perampanel, lamotrigine, and gabapentin, target glutamate receptors. And at least one small study has shown perampanel prescribed off-label can improve RLS symptoms.

“Compared to starting at the beginning and developing an entirely new chemical entity, we could run clinical trials using these alternatives in RLS patients,” said the study’s first author, Steven Bell, PhD, an epidemiologist with the University of Cambridge, Cambridge, England.

The study also confirmed the MIES1 gene, which is related to dopamine expression and iron homeostasis, as a key genetic contributor to RLS risk. Low levels of iron in the blood have long been thought to trigger RLS.
 

The Role of Gene-Environment Interactions

Through additional data analysis, the team confirmed that many of the genes associated with RLS play a role in development of the central nervous system.

“This strongly supports the hypothesis that restless legs syndrome is a neurodevelopmental disorder that develops during the embryo stage but doesn’t clinically manifest until later in life,” said Dr. Winkelmann.

About half of people with RLS report some family history of it.

But not all with a genetic predisposition will develop symptoms.

For instance, the study found that while the same gene regions seem to be associated with risk in both men and women, in practice, RLS is twice as common among women. This suggests that something about women’s lives — menstruation, childbirth, metabolism — may switch a preexisting risk into a reality.

“We know that genetic factors play an important role in making people susceptible to the disease,” said Dr. Winkelmann, “but in the end, it is the interaction between genetic and environmental factors that may lead to its manifestation.”

The study also found associations between RLS and depression and suggests that RLS may increase the risk for type 2 diabetes.
 

Improving RLS Care

A potentially useful tool coming out of the study was a “polygenic risk score,” which the researchers developed based on the genes identified. When they tested how accurately the score could predict whether someone would develop RLS within the next 5 years, the model got it right about 90% of the time.

Dr. Winkelmann imagines a day when someone could use such a polygenic risk score to flag the high risk for RLS early enough to take action to try to prevent it. More research is necessary to determine precisely what that action would be.

As for treatments, Dr. Berkowski thinks it’s unlikely that doctors will suddenly begin using existing, glutamate-targeting drugs off-label to treat RLS, as many are prohibitively expensive and wouldn’t be covered by insurance. But he’s optimistic that the study can spawn new research that could ultimately help fill the treatment gap.

Shalini Paruthi, MD, an adjunct professor at Saint Louis University, St. Louis, Missouri, and chair of the Restless Legs Syndrome Foundation’s board of directors, sees another benefit.

“The associations found in this study between RLS and other medical disorders may help patients and their physicians take RLS more seriously,” Dr. Paruthi said, “as treating RLS can lead to multiple other downstream improvements in their health.”

A version of this article appeared on Medscape.com.

For decades, scientists have been trying to unravel the mysteries of restless legs syndrome (RLS), a poorly understood and underdiagnosed neurological disorder causing itching, crawling, and aching sensations in the limbs that can only be relieved with movement.

A sweeping new genetic study, coauthored by an international team of 70 — including the world’s leading RLS experts — marks a significant advance in that pursuit. Published in Nature Genetics, it is the largest genetic study of the disease to date.

“It’s a huge step forward for patients as well as the scientific community,” said lead author Juliane Winkelmann, MD, a neurologist and geneticist with the Technical University of Munich, Munich, Germany, who’s been studying and treating patients with RLS for 30 years. “We believe it will allow us to better predict the likelihood of developing RLS and investigate new ways to prevent and modify it.”

The common condition, affecting about 1 in 10 adults, was first described centuries ago — by English physician Thomas Willis in the late 1600s. And while we know a lot more about it today — it’s familial in about half of all patients and has been linked to iron deficiency, among other conditions — its exact cause remains unknown.

With preferred drugs long prescribed to quell symptoms shown in recent years to actually worsen the disorder over time, doctors and patients are hungry for alternatives to treat or prevent the sleep-sabotaging condition.

“The main treatments that everybody continues to use are actually making people worse,” said Andrew Berkowski, MD, a Michigan-based neurologist and RLS specialist not involved in the study. These drugs — dopamine agonists such as levodopa and pramipexole — can also potentially cause drug dependence, Dr. Berkowski said.
 

How This Could Lead to New Treatments

In the new study, the group analyzed three genome-wide association studies, collectively including genetic information from 116,647 patients with RLS and more than 1.5 million people without it.

They identified 161 gene regions believed to contribute to RLS, about a dozen of which are already targets for existing drugs for other conditions. Previously, scientists knew of only 22 associated genes.

“It’s useful in that it identifies new genes we haven’t looked at yet and reinforces the science behind some of the older genes,” said Dr. Berkowski. “It’s given us some ideas for different things we should look into more closely.”

Among the top candidates are genes that influence glutamate — a key chemical messenger that helps move signals between nerve cells in the brain.

Several anticonvulsant and antiseizure drugs, including perampanel, lamotrigine, and gabapentin, target glutamate receptors. And at least one small study has shown perampanel prescribed off-label can improve RLS symptoms.

“Compared to starting at the beginning and developing an entirely new chemical entity, we could run clinical trials using these alternatives in RLS patients,” said the study’s first author, Steven Bell, PhD, an epidemiologist with the University of Cambridge, Cambridge, England.

The study also confirmed the MIES1 gene, which is related to dopamine expression and iron homeostasis, as a key genetic contributor to RLS risk. Low levels of iron in the blood have long been thought to trigger RLS.
 

The Role of Gene-Environment Interactions

Through additional data analysis, the team confirmed that many of the genes associated with RLS play a role in development of the central nervous system.

“This strongly supports the hypothesis that restless legs syndrome is a neurodevelopmental disorder that develops during the embryo stage but doesn’t clinically manifest until later in life,” said Dr. Winkelmann.

About half of people with RLS report some family history of it.

But not all with a genetic predisposition will develop symptoms.

For instance, the study found that while the same gene regions seem to be associated with risk in both men and women, in practice, RLS is twice as common among women. This suggests that something about women’s lives — menstruation, childbirth, metabolism — may switch a preexisting risk into a reality.

“We know that genetic factors play an important role in making people susceptible to the disease,” said Dr. Winkelmann, “but in the end, it is the interaction between genetic and environmental factors that may lead to its manifestation.”

The study also found associations between RLS and depression and suggests that RLS may increase the risk for type 2 diabetes.
 

Improving RLS Care

A potentially useful tool coming out of the study was a “polygenic risk score,” which the researchers developed based on the genes identified. When they tested how accurately the score could predict whether someone would develop RLS within the next 5 years, the model got it right about 90% of the time.

Dr. Winkelmann imagines a day when someone could use such a polygenic risk score to flag the high risk for RLS early enough to take action to try to prevent it. More research is necessary to determine precisely what that action would be.

As for treatments, Dr. Berkowski thinks it’s unlikely that doctors will suddenly begin using existing, glutamate-targeting drugs off-label to treat RLS, as many are prohibitively expensive and wouldn’t be covered by insurance. But he’s optimistic that the study can spawn new research that could ultimately help fill the treatment gap.

Shalini Paruthi, MD, an adjunct professor at Saint Louis University, St. Louis, Missouri, and chair of the Restless Legs Syndrome Foundation’s board of directors, sees another benefit.

“The associations found in this study between RLS and other medical disorders may help patients and their physicians take RLS more seriously,” Dr. Paruthi said, “as treating RLS can lead to multiple other downstream improvements in their health.”

A version of this article appeared on Medscape.com.

For decades, scientists have been trying to unravel the mysteries of restless legs syndrome (RLS), a poorly understood and underdiagnosed neurological disorder causing itching, crawling, and aching sensations in the limbs that can only be relieved with movement.

A sweeping new genetic study, coauthored by an international team of 70 — including the world’s leading RLS experts — marks a significant advance in that pursuit. Published in Nature Genetics, it is the largest genetic study of the disease to date.

“It’s a huge step forward for patients as well as the scientific community,” said lead author Juliane Winkelmann, MD, a neurologist and geneticist with the Technical University of Munich, Munich, Germany, who’s been studying and treating patients with RLS for 30 years. “We believe it will allow us to better predict the likelihood of developing RLS and investigate new ways to prevent and modify it.”

The common condition, affecting about 1 in 10 adults, was first described centuries ago — by English physician Thomas Willis in the late 1600s. And while we know a lot more about it today — it’s familial in about half of all patients and has been linked to iron deficiency, among other conditions — its exact cause remains unknown.

With preferred drugs long prescribed to quell symptoms shown in recent years to actually worsen the disorder over time, doctors and patients are hungry for alternatives to treat or prevent the sleep-sabotaging condition.

“The main treatments that everybody continues to use are actually making people worse,” said Andrew Berkowski, MD, a Michigan-based neurologist and RLS specialist not involved in the study. These drugs — dopamine agonists such as levodopa and pramipexole — can also potentially cause drug dependence, Dr. Berkowski said.
 

How This Could Lead to New Treatments

In the new study, the group analyzed three genome-wide association studies, collectively including genetic information from 116,647 patients with RLS and more than 1.5 million people without it.

They identified 161 gene regions believed to contribute to RLS, about a dozen of which are already targets for existing drugs for other conditions. Previously, scientists knew of only 22 associated genes.

“It’s useful in that it identifies new genes we haven’t looked at yet and reinforces the science behind some of the older genes,” said Dr. Berkowski. “It’s given us some ideas for different things we should look into more closely.”

Among the top candidates are genes that influence glutamate — a key chemical messenger that helps move signals between nerve cells in the brain.

Several anticonvulsant and antiseizure drugs, including perampanel, lamotrigine, and gabapentin, target glutamate receptors. And at least one small study has shown perampanel prescribed off-label can improve RLS symptoms.

“Compared to starting at the beginning and developing an entirely new chemical entity, we could run clinical trials using these alternatives in RLS patients,” said the study’s first author, Steven Bell, PhD, an epidemiologist with the University of Cambridge, Cambridge, England.

The study also confirmed the MIES1 gene, which is related to dopamine expression and iron homeostasis, as a key genetic contributor to RLS risk. Low levels of iron in the blood have long been thought to trigger RLS.
 

The Role of Gene-Environment Interactions

Through additional data analysis, the team confirmed that many of the genes associated with RLS play a role in development of the central nervous system.

“This strongly supports the hypothesis that restless legs syndrome is a neurodevelopmental disorder that develops during the embryo stage but doesn’t clinically manifest until later in life,” said Dr. Winkelmann.

About half of people with RLS report some family history of it.

But not all with a genetic predisposition will develop symptoms.

For instance, the study found that while the same gene regions seem to be associated with risk in both men and women, in practice, RLS is twice as common among women. This suggests that something about women’s lives — menstruation, childbirth, metabolism — may switch a preexisting risk into a reality.

“We know that genetic factors play an important role in making people susceptible to the disease,” said Dr. Winkelmann, “but in the end, it is the interaction between genetic and environmental factors that may lead to its manifestation.”

The study also found associations between RLS and depression and suggests that RLS may increase the risk for type 2 diabetes.
 

Improving RLS Care

A potentially useful tool coming out of the study was a “polygenic risk score,” which the researchers developed based on the genes identified. When they tested how accurately the score could predict whether someone would develop RLS within the next 5 years, the model got it right about 90% of the time.

Dr. Winkelmann imagines a day when someone could use such a polygenic risk score to flag the high risk for RLS early enough to take action to try to prevent it. More research is necessary to determine precisely what that action would be.

As for treatments, Dr. Berkowski thinks it’s unlikely that doctors will suddenly begin using existing, glutamate-targeting drugs off-label to treat RLS, as many are prohibitively expensive and wouldn’t be covered by insurance. But he’s optimistic that the study can spawn new research that could ultimately help fill the treatment gap.

Shalini Paruthi, MD, an adjunct professor at Saint Louis University, St. Louis, Missouri, and chair of the Restless Legs Syndrome Foundation’s board of directors, sees another benefit.

“The associations found in this study between RLS and other medical disorders may help patients and their physicians take RLS more seriously,” Dr. Paruthi said, “as treating RLS can lead to multiple other downstream improvements in their health.”

A version of this article appeared on Medscape.com.

VIENNA — Results from the phase 3 SELECT-GCA study showed that the Janus kinase (JAK) inhibitor upadacitinib (Rinvoq) induces significant and sustained remission in people with new-onset or relapsing giant cell arteritis (GCA).

The primary endpoint of sustained remission — the absence of GCA signs or symptoms from weeks 12 to 52 together with adherence to a steroid-tapering regimen — occurred in 46% of 210 individuals randomly assigned to treatment treated with a once-daily 15-mg dose of upadacitinib and 29% of 105 randomly assigned to placebo (P = .0019).

Nine of the 11 secondary endpoints were also positive for upadacitinib 15 mg vs placebo, and no new safety concerns were identified in a late-breaking abstract presented at the at the annual European Congress of Rheumatology.
 

First JAK Trial in GCA

This is the first trial to look at the use of a JAK inhibitor for the treatment of GCA, and it is addressing a real unmet need, the presenting study investigator Daniel Blockmans, MD, PhD, of University Hospitals Leuven in Belgium, told this news organization.

Glucocorticoids remain the mainstay of treatment, and tocilizumab has been licensed for use, but people don’t always get better or can relapse, he explained.

“I have the impression that these only suppress the disease but do not cure it,” Dr. Blockmans said, adding that “patients get very well soon after these treatments are started, but there are more and more reports that there is a kind of smoldering vasculitis that exists, and this can lead to dilatation of the aorta.”

Upadacitinib inhibits two JAK-dependent cytokines, interleukin 6 and interferon gamma, which have been implicated in the pathogenesis of GCA. The latter could be particularly important, Dr. Blockmans suggested.
 

Study Details

SELECT-GCA is an ongoing multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of upadacitinib vs placebo in patients with GCA.

A total of 428 patients have been included: 210 were randomly allocated to treatment with upadacitinib 15 mg, 105 to upadacitinib 7.5 mg, and 105 to placebo. The inclusion of the lower “minimally effective” upadacitinib dose was a requirement of the regulatory authorities, Dr. Blockmans said; the licensed dose in rheumatoid arthritis (RA) is 15 mg.

Dr. Blockmans reported data from the first 52 weeks of the trial during which all patients underwent glucocorticoid tapering — 26 weeks for upadacitinib and 52 weeks for placebo.

No imaging was done in this trial, which Dr. Blockmans said should be considered for future studies.
 

Secondary Endpoints

One of the key secondary endpoints was sustained complete remission, defined as sustained remission plus a normalized erythrocyte sedimentation rate to ≤ 30 mm/h and reducing high-sensitivity C-reactive protein to < 1 mg/dL.

Sustained complete remission occurred in 37% and 16% of patients treated with upadacitinib 15 mg and placebo, respectively (P < .0001).

Additionally, a significantly lower proportion of upadacitinib 15 mg- than placebo-treated patients experienced at least one disease flare through week 52 (34% vs 56%, P = .0014).

Other positive secondary endpoints for upadacitinib 15 mg vs placebo out to week 52 were the number of disease flares per patient, cumulative glucocorticoid exposure, and complete remission (also at week 24).

And significant changes in SF-36 and FACIT-Fatigue from baseline to week 52 were seen for upadacitinib 15 mg.

The only secondary endpoints not showing a clear benefit for upadacitinib 15 mg were the changes in the Treatment Satisfaction Questionnaire for Medication at 52 weeks and the rate of glucocorticoid-related adverse events through week 52.

As for the 7.5-mg dose of upadacitinib, neither the primary nor secondary endpoints were significantly better vs placebo.
 

‘Life-Changing’

The study’s findings could be “really life-changing” for patients with this type of vasculitis if upadacitinib gets approval for use in this indication, Milena Bond, MD, PhD, of Brunico Hospital in Italy, told this news organization at the meeting.

“Unfortunately, nowadays, we still have only a few options for treating these patients,” she said. “So, this drug could be really, really important.”

Dr. Bond added: “The data ... also shows there is a very good safety profile, which was a main concern given the class of the drug. So, I’m very positive about this treatment and very excited to see the preliminary results.”

After his presentation, Dr. Blockmans said, “Of course, if we already had an ideal treatment for GCA, there would be no need for a JAK inhibitor, but I don’t think that steroid treatment or tocilizumab treatment is the ideal treatment.”
 

Judicious Use Still Warranted

Upadacitinib still needs to be used cautiously, following appropriate guidance from the European Medicines Agency (EMA) and the US Food and Drug Administration.

Dr. Bond said: “It is not advised to use to the drug when people are older than 65 years old,” according to the EMA, for example, and “given the rules that we have, I would not use this drug as a first-line treatment. We do not do that for rheumatoid arthritis.”

But, she added, “As for arthritis, when you fail treating patients with the other alternatives, you could use this drug, and you have to discuss risks with the patients.”

Dr. Blockmans reported there had been no increased risk for major adverse cardiovascular events or venous thromboembolism associated with upadacitinib relative to placebo in the population of patients studied, and he pointed out that they had a much higher risk for these events than perhaps an RA population.

He said: “It’s effective, and it’s apparently safe in these older people, despite what we heard about tofacitinib in the ORAL [Surveillance] study; we didn’t see these problems here in this elderly population.”

The SELECT-GCA trial was funded by AbbVie, and the company participated in all aspects of the study, including its design, conduct, interpretation of data, and reporting. Dr. Blockmans received no funding or other honoraria from the company but reported a research grant from Roche and consulting fees from GlaxoSmithKline. Most of his coauthors reported financial relationships with AbbVie, and some are employees of the company. Dr. Bond reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

VIENNA — Results from the phase 3 SELECT-GCA study showed that the Janus kinase (JAK) inhibitor upadacitinib (Rinvoq) induces significant and sustained remission in people with new-onset or relapsing giant cell arteritis (GCA).

The primary endpoint of sustained remission — the absence of GCA signs or symptoms from weeks 12 to 52 together with adherence to a steroid-tapering regimen — occurred in 46% of 210 individuals randomly assigned to treatment treated with a once-daily 15-mg dose of upadacitinib and 29% of 105 randomly assigned to placebo (P = .0019).

Nine of the 11 secondary endpoints were also positive for upadacitinib 15 mg vs placebo, and no new safety concerns were identified in a late-breaking abstract presented at the at the annual European Congress of Rheumatology.
 

First JAK Trial in GCA

This is the first trial to look at the use of a JAK inhibitor for the treatment of GCA, and it is addressing a real unmet need, the presenting study investigator Daniel Blockmans, MD, PhD, of University Hospitals Leuven in Belgium, told this news organization.

Glucocorticoids remain the mainstay of treatment, and tocilizumab has been licensed for use, but people don’t always get better or can relapse, he explained.

“I have the impression that these only suppress the disease but do not cure it,” Dr. Blockmans said, adding that “patients get very well soon after these treatments are started, but there are more and more reports that there is a kind of smoldering vasculitis that exists, and this can lead to dilatation of the aorta.”

Upadacitinib inhibits two JAK-dependent cytokines, interleukin 6 and interferon gamma, which have been implicated in the pathogenesis of GCA. The latter could be particularly important, Dr. Blockmans suggested.
 

Study Details

SELECT-GCA is an ongoing multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of upadacitinib vs placebo in patients with GCA.

A total of 428 patients have been included: 210 were randomly allocated to treatment with upadacitinib 15 mg, 105 to upadacitinib 7.5 mg, and 105 to placebo. The inclusion of the lower “minimally effective” upadacitinib dose was a requirement of the regulatory authorities, Dr. Blockmans said; the licensed dose in rheumatoid arthritis (RA) is 15 mg.

Dr. Blockmans reported data from the first 52 weeks of the trial during which all patients underwent glucocorticoid tapering — 26 weeks for upadacitinib and 52 weeks for placebo.

No imaging was done in this trial, which Dr. Blockmans said should be considered for future studies.
 

Secondary Endpoints

One of the key secondary endpoints was sustained complete remission, defined as sustained remission plus a normalized erythrocyte sedimentation rate to ≤ 30 mm/h and reducing high-sensitivity C-reactive protein to < 1 mg/dL.

Sustained complete remission occurred in 37% and 16% of patients treated with upadacitinib 15 mg and placebo, respectively (P < .0001).

Additionally, a significantly lower proportion of upadacitinib 15 mg- than placebo-treated patients experienced at least one disease flare through week 52 (34% vs 56%, P = .0014).

Other positive secondary endpoints for upadacitinib 15 mg vs placebo out to week 52 were the number of disease flares per patient, cumulative glucocorticoid exposure, and complete remission (also at week 24).

And significant changes in SF-36 and FACIT-Fatigue from baseline to week 52 were seen for upadacitinib 15 mg.

The only secondary endpoints not showing a clear benefit for upadacitinib 15 mg were the changes in the Treatment Satisfaction Questionnaire for Medication at 52 weeks and the rate of glucocorticoid-related adverse events through week 52.

As for the 7.5-mg dose of upadacitinib, neither the primary nor secondary endpoints were significantly better vs placebo.
 

‘Life-Changing’

The study’s findings could be “really life-changing” for patients with this type of vasculitis if upadacitinib gets approval for use in this indication, Milena Bond, MD, PhD, of Brunico Hospital in Italy, told this news organization at the meeting.

“Unfortunately, nowadays, we still have only a few options for treating these patients,” she said. “So, this drug could be really, really important.”

Dr. Bond added: “The data ... also shows there is a very good safety profile, which was a main concern given the class of the drug. So, I’m very positive about this treatment and very excited to see the preliminary results.”

After his presentation, Dr. Blockmans said, “Of course, if we already had an ideal treatment for GCA, there would be no need for a JAK inhibitor, but I don’t think that steroid treatment or tocilizumab treatment is the ideal treatment.”
 

Judicious Use Still Warranted

Upadacitinib still needs to be used cautiously, following appropriate guidance from the European Medicines Agency (EMA) and the US Food and Drug Administration.

Dr. Bond said: “It is not advised to use to the drug when people are older than 65 years old,” according to the EMA, for example, and “given the rules that we have, I would not use this drug as a first-line treatment. We do not do that for rheumatoid arthritis.”

But, she added, “As for arthritis, when you fail treating patients with the other alternatives, you could use this drug, and you have to discuss risks with the patients.”

Dr. Blockmans reported there had been no increased risk for major adverse cardiovascular events or venous thromboembolism associated with upadacitinib relative to placebo in the population of patients studied, and he pointed out that they had a much higher risk for these events than perhaps an RA population.

He said: “It’s effective, and it’s apparently safe in these older people, despite what we heard about tofacitinib in the ORAL [Surveillance] study; we didn’t see these problems here in this elderly population.”

The SELECT-GCA trial was funded by AbbVie, and the company participated in all aspects of the study, including its design, conduct, interpretation of data, and reporting. Dr. Blockmans received no funding or other honoraria from the company but reported a research grant from Roche and consulting fees from GlaxoSmithKline. Most of his coauthors reported financial relationships with AbbVie, and some are employees of the company. Dr. Bond reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

VIENNA — Results from the phase 3 SELECT-GCA study showed that the Janus kinase (JAK) inhibitor upadacitinib (Rinvoq) induces significant and sustained remission in people with new-onset or relapsing giant cell arteritis (GCA).

The primary endpoint of sustained remission — the absence of GCA signs or symptoms from weeks 12 to 52 together with adherence to a steroid-tapering regimen — occurred in 46% of 210 individuals randomly assigned to treatment treated with a once-daily 15-mg dose of upadacitinib and 29% of 105 randomly assigned to placebo (P = .0019).

Nine of the 11 secondary endpoints were also positive for upadacitinib 15 mg vs placebo, and no new safety concerns were identified in a late-breaking abstract presented at the at the annual European Congress of Rheumatology.
 

First JAK Trial in GCA

This is the first trial to look at the use of a JAK inhibitor for the treatment of GCA, and it is addressing a real unmet need, the presenting study investigator Daniel Blockmans, MD, PhD, of University Hospitals Leuven in Belgium, told this news organization.

Glucocorticoids remain the mainstay of treatment, and tocilizumab has been licensed for use, but people don’t always get better or can relapse, he explained.

“I have the impression that these only suppress the disease but do not cure it,” Dr. Blockmans said, adding that “patients get very well soon after these treatments are started, but there are more and more reports that there is a kind of smoldering vasculitis that exists, and this can lead to dilatation of the aorta.”

Upadacitinib inhibits two JAK-dependent cytokines, interleukin 6 and interferon gamma, which have been implicated in the pathogenesis of GCA. The latter could be particularly important, Dr. Blockmans suggested.
 

Study Details

SELECT-GCA is an ongoing multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of upadacitinib vs placebo in patients with GCA.

A total of 428 patients have been included: 210 were randomly allocated to treatment with upadacitinib 15 mg, 105 to upadacitinib 7.5 mg, and 105 to placebo. The inclusion of the lower “minimally effective” upadacitinib dose was a requirement of the regulatory authorities, Dr. Blockmans said; the licensed dose in rheumatoid arthritis (RA) is 15 mg.

Dr. Blockmans reported data from the first 52 weeks of the trial during which all patients underwent glucocorticoid tapering — 26 weeks for upadacitinib and 52 weeks for placebo.

No imaging was done in this trial, which Dr. Blockmans said should be considered for future studies.
 

Secondary Endpoints

One of the key secondary endpoints was sustained complete remission, defined as sustained remission plus a normalized erythrocyte sedimentation rate to ≤ 30 mm/h and reducing high-sensitivity C-reactive protein to < 1 mg/dL.

Sustained complete remission occurred in 37% and 16% of patients treated with upadacitinib 15 mg and placebo, respectively (P < .0001).

Additionally, a significantly lower proportion of upadacitinib 15 mg- than placebo-treated patients experienced at least one disease flare through week 52 (34% vs 56%, P = .0014).

Other positive secondary endpoints for upadacitinib 15 mg vs placebo out to week 52 were the number of disease flares per patient, cumulative glucocorticoid exposure, and complete remission (also at week 24).

And significant changes in SF-36 and FACIT-Fatigue from baseline to week 52 were seen for upadacitinib 15 mg.

The only secondary endpoints not showing a clear benefit for upadacitinib 15 mg were the changes in the Treatment Satisfaction Questionnaire for Medication at 52 weeks and the rate of glucocorticoid-related adverse events through week 52.

As for the 7.5-mg dose of upadacitinib, neither the primary nor secondary endpoints were significantly better vs placebo.
 

‘Life-Changing’

The study’s findings could be “really life-changing” for patients with this type of vasculitis if upadacitinib gets approval for use in this indication, Milena Bond, MD, PhD, of Brunico Hospital in Italy, told this news organization at the meeting.

“Unfortunately, nowadays, we still have only a few options for treating these patients,” she said. “So, this drug could be really, really important.”

Dr. Bond added: “The data ... also shows there is a very good safety profile, which was a main concern given the class of the drug. So, I’m very positive about this treatment and very excited to see the preliminary results.”

After his presentation, Dr. Blockmans said, “Of course, if we already had an ideal treatment for GCA, there would be no need for a JAK inhibitor, but I don’t think that steroid treatment or tocilizumab treatment is the ideal treatment.”
 

Judicious Use Still Warranted

Upadacitinib still needs to be used cautiously, following appropriate guidance from the European Medicines Agency (EMA) and the US Food and Drug Administration.

Dr. Bond said: “It is not advised to use to the drug when people are older than 65 years old,” according to the EMA, for example, and “given the rules that we have, I would not use this drug as a first-line treatment. We do not do that for rheumatoid arthritis.”

But, she added, “As for arthritis, when you fail treating patients with the other alternatives, you could use this drug, and you have to discuss risks with the patients.”

Dr. Blockmans reported there had been no increased risk for major adverse cardiovascular events or venous thromboembolism associated with upadacitinib relative to placebo in the population of patients studied, and he pointed out that they had a much higher risk for these events than perhaps an RA population.

He said: “It’s effective, and it’s apparently safe in these older people, despite what we heard about tofacitinib in the ORAL [Surveillance] study; we didn’t see these problems here in this elderly population.”

The SELECT-GCA trial was funded by AbbVie, and the company participated in all aspects of the study, including its design, conduct, interpretation of data, and reporting. Dr. Blockmans received no funding or other honoraria from the company but reported a research grant from Roche and consulting fees from GlaxoSmithKline. Most of his coauthors reported financial relationships with AbbVie, and some are employees of the company. Dr. Bond reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Nearly 13% of older adults in the United States were treated for traumatic brain injury (TBI) over an 18-year period, a new study showed.

METHODOLOGY:

• Researchers analyzed data from approximately 9200 Medicare enrollees who were part of the Health and Retirement Study (HRS), aged 65 years and older, from 2000 to 2018.
• The baseline date was the date of the first age eligible HRS core interview in the community in 2000 or later.
• Incident TBI cases came from an updated list of the International Classification of Diseases (ICD), 9th and 10th edition codes, from the Defense and Veterans Brain Injury Center and the Armed Forces Health Surveillance Branch for TBI surveillance.
• Codes corresponded with emergency department, CT, and/or fMRI visits.

TAKEAWAY:

• Almost 13% of older individuals (n = 797) experienced TBI during the study, highlighting its significant prevalence in this population.
• Older adults (mean age at baseline, 75 years) who experienced TBI during the study period were more likely to be women and White individuals as well as individuals having higher levels of education and normal cognition (P < .001), challenging previous assumptions about risk factors.
• The study underscored the need for targeted interventions and research focused on TBI prevention and postdischarge care in older adults.

IN PRACTICE:

“The number of people 65 and older with TBI is shockingly high,” senior author Raquel Gardner, MD, said in a press release. “We need evidence-based guidelines to inform postdischarge care of this very large Medicare population and more research on post-TBI dementia prevention and repeat injury prevention.”

SOURCE:

The study was led by Erica Kornblith, PhD, of the University of California, San Francisco. It was published online in JAMA Network Open.

LIMITATIONS:

The study’s reliance on ICD codes for TBI identification may not capture the full spectrum of TBI severity. Self-reported data on sociodemographic factors may have introduced bias, affecting the accuracy of associations with TBI incidence. In addition, the findings’ generalizability may be limited due to the study’s focus on Medicare enrollees, potentially excluding those from diverse socioeconomic backgrounds.

DISCLOSURES:

The study was funded by the Alzheimer’s Association, the US Department of Veterans Affairs, the National Institute on Aging, and the Department of Defense. Disclosures are noted in the original study.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

TOPLINE:

Nearly 13% of older adults in the United States were treated for traumatic brain injury (TBI) over an 18-year period, a new study showed.

METHODOLOGY:

• Researchers analyzed data from approximately 9200 Medicare enrollees who were part of the Health and Retirement Study (HRS), aged 65 years and older, from 2000 to 2018.
• The baseline date was the date of the first age eligible HRS core interview in the community in 2000 or later.
• Incident TBI cases came from an updated list of the International Classification of Diseases (ICD), 9th and 10th edition codes, from the Defense and Veterans Brain Injury Center and the Armed Forces Health Surveillance Branch for TBI surveillance.
• Codes corresponded with emergency department, CT, and/or fMRI visits.

TAKEAWAY:

• Almost 13% of older individuals (n = 797) experienced TBI during the study, highlighting its significant prevalence in this population.
• Older adults (mean age at baseline, 75 years) who experienced TBI during the study period were more likely to be women and White individuals as well as individuals having higher levels of education and normal cognition (P < .001), challenging previous assumptions about risk factors.
• The study underscored the need for targeted interventions and research focused on TBI prevention and postdischarge care in older adults.

IN PRACTICE:

“The number of people 65 and older with TBI is shockingly high,” senior author Raquel Gardner, MD, said in a press release. “We need evidence-based guidelines to inform postdischarge care of this very large Medicare population and more research on post-TBI dementia prevention and repeat injury prevention.”

SOURCE:

The study was led by Erica Kornblith, PhD, of the University of California, San Francisco. It was published online in JAMA Network Open.

LIMITATIONS:

The study’s reliance on ICD codes for TBI identification may not capture the full spectrum of TBI severity. Self-reported data on sociodemographic factors may have introduced bias, affecting the accuracy of associations with TBI incidence. In addition, the findings’ generalizability may be limited due to the study’s focus on Medicare enrollees, potentially excluding those from diverse socioeconomic backgrounds.

DISCLOSURES:

The study was funded by the Alzheimer’s Association, the US Department of Veterans Affairs, the National Institute on Aging, and the Department of Defense. Disclosures are noted in the original study.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

TOPLINE:

Nearly 13% of older adults in the United States were treated for traumatic brain injury (TBI) over an 18-year period, a new study showed.

METHODOLOGY:

• Researchers analyzed data from approximately 9200 Medicare enrollees who were part of the Health and Retirement Study (HRS), aged 65 years and older, from 2000 to 2018.
• The baseline date was the date of the first age eligible HRS core interview in the community in 2000 or later.
• Incident TBI cases came from an updated list of the International Classification of Diseases (ICD), 9th and 10th edition codes, from the Defense and Veterans Brain Injury Center and the Armed Forces Health Surveillance Branch for TBI surveillance.
• Codes corresponded with emergency department, CT, and/or fMRI visits.

TAKEAWAY:

• Almost 13% of older individuals (n = 797) experienced TBI during the study, highlighting its significant prevalence in this population.
• Older adults (mean age at baseline, 75 years) who experienced TBI during the study period were more likely to be women and White individuals as well as individuals having higher levels of education and normal cognition (P < .001), challenging previous assumptions about risk factors.
• The study underscored the need for targeted interventions and research focused on TBI prevention and postdischarge care in older adults.

IN PRACTICE:

“The number of people 65 and older with TBI is shockingly high,” senior author Raquel Gardner, MD, said in a press release. “We need evidence-based guidelines to inform postdischarge care of this very large Medicare population and more research on post-TBI dementia prevention and repeat injury prevention.”

SOURCE:

The study was led by Erica Kornblith, PhD, of the University of California, San Francisco. It was published online in JAMA Network Open.

LIMITATIONS:

The study’s reliance on ICD codes for TBI identification may not capture the full spectrum of TBI severity. Self-reported data on sociodemographic factors may have introduced bias, affecting the accuracy of associations with TBI incidence. In addition, the findings’ generalizability may be limited due to the study’s focus on Medicare enrollees, potentially excluding those from diverse socioeconomic backgrounds.

DISCLOSURES:

The study was funded by the Alzheimer’s Association, the US Department of Veterans Affairs, the National Institute on Aging, and the Department of Defense. Disclosures are noted in the original study.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.