MDedge Neurology

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.

The US Food and Drug Administration has granted accelerated approval to repotrectinib (Augtyro, Bristol Myers Squibb) for all locally advanced, unresectable, or metastatic solid tumors with an NTRK gene fusion that have progressed after initial treatment or that have no satisfactory alternative therapies.

The approval is a label expansion for the tyrosine kinase inhibitor (TKI), which received initial clearance in November 2023 for locally advanced or metastatic ROS1-positive non–small cell lung cancer. 

NTRK gene fusions are genetic abnormalities wherein part of the NTRK gene fuses with an unrelated gene. The abnormal gene can then produce an oncogenic protein. Although rare, these mutations are found in many cancer types.

The approval, for adult and pediatric patients aged 12 years or older, was based on the single-arm open-label TRIDENT-1 trial in 88 adults with locally advanced or metastatic NTRK gene fusion solid tumors.

In the 40 patients who were TKI-naive, the overall response rate was 58%, and the median duration of response was not estimable. In the 48 patients who had a TKI previously, the overall response rate was 50% and median duration of response was 9.9 months.

In 20% or more of participants, treatment caused dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, fatigue, ataxia, cognitive impairment, muscular weakness, and nausea.

Labeling warns of central nervous system reactions, interstitial lung disease/pneumonitis, hepatotoxicity, myalgia with creatine phosphokinase elevation, hyperuricemia, bone fractures, and embryo-fetal toxicity.

The recommended dose is 160 mg orally once daily for 14 days then increased to 160 mg twice daily until disease progression or unacceptable toxicity.

Sixty 40-mg capsules cost around $7,644, according to drugs.com. 
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration has granted accelerated approval to repotrectinib (Augtyro, Bristol Myers Squibb) for all locally advanced, unresectable, or metastatic solid tumors with an NTRK gene fusion that have progressed after initial treatment or that have no satisfactory alternative therapies.

The approval is a label expansion for the tyrosine kinase inhibitor (TKI), which received initial clearance in November 2023 for locally advanced or metastatic ROS1-positive non–small cell lung cancer. 

NTRK gene fusions are genetic abnormalities wherein part of the NTRK gene fuses with an unrelated gene. The abnormal gene can then produce an oncogenic protein. Although rare, these mutations are found in many cancer types.

The approval, for adult and pediatric patients aged 12 years or older, was based on the single-arm open-label TRIDENT-1 trial in 88 adults with locally advanced or metastatic NTRK gene fusion solid tumors.

In the 40 patients who were TKI-naive, the overall response rate was 58%, and the median duration of response was not estimable. In the 48 patients who had a TKI previously, the overall response rate was 50% and median duration of response was 9.9 months.

In 20% or more of participants, treatment caused dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, fatigue, ataxia, cognitive impairment, muscular weakness, and nausea.

Labeling warns of central nervous system reactions, interstitial lung disease/pneumonitis, hepatotoxicity, myalgia with creatine phosphokinase elevation, hyperuricemia, bone fractures, and embryo-fetal toxicity.

The recommended dose is 160 mg orally once daily for 14 days then increased to 160 mg twice daily until disease progression or unacceptable toxicity.

Sixty 40-mg capsules cost around $7,644, according to drugs.com. 
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration has granted accelerated approval to repotrectinib (Augtyro, Bristol Myers Squibb) for all locally advanced, unresectable, or metastatic solid tumors with an NTRK gene fusion that have progressed after initial treatment or that have no satisfactory alternative therapies.

The approval is a label expansion for the tyrosine kinase inhibitor (TKI), which received initial clearance in November 2023 for locally advanced or metastatic ROS1-positive non–small cell lung cancer. 

NTRK gene fusions are genetic abnormalities wherein part of the NTRK gene fuses with an unrelated gene. The abnormal gene can then produce an oncogenic protein. Although rare, these mutations are found in many cancer types.

The approval, for adult and pediatric patients aged 12 years or older, was based on the single-arm open-label TRIDENT-1 trial in 88 adults with locally advanced or metastatic NTRK gene fusion solid tumors.

In the 40 patients who were TKI-naive, the overall response rate was 58%, and the median duration of response was not estimable. In the 48 patients who had a TKI previously, the overall response rate was 50% and median duration of response was 9.9 months.

In 20% or more of participants, treatment caused dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, fatigue, ataxia, cognitive impairment, muscular weakness, and nausea.

Labeling warns of central nervous system reactions, interstitial lung disease/pneumonitis, hepatotoxicity, myalgia with creatine phosphokinase elevation, hyperuricemia, bone fractures, and embryo-fetal toxicity.

The recommended dose is 160 mg orally once daily for 14 days then increased to 160 mg twice daily until disease progression or unacceptable toxicity.

Sixty 40-mg capsules cost around $7,644, according to drugs.com. 
 

A version of this article appeared on Medscape.com.

The largest US physician organization wrestled with the professional risks and rewards of artificial intelligence (AI) at its annual meeting, delaying action even as it adopted new policies on prior authorization and other concerns for clinicians and patients.

Physicians and medical students at the annual meeting of the American Medical Association (AMA) House of Delegates in Chicago intensely debated a report and two key resolutions on AI but could not reach consensus, pushing off decision-making until a future meeting in November.

One resolution would establish “augmented intelligence” as the preferred term for AI, reflecting the desired role of these tools in supporting — not making — physicians’ decisions. The other resolution focused on insurers’ use of AI in determining medical necessity.

(See specific policies adopted at the meeting, held June 8-12, below.)

A comprehensive AMA trustees’ report on AI considered additional issues including requirements for disclosing AI use, liability for harms due to flawed application of AI, data privacy, and cybersecurity.

The AMA intends to “continue to methodically assess these issues and make informed recommendations in proposing new policy,” said Bobby Mukkamala, MD, an otolaryngologist from Flint, Michigan, who became the AMA’s new president-elect.

AMA members at the meeting largely applauded the aim of these AI proposals, but some objected to parts of the trustees’ report.

They raised questions about what, exactly, constitutes an AI-powered service and whether all AI tools need the kind of guardrails the AMA may seek. There also were concerns about calls to make AI use more transparent.

While transparency might be an admirable goal, it might prove too hard to achieve given that AI-powered tools and products are already woven into medical practice in ways that physicians may not know or understand, said Christopher Libby, MD, MPH, a clinical informaticist and emergency physician at Cedars Sinai Medical Center in Los Angeles.

“It’s hard for the practicing clinician to know how every piece of technology works in order to describe it to the patient,” Dr. Libby said at the meeting. “How many people here can identify when algorithms are used in their EHR today?”

He suggested asking for more transparency from the companies that make and sell AI-powered software and tools to insurers and healthcare systems.

Steven H. Kroft, MD, the editor of the American Journal of Clinical Pathology, raised concerns about the unintended harm that unchecked use of AI may pose to scientific research.

He asked the AMA to address “a significant omission in an otherwise comprehensive report” — the need to protect the integrity of study results that can direct patient care.

“While sham science is not a new issue, large language models make it far easier for authors to generate fake papers and far harder for editors, reviewers, and publishers to identify them,” Dr. Kroft said. “This is a rapidly growing phenomenon that is threatening the integrity of the literature. These papers become embedded in the evidence bases that drive clinical decision-making.”

AMA has been working with specialty societies and outside AI experts to refine an effective set of recommendations. The new policies, once finalized, are intended to build on steps AMA already has taken, including last year releasing principles for AI development, deployment, and use.
 

Congress Mulling

The AMA delegates are far from alone in facing AI policy challenges.

Leaders in Congress also are examining AI guardrails, with influential panels such as the Senate Finance and House Energy and Commerce committees holding hearings.

A key congressional AI effort to watch is the expected implementation of a bipartisan Senate “road map,” which Senate Majority Leader Chuck Schumer (D-NY) and colleagues released in May, said Miranda A. Franco, a senior policy advisor at the law firm Holland & Knight.

The product of many months of deliberation, this Senate road map identifies priorities for future legislation, including:

• Creating appropriate guardrails and safety measures to protect patients.
• Making healthcare and biomedical data available for machine learning and data science research while carefully addressing privacy issues.
• Providing transparency for clinicians and the public about the use of AI in medical products and clinical support services, including the data used to train models.
• Examining the Centers for Medicare & Medicaid Services’ reimbursement mechanisms as well as guardrails to ensure accountability, appropriate use, and broad application of AI across all populations.

Congress likely will address issues of AI in healthcare in piecemeal fashion, taking on different aspects of these challenges at different times, Ms. Franco said. The Senate road map gives the key committees directions on where to proceed in their efforts to develop new laws.

“I think this is all going to be slow and rolling, not big and sweeping,” Ms. Franco told this news organization. “I don’t think we’re going to see an encompassing AI bill.”
 

AMA Policies Adopted on Other Issues

At the June meeting, AMA delegates adopted the following policies aiming to:

• Increase oversight and accountability of health insurers’ use of prior authorization controls on patient access to care.
• Encourage policy changes allowing physicians to receive loan forgiveness when they practice in an Indian Health Service, Tribal, or Urban Indian Health Program, similar to physicians practicing in a Veterans Administration facility.
• Advocate for federal policy that limits a patient’s out-of-pocket cost to be the same or less than the amount that a patient with traditional Medicare plus a Medigap plan would pay.
• Oppose state or national legislation that could criminalize in vitro fertilization.
• Limit what the AMA calls the “expensive” cost for Medicare Advantage enrollees who need physician-administered drugs or biologics.
• Help physicians address the handling of de-identified patient data in a rapidly changing digital health ecosystem.
• Support efforts to decriminalize the possession of non-prescribed buprenorphine for personal use by individuals who lack access to a physician for the treatment of opioid use disorder.
• Expand access to hearing, vision, and dental care. The new AMA policy advocates working with state medical associations to support coverage of hearing exams, hearing aids, cochlear implants, and vision exams and aids. The revised AMA policy also supports working with the American Dental Association and other national organizations to improve access to dental care for people enrolled in Medicare, Medicaid, and CHIP programs.
• Increase enrollment of more women and sexual and gender minority populations in clinical trials.

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

The largest US physician organization wrestled with the professional risks and rewards of artificial intelligence (AI) at its annual meeting, delaying action even as it adopted new policies on prior authorization and other concerns for clinicians and patients.

Physicians and medical students at the annual meeting of the American Medical Association (AMA) House of Delegates in Chicago intensely debated a report and two key resolutions on AI but could not reach consensus, pushing off decision-making until a future meeting in November.

One resolution would establish “augmented intelligence” as the preferred term for AI, reflecting the desired role of these tools in supporting — not making — physicians’ decisions. The other resolution focused on insurers’ use of AI in determining medical necessity.

(See specific policies adopted at the meeting, held June 8-12, below.)

A comprehensive AMA trustees’ report on AI considered additional issues including requirements for disclosing AI use, liability for harms due to flawed application of AI, data privacy, and cybersecurity.

The AMA intends to “continue to methodically assess these issues and make informed recommendations in proposing new policy,” said Bobby Mukkamala, MD, an otolaryngologist from Flint, Michigan, who became the AMA’s new president-elect.

AMA members at the meeting largely applauded the aim of these AI proposals, but some objected to parts of the trustees’ report.

They raised questions about what, exactly, constitutes an AI-powered service and whether all AI tools need the kind of guardrails the AMA may seek. There also were concerns about calls to make AI use more transparent.

While transparency might be an admirable goal, it might prove too hard to achieve given that AI-powered tools and products are already woven into medical practice in ways that physicians may not know or understand, said Christopher Libby, MD, MPH, a clinical informaticist and emergency physician at Cedars Sinai Medical Center in Los Angeles.

“It’s hard for the practicing clinician to know how every piece of technology works in order to describe it to the patient,” Dr. Libby said at the meeting. “How many people here can identify when algorithms are used in their EHR today?”

He suggested asking for more transparency from the companies that make and sell AI-powered software and tools to insurers and healthcare systems.

Steven H. Kroft, MD, the editor of the American Journal of Clinical Pathology, raised concerns about the unintended harm that unchecked use of AI may pose to scientific research.

He asked the AMA to address “a significant omission in an otherwise comprehensive report” — the need to protect the integrity of study results that can direct patient care.

“While sham science is not a new issue, large language models make it far easier for authors to generate fake papers and far harder for editors, reviewers, and publishers to identify them,” Dr. Kroft said. “This is a rapidly growing phenomenon that is threatening the integrity of the literature. These papers become embedded in the evidence bases that drive clinical decision-making.”

AMA has been working with specialty societies and outside AI experts to refine an effective set of recommendations. The new policies, once finalized, are intended to build on steps AMA already has taken, including last year releasing principles for AI development, deployment, and use.
 

Congress Mulling

The AMA delegates are far from alone in facing AI policy challenges.

Leaders in Congress also are examining AI guardrails, with influential panels such as the Senate Finance and House Energy and Commerce committees holding hearings.

A key congressional AI effort to watch is the expected implementation of a bipartisan Senate “road map,” which Senate Majority Leader Chuck Schumer (D-NY) and colleagues released in May, said Miranda A. Franco, a senior policy advisor at the law firm Holland & Knight.

The product of many months of deliberation, this Senate road map identifies priorities for future legislation, including:

• Creating appropriate guardrails and safety measures to protect patients.
• Making healthcare and biomedical data available for machine learning and data science research while carefully addressing privacy issues.
• Providing transparency for clinicians and the public about the use of AI in medical products and clinical support services, including the data used to train models.
• Examining the Centers for Medicare & Medicaid Services’ reimbursement mechanisms as well as guardrails to ensure accountability, appropriate use, and broad application of AI across all populations.

Congress likely will address issues of AI in healthcare in piecemeal fashion, taking on different aspects of these challenges at different times, Ms. Franco said. The Senate road map gives the key committees directions on where to proceed in their efforts to develop new laws.

“I think this is all going to be slow and rolling, not big and sweeping,” Ms. Franco told this news organization. “I don’t think we’re going to see an encompassing AI bill.”
 

AMA Policies Adopted on Other Issues

At the June meeting, AMA delegates adopted the following policies aiming to:

• Increase oversight and accountability of health insurers’ use of prior authorization controls on patient access to care.
• Encourage policy changes allowing physicians to receive loan forgiveness when they practice in an Indian Health Service, Tribal, or Urban Indian Health Program, similar to physicians practicing in a Veterans Administration facility.
• Advocate for federal policy that limits a patient’s out-of-pocket cost to be the same or less than the amount that a patient with traditional Medicare plus a Medigap plan would pay.
• Oppose state or national legislation that could criminalize in vitro fertilization.
• Limit what the AMA calls the “expensive” cost for Medicare Advantage enrollees who need physician-administered drugs or biologics.
• Help physicians address the handling of de-identified patient data in a rapidly changing digital health ecosystem.
• Support efforts to decriminalize the possession of non-prescribed buprenorphine for personal use by individuals who lack access to a physician for the treatment of opioid use disorder.
• Expand access to hearing, vision, and dental care. The new AMA policy advocates working with state medical associations to support coverage of hearing exams, hearing aids, cochlear implants, and vision exams and aids. The revised AMA policy also supports working with the American Dental Association and other national organizations to improve access to dental care for people enrolled in Medicare, Medicaid, and CHIP programs.
• Increase enrollment of more women and sexual and gender minority populations in clinical trials.

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

The largest US physician organization wrestled with the professional risks and rewards of artificial intelligence (AI) at its annual meeting, delaying action even as it adopted new policies on prior authorization and other concerns for clinicians and patients.

Physicians and medical students at the annual meeting of the American Medical Association (AMA) House of Delegates in Chicago intensely debated a report and two key resolutions on AI but could not reach consensus, pushing off decision-making until a future meeting in November.

One resolution would establish “augmented intelligence” as the preferred term for AI, reflecting the desired role of these tools in supporting — not making — physicians’ decisions. The other resolution focused on insurers’ use of AI in determining medical necessity.

(See specific policies adopted at the meeting, held June 8-12, below.)

A comprehensive AMA trustees’ report on AI considered additional issues including requirements for disclosing AI use, liability for harms due to flawed application of AI, data privacy, and cybersecurity.

The AMA intends to “continue to methodically assess these issues and make informed recommendations in proposing new policy,” said Bobby Mukkamala, MD, an otolaryngologist from Flint, Michigan, who became the AMA’s new president-elect.

AMA members at the meeting largely applauded the aim of these AI proposals, but some objected to parts of the trustees’ report.

They raised questions about what, exactly, constitutes an AI-powered service and whether all AI tools need the kind of guardrails the AMA may seek. There also were concerns about calls to make AI use more transparent.

While transparency might be an admirable goal, it might prove too hard to achieve given that AI-powered tools and products are already woven into medical practice in ways that physicians may not know or understand, said Christopher Libby, MD, MPH, a clinical informaticist and emergency physician at Cedars Sinai Medical Center in Los Angeles.

“It’s hard for the practicing clinician to know how every piece of technology works in order to describe it to the patient,” Dr. Libby said at the meeting. “How many people here can identify when algorithms are used in their EHR today?”

He suggested asking for more transparency from the companies that make and sell AI-powered software and tools to insurers and healthcare systems.

Steven H. Kroft, MD, the editor of the American Journal of Clinical Pathology, raised concerns about the unintended harm that unchecked use of AI may pose to scientific research.

He asked the AMA to address “a significant omission in an otherwise comprehensive report” — the need to protect the integrity of study results that can direct patient care.

“While sham science is not a new issue, large language models make it far easier for authors to generate fake papers and far harder for editors, reviewers, and publishers to identify them,” Dr. Kroft said. “This is a rapidly growing phenomenon that is threatening the integrity of the literature. These papers become embedded in the evidence bases that drive clinical decision-making.”

AMA has been working with specialty societies and outside AI experts to refine an effective set of recommendations. The new policies, once finalized, are intended to build on steps AMA already has taken, including last year releasing principles for AI development, deployment, and use.
 

Congress Mulling

The AMA delegates are far from alone in facing AI policy challenges.

Leaders in Congress also are examining AI guardrails, with influential panels such as the Senate Finance and House Energy and Commerce committees holding hearings.

A key congressional AI effort to watch is the expected implementation of a bipartisan Senate “road map,” which Senate Majority Leader Chuck Schumer (D-NY) and colleagues released in May, said Miranda A. Franco, a senior policy advisor at the law firm Holland & Knight.

The product of many months of deliberation, this Senate road map identifies priorities for future legislation, including:

• Creating appropriate guardrails and safety measures to protect patients.
• Making healthcare and biomedical data available for machine learning and data science research while carefully addressing privacy issues.
• Providing transparency for clinicians and the public about the use of AI in medical products and clinical support services, including the data used to train models.
• Examining the Centers for Medicare & Medicaid Services’ reimbursement mechanisms as well as guardrails to ensure accountability, appropriate use, and broad application of AI across all populations.

Congress likely will address issues of AI in healthcare in piecemeal fashion, taking on different aspects of these challenges at different times, Ms. Franco said. The Senate road map gives the key committees directions on where to proceed in their efforts to develop new laws.

“I think this is all going to be slow and rolling, not big and sweeping,” Ms. Franco told this news organization. “I don’t think we’re going to see an encompassing AI bill.”
 

AMA Policies Adopted on Other Issues

At the June meeting, AMA delegates adopted the following policies aiming to:

• Increase oversight and accountability of health insurers’ use of prior authorization controls on patient access to care.
• Encourage policy changes allowing physicians to receive loan forgiveness when they practice in an Indian Health Service, Tribal, or Urban Indian Health Program, similar to physicians practicing in a Veterans Administration facility.
• Advocate for federal policy that limits a patient’s out-of-pocket cost to be the same or less than the amount that a patient with traditional Medicare plus a Medigap plan would pay.
• Oppose state or national legislation that could criminalize in vitro fertilization.
• Limit what the AMA calls the “expensive” cost for Medicare Advantage enrollees who need physician-administered drugs or biologics.
• Help physicians address the handling of de-identified patient data in a rapidly changing digital health ecosystem.
• Support efforts to decriminalize the possession of non-prescribed buprenorphine for personal use by individuals who lack access to a physician for the treatment of opioid use disorder.
• Expand access to hearing, vision, and dental care. The new AMA policy advocates working with state medical associations to support coverage of hearing exams, hearing aids, cochlear implants, and vision exams and aids. The revised AMA policy also supports working with the American Dental Association and other national organizations to improve access to dental care for people enrolled in Medicare, Medicaid, and CHIP programs.
• Increase enrollment of more women and sexual and gender minority populations in clinical trials.

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

Women who had overweight or obesity as teens or young adults had more than a twofold increased risk for stroke before age 55, new research suggested.

An analysis of more than five decades of health data on 10,000 adults revealed that close to 5% experienced a stroke during the follow-up period, with the risk for ischemic stroke being more than twice as high in women who had obesity as teens or young adults. The risk was even higher for hemorrhagic stroke in both men and women with a history of obesity in youth.

“Our findings suggest that being overweight may have long-term health effects, even if the excess weight is temporary,” lead author Ursula Mikkola, BM, an investigator in the Research Unit of Population Health at the University of Oulu, Oulu, Finland, said in a news release.

Gender Differences

Childhood obesity has been associated with a heightened risk for cerebrovascular disease later in life, but most studies have focused on body mass index (BMI) at a single time point without considering its fluctuations throughout life, the investigators noted.

For the study, investigators used data from the Northern Finland Birth Cohort 1966, a prospective, general population-based birth cohort that followed 10,491 individuals (5185 women) until 2020 or the first stroke, death, or moving abroad, whichever came first.

Mean (SD) follow-up for each participant was 39 years from age 14 onward and 23 years from age 31 onward. The analysis was conducted between 1980 and 2020.

BMI data were collected from participants at the age of 14 and 31 years. Age 14 covariates included smoking, parental socioeconomic status, and age at menarche (for girls). Age 31 covariates included smoking and participants’ educational level.

During the follow-up period, 4.7% of participants experienced stroke. Of these events, 31% were ischemic strokes and 40% were transient ischemic attacks. The remainder were hemorrhagic or other cerebrovascular events.

Using normal weight as a reference, researchers found that the risk for ischemic stroke was over twice as high for women who had been overweight at ages 14 (hazard ratio [HR], 2.49; 95% confidence interval [CI], 1.44-4.31) and 31 (HR, 2.13; 95% CI, 1.14-3.97) years. The risk was also considerably higher for women who had obesity at ages 14 (HR, 1.87; 95% CI, 0.76-4.58) and 31 (HR, 2.67; 95% CI, 1.26-5.65) years.

The risk for hemorrhagic stroke was even higher, both among women (HR, 3.49; 95% CI, 1.13-10.7) and men (HR, 5.75; 95% CI, 1.43-23.1) who had obesity at age 31.

No similar associations were found among men, and the findings were independent of earlier or later BMI.

The risk for any cerebrovascular disease related to overweight at age 14 was twice as high among girls vs boys (HR, 2.09; 95% CI, 1.06-4.15), and the risk for ischemic stroke related to obesity at age 31 was nearly seven times higher among women vs men (HR, 6.96; 95% CI, 1.36-35.7).

“Stroke at a young age is rare, so the difference of just a few strokes could have an outsized impact on the risk estimates,” the study authors said. “Also, BMI relies solely on a person’s height and weight; therefore, a high BMI may be a misleading way to define obesity, especially in muscular people who may carry little fat even while weighing more.”
 

Caveats

In an accompanying editorial, Larry Goldstein, MD, chair of the Department of Neurology, University of Kentucky, Lexington, Kentucky, and codirector of the Kentucky Neuroscience Institute, said the study “provides additional evidence of an association between overweight/obesity and stroke in young adults.”

However, Dr. Goldstein added that “while it is tempting to assume that reductions in overweight/obesity in younger populations would translate to lower stroke rates in young adults, this remains to be proven.”

Moreover, it is “always important to acknowledge that associations found in observational studies may not reflect causality.”

This study was supported by Orion Research Foundation, Päivikki and Sakari Sohlberg Foundation, and Paulo Foundation. Dr. Mikkola reported no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. Goldstein reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Women who had overweight or obesity as teens or young adults had more than a twofold increased risk for stroke before age 55, new research suggested.

An analysis of more than five decades of health data on 10,000 adults revealed that close to 5% experienced a stroke during the follow-up period, with the risk for ischemic stroke being more than twice as high in women who had obesity as teens or young adults. The risk was even higher for hemorrhagic stroke in both men and women with a history of obesity in youth.

“Our findings suggest that being overweight may have long-term health effects, even if the excess weight is temporary,” lead author Ursula Mikkola, BM, an investigator in the Research Unit of Population Health at the University of Oulu, Oulu, Finland, said in a news release.

Gender Differences

Childhood obesity has been associated with a heightened risk for cerebrovascular disease later in life, but most studies have focused on body mass index (BMI) at a single time point without considering its fluctuations throughout life, the investigators noted.

For the study, investigators used data from the Northern Finland Birth Cohort 1966, a prospective, general population-based birth cohort that followed 10,491 individuals (5185 women) until 2020 or the first stroke, death, or moving abroad, whichever came first.

Mean (SD) follow-up for each participant was 39 years from age 14 onward and 23 years from age 31 onward. The analysis was conducted between 1980 and 2020.

BMI data were collected from participants at the age of 14 and 31 years. Age 14 covariates included smoking, parental socioeconomic status, and age at menarche (for girls). Age 31 covariates included smoking and participants’ educational level.

During the follow-up period, 4.7% of participants experienced stroke. Of these events, 31% were ischemic strokes and 40% were transient ischemic attacks. The remainder were hemorrhagic or other cerebrovascular events.

Using normal weight as a reference, researchers found that the risk for ischemic stroke was over twice as high for women who had been overweight at ages 14 (hazard ratio [HR], 2.49; 95% confidence interval [CI], 1.44-4.31) and 31 (HR, 2.13; 95% CI, 1.14-3.97) years. The risk was also considerably higher for women who had obesity at ages 14 (HR, 1.87; 95% CI, 0.76-4.58) and 31 (HR, 2.67; 95% CI, 1.26-5.65) years.

The risk for hemorrhagic stroke was even higher, both among women (HR, 3.49; 95% CI, 1.13-10.7) and men (HR, 5.75; 95% CI, 1.43-23.1) who had obesity at age 31.

No similar associations were found among men, and the findings were independent of earlier or later BMI.

The risk for any cerebrovascular disease related to overweight at age 14 was twice as high among girls vs boys (HR, 2.09; 95% CI, 1.06-4.15), and the risk for ischemic stroke related to obesity at age 31 was nearly seven times higher among women vs men (HR, 6.96; 95% CI, 1.36-35.7).

“Stroke at a young age is rare, so the difference of just a few strokes could have an outsized impact on the risk estimates,” the study authors said. “Also, BMI relies solely on a person’s height and weight; therefore, a high BMI may be a misleading way to define obesity, especially in muscular people who may carry little fat even while weighing more.”
 

Caveats

In an accompanying editorial, Larry Goldstein, MD, chair of the Department of Neurology, University of Kentucky, Lexington, Kentucky, and codirector of the Kentucky Neuroscience Institute, said the study “provides additional evidence of an association between overweight/obesity and stroke in young adults.”

However, Dr. Goldstein added that “while it is tempting to assume that reductions in overweight/obesity in younger populations would translate to lower stroke rates in young adults, this remains to be proven.”

Moreover, it is “always important to acknowledge that associations found in observational studies may not reflect causality.”

This study was supported by Orion Research Foundation, Päivikki and Sakari Sohlberg Foundation, and Paulo Foundation. Dr. Mikkola reported no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. Goldstein reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Women who had overweight or obesity as teens or young adults had more than a twofold increased risk for stroke before age 55, new research suggested.

An analysis of more than five decades of health data on 10,000 adults revealed that close to 5% experienced a stroke during the follow-up period, with the risk for ischemic stroke being more than twice as high in women who had obesity as teens or young adults. The risk was even higher for hemorrhagic stroke in both men and women with a history of obesity in youth.

“Our findings suggest that being overweight may have long-term health effects, even if the excess weight is temporary,” lead author Ursula Mikkola, BM, an investigator in the Research Unit of Population Health at the University of Oulu, Oulu, Finland, said in a news release.

Gender Differences

Childhood obesity has been associated with a heightened risk for cerebrovascular disease later in life, but most studies have focused on body mass index (BMI) at a single time point without considering its fluctuations throughout life, the investigators noted.

For the study, investigators used data from the Northern Finland Birth Cohort 1966, a prospective, general population-based birth cohort that followed 10,491 individuals (5185 women) until 2020 or the first stroke, death, or moving abroad, whichever came first.

Mean (SD) follow-up for each participant was 39 years from age 14 onward and 23 years from age 31 onward. The analysis was conducted between 1980 and 2020.

BMI data were collected from participants at the age of 14 and 31 years. Age 14 covariates included smoking, parental socioeconomic status, and age at menarche (for girls). Age 31 covariates included smoking and participants’ educational level.

During the follow-up period, 4.7% of participants experienced stroke. Of these events, 31% were ischemic strokes and 40% were transient ischemic attacks. The remainder were hemorrhagic or other cerebrovascular events.

Using normal weight as a reference, researchers found that the risk for ischemic stroke was over twice as high for women who had been overweight at ages 14 (hazard ratio [HR], 2.49; 95% confidence interval [CI], 1.44-4.31) and 31 (HR, 2.13; 95% CI, 1.14-3.97) years. The risk was also considerably higher for women who had obesity at ages 14 (HR, 1.87; 95% CI, 0.76-4.58) and 31 (HR, 2.67; 95% CI, 1.26-5.65) years.

The risk for hemorrhagic stroke was even higher, both among women (HR, 3.49; 95% CI, 1.13-10.7) and men (HR, 5.75; 95% CI, 1.43-23.1) who had obesity at age 31.

No similar associations were found among men, and the findings were independent of earlier or later BMI.

The risk for any cerebrovascular disease related to overweight at age 14 was twice as high among girls vs boys (HR, 2.09; 95% CI, 1.06-4.15), and the risk for ischemic stroke related to obesity at age 31 was nearly seven times higher among women vs men (HR, 6.96; 95% CI, 1.36-35.7).

“Stroke at a young age is rare, so the difference of just a few strokes could have an outsized impact on the risk estimates,” the study authors said. “Also, BMI relies solely on a person’s height and weight; therefore, a high BMI may be a misleading way to define obesity, especially in muscular people who may carry little fat even while weighing more.”
 

Caveats

In an accompanying editorial, Larry Goldstein, MD, chair of the Department of Neurology, University of Kentucky, Lexington, Kentucky, and codirector of the Kentucky Neuroscience Institute, said the study “provides additional evidence of an association between overweight/obesity and stroke in young adults.”

However, Dr. Goldstein added that “while it is tempting to assume that reductions in overweight/obesity in younger populations would translate to lower stroke rates in young adults, this remains to be proven.”

Moreover, it is “always important to acknowledge that associations found in observational studies may not reflect causality.”

This study was supported by Orion Research Foundation, Päivikki and Sakari Sohlberg Foundation, and Paulo Foundation. Dr. Mikkola reported no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. Goldstein reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

NASHVILLE, Tennessee — In a population of Black/African American and Hispanic/Latino patients with multiple sclerosis (MS), ocrelizumab had high efficacy and an acceptable safety profile, according to the results of a 1-year analysis of the CHIMES trial. The study is the first-ever prospective study of an MS disease-modifying therapy (DMT) exclusively performed in under-represented populations, and offers lessons to researchers aiming to design more inclusive clinical trials to bolster participation by under-represented populations.

“The goal was to better understand efficacy of therapy in under-represented populations because we typically have very low numbers of these patients in our clinical trials, although there are multiple studies over the past decades suggesting that there may be poorer outcomes in Black and Hispanic individuals, particularly in the United States, and that there also may be more aggressive disease,” said Mitzi Williams, MD, who presented the study in a poster session at the annual meeting of the Consortium of Multiple Sclerosis Centers.

The team recruited 113 Black participants and 69 Hispanic participants, and, in fact, over-recruited the target number by 25%, and did so 2 months before the launch of the study in July 2020, which just happened to be in the midst of a global pandemic.

After 48 weeks of ocrelizumab treatment, 46.0% of Black participants and 58.0% of Hispanic participants achieved no evidence of disease activity in three components (NEDA-3), while 94.7% and 95.7% were free from relapses, respectively, and 94.7% and 94.2% were free from disease worsening. Serious adverse events occurred in 6.2% and 4.3% of each group, respectively, and there were no new safety signals in either group.

“The good news is that the efficacy and safety was very similar to what we saw in other clinical trials. I don’t think we really expected it to be much different, because when we think about race, it’s a social construct, not a biologic construct. What we do hope to find out is more about some of the interplay of social determinants of health, and how getting on high efficacy treatment can improve and increase productivity and outcomes in the long term,” said Dr. Williams, who is medical director of Joi Life Wellness Group, Smyrna, Georgia.

The researchers succeeded by involving patient advocates and advocacy organizations at the very earliest stages of the trial design. “We were very intentional about looking at things like social determinants of health, childcare, transportation, and things like that to ease some of the burden of participating in the trial, obviously in a legal and compliant way,” said Dr. Williams. The team also ensured complete and accurate translation of patient materials into Spanish.

The study was also a phase 4 trial, which may have simplified recruitment. “So it’s a therapy that’s already approved, which may make people feel more comfortable, but obviously the goal is for our phase 3 trials to make sure that we are recruiting represented populations. We’re taking these learnings and applying them to the broader clinical trial population so that hopefully we won’t have to come back and do phase 4 studies like this,” said Dr. Williams.

She noted that the results of more inclusive studies don’t just benefit underserved populations. “You have groups of people that are suffering and having more disability from a condition, and you need to understand why. When we broaden the population to understand those that are most vulnerable and underserved and [having the worst outcomes], it really helps us to better treat everybody. Because if we can get a hold of those factors that make us do the worst, then we can also better understand the factors that make us do the best,” said Dr. Williams.
 

Inclusive Recruitment in Clinical Trials

Asked for comment, Ahmed Obeidat, MD, PhD, highlighted the importance of inclusive recruitment. “The study is very important because historically and even in most recent clinical trials, these groups were markedly under-represented and most completed clinical trials derive conclusions based on the study of a nondiverse, White-non-Hispanic predominant population,” said Dr. Obeidat, who is an associate professor at the Medical College of Wisconsin, Milwaukee. He pointed to a systematic review showing that the median percentage of White participants in MS clinical trials was 93% and ranged from 86% to 98%.

“Several factors may contribute to the disparity in clinical trial participation, and solutions must be explored and developed. CHIMES is a first step in this direction where the study itself is designed to address disparity in MS clinical trial participation,” said Dr. Obeidat.

Dr. Obeidat also pointed to the need to consider other forms of diversity in clinical trials, such as older patients and those with advanced disability. “Investigators, coordinators, and other staff should all strive to be as inclusive as possible in clinical trials,” he said.

Dr. Williams has received consulting fees from Alexion, Biogen, Bristol Myers Squibb, EMD Serono, Genentech Inc., Janssen, Novartis, Sanofi, and TG Therapeutics, and serves on speakers bureaus for Biogen, Bristol Myers Squibb, EMD Serono, Janssen, Genentech, and TG Therapeutics. Dr. Ahmed Z. Obeidat has financial relationships with Alexion Pharmaceuticals, Banner Life Sciences, BD Biosciences, Biogen, Biologix Solutions, Bristol Myers Squibb, Celgene, EMD Serono, Genentech, GW Pharmaceuticals, Horizon Therapeutics, Jazz Pharmaceuticals, Novartis, Sandoz, Sanofi Genzyme, TG Therapeutics, and Viela Bio.

NASHVILLE, Tennessee — In a population of Black/African American and Hispanic/Latino patients with multiple sclerosis (MS), ocrelizumab had high efficacy and an acceptable safety profile, according to the results of a 1-year analysis of the CHIMES trial. The study is the first-ever prospective study of an MS disease-modifying therapy (DMT) exclusively performed in under-represented populations, and offers lessons to researchers aiming to design more inclusive clinical trials to bolster participation by under-represented populations.

“The goal was to better understand efficacy of therapy in under-represented populations because we typically have very low numbers of these patients in our clinical trials, although there are multiple studies over the past decades suggesting that there may be poorer outcomes in Black and Hispanic individuals, particularly in the United States, and that there also may be more aggressive disease,” said Mitzi Williams, MD, who presented the study in a poster session at the annual meeting of the Consortium of Multiple Sclerosis Centers.

The team recruited 113 Black participants and 69 Hispanic participants, and, in fact, over-recruited the target number by 25%, and did so 2 months before the launch of the study in July 2020, which just happened to be in the midst of a global pandemic.

After 48 weeks of ocrelizumab treatment, 46.0% of Black participants and 58.0% of Hispanic participants achieved no evidence of disease activity in three components (NEDA-3), while 94.7% and 95.7% were free from relapses, respectively, and 94.7% and 94.2% were free from disease worsening. Serious adverse events occurred in 6.2% and 4.3% of each group, respectively, and there were no new safety signals in either group.

“The good news is that the efficacy and safety was very similar to what we saw in other clinical trials. I don’t think we really expected it to be much different, because when we think about race, it’s a social construct, not a biologic construct. What we do hope to find out is more about some of the interplay of social determinants of health, and how getting on high efficacy treatment can improve and increase productivity and outcomes in the long term,” said Dr. Williams, who is medical director of Joi Life Wellness Group, Smyrna, Georgia.

The researchers succeeded by involving patient advocates and advocacy organizations at the very earliest stages of the trial design. “We were very intentional about looking at things like social determinants of health, childcare, transportation, and things like that to ease some of the burden of participating in the trial, obviously in a legal and compliant way,” said Dr. Williams. The team also ensured complete and accurate translation of patient materials into Spanish.

The study was also a phase 4 trial, which may have simplified recruitment. “So it’s a therapy that’s already approved, which may make people feel more comfortable, but obviously the goal is for our phase 3 trials to make sure that we are recruiting represented populations. We’re taking these learnings and applying them to the broader clinical trial population so that hopefully we won’t have to come back and do phase 4 studies like this,” said Dr. Williams.

She noted that the results of more inclusive studies don’t just benefit underserved populations. “You have groups of people that are suffering and having more disability from a condition, and you need to understand why. When we broaden the population to understand those that are most vulnerable and underserved and [having the worst outcomes], it really helps us to better treat everybody. Because if we can get a hold of those factors that make us do the worst, then we can also better understand the factors that make us do the best,” said Dr. Williams.
 

Inclusive Recruitment in Clinical Trials

Asked for comment, Ahmed Obeidat, MD, PhD, highlighted the importance of inclusive recruitment. “The study is very important because historically and even in most recent clinical trials, these groups were markedly under-represented and most completed clinical trials derive conclusions based on the study of a nondiverse, White-non-Hispanic predominant population,” said Dr. Obeidat, who is an associate professor at the Medical College of Wisconsin, Milwaukee. He pointed to a systematic review showing that the median percentage of White participants in MS clinical trials was 93% and ranged from 86% to 98%.

“Several factors may contribute to the disparity in clinical trial participation, and solutions must be explored and developed. CHIMES is a first step in this direction where the study itself is designed to address disparity in MS clinical trial participation,” said Dr. Obeidat.

Dr. Obeidat also pointed to the need to consider other forms of diversity in clinical trials, such as older patients and those with advanced disability. “Investigators, coordinators, and other staff should all strive to be as inclusive as possible in clinical trials,” he said.

Dr. Williams has received consulting fees from Alexion, Biogen, Bristol Myers Squibb, EMD Serono, Genentech Inc., Janssen, Novartis, Sanofi, and TG Therapeutics, and serves on speakers bureaus for Biogen, Bristol Myers Squibb, EMD Serono, Janssen, Genentech, and TG Therapeutics. Dr. Ahmed Z. Obeidat has financial relationships with Alexion Pharmaceuticals, Banner Life Sciences, BD Biosciences, Biogen, Biologix Solutions, Bristol Myers Squibb, Celgene, EMD Serono, Genentech, GW Pharmaceuticals, Horizon Therapeutics, Jazz Pharmaceuticals, Novartis, Sandoz, Sanofi Genzyme, TG Therapeutics, and Viela Bio.

NASHVILLE, Tennessee — In a population of Black/African American and Hispanic/Latino patients with multiple sclerosis (MS), ocrelizumab had high efficacy and an acceptable safety profile, according to the results of a 1-year analysis of the CHIMES trial. The study is the first-ever prospective study of an MS disease-modifying therapy (DMT) exclusively performed in under-represented populations, and offers lessons to researchers aiming to design more inclusive clinical trials to bolster participation by under-represented populations.

“The goal was to better understand efficacy of therapy in under-represented populations because we typically have very low numbers of these patients in our clinical trials, although there are multiple studies over the past decades suggesting that there may be poorer outcomes in Black and Hispanic individuals, particularly in the United States, and that there also may be more aggressive disease,” said Mitzi Williams, MD, who presented the study in a poster session at the annual meeting of the Consortium of Multiple Sclerosis Centers.

The team recruited 113 Black participants and 69 Hispanic participants, and, in fact, over-recruited the target number by 25%, and did so 2 months before the launch of the study in July 2020, which just happened to be in the midst of a global pandemic.

After 48 weeks of ocrelizumab treatment, 46.0% of Black participants and 58.0% of Hispanic participants achieved no evidence of disease activity in three components (NEDA-3), while 94.7% and 95.7% were free from relapses, respectively, and 94.7% and 94.2% were free from disease worsening. Serious adverse events occurred in 6.2% and 4.3% of each group, respectively, and there were no new safety signals in either group.

“The good news is that the efficacy and safety was very similar to what we saw in other clinical trials. I don’t think we really expected it to be much different, because when we think about race, it’s a social construct, not a biologic construct. What we do hope to find out is more about some of the interplay of social determinants of health, and how getting on high efficacy treatment can improve and increase productivity and outcomes in the long term,” said Dr. Williams, who is medical director of Joi Life Wellness Group, Smyrna, Georgia.

The researchers succeeded by involving patient advocates and advocacy organizations at the very earliest stages of the trial design. “We were very intentional about looking at things like social determinants of health, childcare, transportation, and things like that to ease some of the burden of participating in the trial, obviously in a legal and compliant way,” said Dr. Williams. The team also ensured complete and accurate translation of patient materials into Spanish.

The study was also a phase 4 trial, which may have simplified recruitment. “So it’s a therapy that’s already approved, which may make people feel more comfortable, but obviously the goal is for our phase 3 trials to make sure that we are recruiting represented populations. We’re taking these learnings and applying them to the broader clinical trial population so that hopefully we won’t have to come back and do phase 4 studies like this,” said Dr. Williams.

She noted that the results of more inclusive studies don’t just benefit underserved populations. “You have groups of people that are suffering and having more disability from a condition, and you need to understand why. When we broaden the population to understand those that are most vulnerable and underserved and [having the worst outcomes], it really helps us to better treat everybody. Because if we can get a hold of those factors that make us do the worst, then we can also better understand the factors that make us do the best,” said Dr. Williams.
 

Inclusive Recruitment in Clinical Trials

Asked for comment, Ahmed Obeidat, MD, PhD, highlighted the importance of inclusive recruitment. “The study is very important because historically and even in most recent clinical trials, these groups were markedly under-represented and most completed clinical trials derive conclusions based on the study of a nondiverse, White-non-Hispanic predominant population,” said Dr. Obeidat, who is an associate professor at the Medical College of Wisconsin, Milwaukee. He pointed to a systematic review showing that the median percentage of White participants in MS clinical trials was 93% and ranged from 86% to 98%.

“Several factors may contribute to the disparity in clinical trial participation, and solutions must be explored and developed. CHIMES is a first step in this direction where the study itself is designed to address disparity in MS clinical trial participation,” said Dr. Obeidat.

Dr. Obeidat also pointed to the need to consider other forms of diversity in clinical trials, such as older patients and those with advanced disability. “Investigators, coordinators, and other staff should all strive to be as inclusive as possible in clinical trials,” he said.

Dr. Williams has received consulting fees from Alexion, Biogen, Bristol Myers Squibb, EMD Serono, Genentech Inc., Janssen, Novartis, Sanofi, and TG Therapeutics, and serves on speakers bureaus for Biogen, Bristol Myers Squibb, EMD Serono, Janssen, Genentech, and TG Therapeutics. Dr. Ahmed Z. Obeidat has financial relationships with Alexion Pharmaceuticals, Banner Life Sciences, BD Biosciences, Biogen, Biologix Solutions, Bristol Myers Squibb, Celgene, EMD Serono, Genentech, GW Pharmaceuticals, Horizon Therapeutics, Jazz Pharmaceuticals, Novartis, Sandoz, Sanofi Genzyme, TG Therapeutics, and Viela Bio.