This transcript has been edited for clarity.

Dear colleagues, I am Christoph Diener from the medical faculty of the University of Duisburg-Essen in Germany. Today, I would like to discuss what happened in neurology in the past month.
 

Treatment of tension-type headache

I would like to start with headache. You are all aware that we have several new studies regarding the prevention of migraine, but very few studies involving nondrug treatments for tension-type headache.

A working group in Göttingen, Germany, conducted a study in people with frequent episodic and chronic tension-type headache. The first of the four randomized groups received traditional Chinese acupuncture for 3 months. The second group received physical therapy and exercise for 1 hour per week for 12 weeks. The third group received a combination of acupuncture and exercise. The last was a control group that received only standard care.

The outcome parameters of tension-type headache were evaluated after 6 months and again after 12 months. Previously, these same researchers published that the intensity but not the frequency of tension-type headache was reduced by active therapy.

In Cephalalgia, they published the outcome for the endpoints of depression, anxiety, and quality of life. Acupuncture, exercise, and the combination of the two improved depression, anxiety, and quality of life. This shows that nonmedical treatment is effective in people with frequent episodic and chronic tension-type headache.
 

Headache after COVID-19

The next study was published in Headache and discusses headache after COVID-19. In this review of published studies, more than 50% of people with COVID-19 develop headache. It is more frequent in young patients and people with preexisting primary headaches, such as migraine and tension-type headache. Prognosis is usually good, but some patients develop new, daily persistent headache, which is a major problem because treatment is unclear. We desperately need studies investigating how to treat this new, daily persistent headache after COVID-19.

SSRIs during COVID-19 infection

The next study also focuses on COVID-19. We have conflicting results from several studies suggesting that selective serotonin reuptake inhibitors might be effective in people with mild COVID-19 infection. This hypothesis was tested in a study in Brazil and was published in JAMA, The study included 1,288 outpatients with mild COVID-19 who either received 50 mg of fluvoxamine twice daily for 10 days or placebo. There was no benefit of the treatment for any outcome.

Preventing dementia with antihypertensive treatment

The next study was published in the European Heart Journal and addresses the question of whether effective antihypertensive treatment in elderly persons can prevent dementia. This is a meta-analysis of five placebo-controlled trials with more than 28,000 patients. The meta-analysis clearly shows that treating hypertension in elderly patients does prevent dementia. The benefit is higher if the blood pressure is lowered by a larger amount which also stays true for elderly patients. There is no negative impact of lowering blood pressure in this population.

Antiplatelet therapy

The next study was published in Stroke and reexamines whether resumption of antiplatelet therapy should be early or late in people who had an intracerebral hemorrhage while on antiplatelet therapy. In the Taiwanese Health Registry, this was studied in 1,584 patients. The researchers divided participants into groups based on whether antiplatelet therapy was resumed within 30 days or after 30 days. In 1 year, the rate of recurrent intracerebral hemorrhage was 3.2%. There was no difference whether antiplatelet therapy was resumed early or late.

Regular exercise in Parkinson’s disease

The final study is a review of nonmedical therapy. This meta-analysis of 19 randomized trials looked at the benefit of regular exercise in patients with Parkinson’s disease and depression. The analysis clearly showed that rigorous and moderate exercise improved depression in patients with Parkinson’s disease. This is very important because exercise improves not only the symptoms of Parkinson’s disease but also comorbid depression while presenting no serious adverse events or side effects.

Dr. Diener is a professor in the department of neurology at Stroke Center–Headache Center, University Duisburg-Essen, Germany. He disclosed ties with Abbott, Addex Pharma, Alder, Allergan, Almirall, Amgen, Autonomic Technology, AstraZeneca, Bayer Vital, Berlin Chemie, Bristol-Myers Squibb, Boehringer Ingelheim, Chordate, CoAxia, Corimmun, Covidien, Coherex, CoLucid, Daiichi Sankyo, D-Pharm, Electrocore, Fresenius, GlaxoSmithKline, Grunenthal, Janssen-Cilag, Labrys Biologics Lilly, La Roche, Lundbeck, 3M Medica, MSD, Medtronic, Menarini, MindFrame, Minster, Neuroscore, Neurobiological Technologies, Novartis, Novo Nordisk, Johnson & Johnson, Knoll, Paion, Parke-Davis, Pierre Fabre, Pfizer Inc, Schaper and Brummer, Sanofi-Aventis, Schering-Plough, Servier, Solvay, St. Jude, Talecris, Thrombogenics, WebMD Global, Weber and Weber, Wyeth, and Yamanouchi. Dr. Diener has served as editor of Aktuelle Neurologie, Arzneimitteltherapie, Kopfschmerz News, Stroke News, and the Treatment Guidelines of the German Neurological Society; as co-editor of Cephalalgia; and on the editorial board of The Lancet Neurology, Stroke, European Neurology, and Cerebrovascular Disorders. The department of neurology in Essen is supported by the German Research Council, the German Ministry of Education and Research, European Union, National Institutes of Health, Bertelsmann Foundation, and Heinz Nixdorf Foundation. Dr. Diener has no ownership interest and does not own stocks in any pharmaceutical company. A version of this article originally appeared on Medscape.com.

This transcript has been edited for clarity.

Dear colleagues, I am Christoph Diener from the medical faculty of the University of Duisburg-Essen in Germany. Today, I would like to discuss what happened in neurology in the past month.
 

Treatment of tension-type headache

I would like to start with headache. You are all aware that we have several new studies regarding the prevention of migraine, but very few studies involving nondrug treatments for tension-type headache.

A working group in Göttingen, Germany, conducted a study in people with frequent episodic and chronic tension-type headache. The first of the four randomized groups received traditional Chinese acupuncture for 3 months. The second group received physical therapy and exercise for 1 hour per week for 12 weeks. The third group received a combination of acupuncture and exercise. The last was a control group that received only standard care.

The outcome parameters of tension-type headache were evaluated after 6 months and again after 12 months. Previously, these same researchers published that the intensity but not the frequency of tension-type headache was reduced by active therapy.

In Cephalalgia, they published the outcome for the endpoints of depression, anxiety, and quality of life. Acupuncture, exercise, and the combination of the two improved depression, anxiety, and quality of life. This shows that nonmedical treatment is effective in people with frequent episodic and chronic tension-type headache.
 

Headache after COVID-19

The next study was published in Headache and discusses headache after COVID-19. In this review of published studies, more than 50% of people with COVID-19 develop headache. It is more frequent in young patients and people with preexisting primary headaches, such as migraine and tension-type headache. Prognosis is usually good, but some patients develop new, daily persistent headache, which is a major problem because treatment is unclear. We desperately need studies investigating how to treat this new, daily persistent headache after COVID-19.

SSRIs during COVID-19 infection

The next study also focuses on COVID-19. We have conflicting results from several studies suggesting that selective serotonin reuptake inhibitors might be effective in people with mild COVID-19 infection. This hypothesis was tested in a study in Brazil and was published in JAMA, The study included 1,288 outpatients with mild COVID-19 who either received 50 mg of fluvoxamine twice daily for 10 days or placebo. There was no benefit of the treatment for any outcome.

Preventing dementia with antihypertensive treatment

The next study was published in the European Heart Journal and addresses the question of whether effective antihypertensive treatment in elderly persons can prevent dementia. This is a meta-analysis of five placebo-controlled trials with more than 28,000 patients. The meta-analysis clearly shows that treating hypertension in elderly patients does prevent dementia. The benefit is higher if the blood pressure is lowered by a larger amount which also stays true for elderly patients. There is no negative impact of lowering blood pressure in this population.

Antiplatelet therapy

The next study was published in Stroke and reexamines whether resumption of antiplatelet therapy should be early or late in people who had an intracerebral hemorrhage while on antiplatelet therapy. In the Taiwanese Health Registry, this was studied in 1,584 patients. The researchers divided participants into groups based on whether antiplatelet therapy was resumed within 30 days or after 30 days. In 1 year, the rate of recurrent intracerebral hemorrhage was 3.2%. There was no difference whether antiplatelet therapy was resumed early or late.

Regular exercise in Parkinson’s disease

The final study is a review of nonmedical therapy. This meta-analysis of 19 randomized trials looked at the benefit of regular exercise in patients with Parkinson’s disease and depression. The analysis clearly showed that rigorous and moderate exercise improved depression in patients with Parkinson’s disease. This is very important because exercise improves not only the symptoms of Parkinson’s disease but also comorbid depression while presenting no serious adverse events or side effects.

Dr. Diener is a professor in the department of neurology at Stroke Center–Headache Center, University Duisburg-Essen, Germany. He disclosed ties with Abbott, Addex Pharma, Alder, Allergan, Almirall, Amgen, Autonomic Technology, AstraZeneca, Bayer Vital, Berlin Chemie, Bristol-Myers Squibb, Boehringer Ingelheim, Chordate, CoAxia, Corimmun, Covidien, Coherex, CoLucid, Daiichi Sankyo, D-Pharm, Electrocore, Fresenius, GlaxoSmithKline, Grunenthal, Janssen-Cilag, Labrys Biologics Lilly, La Roche, Lundbeck, 3M Medica, MSD, Medtronic, Menarini, MindFrame, Minster, Neuroscore, Neurobiological Technologies, Novartis, Novo Nordisk, Johnson & Johnson, Knoll, Paion, Parke-Davis, Pierre Fabre, Pfizer Inc, Schaper and Brummer, Sanofi-Aventis, Schering-Plough, Servier, Solvay, St. Jude, Talecris, Thrombogenics, WebMD Global, Weber and Weber, Wyeth, and Yamanouchi. Dr. Diener has served as editor of Aktuelle Neurologie, Arzneimitteltherapie, Kopfschmerz News, Stroke News, and the Treatment Guidelines of the German Neurological Society; as co-editor of Cephalalgia; and on the editorial board of The Lancet Neurology, Stroke, European Neurology, and Cerebrovascular Disorders. The department of neurology in Essen is supported by the German Research Council, the German Ministry of Education and Research, European Union, National Institutes of Health, Bertelsmann Foundation, and Heinz Nixdorf Foundation. Dr. Diener has no ownership interest and does not own stocks in any pharmaceutical company. A version of this article originally appeared on Medscape.com.

This transcript has been edited for clarity.

Dear colleagues, I am Christoph Diener from the medical faculty of the University of Duisburg-Essen in Germany. Today, I would like to discuss what happened in neurology in the past month.
 

Treatment of tension-type headache

I would like to start with headache. You are all aware that we have several new studies regarding the prevention of migraine, but very few studies involving nondrug treatments for tension-type headache.

A working group in Göttingen, Germany, conducted a study in people with frequent episodic and chronic tension-type headache. The first of the four randomized groups received traditional Chinese acupuncture for 3 months. The second group received physical therapy and exercise for 1 hour per week for 12 weeks. The third group received a combination of acupuncture and exercise. The last was a control group that received only standard care.

The outcome parameters of tension-type headache were evaluated after 6 months and again after 12 months. Previously, these same researchers published that the intensity but not the frequency of tension-type headache was reduced by active therapy.

In Cephalalgia, they published the outcome for the endpoints of depression, anxiety, and quality of life. Acupuncture, exercise, and the combination of the two improved depression, anxiety, and quality of life. This shows that nonmedical treatment is effective in people with frequent episodic and chronic tension-type headache.
 

Headache after COVID-19

The next study was published in Headache and discusses headache after COVID-19. In this review of published studies, more than 50% of people with COVID-19 develop headache. It is more frequent in young patients and people with preexisting primary headaches, such as migraine and tension-type headache. Prognosis is usually good, but some patients develop new, daily persistent headache, which is a major problem because treatment is unclear. We desperately need studies investigating how to treat this new, daily persistent headache after COVID-19.

SSRIs during COVID-19 infection

The next study also focuses on COVID-19. We have conflicting results from several studies suggesting that selective serotonin reuptake inhibitors might be effective in people with mild COVID-19 infection. This hypothesis was tested in a study in Brazil and was published in JAMA, The study included 1,288 outpatients with mild COVID-19 who either received 50 mg of fluvoxamine twice daily for 10 days or placebo. There was no benefit of the treatment for any outcome.

Preventing dementia with antihypertensive treatment

The next study was published in the European Heart Journal and addresses the question of whether effective antihypertensive treatment in elderly persons can prevent dementia. This is a meta-analysis of five placebo-controlled trials with more than 28,000 patients. The meta-analysis clearly shows that treating hypertension in elderly patients does prevent dementia. The benefit is higher if the blood pressure is lowered by a larger amount which also stays true for elderly patients. There is no negative impact of lowering blood pressure in this population.

Antiplatelet therapy

The next study was published in Stroke and reexamines whether resumption of antiplatelet therapy should be early or late in people who had an intracerebral hemorrhage while on antiplatelet therapy. In the Taiwanese Health Registry, this was studied in 1,584 patients. The researchers divided participants into groups based on whether antiplatelet therapy was resumed within 30 days or after 30 days. In 1 year, the rate of recurrent intracerebral hemorrhage was 3.2%. There was no difference whether antiplatelet therapy was resumed early or late.

Regular exercise in Parkinson’s disease

The final study is a review of nonmedical therapy. This meta-analysis of 19 randomized trials looked at the benefit of regular exercise in patients with Parkinson’s disease and depression. The analysis clearly showed that rigorous and moderate exercise improved depression in patients with Parkinson’s disease. This is very important because exercise improves not only the symptoms of Parkinson’s disease but also comorbid depression while presenting no serious adverse events or side effects.

Dr. Diener is a professor in the department of neurology at Stroke Center–Headache Center, University Duisburg-Essen, Germany. He disclosed ties with Abbott, Addex Pharma, Alder, Allergan, Almirall, Amgen, Autonomic Technology, AstraZeneca, Bayer Vital, Berlin Chemie, Bristol-Myers Squibb, Boehringer Ingelheim, Chordate, CoAxia, Corimmun, Covidien, Coherex, CoLucid, Daiichi Sankyo, D-Pharm, Electrocore, Fresenius, GlaxoSmithKline, Grunenthal, Janssen-Cilag, Labrys Biologics Lilly, La Roche, Lundbeck, 3M Medica, MSD, Medtronic, Menarini, MindFrame, Minster, Neuroscore, Neurobiological Technologies, Novartis, Novo Nordisk, Johnson & Johnson, Knoll, Paion, Parke-Davis, Pierre Fabre, Pfizer Inc, Schaper and Brummer, Sanofi-Aventis, Schering-Plough, Servier, Solvay, St. Jude, Talecris, Thrombogenics, WebMD Global, Weber and Weber, Wyeth, and Yamanouchi. Dr. Diener has served as editor of Aktuelle Neurologie, Arzneimitteltherapie, Kopfschmerz News, Stroke News, and the Treatment Guidelines of the German Neurological Society; as co-editor of Cephalalgia; and on the editorial board of The Lancet Neurology, Stroke, European Neurology, and Cerebrovascular Disorders. The department of neurology in Essen is supported by the German Research Council, the German Ministry of Education and Research, European Union, National Institutes of Health, Bertelsmann Foundation, and Heinz Nixdorf Foundation. Dr. Diener has no ownership interest and does not own stocks in any pharmaceutical company. A version of this article originally appeared on Medscape.com.

A new study says we can slow the pace at which we age by 2%-3% if we lower the number of calories we eat by 25%. That may seem like a little benefit for a large cut in calories. But experts say it’s actually a pretty big deal.

“In other studies, that same difference in pace of aging had meaningful consequences for people’s risk of dying,” says senior study author Daniel W. Belsky, PhD, a researcher at the Butler Columbia Aging Center at Columbia University, New York.

Cutting calories by 25% slowed the pace of aging in young and middle-aged adults by a few percentage points, compared with those who continued eating normally, the new research reveals. This first-of-its-kind study in humans adds to evidence from animal studies that the rate of aging can be changed.

Compared with 75 people who ate normally, the 145 people randomly assigned to cut back their calories slowed their pace of aging by 2%-3% over 2 years in the randomized controlled trial.

For example, a similar slowdown in the pace of aging was associated with a 10%-15% lower risk of dying over 10-15 years in previous work, Dr. Belsky says. “So 2%-3% slower aging doesn’t sound like maybe that big of a deal – but 10%-15% reduction in risk of dying seems like a big deal.”

Results of the study were published in the journal Nature Aging.

Even though the pace of aging slowed, the researchers did not find significant changes on two biological aging measures in the study, suggesting more work is needed.

The findings “are intriguing in that caloric restriction seemed to show a slower pace of aging in healthy adults,” says Vandana Sheth, a registered dietitian-nutritionist and owner of a nutrition consulting firm in Los Angeles. “This can have a significant impact on population health. However, larger studies need to be done to follow up on these findings.”


 

‘Exciting result’

Asked if the findings imply aging could be slowed down in people, Dr. Belsky says. “That is the ... exciting result from the trial. These results suggest it may be possible to slow the pace of biological aging with a behavioral intervention.”

But not everyone is completely convinced.

“This is good suggestive evidence that caloric restriction can modify aspects of biological aging in humans, similar to what has been known in laboratory animals for many decades,” says Matt Kaeberlein, PhD, director of the Healthy Aging and Longevity Research Institute at the University of Washington, Seattle, and senior author of a 2021 review article in Science.

Part of his concern is that cutting your calories by a quarter may not be a sustainable long-term strategy.

“It’s important to keep in mind that these measurements only report on a portion of biological aging and are probably not an accurate overall measurement of biological age or the rate of biological aging,” Dr. Kaeberlein says. The findings might suggest that “at the population level, a 25% reduction in caloric intake is unlikely to have large effects on biological aging unless implemented over many years, which is likely not reasonable for most people.”

Insight into intermittent fasting?

Cutting back on calories is related to other dietary strategies, including intermittent fasting and time-restricted eating, Dr. Belsky says. “Intermittent fasting and time-restricted eating are nutritional interventions that have been developed, in part, because in experiments with animals, they have some of the same biological effects as calorie restriction.”

There remain many unanswered questions.

“There are people who would argue that the reason calorie restriction does what it does is because when people are calorie-restricted, they also tend to restrict the times when they eat,” Dr. Belsky says. “They tend to have these longer fasts during the day.”

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

A new study says we can slow the pace at which we age by 2%-3% if we lower the number of calories we eat by 25%. That may seem like a little benefit for a large cut in calories. But experts say it’s actually a pretty big deal.

“In other studies, that same difference in pace of aging had meaningful consequences for people’s risk of dying,” says senior study author Daniel W. Belsky, PhD, a researcher at the Butler Columbia Aging Center at Columbia University, New York.

Cutting calories by 25% slowed the pace of aging in young and middle-aged adults by a few percentage points, compared with those who continued eating normally, the new research reveals. This first-of-its-kind study in humans adds to evidence from animal studies that the rate of aging can be changed.

Compared with 75 people who ate normally, the 145 people randomly assigned to cut back their calories slowed their pace of aging by 2%-3% over 2 years in the randomized controlled trial.

For example, a similar slowdown in the pace of aging was associated with a 10%-15% lower risk of dying over 10-15 years in previous work, Dr. Belsky says. “So 2%-3% slower aging doesn’t sound like maybe that big of a deal – but 10%-15% reduction in risk of dying seems like a big deal.”

Results of the study were published in the journal Nature Aging.

Even though the pace of aging slowed, the researchers did not find significant changes on two biological aging measures in the study, suggesting more work is needed.

The findings “are intriguing in that caloric restriction seemed to show a slower pace of aging in healthy adults,” says Vandana Sheth, a registered dietitian-nutritionist and owner of a nutrition consulting firm in Los Angeles. “This can have a significant impact on population health. However, larger studies need to be done to follow up on these findings.”


 

‘Exciting result’

Asked if the findings imply aging could be slowed down in people, Dr. Belsky says. “That is the ... exciting result from the trial. These results suggest it may be possible to slow the pace of biological aging with a behavioral intervention.”

But not everyone is completely convinced.

“This is good suggestive evidence that caloric restriction can modify aspects of biological aging in humans, similar to what has been known in laboratory animals for many decades,” says Matt Kaeberlein, PhD, director of the Healthy Aging and Longevity Research Institute at the University of Washington, Seattle, and senior author of a 2021 review article in Science.

Part of his concern is that cutting your calories by a quarter may not be a sustainable long-term strategy.

“It’s important to keep in mind that these measurements only report on a portion of biological aging and are probably not an accurate overall measurement of biological age or the rate of biological aging,” Dr. Kaeberlein says. The findings might suggest that “at the population level, a 25% reduction in caloric intake is unlikely to have large effects on biological aging unless implemented over many years, which is likely not reasonable for most people.”

Insight into intermittent fasting?

Cutting back on calories is related to other dietary strategies, including intermittent fasting and time-restricted eating, Dr. Belsky says. “Intermittent fasting and time-restricted eating are nutritional interventions that have been developed, in part, because in experiments with animals, they have some of the same biological effects as calorie restriction.”

There remain many unanswered questions.

“There are people who would argue that the reason calorie restriction does what it does is because when people are calorie-restricted, they also tend to restrict the times when they eat,” Dr. Belsky says. “They tend to have these longer fasts during the day.”

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

A new study says we can slow the pace at which we age by 2%-3% if we lower the number of calories we eat by 25%. That may seem like a little benefit for a large cut in calories. But experts say it’s actually a pretty big deal.

“In other studies, that same difference in pace of aging had meaningful consequences for people’s risk of dying,” says senior study author Daniel W. Belsky, PhD, a researcher at the Butler Columbia Aging Center at Columbia University, New York.

Cutting calories by 25% slowed the pace of aging in young and middle-aged adults by a few percentage points, compared with those who continued eating normally, the new research reveals. This first-of-its-kind study in humans adds to evidence from animal studies that the rate of aging can be changed.

Compared with 75 people who ate normally, the 145 people randomly assigned to cut back their calories slowed their pace of aging by 2%-3% over 2 years in the randomized controlled trial.

For example, a similar slowdown in the pace of aging was associated with a 10%-15% lower risk of dying over 10-15 years in previous work, Dr. Belsky says. “So 2%-3% slower aging doesn’t sound like maybe that big of a deal – but 10%-15% reduction in risk of dying seems like a big deal.”

Results of the study were published in the journal Nature Aging.

Even though the pace of aging slowed, the researchers did not find significant changes on two biological aging measures in the study, suggesting more work is needed.

The findings “are intriguing in that caloric restriction seemed to show a slower pace of aging in healthy adults,” says Vandana Sheth, a registered dietitian-nutritionist and owner of a nutrition consulting firm in Los Angeles. “This can have a significant impact on population health. However, larger studies need to be done to follow up on these findings.”


 

‘Exciting result’

Asked if the findings imply aging could be slowed down in people, Dr. Belsky says. “That is the ... exciting result from the trial. These results suggest it may be possible to slow the pace of biological aging with a behavioral intervention.”

But not everyone is completely convinced.

“This is good suggestive evidence that caloric restriction can modify aspects of biological aging in humans, similar to what has been known in laboratory animals for many decades,” says Matt Kaeberlein, PhD, director of the Healthy Aging and Longevity Research Institute at the University of Washington, Seattle, and senior author of a 2021 review article in Science.

Part of his concern is that cutting your calories by a quarter may not be a sustainable long-term strategy.

“It’s important to keep in mind that these measurements only report on a portion of biological aging and are probably not an accurate overall measurement of biological age or the rate of biological aging,” Dr. Kaeberlein says. The findings might suggest that “at the population level, a 25% reduction in caloric intake is unlikely to have large effects on biological aging unless implemented over many years, which is likely not reasonable for most people.”

Insight into intermittent fasting?

Cutting back on calories is related to other dietary strategies, including intermittent fasting and time-restricted eating, Dr. Belsky says. “Intermittent fasting and time-restricted eating are nutritional interventions that have been developed, in part, because in experiments with animals, they have some of the same biological effects as calorie restriction.”

There remain many unanswered questions.

“There are people who would argue that the reason calorie restriction does what it does is because when people are calorie-restricted, they also tend to restrict the times when they eat,” Dr. Belsky says. “They tend to have these longer fasts during the day.”

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

Some time ago I was invited to join a bipartisan congressional task force on valley fever, also known as coccidioidomycosis. A large and diverse crowd attended the task force’s first meeting in Bakersfield, Calif. – a meeting for everyone: the medical profession, the public, it even included veterinarians.

The whole thing was a resounding success. Francis Collins was there, the just-retired director of the NIH. Tom Frieden, then-director of the Centers for Disease Control and Prevention was there, as were several congresspeople and also my college roommate, a retired Navy medical corps captain. I was enjoying it.

Afterward, we had a banquet dinner at a restaurant in downtown Bakersfield. One of the people there was a woman I knew well – her husband was a physician friend. The restaurant served steak and salmon, and this woman made the mistake of ordering the steak.

Not long after the entrees were served, I heard a commotion at the table just behind me. I turned around and saw that woman in distress. A piece of steak had wedged in her trachea and she couldn’t breathe.

Almost immediately, the chef showed up. I don’t know how he got there. The chef at this restaurant was a big guy. I mean, probably 6 feet, 5 inches tall and 275 pounds. He tried the Heimlich maneuver. It didn’t work.

At that point, I jumped up. I thought, “Well, maybe I know how to do this better than him.” Probably not, actually. I tried and couldn’t make it work either. So I knew we were going to have to do something.

Paul Krogstad, my friend and research partner who is a pediatric infectious disease physician, stepped up and tried to put his finger in her throat and dig it out. He couldn’t get it. The patient had lost consciousness.

So, I’m thinking, okay, there’s really only one choice. You have to get an airway surgically.

I said, “We have to put her down on the floor.” And then I said, “Knife!”

I was looking at the steak knives on the table and they weren’t to my liking for doing a procedure. My college roommate – the retired Navy man – whipped out this very good pocketknife.

So, there we were, I had Paul Krogstad holding her head, and CDC Director Tom Frieden taking her pulse, which she still had. I took the knife and did a cricothyroidotomy. I had never done this in my life.

While I was making the incision, somebody gave Paul a ballpoint pen and he broke it into pieces to make a tracheostomy tube. Once I’d made the little incision, I put the tube in. She wasn’t breathing, but she still had a pulse.

I leaned forward and blew into the tube and inflated her lungs. I could see her lungs balloon up. It was a nice feeling, because I knew I was clearly in the right place.

I can’t quite explain it, but while I was doing this, I was enormously calm and totally focused. I knew there was a crowd of people around me, all looking at me, but I wasn’t conscious of that.

It was really just the four of us: Paul and Tom and me and our patient. Those were the only people that I was really cognizant of. Paul and Tom were not panic stricken at all. I remember somebody shouting, “We have to start CPR!” and Frieden said, “No. We don’t.”

Moments later, she woke up, sat up, coughed, and shot the piece of steak across the room.

She was breathing on her own, but we still taped that tube into place. Somebody had already summoned an ambulance; they were there not very long after we completed this procedure. I got in the ambulance with her and we rode over to the emergency room at Mercy Truxtun.

She was stable and doing okay. I sat with her until a thoracic surgeon showed up. He checked out the situation and decided we didn’t need that tube and took it out. I didn’t want to take that out until I had a surgeon there who could do a formal tracheostomy.

They kept her in the hospital for 3 or 4 days. Now, this woman had always had difficulties swallowing, so steak may not have been the best choice. She still had trouble swallowing afterward but recovered.

I’ve known her and her husband a long time, so it was certainly rewarding to be able to provide this service. Years later, though, when her husband died, I spoke at his funeral. When she was speaking to the gathering, she said, “And oh, by the way, Royce, thanks for saving my life.”

That surprised me. I didn’t think we were going to go there.

I’d never tried to practice medicine “at the roadside” before. But that’s part of the career.

Royce Johnson, MD, is the chief of the division of infectious disease among other leadership positions at Kern Medical in Bakersfield, Calif., and the medical director of the Valley Fever Institute.

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

Some time ago I was invited to join a bipartisan congressional task force on valley fever, also known as coccidioidomycosis. A large and diverse crowd attended the task force’s first meeting in Bakersfield, Calif. – a meeting for everyone: the medical profession, the public, it even included veterinarians.

The whole thing was a resounding success. Francis Collins was there, the just-retired director of the NIH. Tom Frieden, then-director of the Centers for Disease Control and Prevention was there, as were several congresspeople and also my college roommate, a retired Navy medical corps captain. I was enjoying it.

Afterward, we had a banquet dinner at a restaurant in downtown Bakersfield. One of the people there was a woman I knew well – her husband was a physician friend. The restaurant served steak and salmon, and this woman made the mistake of ordering the steak.

Not long after the entrees were served, I heard a commotion at the table just behind me. I turned around and saw that woman in distress. A piece of steak had wedged in her trachea and she couldn’t breathe.

Almost immediately, the chef showed up. I don’t know how he got there. The chef at this restaurant was a big guy. I mean, probably 6 feet, 5 inches tall and 275 pounds. He tried the Heimlich maneuver. It didn’t work.

At that point, I jumped up. I thought, “Well, maybe I know how to do this better than him.” Probably not, actually. I tried and couldn’t make it work either. So I knew we were going to have to do something.

Paul Krogstad, my friend and research partner who is a pediatric infectious disease physician, stepped up and tried to put his finger in her throat and dig it out. He couldn’t get it. The patient had lost consciousness.

So, I’m thinking, okay, there’s really only one choice. You have to get an airway surgically.

I said, “We have to put her down on the floor.” And then I said, “Knife!”

I was looking at the steak knives on the table and they weren’t to my liking for doing a procedure. My college roommate – the retired Navy man – whipped out this very good pocketknife.

So, there we were, I had Paul Krogstad holding her head, and CDC Director Tom Frieden taking her pulse, which she still had. I took the knife and did a cricothyroidotomy. I had never done this in my life.

While I was making the incision, somebody gave Paul a ballpoint pen and he broke it into pieces to make a tracheostomy tube. Once I’d made the little incision, I put the tube in. She wasn’t breathing, but she still had a pulse.

I leaned forward and blew into the tube and inflated her lungs. I could see her lungs balloon up. It was a nice feeling, because I knew I was clearly in the right place.

I can’t quite explain it, but while I was doing this, I was enormously calm and totally focused. I knew there was a crowd of people around me, all looking at me, but I wasn’t conscious of that.

It was really just the four of us: Paul and Tom and me and our patient. Those were the only people that I was really cognizant of. Paul and Tom were not panic stricken at all. I remember somebody shouting, “We have to start CPR!” and Frieden said, “No. We don’t.”

Moments later, she woke up, sat up, coughed, and shot the piece of steak across the room.

She was breathing on her own, but we still taped that tube into place. Somebody had already summoned an ambulance; they were there not very long after we completed this procedure. I got in the ambulance with her and we rode over to the emergency room at Mercy Truxtun.

She was stable and doing okay. I sat with her until a thoracic surgeon showed up. He checked out the situation and decided we didn’t need that tube and took it out. I didn’t want to take that out until I had a surgeon there who could do a formal tracheostomy.

They kept her in the hospital for 3 or 4 days. Now, this woman had always had difficulties swallowing, so steak may not have been the best choice. She still had trouble swallowing afterward but recovered.

I’ve known her and her husband a long time, so it was certainly rewarding to be able to provide this service. Years later, though, when her husband died, I spoke at his funeral. When she was speaking to the gathering, she said, “And oh, by the way, Royce, thanks for saving my life.”

That surprised me. I didn’t think we were going to go there.

I’d never tried to practice medicine “at the roadside” before. But that’s part of the career.

Royce Johnson, MD, is the chief of the division of infectious disease among other leadership positions at Kern Medical in Bakersfield, Calif., and the medical director of the Valley Fever Institute.

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

Some time ago I was invited to join a bipartisan congressional task force on valley fever, also known as coccidioidomycosis. A large and diverse crowd attended the task force’s first meeting in Bakersfield, Calif. – a meeting for everyone: the medical profession, the public, it even included veterinarians.

The whole thing was a resounding success. Francis Collins was there, the just-retired director of the NIH. Tom Frieden, then-director of the Centers for Disease Control and Prevention was there, as were several congresspeople and also my college roommate, a retired Navy medical corps captain. I was enjoying it.

Afterward, we had a banquet dinner at a restaurant in downtown Bakersfield. One of the people there was a woman I knew well – her husband was a physician friend. The restaurant served steak and salmon, and this woman made the mistake of ordering the steak.

Not long after the entrees were served, I heard a commotion at the table just behind me. I turned around and saw that woman in distress. A piece of steak had wedged in her trachea and she couldn’t breathe.

Almost immediately, the chef showed up. I don’t know how he got there. The chef at this restaurant was a big guy. I mean, probably 6 feet, 5 inches tall and 275 pounds. He tried the Heimlich maneuver. It didn’t work.

At that point, I jumped up. I thought, “Well, maybe I know how to do this better than him.” Probably not, actually. I tried and couldn’t make it work either. So I knew we were going to have to do something.

Paul Krogstad, my friend and research partner who is a pediatric infectious disease physician, stepped up and tried to put his finger in her throat and dig it out. He couldn’t get it. The patient had lost consciousness.

So, I’m thinking, okay, there’s really only one choice. You have to get an airway surgically.

I said, “We have to put her down on the floor.” And then I said, “Knife!”

I was looking at the steak knives on the table and they weren’t to my liking for doing a procedure. My college roommate – the retired Navy man – whipped out this very good pocketknife.

So, there we were, I had Paul Krogstad holding her head, and CDC Director Tom Frieden taking her pulse, which she still had. I took the knife and did a cricothyroidotomy. I had never done this in my life.

While I was making the incision, somebody gave Paul a ballpoint pen and he broke it into pieces to make a tracheostomy tube. Once I’d made the little incision, I put the tube in. She wasn’t breathing, but she still had a pulse.

I leaned forward and blew into the tube and inflated her lungs. I could see her lungs balloon up. It was a nice feeling, because I knew I was clearly in the right place.

I can’t quite explain it, but while I was doing this, I was enormously calm and totally focused. I knew there was a crowd of people around me, all looking at me, but I wasn’t conscious of that.

It was really just the four of us: Paul and Tom and me and our patient. Those were the only people that I was really cognizant of. Paul and Tom were not panic stricken at all. I remember somebody shouting, “We have to start CPR!” and Frieden said, “No. We don’t.”

Moments later, she woke up, sat up, coughed, and shot the piece of steak across the room.

She was breathing on her own, but we still taped that tube into place. Somebody had already summoned an ambulance; they were there not very long after we completed this procedure. I got in the ambulance with her and we rode over to the emergency room at Mercy Truxtun.

She was stable and doing okay. I sat with her until a thoracic surgeon showed up. He checked out the situation and decided we didn’t need that tube and took it out. I didn’t want to take that out until I had a surgeon there who could do a formal tracheostomy.

They kept her in the hospital for 3 or 4 days. Now, this woman had always had difficulties swallowing, so steak may not have been the best choice. She still had trouble swallowing afterward but recovered.

I’ve known her and her husband a long time, so it was certainly rewarding to be able to provide this service. Years later, though, when her husband died, I spoke at his funeral. When she was speaking to the gathering, she said, “And oh, by the way, Royce, thanks for saving my life.”

That surprised me. I didn’t think we were going to go there.

I’d never tried to practice medicine “at the roadside” before. But that’s part of the career.

Royce Johnson, MD, is the chief of the division of infectious disease among other leadership positions at Kern Medical in Bakersfield, Calif., and the medical director of the Valley Fever Institute.

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

A tool that incorporates lupus-related variables with traditional risk factors provides a much more accurate assessment of cardiovascular (CV) risk in patients with systemic lupus erythematosus (SLE), according to data presented at the annual meeting of the Canadian Rheumatology Association.

In the initial clinical assessment of this tool, called the SLECRISK, “it identified high-risk lupus patients who would otherwise be missed by traditional methods of CV risk assessment,” reported May Y. Choi, MD, associate director of translational research at the University of Calgary’s (Alta.) Lupus Centre of Excellence.

bowdenimages/iStock/Getty Images

It is well known that patients with SLE face an increased risk of CV events starting at an age long before risk begins climbing in the general population, according to Dr. Choi. She cited one study that showed women aged 35-44 years have a 50-fold greater risk of myocardial infarction than healthy individuals.

All major guidelines recognize this increased risk and recommend CV risk assessment in patients with SLE, even though Dr. Choi pointed out that traditional tools, such as the American College of Cardiology atherosclerotic cardiovascular disease (ASCVD) risk calculator or the Framingham Risk Score (FRS) have a limited ability to detect the patients with SLE who are most likely to have an event.
 

In SLE, current tools are inadequate

“These risk assessment tools perform poorly in SLE patients because they do not capture SLE-related inflammation,” Dr. Choi said. Of several examples, Dr. Choi cited a study showing “seven times more MIs and strokes observed than expected in SLE patients on the basis of the FRS.”

The disparity between expected and observed MIs and strokes is worse with increasing severity of SLE. In a study she presented 3 years ago, rates of CV events were 12 times higher in those with inactive or mild SLE, rising to a 16-fold increase among those with moderate disease and jumping to a 32-fold increase in those with severe SLE.

The SLECRISK tool was developed from the Brigham and Women’s Hospital SLE Registry, which was initiated in 1992. Patients without a history of CV disease were evaluated for traditional CV risk factors and for SLE-specific characteristics such as disease activity, levels of the complement proteins C3 and C4, kidney function, the presence of nephritis, and SLE duration. The value of these characteristics as predictors of CV events were then assessed over a 10-year follow-up period before being assembled into the SLECRISK tool.

In an example of the risk equation, Dr. Choi described a 50-year-old patient with SLE and a 5% 10-year ASCVD risk score, which is low. After adjustment for SLE risks, which included 10 years disease duration, high disease activity, elevated creatinine, and positive anti–double stranded DNA status, the 10-year CV risk score climbed to 16.2%, which is moderate.

The performance of the SLECRISK was evaluated in 1,243 patients providing 8,946.51 person-years of follow-up. During this period, there were 90 major adverse cardiac events (MACE), of which 82% were adjudicated by cardiologists, and 211 secondary events.

Relative to the ASCVD risk score, the SLECRISK identified about twice as many patients with SLE as having moderate risk and 3.5-fold more patients as having high risk. Among patients who experienced CV events, traditional CV risk factors were more common but so were SLE-specific risk factors, including greater disease severity, a greater likelihood of lupus nephritis, increased complement levels, and greater exposure to glucocorticoids, according to Dr. Choi.

Specificities for CV events higher on SLECRISK

In predicting CV events, the differences in specificities were in the same general range, although somewhat higher for the ASCVD risk score in regard to predicting MACE (83% vs. 72%) and MACE plus secondary events (90% vs. 79%). However, the sensitivities were much higher for SLECRISK relative to the ASCVD risk score for MACE alone (64% vs. 41%) and for MACE plus secondary events (58% vs. 35%).

When comparing those who had an MI or stroke, the ASCVD risk score identified 8 (7%) patients missed by SLECRISK, whereas SLECRISK identified 89 (73%) missed by the ASCVD risk score. The remaining 25 patients (20%) were identified by both. The advantage of SLECRISK was similar for MACE plus secondary outcomes.

Dr. Choi noted that all of the SLE-specific variables in SLECRISK are readily obtained and often already available in patient charts. She said that there is a plan to validate the tool in larger groups, but with a goal of creating a tool available online for clinicians and their patients to use. There is also an even more ambitious plan for the future.

“We have funding to look at machine learning to evaluate predictive variables in SLE patients,” Dr. Choi said. Rather than adding SLE-specific variables to traditional risks, the plan is to “start from scratch,” letting artificial intelligence assemble predictors without prejudice to what might or might not be relevant.

A SLE-specific tool for evaluating CV risk is an important “unmet need,” according to Karen H. Costenbader, MD, professor in the division of rheumatology, inflammation, and immunity at Brigham and Women’s Hospital and Harvard Medical School, both in Boston. In an interview, she reiterated that measuring CV risk in SLE is already guideline recommended, but conventional tools have been shown to be inaccurate.

“I can envision it being used in clinical encounters to help guide shared decision-making with patients,” explained Dr. Costenbader, who was not involved in the presentation at the CRA meeting but worked with Dr. Choi in developing SLECRISK. “It would give us more precise estimates, allowing us to risk stratify our patients and informing us as to which modifiable SLE-specific and nonspecific factors are contributing most to CV risk.’

The problem of using conventional risk assessments in SLE has been well recognized. Of those who have written on this subject, Maureen McMahon, MD, site director of the Lupus Clinical Trials Network at the University of California, Los Angeles, said: “There is a critical need for the development of SLE-specific risk assessment tools like SLECRISK.”

Author of several studies looking at alternatives for CV risk assessment in SLE, including a study looking at a panel of biomarkers that was published in ACR Open Rheumatology, Dr. McMahon said in an interview that CV risk in SLE is high but conventional risk assessments are flawed.

“Multiple previous studies have demonstrated that these currently available calculators are not adequate for identifying risk in the lupus patient population,” she said. According to Dr. McMahon, the fact that rheumatologists remain “dependent upon [these conventional] cardiovascular risk calculators” is a well-recognized problem that needs resolution.

Dr. Choi has financial relationships with AstraZeneca, GlaxoSmithKline, Mallinckrodt. MitogenDx, Organon, and Werfen International. Dr. Costenbader reports no potential conflicts of interest. Dr. McMahon has financial relationships with AstraZeneca, Aurinia Pharmaceuticals, Eli Lilly, and GlaxoSmithKline.

A tool that incorporates lupus-related variables with traditional risk factors provides a much more accurate assessment of cardiovascular (CV) risk in patients with systemic lupus erythematosus (SLE), according to data presented at the annual meeting of the Canadian Rheumatology Association.

In the initial clinical assessment of this tool, called the SLECRISK, “it identified high-risk lupus patients who would otherwise be missed by traditional methods of CV risk assessment,” reported May Y. Choi, MD, associate director of translational research at the University of Calgary’s (Alta.) Lupus Centre of Excellence.

bowdenimages/iStock/Getty Images

It is well known that patients with SLE face an increased risk of CV events starting at an age long before risk begins climbing in the general population, according to Dr. Choi. She cited one study that showed women aged 35-44 years have a 50-fold greater risk of myocardial infarction than healthy individuals.

All major guidelines recognize this increased risk and recommend CV risk assessment in patients with SLE, even though Dr. Choi pointed out that traditional tools, such as the American College of Cardiology atherosclerotic cardiovascular disease (ASCVD) risk calculator or the Framingham Risk Score (FRS) have a limited ability to detect the patients with SLE who are most likely to have an event.
 

In SLE, current tools are inadequate

“These risk assessment tools perform poorly in SLE patients because they do not capture SLE-related inflammation,” Dr. Choi said. Of several examples, Dr. Choi cited a study showing “seven times more MIs and strokes observed than expected in SLE patients on the basis of the FRS.”

The disparity between expected and observed MIs and strokes is worse with increasing severity of SLE. In a study she presented 3 years ago, rates of CV events were 12 times higher in those with inactive or mild SLE, rising to a 16-fold increase among those with moderate disease and jumping to a 32-fold increase in those with severe SLE.

The SLECRISK tool was developed from the Brigham and Women’s Hospital SLE Registry, which was initiated in 1992. Patients without a history of CV disease were evaluated for traditional CV risk factors and for SLE-specific characteristics such as disease activity, levels of the complement proteins C3 and C4, kidney function, the presence of nephritis, and SLE duration. The value of these characteristics as predictors of CV events were then assessed over a 10-year follow-up period before being assembled into the SLECRISK tool.

In an example of the risk equation, Dr. Choi described a 50-year-old patient with SLE and a 5% 10-year ASCVD risk score, which is low. After adjustment for SLE risks, which included 10 years disease duration, high disease activity, elevated creatinine, and positive anti–double stranded DNA status, the 10-year CV risk score climbed to 16.2%, which is moderate.

The performance of the SLECRISK was evaluated in 1,243 patients providing 8,946.51 person-years of follow-up. During this period, there were 90 major adverse cardiac events (MACE), of which 82% were adjudicated by cardiologists, and 211 secondary events.

Relative to the ASCVD risk score, the SLECRISK identified about twice as many patients with SLE as having moderate risk and 3.5-fold more patients as having high risk. Among patients who experienced CV events, traditional CV risk factors were more common but so were SLE-specific risk factors, including greater disease severity, a greater likelihood of lupus nephritis, increased complement levels, and greater exposure to glucocorticoids, according to Dr. Choi.

Specificities for CV events higher on SLECRISK

In predicting CV events, the differences in specificities were in the same general range, although somewhat higher for the ASCVD risk score in regard to predicting MACE (83% vs. 72%) and MACE plus secondary events (90% vs. 79%). However, the sensitivities were much higher for SLECRISK relative to the ASCVD risk score for MACE alone (64% vs. 41%) and for MACE plus secondary events (58% vs. 35%).

When comparing those who had an MI or stroke, the ASCVD risk score identified 8 (7%) patients missed by SLECRISK, whereas SLECRISK identified 89 (73%) missed by the ASCVD risk score. The remaining 25 patients (20%) were identified by both. The advantage of SLECRISK was similar for MACE plus secondary outcomes.

Dr. Choi noted that all of the SLE-specific variables in SLECRISK are readily obtained and often already available in patient charts. She said that there is a plan to validate the tool in larger groups, but with a goal of creating a tool available online for clinicians and their patients to use. There is also an even more ambitious plan for the future.

“We have funding to look at machine learning to evaluate predictive variables in SLE patients,” Dr. Choi said. Rather than adding SLE-specific variables to traditional risks, the plan is to “start from scratch,” letting artificial intelligence assemble predictors without prejudice to what might or might not be relevant.

A SLE-specific tool for evaluating CV risk is an important “unmet need,” according to Karen H. Costenbader, MD, professor in the division of rheumatology, inflammation, and immunity at Brigham and Women’s Hospital and Harvard Medical School, both in Boston. In an interview, she reiterated that measuring CV risk in SLE is already guideline recommended, but conventional tools have been shown to be inaccurate.

“I can envision it being used in clinical encounters to help guide shared decision-making with patients,” explained Dr. Costenbader, who was not involved in the presentation at the CRA meeting but worked with Dr. Choi in developing SLECRISK. “It would give us more precise estimates, allowing us to risk stratify our patients and informing us as to which modifiable SLE-specific and nonspecific factors are contributing most to CV risk.’

The problem of using conventional risk assessments in SLE has been well recognized. Of those who have written on this subject, Maureen McMahon, MD, site director of the Lupus Clinical Trials Network at the University of California, Los Angeles, said: “There is a critical need for the development of SLE-specific risk assessment tools like SLECRISK.”

Author of several studies looking at alternatives for CV risk assessment in SLE, including a study looking at a panel of biomarkers that was published in ACR Open Rheumatology, Dr. McMahon said in an interview that CV risk in SLE is high but conventional risk assessments are flawed.

“Multiple previous studies have demonstrated that these currently available calculators are not adequate for identifying risk in the lupus patient population,” she said. According to Dr. McMahon, the fact that rheumatologists remain “dependent upon [these conventional] cardiovascular risk calculators” is a well-recognized problem that needs resolution.

Dr. Choi has financial relationships with AstraZeneca, GlaxoSmithKline, Mallinckrodt. MitogenDx, Organon, and Werfen International. Dr. Costenbader reports no potential conflicts of interest. Dr. McMahon has financial relationships with AstraZeneca, Aurinia Pharmaceuticals, Eli Lilly, and GlaxoSmithKline.

A tool that incorporates lupus-related variables with traditional risk factors provides a much more accurate assessment of cardiovascular (CV) risk in patients with systemic lupus erythematosus (SLE), according to data presented at the annual meeting of the Canadian Rheumatology Association.

In the initial clinical assessment of this tool, called the SLECRISK, “it identified high-risk lupus patients who would otherwise be missed by traditional methods of CV risk assessment,” reported May Y. Choi, MD, associate director of translational research at the University of Calgary’s (Alta.) Lupus Centre of Excellence.

bowdenimages/iStock/Getty Images

It is well known that patients with SLE face an increased risk of CV events starting at an age long before risk begins climbing in the general population, according to Dr. Choi. She cited one study that showed women aged 35-44 years have a 50-fold greater risk of myocardial infarction than healthy individuals.

All major guidelines recognize this increased risk and recommend CV risk assessment in patients with SLE, even though Dr. Choi pointed out that traditional tools, such as the American College of Cardiology atherosclerotic cardiovascular disease (ASCVD) risk calculator or the Framingham Risk Score (FRS) have a limited ability to detect the patients with SLE who are most likely to have an event.
 

In SLE, current tools are inadequate

“These risk assessment tools perform poorly in SLE patients because they do not capture SLE-related inflammation,” Dr. Choi said. Of several examples, Dr. Choi cited a study showing “seven times more MIs and strokes observed than expected in SLE patients on the basis of the FRS.”

The disparity between expected and observed MIs and strokes is worse with increasing severity of SLE. In a study she presented 3 years ago, rates of CV events were 12 times higher in those with inactive or mild SLE, rising to a 16-fold increase among those with moderate disease and jumping to a 32-fold increase in those with severe SLE.

The SLECRISK tool was developed from the Brigham and Women’s Hospital SLE Registry, which was initiated in 1992. Patients without a history of CV disease were evaluated for traditional CV risk factors and for SLE-specific characteristics such as disease activity, levels of the complement proteins C3 and C4, kidney function, the presence of nephritis, and SLE duration. The value of these characteristics as predictors of CV events were then assessed over a 10-year follow-up period before being assembled into the SLECRISK tool.

In an example of the risk equation, Dr. Choi described a 50-year-old patient with SLE and a 5% 10-year ASCVD risk score, which is low. After adjustment for SLE risks, which included 10 years disease duration, high disease activity, elevated creatinine, and positive anti–double stranded DNA status, the 10-year CV risk score climbed to 16.2%, which is moderate.

The performance of the SLECRISK was evaluated in 1,243 patients providing 8,946.51 person-years of follow-up. During this period, there were 90 major adverse cardiac events (MACE), of which 82% were adjudicated by cardiologists, and 211 secondary events.

Relative to the ASCVD risk score, the SLECRISK identified about twice as many patients with SLE as having moderate risk and 3.5-fold more patients as having high risk. Among patients who experienced CV events, traditional CV risk factors were more common but so were SLE-specific risk factors, including greater disease severity, a greater likelihood of lupus nephritis, increased complement levels, and greater exposure to glucocorticoids, according to Dr. Choi.

Specificities for CV events higher on SLECRISK

In predicting CV events, the differences in specificities were in the same general range, although somewhat higher for the ASCVD risk score in regard to predicting MACE (83% vs. 72%) and MACE plus secondary events (90% vs. 79%). However, the sensitivities were much higher for SLECRISK relative to the ASCVD risk score for MACE alone (64% vs. 41%) and for MACE plus secondary events (58% vs. 35%).

When comparing those who had an MI or stroke, the ASCVD risk score identified 8 (7%) patients missed by SLECRISK, whereas SLECRISK identified 89 (73%) missed by the ASCVD risk score. The remaining 25 patients (20%) were identified by both. The advantage of SLECRISK was similar for MACE plus secondary outcomes.

Dr. Choi noted that all of the SLE-specific variables in SLECRISK are readily obtained and often already available in patient charts. She said that there is a plan to validate the tool in larger groups, but with a goal of creating a tool available online for clinicians and their patients to use. There is also an even more ambitious plan for the future.

“We have funding to look at machine learning to evaluate predictive variables in SLE patients,” Dr. Choi said. Rather than adding SLE-specific variables to traditional risks, the plan is to “start from scratch,” letting artificial intelligence assemble predictors without prejudice to what might or might not be relevant.

A SLE-specific tool for evaluating CV risk is an important “unmet need,” according to Karen H. Costenbader, MD, professor in the division of rheumatology, inflammation, and immunity at Brigham and Women’s Hospital and Harvard Medical School, both in Boston. In an interview, she reiterated that measuring CV risk in SLE is already guideline recommended, but conventional tools have been shown to be inaccurate.

“I can envision it being used in clinical encounters to help guide shared decision-making with patients,” explained Dr. Costenbader, who was not involved in the presentation at the CRA meeting but worked with Dr. Choi in developing SLECRISK. “It would give us more precise estimates, allowing us to risk stratify our patients and informing us as to which modifiable SLE-specific and nonspecific factors are contributing most to CV risk.’

The problem of using conventional risk assessments in SLE has been well recognized. Of those who have written on this subject, Maureen McMahon, MD, site director of the Lupus Clinical Trials Network at the University of California, Los Angeles, said: “There is a critical need for the development of SLE-specific risk assessment tools like SLECRISK.”

Author of several studies looking at alternatives for CV risk assessment in SLE, including a study looking at a panel of biomarkers that was published in ACR Open Rheumatology, Dr. McMahon said in an interview that CV risk in SLE is high but conventional risk assessments are flawed.

“Multiple previous studies have demonstrated that these currently available calculators are not adequate for identifying risk in the lupus patient population,” she said. According to Dr. McMahon, the fact that rheumatologists remain “dependent upon [these conventional] cardiovascular risk calculators” is a well-recognized problem that needs resolution.

Dr. Choi has financial relationships with AstraZeneca, GlaxoSmithKline, Mallinckrodt. MitogenDx, Organon, and Werfen International. Dr. Costenbader reports no potential conflicts of interest. Dr. McMahon has financial relationships with AstraZeneca, Aurinia Pharmaceuticals, Eli Lilly, and GlaxoSmithKline.

A combination of two drugs has shown promising results, including a reduction in cognitive impairment in patients who have had a lacunar stroke, and is seen as a new therapeutic approach for patients with cerebral small-vessel disease. The drugs – isosorbide mononitrate and cilostazol – stabilize endothelial function, which is a new therapeutic target for patients with small-vessel disease stroke.

The phase 2 LACI-2 study, evaluating these drugs individually and in combination in patients with lacunar stroke, showed promising trends toward reductions in recurrent stroke, cognitive impairment, and dependency, some of which became significant when the drugs were given together. There was also some suggestion of positive impacts on mood and quality of life.

“Isosorbide mononitrate was associated with a reduction in recurrent stroke, a tendency toward a reduction in dependency and a reduction in cognitive impairment, and cilostazol also seemed to reduce dependency,” study investigator Joanna M. Wardlaw, MD, professor of applied neuroimaging at Edinburgh University, reported.

“When used together, they seemed to have more benefits than either drug on its own. So this is good preliminary evidence that the drugs are working together in a positive way,” she said. But she cautioned that these potential benefits will need to be confirmed in a larger phase 3 trial.

The LACI-2 study was presented at the International Stroke Conference by Dr. Wardlaw and coinvestigator Philip Bath, DSc, professor of medicine at the University of Nottingham (England).

They both highlighted the effect seen on cognitive impairment at the conference presented by the American Stroke Association, a division of the American Heart Association.

“We saw a significant reduction in the number of patients with cognitive impairment with the two drugs together in this phase 2 study,” Dr. Wardlaw said. “This is very encouraging since no study has previously found any medications that positively affect cognitive impairment in small-vessel disease strokes. We cautiously hope that these medications may have wider implications for other types of small-vessel disease as well.”

Dr. Bath added: “The results on cognitive impairment are particularly important. Many patients rate cognitive impairment as one of the most dreaded outcomes of a stroke even if they also have quite significant physical disability. People simply don’t want to lose their memory and thinking ability.”

“The results of LACI-2 also raise interesting questions about whether these drugs would be beneficial for other types of small-vessel disease which do not present as stroke, but maybe may manifest as headaches or memory impairment,” he noted.
 

‘Very intriguing results’

Outside experts were enthusiastic about these preliminary results. In an ISC highlights presentation, program chair Tudor Jovin, MD, Cooper Neurological Institute, Cherry Hill, N.J., said: “It is refreshing to finally see some positive signals in studies in small-vessel stroke. This is an area where we haven’t had answers for a long time.”

He described the reduction in cognitive impairment seen in the study as “very intriguing and very important.”

“I think we have underestimated the burden that cognitive impairment has in stroke, and the burden in general in society of vascular cognitive impairment. This is a very promising approach that definitely deserves to be investigated more thoroughly in a larger trial.”

Commenting on the study findings, Mitchell Elkind, MD, professor of neurology and epidemiology at Columbia University Irving Medical Center, New York, said this study “provides evidence that points us in at least two important directions.”

“First, it suggests that endothelial dysfunction, or problems with the lining of the blood vessels, may be an important contributor to small-vessel disease and the cognitive decline that often accompanies it. This is a new mechanism of action and different from blood clotting, blood pressure, and other conventional targets of treatment,” Dr. Elkind said.

“Second, and more generally, it suggests that stroke trials, particularly in the subtype of small-vessel disease, can and should explore not only the incidence of recurrent acute events but also the steady decline that occurs after stroke. Poststroke cognitive decline is a relatively new area of stroke research.”

Dr. Wardlaw noted that lacunar stroke is a common type of ischemic stroke, but it has been rather neglected in terms of research. It is assumed to be caused by atherosclerosis of the small vessel but there is now mounting evidence suggesting that it is a result of problems in the endothelium of the small vessels.  

“We looked for potential available drugs that targeted endothelial dysfunction. Both the drugs we tested are already widely used – isosorbide mononitrate for the treatment of coronary artery disease and angina, and cilostazol, mainly in Asia, for stroke prevention,” she said.  

LACI-2 was primarily a feasibility study looking at whether it was possible to recruit enough patients who had had a lacunar stroke and would take the drugs, individually or in combination, for up to a year. Outcomes were investigated on an exploratory basis. The study enrolled 363 patients who had experienced lacunar stroke from 26 stroke centers throughout the United Kingdom. They were randomly assigned to one of four treatment groups for 1 year:

• 40-60 mg/day of oral isosorbide mononitrate alone.
• 200 mg/day of oral cilostazol alone.
• Both medications.
• Neither medication.

Patients completed phone surveys at 6 and 12 months to assess health status, including recurrent stroke, myocardial infarction, cognitive tests, symptoms, quality of life surveys, and they also had brain imaging at 12 months.

Results showed 98% of patients were still taking their study medication at 1 year, and the drugs appeared to be safe on top of usual care with few deaths or hemorrhages in the study.

The composite outcome including recurrent stroke, MI, cognitive impairment, dependency (modified Rankin score > 2) and death was reduced by 20% in the isosorbide mononitrate–alone group (adjusted hazard ratio, 0.80; 95% confidence interval, 0.59-1.09).

The composite endpoint was reduced by 23% in the cilostazol group (aHR, 0.77; 95% CI, 0.57-1.05) and by 42% in the combination group (aHR, 0.58, 95% CI, 0.36-0.92) compared with those taking neither drug.

Isosorbide mononitrate alone showed trends toward a reduction in recurrent stroke, cognitive impairment, and dependency, whereas cilostazol alone reduced dependency with a trend toward a reduction in cognitive impairment. When used together, the drugs showed large reductions in cognitive impairment (aHR, 0.44; 95% CI, 0.19-0.99) and dependency (aHR ,0.14; 95% CI, 0.03-0.59).

During the highlights session, Dr. Jovin commented: “It is obvious that the investigators have put a lot of thought into the design of this trial. Presumably because of the composite score they were able to increase the power. We are used to trials which require thousands of patients, but here we are able to see significant results, although exploratory, with just a few hundred patients.”

Dr. Bath stressed that this was only a phase 2 study. “We now need to see if we can confirm these results in a larger phase 3 study.” That study, LACI-3, is planned to start later this year. He also suggested that it would be interesting to investigate whether these drugs would work in other types of ischemic stroke such as those caused by large-artery disease or cardioembolic strokes, as well as other forms of small-vessel disease such as patients with vascular cognitive impairment.

“There are many areas to investigate in future. It might be that in a few years’ time these drugs may be standard of care across many different forms of small-vessel disease,” he said.

Dr. Wardlaw noted that lacunar strokes are generally quite mild strokes, which could be one of the reasons why they have not been the target of much research to date. But Dr. Bath added: “While they may be labeled as a mild stroke on the NIHSS scale, patients can still be quite badly affected. About half of patients with a lacunar stroke develop cognitive impairment and eventually dementia – that is certainly not mild.”

The study was funded primarily by the British Heart Foundation, with support from the UK Alzheimer’s Society, the UK Dementia Research Institute, the Stroke Association, the Fondation Leducq, NHS Research Scotland, and the UK National Institutes of Health Research Clinical Research Networks. Dr. Bath is an adviser to CoMind, DiaMedica, Phagenesis, and Roche. Dr. Wardlaw reports no relevant financial relationships.

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

A combination of two drugs has shown promising results, including a reduction in cognitive impairment in patients who have had a lacunar stroke, and is seen as a new therapeutic approach for patients with cerebral small-vessel disease. The drugs – isosorbide mononitrate and cilostazol – stabilize endothelial function, which is a new therapeutic target for patients with small-vessel disease stroke.

The phase 2 LACI-2 study, evaluating these drugs individually and in combination in patients with lacunar stroke, showed promising trends toward reductions in recurrent stroke, cognitive impairment, and dependency, some of which became significant when the drugs were given together. There was also some suggestion of positive impacts on mood and quality of life.

“Isosorbide mononitrate was associated with a reduction in recurrent stroke, a tendency toward a reduction in dependency and a reduction in cognitive impairment, and cilostazol also seemed to reduce dependency,” study investigator Joanna M. Wardlaw, MD, professor of applied neuroimaging at Edinburgh University, reported.

“When used together, they seemed to have more benefits than either drug on its own. So this is good preliminary evidence that the drugs are working together in a positive way,” she said. But she cautioned that these potential benefits will need to be confirmed in a larger phase 3 trial.

The LACI-2 study was presented at the International Stroke Conference by Dr. Wardlaw and coinvestigator Philip Bath, DSc, professor of medicine at the University of Nottingham (England).

They both highlighted the effect seen on cognitive impairment at the conference presented by the American Stroke Association, a division of the American Heart Association.

“We saw a significant reduction in the number of patients with cognitive impairment with the two drugs together in this phase 2 study,” Dr. Wardlaw said. “This is very encouraging since no study has previously found any medications that positively affect cognitive impairment in small-vessel disease strokes. We cautiously hope that these medications may have wider implications for other types of small-vessel disease as well.”

Dr. Bath added: “The results on cognitive impairment are particularly important. Many patients rate cognitive impairment as one of the most dreaded outcomes of a stroke even if they also have quite significant physical disability. People simply don’t want to lose their memory and thinking ability.”

“The results of LACI-2 also raise interesting questions about whether these drugs would be beneficial for other types of small-vessel disease which do not present as stroke, but maybe may manifest as headaches or memory impairment,” he noted.
 

‘Very intriguing results’

Outside experts were enthusiastic about these preliminary results. In an ISC highlights presentation, program chair Tudor Jovin, MD, Cooper Neurological Institute, Cherry Hill, N.J., said: “It is refreshing to finally see some positive signals in studies in small-vessel stroke. This is an area where we haven’t had answers for a long time.”

He described the reduction in cognitive impairment seen in the study as “very intriguing and very important.”

“I think we have underestimated the burden that cognitive impairment has in stroke, and the burden in general in society of vascular cognitive impairment. This is a very promising approach that definitely deserves to be investigated more thoroughly in a larger trial.”

Commenting on the study findings, Mitchell Elkind, MD, professor of neurology and epidemiology at Columbia University Irving Medical Center, New York, said this study “provides evidence that points us in at least two important directions.”

“First, it suggests that endothelial dysfunction, or problems with the lining of the blood vessels, may be an important contributor to small-vessel disease and the cognitive decline that often accompanies it. This is a new mechanism of action and different from blood clotting, blood pressure, and other conventional targets of treatment,” Dr. Elkind said.

“Second, and more generally, it suggests that stroke trials, particularly in the subtype of small-vessel disease, can and should explore not only the incidence of recurrent acute events but also the steady decline that occurs after stroke. Poststroke cognitive decline is a relatively new area of stroke research.”

Dr. Wardlaw noted that lacunar stroke is a common type of ischemic stroke, but it has been rather neglected in terms of research. It is assumed to be caused by atherosclerosis of the small vessel but there is now mounting evidence suggesting that it is a result of problems in the endothelium of the small vessels.  

“We looked for potential available drugs that targeted endothelial dysfunction. Both the drugs we tested are already widely used – isosorbide mononitrate for the treatment of coronary artery disease and angina, and cilostazol, mainly in Asia, for stroke prevention,” she said.  

LACI-2 was primarily a feasibility study looking at whether it was possible to recruit enough patients who had had a lacunar stroke and would take the drugs, individually or in combination, for up to a year. Outcomes were investigated on an exploratory basis. The study enrolled 363 patients who had experienced lacunar stroke from 26 stroke centers throughout the United Kingdom. They were randomly assigned to one of four treatment groups for 1 year:

• 40-60 mg/day of oral isosorbide mononitrate alone.
• 200 mg/day of oral cilostazol alone.
• Both medications.
• Neither medication.

Patients completed phone surveys at 6 and 12 months to assess health status, including recurrent stroke, myocardial infarction, cognitive tests, symptoms, quality of life surveys, and they also had brain imaging at 12 months.

Results showed 98% of patients were still taking their study medication at 1 year, and the drugs appeared to be safe on top of usual care with few deaths or hemorrhages in the study.

The composite outcome including recurrent stroke, MI, cognitive impairment, dependency (modified Rankin score > 2) and death was reduced by 20% in the isosorbide mononitrate–alone group (adjusted hazard ratio, 0.80; 95% confidence interval, 0.59-1.09).

The composite endpoint was reduced by 23% in the cilostazol group (aHR, 0.77; 95% CI, 0.57-1.05) and by 42% in the combination group (aHR, 0.58, 95% CI, 0.36-0.92) compared with those taking neither drug.

Isosorbide mononitrate alone showed trends toward a reduction in recurrent stroke, cognitive impairment, and dependency, whereas cilostazol alone reduced dependency with a trend toward a reduction in cognitive impairment. When used together, the drugs showed large reductions in cognitive impairment (aHR, 0.44; 95% CI, 0.19-0.99) and dependency (aHR ,0.14; 95% CI, 0.03-0.59).

During the highlights session, Dr. Jovin commented: “It is obvious that the investigators have put a lot of thought into the design of this trial. Presumably because of the composite score they were able to increase the power. We are used to trials which require thousands of patients, but here we are able to see significant results, although exploratory, with just a few hundred patients.”

Dr. Bath stressed that this was only a phase 2 study. “We now need to see if we can confirm these results in a larger phase 3 study.” That study, LACI-3, is planned to start later this year. He also suggested that it would be interesting to investigate whether these drugs would work in other types of ischemic stroke such as those caused by large-artery disease or cardioembolic strokes, as well as other forms of small-vessel disease such as patients with vascular cognitive impairment.

“There are many areas to investigate in future. It might be that in a few years’ time these drugs may be standard of care across many different forms of small-vessel disease,” he said.

Dr. Wardlaw noted that lacunar strokes are generally quite mild strokes, which could be one of the reasons why they have not been the target of much research to date. But Dr. Bath added: “While they may be labeled as a mild stroke on the NIHSS scale, patients can still be quite badly affected. About half of patients with a lacunar stroke develop cognitive impairment and eventually dementia – that is certainly not mild.”

The study was funded primarily by the British Heart Foundation, with support from the UK Alzheimer’s Society, the UK Dementia Research Institute, the Stroke Association, the Fondation Leducq, NHS Research Scotland, and the UK National Institutes of Health Research Clinical Research Networks. Dr. Bath is an adviser to CoMind, DiaMedica, Phagenesis, and Roche. Dr. Wardlaw reports no relevant financial relationships.

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

A combination of two drugs has shown promising results, including a reduction in cognitive impairment in patients who have had a lacunar stroke, and is seen as a new therapeutic approach for patients with cerebral small-vessel disease. The drugs – isosorbide mononitrate and cilostazol – stabilize endothelial function, which is a new therapeutic target for patients with small-vessel disease stroke.

The phase 2 LACI-2 study, evaluating these drugs individually and in combination in patients with lacunar stroke, showed promising trends toward reductions in recurrent stroke, cognitive impairment, and dependency, some of which became significant when the drugs were given together. There was also some suggestion of positive impacts on mood and quality of life.

“Isosorbide mononitrate was associated with a reduction in recurrent stroke, a tendency toward a reduction in dependency and a reduction in cognitive impairment, and cilostazol also seemed to reduce dependency,” study investigator Joanna M. Wardlaw, MD, professor of applied neuroimaging at Edinburgh University, reported.

“When used together, they seemed to have more benefits than either drug on its own. So this is good preliminary evidence that the drugs are working together in a positive way,” she said. But she cautioned that these potential benefits will need to be confirmed in a larger phase 3 trial.

The LACI-2 study was presented at the International Stroke Conference by Dr. Wardlaw and coinvestigator Philip Bath, DSc, professor of medicine at the University of Nottingham (England).

They both highlighted the effect seen on cognitive impairment at the conference presented by the American Stroke Association, a division of the American Heart Association.

“We saw a significant reduction in the number of patients with cognitive impairment with the two drugs together in this phase 2 study,” Dr. Wardlaw said. “This is very encouraging since no study has previously found any medications that positively affect cognitive impairment in small-vessel disease strokes. We cautiously hope that these medications may have wider implications for other types of small-vessel disease as well.”

Dr. Bath added: “The results on cognitive impairment are particularly important. Many patients rate cognitive impairment as one of the most dreaded outcomes of a stroke even if they also have quite significant physical disability. People simply don’t want to lose their memory and thinking ability.”

“The results of LACI-2 also raise interesting questions about whether these drugs would be beneficial for other types of small-vessel disease which do not present as stroke, but maybe may manifest as headaches or memory impairment,” he noted.
 

‘Very intriguing results’

Outside experts were enthusiastic about these preliminary results. In an ISC highlights presentation, program chair Tudor Jovin, MD, Cooper Neurological Institute, Cherry Hill, N.J., said: “It is refreshing to finally see some positive signals in studies in small-vessel stroke. This is an area where we haven’t had answers for a long time.”

He described the reduction in cognitive impairment seen in the study as “very intriguing and very important.”

“I think we have underestimated the burden that cognitive impairment has in stroke, and the burden in general in society of vascular cognitive impairment. This is a very promising approach that definitely deserves to be investigated more thoroughly in a larger trial.”

Commenting on the study findings, Mitchell Elkind, MD, professor of neurology and epidemiology at Columbia University Irving Medical Center, New York, said this study “provides evidence that points us in at least two important directions.”

“First, it suggests that endothelial dysfunction, or problems with the lining of the blood vessels, may be an important contributor to small-vessel disease and the cognitive decline that often accompanies it. This is a new mechanism of action and different from blood clotting, blood pressure, and other conventional targets of treatment,” Dr. Elkind said.

“Second, and more generally, it suggests that stroke trials, particularly in the subtype of small-vessel disease, can and should explore not only the incidence of recurrent acute events but also the steady decline that occurs after stroke. Poststroke cognitive decline is a relatively new area of stroke research.”

Dr. Wardlaw noted that lacunar stroke is a common type of ischemic stroke, but it has been rather neglected in terms of research. It is assumed to be caused by atherosclerosis of the small vessel but there is now mounting evidence suggesting that it is a result of problems in the endothelium of the small vessels.  

“We looked for potential available drugs that targeted endothelial dysfunction. Both the drugs we tested are already widely used – isosorbide mononitrate for the treatment of coronary artery disease and angina, and cilostazol, mainly in Asia, for stroke prevention,” she said.  

LACI-2 was primarily a feasibility study looking at whether it was possible to recruit enough patients who had had a lacunar stroke and would take the drugs, individually or in combination, for up to a year. Outcomes were investigated on an exploratory basis. The study enrolled 363 patients who had experienced lacunar stroke from 26 stroke centers throughout the United Kingdom. They were randomly assigned to one of four treatment groups for 1 year:

• 40-60 mg/day of oral isosorbide mononitrate alone.
• 200 mg/day of oral cilostazol alone.
• Both medications.
• Neither medication.

Patients completed phone surveys at 6 and 12 months to assess health status, including recurrent stroke, myocardial infarction, cognitive tests, symptoms, quality of life surveys, and they also had brain imaging at 12 months.

Results showed 98% of patients were still taking their study medication at 1 year, and the drugs appeared to be safe on top of usual care with few deaths or hemorrhages in the study.

The composite outcome including recurrent stroke, MI, cognitive impairment, dependency (modified Rankin score > 2) and death was reduced by 20% in the isosorbide mononitrate–alone group (adjusted hazard ratio, 0.80; 95% confidence interval, 0.59-1.09).

The composite endpoint was reduced by 23% in the cilostazol group (aHR, 0.77; 95% CI, 0.57-1.05) and by 42% in the combination group (aHR, 0.58, 95% CI, 0.36-0.92) compared with those taking neither drug.

Isosorbide mononitrate alone showed trends toward a reduction in recurrent stroke, cognitive impairment, and dependency, whereas cilostazol alone reduced dependency with a trend toward a reduction in cognitive impairment. When used together, the drugs showed large reductions in cognitive impairment (aHR, 0.44; 95% CI, 0.19-0.99) and dependency (aHR ,0.14; 95% CI, 0.03-0.59).

During the highlights session, Dr. Jovin commented: “It is obvious that the investigators have put a lot of thought into the design of this trial. Presumably because of the composite score they were able to increase the power. We are used to trials which require thousands of patients, but here we are able to see significant results, although exploratory, with just a few hundred patients.”

Dr. Bath stressed that this was only a phase 2 study. “We now need to see if we can confirm these results in a larger phase 3 study.” That study, LACI-3, is planned to start later this year. He also suggested that it would be interesting to investigate whether these drugs would work in other types of ischemic stroke such as those caused by large-artery disease or cardioembolic strokes, as well as other forms of small-vessel disease such as patients with vascular cognitive impairment.

“There are many areas to investigate in future. It might be that in a few years’ time these drugs may be standard of care across many different forms of small-vessel disease,” he said.

Dr. Wardlaw noted that lacunar strokes are generally quite mild strokes, which could be one of the reasons why they have not been the target of much research to date. But Dr. Bath added: “While they may be labeled as a mild stroke on the NIHSS scale, patients can still be quite badly affected. About half of patients with a lacunar stroke develop cognitive impairment and eventually dementia – that is certainly not mild.”

The study was funded primarily by the British Heart Foundation, with support from the UK Alzheimer’s Society, the UK Dementia Research Institute, the Stroke Association, the Fondation Leducq, NHS Research Scotland, and the UK National Institutes of Health Research Clinical Research Networks. Dr. Bath is an adviser to CoMind, DiaMedica, Phagenesis, and Roche. Dr. Wardlaw reports no relevant financial relationships.

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

Tenecteplase is as effective as alteplase with respect to disability outcomes and safety in Chinese patients with ischemic stroke, a new study has found. “This was a pivotal trial in establishing the safety and efficacy of tenecteplase as an alternative to alteplase in the thrombolytic treatment of acute ischemic stroke within 4.5 hours in Asian patients,” said study author Shuya Li, MD, associate chief physician, department of neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing.

The findings in this all-Chinese population should have an impact on the use of tenecteplase going forward, said Dr. Li. “The results provide further evidence to support a worldwide switch to tenecteplase as the preferred thrombolytic for acute ischemic stroke.”

The findings were presented at the 2023 International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
 

Single bolus

Use of alteplase (tissue plasminogen activator [tPA]) has for years been the main approach to thrombolytic reperfusion therapy for patients with acute stroke, but tenecteplase has recently emerged as a potential successor.

Tenecteplase is a tPA produced by recombinant DNA technology. It has a relatively long half-life and can be delivered in a single bolus instead of requiring an hour-long infusion, as is the case with alteplase.

The phase 3 noninferiority Tenecteplase Reperfusion Therapy in Acute ischemic Cerebrovascular Events (TRACE-2) trial – the first of its kind in an Asian population – included 1,430 adult ischemic stroke patients at 53 Chinese centers. Patients had to have a National Institutes of Health Stroke Scale (NIHSS) score of 5-25 and either not be eligible for or have refused endovascular therapy.

The mean age of study participants was about 66 years, and the percentage of women was about 31%. The mean baseline NIHSS score was 7 in both groups, and the symptom-onset-to-needle time was similar at 180 minutes for the tenecteplase group and 178.5 minutes for the alteplase group.

Researchers randomly assigned patients to receive tenecteplase or alteplase within 4.5 hours of symptom onset.

Those in the tenecteplase group received 0.25 mg/kg of the drug in a single IV bolus (maximum dose, 25 mg). Control group members who were treated with alteplase were given the drug as a 10% bolus, with the remainder given as a 1-hour infusion (0.9 mg/kg with a maximum dose of 90 mg).
 

Showed noninferiority

The primary efficacy outcome was a modified Rankins scale (mRS) score of 0-1 at 90 days, which is considered excellent function. About 62% of tenecteplase patients and 58% of alteplase patients attained this outcome (risk ratio, 1.09; 95% confidence interval, 1.00-1.18).

The P value was .001 for noninferiority and .06 for superiority, but Dr. Li explained that these values may change when considering the site effect.

There were no statistically significant differences between the two drugs on secondary outcomes of favorable function. For example, 73% of tenecteplase patients and 72% of alteplase patients had an mRS score of 0-2 at 3 months, and 50% in the tenecteplase and 49% in the alteplase group improved by 4 or more points on the NIHSS, or had a score of 1 or less, at 24 hours.

The groups also had comparable scores on the European quality-of-life visual analogue scale and on the Barthel index, which measures functional independence related to personal care and mobility.

Tenecteplase also turned out to be as safe at alteplase. About 2% in both groups had symptomatic intracranial hemorrhage within 36 hours, and both groups had that same percentage for such hemorrhages within 90 days. As well, the groups had a similar rate of any intracranial hemorrhage within 90 days (6% and 7%).

The mortality rate was 7% in the tenecteplase group, compared with 5% in the alteplase group.

Adverse events (AEs) occurred in 86% and 87%, and serious AEs in 16% and 15%, of the tenecteplase and alteplase groups, respectively, again with no statistically significant differences.

The research team aims to test the effectiveness of tenecteplase in other stroke patients, including those with minor strokes, those receiving thrombolysis in a later window, and those receiving endovascular therapy, said Dr. Li.
 

Strong evidence

Commenting on the study findings, Larry B. Goldstein, MD, professor and chair of neurology, University of Kentucky, Lexington, said it is important to determine the efficacy of tenecteplase among Asians, as they represent “an entirely different population” with unique concerns, such as bleeding complications from anticoagulants.

He noted an advantage of tenecteplase is ease of administration. “You don’t have to go through the loading dose and then the 1-hour infusion,” which poses an “additional hassle” when transferring patients between institutions, he said.

However, he noted that a possible “downside” to having both drugs available in the emergency department is “using the wrong drug at the wrong dose” because of their similar sounding names.

Also commenting on the study, Tudor G. Jovin, MD, professor and chair, department of neurology, Rowan University, Camden, N.J., said he welcomes another trial that confirms that these two drugs are biologically similar.

“I’m very glad this trial was done because it adds another very strong piece of evidence of equivalency.”

But the two drugs are not the same in some important respects, said Dr. Jovin, whose center switched to using tenecteplase almost 3 years ago. That switch has resulted in cutting 17 minutes from the door-to-needle time “which is quite significant,” he said.

“There’s no question that once we used tenecteplase in lieu of tPA, it’s been just so much easier to administer and affects the interhospital transfer protocols, because you’re not transferring the patient with a critical care IV. It’s a win-win situation for everyone.”

The study received funding from the National Science and Technology Major Project, the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, and the China Shijiazhuang Pharmaceutical Company Recomgen Pharmaceutical (Guangzhou). Dr. Li, Dr. Goldstein, and Dr. Jovin report no relevant financial relationships.

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

Tenecteplase is as effective as alteplase with respect to disability outcomes and safety in Chinese patients with ischemic stroke, a new study has found. “This was a pivotal trial in establishing the safety and efficacy of tenecteplase as an alternative to alteplase in the thrombolytic treatment of acute ischemic stroke within 4.5 hours in Asian patients,” said study author Shuya Li, MD, associate chief physician, department of neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing.

The findings in this all-Chinese population should have an impact on the use of tenecteplase going forward, said Dr. Li. “The results provide further evidence to support a worldwide switch to tenecteplase as the preferred thrombolytic for acute ischemic stroke.”

The findings were presented at the 2023 International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
 

Single bolus

Use of alteplase (tissue plasminogen activator [tPA]) has for years been the main approach to thrombolytic reperfusion therapy for patients with acute stroke, but tenecteplase has recently emerged as a potential successor.

Tenecteplase is a tPA produced by recombinant DNA technology. It has a relatively long half-life and can be delivered in a single bolus instead of requiring an hour-long infusion, as is the case with alteplase.

The phase 3 noninferiority Tenecteplase Reperfusion Therapy in Acute ischemic Cerebrovascular Events (TRACE-2) trial – the first of its kind in an Asian population – included 1,430 adult ischemic stroke patients at 53 Chinese centers. Patients had to have a National Institutes of Health Stroke Scale (NIHSS) score of 5-25 and either not be eligible for or have refused endovascular therapy.

The mean age of study participants was about 66 years, and the percentage of women was about 31%. The mean baseline NIHSS score was 7 in both groups, and the symptom-onset-to-needle time was similar at 180 minutes for the tenecteplase group and 178.5 minutes for the alteplase group.

Researchers randomly assigned patients to receive tenecteplase or alteplase within 4.5 hours of symptom onset.

Those in the tenecteplase group received 0.25 mg/kg of the drug in a single IV bolus (maximum dose, 25 mg). Control group members who were treated with alteplase were given the drug as a 10% bolus, with the remainder given as a 1-hour infusion (0.9 mg/kg with a maximum dose of 90 mg).
 

Showed noninferiority

The primary efficacy outcome was a modified Rankins scale (mRS) score of 0-1 at 90 days, which is considered excellent function. About 62% of tenecteplase patients and 58% of alteplase patients attained this outcome (risk ratio, 1.09; 95% confidence interval, 1.00-1.18).

The P value was .001 for noninferiority and .06 for superiority, but Dr. Li explained that these values may change when considering the site effect.

There were no statistically significant differences between the two drugs on secondary outcomes of favorable function. For example, 73% of tenecteplase patients and 72% of alteplase patients had an mRS score of 0-2 at 3 months, and 50% in the tenecteplase and 49% in the alteplase group improved by 4 or more points on the NIHSS, or had a score of 1 or less, at 24 hours.

The groups also had comparable scores on the European quality-of-life visual analogue scale and on the Barthel index, which measures functional independence related to personal care and mobility.

Tenecteplase also turned out to be as safe at alteplase. About 2% in both groups had symptomatic intracranial hemorrhage within 36 hours, and both groups had that same percentage for such hemorrhages within 90 days. As well, the groups had a similar rate of any intracranial hemorrhage within 90 days (6% and 7%).

The mortality rate was 7% in the tenecteplase group, compared with 5% in the alteplase group.

Adverse events (AEs) occurred in 86% and 87%, and serious AEs in 16% and 15%, of the tenecteplase and alteplase groups, respectively, again with no statistically significant differences.

The research team aims to test the effectiveness of tenecteplase in other stroke patients, including those with minor strokes, those receiving thrombolysis in a later window, and those receiving endovascular therapy, said Dr. Li.
 

Strong evidence

Commenting on the study findings, Larry B. Goldstein, MD, professor and chair of neurology, University of Kentucky, Lexington, said it is important to determine the efficacy of tenecteplase among Asians, as they represent “an entirely different population” with unique concerns, such as bleeding complications from anticoagulants.

He noted an advantage of tenecteplase is ease of administration. “You don’t have to go through the loading dose and then the 1-hour infusion,” which poses an “additional hassle” when transferring patients between institutions, he said.

However, he noted that a possible “downside” to having both drugs available in the emergency department is “using the wrong drug at the wrong dose” because of their similar sounding names.

Also commenting on the study, Tudor G. Jovin, MD, professor and chair, department of neurology, Rowan University, Camden, N.J., said he welcomes another trial that confirms that these two drugs are biologically similar.

“I’m very glad this trial was done because it adds another very strong piece of evidence of equivalency.”

But the two drugs are not the same in some important respects, said Dr. Jovin, whose center switched to using tenecteplase almost 3 years ago. That switch has resulted in cutting 17 minutes from the door-to-needle time “which is quite significant,” he said.

“There’s no question that once we used tenecteplase in lieu of tPA, it’s been just so much easier to administer and affects the interhospital transfer protocols, because you’re not transferring the patient with a critical care IV. It’s a win-win situation for everyone.”

The study received funding from the National Science and Technology Major Project, the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, and the China Shijiazhuang Pharmaceutical Company Recomgen Pharmaceutical (Guangzhou). Dr. Li, Dr. Goldstein, and Dr. Jovin report no relevant financial relationships.

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

Tenecteplase is as effective as alteplase with respect to disability outcomes and safety in Chinese patients with ischemic stroke, a new study has found. “This was a pivotal trial in establishing the safety and efficacy of tenecteplase as an alternative to alteplase in the thrombolytic treatment of acute ischemic stroke within 4.5 hours in Asian patients,” said study author Shuya Li, MD, associate chief physician, department of neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing.

The findings in this all-Chinese population should have an impact on the use of tenecteplase going forward, said Dr. Li. “The results provide further evidence to support a worldwide switch to tenecteplase as the preferred thrombolytic for acute ischemic stroke.”

The findings were presented at the 2023 International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
 

Single bolus

Use of alteplase (tissue plasminogen activator [tPA]) has for years been the main approach to thrombolytic reperfusion therapy for patients with acute stroke, but tenecteplase has recently emerged as a potential successor.

Tenecteplase is a tPA produced by recombinant DNA technology. It has a relatively long half-life and can be delivered in a single bolus instead of requiring an hour-long infusion, as is the case with alteplase.

The phase 3 noninferiority Tenecteplase Reperfusion Therapy in Acute ischemic Cerebrovascular Events (TRACE-2) trial – the first of its kind in an Asian population – included 1,430 adult ischemic stroke patients at 53 Chinese centers. Patients had to have a National Institutes of Health Stroke Scale (NIHSS) score of 5-25 and either not be eligible for or have refused endovascular therapy.

The mean age of study participants was about 66 years, and the percentage of women was about 31%. The mean baseline NIHSS score was 7 in both groups, and the symptom-onset-to-needle time was similar at 180 minutes for the tenecteplase group and 178.5 minutes for the alteplase group.

Researchers randomly assigned patients to receive tenecteplase or alteplase within 4.5 hours of symptom onset.

Those in the tenecteplase group received 0.25 mg/kg of the drug in a single IV bolus (maximum dose, 25 mg). Control group members who were treated with alteplase were given the drug as a 10% bolus, with the remainder given as a 1-hour infusion (0.9 mg/kg with a maximum dose of 90 mg).
 

Showed noninferiority

The primary efficacy outcome was a modified Rankins scale (mRS) score of 0-1 at 90 days, which is considered excellent function. About 62% of tenecteplase patients and 58% of alteplase patients attained this outcome (risk ratio, 1.09; 95% confidence interval, 1.00-1.18).

The P value was .001 for noninferiority and .06 for superiority, but Dr. Li explained that these values may change when considering the site effect.

There were no statistically significant differences between the two drugs on secondary outcomes of favorable function. For example, 73% of tenecteplase patients and 72% of alteplase patients had an mRS score of 0-2 at 3 months, and 50% in the tenecteplase and 49% in the alteplase group improved by 4 or more points on the NIHSS, or had a score of 1 or less, at 24 hours.

The groups also had comparable scores on the European quality-of-life visual analogue scale and on the Barthel index, which measures functional independence related to personal care and mobility.

Tenecteplase also turned out to be as safe at alteplase. About 2% in both groups had symptomatic intracranial hemorrhage within 36 hours, and both groups had that same percentage for such hemorrhages within 90 days. As well, the groups had a similar rate of any intracranial hemorrhage within 90 days (6% and 7%).

The mortality rate was 7% in the tenecteplase group, compared with 5% in the alteplase group.

Adverse events (AEs) occurred in 86% and 87%, and serious AEs in 16% and 15%, of the tenecteplase and alteplase groups, respectively, again with no statistically significant differences.

The research team aims to test the effectiveness of tenecteplase in other stroke patients, including those with minor strokes, those receiving thrombolysis in a later window, and those receiving endovascular therapy, said Dr. Li.
 

Strong evidence

Commenting on the study findings, Larry B. Goldstein, MD, professor and chair of neurology, University of Kentucky, Lexington, said it is important to determine the efficacy of tenecteplase among Asians, as they represent “an entirely different population” with unique concerns, such as bleeding complications from anticoagulants.

He noted an advantage of tenecteplase is ease of administration. “You don’t have to go through the loading dose and then the 1-hour infusion,” which poses an “additional hassle” when transferring patients between institutions, he said.

However, he noted that a possible “downside” to having both drugs available in the emergency department is “using the wrong drug at the wrong dose” because of their similar sounding names.

Also commenting on the study, Tudor G. Jovin, MD, professor and chair, department of neurology, Rowan University, Camden, N.J., said he welcomes another trial that confirms that these two drugs are biologically similar.

“I’m very glad this trial was done because it adds another very strong piece of evidence of equivalency.”

But the two drugs are not the same in some important respects, said Dr. Jovin, whose center switched to using tenecteplase almost 3 years ago. That switch has resulted in cutting 17 minutes from the door-to-needle time “which is quite significant,” he said.

“There’s no question that once we used tenecteplase in lieu of tPA, it’s been just so much easier to administer and affects the interhospital transfer protocols, because you’re not transferring the patient with a critical care IV. It’s a win-win situation for everyone.”

The study received funding from the National Science and Technology Major Project, the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, and the China Shijiazhuang Pharmaceutical Company Recomgen Pharmaceutical (Guangzhou). Dr. Li, Dr. Goldstein, and Dr. Jovin report no relevant financial relationships.

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

In patients with early-phase schizophrenia, long-acting injectable antipsychotics (LAIs) provide no benefit over oral antipsychotics (OAs) in preventing discontinuation of antipsychotic treatment, new research suggests.

In a multicountry, randomized, open-label study of more than 500 adults with schizophrenia, participants received either LAI paliperidone, LAI aripiprazole, or the respective oral formulation of these antipsychotics.

Results showed no significant difference between the combined oral and combined LAI treatment groups in time to all-cause discontinuation.

“We found no substantial advantage for LAI antipsychotic treatment over oral treatment, regarding time to discontinuation in patients with early-phase schizophrenia,” write investigators, led by Inge Winter-van Rossum, PhD, assistant visiting professor at Mount Sinai, New York, and affiliated with King’s College London and UMC Utrecht (the Netherlands).

This indicates that “there is no reason to prescribe LAIs instead of oral antipsychotics if the goal is to prevent discontinuation of antipsychotic medication in daily clinical practice,” they add.

The findings were published online in The Lancet Psychiatry.
 

Previous conflicting results

Maintenance treatment with antipsychotic medication reduces risk for relapse considerably, with treatment discontinuation being “by far the most important reason for relapse,” the investigators write.

LAIs “seem theoretically to be a way to enhance medication continuation and thereby reduce the risk for relapse,” they add. This is because LAIs enable a rapid response to nonadherence and remove the need for patients to remember to take their medications on a daily basis.

However, previous research has “provided conflicting results,” regarding the effectiveness of LAIs in accomplishing this. Moreover, the subject has not been thoroughly investigated in early-stage schizophrenia, the researchers note.

Therefore, they decided to conduct the EULAST study to compare LAI and oral formulations in terms of all-cause discontinuation.

The trial was conducted at 50 general hospitals and psychiatric specialty clinics located in 15 European countries and Israel and included 511 participants in the intention-to-treat sample (67% men; mean age, 30.5 years).

All were randomly assigned 1:1:1 to receive either LAI paliperidone, LAI aripiprazole, or their respective oral formulations.

The combined OA treatment group consisted of 247 patients; the combined LAI group consisted of 264 patients.

Randomization was stratified by country and illness duration (5 months to 3 years vs. 4-7 years). Participants were followed up to 19 months, with all-cause discontinuation during that time serving as the primary endpoint.

All-cause discontinuation was defined as the allocated treatment was stopped or used at doses outside the allowed range, medication was switched or augmented with another antipsychotic after visit four, the patient missed a monthly visit and did not show up after being reminded, the patient withdrew consent for the study, or the clinician withdrew the patient from the study.

After the baseline visit, patients already taking antipsychotics were also randomly assigned. The next 4 weeks were then used to cross-taper between the prestudy antipsychotic and the agent they would be treated with during the study.
 

LAIs not superior

Results showed the LAI group did not have lower rates of hospitalization.

In addition, the discontinuation rates between the two combined groups were very similar at 71% for the oral antipsychotics group versus 64% in the LAIs group (hazard ratio, 1.6; 95% confidence interval, 0.94-1.43; P = .18).

Moreover, “no significant difference was found in the time to all-cause discontinuation between the combined oral and combined LAI treatment groups (P = .17),” the researchers report.

Reasons for discontinuation also did not differ significantly between the groups: 12% of patients in the OA group discontinued treatment because of efficacy vs. 17% of patients in the combined LAI group. The difference was not significant and the time to discontinuation also did not differ.

The main reason for discontinuation in both groups was safety concerns, affecting 10% and 13% of the combined OA and LAI groups, respectively, which was not a significant between-group difference.

Illness duration had a significant effect on time to all-cause discontinuation, with patients who had longer illness duration showing a poorer response, compared with those who had shorter duration (HR, 1.26; 95% CI, 1.01-1.56; P = .038).

However, stratifying participants by illness duration showed no significant difference between the subgroups (P = .25 and .34, respectively).

There was a significant between-group difference in discontinuation due to “other reasons,” with 49% vs. 34% of patients in the OA and LAI groups, respectively, discontinuing (HR, 1.51; 95% CI, 1.15-1.98; P = .0034). Moreover, the LAI group showed significantly longer continued use of medication vs the OA group (P = .0029).

“After separating the reasons for discontinuation into no efficacy, safety reasons, and other reasons, we only found a significant difference in favor of LAI for the ‘other reasons’ category; although the number of patients discontinuing medication for this reason over the follow-up period did not differ, patients on LAI continued treatment for a longer time,” the investigators write.

They acknowledge that this finding is “difficult to interpret, given the wide variety of reasons for discontinuation captured in this category,” which prevented an “informative subgroup analysis.”

Nevertheless, since there is “no consistent evidence supporting the use of LAI over oral antipsychotics” in patients with early-phase schizophrenia, their use should be “carefully considered on an individual risk-benefit basis,” they conclude.
 

No ‘real-world’ implications?

John M. Kane, MD, codirector and professor, Institute of Behavioral Science, Feinstein Institutes for Medical Research, Manhasset, N.Y., said that overall, this was a “large, potentially valuable study.” However, he raised several concerns.

“I think the investigators made a much too emphatic statement about the lack of value of LAIs in early-phase patients when discontinuation is the primary outcome,” he said, noting that other studies have come to the opposite conclusion.

Dr. Kane, who is also a professor of psychiatry at Hofstra/Northwell, New York, was not involved with the current research.

“RCTs [randomized controlled trials] in general are not necessarily the best way to evaluate the impact of LAIs [which] usually represent a small percentage of potentially eligible patients and are likely to include patients who are more adherent than those who would not agree to participate in an RCT,” he said. He added that the investigators “did not report on how many patients were screened and refused to be considered.”

Also, Dr. Kane noted that half of the participants were recruited from inpatient services, and so may have been “more unstable” at baseline. “Patients with residual positive symptoms are more likely to relapse on LAIs than patients who are in remission. This could potentially reduce the advantage of the LAI,” he said.

In addition, he took issue with the definition of all-cause discontinuation, which included the need for augmentation with another antipsychotic or use outside the normal range.

“This happens often in clinical practice. If someone’s symptoms aren’t sufficiently controlled by an LAI alone, for example, they often receive more of that antipsychotic or another drug. This perhaps makes the EULAST study somewhat less ‘real-world’,” Dr. Kane said.
 

More information needed

In an accompanying editorial, Martina Hahn, PharmD, PhD, department of psychiatry, psychosomatics, and psychotherapy, University Hospital-Goethe University, Frankfurt, Germany, and Sibylle Christine Roll, MD, PHD, department of mental health, Varisano Hospital in Frankfurt, note that comedications were neither documented nor analyzed by the researchers.

“Drug-drug interactions could be responsible for relapse or poor tolerability,” they write.

Moreover, pharmacogenetic information was not available nor were serum concentrations that could have been used for dose optimization after switching antipsychotic formulations, they note.

This information would have provided “a deeper understanding of why some patients do not respond or show side effects,” the editorialists write. “The use of therapeutic drug monitoring, drug interaction checks, and pharmacogenetic testing could improve treatment outcomes in both study settings and clinical practice.”

Financial support and study medication was provided by Lundbeck and Otsuka. Dr. Winter-van Rossum reports no relevant financial relationships. Disclosures for the other investigators are fully listed in the original paper. Dr. Kane is or has been a consultant to or received honoraria for lectures from Alkermes , Biogen, Boehringer Ingelheim, Cerevel, Dainippon Sumitomo, H. Lundbeck, HLS, Intracellular Therapies, Janssen, Karuna, Merck, Newron, Otsuka, Roche, Saladax, Sunovion, and TEVA. He is also a shareholder in The Vanguard Research Group, LB Pharma, Health Rhythms, North Shore Therapeutics, and Medincell. Dr. Hahn reports having received honoraria for lecture from Otsuka and advisory board participation for Rovi. Dr. Roll reports advisory board participation for Recordati, Otsuka, and Janssen.

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

In patients with early-phase schizophrenia, long-acting injectable antipsychotics (LAIs) provide no benefit over oral antipsychotics (OAs) in preventing discontinuation of antipsychotic treatment, new research suggests.

In a multicountry, randomized, open-label study of more than 500 adults with schizophrenia, participants received either LAI paliperidone, LAI aripiprazole, or the respective oral formulation of these antipsychotics.

Results showed no significant difference between the combined oral and combined LAI treatment groups in time to all-cause discontinuation.

“We found no substantial advantage for LAI antipsychotic treatment over oral treatment, regarding time to discontinuation in patients with early-phase schizophrenia,” write investigators, led by Inge Winter-van Rossum, PhD, assistant visiting professor at Mount Sinai, New York, and affiliated with King’s College London and UMC Utrecht (the Netherlands).

This indicates that “there is no reason to prescribe LAIs instead of oral antipsychotics if the goal is to prevent discontinuation of antipsychotic medication in daily clinical practice,” they add.

The findings were published online in The Lancet Psychiatry.
 

Previous conflicting results

Maintenance treatment with antipsychotic medication reduces risk for relapse considerably, with treatment discontinuation being “by far the most important reason for relapse,” the investigators write.

LAIs “seem theoretically to be a way to enhance medication continuation and thereby reduce the risk for relapse,” they add. This is because LAIs enable a rapid response to nonadherence and remove the need for patients to remember to take their medications on a daily basis.

However, previous research has “provided conflicting results,” regarding the effectiveness of LAIs in accomplishing this. Moreover, the subject has not been thoroughly investigated in early-stage schizophrenia, the researchers note.

Therefore, they decided to conduct the EULAST study to compare LAI and oral formulations in terms of all-cause discontinuation.

The trial was conducted at 50 general hospitals and psychiatric specialty clinics located in 15 European countries and Israel and included 511 participants in the intention-to-treat sample (67% men; mean age, 30.5 years).

All were randomly assigned 1:1:1 to receive either LAI paliperidone, LAI aripiprazole, or their respective oral formulations.

The combined OA treatment group consisted of 247 patients; the combined LAI group consisted of 264 patients.

Randomization was stratified by country and illness duration (5 months to 3 years vs. 4-7 years). Participants were followed up to 19 months, with all-cause discontinuation during that time serving as the primary endpoint.

All-cause discontinuation was defined as the allocated treatment was stopped or used at doses outside the allowed range, medication was switched or augmented with another antipsychotic after visit four, the patient missed a monthly visit and did not show up after being reminded, the patient withdrew consent for the study, or the clinician withdrew the patient from the study.

After the baseline visit, patients already taking antipsychotics were also randomly assigned. The next 4 weeks were then used to cross-taper between the prestudy antipsychotic and the agent they would be treated with during the study.
 

LAIs not superior

Results showed the LAI group did not have lower rates of hospitalization.

In addition, the discontinuation rates between the two combined groups were very similar at 71% for the oral antipsychotics group versus 64% in the LAIs group (hazard ratio, 1.6; 95% confidence interval, 0.94-1.43; P = .18).

Moreover, “no significant difference was found in the time to all-cause discontinuation between the combined oral and combined LAI treatment groups (P = .17),” the researchers report.

Reasons for discontinuation also did not differ significantly between the groups: 12% of patients in the OA group discontinued treatment because of efficacy vs. 17% of patients in the combined LAI group. The difference was not significant and the time to discontinuation also did not differ.

The main reason for discontinuation in both groups was safety concerns, affecting 10% and 13% of the combined OA and LAI groups, respectively, which was not a significant between-group difference.

Illness duration had a significant effect on time to all-cause discontinuation, with patients who had longer illness duration showing a poorer response, compared with those who had shorter duration (HR, 1.26; 95% CI, 1.01-1.56; P = .038).

However, stratifying participants by illness duration showed no significant difference between the subgroups (P = .25 and .34, respectively).

There was a significant between-group difference in discontinuation due to “other reasons,” with 49% vs. 34% of patients in the OA and LAI groups, respectively, discontinuing (HR, 1.51; 95% CI, 1.15-1.98; P = .0034). Moreover, the LAI group showed significantly longer continued use of medication vs the OA group (P = .0029).

“After separating the reasons for discontinuation into no efficacy, safety reasons, and other reasons, we only found a significant difference in favor of LAI for the ‘other reasons’ category; although the number of patients discontinuing medication for this reason over the follow-up period did not differ, patients on LAI continued treatment for a longer time,” the investigators write.

They acknowledge that this finding is “difficult to interpret, given the wide variety of reasons for discontinuation captured in this category,” which prevented an “informative subgroup analysis.”

Nevertheless, since there is “no consistent evidence supporting the use of LAI over oral antipsychotics” in patients with early-phase schizophrenia, their use should be “carefully considered on an individual risk-benefit basis,” they conclude.
 

No ‘real-world’ implications?

John M. Kane, MD, codirector and professor, Institute of Behavioral Science, Feinstein Institutes for Medical Research, Manhasset, N.Y., said that overall, this was a “large, potentially valuable study.” However, he raised several concerns.

“I think the investigators made a much too emphatic statement about the lack of value of LAIs in early-phase patients when discontinuation is the primary outcome,” he said, noting that other studies have come to the opposite conclusion.

Dr. Kane, who is also a professor of psychiatry at Hofstra/Northwell, New York, was not involved with the current research.

“RCTs [randomized controlled trials] in general are not necessarily the best way to evaluate the impact of LAIs [which] usually represent a small percentage of potentially eligible patients and are likely to include patients who are more adherent than those who would not agree to participate in an RCT,” he said. He added that the investigators “did not report on how many patients were screened and refused to be considered.”

Also, Dr. Kane noted that half of the participants were recruited from inpatient services, and so may have been “more unstable” at baseline. “Patients with residual positive symptoms are more likely to relapse on LAIs than patients who are in remission. This could potentially reduce the advantage of the LAI,” he said.

In addition, he took issue with the definition of all-cause discontinuation, which included the need for augmentation with another antipsychotic or use outside the normal range.

“This happens often in clinical practice. If someone’s symptoms aren’t sufficiently controlled by an LAI alone, for example, they often receive more of that antipsychotic or another drug. This perhaps makes the EULAST study somewhat less ‘real-world’,” Dr. Kane said.
 

More information needed

In an accompanying editorial, Martina Hahn, PharmD, PhD, department of psychiatry, psychosomatics, and psychotherapy, University Hospital-Goethe University, Frankfurt, Germany, and Sibylle Christine Roll, MD, PHD, department of mental health, Varisano Hospital in Frankfurt, note that comedications were neither documented nor analyzed by the researchers.

“Drug-drug interactions could be responsible for relapse or poor tolerability,” they write.

Moreover, pharmacogenetic information was not available nor were serum concentrations that could have been used for dose optimization after switching antipsychotic formulations, they note.

This information would have provided “a deeper understanding of why some patients do not respond or show side effects,” the editorialists write. “The use of therapeutic drug monitoring, drug interaction checks, and pharmacogenetic testing could improve treatment outcomes in both study settings and clinical practice.”

Financial support and study medication was provided by Lundbeck and Otsuka. Dr. Winter-van Rossum reports no relevant financial relationships. Disclosures for the other investigators are fully listed in the original paper. Dr. Kane is or has been a consultant to or received honoraria for lectures from Alkermes , Biogen, Boehringer Ingelheim, Cerevel, Dainippon Sumitomo, H. Lundbeck, HLS, Intracellular Therapies, Janssen, Karuna, Merck, Newron, Otsuka, Roche, Saladax, Sunovion, and TEVA. He is also a shareholder in The Vanguard Research Group, LB Pharma, Health Rhythms, North Shore Therapeutics, and Medincell. Dr. Hahn reports having received honoraria for lecture from Otsuka and advisory board participation for Rovi. Dr. Roll reports advisory board participation for Recordati, Otsuka, and Janssen.

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

In patients with early-phase schizophrenia, long-acting injectable antipsychotics (LAIs) provide no benefit over oral antipsychotics (OAs) in preventing discontinuation of antipsychotic treatment, new research suggests.

In a multicountry, randomized, open-label study of more than 500 adults with schizophrenia, participants received either LAI paliperidone, LAI aripiprazole, or the respective oral formulation of these antipsychotics.

Results showed no significant difference between the combined oral and combined LAI treatment groups in time to all-cause discontinuation.

“We found no substantial advantage for LAI antipsychotic treatment over oral treatment, regarding time to discontinuation in patients with early-phase schizophrenia,” write investigators, led by Inge Winter-van Rossum, PhD, assistant visiting professor at Mount Sinai, New York, and affiliated with King’s College London and UMC Utrecht (the Netherlands).

This indicates that “there is no reason to prescribe LAIs instead of oral antipsychotics if the goal is to prevent discontinuation of antipsychotic medication in daily clinical practice,” they add.

The findings were published online in The Lancet Psychiatry.
 

Previous conflicting results

Maintenance treatment with antipsychotic medication reduces risk for relapse considerably, with treatment discontinuation being “by far the most important reason for relapse,” the investigators write.

LAIs “seem theoretically to be a way to enhance medication continuation and thereby reduce the risk for relapse,” they add. This is because LAIs enable a rapid response to nonadherence and remove the need for patients to remember to take their medications on a daily basis.

However, previous research has “provided conflicting results,” regarding the effectiveness of LAIs in accomplishing this. Moreover, the subject has not been thoroughly investigated in early-stage schizophrenia, the researchers note.

Therefore, they decided to conduct the EULAST study to compare LAI and oral formulations in terms of all-cause discontinuation.

The trial was conducted at 50 general hospitals and psychiatric specialty clinics located in 15 European countries and Israel and included 511 participants in the intention-to-treat sample (67% men; mean age, 30.5 years).

All were randomly assigned 1:1:1 to receive either LAI paliperidone, LAI aripiprazole, or their respective oral formulations.

The combined OA treatment group consisted of 247 patients; the combined LAI group consisted of 264 patients.

Randomization was stratified by country and illness duration (5 months to 3 years vs. 4-7 years). Participants were followed up to 19 months, with all-cause discontinuation during that time serving as the primary endpoint.

All-cause discontinuation was defined as the allocated treatment was stopped or used at doses outside the allowed range, medication was switched or augmented with another antipsychotic after visit four, the patient missed a monthly visit and did not show up after being reminded, the patient withdrew consent for the study, or the clinician withdrew the patient from the study.

After the baseline visit, patients already taking antipsychotics were also randomly assigned. The next 4 weeks were then used to cross-taper between the prestudy antipsychotic and the agent they would be treated with during the study.
 

LAIs not superior

Results showed the LAI group did not have lower rates of hospitalization.

In addition, the discontinuation rates between the two combined groups were very similar at 71% for the oral antipsychotics group versus 64% in the LAIs group (hazard ratio, 1.6; 95% confidence interval, 0.94-1.43; P = .18).

Moreover, “no significant difference was found in the time to all-cause discontinuation between the combined oral and combined LAI treatment groups (P = .17),” the researchers report.

Reasons for discontinuation also did not differ significantly between the groups: 12% of patients in the OA group discontinued treatment because of efficacy vs. 17% of patients in the combined LAI group. The difference was not significant and the time to discontinuation also did not differ.

The main reason for discontinuation in both groups was safety concerns, affecting 10% and 13% of the combined OA and LAI groups, respectively, which was not a significant between-group difference.

Illness duration had a significant effect on time to all-cause discontinuation, with patients who had longer illness duration showing a poorer response, compared with those who had shorter duration (HR, 1.26; 95% CI, 1.01-1.56; P = .038).

However, stratifying participants by illness duration showed no significant difference between the subgroups (P = .25 and .34, respectively).

There was a significant between-group difference in discontinuation due to “other reasons,” with 49% vs. 34% of patients in the OA and LAI groups, respectively, discontinuing (HR, 1.51; 95% CI, 1.15-1.98; P = .0034). Moreover, the LAI group showed significantly longer continued use of medication vs the OA group (P = .0029).

“After separating the reasons for discontinuation into no efficacy, safety reasons, and other reasons, we only found a significant difference in favor of LAI for the ‘other reasons’ category; although the number of patients discontinuing medication for this reason over the follow-up period did not differ, patients on LAI continued treatment for a longer time,” the investigators write.

They acknowledge that this finding is “difficult to interpret, given the wide variety of reasons for discontinuation captured in this category,” which prevented an “informative subgroup analysis.”

Nevertheless, since there is “no consistent evidence supporting the use of LAI over oral antipsychotics” in patients with early-phase schizophrenia, their use should be “carefully considered on an individual risk-benefit basis,” they conclude.
 

No ‘real-world’ implications?

John M. Kane, MD, codirector and professor, Institute of Behavioral Science, Feinstein Institutes for Medical Research, Manhasset, N.Y., said that overall, this was a “large, potentially valuable study.” However, he raised several concerns.

“I think the investigators made a much too emphatic statement about the lack of value of LAIs in early-phase patients when discontinuation is the primary outcome,” he said, noting that other studies have come to the opposite conclusion.

Dr. Kane, who is also a professor of psychiatry at Hofstra/Northwell, New York, was not involved with the current research.

“RCTs [randomized controlled trials] in general are not necessarily the best way to evaluate the impact of LAIs [which] usually represent a small percentage of potentially eligible patients and are likely to include patients who are more adherent than those who would not agree to participate in an RCT,” he said. He added that the investigators “did not report on how many patients were screened and refused to be considered.”

Also, Dr. Kane noted that half of the participants were recruited from inpatient services, and so may have been “more unstable” at baseline. “Patients with residual positive symptoms are more likely to relapse on LAIs than patients who are in remission. This could potentially reduce the advantage of the LAI,” he said.

In addition, he took issue with the definition of all-cause discontinuation, which included the need for augmentation with another antipsychotic or use outside the normal range.

“This happens often in clinical practice. If someone’s symptoms aren’t sufficiently controlled by an LAI alone, for example, they often receive more of that antipsychotic or another drug. This perhaps makes the EULAST study somewhat less ‘real-world’,” Dr. Kane said.
 

More information needed

In an accompanying editorial, Martina Hahn, PharmD, PhD, department of psychiatry, psychosomatics, and psychotherapy, University Hospital-Goethe University, Frankfurt, Germany, and Sibylle Christine Roll, MD, PHD, department of mental health, Varisano Hospital in Frankfurt, note that comedications were neither documented nor analyzed by the researchers.

“Drug-drug interactions could be responsible for relapse or poor tolerability,” they write.

Moreover, pharmacogenetic information was not available nor were serum concentrations that could have been used for dose optimization after switching antipsychotic formulations, they note.

This information would have provided “a deeper understanding of why some patients do not respond or show side effects,” the editorialists write. “The use of therapeutic drug monitoring, drug interaction checks, and pharmacogenetic testing could improve treatment outcomes in both study settings and clinical practice.”

Financial support and study medication was provided by Lundbeck and Otsuka. Dr. Winter-van Rossum reports no relevant financial relationships. Disclosures for the other investigators are fully listed in the original paper. Dr. Kane is or has been a consultant to or received honoraria for lectures from Alkermes , Biogen, Boehringer Ingelheim, Cerevel, Dainippon Sumitomo, H. Lundbeck, HLS, Intracellular Therapies, Janssen, Karuna, Merck, Newron, Otsuka, Roche, Saladax, Sunovion, and TEVA. He is also a shareholder in The Vanguard Research Group, LB Pharma, Health Rhythms, North Shore Therapeutics, and Medincell. Dr. Hahn reports having received honoraria for lecture from Otsuka and advisory board participation for Rovi. Dr. Roll reports advisory board participation for Recordati, Otsuka, and Janssen.

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

Cyclic sighing is more effective than mindfulness meditation for improving mood and reducing stress, new research suggests.

In a randomized controlled study, daily breathwork – especially cyclic breathing, which emphasizes shorter inhalations and prolonged exhalations – was associated with greater improvement in mood and a slower respiratory rate than mindfulness meditation.

“We were pleased that just 5 minutes a day of the breathing exercises positively affected mood and resulted in slower respiratory rate, indicating reduced arousal,” coinvestigator David Spiegel, MD, who directs the Center for Stress and Health at Stanford (Calif.) University, told this news organization.

The findings were published online in Cell Reports Medicine.
 

Intentional breath control

Controlled breathwork has emerged as a potential tool to manage stress and boost well-being.

In the new study, researchers compared three different daily 5-minute breathwork exercises to an equal amount of mindfulness meditation over 1 month in 108 healthy adults recruited mostly from an undergraduate psychology class at Stanford: 33 participants practiced cyclic hyperventilation, which emphasizes robust inhalation, short retention and rapid exhalation, 30 did exhale-focused cyclic sighing, 21 performed box breathing, which emphasizes equal duration of inhalation, breath retention, and exhalation, and 24 practiced mindfulness meditation (the control group).

The primary endpoints were improvement in mood and anxiety, as well as reduced physiologic arousal (respiratory rate, heart rate, and heart rate variability). Physiological data was collected using a wearable WHOOP strap.

All four groups showed significant daily improvement in mood, as well as reduction in anxiety and negative mood, but there were significant differences between mindfulness meditation and breathwork.

Using a mixed-effects model, the researchers showed that breathwork, especially the exhale-focused cyclic sighing, produced greater improvement in mood (P < .05) and reduction in respiratory rate (P < .05), compared with mindfulness meditation.
 

Specific patterns vs. passive attention

The finding supports the team’s hypothesis that intentional control over breath with specific breathing patterns produces more benefit to mood than passive attention to one’s breath, as in mindfulness meditation practice.

“It turned out that the cyclic sighing was indeed most soothing,” Dr. Spiegel noted.

“We expected that because of respiratory sinus arrhythmia. Exhaling is accomplished by increasing pressure in the chest, which increases venous return to the heart, triggering parasympathetic slowing of heart rate via the sinoatrial node,” he said.

Dr. Spiegel added that, conversely, inspiration reduces venous return, triggering sympathetic activity and increased heart rate.

“The magnitude of this heart rate variability is associated with better health, including recovery from myocardial infarction and even cancer survival. So self-soothing is a good thing, and we expected an advantage for cyclic sighing,” he said.

“If you’re looking to improve sleep and reduce daytime stress, recover from intense work, life, and/or training, then interventions that facilitate autonomic control (and indeed you can control it), brief (5 minutes) structured breathwork is among the more powerful (and zero cost) tools,” tweeted senior investigator Andrew Huberman, PhD, professor of neurobiology at Stanford.
 

Immediate application?

Sara Lazar, PhD, Massachusetts General Hospital and Harvard Medical School, Boston, said the findings are “interesting” but cautioned that this is “just one study with a pretty small sample size,” and it only enrolled healthy college students.

courtesy Massachusetts General Hospital

Dr. Lazar, who also runs the Lazar Lab for Meditation Research at Mass General, noted that she would want to see a future study “done with working-age adults and with clinical populations.”

“It should also be noted that mindfulness had a bigger effect on negative affect, which could have implications for conditions such as depression or trauma,” said Dr. Lazar, who was not involved with the current research.

Also weighing in, Steven R. Thorp, PhD, professor at California School of Professional Psychology, Alliant International University, San Diego, said in an interview the study is “really interesting and well done.”

“Although breathing exercises and breathing retraining are commonly found in psychosocial interventions, especially for anxiety disorders, there have been few empirical studies comparing different breathing protocols,” Dr. Thorp said.

In this study, the passive observation of breaths (mindfulness) and specific breathwork interventions “all worked to decrease state anxiety; but the breathwork, particularly the cyclic sighing protocol, produced a greater overall reduction in respiratory rate and increase in positive mood,” he noted.

“These techniques can be recommended by all clinicians because all clients have access to their breath at all times – and only 5 minutes of daily practice can yield the benefits. Moreover, as the authors note, the immediate benefits may encourage clients to engage with the breathwork and potentially other aspects of treatment,” Dr. Thorp said.

The study was funded by Victor and Winnie Koo and Tianren Culture and a Stanford School of Medicine Discovery Innovation Award. WHOOP donated the wrist straps used in the study, but was not involved in the study’s design or analysis. Dr. Huberman is an advisor to WHOOP. Dr. Lazar and Dr. Thorp have reported no relevant financial relationships.

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

Cyclic sighing is more effective than mindfulness meditation for improving mood and reducing stress, new research suggests.

In a randomized controlled study, daily breathwork – especially cyclic breathing, which emphasizes shorter inhalations and prolonged exhalations – was associated with greater improvement in mood and a slower respiratory rate than mindfulness meditation.

“We were pleased that just 5 minutes a day of the breathing exercises positively affected mood and resulted in slower respiratory rate, indicating reduced arousal,” coinvestigator David Spiegel, MD, who directs the Center for Stress and Health at Stanford (Calif.) University, told this news organization.

The findings were published online in Cell Reports Medicine.
 

Intentional breath control

Controlled breathwork has emerged as a potential tool to manage stress and boost well-being.

In the new study, researchers compared three different daily 5-minute breathwork exercises to an equal amount of mindfulness meditation over 1 month in 108 healthy adults recruited mostly from an undergraduate psychology class at Stanford: 33 participants practiced cyclic hyperventilation, which emphasizes robust inhalation, short retention and rapid exhalation, 30 did exhale-focused cyclic sighing, 21 performed box breathing, which emphasizes equal duration of inhalation, breath retention, and exhalation, and 24 practiced mindfulness meditation (the control group).

The primary endpoints were improvement in mood and anxiety, as well as reduced physiologic arousal (respiratory rate, heart rate, and heart rate variability). Physiological data was collected using a wearable WHOOP strap.

All four groups showed significant daily improvement in mood, as well as reduction in anxiety and negative mood, but there were significant differences between mindfulness meditation and breathwork.

Using a mixed-effects model, the researchers showed that breathwork, especially the exhale-focused cyclic sighing, produced greater improvement in mood (P < .05) and reduction in respiratory rate (P < .05), compared with mindfulness meditation.
 

Specific patterns vs. passive attention

The finding supports the team’s hypothesis that intentional control over breath with specific breathing patterns produces more benefit to mood than passive attention to one’s breath, as in mindfulness meditation practice.

“It turned out that the cyclic sighing was indeed most soothing,” Dr. Spiegel noted.

“We expected that because of respiratory sinus arrhythmia. Exhaling is accomplished by increasing pressure in the chest, which increases venous return to the heart, triggering parasympathetic slowing of heart rate via the sinoatrial node,” he said.

Dr. Spiegel added that, conversely, inspiration reduces venous return, triggering sympathetic activity and increased heart rate.

“The magnitude of this heart rate variability is associated with better health, including recovery from myocardial infarction and even cancer survival. So self-soothing is a good thing, and we expected an advantage for cyclic sighing,” he said.

“If you’re looking to improve sleep and reduce daytime stress, recover from intense work, life, and/or training, then interventions that facilitate autonomic control (and indeed you can control it), brief (5 minutes) structured breathwork is among the more powerful (and zero cost) tools,” tweeted senior investigator Andrew Huberman, PhD, professor of neurobiology at Stanford.
 

Immediate application?

Sara Lazar, PhD, Massachusetts General Hospital and Harvard Medical School, Boston, said the findings are “interesting” but cautioned that this is “just one study with a pretty small sample size,” and it only enrolled healthy college students.

courtesy Massachusetts General Hospital

Dr. Lazar, who also runs the Lazar Lab for Meditation Research at Mass General, noted that she would want to see a future study “done with working-age adults and with clinical populations.”

“It should also be noted that mindfulness had a bigger effect on negative affect, which could have implications for conditions such as depression or trauma,” said Dr. Lazar, who was not involved with the current research.

Also weighing in, Steven R. Thorp, PhD, professor at California School of Professional Psychology, Alliant International University, San Diego, said in an interview the study is “really interesting and well done.”

“Although breathing exercises and breathing retraining are commonly found in psychosocial interventions, especially for anxiety disorders, there have been few empirical studies comparing different breathing protocols,” Dr. Thorp said.

In this study, the passive observation of breaths (mindfulness) and specific breathwork interventions “all worked to decrease state anxiety; but the breathwork, particularly the cyclic sighing protocol, produced a greater overall reduction in respiratory rate and increase in positive mood,” he noted.

“These techniques can be recommended by all clinicians because all clients have access to their breath at all times – and only 5 minutes of daily practice can yield the benefits. Moreover, as the authors note, the immediate benefits may encourage clients to engage with the breathwork and potentially other aspects of treatment,” Dr. Thorp said.

The study was funded by Victor and Winnie Koo and Tianren Culture and a Stanford School of Medicine Discovery Innovation Award. WHOOP donated the wrist straps used in the study, but was not involved in the study’s design or analysis. Dr. Huberman is an advisor to WHOOP. Dr. Lazar and Dr. Thorp have reported no relevant financial relationships.

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

Cyclic sighing is more effective than mindfulness meditation for improving mood and reducing stress, new research suggests.

In a randomized controlled study, daily breathwork – especially cyclic breathing, which emphasizes shorter inhalations and prolonged exhalations – was associated with greater improvement in mood and a slower respiratory rate than mindfulness meditation.

“We were pleased that just 5 minutes a day of the breathing exercises positively affected mood and resulted in slower respiratory rate, indicating reduced arousal,” coinvestigator David Spiegel, MD, who directs the Center for Stress and Health at Stanford (Calif.) University, told this news organization.

The findings were published online in Cell Reports Medicine.
 

Intentional breath control

Controlled breathwork has emerged as a potential tool to manage stress and boost well-being.

In the new study, researchers compared three different daily 5-minute breathwork exercises to an equal amount of mindfulness meditation over 1 month in 108 healthy adults recruited mostly from an undergraduate psychology class at Stanford: 33 participants practiced cyclic hyperventilation, which emphasizes robust inhalation, short retention and rapid exhalation, 30 did exhale-focused cyclic sighing, 21 performed box breathing, which emphasizes equal duration of inhalation, breath retention, and exhalation, and 24 practiced mindfulness meditation (the control group).

The primary endpoints were improvement in mood and anxiety, as well as reduced physiologic arousal (respiratory rate, heart rate, and heart rate variability). Physiological data was collected using a wearable WHOOP strap.

All four groups showed significant daily improvement in mood, as well as reduction in anxiety and negative mood, but there were significant differences between mindfulness meditation and breathwork.

Using a mixed-effects model, the researchers showed that breathwork, especially the exhale-focused cyclic sighing, produced greater improvement in mood (P < .05) and reduction in respiratory rate (P < .05), compared with mindfulness meditation.
 

Specific patterns vs. passive attention

The finding supports the team’s hypothesis that intentional control over breath with specific breathing patterns produces more benefit to mood than passive attention to one’s breath, as in mindfulness meditation practice.

“It turned out that the cyclic sighing was indeed most soothing,” Dr. Spiegel noted.

“We expected that because of respiratory sinus arrhythmia. Exhaling is accomplished by increasing pressure in the chest, which increases venous return to the heart, triggering parasympathetic slowing of heart rate via the sinoatrial node,” he said.

Dr. Spiegel added that, conversely, inspiration reduces venous return, triggering sympathetic activity and increased heart rate.

“The magnitude of this heart rate variability is associated with better health, including recovery from myocardial infarction and even cancer survival. So self-soothing is a good thing, and we expected an advantage for cyclic sighing,” he said.

“If you’re looking to improve sleep and reduce daytime stress, recover from intense work, life, and/or training, then interventions that facilitate autonomic control (and indeed you can control it), brief (5 minutes) structured breathwork is among the more powerful (and zero cost) tools,” tweeted senior investigator Andrew Huberman, PhD, professor of neurobiology at Stanford.
 

Immediate application?

Sara Lazar, PhD, Massachusetts General Hospital and Harvard Medical School, Boston, said the findings are “interesting” but cautioned that this is “just one study with a pretty small sample size,” and it only enrolled healthy college students.

courtesy Massachusetts General Hospital

Dr. Lazar, who also runs the Lazar Lab for Meditation Research at Mass General, noted that she would want to see a future study “done with working-age adults and with clinical populations.”

“It should also be noted that mindfulness had a bigger effect on negative affect, which could have implications for conditions such as depression or trauma,” said Dr. Lazar, who was not involved with the current research.

Also weighing in, Steven R. Thorp, PhD, professor at California School of Professional Psychology, Alliant International University, San Diego, said in an interview the study is “really interesting and well done.”

“Although breathing exercises and breathing retraining are commonly found in psychosocial interventions, especially for anxiety disorders, there have been few empirical studies comparing different breathing protocols,” Dr. Thorp said.

In this study, the passive observation of breaths (mindfulness) and specific breathwork interventions “all worked to decrease state anxiety; but the breathwork, particularly the cyclic sighing protocol, produced a greater overall reduction in respiratory rate and increase in positive mood,” he noted.

“These techniques can be recommended by all clinicians because all clients have access to their breath at all times – and only 5 minutes of daily practice can yield the benefits. Moreover, as the authors note, the immediate benefits may encourage clients to engage with the breathwork and potentially other aspects of treatment,” Dr. Thorp said.

The study was funded by Victor and Winnie Koo and Tianren Culture and a Stanford School of Medicine Discovery Innovation Award. WHOOP donated the wrist straps used in the study, but was not involved in the study’s design or analysis. Dr. Huberman is an advisor to WHOOP. Dr. Lazar and Dr. Thorp have reported no relevant financial relationships.

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

We’re gonna need a bigger meth lab

In case you’ve been living under a rock for the past 15 years, the TV show “Breaking Bad” details the spiraling rise and downfall of a high school chemistry teacher who, after developing a case of terminal lung cancer, starts producing methamphetamine to provide for his family in response to the steep cost of treatment for his cancer.

TheaDesign/Thinkstock

Meanwhile, here in 2023 in the real world, we have Paul Davis, a retired physician in Ohio, who’s being forced to choose between an expensive cancer treatment and bankrupting his family, since Medicare’s decided it doesn’t want to cover the cost. Hey, we’ve seen this one before!

A bit of backstory: In November 2019, Dr. Davis was diagnosed with uveal melanoma, a very rare type of cancer that affects eye tissue. The news got worse in 2022 when the cancer spread to his liver, a move which typically proves fatal within a year. However, in a stroke of great news, the Food and Drug Administration approved the drug Kimmtrak earlier that year, which could be used to treat his cancer. Not cure, of course, but it would give him more time.

His initial treatments with the drug went fine and were covered, but when he transferred his care from a hospital in Columbus to one closer to home, big problem. Medicare decided it didn’t like that hospital and abruptly cut off coverage, denying the local hospital’s claims. That leaves Dr. Davis on the hook for his cancer treatment, and it’s what you might call expensive. Expensive to the tune of $50,000.

A week.

Apparently the coding the local hospital submitted was wrong, indicating that Dr. Davis was receiving Kimmtrak for a type of cancer that the FDA hadn’t approved the drug for. So until the government bureaucracy works itself out, his treatment is on hold, leaving all his faith in Medicare working quickly to rectify its mistake. If it can rectify its mistake. We’re not hopeful.

And in case you were wondering, if Dr. Davis wanted to go full Walter White, the average street price of meth is about $20-$60 per gram, so to pay for his treatment, he’d need to make at least a kilogram of meth every week. That’s, uh, quite a lot of illegal drug, or what we here at the LOTME office would call a fun Saturday night.
 

When you give a mouse a movie

Researchers have been successfully testing Alzheimer drugs on mice for years, but none of the drugs has proved successful in humans. Recent work, however, might have found the missing link, and it’s a combination no one ever thought of before: mice and movies.

procesocreativo/PxHere

Turns out that Orson Welles’ 1958 film noir classic “Touch of Evil” tapped a part of the mouse brain that has been overlooked: the hippocampus, which is crucial for learning and memory. Previous researchers thought it was just used as a kind of GPS system, but that’s only partially true.

Not only did the mice choose to pay attention to the movie clip, but the hippocampus responded to the visual stimuli only when the rodents saw the scenes from the clip later in the order that they were presented and not in a scrambled order. These findings represent a “major paradigm shift” in studying mouse recall, Mayank Mehta, PhD, of the University of California, Los Angeles, said in a statement from the school.

This breakthrough could run parallel to Alzheimer’s patients struggling with similar defects. “Selective and episodic activation of the mouse hippocampus using a human movie opens up the possibility of directly testing human episodic memory disorders and therapies using mouse neurons, a major step forward,” said coauthor Chinmay Purandare, PhD, who is now at the University of California, San Francisco.

Who would have thought that a classic film would help advance Alzheimer research?
 

A less human way to study mosquitoes

We here at LOTME have a history with mosquitoes. We know they don’t like us, and they know that we don’t like them. Trust us, they know. So when humans gain a little ground in the war against the buzzy little bloodsuckers, we want to share the joy.

Wesson Group/Tulane University

To know the enemy, scientists have to study the enemy, but there is a problem. “Many mosquito experiments still rely on human volunteers and animal subjects,” bioengineering graduate student Kevin Janson, said in a statement from Rice University. Most people don’t like being bitten by mosquitoes, so that kind of testing can be expensive.

Is there a way to automate the collection and processing of mosquito behavior data using inexpensive cameras and machine-learning software? We’re glad you asked, because Mr. Janson and the research team, which includes bioengineers from Rice and tropical medicine experts from Tulane University, have managed to eliminate the need for live volunteers by using patches of synthetic skin made with a 3D printer.

“Each patch of gelatin-like hydrogel comes complete with tiny passageways that can be filled with flowing blood” from a chicken, sheep, or cow, they explained, and proof-of-concept testing showed that mosquitoes would feed on hydrogels without any repellent and stay away from those treated with a repellent.

To conduct the feeding tests, the blood-infused hydrogels are placed in a clear plastic box that is surrounded by cameras.

A bunch of mosquitoes are then tossed in the box and the cameras record all their insect activities: how often they land at each location, how long they stay, whether or not they bite, how long they feed, etc. Humans don’t have to watch and don’t have to be food sources.

Humans don’t have to be food sources, and we just pictured the future of mosquito control. Imagine a dozen Arnold Schwarzenegger–style Terminators, covered in 3D-printed skin, walking through your neighborhood in the summer while wearing sweat-soaked, brightly colored clothing. The mosquitoes wouldn’t be able to stay away, but guess what? They’re feeding off robots with nonhuman skin and nonhuman blood, so we win. It’s good to have a cerebral cortex.
 

Getting medieval on brain surgery

Let’s get one thing clear: The so-called “Dark Ages” were not nearly as dark as they’re made out to be. For one thing, there’s a world beyond Western Europe. The Roman Empire didn’t collapse everywhere. But even in Western Europe, the centuries between the fall of Rome and the Renaissance were hardly lacking in cultural development.

Gleb Lucky/Unsplash

That said, we wouldn’t want to be in the position of the seventh-century noblewoman whose remains were recently uncovered in a Byzantine fortress in central Italy with multiple cross-shaped incisions in her skull. Yes, this unfortunate woman underwent at least two brain surgeries.

Then again, maybe not. Nothing like it had been discovered at the site, and while the markings – signs of a procedure called trepanation – can be surgical in nature, there are other explanations. For example, the Avar people practiced ritual trepanation during the same time period, but they were hundreds of miles away in the Carpathian mountains, and there was no evidence to support that a different form of ritualistic trepanation ever took place in Byzantine-era Italy.

The investigators then moved on to a form of judicial punishment called decalvatio, which involves mutilation by scalping. Look, the Dark Ages weren’t dark, but no one said they were fun. Anyway, this was discarded, since decalvatio was only meted out to soldiers who deserted the battlefield.

That brings us back to surgery. While one of the trepanations was fully engraved into her skull, indicating that the woman died soon after the surgery, she also bore indications of a healed trepanation. A 50% success rate isn’t terrible for our medieval surgeon. Sure, the Incas managed 80%, but even during the Civil War brain surgery only had a 50% success rate. And that’s the end of the story, nothing more to say about our medieval Italian woman.

Nope. Nothing at all.

Fine. While a surgical procedure was deemed most likely, the study investigators found no direct evidence of a medical condition. No trauma, no tumor, nothing. Just a couple of suggestions of “a systemic pathological condition,” they said. Okay, we swear, it really wasn’t that bad in the Middle [Editor’s note: Approximately 5,000 more words on medieval culture not included. This is a medical column, thank you very much.]

We’re gonna need a bigger meth lab

In case you’ve been living under a rock for the past 15 years, the TV show “Breaking Bad” details the spiraling rise and downfall of a high school chemistry teacher who, after developing a case of terminal lung cancer, starts producing methamphetamine to provide for his family in response to the steep cost of treatment for his cancer.

TheaDesign/Thinkstock

Meanwhile, here in 2023 in the real world, we have Paul Davis, a retired physician in Ohio, who’s being forced to choose between an expensive cancer treatment and bankrupting his family, since Medicare’s decided it doesn’t want to cover the cost. Hey, we’ve seen this one before!

A bit of backstory: In November 2019, Dr. Davis was diagnosed with uveal melanoma, a very rare type of cancer that affects eye tissue. The news got worse in 2022 when the cancer spread to his liver, a move which typically proves fatal within a year. However, in a stroke of great news, the Food and Drug Administration approved the drug Kimmtrak earlier that year, which could be used to treat his cancer. Not cure, of course, but it would give him more time.

His initial treatments with the drug went fine and were covered, but when he transferred his care from a hospital in Columbus to one closer to home, big problem. Medicare decided it didn’t like that hospital and abruptly cut off coverage, denying the local hospital’s claims. That leaves Dr. Davis on the hook for his cancer treatment, and it’s what you might call expensive. Expensive to the tune of $50,000.

A week.

Apparently the coding the local hospital submitted was wrong, indicating that Dr. Davis was receiving Kimmtrak for a type of cancer that the FDA hadn’t approved the drug for. So until the government bureaucracy works itself out, his treatment is on hold, leaving all his faith in Medicare working quickly to rectify its mistake. If it can rectify its mistake. We’re not hopeful.

And in case you were wondering, if Dr. Davis wanted to go full Walter White, the average street price of meth is about $20-$60 per gram, so to pay for his treatment, he’d need to make at least a kilogram of meth every week. That’s, uh, quite a lot of illegal drug, or what we here at the LOTME office would call a fun Saturday night.
 

When you give a mouse a movie

Researchers have been successfully testing Alzheimer drugs on mice for years, but none of the drugs has proved successful in humans. Recent work, however, might have found the missing link, and it’s a combination no one ever thought of before: mice and movies.

procesocreativo/PxHere

Turns out that Orson Welles’ 1958 film noir classic “Touch of Evil” tapped a part of the mouse brain that has been overlooked: the hippocampus, which is crucial for learning and memory. Previous researchers thought it was just used as a kind of GPS system, but that’s only partially true.

Not only did the mice choose to pay attention to the movie clip, but the hippocampus responded to the visual stimuli only when the rodents saw the scenes from the clip later in the order that they were presented and not in a scrambled order. These findings represent a “major paradigm shift” in studying mouse recall, Mayank Mehta, PhD, of the University of California, Los Angeles, said in a statement from the school.

This breakthrough could run parallel to Alzheimer’s patients struggling with similar defects. “Selective and episodic activation of the mouse hippocampus using a human movie opens up the possibility of directly testing human episodic memory disorders and therapies using mouse neurons, a major step forward,” said coauthor Chinmay Purandare, PhD, who is now at the University of California, San Francisco.

Who would have thought that a classic film would help advance Alzheimer research?
 

A less human way to study mosquitoes

We here at LOTME have a history with mosquitoes. We know they don’t like us, and they know that we don’t like them. Trust us, they know. So when humans gain a little ground in the war against the buzzy little bloodsuckers, we want to share the joy.

Wesson Group/Tulane University

To know the enemy, scientists have to study the enemy, but there is a problem. “Many mosquito experiments still rely on human volunteers and animal subjects,” bioengineering graduate student Kevin Janson, said in a statement from Rice University. Most people don’t like being bitten by mosquitoes, so that kind of testing can be expensive.

Is there a way to automate the collection and processing of mosquito behavior data using inexpensive cameras and machine-learning software? We’re glad you asked, because Mr. Janson and the research team, which includes bioengineers from Rice and tropical medicine experts from Tulane University, have managed to eliminate the need for live volunteers by using patches of synthetic skin made with a 3D printer.

“Each patch of gelatin-like hydrogel comes complete with tiny passageways that can be filled with flowing blood” from a chicken, sheep, or cow, they explained, and proof-of-concept testing showed that mosquitoes would feed on hydrogels without any repellent and stay away from those treated with a repellent.

To conduct the feeding tests, the blood-infused hydrogels are placed in a clear plastic box that is surrounded by cameras.

A bunch of mosquitoes are then tossed in the box and the cameras record all their insect activities: how often they land at each location, how long they stay, whether or not they bite, how long they feed, etc. Humans don’t have to watch and don’t have to be food sources.

Humans don’t have to be food sources, and we just pictured the future of mosquito control. Imagine a dozen Arnold Schwarzenegger–style Terminators, covered in 3D-printed skin, walking through your neighborhood in the summer while wearing sweat-soaked, brightly colored clothing. The mosquitoes wouldn’t be able to stay away, but guess what? They’re feeding off robots with nonhuman skin and nonhuman blood, so we win. It’s good to have a cerebral cortex.
 

Getting medieval on brain surgery

Let’s get one thing clear: The so-called “Dark Ages” were not nearly as dark as they’re made out to be. For one thing, there’s a world beyond Western Europe. The Roman Empire didn’t collapse everywhere. But even in Western Europe, the centuries between the fall of Rome and the Renaissance were hardly lacking in cultural development.

Gleb Lucky/Unsplash

That said, we wouldn’t want to be in the position of the seventh-century noblewoman whose remains were recently uncovered in a Byzantine fortress in central Italy with multiple cross-shaped incisions in her skull. Yes, this unfortunate woman underwent at least two brain surgeries.

Then again, maybe not. Nothing like it had been discovered at the site, and while the markings – signs of a procedure called trepanation – can be surgical in nature, there are other explanations. For example, the Avar people practiced ritual trepanation during the same time period, but they were hundreds of miles away in the Carpathian mountains, and there was no evidence to support that a different form of ritualistic trepanation ever took place in Byzantine-era Italy.

The investigators then moved on to a form of judicial punishment called decalvatio, which involves mutilation by scalping. Look, the Dark Ages weren’t dark, but no one said they were fun. Anyway, this was discarded, since decalvatio was only meted out to soldiers who deserted the battlefield.

That brings us back to surgery. While one of the trepanations was fully engraved into her skull, indicating that the woman died soon after the surgery, she also bore indications of a healed trepanation. A 50% success rate isn’t terrible for our medieval surgeon. Sure, the Incas managed 80%, but even during the Civil War brain surgery only had a 50% success rate. And that’s the end of the story, nothing more to say about our medieval Italian woman.

Nope. Nothing at all.

Fine. While a surgical procedure was deemed most likely, the study investigators found no direct evidence of a medical condition. No trauma, no tumor, nothing. Just a couple of suggestions of “a systemic pathological condition,” they said. Okay, we swear, it really wasn’t that bad in the Middle [Editor’s note: Approximately 5,000 more words on medieval culture not included. This is a medical column, thank you very much.]

We’re gonna need a bigger meth lab

In case you’ve been living under a rock for the past 15 years, the TV show “Breaking Bad” details the spiraling rise and downfall of a high school chemistry teacher who, after developing a case of terminal lung cancer, starts producing methamphetamine to provide for his family in response to the steep cost of treatment for his cancer.

TheaDesign/Thinkstock

Meanwhile, here in 2023 in the real world, we have Paul Davis, a retired physician in Ohio, who’s being forced to choose between an expensive cancer treatment and bankrupting his family, since Medicare’s decided it doesn’t want to cover the cost. Hey, we’ve seen this one before!

A bit of backstory: In November 2019, Dr. Davis was diagnosed with uveal melanoma, a very rare type of cancer that affects eye tissue. The news got worse in 2022 when the cancer spread to his liver, a move which typically proves fatal within a year. However, in a stroke of great news, the Food and Drug Administration approved the drug Kimmtrak earlier that year, which could be used to treat his cancer. Not cure, of course, but it would give him more time.

His initial treatments with the drug went fine and were covered, but when he transferred his care from a hospital in Columbus to one closer to home, big problem. Medicare decided it didn’t like that hospital and abruptly cut off coverage, denying the local hospital’s claims. That leaves Dr. Davis on the hook for his cancer treatment, and it’s what you might call expensive. Expensive to the tune of $50,000.

A week.

Apparently the coding the local hospital submitted was wrong, indicating that Dr. Davis was receiving Kimmtrak for a type of cancer that the FDA hadn’t approved the drug for. So until the government bureaucracy works itself out, his treatment is on hold, leaving all his faith in Medicare working quickly to rectify its mistake. If it can rectify its mistake. We’re not hopeful.

And in case you were wondering, if Dr. Davis wanted to go full Walter White, the average street price of meth is about $20-$60 per gram, so to pay for his treatment, he’d need to make at least a kilogram of meth every week. That’s, uh, quite a lot of illegal drug, or what we here at the LOTME office would call a fun Saturday night.
 

When you give a mouse a movie

Researchers have been successfully testing Alzheimer drugs on mice for years, but none of the drugs has proved successful in humans. Recent work, however, might have found the missing link, and it’s a combination no one ever thought of before: mice and movies.

procesocreativo/PxHere

Turns out that Orson Welles’ 1958 film noir classic “Touch of Evil” tapped a part of the mouse brain that has been overlooked: the hippocampus, which is crucial for learning and memory. Previous researchers thought it was just used as a kind of GPS system, but that’s only partially true.

Not only did the mice choose to pay attention to the movie clip, but the hippocampus responded to the visual stimuli only when the rodents saw the scenes from the clip later in the order that they were presented and not in a scrambled order. These findings represent a “major paradigm shift” in studying mouse recall, Mayank Mehta, PhD, of the University of California, Los Angeles, said in a statement from the school.

This breakthrough could run parallel to Alzheimer’s patients struggling with similar defects. “Selective and episodic activation of the mouse hippocampus using a human movie opens up the possibility of directly testing human episodic memory disorders and therapies using mouse neurons, a major step forward,” said coauthor Chinmay Purandare, PhD, who is now at the University of California, San Francisco.

Who would have thought that a classic film would help advance Alzheimer research?
 

A less human way to study mosquitoes

We here at LOTME have a history with mosquitoes. We know they don’t like us, and they know that we don’t like them. Trust us, they know. So when humans gain a little ground in the war against the buzzy little bloodsuckers, we want to share the joy.

Wesson Group/Tulane University

To know the enemy, scientists have to study the enemy, but there is a problem. “Many mosquito experiments still rely on human volunteers and animal subjects,” bioengineering graduate student Kevin Janson, said in a statement from Rice University. Most people don’t like being bitten by mosquitoes, so that kind of testing can be expensive.

Is there a way to automate the collection and processing of mosquito behavior data using inexpensive cameras and machine-learning software? We’re glad you asked, because Mr. Janson and the research team, which includes bioengineers from Rice and tropical medicine experts from Tulane University, have managed to eliminate the need for live volunteers by using patches of synthetic skin made with a 3D printer.

“Each patch of gelatin-like hydrogel comes complete with tiny passageways that can be filled with flowing blood” from a chicken, sheep, or cow, they explained, and proof-of-concept testing showed that mosquitoes would feed on hydrogels without any repellent and stay away from those treated with a repellent.

To conduct the feeding tests, the blood-infused hydrogels are placed in a clear plastic box that is surrounded by cameras.

A bunch of mosquitoes are then tossed in the box and the cameras record all their insect activities: how often they land at each location, how long they stay, whether or not they bite, how long they feed, etc. Humans don’t have to watch and don’t have to be food sources.

Humans don’t have to be food sources, and we just pictured the future of mosquito control. Imagine a dozen Arnold Schwarzenegger–style Terminators, covered in 3D-printed skin, walking through your neighborhood in the summer while wearing sweat-soaked, brightly colored clothing. The mosquitoes wouldn’t be able to stay away, but guess what? They’re feeding off robots with nonhuman skin and nonhuman blood, so we win. It’s good to have a cerebral cortex.
 

Getting medieval on brain surgery

Let’s get one thing clear: The so-called “Dark Ages” were not nearly as dark as they’re made out to be. For one thing, there’s a world beyond Western Europe. The Roman Empire didn’t collapse everywhere. But even in Western Europe, the centuries between the fall of Rome and the Renaissance were hardly lacking in cultural development.

Gleb Lucky/Unsplash

That said, we wouldn’t want to be in the position of the seventh-century noblewoman whose remains were recently uncovered in a Byzantine fortress in central Italy with multiple cross-shaped incisions in her skull. Yes, this unfortunate woman underwent at least two brain surgeries.

Then again, maybe not. Nothing like it had been discovered at the site, and while the markings – signs of a procedure called trepanation – can be surgical in nature, there are other explanations. For example, the Avar people practiced ritual trepanation during the same time period, but they were hundreds of miles away in the Carpathian mountains, and there was no evidence to support that a different form of ritualistic trepanation ever took place in Byzantine-era Italy.

The investigators then moved on to a form of judicial punishment called decalvatio, which involves mutilation by scalping. Look, the Dark Ages weren’t dark, but no one said they were fun. Anyway, this was discarded, since decalvatio was only meted out to soldiers who deserted the battlefield.

That brings us back to surgery. While one of the trepanations was fully engraved into her skull, indicating that the woman died soon after the surgery, she also bore indications of a healed trepanation. A 50% success rate isn’t terrible for our medieval surgeon. Sure, the Incas managed 80%, but even during the Civil War brain surgery only had a 50% success rate. And that’s the end of the story, nothing more to say about our medieval Italian woman.

Nope. Nothing at all.

Fine. While a surgical procedure was deemed most likely, the study investigators found no direct evidence of a medical condition. No trauma, no tumor, nothing. Just a couple of suggestions of “a systemic pathological condition,” they said. Okay, we swear, it really wasn’t that bad in the Middle [Editor’s note: Approximately 5,000 more words on medieval culture not included. This is a medical column, thank you very much.]

A new tool for predicting which patients with psoriasis will develop psoriatic arthritis (PsA) is showing promise for such clinical applications as early treatment in those at risk or trials to prevent PsA, according to a summary of progress at the annual meeting of the Canadian Rheumatology Association.

Based on current levels of sensitivity and specificity, psoriasis “can be predicted with reasonable accuracy,” reported Lihi Eder, MD, PhD, director of research in the rheumatology division at the University of Toronto.

The predictive method, called PRESTO (Prediction of Psoriatic Arthritis Tool), is based on variables readily available in clinical practice, according to Dr. Eder. Once values are assigned to the risk factors, the risk of PsA over a 1-year or 5-year time frame can be estimated with a calculator.

She called PRESTO the “first clinical tool for predicting PsA among psoriasis patients.”

The work on this tool began in 2006 when the International Psoriasis and Arthritis Research Team (IPART) initiated a prospectively collected cohort of psoriasis patients. To be enrolled, patients had to be free of signs and symptoms of arthritis upon examination by a rheumatologist. They were then invited to return annually for follow-up that again included screening for joint involvement by a rheumatologist.

At baseline and at follow-up evaluations, 13 predictors were evaluated. These involved psoriasis characteristics, such as nail pitting; symptoms, such as stiffness; comorbidities, such as additional inflammatory diseases; and laboratory values, such as upregulated markers of inflammation.

Symptoms and signs used to predict PsA

Dr. Eder and her colleagues applied regression models to select an optimal combination of variables weighted for predictive value. Variables offering predictive value included higher PASI (Psoriasis Area and Severity Index), greater fatigue score as measured by FACIT (Functional Assessment of Chronic Illness Therapy) score, greater morning stiffness, and greater pain.

When applied to 635 patients in the IPART cohort, in which there were 51 incident PsA cases over 1 year and 75 incident cases over 5 years, the area under the curve (AUC) for PRESTO at the cutoffs studied was 72% for the 1-year time window and 75% for the 5-year time window.

These levels are associated with adequate accuracy, according to Dr. Eder, who explained that “an AUC greater than 70% is considered reasonable” for clinical applicability.

Moreover, the cutoffs can be adjusted for the specific purpose of the predictive tool. For example, to screen patients for risk, lower cutoffs could be employed to increase sensitivity. In order to select patients for a clinical trial to prevent PsA, higher cutoffs could be employed to increase specificity.

But sensitivities and specificities move in opposite directions when cutoffs are adjusted. Showing data from the 5-year prediction model, Dr. Eder reported that specificities climbed from about 58% to 97% as cutoffs were increased. The sensitivities with these adjustments fell from 79% to 14%.

In general, Dr. Eder said there was “excellent calibration” for the cutoffs employed when they compared the predicted and observed rates of PsA according to quintile of predictive probability. The differences were particularly minor over a 1-year time period. Over the 5-year period, observed rates were somewhat higher than predicted in the fourth and fifth quintile, but, again, this discrepancy could be modified for specific applications with cutoff adjustments.

Validation studies are planned

Even though psoriasis patients in IPART represents one of the largest cohorts of prospectively collected psoriasis patients, Dr. Eder acknowledged that the sample size would be considered “moderate” for developing a predictive model. However, the fact that the data were collected prospectively using standardized methodology strengthens the findings and provides the basis for the next step.

“Validation studies are planned with external cohorts,” said Dr. Eder, who indicated that a viable tool for identifying psoriasis patients at risk for PsA is likely. Even if it is not employed routinely in its current form at the level of individual patient care, she predicted that it will have value at a research level for understanding the relationship of psoriasis to PsA.

Christopher T. Ritchlin, MD, a professor and researcher at the University of Rochester (N.Y.), agreed that PRESTO has important potential as a clinical tool. Dr. Ritchlin has been involved in the development of PRESTO but was not involved in the presentation made at the CRA annual meeting.

“The PRESTO tool has the ability to predict the 2- and 5-year risk of developing psoriatic arthritis, which is an important advance if confirmed,” he said in an interview. He pointed out that approximately 25%-30% who develop psoriasis will go on to develop PsA but until now there has been no way to identify them.

“This tool may provide a pathway to early intervention,” he said.

Dr. Eder has financial relationships with AbbVie, Eli Lilly, Fresenius Kabi, Janssen, Novartis, Pfizer, Sandoz, and UCB. Dr. Ritchlin has financial relationships with many of the same companies.

A new tool for predicting which patients with psoriasis will develop psoriatic arthritis (PsA) is showing promise for such clinical applications as early treatment in those at risk or trials to prevent PsA, according to a summary of progress at the annual meeting of the Canadian Rheumatology Association.

Based on current levels of sensitivity and specificity, psoriasis “can be predicted with reasonable accuracy,” reported Lihi Eder, MD, PhD, director of research in the rheumatology division at the University of Toronto.

The predictive method, called PRESTO (Prediction of Psoriatic Arthritis Tool), is based on variables readily available in clinical practice, according to Dr. Eder. Once values are assigned to the risk factors, the risk of PsA over a 1-year or 5-year time frame can be estimated with a calculator.

She called PRESTO the “first clinical tool for predicting PsA among psoriasis patients.”

The work on this tool began in 2006 when the International Psoriasis and Arthritis Research Team (IPART) initiated a prospectively collected cohort of psoriasis patients. To be enrolled, patients had to be free of signs and symptoms of arthritis upon examination by a rheumatologist. They were then invited to return annually for follow-up that again included screening for joint involvement by a rheumatologist.

At baseline and at follow-up evaluations, 13 predictors were evaluated. These involved psoriasis characteristics, such as nail pitting; symptoms, such as stiffness; comorbidities, such as additional inflammatory diseases; and laboratory values, such as upregulated markers of inflammation.

Symptoms and signs used to predict PsA

Dr. Eder and her colleagues applied regression models to select an optimal combination of variables weighted for predictive value. Variables offering predictive value included higher PASI (Psoriasis Area and Severity Index), greater fatigue score as measured by FACIT (Functional Assessment of Chronic Illness Therapy) score, greater morning stiffness, and greater pain.

When applied to 635 patients in the IPART cohort, in which there were 51 incident PsA cases over 1 year and 75 incident cases over 5 years, the area under the curve (AUC) for PRESTO at the cutoffs studied was 72% for the 1-year time window and 75% for the 5-year time window.

These levels are associated with adequate accuracy, according to Dr. Eder, who explained that “an AUC greater than 70% is considered reasonable” for clinical applicability.

Moreover, the cutoffs can be adjusted for the specific purpose of the predictive tool. For example, to screen patients for risk, lower cutoffs could be employed to increase sensitivity. In order to select patients for a clinical trial to prevent PsA, higher cutoffs could be employed to increase specificity.

But sensitivities and specificities move in opposite directions when cutoffs are adjusted. Showing data from the 5-year prediction model, Dr. Eder reported that specificities climbed from about 58% to 97% as cutoffs were increased. The sensitivities with these adjustments fell from 79% to 14%.

In general, Dr. Eder said there was “excellent calibration” for the cutoffs employed when they compared the predicted and observed rates of PsA according to quintile of predictive probability. The differences were particularly minor over a 1-year time period. Over the 5-year period, observed rates were somewhat higher than predicted in the fourth and fifth quintile, but, again, this discrepancy could be modified for specific applications with cutoff adjustments.

Validation studies are planned

Even though psoriasis patients in IPART represents one of the largest cohorts of prospectively collected psoriasis patients, Dr. Eder acknowledged that the sample size would be considered “moderate” for developing a predictive model. However, the fact that the data were collected prospectively using standardized methodology strengthens the findings and provides the basis for the next step.

“Validation studies are planned with external cohorts,” said Dr. Eder, who indicated that a viable tool for identifying psoriasis patients at risk for PsA is likely. Even if it is not employed routinely in its current form at the level of individual patient care, she predicted that it will have value at a research level for understanding the relationship of psoriasis to PsA.

Christopher T. Ritchlin, MD, a professor and researcher at the University of Rochester (N.Y.), agreed that PRESTO has important potential as a clinical tool. Dr. Ritchlin has been involved in the development of PRESTO but was not involved in the presentation made at the CRA annual meeting.

“The PRESTO tool has the ability to predict the 2- and 5-year risk of developing psoriatic arthritis, which is an important advance if confirmed,” he said in an interview. He pointed out that approximately 25%-30% who develop psoriasis will go on to develop PsA but until now there has been no way to identify them.

“This tool may provide a pathway to early intervention,” he said.

Dr. Eder has financial relationships with AbbVie, Eli Lilly, Fresenius Kabi, Janssen, Novartis, Pfizer, Sandoz, and UCB. Dr. Ritchlin has financial relationships with many of the same companies.

A new tool for predicting which patients with psoriasis will develop psoriatic arthritis (PsA) is showing promise for such clinical applications as early treatment in those at risk or trials to prevent PsA, according to a summary of progress at the annual meeting of the Canadian Rheumatology Association.

Based on current levels of sensitivity and specificity, psoriasis “can be predicted with reasonable accuracy,” reported Lihi Eder, MD, PhD, director of research in the rheumatology division at the University of Toronto.

The predictive method, called PRESTO (Prediction of Psoriatic Arthritis Tool), is based on variables readily available in clinical practice, according to Dr. Eder. Once values are assigned to the risk factors, the risk of PsA over a 1-year or 5-year time frame can be estimated with a calculator.

She called PRESTO the “first clinical tool for predicting PsA among psoriasis patients.”

The work on this tool began in 2006 when the International Psoriasis and Arthritis Research Team (IPART) initiated a prospectively collected cohort of psoriasis patients. To be enrolled, patients had to be free of signs and symptoms of arthritis upon examination by a rheumatologist. They were then invited to return annually for follow-up that again included screening for joint involvement by a rheumatologist.

At baseline and at follow-up evaluations, 13 predictors were evaluated. These involved psoriasis characteristics, such as nail pitting; symptoms, such as stiffness; comorbidities, such as additional inflammatory diseases; and laboratory values, such as upregulated markers of inflammation.

Symptoms and signs used to predict PsA

Dr. Eder and her colleagues applied regression models to select an optimal combination of variables weighted for predictive value. Variables offering predictive value included higher PASI (Psoriasis Area and Severity Index), greater fatigue score as measured by FACIT (Functional Assessment of Chronic Illness Therapy) score, greater morning stiffness, and greater pain.

When applied to 635 patients in the IPART cohort, in which there were 51 incident PsA cases over 1 year and 75 incident cases over 5 years, the area under the curve (AUC) for PRESTO at the cutoffs studied was 72% for the 1-year time window and 75% for the 5-year time window.

These levels are associated with adequate accuracy, according to Dr. Eder, who explained that “an AUC greater than 70% is considered reasonable” for clinical applicability.

Moreover, the cutoffs can be adjusted for the specific purpose of the predictive tool. For example, to screen patients for risk, lower cutoffs could be employed to increase sensitivity. In order to select patients for a clinical trial to prevent PsA, higher cutoffs could be employed to increase specificity.

But sensitivities and specificities move in opposite directions when cutoffs are adjusted. Showing data from the 5-year prediction model, Dr. Eder reported that specificities climbed from about 58% to 97% as cutoffs were increased. The sensitivities with these adjustments fell from 79% to 14%.

In general, Dr. Eder said there was “excellent calibration” for the cutoffs employed when they compared the predicted and observed rates of PsA according to quintile of predictive probability. The differences were particularly minor over a 1-year time period. Over the 5-year period, observed rates were somewhat higher than predicted in the fourth and fifth quintile, but, again, this discrepancy could be modified for specific applications with cutoff adjustments.

Validation studies are planned

Even though psoriasis patients in IPART represents one of the largest cohorts of prospectively collected psoriasis patients, Dr. Eder acknowledged that the sample size would be considered “moderate” for developing a predictive model. However, the fact that the data were collected prospectively using standardized methodology strengthens the findings and provides the basis for the next step.

“Validation studies are planned with external cohorts,” said Dr. Eder, who indicated that a viable tool for identifying psoriasis patients at risk for PsA is likely. Even if it is not employed routinely in its current form at the level of individual patient care, she predicted that it will have value at a research level for understanding the relationship of psoriasis to PsA.

Christopher T. Ritchlin, MD, a professor and researcher at the University of Rochester (N.Y.), agreed that PRESTO has important potential as a clinical tool. Dr. Ritchlin has been involved in the development of PRESTO but was not involved in the presentation made at the CRA annual meeting.

“The PRESTO tool has the ability to predict the 2- and 5-year risk of developing psoriatic arthritis, which is an important advance if confirmed,” he said in an interview. He pointed out that approximately 25%-30% who develop psoriasis will go on to develop PsA but until now there has been no way to identify them.

“This tool may provide a pathway to early intervention,” he said.

Dr. Eder has financial relationships with AbbVie, Eli Lilly, Fresenius Kabi, Janssen, Novartis, Pfizer, Sandoz, and UCB. Dr. Ritchlin has financial relationships with many of the same companies.