Neurology Reviews

Surgeon goes the extra half mile for his patient

Sorry medical profession, but it’s Adam Bodzin’s world now. When a donor liver got stuck in the middle of the Philadelphia Half Marathon’s 30,000 participants, Dr. Bodzin, the transplant team’s lead surgeon, took matters into his own hands. And by hands, of course, we mean feet.

Pixnio

Still wearing his hospital scrubs, Dr. Bodzin ran more than half a mile to where the van carrying the liver was stranded, according to the Philadelphia Inquirer. Fortunately, he was able to hitch a ride in a police car for the return trip and didn’t have to run back through the crowd carrying his somewhat unusual package. By package, of course, we mean human liver.

It’s been 3 months since the surgery/marathon and it’s still not clear why the driver had such trouble getting through – he had been trying for more than an hour and half by the time Dr. Bodzin reached him – but the surgery half of the big event was deemed a success and the patient has recovered.

Rick Hasz, president and chief executive officer of the Gift of Life Donor Program, which coordinates organ donation for transplants in the Philadelphia region, told the newspaper that “Dr. Bodzin’s quick action demonstrated his commitment to honoring the selfless generosity of all donors and their families and gives hope to everyone waiting for a second chance at life.”

Should Dr. Bodzin consider a step up from the transplant team to another group that’s fighting for the common good? The recipient of the liver in question seems to think so. “I guess he has a cape on under that white jacket,” 66-year-old Charles Rowe told Fox29. You already know where we’re going with this, right?

Avengers … Assemble.
 

Your spleen’s due for its 5,000-mile oil change

The human body is an incredible biological machine, capable of performing a countless array of tasks automatically and essentially without flaw, but there’s always room for improvement. After all, there are animals that can regrow entire missing limbs or live for up to 500 years. It would be nice if we could get some of that going.

Sigmund/Unsplash

Rather than any of that cool stuff, a recent survey of 2,000 average Americans revealed that our ambitions for improving the human body are a bit more mundane. The big thing that would make our lives better and easier, according to three-fourths of Americans, would be a built-in “check engine” light in our bodies. Come on guys, starfish can literally be cut in half and not only survive, but become two starfish. Mantis shrimp can punch with a force thousands of times their own weight. If we could punch like they could, we could literally break steel with our fists. Wouldn’t we rather have that?

Apparently not. Fine, we’ll stick with the check engine light.

Maybe it isn’t a huge surprise that we’d like the extra help in figuring out what our body needs. According to the survey, more than 60% of Americans struggle to identify when their body is trying to tell them something important, and only one-third actively checked in with their health every day. Considering about 40% said they feel tired for much of the day and nearly half reported not having a meal with fruits or vegetables in the past 3 days, perhaps a gentle reminder wouldn’t be the worst thing in the world.

So, if we did have a built-in check engine light, what would we use it for? A majority said they’d like to be reminded to drink a glass of water, with 45% saying they wanted to know when to take a nap. Feeling thirsty or tired isn’t quite enough, it seems.

Of course, the technology certainly exists to make the human check engine light a reality. An implanted microchip could absolutely tell us to drink a glass of water, but that would put our health in the hands of tech companies, and you just know Meta and Elon Muskrat wouldn’t pass up the chance for monetization. “Oh, sorry, we could have notified the hospital that you were about to have a heart attack, but you didn’t pay your life subscription this month.”
 

Sext offenders show more than their, well, you know

As we have become more and more attached to our phones, especially post pandemic, it’s no surprise that sexting – sending sexually explicit images and messages with those phones – has become a fairly common way for people to sexually communicate. And with dating apps just another venture in the dating landscape, regardless of age, sexting is an easy avenue to incite a mood without being physically present.

©agmit/istockphoto.com

A recent study, though, has linked sexting with anxiety, sleep issues, depression, and compulsive sexual behaviors. Yikes.

Although the researchers noted that sexting was primarily reciprocal (sending and receiving), “over 50% of adults report sending a sext, while women are up to four times more likely than men to report having received nonconsensual sexts,” said Brenda K. Wiederhold, PhD, editor-in-chief of Cyberpsychology, Behavior, and Social Networking, which published the study, in which Dr. Wiederhold was not involved.

Among the 2,160 U.S. college students who were involved, participants who had only sent sexts reported more anxiety, depression, and sleep problems than other groups (no sexting, received only, reciprocal). There was also a possible connection between sexting, marijuana use, and compulsive sexual behavior, the investigators said in a written statement.

Considering the study population, these data are perhaps not that surprising. For young adults, to receive or send an elusive nude is as common as it once was to give someone flowers. Not that the two things elicit the same reactions. “Many individuals reveal they enjoy consensual sexting and feel it empowers them and builds self-confidence,” Dr. Wiederhold added.

Receiving a nonconsensual sext, though, is definitely going to result in feeling violated and super awkward. Senders beware: Don’t be surprised if you’re ghosted after that.

Surgeon goes the extra half mile for his patient

Sorry medical profession, but it’s Adam Bodzin’s world now. When a donor liver got stuck in the middle of the Philadelphia Half Marathon’s 30,000 participants, Dr. Bodzin, the transplant team’s lead surgeon, took matters into his own hands. And by hands, of course, we mean feet.

Pixnio

Still wearing his hospital scrubs, Dr. Bodzin ran more than half a mile to where the van carrying the liver was stranded, according to the Philadelphia Inquirer. Fortunately, he was able to hitch a ride in a police car for the return trip and didn’t have to run back through the crowd carrying his somewhat unusual package. By package, of course, we mean human liver.

It’s been 3 months since the surgery/marathon and it’s still not clear why the driver had such trouble getting through – he had been trying for more than an hour and half by the time Dr. Bodzin reached him – but the surgery half of the big event was deemed a success and the patient has recovered.

Rick Hasz, president and chief executive officer of the Gift of Life Donor Program, which coordinates organ donation for transplants in the Philadelphia region, told the newspaper that “Dr. Bodzin’s quick action demonstrated his commitment to honoring the selfless generosity of all donors and their families and gives hope to everyone waiting for a second chance at life.”

Should Dr. Bodzin consider a step up from the transplant team to another group that’s fighting for the common good? The recipient of the liver in question seems to think so. “I guess he has a cape on under that white jacket,” 66-year-old Charles Rowe told Fox29. You already know where we’re going with this, right?

Avengers … Assemble.
 

Your spleen’s due for its 5,000-mile oil change

The human body is an incredible biological machine, capable of performing a countless array of tasks automatically and essentially without flaw, but there’s always room for improvement. After all, there are animals that can regrow entire missing limbs or live for up to 500 years. It would be nice if we could get some of that going.

Sigmund/Unsplash

Rather than any of that cool stuff, a recent survey of 2,000 average Americans revealed that our ambitions for improving the human body are a bit more mundane. The big thing that would make our lives better and easier, according to three-fourths of Americans, would be a built-in “check engine” light in our bodies. Come on guys, starfish can literally be cut in half and not only survive, but become two starfish. Mantis shrimp can punch with a force thousands of times their own weight. If we could punch like they could, we could literally break steel with our fists. Wouldn’t we rather have that?

Apparently not. Fine, we’ll stick with the check engine light.

Maybe it isn’t a huge surprise that we’d like the extra help in figuring out what our body needs. According to the survey, more than 60% of Americans struggle to identify when their body is trying to tell them something important, and only one-third actively checked in with their health every day. Considering about 40% said they feel tired for much of the day and nearly half reported not having a meal with fruits or vegetables in the past 3 days, perhaps a gentle reminder wouldn’t be the worst thing in the world.

So, if we did have a built-in check engine light, what would we use it for? A majority said they’d like to be reminded to drink a glass of water, with 45% saying they wanted to know when to take a nap. Feeling thirsty or tired isn’t quite enough, it seems.

Of course, the technology certainly exists to make the human check engine light a reality. An implanted microchip could absolutely tell us to drink a glass of water, but that would put our health in the hands of tech companies, and you just know Meta and Elon Muskrat wouldn’t pass up the chance for monetization. “Oh, sorry, we could have notified the hospital that you were about to have a heart attack, but you didn’t pay your life subscription this month.”
 

Sext offenders show more than their, well, you know

As we have become more and more attached to our phones, especially post pandemic, it’s no surprise that sexting – sending sexually explicit images and messages with those phones – has become a fairly common way for people to sexually communicate. And with dating apps just another venture in the dating landscape, regardless of age, sexting is an easy avenue to incite a mood without being physically present.

©agmit/istockphoto.com

A recent study, though, has linked sexting with anxiety, sleep issues, depression, and compulsive sexual behaviors. Yikes.

Although the researchers noted that sexting was primarily reciprocal (sending and receiving), “over 50% of adults report sending a sext, while women are up to four times more likely than men to report having received nonconsensual sexts,” said Brenda K. Wiederhold, PhD, editor-in-chief of Cyberpsychology, Behavior, and Social Networking, which published the study, in which Dr. Wiederhold was not involved.

Among the 2,160 U.S. college students who were involved, participants who had only sent sexts reported more anxiety, depression, and sleep problems than other groups (no sexting, received only, reciprocal). There was also a possible connection between sexting, marijuana use, and compulsive sexual behavior, the investigators said in a written statement.

Considering the study population, these data are perhaps not that surprising. For young adults, to receive or send an elusive nude is as common as it once was to give someone flowers. Not that the two things elicit the same reactions. “Many individuals reveal they enjoy consensual sexting and feel it empowers them and builds self-confidence,” Dr. Wiederhold added.

Receiving a nonconsensual sext, though, is definitely going to result in feeling violated and super awkward. Senders beware: Don’t be surprised if you’re ghosted after that.

Surgeon goes the extra half mile for his patient

Sorry medical profession, but it’s Adam Bodzin’s world now. When a donor liver got stuck in the middle of the Philadelphia Half Marathon’s 30,000 participants, Dr. Bodzin, the transplant team’s lead surgeon, took matters into his own hands. And by hands, of course, we mean feet.

Pixnio

Still wearing his hospital scrubs, Dr. Bodzin ran more than half a mile to where the van carrying the liver was stranded, according to the Philadelphia Inquirer. Fortunately, he was able to hitch a ride in a police car for the return trip and didn’t have to run back through the crowd carrying his somewhat unusual package. By package, of course, we mean human liver.

It’s been 3 months since the surgery/marathon and it’s still not clear why the driver had such trouble getting through – he had been trying for more than an hour and half by the time Dr. Bodzin reached him – but the surgery half of the big event was deemed a success and the patient has recovered.

Rick Hasz, president and chief executive officer of the Gift of Life Donor Program, which coordinates organ donation for transplants in the Philadelphia region, told the newspaper that “Dr. Bodzin’s quick action demonstrated his commitment to honoring the selfless generosity of all donors and their families and gives hope to everyone waiting for a second chance at life.”

Should Dr. Bodzin consider a step up from the transplant team to another group that’s fighting for the common good? The recipient of the liver in question seems to think so. “I guess he has a cape on under that white jacket,” 66-year-old Charles Rowe told Fox29. You already know where we’re going with this, right?

Avengers … Assemble.
 

Your spleen’s due for its 5,000-mile oil change

The human body is an incredible biological machine, capable of performing a countless array of tasks automatically and essentially without flaw, but there’s always room for improvement. After all, there are animals that can regrow entire missing limbs or live for up to 500 years. It would be nice if we could get some of that going.

Sigmund/Unsplash

Rather than any of that cool stuff, a recent survey of 2,000 average Americans revealed that our ambitions for improving the human body are a bit more mundane. The big thing that would make our lives better and easier, according to three-fourths of Americans, would be a built-in “check engine” light in our bodies. Come on guys, starfish can literally be cut in half and not only survive, but become two starfish. Mantis shrimp can punch with a force thousands of times their own weight. If we could punch like they could, we could literally break steel with our fists. Wouldn’t we rather have that?

Apparently not. Fine, we’ll stick with the check engine light.

Maybe it isn’t a huge surprise that we’d like the extra help in figuring out what our body needs. According to the survey, more than 60% of Americans struggle to identify when their body is trying to tell them something important, and only one-third actively checked in with their health every day. Considering about 40% said they feel tired for much of the day and nearly half reported not having a meal with fruits or vegetables in the past 3 days, perhaps a gentle reminder wouldn’t be the worst thing in the world.

So, if we did have a built-in check engine light, what would we use it for? A majority said they’d like to be reminded to drink a glass of water, with 45% saying they wanted to know when to take a nap. Feeling thirsty or tired isn’t quite enough, it seems.

Of course, the technology certainly exists to make the human check engine light a reality. An implanted microchip could absolutely tell us to drink a glass of water, but that would put our health in the hands of tech companies, and you just know Meta and Elon Muskrat wouldn’t pass up the chance for monetization. “Oh, sorry, we could have notified the hospital that you were about to have a heart attack, but you didn’t pay your life subscription this month.”
 

Sext offenders show more than their, well, you know

As we have become more and more attached to our phones, especially post pandemic, it’s no surprise that sexting – sending sexually explicit images and messages with those phones – has become a fairly common way for people to sexually communicate. And with dating apps just another venture in the dating landscape, regardless of age, sexting is an easy avenue to incite a mood without being physically present.

©agmit/istockphoto.com

A recent study, though, has linked sexting with anxiety, sleep issues, depression, and compulsive sexual behaviors. Yikes.

Although the researchers noted that sexting was primarily reciprocal (sending and receiving), “over 50% of adults report sending a sext, while women are up to four times more likely than men to report having received nonconsensual sexts,” said Brenda K. Wiederhold, PhD, editor-in-chief of Cyberpsychology, Behavior, and Social Networking, which published the study, in which Dr. Wiederhold was not involved.

Among the 2,160 U.S. college students who were involved, participants who had only sent sexts reported more anxiety, depression, and sleep problems than other groups (no sexting, received only, reciprocal). There was also a possible connection between sexting, marijuana use, and compulsive sexual behavior, the investigators said in a written statement.

Considering the study population, these data are perhaps not that surprising. For young adults, to receive or send an elusive nude is as common as it once was to give someone flowers. Not that the two things elicit the same reactions. “Many individuals reveal they enjoy consensual sexting and feel it empowers them and builds self-confidence,” Dr. Wiederhold added.

Receiving a nonconsensual sext, though, is definitely going to result in feeling violated and super awkward. Senders beware: Don’t be surprised if you’re ghosted after that.

SAN DIEGO – A new retrospective analysis of patients with myelin oligodendrocyte glycoprotein antibody disease (MOGAD) indicates that treatment with immunotherapy is associated with a lower risk of relapse. The authors note that many MOGAD patients never experience a relapse and it is difficult to predict which ones will.

MOGAD can cause optic neuritis, transverse myelitis, and acute disseminated encephalomyelitis (ADEM). It was first described in 2007, and the best approaches to therapy are not yet understood. The new study is at least a starting point for understanding treatment outcomes, according to Philippe Bilodeau, MD, who presented the study during a poster session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
 

Predicting which patients will relapse

“I think one of the biggest unanswered clinical questions in MOGAD is trying to determine who’s going to go on to have relapsing MOGAD. About 30% to 40% of patients with MOGAD will never have a second attack. So one of the big questions is: How can we identify patients who would benefit from immunotherapy, and how can we identify patients who will have a more benign disease course and may not need to be started on a treatment,” said Dr. Bilodeau, a neurology resident at Massachusetts General Hospital/Brigham and Women’s Hospital, Boston.

The researchers analyzed data from 143 patients seen at Massachusetts General or Brigham and Women’s Hospital who had presented with their first attack. Over a follow-up period of 5 years, the relapse rate was 61.8%. The researchers examined various factors, including age of onset, high MOG titer, attack type, and male sex, and found that only the latter came close to predicting relapse, though it fell short of clinical significance (hazard ratio [HR], 0.61; P = .07).

However, treatment with mycophenolate, azathioprine, intravenous immunoglobulins (IVIG), rituximab, or tocilizumab strongly predicted a lower probability of relapse (HR, 0.25; P < .0001).
 

The most effective treatment for relapsing MOGAD

In a separate poster, his team examined a subset of the cohort of 88 patients who were treated with mycophenolate mofetil, B-cell depletion, rituximab, or IV immunoglobulins (IVIG) during a first or second relapse, as well as an analysis of every relapse experienced by any patient during the course of their disease. “Using a negative binomial regression, we looked at the annualized relapse rates and incidence rate ratios between the different treatments. No matter how you looked at the data – even if you looked at total time on IVIG, if you looked at time on monotherapy, excluding if they were on prednisone at the same time if they were on both IVIG and rituximab, if you only consider patients that were on high dose IVIG – IVIG was by far the best treatment and rituximab was always the least effective, and mycophenolate was always between IVIG and rituximab. So I think in that cohort, we can say with some confidence that IVIG is the most effective treatment for relapsing MOGAD,” said Dr. Bilodeau.

Other studies had suggested efficacy of individual treatments, but “I think what hadn’t been done is taking one cohort and comparing those treatments head to head, so that’s what we were trying to do,” said Dr. Bilodeau.

Both studies have the usual caveats of a retrospective study and so cannot prove causality. “We need to find more covariates to make sure that there’s no confounding (factor) explaining this and to make sure that there aren’t other demographic or clinical factors that explain the association. But as it stands, I think at this time starting treatment with immunotherapy is the only thing that we know will reduce the risk of having a future relapse. There’s a lot of further analysis that we need to do,” said Dr. Bilodeau.

He said that the study also provided some preliminary insight into treatment of pediatric disease. “We have interesting data from that analysis that pediatric-onset MOGAD actually had a particularly good response to [mycophenolate], more so than in adults,” he said.

“At this point, I think a rational approach if you have someone coming in with a first relapse is, you have to assess their risk tolerance. If they’re a very risk-averse patient, I think it’s reasonable to start them on treatment. I think it’s reasonable to monitor their titer. There’s some data that if they seroconvert to negative, you might be able to stop immunotherapy. If someone has established relapsing disease, and they have adult onset [disease], IVIG should be the first-line treatment. If they’re pediatric onset, either [mycophenolate] or IVIG are probably good first line treatments,” he said.
 

‘A good beginning’

The studies are a good beginning to getting a better understanding of MOGAD treatment, according to Michael Cossoy, MD, who attended the poster session and was asked to comment on the study.

“It’s interesting because MOG antibody-associated disease is so relatively new that we don’t have a great idea yet about who needs to be treated. Should we put them on some immunosuppressive therapy or should we wait? At the moment this is a bit of a tautology. You know that if you put people on therapy from the very first event, some of those people are not going to have a second event. And some of the people are, but you’ve decreased the risk of them having that second (event) if your treatment is effective. So that’s what they’ve shown, which is great. But the question is, can you predict who’s going to have a second event and know who to put on treatment and not put on treatment? It’s too early to know, but this is a good start,” said Dr. Cossoy, assistant professor of ophthalmology at the University of Manitoba.

Dr. Bilodeau and Dr. Cossoy have no relevant financial disclosures.

SAN DIEGO – A new retrospective analysis of patients with myelin oligodendrocyte glycoprotein antibody disease (MOGAD) indicates that treatment with immunotherapy is associated with a lower risk of relapse. The authors note that many MOGAD patients never experience a relapse and it is difficult to predict which ones will.

MOGAD can cause optic neuritis, transverse myelitis, and acute disseminated encephalomyelitis (ADEM). It was first described in 2007, and the best approaches to therapy are not yet understood. The new study is at least a starting point for understanding treatment outcomes, according to Philippe Bilodeau, MD, who presented the study during a poster session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
 

Predicting which patients will relapse

“I think one of the biggest unanswered clinical questions in MOGAD is trying to determine who’s going to go on to have relapsing MOGAD. About 30% to 40% of patients with MOGAD will never have a second attack. So one of the big questions is: How can we identify patients who would benefit from immunotherapy, and how can we identify patients who will have a more benign disease course and may not need to be started on a treatment,” said Dr. Bilodeau, a neurology resident at Massachusetts General Hospital/Brigham and Women’s Hospital, Boston.

The researchers analyzed data from 143 patients seen at Massachusetts General or Brigham and Women’s Hospital who had presented with their first attack. Over a follow-up period of 5 years, the relapse rate was 61.8%. The researchers examined various factors, including age of onset, high MOG titer, attack type, and male sex, and found that only the latter came close to predicting relapse, though it fell short of clinical significance (hazard ratio [HR], 0.61; P = .07).

However, treatment with mycophenolate, azathioprine, intravenous immunoglobulins (IVIG), rituximab, or tocilizumab strongly predicted a lower probability of relapse (HR, 0.25; P < .0001).
 

The most effective treatment for relapsing MOGAD

In a separate poster, his team examined a subset of the cohort of 88 patients who were treated with mycophenolate mofetil, B-cell depletion, rituximab, or IV immunoglobulins (IVIG) during a first or second relapse, as well as an analysis of every relapse experienced by any patient during the course of their disease. “Using a negative binomial regression, we looked at the annualized relapse rates and incidence rate ratios between the different treatments. No matter how you looked at the data – even if you looked at total time on IVIG, if you looked at time on monotherapy, excluding if they were on prednisone at the same time if they were on both IVIG and rituximab, if you only consider patients that were on high dose IVIG – IVIG was by far the best treatment and rituximab was always the least effective, and mycophenolate was always between IVIG and rituximab. So I think in that cohort, we can say with some confidence that IVIG is the most effective treatment for relapsing MOGAD,” said Dr. Bilodeau.

Other studies had suggested efficacy of individual treatments, but “I think what hadn’t been done is taking one cohort and comparing those treatments head to head, so that’s what we were trying to do,” said Dr. Bilodeau.

Both studies have the usual caveats of a retrospective study and so cannot prove causality. “We need to find more covariates to make sure that there’s no confounding (factor) explaining this and to make sure that there aren’t other demographic or clinical factors that explain the association. But as it stands, I think at this time starting treatment with immunotherapy is the only thing that we know will reduce the risk of having a future relapse. There’s a lot of further analysis that we need to do,” said Dr. Bilodeau.

He said that the study also provided some preliminary insight into treatment of pediatric disease. “We have interesting data from that analysis that pediatric-onset MOGAD actually had a particularly good response to [mycophenolate], more so than in adults,” he said.

“At this point, I think a rational approach if you have someone coming in with a first relapse is, you have to assess their risk tolerance. If they’re a very risk-averse patient, I think it’s reasonable to start them on treatment. I think it’s reasonable to monitor their titer. There’s some data that if they seroconvert to negative, you might be able to stop immunotherapy. If someone has established relapsing disease, and they have adult onset [disease], IVIG should be the first-line treatment. If they’re pediatric onset, either [mycophenolate] or IVIG are probably good first line treatments,” he said.
 

‘A good beginning’

The studies are a good beginning to getting a better understanding of MOGAD treatment, according to Michael Cossoy, MD, who attended the poster session and was asked to comment on the study.

“It’s interesting because MOG antibody-associated disease is so relatively new that we don’t have a great idea yet about who needs to be treated. Should we put them on some immunosuppressive therapy or should we wait? At the moment this is a bit of a tautology. You know that if you put people on therapy from the very first event, some of those people are not going to have a second event. And some of the people are, but you’ve decreased the risk of them having that second (event) if your treatment is effective. So that’s what they’ve shown, which is great. But the question is, can you predict who’s going to have a second event and know who to put on treatment and not put on treatment? It’s too early to know, but this is a good start,” said Dr. Cossoy, assistant professor of ophthalmology at the University of Manitoba.

Dr. Bilodeau and Dr. Cossoy have no relevant financial disclosures.

SAN DIEGO – A new retrospective analysis of patients with myelin oligodendrocyte glycoprotein antibody disease (MOGAD) indicates that treatment with immunotherapy is associated with a lower risk of relapse. The authors note that many MOGAD patients never experience a relapse and it is difficult to predict which ones will.

MOGAD can cause optic neuritis, transverse myelitis, and acute disseminated encephalomyelitis (ADEM). It was first described in 2007, and the best approaches to therapy are not yet understood. The new study is at least a starting point for understanding treatment outcomes, according to Philippe Bilodeau, MD, who presented the study during a poster session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
 

Predicting which patients will relapse

“I think one of the biggest unanswered clinical questions in MOGAD is trying to determine who’s going to go on to have relapsing MOGAD. About 30% to 40% of patients with MOGAD will never have a second attack. So one of the big questions is: How can we identify patients who would benefit from immunotherapy, and how can we identify patients who will have a more benign disease course and may not need to be started on a treatment,” said Dr. Bilodeau, a neurology resident at Massachusetts General Hospital/Brigham and Women’s Hospital, Boston.

The researchers analyzed data from 143 patients seen at Massachusetts General or Brigham and Women’s Hospital who had presented with their first attack. Over a follow-up period of 5 years, the relapse rate was 61.8%. The researchers examined various factors, including age of onset, high MOG titer, attack type, and male sex, and found that only the latter came close to predicting relapse, though it fell short of clinical significance (hazard ratio [HR], 0.61; P = .07).

However, treatment with mycophenolate, azathioprine, intravenous immunoglobulins (IVIG), rituximab, or tocilizumab strongly predicted a lower probability of relapse (HR, 0.25; P < .0001).
 

The most effective treatment for relapsing MOGAD

In a separate poster, his team examined a subset of the cohort of 88 patients who were treated with mycophenolate mofetil, B-cell depletion, rituximab, or IV immunoglobulins (IVIG) during a first or second relapse, as well as an analysis of every relapse experienced by any patient during the course of their disease. “Using a negative binomial regression, we looked at the annualized relapse rates and incidence rate ratios between the different treatments. No matter how you looked at the data – even if you looked at total time on IVIG, if you looked at time on monotherapy, excluding if they were on prednisone at the same time if they were on both IVIG and rituximab, if you only consider patients that were on high dose IVIG – IVIG was by far the best treatment and rituximab was always the least effective, and mycophenolate was always between IVIG and rituximab. So I think in that cohort, we can say with some confidence that IVIG is the most effective treatment for relapsing MOGAD,” said Dr. Bilodeau.

Other studies had suggested efficacy of individual treatments, but “I think what hadn’t been done is taking one cohort and comparing those treatments head to head, so that’s what we were trying to do,” said Dr. Bilodeau.

Both studies have the usual caveats of a retrospective study and so cannot prove causality. “We need to find more covariates to make sure that there’s no confounding (factor) explaining this and to make sure that there aren’t other demographic or clinical factors that explain the association. But as it stands, I think at this time starting treatment with immunotherapy is the only thing that we know will reduce the risk of having a future relapse. There’s a lot of further analysis that we need to do,” said Dr. Bilodeau.

He said that the study also provided some preliminary insight into treatment of pediatric disease. “We have interesting data from that analysis that pediatric-onset MOGAD actually had a particularly good response to [mycophenolate], more so than in adults,” he said.

“At this point, I think a rational approach if you have someone coming in with a first relapse is, you have to assess their risk tolerance. If they’re a very risk-averse patient, I think it’s reasonable to start them on treatment. I think it’s reasonable to monitor their titer. There’s some data that if they seroconvert to negative, you might be able to stop immunotherapy. If someone has established relapsing disease, and they have adult onset [disease], IVIG should be the first-line treatment. If they’re pediatric onset, either [mycophenolate] or IVIG are probably good first line treatments,” he said.
 

‘A good beginning’

The studies are a good beginning to getting a better understanding of MOGAD treatment, according to Michael Cossoy, MD, who attended the poster session and was asked to comment on the study.

“It’s interesting because MOG antibody-associated disease is so relatively new that we don’t have a great idea yet about who needs to be treated. Should we put them on some immunosuppressive therapy or should we wait? At the moment this is a bit of a tautology. You know that if you put people on therapy from the very first event, some of those people are not going to have a second event. And some of the people are, but you’ve decreased the risk of them having that second (event) if your treatment is effective. So that’s what they’ve shown, which is great. But the question is, can you predict who’s going to have a second event and know who to put on treatment and not put on treatment? It’s too early to know, but this is a good start,” said Dr. Cossoy, assistant professor of ophthalmology at the University of Manitoba.

Dr. Bilodeau and Dr. Cossoy have no relevant financial disclosures.

SAN DIEGO – Epstein-Barr Virus (EBV) infection is widely recognized as a contributor to risk of multiple sclerosis (MS). Although most adults have been exposed, it is very rare to find MS in an individual with no prior EBV exposure.

That apparent relationship has driven interest in a vaccine against EBV in an effort to reduce MS incidence on a population level.

At a session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS), two researchers debated the potential benefits and pitfalls of such a program. The issues included the possible benefit in MS and other EBV-related conditions such as mononucleosis and various cancers, and whether EBV infection is a sufficient cause for MS, as well as concerns about vaccinating a healthy at-risk population.
 

Reducing the risk of MS by targeting EBV

Jeffrey I. Cohen, MD, spoke first, and cited several lines of evidence supporting the importance of EBV in MS. One study showed a 32-fold increased risk of MS following primary infection with EBV, and another showed that higher EBV nuclear antigen (EBNA) antibody titers were associated with a 36-fold higher risk of MS. “So we have two completely independent studies suggesting that EBV is really very important as a cofactor for development of MS,” said Dr. Cohen, chief of the laboratory of infectious diseases and chief of the medical virology section at the National Institutes of Health, Bethesda, Md.

NIH

EBV is also latent in B cells, and anti-B cell therapy is an effective therapeutic strategy for MS. However, the mechanism remains unknown.

Targeting EBV could involve attacking infected cells, or a therapeutic vaccine could be employed to treat EVB-infected individuals, similar to the shingles vaccine. “In all of these methods, one would end up with fewer EBV infected B cells and as a result, presumably you’d have reduced antigenic stimulation of EBV-infected B cells to stimulate either antibodies or T cells that could damage the nervous system. By reducing this, one might be able to [treat] multiple sclerosis,” said Dr. Cohen.

He did acknowledge concerns. It isn’t yet understood whether destroying EBV-infected cells would actually improve outcomes. It also may be more difficult to reduce a latent infection than to prevent infection, since almost all B cells become latently infected. “Thus we think perhaps a role for preventing infection or modifying the initial infection could be important,” said Dr. Cohen.

The most advanced vaccine candidate is a soluble form of EBV glycoprotein gp 350, which is the dominant glycoprotein on the surface of the virus and infected cells. It reduced the risk of mononucleosis by 78%, but it did not prevent EBV infection. There were no safety concerns. Two more vaccines are currently in clinical trials – an mRNA vaccine against a gp 350 sponsored by Moderna, and a gp 350 nanoparticle vaccine by the NIH.

Dr. Cohen acknowledged that safety is the most important factor, since it would be given to healthy individuals, and probably children. There are worries that a vaccine using EBV proteins could worsen MS. In particular, higher titers of antibodies against EBNA have been linked to developing MS and the anti-EBNA antibody has been implicated in molecular mimicry related to MS. However, the current vaccines avoid EBNA. Another worry is that a vaccine could delay onset of disease to an older age, when infection might be more dangerous. However, no delay in onset has been noted with the varicella vaccine or polio vaccines, which prompted similar concerns.

Vaccinating against EBV could also reduce other conditions such as mononucleosis and several cancers.
 

Does EBV infection even matter?

In his talk, Peter Calabresi, MD, made the case that EBV is not the sole cause of MS, and thus targeting it may prove ineffective. Dr. Calabresi is director of the division of neuroimmunology at Johns Hopkins Medicine, Baltimore.

Why was he asked to provide a rebuttal? “About this time last year, I commented at a meeting that we should be thoughtful as we think about what to do about EBV and MS. I do believe that constructive dialogue is the foundation of science,” he said. He also stated that he is not opposed to vaccines. “I congratulate Dr. Cohen on all of his vaccine successes,” he said.

Johns Hopkins Medicine

SAN DIEGO – Epstein-Barr Virus (EBV) infection is widely recognized as a contributor to risk of multiple sclerosis (MS). Although most adults have been exposed, it is very rare to find MS in an individual with no prior EBV exposure.

That apparent relationship has driven interest in a vaccine against EBV in an effort to reduce MS incidence on a population level.

At a session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS), two researchers debated the potential benefits and pitfalls of such a program. The issues included the possible benefit in MS and other EBV-related conditions such as mononucleosis and various cancers, and whether EBV infection is a sufficient cause for MS, as well as concerns about vaccinating a healthy at-risk population.
 

Reducing the risk of MS by targeting EBV

Jeffrey I. Cohen, MD, spoke first, and cited several lines of evidence supporting the importance of EBV in MS. One study showed a 32-fold increased risk of MS following primary infection with EBV, and another showed that higher EBV nuclear antigen (EBNA) antibody titers were associated with a 36-fold higher risk of MS. “So we have two completely independent studies suggesting that EBV is really very important as a cofactor for development of MS,” said Dr. Cohen, chief of the laboratory of infectious diseases and chief of the medical virology section at the National Institutes of Health, Bethesda, Md.

NIH

EBV is also latent in B cells, and anti-B cell therapy is an effective therapeutic strategy for MS. However, the mechanism remains unknown.

Targeting EBV could involve attacking infected cells, or a therapeutic vaccine could be employed to treat EVB-infected individuals, similar to the shingles vaccine. “In all of these methods, one would end up with fewer EBV infected B cells and as a result, presumably you’d have reduced antigenic stimulation of EBV-infected B cells to stimulate either antibodies or T cells that could damage the nervous system. By reducing this, one might be able to [treat] multiple sclerosis,” said Dr. Cohen.

He did acknowledge concerns. It isn’t yet understood whether destroying EBV-infected cells would actually improve outcomes. It also may be more difficult to reduce a latent infection than to prevent infection, since almost all B cells become latently infected. “Thus we think perhaps a role for preventing infection or modifying the initial infection could be important,” said Dr. Cohen.

The most advanced vaccine candidate is a soluble form of EBV glycoprotein gp 350, which is the dominant glycoprotein on the surface of the virus and infected cells. It reduced the risk of mononucleosis by 78%, but it did not prevent EBV infection. There were no safety concerns. Two more vaccines are currently in clinical trials – an mRNA vaccine against a gp 350 sponsored by Moderna, and a gp 350 nanoparticle vaccine by the NIH.

Dr. Cohen acknowledged that safety is the most important factor, since it would be given to healthy individuals, and probably children. There are worries that a vaccine using EBV proteins could worsen MS. In particular, higher titers of antibodies against EBNA have been linked to developing MS and the anti-EBNA antibody has been implicated in molecular mimicry related to MS. However, the current vaccines avoid EBNA. Another worry is that a vaccine could delay onset of disease to an older age, when infection might be more dangerous. However, no delay in onset has been noted with the varicella vaccine or polio vaccines, which prompted similar concerns.

Vaccinating against EBV could also reduce other conditions such as mononucleosis and several cancers.
 

Does EBV infection even matter?

In his talk, Peter Calabresi, MD, made the case that EBV is not the sole cause of MS, and thus targeting it may prove ineffective. Dr. Calabresi is director of the division of neuroimmunology at Johns Hopkins Medicine, Baltimore.

Why was he asked to provide a rebuttal? “About this time last year, I commented at a meeting that we should be thoughtful as we think about what to do about EBV and MS. I do believe that constructive dialogue is the foundation of science,” he said. He also stated that he is not opposed to vaccines. “I congratulate Dr. Cohen on all of his vaccine successes,” he said.

Johns Hopkins Medicine

SAN DIEGO – Epstein-Barr Virus (EBV) infection is widely recognized as a contributor to risk of multiple sclerosis (MS). Although most adults have been exposed, it is very rare to find MS in an individual with no prior EBV exposure.

That apparent relationship has driven interest in a vaccine against EBV in an effort to reduce MS incidence on a population level.

At a session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS), two researchers debated the potential benefits and pitfalls of such a program. The issues included the possible benefit in MS and other EBV-related conditions such as mononucleosis and various cancers, and whether EBV infection is a sufficient cause for MS, as well as concerns about vaccinating a healthy at-risk population.
 

Reducing the risk of MS by targeting EBV

Jeffrey I. Cohen, MD, spoke first, and cited several lines of evidence supporting the importance of EBV in MS. One study showed a 32-fold increased risk of MS following primary infection with EBV, and another showed that higher EBV nuclear antigen (EBNA) antibody titers were associated with a 36-fold higher risk of MS. “So we have two completely independent studies suggesting that EBV is really very important as a cofactor for development of MS,” said Dr. Cohen, chief of the laboratory of infectious diseases and chief of the medical virology section at the National Institutes of Health, Bethesda, Md.

NIH

EBV is also latent in B cells, and anti-B cell therapy is an effective therapeutic strategy for MS. However, the mechanism remains unknown.

Targeting EBV could involve attacking infected cells, or a therapeutic vaccine could be employed to treat EVB-infected individuals, similar to the shingles vaccine. “In all of these methods, one would end up with fewer EBV infected B cells and as a result, presumably you’d have reduced antigenic stimulation of EBV-infected B cells to stimulate either antibodies or T cells that could damage the nervous system. By reducing this, one might be able to [treat] multiple sclerosis,” said Dr. Cohen.

He did acknowledge concerns. It isn’t yet understood whether destroying EBV-infected cells would actually improve outcomes. It also may be more difficult to reduce a latent infection than to prevent infection, since almost all B cells become latently infected. “Thus we think perhaps a role for preventing infection or modifying the initial infection could be important,” said Dr. Cohen.

The most advanced vaccine candidate is a soluble form of EBV glycoprotein gp 350, which is the dominant glycoprotein on the surface of the virus and infected cells. It reduced the risk of mononucleosis by 78%, but it did not prevent EBV infection. There were no safety concerns. Two more vaccines are currently in clinical trials – an mRNA vaccine against a gp 350 sponsored by Moderna, and a gp 350 nanoparticle vaccine by the NIH.

Dr. Cohen acknowledged that safety is the most important factor, since it would be given to healthy individuals, and probably children. There are worries that a vaccine using EBV proteins could worsen MS. In particular, higher titers of antibodies against EBNA have been linked to developing MS and the anti-EBNA antibody has been implicated in molecular mimicry related to MS. However, the current vaccines avoid EBNA. Another worry is that a vaccine could delay onset of disease to an older age, when infection might be more dangerous. However, no delay in onset has been noted with the varicella vaccine or polio vaccines, which prompted similar concerns.

Vaccinating against EBV could also reduce other conditions such as mononucleosis and several cancers.
 

Does EBV infection even matter?

In his talk, Peter Calabresi, MD, made the case that EBV is not the sole cause of MS, and thus targeting it may prove ineffective. Dr. Calabresi is director of the division of neuroimmunology at Johns Hopkins Medicine, Baltimore.

Why was he asked to provide a rebuttal? “About this time last year, I commented at a meeting that we should be thoughtful as we think about what to do about EBV and MS. I do believe that constructive dialogue is the foundation of science,” he said. He also stated that he is not opposed to vaccines. “I congratulate Dr. Cohen on all of his vaccine successes,” he said.

Johns Hopkins Medicine

A multipart study reports that erythritol – a sugar alcohol (polyol) increasingly used as an artificial sweetener that is also made in the body – is associated with risk of major adverse cardiovascular events (MACE) and promotes clotting (thrombosis).

Erythritol is one of the most widely used artificial sweeteners with rapidly increasing prevalence in processed and “keto-related” foods. Artificial sweeteners are “generally recognized as safe” (GRAS) by the U.S. Food and Drug Administration, so there is no requirement for long-term safety studies, and little is known about the long-term health effects.

The current research, published online in Nature Medicine by Marco Witkowski, MD, of the Lerner Research Institute at Cleveland Clinic and colleagues, had multiple parts.

First, in a group of patients undergoing cardiac risk assessment, the researchers found that high levels of polyols, especially erythritol, were associated with increased 3-year risk of MACE, defined as cardiovascular death or nonfatal myocardial infarction or stroke. 

Next, the association of erythritol with this outcome was reproduced in two large U.S. and European groups of stable patients undergoing elective cardiac evaluation.

Next, adding erythritol to whole blood or platelets led to clot activation. And lastly, in eight healthy volunteers, ingesting 30 g of an erythritol-sweetened drink – comparable to a single can of commercially available beverage or a pint of keto ice cream – induced marked and sustained (> 2 day) increases in levels of plasma erythritol.

“Our study shows that when participants consumed an artificially sweetened beverage with an amount of erythritol found in many processed foods, markedly elevated levels in the blood are observed for days – levels well above those observed to enhance clotting risks,” said senior author Stanley L. Hazen, MD, PhD.  

“It is important that further safety studies are conducted to examine the long-term effects of artificial sweeteners in general, and erythritol specifically, on risks for heart attack and stroke, particularly in people at higher risk for cardiovascular disease,” Dr. Hazen, co–section head of preventive cardiology at Cleveland Clinic, said in a press release from his institution.

“Sweeteners like erythritol have rapidly increased in popularity in recent years, but there needs to be more in-depth research into their long-term effects. Cardiovascular disease builds over time, and heart disease is the leading cause of death globally. We need to make sure the foods we eat aren’t hidden contributors,” Dr. Hazen urged.

The topic remains controversial.

Duane Mellor, PhD, a registered dietitian and senior teaching fellow at Aston University, Birmingham, England, told the U.K. Science Media Centre: “This paper effectively shows multiple pieces of a jigsaw exploring the effects of erythritol – although it claims to show an associated risk with the use of erythritol as an artificial sweetener and cardiovascular disease, I believe it fails to do so, as ultimately, erythritol can be made inside our bodies and the intake in most people’s diet is much lower than the amount given in this study.” 

Dr. Hazen countered that data from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) in the United States show that, in some individuals, daily intake of erythritol is estimated to reach 30 g/day. 

“Many try and reduce sugar intake by taking many teaspoons of erythritol in their tea, coffee, etc., instead of sugar,” Dr. Hazen added. “Or they eat keto processed foods that have significant quantities of erythritol within it.”

“These studies are a warning for how our processed food (keto and zero sugar, especially) may inadvertently be causing risk/harm. … in the very subset of subjects who are most vulnerable,” according to Dr. Hazen.
 

Erythritol marketed as ‘zero calorie’, ‘non-nutritive’, or ‘natural’

Patients with type 2 diabetes and obesity are often advised to replace sugar with artificial sweeteners for better glucose control and weight loss, but growing epidemiologic evidence links artificial sweetener consumption with weight gain, insulin resistance, type 2 diabetes, and cardiovascular disease, the researchers write.

Erythritol is naturally present in low amounts in fruits and vegetables; the artificial sweetener erythritol that is produced from corn is only 70% as sweet as sugar.

Upon ingestion it is poorly metabolized, and most is excreted in the urine, so it is characterized as a “zero-calorie,” “non-nutritive,” or “natural sweetener.” It is predicted to double in marketshare in the sweetener sector in the next 5 years.
 

Multipart study

In the first part of their study, in a discovery cohort in 1,157 patients undergoing cardiovascular assessment with 3-year outcomes, the researchers identified polyols that were associated with MACE, and erythritol was among the top MACE-associated molecules.

Next, in a U.S. validation cohort of 2,149 patients, over a 3-year follow-up, patients with plasma levels of erythritol in the highest quartile had a 1.8-fold higher risk of MACE than patients in the lowest quartile (P = .007), after adjusting for cardiovascular risk factors.

In a European validation cohort of 833 patients, over a 3-year follow-up, patients with plasma levels of erythritol in the highest quartile had a 2.21-fold higher risk of MACE than patients in the lowest quartile (P = .010, after adjustment).

At physiologic levels, erythritol enhanced platelet reactivity in vitro and thrombosis formation in vivo.

Finally, in a prospective pilot intervention study, erythritol ingestion in healthy volunteers induced marked and sustained increases in plasma erythritol levels well above thresholds associated with heightened platelet reactivity and thrombosis potential in in vitro and in vivo studies.
 

Others weigh in

“While I think the finding certainly warrants further investigation, don’t throw out your sweeteners just yet,” commented Oliver Jones, PhD, professor of chemistry at the Royal Melbourne Institute of Technology.

“This study only looks at erythritol, and artificial sweeteners are generally considered safe. Any possible (and, as yet unproven) risks of excess erythritol would also need to be balanced against the very real health risks of excess glucose consumption,” he said.

Dr. Hazen responded: “True enough. Erythritol is but one of many artificial sweeteners. That is why it is important to read labels. This study can make patients be informed about how to potentially avoid something that might cause them inadvertent harm.”

“The key findings of this study are that high blood levels of erythritol are strongly associated with cardiovascular outcomes in high-risk patients, which has been replicated in separate validation studies,” said Tom Sanders, DSc, PhD, professor emeritus of nutrition and dietetics, King’s College London.

“Diabetes UK currently advises diabetes patients not to use polyols,” he added.

Dr. Hazen noted that “About three-quarters of the participants had coronary disease, high blood pressure, and about a fifth had diabetes.”

The researchers acknowledge, however, that the observational studies cannot show cause and effect.

The study was supported by the Office of Dietary Supplements at the National Institutes of Health, the Leducq Foundation, and the German Research Foundation (Deutsche Forschungsgemeinschaft). Dr. Mellor, Dr. Jones, and Dr. Sanders have reported no relevant financial relationships.

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

A multipart study reports that erythritol – a sugar alcohol (polyol) increasingly used as an artificial sweetener that is also made in the body – is associated with risk of major adverse cardiovascular events (MACE) and promotes clotting (thrombosis).

Erythritol is one of the most widely used artificial sweeteners with rapidly increasing prevalence in processed and “keto-related” foods. Artificial sweeteners are “generally recognized as safe” (GRAS) by the U.S. Food and Drug Administration, so there is no requirement for long-term safety studies, and little is known about the long-term health effects.

The current research, published online in Nature Medicine by Marco Witkowski, MD, of the Lerner Research Institute at Cleveland Clinic and colleagues, had multiple parts.

First, in a group of patients undergoing cardiac risk assessment, the researchers found that high levels of polyols, especially erythritol, were associated with increased 3-year risk of MACE, defined as cardiovascular death or nonfatal myocardial infarction or stroke. 

Next, the association of erythritol with this outcome was reproduced in two large U.S. and European groups of stable patients undergoing elective cardiac evaluation.

Next, adding erythritol to whole blood or platelets led to clot activation. And lastly, in eight healthy volunteers, ingesting 30 g of an erythritol-sweetened drink – comparable to a single can of commercially available beverage or a pint of keto ice cream – induced marked and sustained (> 2 day) increases in levels of plasma erythritol.

“Our study shows that when participants consumed an artificially sweetened beverage with an amount of erythritol found in many processed foods, markedly elevated levels in the blood are observed for days – levels well above those observed to enhance clotting risks,” said senior author Stanley L. Hazen, MD, PhD.  

“It is important that further safety studies are conducted to examine the long-term effects of artificial sweeteners in general, and erythritol specifically, on risks for heart attack and stroke, particularly in people at higher risk for cardiovascular disease,” Dr. Hazen, co–section head of preventive cardiology at Cleveland Clinic, said in a press release from his institution.

“Sweeteners like erythritol have rapidly increased in popularity in recent years, but there needs to be more in-depth research into their long-term effects. Cardiovascular disease builds over time, and heart disease is the leading cause of death globally. We need to make sure the foods we eat aren’t hidden contributors,” Dr. Hazen urged.

The topic remains controversial.

Duane Mellor, PhD, a registered dietitian and senior teaching fellow at Aston University, Birmingham, England, told the U.K. Science Media Centre: “This paper effectively shows multiple pieces of a jigsaw exploring the effects of erythritol – although it claims to show an associated risk with the use of erythritol as an artificial sweetener and cardiovascular disease, I believe it fails to do so, as ultimately, erythritol can be made inside our bodies and the intake in most people’s diet is much lower than the amount given in this study.” 

Dr. Hazen countered that data from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) in the United States show that, in some individuals, daily intake of erythritol is estimated to reach 30 g/day. 

“Many try and reduce sugar intake by taking many teaspoons of erythritol in their tea, coffee, etc., instead of sugar,” Dr. Hazen added. “Or they eat keto processed foods that have significant quantities of erythritol within it.”

“These studies are a warning for how our processed food (keto and zero sugar, especially) may inadvertently be causing risk/harm. … in the very subset of subjects who are most vulnerable,” according to Dr. Hazen.
 

Erythritol marketed as ‘zero calorie’, ‘non-nutritive’, or ‘natural’

Patients with type 2 diabetes and obesity are often advised to replace sugar with artificial sweeteners for better glucose control and weight loss, but growing epidemiologic evidence links artificial sweetener consumption with weight gain, insulin resistance, type 2 diabetes, and cardiovascular disease, the researchers write.

Erythritol is naturally present in low amounts in fruits and vegetables; the artificial sweetener erythritol that is produced from corn is only 70% as sweet as sugar.

Upon ingestion it is poorly metabolized, and most is excreted in the urine, so it is characterized as a “zero-calorie,” “non-nutritive,” or “natural sweetener.” It is predicted to double in marketshare in the sweetener sector in the next 5 years.
 

Multipart study

In the first part of their study, in a discovery cohort in 1,157 patients undergoing cardiovascular assessment with 3-year outcomes, the researchers identified polyols that were associated with MACE, and erythritol was among the top MACE-associated molecules.

Next, in a U.S. validation cohort of 2,149 patients, over a 3-year follow-up, patients with plasma levels of erythritol in the highest quartile had a 1.8-fold higher risk of MACE than patients in the lowest quartile (P = .007), after adjusting for cardiovascular risk factors.

In a European validation cohort of 833 patients, over a 3-year follow-up, patients with plasma levels of erythritol in the highest quartile had a 2.21-fold higher risk of MACE than patients in the lowest quartile (P = .010, after adjustment).

At physiologic levels, erythritol enhanced platelet reactivity in vitro and thrombosis formation in vivo.

Finally, in a prospective pilot intervention study, erythritol ingestion in healthy volunteers induced marked and sustained increases in plasma erythritol levels well above thresholds associated with heightened platelet reactivity and thrombosis potential in in vitro and in vivo studies.
 

Others weigh in

“While I think the finding certainly warrants further investigation, don’t throw out your sweeteners just yet,” commented Oliver Jones, PhD, professor of chemistry at the Royal Melbourne Institute of Technology.

“This study only looks at erythritol, and artificial sweeteners are generally considered safe. Any possible (and, as yet unproven) risks of excess erythritol would also need to be balanced against the very real health risks of excess glucose consumption,” he said.

Dr. Hazen responded: “True enough. Erythritol is but one of many artificial sweeteners. That is why it is important to read labels. This study can make patients be informed about how to potentially avoid something that might cause them inadvertent harm.”

“The key findings of this study are that high blood levels of erythritol are strongly associated with cardiovascular outcomes in high-risk patients, which has been replicated in separate validation studies,” said Tom Sanders, DSc, PhD, professor emeritus of nutrition and dietetics, King’s College London.

“Diabetes UK currently advises diabetes patients not to use polyols,” he added.

Dr. Hazen noted that “About three-quarters of the participants had coronary disease, high blood pressure, and about a fifth had diabetes.”

The researchers acknowledge, however, that the observational studies cannot show cause and effect.

The study was supported by the Office of Dietary Supplements at the National Institutes of Health, the Leducq Foundation, and the German Research Foundation (Deutsche Forschungsgemeinschaft). Dr. Mellor, Dr. Jones, and Dr. Sanders have reported no relevant financial relationships.

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

A multipart study reports that erythritol – a sugar alcohol (polyol) increasingly used as an artificial sweetener that is also made in the body – is associated with risk of major adverse cardiovascular events (MACE) and promotes clotting (thrombosis).

Erythritol is one of the most widely used artificial sweeteners with rapidly increasing prevalence in processed and “keto-related” foods. Artificial sweeteners are “generally recognized as safe” (GRAS) by the U.S. Food and Drug Administration, so there is no requirement for long-term safety studies, and little is known about the long-term health effects.

The current research, published online in Nature Medicine by Marco Witkowski, MD, of the Lerner Research Institute at Cleveland Clinic and colleagues, had multiple parts.

First, in a group of patients undergoing cardiac risk assessment, the researchers found that high levels of polyols, especially erythritol, were associated with increased 3-year risk of MACE, defined as cardiovascular death or nonfatal myocardial infarction or stroke. 

Next, the association of erythritol with this outcome was reproduced in two large U.S. and European groups of stable patients undergoing elective cardiac evaluation.

Next, adding erythritol to whole blood or platelets led to clot activation. And lastly, in eight healthy volunteers, ingesting 30 g of an erythritol-sweetened drink – comparable to a single can of commercially available beverage or a pint of keto ice cream – induced marked and sustained (> 2 day) increases in levels of plasma erythritol.

“Our study shows that when participants consumed an artificially sweetened beverage with an amount of erythritol found in many processed foods, markedly elevated levels in the blood are observed for days – levels well above those observed to enhance clotting risks,” said senior author Stanley L. Hazen, MD, PhD.  

“It is important that further safety studies are conducted to examine the long-term effects of artificial sweeteners in general, and erythritol specifically, on risks for heart attack and stroke, particularly in people at higher risk for cardiovascular disease,” Dr. Hazen, co–section head of preventive cardiology at Cleveland Clinic, said in a press release from his institution.

“Sweeteners like erythritol have rapidly increased in popularity in recent years, but there needs to be more in-depth research into their long-term effects. Cardiovascular disease builds over time, and heart disease is the leading cause of death globally. We need to make sure the foods we eat aren’t hidden contributors,” Dr. Hazen urged.

The topic remains controversial.

Duane Mellor, PhD, a registered dietitian and senior teaching fellow at Aston University, Birmingham, England, told the U.K. Science Media Centre: “This paper effectively shows multiple pieces of a jigsaw exploring the effects of erythritol – although it claims to show an associated risk with the use of erythritol as an artificial sweetener and cardiovascular disease, I believe it fails to do so, as ultimately, erythritol can be made inside our bodies and the intake in most people’s diet is much lower than the amount given in this study.” 

Dr. Hazen countered that data from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) in the United States show that, in some individuals, daily intake of erythritol is estimated to reach 30 g/day. 

“Many try and reduce sugar intake by taking many teaspoons of erythritol in their tea, coffee, etc., instead of sugar,” Dr. Hazen added. “Or they eat keto processed foods that have significant quantities of erythritol within it.”

“These studies are a warning for how our processed food (keto and zero sugar, especially) may inadvertently be causing risk/harm. … in the very subset of subjects who are most vulnerable,” according to Dr. Hazen.
 

Erythritol marketed as ‘zero calorie’, ‘non-nutritive’, or ‘natural’

Patients with type 2 diabetes and obesity are often advised to replace sugar with artificial sweeteners for better glucose control and weight loss, but growing epidemiologic evidence links artificial sweetener consumption with weight gain, insulin resistance, type 2 diabetes, and cardiovascular disease, the researchers write.

Erythritol is naturally present in low amounts in fruits and vegetables; the artificial sweetener erythritol that is produced from corn is only 70% as sweet as sugar.

Upon ingestion it is poorly metabolized, and most is excreted in the urine, so it is characterized as a “zero-calorie,” “non-nutritive,” or “natural sweetener.” It is predicted to double in marketshare in the sweetener sector in the next 5 years.
 

Multipart study

In the first part of their study, in a discovery cohort in 1,157 patients undergoing cardiovascular assessment with 3-year outcomes, the researchers identified polyols that were associated with MACE, and erythritol was among the top MACE-associated molecules.

Next, in a U.S. validation cohort of 2,149 patients, over a 3-year follow-up, patients with plasma levels of erythritol in the highest quartile had a 1.8-fold higher risk of MACE than patients in the lowest quartile (P = .007), after adjusting for cardiovascular risk factors.

In a European validation cohort of 833 patients, over a 3-year follow-up, patients with plasma levels of erythritol in the highest quartile had a 2.21-fold higher risk of MACE than patients in the lowest quartile (P = .010, after adjustment).

At physiologic levels, erythritol enhanced platelet reactivity in vitro and thrombosis formation in vivo.

Finally, in a prospective pilot intervention study, erythritol ingestion in healthy volunteers induced marked and sustained increases in plasma erythritol levels well above thresholds associated with heightened platelet reactivity and thrombosis potential in in vitro and in vivo studies.
 

Others weigh in

“While I think the finding certainly warrants further investigation, don’t throw out your sweeteners just yet,” commented Oliver Jones, PhD, professor of chemistry at the Royal Melbourne Institute of Technology.

“This study only looks at erythritol, and artificial sweeteners are generally considered safe. Any possible (and, as yet unproven) risks of excess erythritol would also need to be balanced against the very real health risks of excess glucose consumption,” he said.

Dr. Hazen responded: “True enough. Erythritol is but one of many artificial sweeteners. That is why it is important to read labels. This study can make patients be informed about how to potentially avoid something that might cause them inadvertent harm.”

“The key findings of this study are that high blood levels of erythritol are strongly associated with cardiovascular outcomes in high-risk patients, which has been replicated in separate validation studies,” said Tom Sanders, DSc, PhD, professor emeritus of nutrition and dietetics, King’s College London.

“Diabetes UK currently advises diabetes patients not to use polyols,” he added.

Dr. Hazen noted that “About three-quarters of the participants had coronary disease, high blood pressure, and about a fifth had diabetes.”

The researchers acknowledge, however, that the observational studies cannot show cause and effect.

The study was supported by the Office of Dietary Supplements at the National Institutes of Health, the Leducq Foundation, and the German Research Foundation (Deutsche Forschungsgemeinschaft). Dr. Mellor, Dr. Jones, and Dr. Sanders have reported no relevant financial relationships.

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

SAN DIEGO – Diagnosis of multiple sclerosis (MS) presents a number of challenges, and differential diagnosis is critical to get patients on therapy earlier in the disease process.

The problem is that MS can vary greatly in its presentation, and many symptoms can mimic other conditions, according to Eoin Flanagan, MBBCh, who discussed the issue during a session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
 

Mimics and red flags

Dr. Flanagan noted a study that found common themes among MS misdiagnoses. “Many of these conditions are common conditions that we see in our neurology clinic – for example, migraine, fibromyalgia, nonspecific symptoms with an abnormal MRI, or functional neurologic disorder. If you’re teaching medical students or trainees about MS misdiagnosis, it’s important to give this example to show that these are not the zebras that are misdiagnosed, but actually common conditions that we see in our clinics,” said Dr. Flanagan, a neurologist at Mayo Clinic in Rochester, Minn.

Evaluation of MS mimics isn’t always necessary. Much of the time, typical clinical, neurologic, and imaging features provide a clear diagnosis. But some features can be red flags that MS may not be the cause. These can include a cerebrospinal fluid white blood cell count higher than 50, elevated CSF protein with normal white cell counts, low glucose, and negative oligoclonal bands, all of which could signify a range of other conditions.

These and other red flags should prompt a careful look to get the right diagnosis.
 

Earlier diagnosis = better outcomes

“[Evidence has] shown recently that as the diagnostic criteria have become more sensitive and we diagnose MS earlier, patients have had better outcomes because they’ve been able to initiate treatment earlier,” said Andrew Solomon, MD, who is an associate professor of neurologic sciences and division chief of multiple sclerosis at University of Vermont, Burlington. Dr. Solomon, Dr. Flanagan, and others are currently writing a review article on differential diagnosis of MS that will update the last review, published in 2008.

“Differential diagnosis has become more complex as we’ve had a broader understanding of disorders that can mimic MS. In the meantime, we still don’t have a highly sensitive and specific biomarker for MS that can help guide us when we first see somebody,” said Dr. Solomon.
 

Look for patterns and imaging clues

Dr. Flanagan’s talk had several points of emphasis. A key feature is the length of time between when the patient develops the first symptom and maximal symptoms. “If that’s very quick, then that suggests it’s a spinal cord stroke. If it comes down over days to a few weeks, then that suggests inflammation like MS, or like neuromyelitis optica [NMO] or myelin oligodendrocyte glycoprotein antibody-associated disease [MOGAD]. As it progresses beyond 21 days, then we’re going to be thinking about a different diagnosis,” said Dr. Flanagan.

Dr. Flanagan also noted the usefulness of specific features of the spinal cord MRI. Variables like lesion length, location in the center or periphery of the spinal cord, and characteristics of the enhancement pattern may be useful. “The pattern of gadolinium enhancement can be useful in narrowing your differential diagnosis and suggesting the correct diagnosis. For example, the flat pancake-like enhancement on sagittal images can suggest cervical spondylosis, while trident sign on axial images can suggest spinal cord sarcoidosis. Prior studies have shown that education on these patterns can enhance diagnosis.”

Dr. Flanagan suggested that both radiologists and neurologists should be trained to recognize such patterns. “If you educate radiologists or neurologists on these patterns, it can help them with diagnosis.”
 

Common mistakes

MOGAD and aquaporin 4–positive NMO spectrum disorder (AQP4+NMOSD) can be easily mistaken for MS, but there are some key differences. MOGAD and AQP4+NMOSD attacks are more severe than MS attacks, leaving patients more likely to be blind following an optic neuritis attack or wheelchair bound because of myelitis. More than 85% of CSF from patients with MS have oligoclonal bands versus about 15% of CSF from patients with MOGAD or AQP4+NMOSD. There is also a difference in lesion dynamics over time: MOGAD T2 lesions frequently resolve over follow-up while AQP4+NMOSD and MS lesions typically continue and leave a scar and persist. Silent lesions are more likely during surveillance MRI among MS patients, but are rare in MOGAD and AQP4+NMOSD, according to Dr. Flanagan. “One caveat to this is that with stronger MS medications we are seeing less silent lesions accumulating as we use those treatments more often.”

Dr. Solomon has been done nonpromotional speaking for EMD Serono. He has received research funding from Bristol-Myers Squibb. He has been on an advisory board or consulted for Greenwich Biosciences, TG Therapeutics, Octave Bioscience, and Horizon Therapeutics. Dr. Flanagan has no relevant financial disclosures. Dr. Flanagan has served on advisory boards for Alexion, Genentech, Horizon Therapeutics, and UCB.

SAN DIEGO – Diagnosis of multiple sclerosis (MS) presents a number of challenges, and differential diagnosis is critical to get patients on therapy earlier in the disease process.

The problem is that MS can vary greatly in its presentation, and many symptoms can mimic other conditions, according to Eoin Flanagan, MBBCh, who discussed the issue during a session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
 

Mimics and red flags

Dr. Flanagan noted a study that found common themes among MS misdiagnoses. “Many of these conditions are common conditions that we see in our neurology clinic – for example, migraine, fibromyalgia, nonspecific symptoms with an abnormal MRI, or functional neurologic disorder. If you’re teaching medical students or trainees about MS misdiagnosis, it’s important to give this example to show that these are not the zebras that are misdiagnosed, but actually common conditions that we see in our clinics,” said Dr. Flanagan, a neurologist at Mayo Clinic in Rochester, Minn.

Evaluation of MS mimics isn’t always necessary. Much of the time, typical clinical, neurologic, and imaging features provide a clear diagnosis. But some features can be red flags that MS may not be the cause. These can include a cerebrospinal fluid white blood cell count higher than 50, elevated CSF protein with normal white cell counts, low glucose, and negative oligoclonal bands, all of which could signify a range of other conditions.

These and other red flags should prompt a careful look to get the right diagnosis.
 

Earlier diagnosis = better outcomes

“[Evidence has] shown recently that as the diagnostic criteria have become more sensitive and we diagnose MS earlier, patients have had better outcomes because they’ve been able to initiate treatment earlier,” said Andrew Solomon, MD, who is an associate professor of neurologic sciences and division chief of multiple sclerosis at University of Vermont, Burlington. Dr. Solomon, Dr. Flanagan, and others are currently writing a review article on differential diagnosis of MS that will update the last review, published in 2008.

“Differential diagnosis has become more complex as we’ve had a broader understanding of disorders that can mimic MS. In the meantime, we still don’t have a highly sensitive and specific biomarker for MS that can help guide us when we first see somebody,” said Dr. Solomon.
 

Look for patterns and imaging clues

Dr. Flanagan’s talk had several points of emphasis. A key feature is the length of time between when the patient develops the first symptom and maximal symptoms. “If that’s very quick, then that suggests it’s a spinal cord stroke. If it comes down over days to a few weeks, then that suggests inflammation like MS, or like neuromyelitis optica [NMO] or myelin oligodendrocyte glycoprotein antibody-associated disease [MOGAD]. As it progresses beyond 21 days, then we’re going to be thinking about a different diagnosis,” said Dr. Flanagan.

Dr. Flanagan also noted the usefulness of specific features of the spinal cord MRI. Variables like lesion length, location in the center or periphery of the spinal cord, and characteristics of the enhancement pattern may be useful. “The pattern of gadolinium enhancement can be useful in narrowing your differential diagnosis and suggesting the correct diagnosis. For example, the flat pancake-like enhancement on sagittal images can suggest cervical spondylosis, while trident sign on axial images can suggest spinal cord sarcoidosis. Prior studies have shown that education on these patterns can enhance diagnosis.”

Dr. Flanagan suggested that both radiologists and neurologists should be trained to recognize such patterns. “If you educate radiologists or neurologists on these patterns, it can help them with diagnosis.”
 

Common mistakes

MOGAD and aquaporin 4–positive NMO spectrum disorder (AQP4+NMOSD) can be easily mistaken for MS, but there are some key differences. MOGAD and AQP4+NMOSD attacks are more severe than MS attacks, leaving patients more likely to be blind following an optic neuritis attack or wheelchair bound because of myelitis. More than 85% of CSF from patients with MS have oligoclonal bands versus about 15% of CSF from patients with MOGAD or AQP4+NMOSD. There is also a difference in lesion dynamics over time: MOGAD T2 lesions frequently resolve over follow-up while AQP4+NMOSD and MS lesions typically continue and leave a scar and persist. Silent lesions are more likely during surveillance MRI among MS patients, but are rare in MOGAD and AQP4+NMOSD, according to Dr. Flanagan. “One caveat to this is that with stronger MS medications we are seeing less silent lesions accumulating as we use those treatments more often.”

Dr. Solomon has been done nonpromotional speaking for EMD Serono. He has received research funding from Bristol-Myers Squibb. He has been on an advisory board or consulted for Greenwich Biosciences, TG Therapeutics, Octave Bioscience, and Horizon Therapeutics. Dr. Flanagan has no relevant financial disclosures. Dr. Flanagan has served on advisory boards for Alexion, Genentech, Horizon Therapeutics, and UCB.

SAN DIEGO – Diagnosis of multiple sclerosis (MS) presents a number of challenges, and differential diagnosis is critical to get patients on therapy earlier in the disease process.

The problem is that MS can vary greatly in its presentation, and many symptoms can mimic other conditions, according to Eoin Flanagan, MBBCh, who discussed the issue during a session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
 

Mimics and red flags

Dr. Flanagan noted a study that found common themes among MS misdiagnoses. “Many of these conditions are common conditions that we see in our neurology clinic – for example, migraine, fibromyalgia, nonspecific symptoms with an abnormal MRI, or functional neurologic disorder. If you’re teaching medical students or trainees about MS misdiagnosis, it’s important to give this example to show that these are not the zebras that are misdiagnosed, but actually common conditions that we see in our clinics,” said Dr. Flanagan, a neurologist at Mayo Clinic in Rochester, Minn.

Evaluation of MS mimics isn’t always necessary. Much of the time, typical clinical, neurologic, and imaging features provide a clear diagnosis. But some features can be red flags that MS may not be the cause. These can include a cerebrospinal fluid white blood cell count higher than 50, elevated CSF protein with normal white cell counts, low glucose, and negative oligoclonal bands, all of which could signify a range of other conditions.

These and other red flags should prompt a careful look to get the right diagnosis.
 

Earlier diagnosis = better outcomes

“[Evidence has] shown recently that as the diagnostic criteria have become more sensitive and we diagnose MS earlier, patients have had better outcomes because they’ve been able to initiate treatment earlier,” said Andrew Solomon, MD, who is an associate professor of neurologic sciences and division chief of multiple sclerosis at University of Vermont, Burlington. Dr. Solomon, Dr. Flanagan, and others are currently writing a review article on differential diagnosis of MS that will update the last review, published in 2008.

“Differential diagnosis has become more complex as we’ve had a broader understanding of disorders that can mimic MS. In the meantime, we still don’t have a highly sensitive and specific biomarker for MS that can help guide us when we first see somebody,” said Dr. Solomon.
 

Look for patterns and imaging clues

Dr. Flanagan’s talk had several points of emphasis. A key feature is the length of time between when the patient develops the first symptom and maximal symptoms. “If that’s very quick, then that suggests it’s a spinal cord stroke. If it comes down over days to a few weeks, then that suggests inflammation like MS, or like neuromyelitis optica [NMO] or myelin oligodendrocyte glycoprotein antibody-associated disease [MOGAD]. As it progresses beyond 21 days, then we’re going to be thinking about a different diagnosis,” said Dr. Flanagan.

Dr. Flanagan also noted the usefulness of specific features of the spinal cord MRI. Variables like lesion length, location in the center or periphery of the spinal cord, and characteristics of the enhancement pattern may be useful. “The pattern of gadolinium enhancement can be useful in narrowing your differential diagnosis and suggesting the correct diagnosis. For example, the flat pancake-like enhancement on sagittal images can suggest cervical spondylosis, while trident sign on axial images can suggest spinal cord sarcoidosis. Prior studies have shown that education on these patterns can enhance diagnosis.”

Dr. Flanagan suggested that both radiologists and neurologists should be trained to recognize such patterns. “If you educate radiologists or neurologists on these patterns, it can help them with diagnosis.”
 

Common mistakes

MOGAD and aquaporin 4–positive NMO spectrum disorder (AQP4+NMOSD) can be easily mistaken for MS, but there are some key differences. MOGAD and AQP4+NMOSD attacks are more severe than MS attacks, leaving patients more likely to be blind following an optic neuritis attack or wheelchair bound because of myelitis. More than 85% of CSF from patients with MS have oligoclonal bands versus about 15% of CSF from patients with MOGAD or AQP4+NMOSD. There is also a difference in lesion dynamics over time: MOGAD T2 lesions frequently resolve over follow-up while AQP4+NMOSD and MS lesions typically continue and leave a scar and persist. Silent lesions are more likely during surveillance MRI among MS patients, but are rare in MOGAD and AQP4+NMOSD, according to Dr. Flanagan. “One caveat to this is that with stronger MS medications we are seeing less silent lesions accumulating as we use those treatments more often.”

Dr. Solomon has been done nonpromotional speaking for EMD Serono. He has received research funding from Bristol-Myers Squibb. He has been on an advisory board or consulted for Greenwich Biosciences, TG Therapeutics, Octave Bioscience, and Horizon Therapeutics. Dr. Flanagan has no relevant financial disclosures. Dr. Flanagan has served on advisory boards for Alexion, Genentech, Horizon Therapeutics, and UCB.

SAN DIEGO – Cognitive-behavioral therapy (CBT), the wakefulness-promoting drug modafinil (Provigil), and a combination of both treatments all reduce fatigue in patients with multiple sclerosis (MS) – but the combination has an edge when it comes to overall perceived benefits, new research shows.

As well, study results suggest that individuals with poorer sleep hygiene may benefit more from CBT, researchers noted.

“Clinicians should consider clinical characteristics and overall treatment goals when selecting fatigue interventions, to offer a more personalized approach for MS fatigue,” said study investigator Tiffany Braley, MD, associate professor of neurology, University of Michigan, Ann Arbor.

The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
 

Incapacitating symptom

Dr. Braley noted that fatigue affects up to 90% of patients with MS and is the most incapacitating symptom for more than 40% of these patients. In addition, fatigue is a strong predictor of reduced work productivity, unemployment, reduced social participation, and reduced quality of life.

“Given the impact that fatigue has on the health and well-being of people with MS, it is essential to find ways to optimize the current treatments that we have at hand for fatigue in MS in the most patient-centered way possible,” Dr. Braley said.

CBT, which teaches strategies to target maladaptive thoughts and beliefs, is one of the most promising behavioral strategies, the investigators noted. It has been shown to be effective for multiple conditions including depression, posttraumatic stress disorder, insomnia, and pain.

For MS fatigue, CBT is considered a second-line treatment. Moderate and sustained efficacy have been shown across trials but access remains limited, Dr. Braley reported.

Modafinil, which is approved by the U.S. Food and Drug Administration to treat sleepiness secondary to obstructive sleep apnea and narcolepsy, is commonly used off-label to treat MS-related fatigue. However, prior trials have yielded mixed results regarding the efficacy of the drug for MS fatigue, said Dr. Braley.

Also, different behavioral and pharmacologic therapies have never been combined to determine if there might be a synergistic benefit, she added.

The new 12-week parallel-arm, analyst-blinded COMBO-MS trial included 336 participants (76.2% women; mean age, 48.8 years). Most of the patients (85.1%) were White and most (71.1%) had relapsing remitting MS (RRMS).

Participants were randomly assigned to receive 8 weekly and then two “booster” sessions of telephone-delivered one-on-one CBT, or modafinil with the dose generally ranging from 100 to 200 mg per day, or a combination of the two therapies.

The primary outcome measure was change in fatigue on the self-report Modified Fatigue Impact Scale (MFIS), using online surveys. The mean baseline MFIS was 52.7.

Study participants also completed questionnaires on disability, sleep disorders, sleep hygiene, and sleepiness (Epworth sleepiness scale).

Covariates included demographics, anxiety based on the Generalized Anxiety Disorder-7, pain score on the Brief Pain Inventory, baseline fatigue score, and physical activity.
 

Clinically, statistically significant

The overall treatment effect on the total MFIS score at 12 weeks was positive for each group. “Each treatment arm was associated with a clinically significant and a statistically significant within-group reduction in MSIF score from 15 to 17 points,” Dr. Braley reported.

“But even though the combination therapy ended up having the highest absolute reduction, it ultimately was not statistically significant,” she added.

Responder analyses showed almost two-thirds of each treatment group experienced at least a 10-point reduction in MSIF, which is considered clinically significant. In addition, more than 50% experienced at least 25% reduction in MSIF. “Again, although the combination therapy seemed to have a higher proportion of responders, this was not statistically significant,” said Dr. Braley.

A secondary outcome was the self-reported Patient Global Impression of Change, which rates overall symptoms and quality of life. More participants in all groups said their symptoms and quality of life at study’s end were somewhat better, moderately better, a definite improvement, or a great deal better.

But here the combination therapy was significantly better than the other interventions. “This suggests there may be more subjective benefits of combination therapy that we’re not capturing” with other measures, Dr. Braley noted.

Sleep hygiene significantly moderated the treatment effect (P = .03). As sleep hygiene worsened, the effect of modafinil monotherapy relative to CBT monotherapy appeared to diminish, and behavior therapy started to have more benefit relative to modafinil therapy, the investigators noted.

“Our results suggest that people with MS who have problems maintaining healthy sleep behaviors could potentially see more benefit from behaviorally based treatments that target sleep habits as part of the fatigue management plan, as opposed to a stimulant medication that could make sleep more difficult to maintain,” Dr. Braley said.

“On the other hand, people with good sleep hygiene may sufficiently respond to modafinil. For those who believe their mood, activity limitations, and quality of life are closely linked to their fatigue, combination therapy may offer more global benefits,” she added.

Sleepiness, as assessed with the Epworth sleepiness scale, had a direct effect on treatment response (P = .0087) that did not vary by intervention. Those who were sleepier had greater reductions on MSIF scores.

Dr. Braley noted that there was an excellent adherence rate, with only 26 participants discontinuing the study. Of these, 20 were from the modafinil group and discontinued because of side effects, and 6 were from the CBT group and discontinued because of time constraints. There were no serious adverse events reported.
 

Important lifestyle factor

Session cochair Deepak Kaushik, PhD, of the department of biomedical sciences, Memorial University, St John’s, Nfld., said the benefit of CBT for MS fatigue “definitely needs to be looked into further.”

Sleep deprivation, along with ensuing fatigue, is among the lifestyle factors that play a vital role in MS, said Dr. Kaushik, who was not involved with the research.

The effect of CBT on fatigue is likely through stress reduction, he said, adding that the immune system is significantly affected by stress. “We know the immune system has a direct linkage to the way you feel [and] your stress response to situations,” so it makes sense that CBT lowers fatigue because it reduces stress, Dr. Kaushik said.

The study received funding from the Patient-Centered Outcomes Research Institute. Dr. Braley and Dr. Kaushik have reported no relevant financial relationships.

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

SAN DIEGO – Cognitive-behavioral therapy (CBT), the wakefulness-promoting drug modafinil (Provigil), and a combination of both treatments all reduce fatigue in patients with multiple sclerosis (MS) – but the combination has an edge when it comes to overall perceived benefits, new research shows.

As well, study results suggest that individuals with poorer sleep hygiene may benefit more from CBT, researchers noted.

“Clinicians should consider clinical characteristics and overall treatment goals when selecting fatigue interventions, to offer a more personalized approach for MS fatigue,” said study investigator Tiffany Braley, MD, associate professor of neurology, University of Michigan, Ann Arbor.

The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
 

Incapacitating symptom

Dr. Braley noted that fatigue affects up to 90% of patients with MS and is the most incapacitating symptom for more than 40% of these patients. In addition, fatigue is a strong predictor of reduced work productivity, unemployment, reduced social participation, and reduced quality of life.

“Given the impact that fatigue has on the health and well-being of people with MS, it is essential to find ways to optimize the current treatments that we have at hand for fatigue in MS in the most patient-centered way possible,” Dr. Braley said.

CBT, which teaches strategies to target maladaptive thoughts and beliefs, is one of the most promising behavioral strategies, the investigators noted. It has been shown to be effective for multiple conditions including depression, posttraumatic stress disorder, insomnia, and pain.

For MS fatigue, CBT is considered a second-line treatment. Moderate and sustained efficacy have been shown across trials but access remains limited, Dr. Braley reported.

Modafinil, which is approved by the U.S. Food and Drug Administration to treat sleepiness secondary to obstructive sleep apnea and narcolepsy, is commonly used off-label to treat MS-related fatigue. However, prior trials have yielded mixed results regarding the efficacy of the drug for MS fatigue, said Dr. Braley.

Also, different behavioral and pharmacologic therapies have never been combined to determine if there might be a synergistic benefit, she added.

The new 12-week parallel-arm, analyst-blinded COMBO-MS trial included 336 participants (76.2% women; mean age, 48.8 years). Most of the patients (85.1%) were White and most (71.1%) had relapsing remitting MS (RRMS).

Participants were randomly assigned to receive 8 weekly and then two “booster” sessions of telephone-delivered one-on-one CBT, or modafinil with the dose generally ranging from 100 to 200 mg per day, or a combination of the two therapies.

The primary outcome measure was change in fatigue on the self-report Modified Fatigue Impact Scale (MFIS), using online surveys. The mean baseline MFIS was 52.7.

Study participants also completed questionnaires on disability, sleep disorders, sleep hygiene, and sleepiness (Epworth sleepiness scale).

Covariates included demographics, anxiety based on the Generalized Anxiety Disorder-7, pain score on the Brief Pain Inventory, baseline fatigue score, and physical activity.
 

Clinically, statistically significant

The overall treatment effect on the total MFIS score at 12 weeks was positive for each group. “Each treatment arm was associated with a clinically significant and a statistically significant within-group reduction in MSIF score from 15 to 17 points,” Dr. Braley reported.

“But even though the combination therapy ended up having the highest absolute reduction, it ultimately was not statistically significant,” she added.

Responder analyses showed almost two-thirds of each treatment group experienced at least a 10-point reduction in MSIF, which is considered clinically significant. In addition, more than 50% experienced at least 25% reduction in MSIF. “Again, although the combination therapy seemed to have a higher proportion of responders, this was not statistically significant,” said Dr. Braley.

A secondary outcome was the self-reported Patient Global Impression of Change, which rates overall symptoms and quality of life. More participants in all groups said their symptoms and quality of life at study’s end were somewhat better, moderately better, a definite improvement, or a great deal better.

But here the combination therapy was significantly better than the other interventions. “This suggests there may be more subjective benefits of combination therapy that we’re not capturing” with other measures, Dr. Braley noted.

Sleep hygiene significantly moderated the treatment effect (P = .03). As sleep hygiene worsened, the effect of modafinil monotherapy relative to CBT monotherapy appeared to diminish, and behavior therapy started to have more benefit relative to modafinil therapy, the investigators noted.

“Our results suggest that people with MS who have problems maintaining healthy sleep behaviors could potentially see more benefit from behaviorally based treatments that target sleep habits as part of the fatigue management plan, as opposed to a stimulant medication that could make sleep more difficult to maintain,” Dr. Braley said.

“On the other hand, people with good sleep hygiene may sufficiently respond to modafinil. For those who believe their mood, activity limitations, and quality of life are closely linked to their fatigue, combination therapy may offer more global benefits,” she added.

Sleepiness, as assessed with the Epworth sleepiness scale, had a direct effect on treatment response (P = .0087) that did not vary by intervention. Those who were sleepier had greater reductions on MSIF scores.

Dr. Braley noted that there was an excellent adherence rate, with only 26 participants discontinuing the study. Of these, 20 were from the modafinil group and discontinued because of side effects, and 6 were from the CBT group and discontinued because of time constraints. There were no serious adverse events reported.
 

Important lifestyle factor

Session cochair Deepak Kaushik, PhD, of the department of biomedical sciences, Memorial University, St John’s, Nfld., said the benefit of CBT for MS fatigue “definitely needs to be looked into further.”

Sleep deprivation, along with ensuing fatigue, is among the lifestyle factors that play a vital role in MS, said Dr. Kaushik, who was not involved with the research.

The effect of CBT on fatigue is likely through stress reduction, he said, adding that the immune system is significantly affected by stress. “We know the immune system has a direct linkage to the way you feel [and] your stress response to situations,” so it makes sense that CBT lowers fatigue because it reduces stress, Dr. Kaushik said.

The study received funding from the Patient-Centered Outcomes Research Institute. Dr. Braley and Dr. Kaushik have reported no relevant financial relationships.

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

SAN DIEGO – Cognitive-behavioral therapy (CBT), the wakefulness-promoting drug modafinil (Provigil), and a combination of both treatments all reduce fatigue in patients with multiple sclerosis (MS) – but the combination has an edge when it comes to overall perceived benefits, new research shows.

As well, study results suggest that individuals with poorer sleep hygiene may benefit more from CBT, researchers noted.

“Clinicians should consider clinical characteristics and overall treatment goals when selecting fatigue interventions, to offer a more personalized approach for MS fatigue,” said study investigator Tiffany Braley, MD, associate professor of neurology, University of Michigan, Ann Arbor.

The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
 

Incapacitating symptom

Dr. Braley noted that fatigue affects up to 90% of patients with MS and is the most incapacitating symptom for more than 40% of these patients. In addition, fatigue is a strong predictor of reduced work productivity, unemployment, reduced social participation, and reduced quality of life.

“Given the impact that fatigue has on the health and well-being of people with MS, it is essential to find ways to optimize the current treatments that we have at hand for fatigue in MS in the most patient-centered way possible,” Dr. Braley said.

CBT, which teaches strategies to target maladaptive thoughts and beliefs, is one of the most promising behavioral strategies, the investigators noted. It has been shown to be effective for multiple conditions including depression, posttraumatic stress disorder, insomnia, and pain.

For MS fatigue, CBT is considered a second-line treatment. Moderate and sustained efficacy have been shown across trials but access remains limited, Dr. Braley reported.

Modafinil, which is approved by the U.S. Food and Drug Administration to treat sleepiness secondary to obstructive sleep apnea and narcolepsy, is commonly used off-label to treat MS-related fatigue. However, prior trials have yielded mixed results regarding the efficacy of the drug for MS fatigue, said Dr. Braley.

Also, different behavioral and pharmacologic therapies have never been combined to determine if there might be a synergistic benefit, she added.

The new 12-week parallel-arm, analyst-blinded COMBO-MS trial included 336 participants (76.2% women; mean age, 48.8 years). Most of the patients (85.1%) were White and most (71.1%) had relapsing remitting MS (RRMS).

Participants were randomly assigned to receive 8 weekly and then two “booster” sessions of telephone-delivered one-on-one CBT, or modafinil with the dose generally ranging from 100 to 200 mg per day, or a combination of the two therapies.

The primary outcome measure was change in fatigue on the self-report Modified Fatigue Impact Scale (MFIS), using online surveys. The mean baseline MFIS was 52.7.

Study participants also completed questionnaires on disability, sleep disorders, sleep hygiene, and sleepiness (Epworth sleepiness scale).

Covariates included demographics, anxiety based on the Generalized Anxiety Disorder-7, pain score on the Brief Pain Inventory, baseline fatigue score, and physical activity.
 

Clinically, statistically significant

The overall treatment effect on the total MFIS score at 12 weeks was positive for each group. “Each treatment arm was associated with a clinically significant and a statistically significant within-group reduction in MSIF score from 15 to 17 points,” Dr. Braley reported.

“But even though the combination therapy ended up having the highest absolute reduction, it ultimately was not statistically significant,” she added.

Responder analyses showed almost two-thirds of each treatment group experienced at least a 10-point reduction in MSIF, which is considered clinically significant. In addition, more than 50% experienced at least 25% reduction in MSIF. “Again, although the combination therapy seemed to have a higher proportion of responders, this was not statistically significant,” said Dr. Braley.

A secondary outcome was the self-reported Patient Global Impression of Change, which rates overall symptoms and quality of life. More participants in all groups said their symptoms and quality of life at study’s end were somewhat better, moderately better, a definite improvement, or a great deal better.

But here the combination therapy was significantly better than the other interventions. “This suggests there may be more subjective benefits of combination therapy that we’re not capturing” with other measures, Dr. Braley noted.

Sleep hygiene significantly moderated the treatment effect (P = .03). As sleep hygiene worsened, the effect of modafinil monotherapy relative to CBT monotherapy appeared to diminish, and behavior therapy started to have more benefit relative to modafinil therapy, the investigators noted.

“Our results suggest that people with MS who have problems maintaining healthy sleep behaviors could potentially see more benefit from behaviorally based treatments that target sleep habits as part of the fatigue management plan, as opposed to a stimulant medication that could make sleep more difficult to maintain,” Dr. Braley said.

“On the other hand, people with good sleep hygiene may sufficiently respond to modafinil. For those who believe their mood, activity limitations, and quality of life are closely linked to their fatigue, combination therapy may offer more global benefits,” she added.

Sleepiness, as assessed with the Epworth sleepiness scale, had a direct effect on treatment response (P = .0087) that did not vary by intervention. Those who were sleepier had greater reductions on MSIF scores.

Dr. Braley noted that there was an excellent adherence rate, with only 26 participants discontinuing the study. Of these, 20 were from the modafinil group and discontinued because of side effects, and 6 were from the CBT group and discontinued because of time constraints. There were no serious adverse events reported.
 

Important lifestyle factor

Session cochair Deepak Kaushik, PhD, of the department of biomedical sciences, Memorial University, St John’s, Nfld., said the benefit of CBT for MS fatigue “definitely needs to be looked into further.”

Sleep deprivation, along with ensuing fatigue, is among the lifestyle factors that play a vital role in MS, said Dr. Kaushik, who was not involved with the research.

The effect of CBT on fatigue is likely through stress reduction, he said, adding that the immune system is significantly affected by stress. “We know the immune system has a direct linkage to the way you feel [and] your stress response to situations,” so it makes sense that CBT lowers fatigue because it reduces stress, Dr. Kaushik said.

The study received funding from the Patient-Centered Outcomes Research Institute. Dr. Braley and Dr. Kaushik have reported no relevant financial relationships.

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

A recent report in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association suggested that, at least for now, we need to lower the bar in Alzheimer’s disease drug trials.

Their point is that there’s no consensus on “clinically meaningful benefit.” Does it mean a complete cure for Alzheimer’s disease, with reversal of deficits? Or stopping disease progression where it is? Or just slowing things down enough that it means something to patients, family members, and caregivers?

The last one is, realistically, where we are now.

The problem with this is that many nonmedical people equate “treatment” with “cure,” which isn’t close to the truth for many diseases. In Alzheimer’s disease, it’s even trickier to figure out. There’s a disparity between imaging (which suggests something that should be quite effective) and clinical results (which aren’t nearly as impressive as the PET scans).

So when I prescribe any of the Alzheimer’s medications, I make it pretty clear to patients, and more importantly the patient’s family, what they can and can’t expect. This isn’t easy, because most will come back a month later, tell me their loved one is no better, and want to try something else. So I have to explain it again. These people aren’t stupid. They’re hopeful, and also facing an impossible question. “Better” is a lot easier to judge than “slowed progression.”

“Better” is a great word for migraines. Or seizures. Or Parkinson’s disease. These are condition where patients and families can tell us whether they’ve seen an improvement.

But with the current treatments for Alzheimer’s disease we’re asking patients and families “do you think you’ve gotten any worse than you would have if you hadn’t taken the drug at all?”

That’s an impossible question to answer, unless you’re following people with objective cognitive data over time and comparing them against a placebo group, which is how these drugs got here in the first place – we know they do that.

But to a family watching their loved ones go downhill, such reassurances aren’t what they want to hear.

Regrettably, it’s where things stand. While I want to strive for absolute success in these things, today it’s simply not possible. Maybe it never will be, though I hope it is.

But, for now, I agree that we need to reframe what we’re going to consider clinically meaningful. Sometimes you have to settle for a flight of stairs instead of an elevator, but still hope that you’ll get to the top. It just takes longer, and it’s better than not going anywhere at all.

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

A recent report in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association suggested that, at least for now, we need to lower the bar in Alzheimer’s disease drug trials.

Their point is that there’s no consensus on “clinically meaningful benefit.” Does it mean a complete cure for Alzheimer’s disease, with reversal of deficits? Or stopping disease progression where it is? Or just slowing things down enough that it means something to patients, family members, and caregivers?

The last one is, realistically, where we are now.

The problem with this is that many nonmedical people equate “treatment” with “cure,” which isn’t close to the truth for many diseases. In Alzheimer’s disease, it’s even trickier to figure out. There’s a disparity between imaging (which suggests something that should be quite effective) and clinical results (which aren’t nearly as impressive as the PET scans).

So when I prescribe any of the Alzheimer’s medications, I make it pretty clear to patients, and more importantly the patient’s family, what they can and can’t expect. This isn’t easy, because most will come back a month later, tell me their loved one is no better, and want to try something else. So I have to explain it again. These people aren’t stupid. They’re hopeful, and also facing an impossible question. “Better” is a lot easier to judge than “slowed progression.”

“Better” is a great word for migraines. Or seizures. Or Parkinson’s disease. These are condition where patients and families can tell us whether they’ve seen an improvement.

But with the current treatments for Alzheimer’s disease we’re asking patients and families “do you think you’ve gotten any worse than you would have if you hadn’t taken the drug at all?”

That’s an impossible question to answer, unless you’re following people with objective cognitive data over time and comparing them against a placebo group, which is how these drugs got here in the first place – we know they do that.

But to a family watching their loved ones go downhill, such reassurances aren’t what they want to hear.

Regrettably, it’s where things stand. While I want to strive for absolute success in these things, today it’s simply not possible. Maybe it never will be, though I hope it is.

But, for now, I agree that we need to reframe what we’re going to consider clinically meaningful. Sometimes you have to settle for a flight of stairs instead of an elevator, but still hope that you’ll get to the top. It just takes longer, and it’s better than not going anywhere at all.

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

A recent report in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association suggested that, at least for now, we need to lower the bar in Alzheimer’s disease drug trials.

Their point is that there’s no consensus on “clinically meaningful benefit.” Does it mean a complete cure for Alzheimer’s disease, with reversal of deficits? Or stopping disease progression where it is? Or just slowing things down enough that it means something to patients, family members, and caregivers?

The last one is, realistically, where we are now.

The problem with this is that many nonmedical people equate “treatment” with “cure,” which isn’t close to the truth for many diseases. In Alzheimer’s disease, it’s even trickier to figure out. There’s a disparity between imaging (which suggests something that should be quite effective) and clinical results (which aren’t nearly as impressive as the PET scans).

So when I prescribe any of the Alzheimer’s medications, I make it pretty clear to patients, and more importantly the patient’s family, what they can and can’t expect. This isn’t easy, because most will come back a month later, tell me their loved one is no better, and want to try something else. So I have to explain it again. These people aren’t stupid. They’re hopeful, and also facing an impossible question. “Better” is a lot easier to judge than “slowed progression.”

“Better” is a great word for migraines. Or seizures. Or Parkinson’s disease. These are condition where patients and families can tell us whether they’ve seen an improvement.

But with the current treatments for Alzheimer’s disease we’re asking patients and families “do you think you’ve gotten any worse than you would have if you hadn’t taken the drug at all?”

That’s an impossible question to answer, unless you’re following people with objective cognitive data over time and comparing them against a placebo group, which is how these drugs got here in the first place – we know they do that.

But to a family watching their loved ones go downhill, such reassurances aren’t what they want to hear.

Regrettably, it’s where things stand. While I want to strive for absolute success in these things, today it’s simply not possible. Maybe it never will be, though I hope it is.

But, for now, I agree that we need to reframe what we’re going to consider clinically meaningful. Sometimes you have to settle for a flight of stairs instead of an elevator, but still hope that you’ll get to the top. It just takes longer, and it’s better than not going anywhere at all.

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

Dementia risk is significantly higher in women than in men worldwide, and social and economic disadvantages among women could be to blame, a study suggests.

Prior research has found a higher lifetime dementia risk in women, and one explanation cited has been that women tend to live longer than men.

However, this new analysis of data from nearly 30,000 people in 18 countries found almost no evidence of sex differences in most known risk factors for dementia, including age.

The risk of dementia among women was significantly higher in poorer countries, pointing to economic disadvantages as a possible explanation.

“In general, we found that the greater dementia risk found in women compared to men was more pronounced in poorer countries, which points to the need for greater efforts to narrow the gaps in health disparities between women and men in these countries,” lead investigator Jessica Gong, MSc, a doctoral student at the George Institute for Global Health, Newtown, Australia, told this news organization. “It is likely that socioeconomic factors are potentially more important than biological factors when assessing dementia risk.”

The findings were published online in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
 

Global data

Most previous studies that examined sex differences in dementia risk were conducted in high-income countries, Ms. Gong noted, leaving a gap in the literature on risk in low- and middle-income countries.

To address this issue, researchers conducted an individual participant meta-analysis of 21 studies from the Cohort Studies of Memory in an International Consortium. Data analysis included information on 29,850 people from 18 countries on six continents. None of the participants had dementia at baseline, and the average age was 71.6 years.

Over a median of 4.6 years, incident dementia was reported in 2,089 people, 66% of whom were women.

Overall, women had higher dementia risk (hazard ratio, 1.12; 95% confidence interval, 1.02-1.23) than men, but the rates were highest in low- to middle-income economies (HR, 1.73; P = .03).

Dementia risk in women was higher than in men in 14 countries. Risk was highest in Nigeria, where dementia risk was more than double in women (aHR, 2.11; 95% CI, 1.46-3.04), and lowest in Brazil, where risk was 46% lower in women than in men (aHR, 0.54; 95% CI, 0.29-1.00).

In the United States, dementia risk was 7% higher in women than men (aHR, 1.07; 0.73-1.57).
 

Similar risk factors

In both women and men, older age, diabetes, depression, hearing impairment, and apo E–epsilon 4 carriage were associated with a greater risk of dementia, and more years of education, higher hip circumference, current alcohol use (vs. never), and high physical activity (vs. none to minimal) were associated with a lower risk of dementia.

Among all these risk factors, sex differences were only significant for longer education and former alcohol use, with both demonstrating a stronger association in men than women.

Global dementia rates are expected to triple over the next 25 years unless steps are taken to reduce risk factors. A 2020 report found that dementia risk could be reduced by addressing 12 modifiable risk factors, including obesity, air pollution, diabetes, social isolation, and hypertension. All of these risk factors are more common in low- to middle-income countries, Ms. Gong noted.

“These findings justify ongoing efforts to support programs to improve sex and gender equity in brain health, particularly in underrepresented and underserved populations, in turn to narrow the gaps within and between country,” Ms. Gong said.
 

Understanding the puzzle

Commenting on the findings for Medscape Medical News, Heather Snyder, PhD, Alzheimer’s Association vice president of medical and scientific relations, said the findings add to the body of work about sex differences in dementia risk.

“This is an interesting study looking at risk factors for dementia and suggests that, while some risk factors are more pronounced in men than in women, women may be more at risk of progressing to dementia,” Dr. Snyder said. “The findings outline the importance of understanding how the underlying biology, particularly biology that differs in males and females, may be contributing to risk.”

Data on the country and geographical variations highlighted in the study also point to a potential risk influencer, she said.

“Studying geography-specific risk factors is important because it helps us understand the ‘why’ behind geographic differences in dementia risk,” Dr. Snyder said. “This type of collaboration among countries and researchers is essential for us to understand these puzzle pieces.”

Funding for the study was provided by the U.K. Medical Research Council Skills Development Fellowship, Australian National Health and Medical Research Council Investigator Grant, National Institute on Aging, among others. See the original article for full funding sources. Ms. Gong reported no relevant financial conflicts. Dr. Snyder is employed by the Alzheimer’s Association.

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

Dementia risk is significantly higher in women than in men worldwide, and social and economic disadvantages among women could be to blame, a study suggests.

Prior research has found a higher lifetime dementia risk in women, and one explanation cited has been that women tend to live longer than men.

However, this new analysis of data from nearly 30,000 people in 18 countries found almost no evidence of sex differences in most known risk factors for dementia, including age.

The risk of dementia among women was significantly higher in poorer countries, pointing to economic disadvantages as a possible explanation.

“In general, we found that the greater dementia risk found in women compared to men was more pronounced in poorer countries, which points to the need for greater efforts to narrow the gaps in health disparities between women and men in these countries,” lead investigator Jessica Gong, MSc, a doctoral student at the George Institute for Global Health, Newtown, Australia, told this news organization. “It is likely that socioeconomic factors are potentially more important than biological factors when assessing dementia risk.”

The findings were published online in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
 

Global data

Most previous studies that examined sex differences in dementia risk were conducted in high-income countries, Ms. Gong noted, leaving a gap in the literature on risk in low- and middle-income countries.

To address this issue, researchers conducted an individual participant meta-analysis of 21 studies from the Cohort Studies of Memory in an International Consortium. Data analysis included information on 29,850 people from 18 countries on six continents. None of the participants had dementia at baseline, and the average age was 71.6 years.

Over a median of 4.6 years, incident dementia was reported in 2,089 people, 66% of whom were women.

Overall, women had higher dementia risk (hazard ratio, 1.12; 95% confidence interval, 1.02-1.23) than men, but the rates were highest in low- to middle-income economies (HR, 1.73; P = .03).

Dementia risk in women was higher than in men in 14 countries. Risk was highest in Nigeria, where dementia risk was more than double in women (aHR, 2.11; 95% CI, 1.46-3.04), and lowest in Brazil, where risk was 46% lower in women than in men (aHR, 0.54; 95% CI, 0.29-1.00).

In the United States, dementia risk was 7% higher in women than men (aHR, 1.07; 0.73-1.57).
 

Similar risk factors

In both women and men, older age, diabetes, depression, hearing impairment, and apo E–epsilon 4 carriage were associated with a greater risk of dementia, and more years of education, higher hip circumference, current alcohol use (vs. never), and high physical activity (vs. none to minimal) were associated with a lower risk of dementia.

Among all these risk factors, sex differences were only significant for longer education and former alcohol use, with both demonstrating a stronger association in men than women.

Global dementia rates are expected to triple over the next 25 years unless steps are taken to reduce risk factors. A 2020 report found that dementia risk could be reduced by addressing 12 modifiable risk factors, including obesity, air pollution, diabetes, social isolation, and hypertension. All of these risk factors are more common in low- to middle-income countries, Ms. Gong noted.

“These findings justify ongoing efforts to support programs to improve sex and gender equity in brain health, particularly in underrepresented and underserved populations, in turn to narrow the gaps within and between country,” Ms. Gong said.
 

Understanding the puzzle

Commenting on the findings for Medscape Medical News, Heather Snyder, PhD, Alzheimer’s Association vice president of medical and scientific relations, said the findings add to the body of work about sex differences in dementia risk.

“This is an interesting study looking at risk factors for dementia and suggests that, while some risk factors are more pronounced in men than in women, women may be more at risk of progressing to dementia,” Dr. Snyder said. “The findings outline the importance of understanding how the underlying biology, particularly biology that differs in males and females, may be contributing to risk.”

Data on the country and geographical variations highlighted in the study also point to a potential risk influencer, she said.

“Studying geography-specific risk factors is important because it helps us understand the ‘why’ behind geographic differences in dementia risk,” Dr. Snyder said. “This type of collaboration among countries and researchers is essential for us to understand these puzzle pieces.”

Funding for the study was provided by the U.K. Medical Research Council Skills Development Fellowship, Australian National Health and Medical Research Council Investigator Grant, National Institute on Aging, among others. See the original article for full funding sources. Ms. Gong reported no relevant financial conflicts. Dr. Snyder is employed by the Alzheimer’s Association.

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

Dementia risk is significantly higher in women than in men worldwide, and social and economic disadvantages among women could be to blame, a study suggests.

Prior research has found a higher lifetime dementia risk in women, and one explanation cited has been that women tend to live longer than men.

However, this new analysis of data from nearly 30,000 people in 18 countries found almost no evidence of sex differences in most known risk factors for dementia, including age.

The risk of dementia among women was significantly higher in poorer countries, pointing to economic disadvantages as a possible explanation.

“In general, we found that the greater dementia risk found in women compared to men was more pronounced in poorer countries, which points to the need for greater efforts to narrow the gaps in health disparities between women and men in these countries,” lead investigator Jessica Gong, MSc, a doctoral student at the George Institute for Global Health, Newtown, Australia, told this news organization. “It is likely that socioeconomic factors are potentially more important than biological factors when assessing dementia risk.”

The findings were published online in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
 

Global data

Most previous studies that examined sex differences in dementia risk were conducted in high-income countries, Ms. Gong noted, leaving a gap in the literature on risk in low- and middle-income countries.

To address this issue, researchers conducted an individual participant meta-analysis of 21 studies from the Cohort Studies of Memory in an International Consortium. Data analysis included information on 29,850 people from 18 countries on six continents. None of the participants had dementia at baseline, and the average age was 71.6 years.

Over a median of 4.6 years, incident dementia was reported in 2,089 people, 66% of whom were women.

Overall, women had higher dementia risk (hazard ratio, 1.12; 95% confidence interval, 1.02-1.23) than men, but the rates were highest in low- to middle-income economies (HR, 1.73; P = .03).

Dementia risk in women was higher than in men in 14 countries. Risk was highest in Nigeria, where dementia risk was more than double in women (aHR, 2.11; 95% CI, 1.46-3.04), and lowest in Brazil, where risk was 46% lower in women than in men (aHR, 0.54; 95% CI, 0.29-1.00).

In the United States, dementia risk was 7% higher in women than men (aHR, 1.07; 0.73-1.57).
 

Similar risk factors

In both women and men, older age, diabetes, depression, hearing impairment, and apo E–epsilon 4 carriage were associated with a greater risk of dementia, and more years of education, higher hip circumference, current alcohol use (vs. never), and high physical activity (vs. none to minimal) were associated with a lower risk of dementia.

Among all these risk factors, sex differences were only significant for longer education and former alcohol use, with both demonstrating a stronger association in men than women.

Global dementia rates are expected to triple over the next 25 years unless steps are taken to reduce risk factors. A 2020 report found that dementia risk could be reduced by addressing 12 modifiable risk factors, including obesity, air pollution, diabetes, social isolation, and hypertension. All of these risk factors are more common in low- to middle-income countries, Ms. Gong noted.

“These findings justify ongoing efforts to support programs to improve sex and gender equity in brain health, particularly in underrepresented and underserved populations, in turn to narrow the gaps within and between country,” Ms. Gong said.
 

Understanding the puzzle

Commenting on the findings for Medscape Medical News, Heather Snyder, PhD, Alzheimer’s Association vice president of medical and scientific relations, said the findings add to the body of work about sex differences in dementia risk.

“This is an interesting study looking at risk factors for dementia and suggests that, while some risk factors are more pronounced in men than in women, women may be more at risk of progressing to dementia,” Dr. Snyder said. “The findings outline the importance of understanding how the underlying biology, particularly biology that differs in males and females, may be contributing to risk.”

Data on the country and geographical variations highlighted in the study also point to a potential risk influencer, she said.

“Studying geography-specific risk factors is important because it helps us understand the ‘why’ behind geographic differences in dementia risk,” Dr. Snyder said. “This type of collaboration among countries and researchers is essential for us to understand these puzzle pieces.”

Funding for the study was provided by the U.K. Medical Research Council Skills Development Fellowship, Australian National Health and Medical Research Council Investigator Grant, National Institute on Aging, among others. See the original article for full funding sources. Ms. Gong reported no relevant financial conflicts. Dr. Snyder is employed by the Alzheimer’s Association.

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

An Ohio physician pled guilty to charges that he prescribed opioids for nonmedical purposes and continued to prescribe to patients he knew had psychiatric and substance use disorders, admitting that he also engaged in sex with at least three patients in exchange for opioids.

Jeffrey B. Sutton, DO, a neuromuscular medicine specialist, pled guilty on January 30 in federal court to 31 counts of illegally prescribing opioids and other controlled substances, 1 count of illegally distributing controlled substances, and 20 counts of health care fraud.

Prosecutors said Dr. Sutton admitted that he ignored warnings from prescription drug management organizations, insurers, and state authorities that he was prescribing excessively high dosages of opioids.

Dr. Sutton also admitted to ignoring patient requests to lower dosages and that he also ignored signs that patients were selling prescribed medications or otherwise engaging in illicit activity, including violations of a “pain management agreement” that he required them to sign.

The fraud counts pertained to Dr. Sutton billing Medicare, Medicaid, and other insurers for medically unnecessary visits that he required of patients so that he could prescribe inappropriate or unnecessary opioids.

In the charging document shared with this news organization, prosecutors said Dr. Sutton had sex with at least three patients, including during office visits and outside of the office. Occasionally, the physician would give opioids or other controlled substances – often benzodiazepines – to these patients, without a prescription or valid medical need.

Dr. Sutton escalated the dosage for one of those patients, even as the subjective pain score did not improve and when the patient’s urine tests showed the presence of THC and buprenorphine, but not any of the prescribed medications.

Another patient came to Dr. Sutton in 2007 with a warning that she had a history of “narcotic-seeking” behavior and diagnoses of depression, anxiety, paranoid schizophrenia, and obsessive-compulsive disorder.

The patient was hospitalized in 2018 for complications from benzodiazepine use (prescribed by Dr. Sutton). She weighed 80 pounds at the time. Dr. Sutton continued to prescribe benzodiazepines and extreme doses of opioids – in excess of 2,000 morphine equivalent dose – “despite recognizing and documenting repeated instances of noncompliance with treatment for psychiatric conditions, and despite the known contraindications of long-term opioid use for patients with these mental illnesses,” according to the charging document.

Dr. Sutton continued to prescribe opioids despite two hospitalizations for overdoses, more than 20 failed urine drug screens that showed presence of illicit drugs such as cocaine, and documented excessive use of alprazolam (Xanax) and methadone.

The physician surrendered his Drug Enforcement Administration Certificate of Registration of Controlled Substances Privileges in February 2022 “as an indication of your good faith in desiring to remedy any incorrect or unlawful practices on your part,” according to a letter to Dr. Sutton from the State Medical Board of Ohio. In that September 2022 letter, the Board notified Dr. Sutton of its intention to possibly suspend or revoke his license.

Dr. Sutton did not request a hearing, and the Board permanently revoked his medical license on January 16.

The court will sentence Dr. Sutton on May 23, according to a report by WFMJ.

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

An Ohio physician pled guilty to charges that he prescribed opioids for nonmedical purposes and continued to prescribe to patients he knew had psychiatric and substance use disorders, admitting that he also engaged in sex with at least three patients in exchange for opioids.

Jeffrey B. Sutton, DO, a neuromuscular medicine specialist, pled guilty on January 30 in federal court to 31 counts of illegally prescribing opioids and other controlled substances, 1 count of illegally distributing controlled substances, and 20 counts of health care fraud.

Prosecutors said Dr. Sutton admitted that he ignored warnings from prescription drug management organizations, insurers, and state authorities that he was prescribing excessively high dosages of opioids.

Dr. Sutton also admitted to ignoring patient requests to lower dosages and that he also ignored signs that patients were selling prescribed medications or otherwise engaging in illicit activity, including violations of a “pain management agreement” that he required them to sign.

The fraud counts pertained to Dr. Sutton billing Medicare, Medicaid, and other insurers for medically unnecessary visits that he required of patients so that he could prescribe inappropriate or unnecessary opioids.

In the charging document shared with this news organization, prosecutors said Dr. Sutton had sex with at least three patients, including during office visits and outside of the office. Occasionally, the physician would give opioids or other controlled substances – often benzodiazepines – to these patients, without a prescription or valid medical need.

Dr. Sutton escalated the dosage for one of those patients, even as the subjective pain score did not improve and when the patient’s urine tests showed the presence of THC and buprenorphine, but not any of the prescribed medications.

Another patient came to Dr. Sutton in 2007 with a warning that she had a history of “narcotic-seeking” behavior and diagnoses of depression, anxiety, paranoid schizophrenia, and obsessive-compulsive disorder.

The patient was hospitalized in 2018 for complications from benzodiazepine use (prescribed by Dr. Sutton). She weighed 80 pounds at the time. Dr. Sutton continued to prescribe benzodiazepines and extreme doses of opioids – in excess of 2,000 morphine equivalent dose – “despite recognizing and documenting repeated instances of noncompliance with treatment for psychiatric conditions, and despite the known contraindications of long-term opioid use for patients with these mental illnesses,” according to the charging document.

Dr. Sutton continued to prescribe opioids despite two hospitalizations for overdoses, more than 20 failed urine drug screens that showed presence of illicit drugs such as cocaine, and documented excessive use of alprazolam (Xanax) and methadone.

The physician surrendered his Drug Enforcement Administration Certificate of Registration of Controlled Substances Privileges in February 2022 “as an indication of your good faith in desiring to remedy any incorrect or unlawful practices on your part,” according to a letter to Dr. Sutton from the State Medical Board of Ohio. In that September 2022 letter, the Board notified Dr. Sutton of its intention to possibly suspend or revoke his license.

Dr. Sutton did not request a hearing, and the Board permanently revoked his medical license on January 16.

The court will sentence Dr. Sutton on May 23, according to a report by WFMJ.

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

An Ohio physician pled guilty to charges that he prescribed opioids for nonmedical purposes and continued to prescribe to patients he knew had psychiatric and substance use disorders, admitting that he also engaged in sex with at least three patients in exchange for opioids.

Jeffrey B. Sutton, DO, a neuromuscular medicine specialist, pled guilty on January 30 in federal court to 31 counts of illegally prescribing opioids and other controlled substances, 1 count of illegally distributing controlled substances, and 20 counts of health care fraud.

Prosecutors said Dr. Sutton admitted that he ignored warnings from prescription drug management organizations, insurers, and state authorities that he was prescribing excessively high dosages of opioids.

Dr. Sutton also admitted to ignoring patient requests to lower dosages and that he also ignored signs that patients were selling prescribed medications or otherwise engaging in illicit activity, including violations of a “pain management agreement” that he required them to sign.

The fraud counts pertained to Dr. Sutton billing Medicare, Medicaid, and other insurers for medically unnecessary visits that he required of patients so that he could prescribe inappropriate or unnecessary opioids.

In the charging document shared with this news organization, prosecutors said Dr. Sutton had sex with at least three patients, including during office visits and outside of the office. Occasionally, the physician would give opioids or other controlled substances – often benzodiazepines – to these patients, without a prescription or valid medical need.

Dr. Sutton escalated the dosage for one of those patients, even as the subjective pain score did not improve and when the patient’s urine tests showed the presence of THC and buprenorphine, but not any of the prescribed medications.

Another patient came to Dr. Sutton in 2007 with a warning that she had a history of “narcotic-seeking” behavior and diagnoses of depression, anxiety, paranoid schizophrenia, and obsessive-compulsive disorder.

The patient was hospitalized in 2018 for complications from benzodiazepine use (prescribed by Dr. Sutton). She weighed 80 pounds at the time. Dr. Sutton continued to prescribe benzodiazepines and extreme doses of opioids – in excess of 2,000 morphine equivalent dose – “despite recognizing and documenting repeated instances of noncompliance with treatment for psychiatric conditions, and despite the known contraindications of long-term opioid use for patients with these mental illnesses,” according to the charging document.

Dr. Sutton continued to prescribe opioids despite two hospitalizations for overdoses, more than 20 failed urine drug screens that showed presence of illicit drugs such as cocaine, and documented excessive use of alprazolam (Xanax) and methadone.

The physician surrendered his Drug Enforcement Administration Certificate of Registration of Controlled Substances Privileges in February 2022 “as an indication of your good faith in desiring to remedy any incorrect or unlawful practices on your part,” according to a letter to Dr. Sutton from the State Medical Board of Ohio. In that September 2022 letter, the Board notified Dr. Sutton of its intention to possibly suspend or revoke his license.

Dr. Sutton did not request a hearing, and the Board permanently revoked his medical license on January 16.

The court will sentence Dr. Sutton on May 23, according to a report by WFMJ.

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