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Does ‘Brain Training’ Really Improve Cognition and Forestall Cognitive Decline?

Article Type
Changed
Wed, 05/08/2024 - 10:53

The concept that cognitive health can be preserved or improved is often expressed as “use it or lose it.” Numerous modifiable risk factors are associated with “losing” cognitive abilities with age, and a cognitively active lifestyle may have a protective effect.

But what is a “cognitively active lifestyle” — do crosswords and Sudoku count?

One popular approach is “brain training.” While not a scientific term with an established definition, it “typically refers to tasks or drills that are designed to strengthen specific aspects of one’s cognitive function,” explained Yuko Hara, PhD, director of Aging and Alzheimer’s Prevention at the Alzheimer’s Drug Discovery Foundation.

Manuel Montero-Odasso, MD, PhD, director of the Gait and Brain Lab, Parkwood Institute, London, Ontario, Canada, elaborated: “Cognitive training involves performing a definitive task or set of tasks where you increase attentional demands to improve focus and concentration and memory. You try to execute the new things that you’ve learned and to remember them.”

In a commentary published by this news organization in 2022, neuroscientist Michael Merzenich, PhD, professor emeritus at University of California San Francisco, said that growing a person’s cognitive reserve and actively managing brain health can play an important role in preventing or delaying Alzheimer’s disease. Important components of this include brain training and physical exercise.
 

Brain Training: Mechanism of Action

Dr. Montero-Odasso, team leader at the Canadian Consortium on Neurodegeneration in Aging and team co-leader at the Ontario Neurodegenerative Research Initiative, explained that cognitive training creates new synapses in the brain, thus stimulating neuroplasticity.

“When we try to activate networks mainly in the frontal lobe, the prefrontal cortex, a key mechanism underlying this process is enhancement of the synaptic plasticity at excitatory synapses, which connect neurons into networks; in other words, we generate new synapses, and that’s how we enhance brain health and cognitive abilities.”

The more neural connections, the greater the processing speed of the brain, he continued. “Cognitive training creates an anatomical change in the brain.”

Executive functions, which include attention, inhibition, planning, and multitasking, are regulated predominantly by the prefrontal cortex. Damage in this region of the brain is also implicated in dementia. Alterations in the connectivity of this area are associated with cognitive impairment, independent of other structural pathological aberrations (eg, gray matter atrophy). These patterns may precede structural pathological changes associated with cognitive impairment and dementia.

Neuroplasticity changes have been corroborated through neuroimaging, which has demonstrated that after cognitive training, there is more activation in the prefrontal cortex that correlates with new synapses, Dr. Montero-Odasso said.

Henry Mahncke, PhD, CEO of the brain training company Posit Science/BrainHQ, explained that early research was conducted on rodents and monkeys, with Dr. Merzenich as one of the leading pioneers in developing the concept of brain plasticity. Dr. Merzenich cofounded Posit Science and is currently its chief scientific officer.

Dr. Mahncke recounted that as a graduate student, he had worked with Dr. Merzenich researching brain plasticity. When Dr. Merzenich founded Posit Science, he asked Dr. Mahncke to join the company to help develop approaches to enhance brain plasticity — building the brain-training exercises and running the clinical trials.

“It’s now well understood that the brain can rewire itself at any age and in almost any condition,” Dr. Mahncke said. “In kids and in younger and older adults, whether with healthy or unhealthy brains, the fundamental way the brain works is by continually rewiring and rebuilding itself, based on what we ask it to do.”

If we understand the principles of brain plasticity, “we can build an adaptive brain and give it exercises to rewire in a healthy direction, improving cognitive abilities like memory, speed, and attention,” Dr. Mahncke said.
 

 

 

Unsubstantiated Claims and Controversy

Brain training is not without controversy, Dr. Hara pointed out. “Some manufacturers of brain games have been criticized and even fined for making unsubstantiated claims,” she said.

2016 review found that brain-training interventions do improve performance on specific trained tasks, but there is less evidence that they improve performance on closely related tasks and little evidence that training improves everyday cognitive performance. A 2017 review  reached similar conclusions, calling evidence regarding prevention or delay of cognitive decline or dementia through brain games “insufficient,” although cognitive training could “improve cognition in the domain trained.”

“The general consensus is that for most brain-training programs, people may get better at specific tasks through practice, but these improvements don’t necessarily translate into improvement in other tasks that require other cognitive domains or prevention of dementia or age-related cognitive decline,” Dr. Hara said.

She noted that most brain-training programs “have not been rigorously tested in clinical trials” — although some, such as those featured in the ACTIVE trial, did show evidence of effectiveness.

Dr. Mahncke agreed. “Asking whether brain training works is like asking whether small molecules improve health,” he said noting that some brain-training programs are nonsense and not evidence based. He believes that his company’s product, BrainHQ, and some others are “backed by robust evidence in their ability to stave off, slow, or even reverse cognitive changes.”

BrainHQ is a web-based brain game suite that can be used independently as an app or in group settings (classes and webinars) and is covered by some Medicare Advantage insurance plans. It encompasses “dozens of individual brain-training exercises, linked by a common thread. Each one is intensively designed to make the brain faster and more accurate,” said Dr. Mahncke.

He explained that human brains “get noisy as people get older, like a radio which is wearing out, so there’s static in the background. This makes the music hard to hear, and in the case of the human brain, it makes it difficult to pay attention.” The exercises are “designed to tamp down the ‘noise,’ speed up the brain, and make information processing more accurate.”

Dr. Mahncke called this a “bottom-up” approach, in contrast to many previous cognitive-training approaches that come from the brain injury rehabilitation field. They teach “top-down” skills and strategies designed to compensate for deficits in specific domains, such as reading, concentration, or fine motor skills.

By contrast, the approach of BrainHQ is “to improve the overall processing system of the brain with speed, attention, working memory, and executive function, which will in turn impact all skills and activities.”
 

Supporting Evidence

Dr. Mahncke cited several supporting studies. For example, the IMPACT study randomized 487 adults (aged ≥ 65 years) to receive either a brain plasticity–based computerized cognitive training program (BrainHQ) or a novelty- and intensity-matched general cognitive stimulation treatment program (intervention and control group, respectively) for an 8-week period.

Those who underwent brain training showed significantly greater improvement in the repeatable Battery for the Assessment of Neuropsychological Status (RBANS Auditory Memory/Attention) compared with those in the control group (3.9 vs 1.8, respectively; P =.02). The intervention group also showed significant improvements on multiple secondary measures of attention and memory. The magnitude of the effect sizes suggests that the results are clinically significant, according to the authors.

The ACTIVE study tested the effects of different cognitive training programs on cognitive function and time to dementia. The researchers randomized 2802 healthy older adults (mean age, 74 years) to a control group with no cognitive training or one of three brain-training groups comprising:

1. In-person training on verbal memory skills

2. In-person training on reasoning and problem-solving

3. Computer-based speed-of-processing training on visual attention

Participants in the training groups completed 10 sessions, each lasting 60-75 minutes, over a 5- to 6-week period. A random subsample of each training group was selected to receive “booster” sessions, with four-session booster training delivered at 11 and 35 months. All study participants completed follow-up tests of cognition and function after 1, 2, 3, 5, and 10 years.

At the end of 10 years, those assigned to the speed-of-processing training, now part of BrainHQ, had a 29% lower risk for dementia than those in the control group who received no training. No reduction was found in the memory or reasoning training groups. Participants who completed the “booster” sessions had an even greater reduction: Each additional booster session was associated with a 10% lower risk for dementia.

Dr. Montero-Odasso was involved in the SYNERGIC study that randomized 175 participants with mild cognitive impairment (MCI; average age, 73 years) to one of five study arms:

1. Multidomain intervention with exercise, cognitive training, and vitamin D

2. Exercise, cognitive training, and placebo

3. Exercise, sham cognitive training, and vitamin D

4. Exercise, sham cognitive training, and placebo

5. Control group with balance-toning exercise, sham cognitive training, and placebo

“Sham” cognitive training consisted of alternating between two tasks (touristic search and video watching) performed on a tablet, with the same time exposure as the intervention training.

The researchers found that after 6 months of interventions, all active arms with aerobic-resistance exercise showed improvement in the ADAS-Cog-13, an established outcome to evaluate dementia treatments, when compared with the control group — regardless of the addition of cognitive training or vitamin D.

Compared with exercise alone (arms 3 and 4), those who did exercise plus cognitive training (arms 1 and 2) showed greater improvements in their ADAS-Cog-13l score, with a mean difference of −1.45 points (P = .02). The greatest improvement was seen in those who underwent the multidomain intervention in arm 1.

The authors noted that the mean 2.64-point improvement seen in the ADAS-Cog-13 for the multidomain intervention is actually larger than changes seen in previous pharmaceutical trials among individuals with MCI or mild dementia and “approaches” the three points considered clinically meaningful.

“We found that older adults with MCI who received aerobic-resistance exercise with sequential computerized cognitive training significantly improved cognition,” Dr. Montero-Odasso said. “The cognitive training we used was called Neuropeak, a multidomain lifestyle training delivered through a web-based platform developed by our co-leader Louis Bherer at Université de Montréal.”

He explained that the purpose “is to challenge your brain to the point where you need to make an effort to remember things, pay attention, and later to execute tasks. The evidence from clinical trials, including ours, shows this type of brain challenge is effective in slowing and even reversing cognitive decline.”

A follow-up study, SYNERGIC 2.0, is ongoing.
 

 

 

Puzzles, Board Games, and New Challenges

Formal brain-training programs aren’t the only way to improve brain plasticity, Dr. Hara said. Observational studies suggested an association between improved cognitive performance and/or lower dementia risk and engaging in number and word puzzles, such as crosswordscards, or board games.

Some studies suggested that older adults who use technology might also protect their cognitive reserve. Dr. Hara cited a US longitudinal study of more than 18,000 older adults suggesting that regular Internet users had roughly half the risk for dementia compared to nonregular Internet users. Estimates of daily Internet use suggested a U-shaped relationship with dementia with 0.1-2.0 hours daily (excluding time spent watching television or movies online) associated with the lowest risk. Similar associations between Internet use and a lower risk for cognitive decline have been reported in the United Kingdom and Europe.

“Engaging in mentally stimulating activities can increase ‘cognitive reserve’ — meaning, capacity of the brain to resist the effects of age-related changes or disease-related pathology, such that one can maintain cognitive function for longer,” Dr. Hara said. “Cognitively stimulating activities, regardless of the type, may help delay the onset of cognitive decline.”

She listed several examples of activities that are stimulating to the brain, including learning a new game or puzzle, a new language, or a new dance, and learning how to play a musical instrument.

Dr. Montero-Odasso emphasized that the “newness” is key to increasing and preserving cognitive reserve. “Just surfing the Internet, playing word or board games, or doing crossword puzzles won’t be enough if you’ve been doing these things all your life,” he said. “It won’t hurt, of course, but it won’t necessarily increase your cognitive abilities.

“For example, a person who regularly engages in public speaking may not improve cognition by taking a public-speaking course, but someone who has never spoken before an audience might show cognitive improvements as a result of learning a new skill,” he said. “Or someone who knows several languages already might gain from learning a brand-new language.”

He cited research supporting the benefits of dancing, which he called “an ideal activity because it’s physical, so it provides the exercise that’s been associated with improved cognition. But it also requires learning new steps and moves, which builds the synapses in the brain. And the socialization of dance classes adds another component that can improve cognition.”

Dr. Mahncke hopes that beyond engaging in day-to-day new activities, seniors will participate in computerized brain training. “There’s no reason that evidence-based training can’t be offered in senior and community centers, as yoga and swimming are,” he said. “It doesn’t have to be simply something people do on their own virtually.”

Zoom classes and Medicare reimbursements are “good steps in the right direction, but it’s time to expand this potentially life-transformative intervention so that it reaches the ever-expanding population of seniors in the United States and beyond.”

Dr. Hara reported having no disclosures. Dr. Montero-Odasso reported having no commercial or financial interest related to this topic. He serves as the president of the Canadian Geriatrics Société and is team leader in the Canadian Consortium of Neurodegeneration in Aging. Dr. Mahncke is CEO of the brain training company Posit Science/BrainHQ.

A version of this article appeared on Medscape.com.

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The concept that cognitive health can be preserved or improved is often expressed as “use it or lose it.” Numerous modifiable risk factors are associated with “losing” cognitive abilities with age, and a cognitively active lifestyle may have a protective effect.

But what is a “cognitively active lifestyle” — do crosswords and Sudoku count?

One popular approach is “brain training.” While not a scientific term with an established definition, it “typically refers to tasks or drills that are designed to strengthen specific aspects of one’s cognitive function,” explained Yuko Hara, PhD, director of Aging and Alzheimer’s Prevention at the Alzheimer’s Drug Discovery Foundation.

Manuel Montero-Odasso, MD, PhD, director of the Gait and Brain Lab, Parkwood Institute, London, Ontario, Canada, elaborated: “Cognitive training involves performing a definitive task or set of tasks where you increase attentional demands to improve focus and concentration and memory. You try to execute the new things that you’ve learned and to remember them.”

In a commentary published by this news organization in 2022, neuroscientist Michael Merzenich, PhD, professor emeritus at University of California San Francisco, said that growing a person’s cognitive reserve and actively managing brain health can play an important role in preventing or delaying Alzheimer’s disease. Important components of this include brain training and physical exercise.
 

Brain Training: Mechanism of Action

Dr. Montero-Odasso, team leader at the Canadian Consortium on Neurodegeneration in Aging and team co-leader at the Ontario Neurodegenerative Research Initiative, explained that cognitive training creates new synapses in the brain, thus stimulating neuroplasticity.

“When we try to activate networks mainly in the frontal lobe, the prefrontal cortex, a key mechanism underlying this process is enhancement of the synaptic plasticity at excitatory synapses, which connect neurons into networks; in other words, we generate new synapses, and that’s how we enhance brain health and cognitive abilities.”

The more neural connections, the greater the processing speed of the brain, he continued. “Cognitive training creates an anatomical change in the brain.”

Executive functions, which include attention, inhibition, planning, and multitasking, are regulated predominantly by the prefrontal cortex. Damage in this region of the brain is also implicated in dementia. Alterations in the connectivity of this area are associated with cognitive impairment, independent of other structural pathological aberrations (eg, gray matter atrophy). These patterns may precede structural pathological changes associated with cognitive impairment and dementia.

Neuroplasticity changes have been corroborated through neuroimaging, which has demonstrated that after cognitive training, there is more activation in the prefrontal cortex that correlates with new synapses, Dr. Montero-Odasso said.

Henry Mahncke, PhD, CEO of the brain training company Posit Science/BrainHQ, explained that early research was conducted on rodents and monkeys, with Dr. Merzenich as one of the leading pioneers in developing the concept of brain plasticity. Dr. Merzenich cofounded Posit Science and is currently its chief scientific officer.

Dr. Mahncke recounted that as a graduate student, he had worked with Dr. Merzenich researching brain plasticity. When Dr. Merzenich founded Posit Science, he asked Dr. Mahncke to join the company to help develop approaches to enhance brain plasticity — building the brain-training exercises and running the clinical trials.

“It’s now well understood that the brain can rewire itself at any age and in almost any condition,” Dr. Mahncke said. “In kids and in younger and older adults, whether with healthy or unhealthy brains, the fundamental way the brain works is by continually rewiring and rebuilding itself, based on what we ask it to do.”

If we understand the principles of brain plasticity, “we can build an adaptive brain and give it exercises to rewire in a healthy direction, improving cognitive abilities like memory, speed, and attention,” Dr. Mahncke said.
 

 

 

Unsubstantiated Claims and Controversy

Brain training is not without controversy, Dr. Hara pointed out. “Some manufacturers of brain games have been criticized and even fined for making unsubstantiated claims,” she said.

2016 review found that brain-training interventions do improve performance on specific trained tasks, but there is less evidence that they improve performance on closely related tasks and little evidence that training improves everyday cognitive performance. A 2017 review  reached similar conclusions, calling evidence regarding prevention or delay of cognitive decline or dementia through brain games “insufficient,” although cognitive training could “improve cognition in the domain trained.”

“The general consensus is that for most brain-training programs, people may get better at specific tasks through practice, but these improvements don’t necessarily translate into improvement in other tasks that require other cognitive domains or prevention of dementia or age-related cognitive decline,” Dr. Hara said.

She noted that most brain-training programs “have not been rigorously tested in clinical trials” — although some, such as those featured in the ACTIVE trial, did show evidence of effectiveness.

Dr. Mahncke agreed. “Asking whether brain training works is like asking whether small molecules improve health,” he said noting that some brain-training programs are nonsense and not evidence based. He believes that his company’s product, BrainHQ, and some others are “backed by robust evidence in their ability to stave off, slow, or even reverse cognitive changes.”

BrainHQ is a web-based brain game suite that can be used independently as an app or in group settings (classes and webinars) and is covered by some Medicare Advantage insurance plans. It encompasses “dozens of individual brain-training exercises, linked by a common thread. Each one is intensively designed to make the brain faster and more accurate,” said Dr. Mahncke.

He explained that human brains “get noisy as people get older, like a radio which is wearing out, so there’s static in the background. This makes the music hard to hear, and in the case of the human brain, it makes it difficult to pay attention.” The exercises are “designed to tamp down the ‘noise,’ speed up the brain, and make information processing more accurate.”

Dr. Mahncke called this a “bottom-up” approach, in contrast to many previous cognitive-training approaches that come from the brain injury rehabilitation field. They teach “top-down” skills and strategies designed to compensate for deficits in specific domains, such as reading, concentration, or fine motor skills.

By contrast, the approach of BrainHQ is “to improve the overall processing system of the brain with speed, attention, working memory, and executive function, which will in turn impact all skills and activities.”
 

Supporting Evidence

Dr. Mahncke cited several supporting studies. For example, the IMPACT study randomized 487 adults (aged ≥ 65 years) to receive either a brain plasticity–based computerized cognitive training program (BrainHQ) or a novelty- and intensity-matched general cognitive stimulation treatment program (intervention and control group, respectively) for an 8-week period.

Those who underwent brain training showed significantly greater improvement in the repeatable Battery for the Assessment of Neuropsychological Status (RBANS Auditory Memory/Attention) compared with those in the control group (3.9 vs 1.8, respectively; P =.02). The intervention group also showed significant improvements on multiple secondary measures of attention and memory. The magnitude of the effect sizes suggests that the results are clinically significant, according to the authors.

The ACTIVE study tested the effects of different cognitive training programs on cognitive function and time to dementia. The researchers randomized 2802 healthy older adults (mean age, 74 years) to a control group with no cognitive training or one of three brain-training groups comprising:

1. In-person training on verbal memory skills

2. In-person training on reasoning and problem-solving

3. Computer-based speed-of-processing training on visual attention

Participants in the training groups completed 10 sessions, each lasting 60-75 minutes, over a 5- to 6-week period. A random subsample of each training group was selected to receive “booster” sessions, with four-session booster training delivered at 11 and 35 months. All study participants completed follow-up tests of cognition and function after 1, 2, 3, 5, and 10 years.

At the end of 10 years, those assigned to the speed-of-processing training, now part of BrainHQ, had a 29% lower risk for dementia than those in the control group who received no training. No reduction was found in the memory or reasoning training groups. Participants who completed the “booster” sessions had an even greater reduction: Each additional booster session was associated with a 10% lower risk for dementia.

Dr. Montero-Odasso was involved in the SYNERGIC study that randomized 175 participants with mild cognitive impairment (MCI; average age, 73 years) to one of five study arms:

1. Multidomain intervention with exercise, cognitive training, and vitamin D

2. Exercise, cognitive training, and placebo

3. Exercise, sham cognitive training, and vitamin D

4. Exercise, sham cognitive training, and placebo

5. Control group with balance-toning exercise, sham cognitive training, and placebo

“Sham” cognitive training consisted of alternating between two tasks (touristic search and video watching) performed on a tablet, with the same time exposure as the intervention training.

The researchers found that after 6 months of interventions, all active arms with aerobic-resistance exercise showed improvement in the ADAS-Cog-13, an established outcome to evaluate dementia treatments, when compared with the control group — regardless of the addition of cognitive training or vitamin D.

Compared with exercise alone (arms 3 and 4), those who did exercise plus cognitive training (arms 1 and 2) showed greater improvements in their ADAS-Cog-13l score, with a mean difference of −1.45 points (P = .02). The greatest improvement was seen in those who underwent the multidomain intervention in arm 1.

The authors noted that the mean 2.64-point improvement seen in the ADAS-Cog-13 for the multidomain intervention is actually larger than changes seen in previous pharmaceutical trials among individuals with MCI or mild dementia and “approaches” the three points considered clinically meaningful.

“We found that older adults with MCI who received aerobic-resistance exercise with sequential computerized cognitive training significantly improved cognition,” Dr. Montero-Odasso said. “The cognitive training we used was called Neuropeak, a multidomain lifestyle training delivered through a web-based platform developed by our co-leader Louis Bherer at Université de Montréal.”

He explained that the purpose “is to challenge your brain to the point where you need to make an effort to remember things, pay attention, and later to execute tasks. The evidence from clinical trials, including ours, shows this type of brain challenge is effective in slowing and even reversing cognitive decline.”

A follow-up study, SYNERGIC 2.0, is ongoing.
 

 

 

Puzzles, Board Games, and New Challenges

Formal brain-training programs aren’t the only way to improve brain plasticity, Dr. Hara said. Observational studies suggested an association between improved cognitive performance and/or lower dementia risk and engaging in number and word puzzles, such as crosswordscards, or board games.

Some studies suggested that older adults who use technology might also protect their cognitive reserve. Dr. Hara cited a US longitudinal study of more than 18,000 older adults suggesting that regular Internet users had roughly half the risk for dementia compared to nonregular Internet users. Estimates of daily Internet use suggested a U-shaped relationship with dementia with 0.1-2.0 hours daily (excluding time spent watching television or movies online) associated with the lowest risk. Similar associations between Internet use and a lower risk for cognitive decline have been reported in the United Kingdom and Europe.

“Engaging in mentally stimulating activities can increase ‘cognitive reserve’ — meaning, capacity of the brain to resist the effects of age-related changes or disease-related pathology, such that one can maintain cognitive function for longer,” Dr. Hara said. “Cognitively stimulating activities, regardless of the type, may help delay the onset of cognitive decline.”

She listed several examples of activities that are stimulating to the brain, including learning a new game or puzzle, a new language, or a new dance, and learning how to play a musical instrument.

Dr. Montero-Odasso emphasized that the “newness” is key to increasing and preserving cognitive reserve. “Just surfing the Internet, playing word or board games, or doing crossword puzzles won’t be enough if you’ve been doing these things all your life,” he said. “It won’t hurt, of course, but it won’t necessarily increase your cognitive abilities.

“For example, a person who regularly engages in public speaking may not improve cognition by taking a public-speaking course, but someone who has never spoken before an audience might show cognitive improvements as a result of learning a new skill,” he said. “Or someone who knows several languages already might gain from learning a brand-new language.”

He cited research supporting the benefits of dancing, which he called “an ideal activity because it’s physical, so it provides the exercise that’s been associated with improved cognition. But it also requires learning new steps and moves, which builds the synapses in the brain. And the socialization of dance classes adds another component that can improve cognition.”

Dr. Mahncke hopes that beyond engaging in day-to-day new activities, seniors will participate in computerized brain training. “There’s no reason that evidence-based training can’t be offered in senior and community centers, as yoga and swimming are,” he said. “It doesn’t have to be simply something people do on their own virtually.”

Zoom classes and Medicare reimbursements are “good steps in the right direction, but it’s time to expand this potentially life-transformative intervention so that it reaches the ever-expanding population of seniors in the United States and beyond.”

Dr. Hara reported having no disclosures. Dr. Montero-Odasso reported having no commercial or financial interest related to this topic. He serves as the president of the Canadian Geriatrics Société and is team leader in the Canadian Consortium of Neurodegeneration in Aging. Dr. Mahncke is CEO of the brain training company Posit Science/BrainHQ.

A version of this article appeared on Medscape.com.

The concept that cognitive health can be preserved or improved is often expressed as “use it or lose it.” Numerous modifiable risk factors are associated with “losing” cognitive abilities with age, and a cognitively active lifestyle may have a protective effect.

But what is a “cognitively active lifestyle” — do crosswords and Sudoku count?

One popular approach is “brain training.” While not a scientific term with an established definition, it “typically refers to tasks or drills that are designed to strengthen specific aspects of one’s cognitive function,” explained Yuko Hara, PhD, director of Aging and Alzheimer’s Prevention at the Alzheimer’s Drug Discovery Foundation.

Manuel Montero-Odasso, MD, PhD, director of the Gait and Brain Lab, Parkwood Institute, London, Ontario, Canada, elaborated: “Cognitive training involves performing a definitive task or set of tasks where you increase attentional demands to improve focus and concentration and memory. You try to execute the new things that you’ve learned and to remember them.”

In a commentary published by this news organization in 2022, neuroscientist Michael Merzenich, PhD, professor emeritus at University of California San Francisco, said that growing a person’s cognitive reserve and actively managing brain health can play an important role in preventing or delaying Alzheimer’s disease. Important components of this include brain training and physical exercise.
 

Brain Training: Mechanism of Action

Dr. Montero-Odasso, team leader at the Canadian Consortium on Neurodegeneration in Aging and team co-leader at the Ontario Neurodegenerative Research Initiative, explained that cognitive training creates new synapses in the brain, thus stimulating neuroplasticity.

“When we try to activate networks mainly in the frontal lobe, the prefrontal cortex, a key mechanism underlying this process is enhancement of the synaptic plasticity at excitatory synapses, which connect neurons into networks; in other words, we generate new synapses, and that’s how we enhance brain health and cognitive abilities.”

The more neural connections, the greater the processing speed of the brain, he continued. “Cognitive training creates an anatomical change in the brain.”

Executive functions, which include attention, inhibition, planning, and multitasking, are regulated predominantly by the prefrontal cortex. Damage in this region of the brain is also implicated in dementia. Alterations in the connectivity of this area are associated with cognitive impairment, independent of other structural pathological aberrations (eg, gray matter atrophy). These patterns may precede structural pathological changes associated with cognitive impairment and dementia.

Neuroplasticity changes have been corroborated through neuroimaging, which has demonstrated that after cognitive training, there is more activation in the prefrontal cortex that correlates with new synapses, Dr. Montero-Odasso said.

Henry Mahncke, PhD, CEO of the brain training company Posit Science/BrainHQ, explained that early research was conducted on rodents and monkeys, with Dr. Merzenich as one of the leading pioneers in developing the concept of brain plasticity. Dr. Merzenich cofounded Posit Science and is currently its chief scientific officer.

Dr. Mahncke recounted that as a graduate student, he had worked with Dr. Merzenich researching brain plasticity. When Dr. Merzenich founded Posit Science, he asked Dr. Mahncke to join the company to help develop approaches to enhance brain plasticity — building the brain-training exercises and running the clinical trials.

“It’s now well understood that the brain can rewire itself at any age and in almost any condition,” Dr. Mahncke said. “In kids and in younger and older adults, whether with healthy or unhealthy brains, the fundamental way the brain works is by continually rewiring and rebuilding itself, based on what we ask it to do.”

If we understand the principles of brain plasticity, “we can build an adaptive brain and give it exercises to rewire in a healthy direction, improving cognitive abilities like memory, speed, and attention,” Dr. Mahncke said.
 

 

 

Unsubstantiated Claims and Controversy

Brain training is not without controversy, Dr. Hara pointed out. “Some manufacturers of brain games have been criticized and even fined for making unsubstantiated claims,” she said.

2016 review found that brain-training interventions do improve performance on specific trained tasks, but there is less evidence that they improve performance on closely related tasks and little evidence that training improves everyday cognitive performance. A 2017 review  reached similar conclusions, calling evidence regarding prevention or delay of cognitive decline or dementia through brain games “insufficient,” although cognitive training could “improve cognition in the domain trained.”

“The general consensus is that for most brain-training programs, people may get better at specific tasks through practice, but these improvements don’t necessarily translate into improvement in other tasks that require other cognitive domains or prevention of dementia or age-related cognitive decline,” Dr. Hara said.

She noted that most brain-training programs “have not been rigorously tested in clinical trials” — although some, such as those featured in the ACTIVE trial, did show evidence of effectiveness.

Dr. Mahncke agreed. “Asking whether brain training works is like asking whether small molecules improve health,” he said noting that some brain-training programs are nonsense and not evidence based. He believes that his company’s product, BrainHQ, and some others are “backed by robust evidence in their ability to stave off, slow, or even reverse cognitive changes.”

BrainHQ is a web-based brain game suite that can be used independently as an app or in group settings (classes and webinars) and is covered by some Medicare Advantage insurance plans. It encompasses “dozens of individual brain-training exercises, linked by a common thread. Each one is intensively designed to make the brain faster and more accurate,” said Dr. Mahncke.

He explained that human brains “get noisy as people get older, like a radio which is wearing out, so there’s static in the background. This makes the music hard to hear, and in the case of the human brain, it makes it difficult to pay attention.” The exercises are “designed to tamp down the ‘noise,’ speed up the brain, and make information processing more accurate.”

Dr. Mahncke called this a “bottom-up” approach, in contrast to many previous cognitive-training approaches that come from the brain injury rehabilitation field. They teach “top-down” skills and strategies designed to compensate for deficits in specific domains, such as reading, concentration, or fine motor skills.

By contrast, the approach of BrainHQ is “to improve the overall processing system of the brain with speed, attention, working memory, and executive function, which will in turn impact all skills and activities.”
 

Supporting Evidence

Dr. Mahncke cited several supporting studies. For example, the IMPACT study randomized 487 adults (aged ≥ 65 years) to receive either a brain plasticity–based computerized cognitive training program (BrainHQ) or a novelty- and intensity-matched general cognitive stimulation treatment program (intervention and control group, respectively) for an 8-week period.

Those who underwent brain training showed significantly greater improvement in the repeatable Battery for the Assessment of Neuropsychological Status (RBANS Auditory Memory/Attention) compared with those in the control group (3.9 vs 1.8, respectively; P =.02). The intervention group also showed significant improvements on multiple secondary measures of attention and memory. The magnitude of the effect sizes suggests that the results are clinically significant, according to the authors.

The ACTIVE study tested the effects of different cognitive training programs on cognitive function and time to dementia. The researchers randomized 2802 healthy older adults (mean age, 74 years) to a control group with no cognitive training or one of three brain-training groups comprising:

1. In-person training on verbal memory skills

2. In-person training on reasoning and problem-solving

3. Computer-based speed-of-processing training on visual attention

Participants in the training groups completed 10 sessions, each lasting 60-75 minutes, over a 5- to 6-week period. A random subsample of each training group was selected to receive “booster” sessions, with four-session booster training delivered at 11 and 35 months. All study participants completed follow-up tests of cognition and function after 1, 2, 3, 5, and 10 years.

At the end of 10 years, those assigned to the speed-of-processing training, now part of BrainHQ, had a 29% lower risk for dementia than those in the control group who received no training. No reduction was found in the memory or reasoning training groups. Participants who completed the “booster” sessions had an even greater reduction: Each additional booster session was associated with a 10% lower risk for dementia.

Dr. Montero-Odasso was involved in the SYNERGIC study that randomized 175 participants with mild cognitive impairment (MCI; average age, 73 years) to one of five study arms:

1. Multidomain intervention with exercise, cognitive training, and vitamin D

2. Exercise, cognitive training, and placebo

3. Exercise, sham cognitive training, and vitamin D

4. Exercise, sham cognitive training, and placebo

5. Control group with balance-toning exercise, sham cognitive training, and placebo

“Sham” cognitive training consisted of alternating between two tasks (touristic search and video watching) performed on a tablet, with the same time exposure as the intervention training.

The researchers found that after 6 months of interventions, all active arms with aerobic-resistance exercise showed improvement in the ADAS-Cog-13, an established outcome to evaluate dementia treatments, when compared with the control group — regardless of the addition of cognitive training or vitamin D.

Compared with exercise alone (arms 3 and 4), those who did exercise plus cognitive training (arms 1 and 2) showed greater improvements in their ADAS-Cog-13l score, with a mean difference of −1.45 points (P = .02). The greatest improvement was seen in those who underwent the multidomain intervention in arm 1.

The authors noted that the mean 2.64-point improvement seen in the ADAS-Cog-13 for the multidomain intervention is actually larger than changes seen in previous pharmaceutical trials among individuals with MCI or mild dementia and “approaches” the three points considered clinically meaningful.

“We found that older adults with MCI who received aerobic-resistance exercise with sequential computerized cognitive training significantly improved cognition,” Dr. Montero-Odasso said. “The cognitive training we used was called Neuropeak, a multidomain lifestyle training delivered through a web-based platform developed by our co-leader Louis Bherer at Université de Montréal.”

He explained that the purpose “is to challenge your brain to the point where you need to make an effort to remember things, pay attention, and later to execute tasks. The evidence from clinical trials, including ours, shows this type of brain challenge is effective in slowing and even reversing cognitive decline.”

A follow-up study, SYNERGIC 2.0, is ongoing.
 

 

 

Puzzles, Board Games, and New Challenges

Formal brain-training programs aren’t the only way to improve brain plasticity, Dr. Hara said. Observational studies suggested an association between improved cognitive performance and/or lower dementia risk and engaging in number and word puzzles, such as crosswordscards, or board games.

Some studies suggested that older adults who use technology might also protect their cognitive reserve. Dr. Hara cited a US longitudinal study of more than 18,000 older adults suggesting that regular Internet users had roughly half the risk for dementia compared to nonregular Internet users. Estimates of daily Internet use suggested a U-shaped relationship with dementia with 0.1-2.0 hours daily (excluding time spent watching television or movies online) associated with the lowest risk. Similar associations between Internet use and a lower risk for cognitive decline have been reported in the United Kingdom and Europe.

“Engaging in mentally stimulating activities can increase ‘cognitive reserve’ — meaning, capacity of the brain to resist the effects of age-related changes or disease-related pathology, such that one can maintain cognitive function for longer,” Dr. Hara said. “Cognitively stimulating activities, regardless of the type, may help delay the onset of cognitive decline.”

She listed several examples of activities that are stimulating to the brain, including learning a new game or puzzle, a new language, or a new dance, and learning how to play a musical instrument.

Dr. Montero-Odasso emphasized that the “newness” is key to increasing and preserving cognitive reserve. “Just surfing the Internet, playing word or board games, or doing crossword puzzles won’t be enough if you’ve been doing these things all your life,” he said. “It won’t hurt, of course, but it won’t necessarily increase your cognitive abilities.

“For example, a person who regularly engages in public speaking may not improve cognition by taking a public-speaking course, but someone who has never spoken before an audience might show cognitive improvements as a result of learning a new skill,” he said. “Or someone who knows several languages already might gain from learning a brand-new language.”

He cited research supporting the benefits of dancing, which he called “an ideal activity because it’s physical, so it provides the exercise that’s been associated with improved cognition. But it also requires learning new steps and moves, which builds the synapses in the brain. And the socialization of dance classes adds another component that can improve cognition.”

Dr. Mahncke hopes that beyond engaging in day-to-day new activities, seniors will participate in computerized brain training. “There’s no reason that evidence-based training can’t be offered in senior and community centers, as yoga and swimming are,” he said. “It doesn’t have to be simply something people do on their own virtually.”

Zoom classes and Medicare reimbursements are “good steps in the right direction, but it’s time to expand this potentially life-transformative intervention so that it reaches the ever-expanding population of seniors in the United States and beyond.”

Dr. Hara reported having no disclosures. Dr. Montero-Odasso reported having no commercial or financial interest related to this topic. He serves as the president of the Canadian Geriatrics Société and is team leader in the Canadian Consortium of Neurodegeneration in Aging. Dr. Mahncke is CEO of the brain training company Posit Science/BrainHQ.

A version of this article appeared on Medscape.com.

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Working Hard or Work Addiction — Have You Crossed the Line?

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Mon, 04/29/2024 - 11:13

When child psychiatrist Javeed Sukhera, MD, PhD, was a few years into his career, he found himself doing it all. “I was in a leadership role academically at the medical school, I had a leadership role at the hospital, and I was seeing as many patients as I could. I could work all day every day.”

“It still wouldn’t have been enough,” he said.

Whenever there was a shift available, Dr. Sukhera would take it. His job was stressful, but as a new physician with a young family, he saw this obsession with work as necessary. “I began to cope with the stress from work by doing extra work and feeling like I needed to be everywhere. It was like I became a hamster on a spinning wheel. I was just running, running, running.”

Things shifted for Dr. Sukhera when he realized that while he was emotionally available for the children who were his patients, at home, his own children weren’t getting the best of him. “There was a specific moment when I thought my son was afraid of me,” he said. “I just stopped and realized that there was something happening that I needed to break. I needed to make a change.”

Dr. Sukhera, now chair of psychiatry at the Institute of Living and chief of the Department of Psychiatry at Hartford Hospital, Hartford, Connecticut, believes what he experienced was a steep fall into work addiction. “Workaholism,” often dismissed as simply working hard, is a nonclinical addiction that could fall under the umbrella of a behavioral addiction, and healthcare professionals may be especially at risk.
 

What Does Work Addiction Look Like for Doctors?

Behavioral addictions are fairly new in the addiction space. When gambling disorder, the first and only behavioral addiction in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, was added in 2013, it was seen as a “breakthrough addiction,” said Mark D. Griffiths, PhD, a leading behavioral addiction researcher and a distinguished professor at Nottingham Trent University.

Because there is not enough evidence yet to classify work addiction as a formal diagnosis, there is no clear consensus on how to define it. To further complicate things, the terms “workaholism” and “work addiction” can be used interchangeably, and some experts say the two are not the same, though they can overlap.

That said, a 2018 review of literature from several countries found that work addiction “fits very well into recently postulated criteria for conceptualization of a behavioral addiction.

“If you accept that gambling can be genuinely addictive, then there’s no reason to think that something like work, exercise, or video game playing couldn’t be an addiction as well,” said Dr. Griffiths.

“The neurobiology of addiction is that we get drawn to something that gives us a dopamine hit,” Dr. Sukhera added. “But to do that all day, every day, has consequences. It drains our emotional reserves, and it can greatly impact our relationships.”

On top of that, work addiction has been linked with poor sleep, poor cardiovascular health, high blood pressure, burnout, the development of autoimmune disorders, and other health issues.

Physicians are particularly susceptible. Doctors, after all, are expected to work long hours and put their patients’ needs first, even at the expense of their own health and well-being.

“Workaholism is not just socially acceptable in medicine,” said Dr. Sukhera. “It’s baked into the system and built into the structures. The healthcare system has largely functioned on the emotional labor of health workers, whose tendency to show up and work harder can, at times, in certain organizations, be exploited.”

Dr. Griffiths agreed that with the limited amount of data available, work addiction does appear to exist at higher rates in medicine than in other fields. As early as the 1970s, medical literature describes work as a “socially acceptable” addiction among doctors. A 2014 study published in Occupational Medicine reported that of 445 physicians who took part in the research, nearly half exhibited some level of work addiction with 13% “highly work addicted.”

Of course, working hard or even meeting unreasonable demands from work is not the same as work addiction, as Dr. Griffiths clarified in a 2023 editorial in BMJ Quality & Safety. The difference, as with other behavioral addictions, is when people obsess about work and use it to cope with stress. It can be easier to stay distracted and busy to gain a sense of control rather than learning to deal with complex emotions.

2021 study that Dr. Sukhera conducted with resident physicians found that working harder was one of the main ways they dealt with stress during the COVID-19 pandemic. “This idea that we deal with the stress of being burnt out by doing more and more of what burns us out is fairly ubiquitous at all stages of medical professionals’ careers,” he said.

Financial incentives also can fuel work addiction, said Dr. Sukhera. In residency, there are some safeguards around overwork and duty hours. When you become an attending, those limits no longer exist. As a young physician, Dr. Sukhera had student debt to pay off and a family to support. When he found opportunities to earn more by working more, his answer was always “yes.”

Pressure to produce medical research also can pose issues. Some physicians can become addicted to publishing studies, fearing that they might lose their professional status or position if they stop. It’s a cycle that can force a doctor to not only work long hours doing their job but also practically take on a second one.
 

 

 

How Physicians Can Recognize Work Addiction in Themselves

Work addiction can look and feel different for every person, said Malissa Clark, PhD, associate professor at the University of Georgia and author of the recent book Never Not Working: Why the Always-On Culture Is Bad for Business—and How to Fix It.

Dr. Clark noted that people who are highly engaged in their work tend to be driven by intrinsic motivation: “You work because you love it.” With work addiction, “you work because you feel like you ought to be working all the time.”

Of course, it’s not always so cut and dried; you can experience both forms of motivation and not necessarily become addicted to work. But if you are solely driven by the feeling that you ought to be working all the time, that can be a red flag.

Dr. Griffiths said that while many people may have problematic work habits or work too much, true work addicts must meet six criteria that apply to all addictions:

1. Salience: Work is the single most important thing in your life, to the point of neglecting everything else. Even if you’re on vacation, your mind might be flooded with work thoughts.

2. Mood modification: You use work to modify your mood, either to get a “high” or to cope with stress.

3. Tolerance: Over time, you’ve gone from working 8 or 10 hours a day to 12 hours a day, to a point where you’re working all the time.

4. Withdrawal: On a physiological level, you will have symptoms such as anxiety, nausea, or headaches when unable to work.

5. Conflict: You feel conflicted with yourself (you know you’re working too much) or with others (partners, friends, and children) about work, but you can’t stop.

6. Relapse: If you manage to cut down your hours but can’t resist overworking 1 day, you wind up right back where you were.
 

When It’s Time to Address Work Addiction

The lack of a formal diagnosis for work addiction makes getting treatment difficult. But there are ways to seek help. Unlike the drug and alcohol literature, abstinence is not the goal. “The therapeutic goal is getting a behavior under control and looking for the triggers of why you’re compulsively working,” said Dr. Griffiths.

Practice self-compassion

Dr. Sukhera eventually realized that his work addiction stemmed from the fear of being somehow excluded or unworthy. He actively corrected much of this through self-compassion and self-kindness, which helped him set boundaries. “Self-compassion is the root of everything,” he said. “Reminding ourselves that we’re doing our best is an important ingredient in breaking the cycle.”

Slowly expose yourself to relaxation

Many workaholics find rest very difficult. “When I conducted interviews with people [who considered themselves workaholics], a very common thing I heard was, ‘I have a very hard time being idle,’ ” said Dr. Clark. If rest feels hard, Dr. Sukhera suggests practicing relaxation for 2 minutes to start. Even small periods of downtime can challenge the belief that you must be constantly productive.

Reframe your to-do list 

For work addicts, to-do lists can seem like they must be finished, which prolongs work hours. Instead, use to-do lists to help prioritize what is urgent, identify what can wait, and delegate out tasks to others, Dr. Clark recommends.

Pick up a mastery experience

Research from professor Sabine Sonnentag, Dr. rer. nat., at the University of Mannheim, Mannheim, Germany, suggests that mastery experiences — leisure activities that require thought and focus like learning a new language or taking a woodworking class — can help you actively disengage from work.

Try cognitive behavioral therapy

Widely used for other forms of addiction, cognitive behavioral therapy centers around recognizing emotions, challenging thought patterns, and changing behaviors. However, Dr. Clark admits the research on its impact on work addiction, in particular, is “pretty nascent.”

Shift your mindset

It seems logical to think that detaching from your feelings will allow you to “do more,” but experts say that idea is both untrue and dangerous. “The safest hospitals are the hospitals where people are attuned to their humanness,” said Dr. Sukhera. “It’s normal to overwork in medicine, and if you’re challenging a norm, you really have to be thoughtful about how you frame that for yourself.”

Most importantly: Seek support

Today, there is increased awareness about work addiction and more resources for physicians who are struggling, including programs such as Workaholics Anonymous or Physicians Anonymous and workplace wellness initiatives. But try not to overwhelm yourself with choosing whom to talk to or what specific resource to utilize, Dr. Sukhera advised. “Just talk to someone about it. You don’t have to carry this on your own.”
 

A version of this article appeared on Medscape.com.

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When child psychiatrist Javeed Sukhera, MD, PhD, was a few years into his career, he found himself doing it all. “I was in a leadership role academically at the medical school, I had a leadership role at the hospital, and I was seeing as many patients as I could. I could work all day every day.”

“It still wouldn’t have been enough,” he said.

Whenever there was a shift available, Dr. Sukhera would take it. His job was stressful, but as a new physician with a young family, he saw this obsession with work as necessary. “I began to cope with the stress from work by doing extra work and feeling like I needed to be everywhere. It was like I became a hamster on a spinning wheel. I was just running, running, running.”

Things shifted for Dr. Sukhera when he realized that while he was emotionally available for the children who were his patients, at home, his own children weren’t getting the best of him. “There was a specific moment when I thought my son was afraid of me,” he said. “I just stopped and realized that there was something happening that I needed to break. I needed to make a change.”

Dr. Sukhera, now chair of psychiatry at the Institute of Living and chief of the Department of Psychiatry at Hartford Hospital, Hartford, Connecticut, believes what he experienced was a steep fall into work addiction. “Workaholism,” often dismissed as simply working hard, is a nonclinical addiction that could fall under the umbrella of a behavioral addiction, and healthcare professionals may be especially at risk.
 

What Does Work Addiction Look Like for Doctors?

Behavioral addictions are fairly new in the addiction space. When gambling disorder, the first and only behavioral addiction in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, was added in 2013, it was seen as a “breakthrough addiction,” said Mark D. Griffiths, PhD, a leading behavioral addiction researcher and a distinguished professor at Nottingham Trent University.

Because there is not enough evidence yet to classify work addiction as a formal diagnosis, there is no clear consensus on how to define it. To further complicate things, the terms “workaholism” and “work addiction” can be used interchangeably, and some experts say the two are not the same, though they can overlap.

That said, a 2018 review of literature from several countries found that work addiction “fits very well into recently postulated criteria for conceptualization of a behavioral addiction.

“If you accept that gambling can be genuinely addictive, then there’s no reason to think that something like work, exercise, or video game playing couldn’t be an addiction as well,” said Dr. Griffiths.

“The neurobiology of addiction is that we get drawn to something that gives us a dopamine hit,” Dr. Sukhera added. “But to do that all day, every day, has consequences. It drains our emotional reserves, and it can greatly impact our relationships.”

On top of that, work addiction has been linked with poor sleep, poor cardiovascular health, high blood pressure, burnout, the development of autoimmune disorders, and other health issues.

Physicians are particularly susceptible. Doctors, after all, are expected to work long hours and put their patients’ needs first, even at the expense of their own health and well-being.

“Workaholism is not just socially acceptable in medicine,” said Dr. Sukhera. “It’s baked into the system and built into the structures. The healthcare system has largely functioned on the emotional labor of health workers, whose tendency to show up and work harder can, at times, in certain organizations, be exploited.”

Dr. Griffiths agreed that with the limited amount of data available, work addiction does appear to exist at higher rates in medicine than in other fields. As early as the 1970s, medical literature describes work as a “socially acceptable” addiction among doctors. A 2014 study published in Occupational Medicine reported that of 445 physicians who took part in the research, nearly half exhibited some level of work addiction with 13% “highly work addicted.”

Of course, working hard or even meeting unreasonable demands from work is not the same as work addiction, as Dr. Griffiths clarified in a 2023 editorial in BMJ Quality & Safety. The difference, as with other behavioral addictions, is when people obsess about work and use it to cope with stress. It can be easier to stay distracted and busy to gain a sense of control rather than learning to deal with complex emotions.

2021 study that Dr. Sukhera conducted with resident physicians found that working harder was one of the main ways they dealt with stress during the COVID-19 pandemic. “This idea that we deal with the stress of being burnt out by doing more and more of what burns us out is fairly ubiquitous at all stages of medical professionals’ careers,” he said.

Financial incentives also can fuel work addiction, said Dr. Sukhera. In residency, there are some safeguards around overwork and duty hours. When you become an attending, those limits no longer exist. As a young physician, Dr. Sukhera had student debt to pay off and a family to support. When he found opportunities to earn more by working more, his answer was always “yes.”

Pressure to produce medical research also can pose issues. Some physicians can become addicted to publishing studies, fearing that they might lose their professional status or position if they stop. It’s a cycle that can force a doctor to not only work long hours doing their job but also practically take on a second one.
 

 

 

How Physicians Can Recognize Work Addiction in Themselves

Work addiction can look and feel different for every person, said Malissa Clark, PhD, associate professor at the University of Georgia and author of the recent book Never Not Working: Why the Always-On Culture Is Bad for Business—and How to Fix It.

Dr. Clark noted that people who are highly engaged in their work tend to be driven by intrinsic motivation: “You work because you love it.” With work addiction, “you work because you feel like you ought to be working all the time.”

Of course, it’s not always so cut and dried; you can experience both forms of motivation and not necessarily become addicted to work. But if you are solely driven by the feeling that you ought to be working all the time, that can be a red flag.

Dr. Griffiths said that while many people may have problematic work habits or work too much, true work addicts must meet six criteria that apply to all addictions:

1. Salience: Work is the single most important thing in your life, to the point of neglecting everything else. Even if you’re on vacation, your mind might be flooded with work thoughts.

2. Mood modification: You use work to modify your mood, either to get a “high” or to cope with stress.

3. Tolerance: Over time, you’ve gone from working 8 or 10 hours a day to 12 hours a day, to a point where you’re working all the time.

4. Withdrawal: On a physiological level, you will have symptoms such as anxiety, nausea, or headaches when unable to work.

5. Conflict: You feel conflicted with yourself (you know you’re working too much) or with others (partners, friends, and children) about work, but you can’t stop.

6. Relapse: If you manage to cut down your hours but can’t resist overworking 1 day, you wind up right back where you were.
 

When It’s Time to Address Work Addiction

The lack of a formal diagnosis for work addiction makes getting treatment difficult. But there are ways to seek help. Unlike the drug and alcohol literature, abstinence is not the goal. “The therapeutic goal is getting a behavior under control and looking for the triggers of why you’re compulsively working,” said Dr. Griffiths.

Practice self-compassion

Dr. Sukhera eventually realized that his work addiction stemmed from the fear of being somehow excluded or unworthy. He actively corrected much of this through self-compassion and self-kindness, which helped him set boundaries. “Self-compassion is the root of everything,” he said. “Reminding ourselves that we’re doing our best is an important ingredient in breaking the cycle.”

Slowly expose yourself to relaxation

Many workaholics find rest very difficult. “When I conducted interviews with people [who considered themselves workaholics], a very common thing I heard was, ‘I have a very hard time being idle,’ ” said Dr. Clark. If rest feels hard, Dr. Sukhera suggests practicing relaxation for 2 minutes to start. Even small periods of downtime can challenge the belief that you must be constantly productive.

Reframe your to-do list 

For work addicts, to-do lists can seem like they must be finished, which prolongs work hours. Instead, use to-do lists to help prioritize what is urgent, identify what can wait, and delegate out tasks to others, Dr. Clark recommends.

Pick up a mastery experience

Research from professor Sabine Sonnentag, Dr. rer. nat., at the University of Mannheim, Mannheim, Germany, suggests that mastery experiences — leisure activities that require thought and focus like learning a new language or taking a woodworking class — can help you actively disengage from work.

Try cognitive behavioral therapy

Widely used for other forms of addiction, cognitive behavioral therapy centers around recognizing emotions, challenging thought patterns, and changing behaviors. However, Dr. Clark admits the research on its impact on work addiction, in particular, is “pretty nascent.”

Shift your mindset

It seems logical to think that detaching from your feelings will allow you to “do more,” but experts say that idea is both untrue and dangerous. “The safest hospitals are the hospitals where people are attuned to their humanness,” said Dr. Sukhera. “It’s normal to overwork in medicine, and if you’re challenging a norm, you really have to be thoughtful about how you frame that for yourself.”

Most importantly: Seek support

Today, there is increased awareness about work addiction and more resources for physicians who are struggling, including programs such as Workaholics Anonymous or Physicians Anonymous and workplace wellness initiatives. But try not to overwhelm yourself with choosing whom to talk to or what specific resource to utilize, Dr. Sukhera advised. “Just talk to someone about it. You don’t have to carry this on your own.”
 

A version of this article appeared on Medscape.com.

When child psychiatrist Javeed Sukhera, MD, PhD, was a few years into his career, he found himself doing it all. “I was in a leadership role academically at the medical school, I had a leadership role at the hospital, and I was seeing as many patients as I could. I could work all day every day.”

“It still wouldn’t have been enough,” he said.

Whenever there was a shift available, Dr. Sukhera would take it. His job was stressful, but as a new physician with a young family, he saw this obsession with work as necessary. “I began to cope with the stress from work by doing extra work and feeling like I needed to be everywhere. It was like I became a hamster on a spinning wheel. I was just running, running, running.”

Things shifted for Dr. Sukhera when he realized that while he was emotionally available for the children who were his patients, at home, his own children weren’t getting the best of him. “There was a specific moment when I thought my son was afraid of me,” he said. “I just stopped and realized that there was something happening that I needed to break. I needed to make a change.”

Dr. Sukhera, now chair of psychiatry at the Institute of Living and chief of the Department of Psychiatry at Hartford Hospital, Hartford, Connecticut, believes what he experienced was a steep fall into work addiction. “Workaholism,” often dismissed as simply working hard, is a nonclinical addiction that could fall under the umbrella of a behavioral addiction, and healthcare professionals may be especially at risk.
 

What Does Work Addiction Look Like for Doctors?

Behavioral addictions are fairly new in the addiction space. When gambling disorder, the first and only behavioral addiction in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, was added in 2013, it was seen as a “breakthrough addiction,” said Mark D. Griffiths, PhD, a leading behavioral addiction researcher and a distinguished professor at Nottingham Trent University.

Because there is not enough evidence yet to classify work addiction as a formal diagnosis, there is no clear consensus on how to define it. To further complicate things, the terms “workaholism” and “work addiction” can be used interchangeably, and some experts say the two are not the same, though they can overlap.

That said, a 2018 review of literature from several countries found that work addiction “fits very well into recently postulated criteria for conceptualization of a behavioral addiction.

“If you accept that gambling can be genuinely addictive, then there’s no reason to think that something like work, exercise, or video game playing couldn’t be an addiction as well,” said Dr. Griffiths.

“The neurobiology of addiction is that we get drawn to something that gives us a dopamine hit,” Dr. Sukhera added. “But to do that all day, every day, has consequences. It drains our emotional reserves, and it can greatly impact our relationships.”

On top of that, work addiction has been linked with poor sleep, poor cardiovascular health, high blood pressure, burnout, the development of autoimmune disorders, and other health issues.

Physicians are particularly susceptible. Doctors, after all, are expected to work long hours and put their patients’ needs first, even at the expense of their own health and well-being.

“Workaholism is not just socially acceptable in medicine,” said Dr. Sukhera. “It’s baked into the system and built into the structures. The healthcare system has largely functioned on the emotional labor of health workers, whose tendency to show up and work harder can, at times, in certain organizations, be exploited.”

Dr. Griffiths agreed that with the limited amount of data available, work addiction does appear to exist at higher rates in medicine than in other fields. As early as the 1970s, medical literature describes work as a “socially acceptable” addiction among doctors. A 2014 study published in Occupational Medicine reported that of 445 physicians who took part in the research, nearly half exhibited some level of work addiction with 13% “highly work addicted.”

Of course, working hard or even meeting unreasonable demands from work is not the same as work addiction, as Dr. Griffiths clarified in a 2023 editorial in BMJ Quality & Safety. The difference, as with other behavioral addictions, is when people obsess about work and use it to cope with stress. It can be easier to stay distracted and busy to gain a sense of control rather than learning to deal with complex emotions.

2021 study that Dr. Sukhera conducted with resident physicians found that working harder was one of the main ways they dealt with stress during the COVID-19 pandemic. “This idea that we deal with the stress of being burnt out by doing more and more of what burns us out is fairly ubiquitous at all stages of medical professionals’ careers,” he said.

Financial incentives also can fuel work addiction, said Dr. Sukhera. In residency, there are some safeguards around overwork and duty hours. When you become an attending, those limits no longer exist. As a young physician, Dr. Sukhera had student debt to pay off and a family to support. When he found opportunities to earn more by working more, his answer was always “yes.”

Pressure to produce medical research also can pose issues. Some physicians can become addicted to publishing studies, fearing that they might lose their professional status or position if they stop. It’s a cycle that can force a doctor to not only work long hours doing their job but also practically take on a second one.
 

 

 

How Physicians Can Recognize Work Addiction in Themselves

Work addiction can look and feel different for every person, said Malissa Clark, PhD, associate professor at the University of Georgia and author of the recent book Never Not Working: Why the Always-On Culture Is Bad for Business—and How to Fix It.

Dr. Clark noted that people who are highly engaged in their work tend to be driven by intrinsic motivation: “You work because you love it.” With work addiction, “you work because you feel like you ought to be working all the time.”

Of course, it’s not always so cut and dried; you can experience both forms of motivation and not necessarily become addicted to work. But if you are solely driven by the feeling that you ought to be working all the time, that can be a red flag.

Dr. Griffiths said that while many people may have problematic work habits or work too much, true work addicts must meet six criteria that apply to all addictions:

1. Salience: Work is the single most important thing in your life, to the point of neglecting everything else. Even if you’re on vacation, your mind might be flooded with work thoughts.

2. Mood modification: You use work to modify your mood, either to get a “high” or to cope with stress.

3. Tolerance: Over time, you’ve gone from working 8 or 10 hours a day to 12 hours a day, to a point where you’re working all the time.

4. Withdrawal: On a physiological level, you will have symptoms such as anxiety, nausea, or headaches when unable to work.

5. Conflict: You feel conflicted with yourself (you know you’re working too much) or with others (partners, friends, and children) about work, but you can’t stop.

6. Relapse: If you manage to cut down your hours but can’t resist overworking 1 day, you wind up right back where you were.
 

When It’s Time to Address Work Addiction

The lack of a formal diagnosis for work addiction makes getting treatment difficult. But there are ways to seek help. Unlike the drug and alcohol literature, abstinence is not the goal. “The therapeutic goal is getting a behavior under control and looking for the triggers of why you’re compulsively working,” said Dr. Griffiths.

Practice self-compassion

Dr. Sukhera eventually realized that his work addiction stemmed from the fear of being somehow excluded or unworthy. He actively corrected much of this through self-compassion and self-kindness, which helped him set boundaries. “Self-compassion is the root of everything,” he said. “Reminding ourselves that we’re doing our best is an important ingredient in breaking the cycle.”

Slowly expose yourself to relaxation

Many workaholics find rest very difficult. “When I conducted interviews with people [who considered themselves workaholics], a very common thing I heard was, ‘I have a very hard time being idle,’ ” said Dr. Clark. If rest feels hard, Dr. Sukhera suggests practicing relaxation for 2 minutes to start. Even small periods of downtime can challenge the belief that you must be constantly productive.

Reframe your to-do list 

For work addicts, to-do lists can seem like they must be finished, which prolongs work hours. Instead, use to-do lists to help prioritize what is urgent, identify what can wait, and delegate out tasks to others, Dr. Clark recommends.

Pick up a mastery experience

Research from professor Sabine Sonnentag, Dr. rer. nat., at the University of Mannheim, Mannheim, Germany, suggests that mastery experiences — leisure activities that require thought and focus like learning a new language or taking a woodworking class — can help you actively disengage from work.

Try cognitive behavioral therapy

Widely used for other forms of addiction, cognitive behavioral therapy centers around recognizing emotions, challenging thought patterns, and changing behaviors. However, Dr. Clark admits the research on its impact on work addiction, in particular, is “pretty nascent.”

Shift your mindset

It seems logical to think that detaching from your feelings will allow you to “do more,” but experts say that idea is both untrue and dangerous. “The safest hospitals are the hospitals where people are attuned to their humanness,” said Dr. Sukhera. “It’s normal to overwork in medicine, and if you’re challenging a norm, you really have to be thoughtful about how you frame that for yourself.”

Most importantly: Seek support

Today, there is increased awareness about work addiction and more resources for physicians who are struggling, including programs such as Workaholics Anonymous or Physicians Anonymous and workplace wellness initiatives. But try not to overwhelm yourself with choosing whom to talk to or what specific resource to utilize, Dr. Sukhera advised. “Just talk to someone about it. You don’t have to carry this on your own.”
 

A version of this article appeared on Medscape.com.

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Could Bedside Training Help End the US Neurologist Shortage?

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Fri, 04/26/2024 - 16:15

 

A medical education initiative for internal medicine residents and medical students that offers instruction on assessing common neurologic conditions boosted trainees’ confidence in caring for neurology patients and could help address the US neurologist shortage, a new report suggested.

Bedside Rounding Alliance for Internal Medicine and Neurology Residents (BRAINs) moves training from the lecture hall to the bedside, offering instruction on obtaining a focused neurologic history and performing a focused neurologic physical exam for common neurologic symptoms.

Almost 100% of trainees surveyed gave the program a favorable rating, citing patient exposure and bedside training from neurology educators as keys to its success.

As internal medicine providers are often “the first to lay eyes” on patients with a neurology complaint, it’s important they “have a basic level of comfort” in addressing patients’ common questions and concerns, study author Prashanth Rajarajan, MD, PhD, a resident in the Department of Neurology at Brigham and Women’s Hospital, Boston, told this news organization.

The findings were presented at the 2024 annual meeting of the American Academy of Neurology.
 

Addressing ‘Neurophobia’

Neurology is often viewed by medical trainees as the most difficult subspecialty, Dr. Rajarajan said. Many have what he calls “neurophobia,” which he defines as “a discomfort with assessing and treating neurologic complaints.”

A survey at his institution showed 62% of internal medicine residents lacked the confidence to diagnose and treat neurologic diseases, he reported.

BRAINs is a structured neurology trainee-led, inpatient bedside teaching session for internal medicine residents, medical students, and others that aims to increase trainees’ confidence in assessing patients with common neurologic symptoms.

The program includes a biweekly 45-minute session. Most of the session is spent at the bedside and involves demonstrations and practice of a focused neurologic history and physical exam.

Participants receive feedback from educators, typically neurology residents or fellows in epilepsy, stroke, or some other neurology subspecialty. It also includes a short discussion on pertinent diagnostics, management, and other topics.

Surveys evaluating the program and teaching skill development were completed by 59 residents and 15 neurology educators who participated in BRAINs between 2022 and 2024.

Over 90% of trainees (54) agreed BRAINs sessions met the program’s objective (5 were neutral); 49 agreed it increased confidence in taking a neuro history (9 were neutral and 1 disagreed); 56 felt it boosted their confidence in doing a neuro exam (3 were neutral); and 56 said BRAINs is more effective than traditional lecture-based didactics (3 were neutral).

All the residents rated the material covered as appropriate for their level of training; 88% considered the 45-minute session length appropriate; and 98% had a favorable impression of the program as a whole.

When asked to identify the most helpful aspect of the program, 82% cited more patient exposure and 81% more bedside teaching.

All educators reported that the sessions were an effective way to practice near-peer teaching skills. Most (87%) felt the experience was more effective at accomplishing learning objectives than preparing and giving traditional didactic lectures, and 80% agreed it also gave them an opportunity to get to know their medical colleagues.
 

 

 

Use It or Lose It

Dr. Rajarajan noted that the program doesn’t require significant planning or extra staff, is not resource-intensive, and can be adapted to different services such as emergency departments and other learner populations.

But time will tell if the newfound confidence of those taking the program actually lasts.

“You have to keep using it,” he said. “You use it or lose it when comes to these skills.”

Commenting on the initiative, Denney Zimmerman, DO, Neurocritical Care Faculty, Blount Memorial Hospital, Maryville, Tennessee, and cochair of the AAN session featuring the study, called the program a good example of one way to counteract “neurophobia” and address the widespread neurologist shortage in the United States.

A 2019 AAN report showed that by 2025, almost every state in the United States will have a mismatch between the number of practicing neurologists and the demand from patients with neurologic conditions. The report offered several ways to address the shortage, including more neurology-focused training for internal medicine doctors during their residency.

“They’re usually on the front line, both in the hospital and in the clinics, and can help expedite patients who need to be seen by neurology sooner rather than later,” Dr. Zimmerman said.

Dr. Zimmerman noted that the study assessed how well participants perceived the program but not whether it improved their skills.

He pointed out that different groups may assess different diseases during their training session. “I think it’s important to ensure you’re hitting all the major topics.”

The study received funding from MGB Centers of Expertise Education Grant. Drs. Rajarajan and Zimmerman reported no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

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A medical education initiative for internal medicine residents and medical students that offers instruction on assessing common neurologic conditions boosted trainees’ confidence in caring for neurology patients and could help address the US neurologist shortage, a new report suggested.

Bedside Rounding Alliance for Internal Medicine and Neurology Residents (BRAINs) moves training from the lecture hall to the bedside, offering instruction on obtaining a focused neurologic history and performing a focused neurologic physical exam for common neurologic symptoms.

Almost 100% of trainees surveyed gave the program a favorable rating, citing patient exposure and bedside training from neurology educators as keys to its success.

As internal medicine providers are often “the first to lay eyes” on patients with a neurology complaint, it’s important they “have a basic level of comfort” in addressing patients’ common questions and concerns, study author Prashanth Rajarajan, MD, PhD, a resident in the Department of Neurology at Brigham and Women’s Hospital, Boston, told this news organization.

The findings were presented at the 2024 annual meeting of the American Academy of Neurology.
 

Addressing ‘Neurophobia’

Neurology is often viewed by medical trainees as the most difficult subspecialty, Dr. Rajarajan said. Many have what he calls “neurophobia,” which he defines as “a discomfort with assessing and treating neurologic complaints.”

A survey at his institution showed 62% of internal medicine residents lacked the confidence to diagnose and treat neurologic diseases, he reported.

BRAINs is a structured neurology trainee-led, inpatient bedside teaching session for internal medicine residents, medical students, and others that aims to increase trainees’ confidence in assessing patients with common neurologic symptoms.

The program includes a biweekly 45-minute session. Most of the session is spent at the bedside and involves demonstrations and practice of a focused neurologic history and physical exam.

Participants receive feedback from educators, typically neurology residents or fellows in epilepsy, stroke, or some other neurology subspecialty. It also includes a short discussion on pertinent diagnostics, management, and other topics.

Surveys evaluating the program and teaching skill development were completed by 59 residents and 15 neurology educators who participated in BRAINs between 2022 and 2024.

Over 90% of trainees (54) agreed BRAINs sessions met the program’s objective (5 were neutral); 49 agreed it increased confidence in taking a neuro history (9 were neutral and 1 disagreed); 56 felt it boosted their confidence in doing a neuro exam (3 were neutral); and 56 said BRAINs is more effective than traditional lecture-based didactics (3 were neutral).

All the residents rated the material covered as appropriate for their level of training; 88% considered the 45-minute session length appropriate; and 98% had a favorable impression of the program as a whole.

When asked to identify the most helpful aspect of the program, 82% cited more patient exposure and 81% more bedside teaching.

All educators reported that the sessions were an effective way to practice near-peer teaching skills. Most (87%) felt the experience was more effective at accomplishing learning objectives than preparing and giving traditional didactic lectures, and 80% agreed it also gave them an opportunity to get to know their medical colleagues.
 

 

 

Use It or Lose It

Dr. Rajarajan noted that the program doesn’t require significant planning or extra staff, is not resource-intensive, and can be adapted to different services such as emergency departments and other learner populations.

But time will tell if the newfound confidence of those taking the program actually lasts.

“You have to keep using it,” he said. “You use it or lose it when comes to these skills.”

Commenting on the initiative, Denney Zimmerman, DO, Neurocritical Care Faculty, Blount Memorial Hospital, Maryville, Tennessee, and cochair of the AAN session featuring the study, called the program a good example of one way to counteract “neurophobia” and address the widespread neurologist shortage in the United States.

A 2019 AAN report showed that by 2025, almost every state in the United States will have a mismatch between the number of practicing neurologists and the demand from patients with neurologic conditions. The report offered several ways to address the shortage, including more neurology-focused training for internal medicine doctors during their residency.

“They’re usually on the front line, both in the hospital and in the clinics, and can help expedite patients who need to be seen by neurology sooner rather than later,” Dr. Zimmerman said.

Dr. Zimmerman noted that the study assessed how well participants perceived the program but not whether it improved their skills.

He pointed out that different groups may assess different diseases during their training session. “I think it’s important to ensure you’re hitting all the major topics.”

The study received funding from MGB Centers of Expertise Education Grant. Drs. Rajarajan and Zimmerman reported no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

 

A medical education initiative for internal medicine residents and medical students that offers instruction on assessing common neurologic conditions boosted trainees’ confidence in caring for neurology patients and could help address the US neurologist shortage, a new report suggested.

Bedside Rounding Alliance for Internal Medicine and Neurology Residents (BRAINs) moves training from the lecture hall to the bedside, offering instruction on obtaining a focused neurologic history and performing a focused neurologic physical exam for common neurologic symptoms.

Almost 100% of trainees surveyed gave the program a favorable rating, citing patient exposure and bedside training from neurology educators as keys to its success.

As internal medicine providers are often “the first to lay eyes” on patients with a neurology complaint, it’s important they “have a basic level of comfort” in addressing patients’ common questions and concerns, study author Prashanth Rajarajan, MD, PhD, a resident in the Department of Neurology at Brigham and Women’s Hospital, Boston, told this news organization.

The findings were presented at the 2024 annual meeting of the American Academy of Neurology.
 

Addressing ‘Neurophobia’

Neurology is often viewed by medical trainees as the most difficult subspecialty, Dr. Rajarajan said. Many have what he calls “neurophobia,” which he defines as “a discomfort with assessing and treating neurologic complaints.”

A survey at his institution showed 62% of internal medicine residents lacked the confidence to diagnose and treat neurologic diseases, he reported.

BRAINs is a structured neurology trainee-led, inpatient bedside teaching session for internal medicine residents, medical students, and others that aims to increase trainees’ confidence in assessing patients with common neurologic symptoms.

The program includes a biweekly 45-minute session. Most of the session is spent at the bedside and involves demonstrations and practice of a focused neurologic history and physical exam.

Participants receive feedback from educators, typically neurology residents or fellows in epilepsy, stroke, or some other neurology subspecialty. It also includes a short discussion on pertinent diagnostics, management, and other topics.

Surveys evaluating the program and teaching skill development were completed by 59 residents and 15 neurology educators who participated in BRAINs between 2022 and 2024.

Over 90% of trainees (54) agreed BRAINs sessions met the program’s objective (5 were neutral); 49 agreed it increased confidence in taking a neuro history (9 were neutral and 1 disagreed); 56 felt it boosted their confidence in doing a neuro exam (3 were neutral); and 56 said BRAINs is more effective than traditional lecture-based didactics (3 were neutral).

All the residents rated the material covered as appropriate for their level of training; 88% considered the 45-minute session length appropriate; and 98% had a favorable impression of the program as a whole.

When asked to identify the most helpful aspect of the program, 82% cited more patient exposure and 81% more bedside teaching.

All educators reported that the sessions were an effective way to practice near-peer teaching skills. Most (87%) felt the experience was more effective at accomplishing learning objectives than preparing and giving traditional didactic lectures, and 80% agreed it also gave them an opportunity to get to know their medical colleagues.
 

 

 

Use It or Lose It

Dr. Rajarajan noted that the program doesn’t require significant planning or extra staff, is not resource-intensive, and can be adapted to different services such as emergency departments and other learner populations.

But time will tell if the newfound confidence of those taking the program actually lasts.

“You have to keep using it,” he said. “You use it or lose it when comes to these skills.”

Commenting on the initiative, Denney Zimmerman, DO, Neurocritical Care Faculty, Blount Memorial Hospital, Maryville, Tennessee, and cochair of the AAN session featuring the study, called the program a good example of one way to counteract “neurophobia” and address the widespread neurologist shortage in the United States.

A 2019 AAN report showed that by 2025, almost every state in the United States will have a mismatch between the number of practicing neurologists and the demand from patients with neurologic conditions. The report offered several ways to address the shortage, including more neurology-focused training for internal medicine doctors during their residency.

“They’re usually on the front line, both in the hospital and in the clinics, and can help expedite patients who need to be seen by neurology sooner rather than later,” Dr. Zimmerman said.

Dr. Zimmerman noted that the study assessed how well participants perceived the program but not whether it improved their skills.

He pointed out that different groups may assess different diseases during their training session. “I think it’s important to ensure you’re hitting all the major topics.”

The study received funding from MGB Centers of Expertise Education Grant. Drs. Rajarajan and Zimmerman reported no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

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Few Cancer Survivors Meet ACS Nutrition, Exercise Guidelines

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Mon, 04/29/2024 - 17:35

 

TOPLINE:

A recent survey-based study found that only 4% of cancer survivors reported adhering to all four American Cancer Society (ACS) nutrition and physical activity guidelines, which include maintaining a healthy weight and diet, avoiding alcohol, and exercising regularly.

METHODOLOGY:

  • The ACS has published nutrition and exercise guidelines for cancer survivors, which include recommendations to maintain a healthy weight and diet, cut out alcohol, and participate in regular physical activities. Engaging in these behaviors is associated with longer survival among cancer survivors, but whether survivors follow these nutrition and activity recommendations has not been systematically tracked.
  • Researchers evaluated data on 10,020 individuals (mean age, 64.2 years) who had completed cancer treatment. Data came from the Behavioral Risk Factor Surveillance System telephone-based survey administered in 2017, 2019, and 2021, which represents 2.7 million cancer survivors.
  • The researchers estimated survivors’ adherence to guidelines across four domains: Weight, physical activity, fruit and vegetable consumption, and alcohol intake. Factors associated with adherence were also evaluated.
  • Overall, 9,121 survivors (91%) completed questionnaires for all four domains.

TAKEAWAY:

Only 4% of patients (365 of 9121) followed ACS guidelines in all four categories.

When assessing adherence to each category, the researchers found that 72% of cancer survivors reported engaging in recommended levels of physical activity, 68% maintained a nonobese weight, 50% said they did not consume alcohol, and 12% said they consumed recommended quantities of fruits and vegetables.

Compared with people in the general population, cancer survivors generally engaged in fewer healthy behaviors than those who had never been diagnosed with cancer.

The authors identified certain factors associated with greater guideline adherence, including female sex, older age, Black (vs White) race, and higher education level (college graduate).

IN PRACTICE:

This study highlights a potential “gap between published guidelines regarding behavioral modifications for cancer survivors and uptake of these behaviors,” the authors wrote, adding that “it is essential for oncologists and general internists to improve widespread and systematic counseling on these guidelines to improve uptake of healthy behaviors in this vulnerable patient population.”

SOURCE:

This work, led by Carter Baughman, MD, from the Division of Internal Medicine at Beth Israel Deaconess Medical Center, Boston, Massachusetts, was published online in JAMA Oncology.

LIMITATIONS:

The authors reported several study limitations, most notably that self-reported data may introduce biases.

DISCLOSURES:

The study funding source was not reported. One author received grants from the US Highbush Blueberry Council outside the submitted work. No other disclosures were reported.

A version of this article appeared on Medscape.com.

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TOPLINE:

A recent survey-based study found that only 4% of cancer survivors reported adhering to all four American Cancer Society (ACS) nutrition and physical activity guidelines, which include maintaining a healthy weight and diet, avoiding alcohol, and exercising regularly.

METHODOLOGY:

  • The ACS has published nutrition and exercise guidelines for cancer survivors, which include recommendations to maintain a healthy weight and diet, cut out alcohol, and participate in regular physical activities. Engaging in these behaviors is associated with longer survival among cancer survivors, but whether survivors follow these nutrition and activity recommendations has not been systematically tracked.
  • Researchers evaluated data on 10,020 individuals (mean age, 64.2 years) who had completed cancer treatment. Data came from the Behavioral Risk Factor Surveillance System telephone-based survey administered in 2017, 2019, and 2021, which represents 2.7 million cancer survivors.
  • The researchers estimated survivors’ adherence to guidelines across four domains: Weight, physical activity, fruit and vegetable consumption, and alcohol intake. Factors associated with adherence were also evaluated.
  • Overall, 9,121 survivors (91%) completed questionnaires for all four domains.

TAKEAWAY:

Only 4% of patients (365 of 9121) followed ACS guidelines in all four categories.

When assessing adherence to each category, the researchers found that 72% of cancer survivors reported engaging in recommended levels of physical activity, 68% maintained a nonobese weight, 50% said they did not consume alcohol, and 12% said they consumed recommended quantities of fruits and vegetables.

Compared with people in the general population, cancer survivors generally engaged in fewer healthy behaviors than those who had never been diagnosed with cancer.

The authors identified certain factors associated with greater guideline adherence, including female sex, older age, Black (vs White) race, and higher education level (college graduate).

IN PRACTICE:

This study highlights a potential “gap between published guidelines regarding behavioral modifications for cancer survivors and uptake of these behaviors,” the authors wrote, adding that “it is essential for oncologists and general internists to improve widespread and systematic counseling on these guidelines to improve uptake of healthy behaviors in this vulnerable patient population.”

SOURCE:

This work, led by Carter Baughman, MD, from the Division of Internal Medicine at Beth Israel Deaconess Medical Center, Boston, Massachusetts, was published online in JAMA Oncology.

LIMITATIONS:

The authors reported several study limitations, most notably that self-reported data may introduce biases.

DISCLOSURES:

The study funding source was not reported. One author received grants from the US Highbush Blueberry Council outside the submitted work. No other disclosures were reported.

A version of this article appeared on Medscape.com.

 

TOPLINE:

A recent survey-based study found that only 4% of cancer survivors reported adhering to all four American Cancer Society (ACS) nutrition and physical activity guidelines, which include maintaining a healthy weight and diet, avoiding alcohol, and exercising regularly.

METHODOLOGY:

  • The ACS has published nutrition and exercise guidelines for cancer survivors, which include recommendations to maintain a healthy weight and diet, cut out alcohol, and participate in regular physical activities. Engaging in these behaviors is associated with longer survival among cancer survivors, but whether survivors follow these nutrition and activity recommendations has not been systematically tracked.
  • Researchers evaluated data on 10,020 individuals (mean age, 64.2 years) who had completed cancer treatment. Data came from the Behavioral Risk Factor Surveillance System telephone-based survey administered in 2017, 2019, and 2021, which represents 2.7 million cancer survivors.
  • The researchers estimated survivors’ adherence to guidelines across four domains: Weight, physical activity, fruit and vegetable consumption, and alcohol intake. Factors associated with adherence were also evaluated.
  • Overall, 9,121 survivors (91%) completed questionnaires for all four domains.

TAKEAWAY:

Only 4% of patients (365 of 9121) followed ACS guidelines in all four categories.

When assessing adherence to each category, the researchers found that 72% of cancer survivors reported engaging in recommended levels of physical activity, 68% maintained a nonobese weight, 50% said they did not consume alcohol, and 12% said they consumed recommended quantities of fruits and vegetables.

Compared with people in the general population, cancer survivors generally engaged in fewer healthy behaviors than those who had never been diagnosed with cancer.

The authors identified certain factors associated with greater guideline adherence, including female sex, older age, Black (vs White) race, and higher education level (college graduate).

IN PRACTICE:

This study highlights a potential “gap between published guidelines regarding behavioral modifications for cancer survivors and uptake of these behaviors,” the authors wrote, adding that “it is essential for oncologists and general internists to improve widespread and systematic counseling on these guidelines to improve uptake of healthy behaviors in this vulnerable patient population.”

SOURCE:

This work, led by Carter Baughman, MD, from the Division of Internal Medicine at Beth Israel Deaconess Medical Center, Boston, Massachusetts, was published online in JAMA Oncology.

LIMITATIONS:

The authors reported several study limitations, most notably that self-reported data may introduce biases.

DISCLOSURES:

The study funding source was not reported. One author received grants from the US Highbush Blueberry Council outside the submitted work. No other disclosures were reported.

A version of this article appeared on Medscape.com.

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Oregon Physician Assistants Get Name Change

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Mon, 04/29/2024 - 17:36

 

On April 4, Oregon’s Governor Tina Kotek signed a bill into law that officially changed the title of “physician assistants” to “physician associates” in the state. The switch is the first of its kind in the United States and comes on the heels of a decision from 2021 by the American Academy of Physician Associates (AAPA) to change the meaning of “PA” to “physician associate” from “physician assistant.”

In the Medscape Physician Assistant Career Satisfaction Report 2023, a diverse range of opinions on the title switch was reflected. Only 40% of PAs favored the name change at the time, 45% neither opposed nor favored it, and 15% opposed the name change, reflecting the complexity of the issue.

According to the AAPA, the change came about to better reflect the work PAs do in not just “assisting” physicians but in working independently with patients. Some also felt that the word “assistant” implies dependence. However, despite associate’s more accurate reflection of the job, PAs mostly remain split on whether they want the new moniker.

Many say that the name change will be confusing for the public and their patients, while others say that physician assistant was already not well understood, as patients often thought of the profession as a doctor’s helper or an assistant, like a medical assistant.

Yet many long-time PAs say that they prefer the title they’ve always had and that explaining to patients the new associate title will be equally confusing. Some mentioned patients may think they’re a business associate of the physician.

Oregon PAs won’t immediately switch to the new name. The new law takes effect on June 6, 2024. The Oregon Medical Board will establish regulations and guidance before PAs adopt the new name in their practices.

The law only changes the name of PAs in Oregon, not in other states. In fact, prematurely using the title of physician associate could subject a PA to regulatory challenges or disciplinary actions.

A version of this article appeared on Medscape.com.

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On April 4, Oregon’s Governor Tina Kotek signed a bill into law that officially changed the title of “physician assistants” to “physician associates” in the state. The switch is the first of its kind in the United States and comes on the heels of a decision from 2021 by the American Academy of Physician Associates (AAPA) to change the meaning of “PA” to “physician associate” from “physician assistant.”

In the Medscape Physician Assistant Career Satisfaction Report 2023, a diverse range of opinions on the title switch was reflected. Only 40% of PAs favored the name change at the time, 45% neither opposed nor favored it, and 15% opposed the name change, reflecting the complexity of the issue.

According to the AAPA, the change came about to better reflect the work PAs do in not just “assisting” physicians but in working independently with patients. Some also felt that the word “assistant” implies dependence. However, despite associate’s more accurate reflection of the job, PAs mostly remain split on whether they want the new moniker.

Many say that the name change will be confusing for the public and their patients, while others say that physician assistant was already not well understood, as patients often thought of the profession as a doctor’s helper or an assistant, like a medical assistant.

Yet many long-time PAs say that they prefer the title they’ve always had and that explaining to patients the new associate title will be equally confusing. Some mentioned patients may think they’re a business associate of the physician.

Oregon PAs won’t immediately switch to the new name. The new law takes effect on June 6, 2024. The Oregon Medical Board will establish regulations and guidance before PAs adopt the new name in their practices.

The law only changes the name of PAs in Oregon, not in other states. In fact, prematurely using the title of physician associate could subject a PA to regulatory challenges or disciplinary actions.

A version of this article appeared on Medscape.com.

 

On April 4, Oregon’s Governor Tina Kotek signed a bill into law that officially changed the title of “physician assistants” to “physician associates” in the state. The switch is the first of its kind in the United States and comes on the heels of a decision from 2021 by the American Academy of Physician Associates (AAPA) to change the meaning of “PA” to “physician associate” from “physician assistant.”

In the Medscape Physician Assistant Career Satisfaction Report 2023, a diverse range of opinions on the title switch was reflected. Only 40% of PAs favored the name change at the time, 45% neither opposed nor favored it, and 15% opposed the name change, reflecting the complexity of the issue.

According to the AAPA, the change came about to better reflect the work PAs do in not just “assisting” physicians but in working independently with patients. Some also felt that the word “assistant” implies dependence. However, despite associate’s more accurate reflection of the job, PAs mostly remain split on whether they want the new moniker.

Many say that the name change will be confusing for the public and their patients, while others say that physician assistant was already not well understood, as patients often thought of the profession as a doctor’s helper or an assistant, like a medical assistant.

Yet many long-time PAs say that they prefer the title they’ve always had and that explaining to patients the new associate title will be equally confusing. Some mentioned patients may think they’re a business associate of the physician.

Oregon PAs won’t immediately switch to the new name. The new law takes effect on June 6, 2024. The Oregon Medical Board will establish regulations and guidance before PAs adopt the new name in their practices.

The law only changes the name of PAs in Oregon, not in other states. In fact, prematurely using the title of physician associate could subject a PA to regulatory challenges or disciplinary actions.

A version of this article appeared on Medscape.com.

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Vaccine Safety and DMT for Highly Active Multiple Sclerosis: New Data

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Fri, 04/26/2024 - 11:35

 

Immunization with inactivated vaccines while receiving the natalizumab for highly active multiple sclerosis (MS) is safe and immunogenic, with no increased risk for disease progression, new research shows. 

The study, the first to examine vaccine safety and immunogenicity in highly active MS, revealed high seroprotection rates following receipt of vaccines for COVID-19 and hepatitis A and B, regardless of the duration of treatment with natalizumab.

On the basis of these findings, investigators created an algorithm that clinicians can use to map an immunization schedule in patients who might otherwise delay initiation of disease-modifying therapy until they are fully vaccinated.

“We observed seroprotection rates exceeding 90% for hepatitis A and B, and mRNA COVID-19 vaccines, and all vaccines demonstrated a favorable safety profile, with no exacerbation of disease activity detected,” said lead author René Carvajal, MD, of the Department of Neurology-Neuroimmunology, Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. “This points to potential benefits for patients with highly active MS who require both immunization and high-efficacy therapies that may impact vaccine responses.” 

The study was published online in JAMA Network Open.
 

A Controversial Issue

Today’s high-efficacy therapies for MS may increase the risk of acquiring new infections, reactivate latent pathogens, or worsen ongoing infectious conditions, and immunogenicity of vaccination can be compromised by immunosuppressive agents, particularly CD20 therapies, researchers noted.

As a result, many clinicians opt to delay initiation of such therapies until vaccination schedules are complete to avoid exposure to vaccine-preventable infections. But delaying treatment can potentially affect disease progression. 

Reports of disease worsening following vaccination “have raised controversy around vaccine safety,” the authors wrote. The issue is especially relevant to those with highly active MS due to the scarcity of available data in this population.

The motivation for the study “stemmed from the complex balance clinicians face between initiating highly effective therapies promptly in patients with highly active MS and ensuring adequate protection against preventable infections through vaccination,” Dr. Carvajal said.
 

High Seroprotection Rate

Researchers analyzed data on 60 patients (mean age, 43 years; 44 female; mean disease duration, 17 years) participating in one of two prospectively followed cohorts: The Barcelona Clinically Isolated Syndromes Inception Cohort and the Barcelona Treatment Cohort. Data included demographic, clinical, radiologic, and biological data as well as regular clinical assessments, evaluations of the Expanded Disability Status Scale (EDSS), and MRI scans.

Patients enrolled in the current study had received at least one of these vaccines between September 2016 and February 2022: hepatitis A virus (HAV), hepatitis B virus (HBV; enhanced immunity high load or adjuvanted), or COVID-19 (BNT162b2 [Pfizer-BioNTech], mRAN-1273 [Moderna], or ChAdOx1-S [recombinant; AstraZeneca]).

The researchers conducted a retrospective, self-controlled analysis to compare the annualized relapse rate, EDSS score, and new T2 lesions counts during the 12 months before and after vaccination in patients with short- and long-term treatment duration.

They also compared John Cunningham virus serostatus between the two periods, as well as immunoglobulin G titers for each vaccine.

The global seroprotection rate was 93% (95% CI, 86%-98%). Individual vaccine rates were 92% for HAV, 93% for HBV, and 100% for COVID-19.

There was a significant reduction between the pre- and postvaccination periods in mean relapse rates (P = .004) and median number of new T2 lesions (P  = .01).

There were no changes in EDSS scores before and after vaccinations and duration of natalizumab treatment had no impact on safety and immunogenicity.
 

 

 

‘Viable Option’

The researchers used their findings to create a proposed algorithm to inform immunization decisions in patients with highly active MS who require prompt initiation of high-efficacy disease-modifying therapy.

The algorithm is “integrated into a risk-minimization strategy tailored for patients with highly active MS, emphasizing in this case the pivotal role of natalizumab in averting treatment delays and providing adequate protection against potentially severe infections,” Dr. Carvajal said.

Participants who initiated or continued treatment with natalizumab completed their vaccination regimen without any incidents of progressive multifocal leukoencephalopathy (PML) or disease activity rebound following natalizumab discontinuation.

This suggests that using natalizumab for a brief duration might be a “viable option to contemplate,” the authors noted.

Commenting on the findings, Grace Gombolay, MD, assistant professor of pediatrics in the Division of Pediatric Neurology and director of the Pediatric Neuroimmunology and Multiple Sclerosis Clinic, Emory University, Atlanta, Georgia, said the study “demonstrates that vaccines are safe and do not trigger attacks in patients with MS on natalizumab, and that immunity — as measured by antibodies — is preserved in MS patients who receive natalizumab.”

This “contrasts with other treatments, as decreased antibody responses in COVID-19 are noted in certain treatments,” said Dr. Gombolay, who was not part of the study. “If both disease control and immunity against infection are the goals for the patient, then natalizumab is a reasonable option.” 

“However, this must be balanced with other considerations,” she added, including the risk for PML and pregnancy. 

This study was supported by grants from the European Committee for Treatment and Research in Multiple Sclerosis, Instituto de Salud Carlos III, and the European Union. Dr. Carvajal reported receiving grants from Vall d’Hebron Institut de Recerca and the European Committee for Treatment and Research in Multiple Sclerosis and honoraria from Roche, Novartis, BIIB-Colombia, Merck, and Sanofi outside the submitted work. Dr. Gombolay serves as media editor for Pediatric Neurology and as associate editor of the Annals of the Child Neurology Society. She is also a part-time CDC consultant for acute flaccid myelitis and received an honorarium as a speaker at the Georgia Neurological Society meeting, sponsored by Academic CME and TG Therapeutics.

A version of this article appeared on Medscape.com.

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Immunization with inactivated vaccines while receiving the natalizumab for highly active multiple sclerosis (MS) is safe and immunogenic, with no increased risk for disease progression, new research shows. 

The study, the first to examine vaccine safety and immunogenicity in highly active MS, revealed high seroprotection rates following receipt of vaccines for COVID-19 and hepatitis A and B, regardless of the duration of treatment with natalizumab.

On the basis of these findings, investigators created an algorithm that clinicians can use to map an immunization schedule in patients who might otherwise delay initiation of disease-modifying therapy until they are fully vaccinated.

“We observed seroprotection rates exceeding 90% for hepatitis A and B, and mRNA COVID-19 vaccines, and all vaccines demonstrated a favorable safety profile, with no exacerbation of disease activity detected,” said lead author René Carvajal, MD, of the Department of Neurology-Neuroimmunology, Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. “This points to potential benefits for patients with highly active MS who require both immunization and high-efficacy therapies that may impact vaccine responses.” 

The study was published online in JAMA Network Open.
 

A Controversial Issue

Today’s high-efficacy therapies for MS may increase the risk of acquiring new infections, reactivate latent pathogens, or worsen ongoing infectious conditions, and immunogenicity of vaccination can be compromised by immunosuppressive agents, particularly CD20 therapies, researchers noted.

As a result, many clinicians opt to delay initiation of such therapies until vaccination schedules are complete to avoid exposure to vaccine-preventable infections. But delaying treatment can potentially affect disease progression. 

Reports of disease worsening following vaccination “have raised controversy around vaccine safety,” the authors wrote. The issue is especially relevant to those with highly active MS due to the scarcity of available data in this population.

The motivation for the study “stemmed from the complex balance clinicians face between initiating highly effective therapies promptly in patients with highly active MS and ensuring adequate protection against preventable infections through vaccination,” Dr. Carvajal said.
 

High Seroprotection Rate

Researchers analyzed data on 60 patients (mean age, 43 years; 44 female; mean disease duration, 17 years) participating in one of two prospectively followed cohorts: The Barcelona Clinically Isolated Syndromes Inception Cohort and the Barcelona Treatment Cohort. Data included demographic, clinical, radiologic, and biological data as well as regular clinical assessments, evaluations of the Expanded Disability Status Scale (EDSS), and MRI scans.

Patients enrolled in the current study had received at least one of these vaccines between September 2016 and February 2022: hepatitis A virus (HAV), hepatitis B virus (HBV; enhanced immunity high load or adjuvanted), or COVID-19 (BNT162b2 [Pfizer-BioNTech], mRAN-1273 [Moderna], or ChAdOx1-S [recombinant; AstraZeneca]).

The researchers conducted a retrospective, self-controlled analysis to compare the annualized relapse rate, EDSS score, and new T2 lesions counts during the 12 months before and after vaccination in patients with short- and long-term treatment duration.

They also compared John Cunningham virus serostatus between the two periods, as well as immunoglobulin G titers for each vaccine.

The global seroprotection rate was 93% (95% CI, 86%-98%). Individual vaccine rates were 92% for HAV, 93% for HBV, and 100% for COVID-19.

There was a significant reduction between the pre- and postvaccination periods in mean relapse rates (P = .004) and median number of new T2 lesions (P  = .01).

There were no changes in EDSS scores before and after vaccinations and duration of natalizumab treatment had no impact on safety and immunogenicity.
 

 

 

‘Viable Option’

The researchers used their findings to create a proposed algorithm to inform immunization decisions in patients with highly active MS who require prompt initiation of high-efficacy disease-modifying therapy.

The algorithm is “integrated into a risk-minimization strategy tailored for patients with highly active MS, emphasizing in this case the pivotal role of natalizumab in averting treatment delays and providing adequate protection against potentially severe infections,” Dr. Carvajal said.

Participants who initiated or continued treatment with natalizumab completed their vaccination regimen without any incidents of progressive multifocal leukoencephalopathy (PML) or disease activity rebound following natalizumab discontinuation.

This suggests that using natalizumab for a brief duration might be a “viable option to contemplate,” the authors noted.

Commenting on the findings, Grace Gombolay, MD, assistant professor of pediatrics in the Division of Pediatric Neurology and director of the Pediatric Neuroimmunology and Multiple Sclerosis Clinic, Emory University, Atlanta, Georgia, said the study “demonstrates that vaccines are safe and do not trigger attacks in patients with MS on natalizumab, and that immunity — as measured by antibodies — is preserved in MS patients who receive natalizumab.”

This “contrasts with other treatments, as decreased antibody responses in COVID-19 are noted in certain treatments,” said Dr. Gombolay, who was not part of the study. “If both disease control and immunity against infection are the goals for the patient, then natalizumab is a reasonable option.” 

“However, this must be balanced with other considerations,” she added, including the risk for PML and pregnancy. 

This study was supported by grants from the European Committee for Treatment and Research in Multiple Sclerosis, Instituto de Salud Carlos III, and the European Union. Dr. Carvajal reported receiving grants from Vall d’Hebron Institut de Recerca and the European Committee for Treatment and Research in Multiple Sclerosis and honoraria from Roche, Novartis, BIIB-Colombia, Merck, and Sanofi outside the submitted work. Dr. Gombolay serves as media editor for Pediatric Neurology and as associate editor of the Annals of the Child Neurology Society. She is also a part-time CDC consultant for acute flaccid myelitis and received an honorarium as a speaker at the Georgia Neurological Society meeting, sponsored by Academic CME and TG Therapeutics.

A version of this article appeared on Medscape.com.

 

Immunization with inactivated vaccines while receiving the natalizumab for highly active multiple sclerosis (MS) is safe and immunogenic, with no increased risk for disease progression, new research shows. 

The study, the first to examine vaccine safety and immunogenicity in highly active MS, revealed high seroprotection rates following receipt of vaccines for COVID-19 and hepatitis A and B, regardless of the duration of treatment with natalizumab.

On the basis of these findings, investigators created an algorithm that clinicians can use to map an immunization schedule in patients who might otherwise delay initiation of disease-modifying therapy until they are fully vaccinated.

“We observed seroprotection rates exceeding 90% for hepatitis A and B, and mRNA COVID-19 vaccines, and all vaccines demonstrated a favorable safety profile, with no exacerbation of disease activity detected,” said lead author René Carvajal, MD, of the Department of Neurology-Neuroimmunology, Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. “This points to potential benefits for patients with highly active MS who require both immunization and high-efficacy therapies that may impact vaccine responses.” 

The study was published online in JAMA Network Open.
 

A Controversial Issue

Today’s high-efficacy therapies for MS may increase the risk of acquiring new infections, reactivate latent pathogens, or worsen ongoing infectious conditions, and immunogenicity of vaccination can be compromised by immunosuppressive agents, particularly CD20 therapies, researchers noted.

As a result, many clinicians opt to delay initiation of such therapies until vaccination schedules are complete to avoid exposure to vaccine-preventable infections. But delaying treatment can potentially affect disease progression. 

Reports of disease worsening following vaccination “have raised controversy around vaccine safety,” the authors wrote. The issue is especially relevant to those with highly active MS due to the scarcity of available data in this population.

The motivation for the study “stemmed from the complex balance clinicians face between initiating highly effective therapies promptly in patients with highly active MS and ensuring adequate protection against preventable infections through vaccination,” Dr. Carvajal said.
 

High Seroprotection Rate

Researchers analyzed data on 60 patients (mean age, 43 years; 44 female; mean disease duration, 17 years) participating in one of two prospectively followed cohorts: The Barcelona Clinically Isolated Syndromes Inception Cohort and the Barcelona Treatment Cohort. Data included demographic, clinical, radiologic, and biological data as well as regular clinical assessments, evaluations of the Expanded Disability Status Scale (EDSS), and MRI scans.

Patients enrolled in the current study had received at least one of these vaccines between September 2016 and February 2022: hepatitis A virus (HAV), hepatitis B virus (HBV; enhanced immunity high load or adjuvanted), or COVID-19 (BNT162b2 [Pfizer-BioNTech], mRAN-1273 [Moderna], or ChAdOx1-S [recombinant; AstraZeneca]).

The researchers conducted a retrospective, self-controlled analysis to compare the annualized relapse rate, EDSS score, and new T2 lesions counts during the 12 months before and after vaccination in patients with short- and long-term treatment duration.

They also compared John Cunningham virus serostatus between the two periods, as well as immunoglobulin G titers for each vaccine.

The global seroprotection rate was 93% (95% CI, 86%-98%). Individual vaccine rates were 92% for HAV, 93% for HBV, and 100% for COVID-19.

There was a significant reduction between the pre- and postvaccination periods in mean relapse rates (P = .004) and median number of new T2 lesions (P  = .01).

There were no changes in EDSS scores before and after vaccinations and duration of natalizumab treatment had no impact on safety and immunogenicity.
 

 

 

‘Viable Option’

The researchers used their findings to create a proposed algorithm to inform immunization decisions in patients with highly active MS who require prompt initiation of high-efficacy disease-modifying therapy.

The algorithm is “integrated into a risk-minimization strategy tailored for patients with highly active MS, emphasizing in this case the pivotal role of natalizumab in averting treatment delays and providing adequate protection against potentially severe infections,” Dr. Carvajal said.

Participants who initiated or continued treatment with natalizumab completed their vaccination regimen without any incidents of progressive multifocal leukoencephalopathy (PML) or disease activity rebound following natalizumab discontinuation.

This suggests that using natalizumab for a brief duration might be a “viable option to contemplate,” the authors noted.

Commenting on the findings, Grace Gombolay, MD, assistant professor of pediatrics in the Division of Pediatric Neurology and director of the Pediatric Neuroimmunology and Multiple Sclerosis Clinic, Emory University, Atlanta, Georgia, said the study “demonstrates that vaccines are safe and do not trigger attacks in patients with MS on natalizumab, and that immunity — as measured by antibodies — is preserved in MS patients who receive natalizumab.”

This “contrasts with other treatments, as decreased antibody responses in COVID-19 are noted in certain treatments,” said Dr. Gombolay, who was not part of the study. “If both disease control and immunity against infection are the goals for the patient, then natalizumab is a reasonable option.” 

“However, this must be balanced with other considerations,” she added, including the risk for PML and pregnancy. 

This study was supported by grants from the European Committee for Treatment and Research in Multiple Sclerosis, Instituto de Salud Carlos III, and the European Union. Dr. Carvajal reported receiving grants from Vall d’Hebron Institut de Recerca and the European Committee for Treatment and Research in Multiple Sclerosis and honoraria from Roche, Novartis, BIIB-Colombia, Merck, and Sanofi outside the submitted work. Dr. Gombolay serves as media editor for Pediatric Neurology and as associate editor of the Annals of the Child Neurology Society. She is also a part-time CDC consultant for acute flaccid myelitis and received an honorarium as a speaker at the Georgia Neurological Society meeting, sponsored by Academic CME and TG Therapeutics.

A version of this article appeared on Medscape.com.

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A Welcome Trade-off

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Thu, 04/25/2024 - 15:32

 

At the end of March, in an anniversary no one but I noticed, I passed 4 years since I’d last rounded at the hospital.

It’s hard to comprehend that. I was at the hospital regularly for the first 22 years of my career, though admittedly it had dwindled from daily (1998-2011) to 1-2 weekends a month at the end.

Looking back, I still don’t miss it, and have no desire to go back. That’s not to say I don’t keep up on inpatient neurology, in case circumstances change, but at this point, honestly, I don’t want to. I’ve become accustomed to my non-hospital world, no late-night consults, no weekends spent rounding, no taking separate cars to restaurants or family events in case I get called in.

Dr. Allan M. Block, a neurologist in Scottsdale, Arizona.
Dr. Allan M. Block


There are certainly things I miss about it. As odd as it may seem (and as much as I’d complain about it) I liked the wee hours of the really late night and early morning. It was quieter. Less chasing patients to tests or therapy. Pleasant idle chatter with staff and the few others docs around. Sitting at the computer and trying to think out a case on the fly. There was always junk food lying around.

But at this point in my life I’ll take the quiet of being home and my routine office hours. I know when my office day starts and ends. Aside from the occasional stop at Costco, I won’t be going anywhere else on my way home. I still get the occasional after-hours call, but none that require me to run to the ER.

On Fridays I’m glad the week is over, and don’t dread the 5:00 answering service switchover, or my call partner giving me the patient list.

There’s some revenue lost in the deal, but I’ll still take the trade-off.

It’s not like I ever had some grand plan to leave the hospital — I actually had thought I’d be there, at least occasionally, until retirement. But here I am.

Inpatient medicine these days, for better or worse, is a younger person’s game. Not to say there aren’t docs my age (and older) who still do it. Certainly our experience makes us good at it. But younger docs are closer to residency, which is primarily inpatient, so it’s an easier transition for many.

They probably have more energy, too.
 

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

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At the end of March, in an anniversary no one but I noticed, I passed 4 years since I’d last rounded at the hospital.

It’s hard to comprehend that. I was at the hospital regularly for the first 22 years of my career, though admittedly it had dwindled from daily (1998-2011) to 1-2 weekends a month at the end.

Looking back, I still don’t miss it, and have no desire to go back. That’s not to say I don’t keep up on inpatient neurology, in case circumstances change, but at this point, honestly, I don’t want to. I’ve become accustomed to my non-hospital world, no late-night consults, no weekends spent rounding, no taking separate cars to restaurants or family events in case I get called in.

Dr. Allan M. Block, a neurologist in Scottsdale, Arizona.
Dr. Allan M. Block


There are certainly things I miss about it. As odd as it may seem (and as much as I’d complain about it) I liked the wee hours of the really late night and early morning. It was quieter. Less chasing patients to tests or therapy. Pleasant idle chatter with staff and the few others docs around. Sitting at the computer and trying to think out a case on the fly. There was always junk food lying around.

But at this point in my life I’ll take the quiet of being home and my routine office hours. I know when my office day starts and ends. Aside from the occasional stop at Costco, I won’t be going anywhere else on my way home. I still get the occasional after-hours call, but none that require me to run to the ER.

On Fridays I’m glad the week is over, and don’t dread the 5:00 answering service switchover, or my call partner giving me the patient list.

There’s some revenue lost in the deal, but I’ll still take the trade-off.

It’s not like I ever had some grand plan to leave the hospital — I actually had thought I’d be there, at least occasionally, until retirement. But here I am.

Inpatient medicine these days, for better or worse, is a younger person’s game. Not to say there aren’t docs my age (and older) who still do it. Certainly our experience makes us good at it. But younger docs are closer to residency, which is primarily inpatient, so it’s an easier transition for many.

They probably have more energy, too.
 

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

 

At the end of March, in an anniversary no one but I noticed, I passed 4 years since I’d last rounded at the hospital.

It’s hard to comprehend that. I was at the hospital regularly for the first 22 years of my career, though admittedly it had dwindled from daily (1998-2011) to 1-2 weekends a month at the end.

Looking back, I still don’t miss it, and have no desire to go back. That’s not to say I don’t keep up on inpatient neurology, in case circumstances change, but at this point, honestly, I don’t want to. I’ve become accustomed to my non-hospital world, no late-night consults, no weekends spent rounding, no taking separate cars to restaurants or family events in case I get called in.

Dr. Allan M. Block, a neurologist in Scottsdale, Arizona.
Dr. Allan M. Block


There are certainly things I miss about it. As odd as it may seem (and as much as I’d complain about it) I liked the wee hours of the really late night and early morning. It was quieter. Less chasing patients to tests or therapy. Pleasant idle chatter with staff and the few others docs around. Sitting at the computer and trying to think out a case on the fly. There was always junk food lying around.

But at this point in my life I’ll take the quiet of being home and my routine office hours. I know when my office day starts and ends. Aside from the occasional stop at Costco, I won’t be going anywhere else on my way home. I still get the occasional after-hours call, but none that require me to run to the ER.

On Fridays I’m glad the week is over, and don’t dread the 5:00 answering service switchover, or my call partner giving me the patient list.

There’s some revenue lost in the deal, but I’ll still take the trade-off.

It’s not like I ever had some grand plan to leave the hospital — I actually had thought I’d be there, at least occasionally, until retirement. But here I am.

Inpatient medicine these days, for better or worse, is a younger person’s game. Not to say there aren’t docs my age (and older) who still do it. Certainly our experience makes us good at it. But younger docs are closer to residency, which is primarily inpatient, so it’s an easier transition for many.

They probably have more energy, too.
 

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

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Migraine Drug Reduces Rosacea Flushing, Erythema in Small Study

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Thu, 04/25/2024 - 14:25

 

In a small, nonrandomized controlled trial, the injectable calcitonin gene-related peptide (CGRP) inhibitor erenumab significantly reduced treatment-resistant flushing and erythema associated with rosacea. Skin-related quality-of-life (QOL) measures also improved, albeit modestly.

The study was published in JAMA Dermatology.

National Rosacea Society
Persistent erythema in a patient with rosacea.

“The transient erythema of rosacea is one of the most challenging rosacea symptoms to treat,” Emmy Graber, MD, MBA, who was not involved with the study, said in an interview. “As flushing can adversely impact quality of life in our rosacea patients, it is important to find therapeutic options for our patients. This study is exciting, not only because the treatment was successful for a notable number of patients, but also because it involved a drug with a novel mode of action in rosacea.” Dr. Graber practices in Boston and is an affiliate clinical instructor at Northeastern University, Boston.

Dr. Emmy Graber


Guy F. Webster, MD, PhD, clinical professor of dermatology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, added, “The interesting thing about this study is that it gives us a new target to think about for therapy. But it’s a long way from saying we can use it tomorrow.” He was not involved with the study but was also asked to comment on the findings.
Guy Webster, MD
Dr. Guy F. Webster

 

Spotlight on CGRP

Rosacea’s pathophysiology remains incompletely understood, wrote Nita K.F. Wienholtz, MD, PhD, Department of Dermatology, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Denmark, and coinvestigators. However, they added, mounting evidence suggests a possible role for CGRP. For example, a study published in JAMA Dermatology in 2015 revealed elevated CGRP levels in facial skin biopsies from patients with rosacea.

For the present study, the investigators enrolled 30 adults (including 23 women) with rosacea who experienced at least 15 days of moderate to severe erythema or extreme flushing during a 4-week, treatment-free run-in period. Most participants (87%) had previously failed one or more rosacea treatments because of a lack of efficacy or adverse reactions, and 43% had failed three or more treatments.

Participants received 3-monthly 140-mg doses of erenumab, which is approved by the Food and Drug Administration for migraine prevention. Patients recorded scores on the Patient Self-Assessment (PSA) and item 2 of the Flushing Assessment Tool online daily and made a final follow-up visit 12 weeks after the third dose.

Among the 27 patients who completed the study, the mean number of days with moderate to severe flushing from week 9 to week 12 fell by 6.9 from 23.6 days over 4 weeks at baseline (P < .001). Patients most severely affected by flushing at baseline experienced an 81% decline in days with severe to extreme flushing. Overall, 26% of patients experienced at least 50% reductions in moderate to extreme flushing days. The number of days with moderate to severe erythema as measured by PSA fell by 8.1 (mean) from baseline, and 56% of patients experienced at least 50% reductions in PSA scores. No unexpected safety signals emerged.
 

 

 

Questions Over QOL Data

“Although there were significant decreases in flushing and erythema,” wrote John S. Barbieri, MD, MBA, in an accompanying Editor’s Note, “the present study had relatively modest improvements in quality of life.” He is director of the Advanced Acne Therapeutics Clinic, Brigham and Women’s Hospital, Boston, and associate editor and evidence-based practice editor of JAMA Dermatology.

Brigham and Women&#039;s Hospital
Dr. John Barbieri

Compared with baseline (6.22), mean Dermatology Life Quality Index scores fell 2.08 points and 2.73 points at weeks 8 and 20, respectively (P = .004 and .003). At the same intervals, the mean baseline Rosacea Quality of Life score (48.22) decreased by 2.58 points and 4.14 points, respectively (P = .04 and .02).

No significant changes appeared in gauges of anxiety and depression. These findings, authors wrote, could stem from their decision to omit a follow-up visit at week 12 — where they may have seen mental-health effects which disappeared by week 20 — in response to patients’ logistical concerns.

However, Dr. Webster questioned the value of QOL measurements in rosacea. “Quality-of-life measures are blunt instruments,” he explained, and reducing severe itching or chronic pain improves the lives of affected patients. “But what question are you going to ask to tease out whether being less red-cheeked has made someone’s life easier? It’s not a problem that lends itself to quality-of-life assessments.” Moreover, he said, regulators who increasingly require such measures in clinical trials ignore this point, creating challenges for drug developers and researchers.

Because the study was neither blinded nor controlled, Dr. Webster suggested considering it a tantalizing proof of concept. “If I were putting money into a CGRP inhibitor, I’d want at least a small, placebo-controlled, double-blinded study.”

Study authors and Dr. Barbieri recommended larger randomized studies involving different populations and erenumab doses. For now, Dr. Barbieri wrote, CGRP inhibition represents a promising potential strategy for patients who have rosacea with comorbid migraine or recalcitrant flushing and erythema.

Dr. Wienholtz reported no relevant financial interests. Dr. Barbieri had no related disclosures. Dr. Webster reported no relevant financial interests. Dr. Graber reported no conflicts related to erenumab but consults for other companies with rosacea-related products including Galderma. The study was supported by and conducted in collaboration with Novartis Pharma AG. Additional funding came from the Novo Nordisk Foundation and the Lundbeck Foundation.

A version of this article appeared on Medscape.com.

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In a small, nonrandomized controlled trial, the injectable calcitonin gene-related peptide (CGRP) inhibitor erenumab significantly reduced treatment-resistant flushing and erythema associated with rosacea. Skin-related quality-of-life (QOL) measures also improved, albeit modestly.

The study was published in JAMA Dermatology.

National Rosacea Society
Persistent erythema in a patient with rosacea.

“The transient erythema of rosacea is one of the most challenging rosacea symptoms to treat,” Emmy Graber, MD, MBA, who was not involved with the study, said in an interview. “As flushing can adversely impact quality of life in our rosacea patients, it is important to find therapeutic options for our patients. This study is exciting, not only because the treatment was successful for a notable number of patients, but also because it involved a drug with a novel mode of action in rosacea.” Dr. Graber practices in Boston and is an affiliate clinical instructor at Northeastern University, Boston.

Dr. Emmy Graber


Guy F. Webster, MD, PhD, clinical professor of dermatology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, added, “The interesting thing about this study is that it gives us a new target to think about for therapy. But it’s a long way from saying we can use it tomorrow.” He was not involved with the study but was also asked to comment on the findings.
Guy Webster, MD
Dr. Guy F. Webster

 

Spotlight on CGRP

Rosacea’s pathophysiology remains incompletely understood, wrote Nita K.F. Wienholtz, MD, PhD, Department of Dermatology, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Denmark, and coinvestigators. However, they added, mounting evidence suggests a possible role for CGRP. For example, a study published in JAMA Dermatology in 2015 revealed elevated CGRP levels in facial skin biopsies from patients with rosacea.

For the present study, the investigators enrolled 30 adults (including 23 women) with rosacea who experienced at least 15 days of moderate to severe erythema or extreme flushing during a 4-week, treatment-free run-in period. Most participants (87%) had previously failed one or more rosacea treatments because of a lack of efficacy or adverse reactions, and 43% had failed three or more treatments.

Participants received 3-monthly 140-mg doses of erenumab, which is approved by the Food and Drug Administration for migraine prevention. Patients recorded scores on the Patient Self-Assessment (PSA) and item 2 of the Flushing Assessment Tool online daily and made a final follow-up visit 12 weeks after the third dose.

Among the 27 patients who completed the study, the mean number of days with moderate to severe flushing from week 9 to week 12 fell by 6.9 from 23.6 days over 4 weeks at baseline (P < .001). Patients most severely affected by flushing at baseline experienced an 81% decline in days with severe to extreme flushing. Overall, 26% of patients experienced at least 50% reductions in moderate to extreme flushing days. The number of days with moderate to severe erythema as measured by PSA fell by 8.1 (mean) from baseline, and 56% of patients experienced at least 50% reductions in PSA scores. No unexpected safety signals emerged.
 

 

 

Questions Over QOL Data

“Although there were significant decreases in flushing and erythema,” wrote John S. Barbieri, MD, MBA, in an accompanying Editor’s Note, “the present study had relatively modest improvements in quality of life.” He is director of the Advanced Acne Therapeutics Clinic, Brigham and Women’s Hospital, Boston, and associate editor and evidence-based practice editor of JAMA Dermatology.

Brigham and Women&#039;s Hospital
Dr. John Barbieri

Compared with baseline (6.22), mean Dermatology Life Quality Index scores fell 2.08 points and 2.73 points at weeks 8 and 20, respectively (P = .004 and .003). At the same intervals, the mean baseline Rosacea Quality of Life score (48.22) decreased by 2.58 points and 4.14 points, respectively (P = .04 and .02).

No significant changes appeared in gauges of anxiety and depression. These findings, authors wrote, could stem from their decision to omit a follow-up visit at week 12 — where they may have seen mental-health effects which disappeared by week 20 — in response to patients’ logistical concerns.

However, Dr. Webster questioned the value of QOL measurements in rosacea. “Quality-of-life measures are blunt instruments,” he explained, and reducing severe itching or chronic pain improves the lives of affected patients. “But what question are you going to ask to tease out whether being less red-cheeked has made someone’s life easier? It’s not a problem that lends itself to quality-of-life assessments.” Moreover, he said, regulators who increasingly require such measures in clinical trials ignore this point, creating challenges for drug developers and researchers.

Because the study was neither blinded nor controlled, Dr. Webster suggested considering it a tantalizing proof of concept. “If I were putting money into a CGRP inhibitor, I’d want at least a small, placebo-controlled, double-blinded study.”

Study authors and Dr. Barbieri recommended larger randomized studies involving different populations and erenumab doses. For now, Dr. Barbieri wrote, CGRP inhibition represents a promising potential strategy for patients who have rosacea with comorbid migraine or recalcitrant flushing and erythema.

Dr. Wienholtz reported no relevant financial interests. Dr. Barbieri had no related disclosures. Dr. Webster reported no relevant financial interests. Dr. Graber reported no conflicts related to erenumab but consults for other companies with rosacea-related products including Galderma. The study was supported by and conducted in collaboration with Novartis Pharma AG. Additional funding came from the Novo Nordisk Foundation and the Lundbeck Foundation.

A version of this article appeared on Medscape.com.

 

In a small, nonrandomized controlled trial, the injectable calcitonin gene-related peptide (CGRP) inhibitor erenumab significantly reduced treatment-resistant flushing and erythema associated with rosacea. Skin-related quality-of-life (QOL) measures also improved, albeit modestly.

The study was published in JAMA Dermatology.

National Rosacea Society
Persistent erythema in a patient with rosacea.

“The transient erythema of rosacea is one of the most challenging rosacea symptoms to treat,” Emmy Graber, MD, MBA, who was not involved with the study, said in an interview. “As flushing can adversely impact quality of life in our rosacea patients, it is important to find therapeutic options for our patients. This study is exciting, not only because the treatment was successful for a notable number of patients, but also because it involved a drug with a novel mode of action in rosacea.” Dr. Graber practices in Boston and is an affiliate clinical instructor at Northeastern University, Boston.

Dr. Emmy Graber


Guy F. Webster, MD, PhD, clinical professor of dermatology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, added, “The interesting thing about this study is that it gives us a new target to think about for therapy. But it’s a long way from saying we can use it tomorrow.” He was not involved with the study but was also asked to comment on the findings.
Guy Webster, MD
Dr. Guy F. Webster

 

Spotlight on CGRP

Rosacea’s pathophysiology remains incompletely understood, wrote Nita K.F. Wienholtz, MD, PhD, Department of Dermatology, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Denmark, and coinvestigators. However, they added, mounting evidence suggests a possible role for CGRP. For example, a study published in JAMA Dermatology in 2015 revealed elevated CGRP levels in facial skin biopsies from patients with rosacea.

For the present study, the investigators enrolled 30 adults (including 23 women) with rosacea who experienced at least 15 days of moderate to severe erythema or extreme flushing during a 4-week, treatment-free run-in period. Most participants (87%) had previously failed one or more rosacea treatments because of a lack of efficacy or adverse reactions, and 43% had failed three or more treatments.

Participants received 3-monthly 140-mg doses of erenumab, which is approved by the Food and Drug Administration for migraine prevention. Patients recorded scores on the Patient Self-Assessment (PSA) and item 2 of the Flushing Assessment Tool online daily and made a final follow-up visit 12 weeks after the third dose.

Among the 27 patients who completed the study, the mean number of days with moderate to severe flushing from week 9 to week 12 fell by 6.9 from 23.6 days over 4 weeks at baseline (P < .001). Patients most severely affected by flushing at baseline experienced an 81% decline in days with severe to extreme flushing. Overall, 26% of patients experienced at least 50% reductions in moderate to extreme flushing days. The number of days with moderate to severe erythema as measured by PSA fell by 8.1 (mean) from baseline, and 56% of patients experienced at least 50% reductions in PSA scores. No unexpected safety signals emerged.
 

 

 

Questions Over QOL Data

“Although there were significant decreases in flushing and erythema,” wrote John S. Barbieri, MD, MBA, in an accompanying Editor’s Note, “the present study had relatively modest improvements in quality of life.” He is director of the Advanced Acne Therapeutics Clinic, Brigham and Women’s Hospital, Boston, and associate editor and evidence-based practice editor of JAMA Dermatology.

Brigham and Women&#039;s Hospital
Dr. John Barbieri

Compared with baseline (6.22), mean Dermatology Life Quality Index scores fell 2.08 points and 2.73 points at weeks 8 and 20, respectively (P = .004 and .003). At the same intervals, the mean baseline Rosacea Quality of Life score (48.22) decreased by 2.58 points and 4.14 points, respectively (P = .04 and .02).

No significant changes appeared in gauges of anxiety and depression. These findings, authors wrote, could stem from their decision to omit a follow-up visit at week 12 — where they may have seen mental-health effects which disappeared by week 20 — in response to patients’ logistical concerns.

However, Dr. Webster questioned the value of QOL measurements in rosacea. “Quality-of-life measures are blunt instruments,” he explained, and reducing severe itching or chronic pain improves the lives of affected patients. “But what question are you going to ask to tease out whether being less red-cheeked has made someone’s life easier? It’s not a problem that lends itself to quality-of-life assessments.” Moreover, he said, regulators who increasingly require such measures in clinical trials ignore this point, creating challenges for drug developers and researchers.

Because the study was neither blinded nor controlled, Dr. Webster suggested considering it a tantalizing proof of concept. “If I were putting money into a CGRP inhibitor, I’d want at least a small, placebo-controlled, double-blinded study.”

Study authors and Dr. Barbieri recommended larger randomized studies involving different populations and erenumab doses. For now, Dr. Barbieri wrote, CGRP inhibition represents a promising potential strategy for patients who have rosacea with comorbid migraine or recalcitrant flushing and erythema.

Dr. Wienholtz reported no relevant financial interests. Dr. Barbieri had no related disclosures. Dr. Webster reported no relevant financial interests. Dr. Graber reported no conflicts related to erenumab but consults for other companies with rosacea-related products including Galderma. The study was supported by and conducted in collaboration with Novartis Pharma AG. Additional funding came from the Novo Nordisk Foundation and the Lundbeck Foundation.

A version of this article appeared on Medscape.com.

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Teleneurology for Suspected Stroke Speeds Treatment

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Wed, 04/24/2024 - 15:14

 

Alerting neurologists via telemedicine that a patient with suspected acute stroke is en route to the hospital significantly enhances the speed at which thrombolysis is administered and increases the number of patients who receive timelier, potentially lifesaving treatment, new research showed.

“This preliminary evidence supports adopting teleneurology prenotification as a best practice within health systems that have telestroke capabilities,” said study investigator Mark McDonald, MD, a neurologist at TeleSpecialists, Fort Myers, Florida.

The findings were presented at the 2024 annual meeting of the American Academy of Neurology.
 

Best Practices

The impact of emergency medical services prenotification, which refers to paramedics alerting receiving hospital emergency departments (EDs) of a suspected stroke on the way for appropriate preparations to be made, is well-defined, said Dr. McDonald.

“What we’re proposing as a best practice is not only should the ED or ED provider be aware, but there needs to be a system in place for standardizing communication to the neurology team so they’re aware, too.”

Prenotification allows a neurologist to “get on the screen to begin coordinating with the ED team to adequately prepare for the possibility of thrombolytic treatment,” he added.

Currently, teleneurology prenotification, he said, is variable and its benefits unclear.

Dr. McDonald said “his organization, TeleSpecialists, maintains a large detailed medical records database for emergency-related, teleneurology, and other cases. For stroke, it recommends 15 best practices” for facilities including prenotification of teleneurology.

Other best practices include evaluating and administering thrombolysis in the CT imaging suite, a preassembled stroke kit that includes antihypertensives and thrombolytic agents, ensuring a weigh bed is available to determine the exact dose of thrombolysis treatment, and implementing “mock” stroke alerts, said Dr. McDonald.

From the database, researchers extracted acute telestroke consultations seen in the ED in 103 facilities in 15 states. Facilities that did not adhere to the 14 best practices other than teleneurologist prenotification were excluded from the analysis.

Of 9290 patients included in the study, 731 were treated with thrombolysis at prenotification facilities (median age, 69 years; median National Institutes of Health Stroke Score [NIHSS], 8) and 31 were treated at facilities without prenotification (median age, 63 years; median NIHSS score, 4). The thrombolytic treatment rate was 8.5% at prenotification facilities versus 4.8% at facilities without prenotification — a difference that was statistically significant.

Prenotification facilities had a significantly shorter median door-to-needle (DTN) time than those without such a process at 35 versus 43 minutes. In addition, there was a statistically significant difference in the percentage of patients with times less than 60 minutes at approximately 88% at prenotification facilities versus about 68% at the facilities without prenotification.
 

Case-Level Analysis

However, just because a facility adheres to teleneurology prenotification as a whole, doesn’t mean it occurs in every case. Researchers explored the impact of teleneurology prenotification at the case level rather than the facility level.

“That gave us a bit more insight into the real impact because it’s not just being at a facility with the best practice; it’s actually working case by case to see whether it happened or not and that’s where we get the most compelling findings,” said Dr. McDonald.

Of 761 treatment cases, there was prenotification to the neurology team in 401 cases. In 360 cases, prenotification did not occur.

The median DTN time was 29 minutes in the group with actual prenotification vs 41.5 minutes in the group without actual prenotification, a difference that was statistically significant, Dr. McDonald said.

As for treatment within 30 minutes of arrival, 50.4% of patients in the teleneurology prenotification group versus 18.9% in the no prenotification group — a statistically significant difference.

DTN time of less than 30 minutes is increasingly used as a target. “Being treated within this time frame improves outcomes and reduces length of hospital stay,” said Dr. McDonald.

The prenotification group also had a statistically significant higher percentage of treatment within 60 minutes of hospital arrival (93.5% vs 80%).

These new findings should help convince health and telestroke systems that teleneurology prenotification is worth implementing. “We want to achieve consensus on this as a best practice,” said Dr. McDonald.

Prenotification, he added, “coordinates the process and eliminates unnecessary and time-consuming steps.”

Dr. McDonald plans to prospectively study prenotification by collecting data on a facility before and after implementing a prenotification process.
 

 

 

Compelling Evidence

Commenting on the research, David L. Tirschwell, MD, Harborview Medical Center, Department of Neurology, Seattle, who cochaired the AAN session featuring the research, said the study provides compelling evidence that teleneurologist prenotification improves DTN time.

“Prenotifications are often standard of care in many healthcare settings and should likely be considered a best practice. When possible, extending such prenotification to a teleconsultant would make sense, and these preliminary data support that approach.”

However, more details are needed “to consider whether the intervention is possibly generalizable to other telestroke practices across the United States,” said Dr. Tirschwell.

Dr. McDonald reported receiving personal compensation for serving as a consultant for Syntrillo Inc. and has stock in Syntrillo Inc. Dr. Tirschwell reported no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

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Alerting neurologists via telemedicine that a patient with suspected acute stroke is en route to the hospital significantly enhances the speed at which thrombolysis is administered and increases the number of patients who receive timelier, potentially lifesaving treatment, new research showed.

“This preliminary evidence supports adopting teleneurology prenotification as a best practice within health systems that have telestroke capabilities,” said study investigator Mark McDonald, MD, a neurologist at TeleSpecialists, Fort Myers, Florida.

The findings were presented at the 2024 annual meeting of the American Academy of Neurology.
 

Best Practices

The impact of emergency medical services prenotification, which refers to paramedics alerting receiving hospital emergency departments (EDs) of a suspected stroke on the way for appropriate preparations to be made, is well-defined, said Dr. McDonald.

“What we’re proposing as a best practice is not only should the ED or ED provider be aware, but there needs to be a system in place for standardizing communication to the neurology team so they’re aware, too.”

Prenotification allows a neurologist to “get on the screen to begin coordinating with the ED team to adequately prepare for the possibility of thrombolytic treatment,” he added.

Currently, teleneurology prenotification, he said, is variable and its benefits unclear.

Dr. McDonald said “his organization, TeleSpecialists, maintains a large detailed medical records database for emergency-related, teleneurology, and other cases. For stroke, it recommends 15 best practices” for facilities including prenotification of teleneurology.

Other best practices include evaluating and administering thrombolysis in the CT imaging suite, a preassembled stroke kit that includes antihypertensives and thrombolytic agents, ensuring a weigh bed is available to determine the exact dose of thrombolysis treatment, and implementing “mock” stroke alerts, said Dr. McDonald.

From the database, researchers extracted acute telestroke consultations seen in the ED in 103 facilities in 15 states. Facilities that did not adhere to the 14 best practices other than teleneurologist prenotification were excluded from the analysis.

Of 9290 patients included in the study, 731 were treated with thrombolysis at prenotification facilities (median age, 69 years; median National Institutes of Health Stroke Score [NIHSS], 8) and 31 were treated at facilities without prenotification (median age, 63 years; median NIHSS score, 4). The thrombolytic treatment rate was 8.5% at prenotification facilities versus 4.8% at facilities without prenotification — a difference that was statistically significant.

Prenotification facilities had a significantly shorter median door-to-needle (DTN) time than those without such a process at 35 versus 43 minutes. In addition, there was a statistically significant difference in the percentage of patients with times less than 60 minutes at approximately 88% at prenotification facilities versus about 68% at the facilities without prenotification.
 

Case-Level Analysis

However, just because a facility adheres to teleneurology prenotification as a whole, doesn’t mean it occurs in every case. Researchers explored the impact of teleneurology prenotification at the case level rather than the facility level.

“That gave us a bit more insight into the real impact because it’s not just being at a facility with the best practice; it’s actually working case by case to see whether it happened or not and that’s where we get the most compelling findings,” said Dr. McDonald.

Of 761 treatment cases, there was prenotification to the neurology team in 401 cases. In 360 cases, prenotification did not occur.

The median DTN time was 29 minutes in the group with actual prenotification vs 41.5 minutes in the group without actual prenotification, a difference that was statistically significant, Dr. McDonald said.

As for treatment within 30 minutes of arrival, 50.4% of patients in the teleneurology prenotification group versus 18.9% in the no prenotification group — a statistically significant difference.

DTN time of less than 30 minutes is increasingly used as a target. “Being treated within this time frame improves outcomes and reduces length of hospital stay,” said Dr. McDonald.

The prenotification group also had a statistically significant higher percentage of treatment within 60 minutes of hospital arrival (93.5% vs 80%).

These new findings should help convince health and telestroke systems that teleneurology prenotification is worth implementing. “We want to achieve consensus on this as a best practice,” said Dr. McDonald.

Prenotification, he added, “coordinates the process and eliminates unnecessary and time-consuming steps.”

Dr. McDonald plans to prospectively study prenotification by collecting data on a facility before and after implementing a prenotification process.
 

 

 

Compelling Evidence

Commenting on the research, David L. Tirschwell, MD, Harborview Medical Center, Department of Neurology, Seattle, who cochaired the AAN session featuring the research, said the study provides compelling evidence that teleneurologist prenotification improves DTN time.

“Prenotifications are often standard of care in many healthcare settings and should likely be considered a best practice. When possible, extending such prenotification to a teleconsultant would make sense, and these preliminary data support that approach.”

However, more details are needed “to consider whether the intervention is possibly generalizable to other telestroke practices across the United States,” said Dr. Tirschwell.

Dr. McDonald reported receiving personal compensation for serving as a consultant for Syntrillo Inc. and has stock in Syntrillo Inc. Dr. Tirschwell reported no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

 

Alerting neurologists via telemedicine that a patient with suspected acute stroke is en route to the hospital significantly enhances the speed at which thrombolysis is administered and increases the number of patients who receive timelier, potentially lifesaving treatment, new research showed.

“This preliminary evidence supports adopting teleneurology prenotification as a best practice within health systems that have telestroke capabilities,” said study investigator Mark McDonald, MD, a neurologist at TeleSpecialists, Fort Myers, Florida.

The findings were presented at the 2024 annual meeting of the American Academy of Neurology.
 

Best Practices

The impact of emergency medical services prenotification, which refers to paramedics alerting receiving hospital emergency departments (EDs) of a suspected stroke on the way for appropriate preparations to be made, is well-defined, said Dr. McDonald.

“What we’re proposing as a best practice is not only should the ED or ED provider be aware, but there needs to be a system in place for standardizing communication to the neurology team so they’re aware, too.”

Prenotification allows a neurologist to “get on the screen to begin coordinating with the ED team to adequately prepare for the possibility of thrombolytic treatment,” he added.

Currently, teleneurology prenotification, he said, is variable and its benefits unclear.

Dr. McDonald said “his organization, TeleSpecialists, maintains a large detailed medical records database for emergency-related, teleneurology, and other cases. For stroke, it recommends 15 best practices” for facilities including prenotification of teleneurology.

Other best practices include evaluating and administering thrombolysis in the CT imaging suite, a preassembled stroke kit that includes antihypertensives and thrombolytic agents, ensuring a weigh bed is available to determine the exact dose of thrombolysis treatment, and implementing “mock” stroke alerts, said Dr. McDonald.

From the database, researchers extracted acute telestroke consultations seen in the ED in 103 facilities in 15 states. Facilities that did not adhere to the 14 best practices other than teleneurologist prenotification were excluded from the analysis.

Of 9290 patients included in the study, 731 were treated with thrombolysis at prenotification facilities (median age, 69 years; median National Institutes of Health Stroke Score [NIHSS], 8) and 31 were treated at facilities without prenotification (median age, 63 years; median NIHSS score, 4). The thrombolytic treatment rate was 8.5% at prenotification facilities versus 4.8% at facilities without prenotification — a difference that was statistically significant.

Prenotification facilities had a significantly shorter median door-to-needle (DTN) time than those without such a process at 35 versus 43 minutes. In addition, there was a statistically significant difference in the percentage of patients with times less than 60 minutes at approximately 88% at prenotification facilities versus about 68% at the facilities without prenotification.
 

Case-Level Analysis

However, just because a facility adheres to teleneurology prenotification as a whole, doesn’t mean it occurs in every case. Researchers explored the impact of teleneurology prenotification at the case level rather than the facility level.

“That gave us a bit more insight into the real impact because it’s not just being at a facility with the best practice; it’s actually working case by case to see whether it happened or not and that’s where we get the most compelling findings,” said Dr. McDonald.

Of 761 treatment cases, there was prenotification to the neurology team in 401 cases. In 360 cases, prenotification did not occur.

The median DTN time was 29 minutes in the group with actual prenotification vs 41.5 minutes in the group without actual prenotification, a difference that was statistically significant, Dr. McDonald said.

As for treatment within 30 minutes of arrival, 50.4% of patients in the teleneurology prenotification group versus 18.9% in the no prenotification group — a statistically significant difference.

DTN time of less than 30 minutes is increasingly used as a target. “Being treated within this time frame improves outcomes and reduces length of hospital stay,” said Dr. McDonald.

The prenotification group also had a statistically significant higher percentage of treatment within 60 minutes of hospital arrival (93.5% vs 80%).

These new findings should help convince health and telestroke systems that teleneurology prenotification is worth implementing. “We want to achieve consensus on this as a best practice,” said Dr. McDonald.

Prenotification, he added, “coordinates the process and eliminates unnecessary and time-consuming steps.”

Dr. McDonald plans to prospectively study prenotification by collecting data on a facility before and after implementing a prenotification process.
 

 

 

Compelling Evidence

Commenting on the research, David L. Tirschwell, MD, Harborview Medical Center, Department of Neurology, Seattle, who cochaired the AAN session featuring the research, said the study provides compelling evidence that teleneurologist prenotification improves DTN time.

“Prenotifications are often standard of care in many healthcare settings and should likely be considered a best practice. When possible, extending such prenotification to a teleconsultant would make sense, and these preliminary data support that approach.”

However, more details are needed “to consider whether the intervention is possibly generalizable to other telestroke practices across the United States,” said Dr. Tirschwell.

Dr. McDonald reported receiving personal compensation for serving as a consultant for Syntrillo Inc. and has stock in Syntrillo Inc. Dr. Tirschwell reported no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

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Novel Agent Curbs Alzheimer’s-Related Agitation

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Wed, 04/24/2024 - 14:52

 

Treatment with AXS-05, a combination of dextromethorphan and bupropion, demonstrated rapid, sustained, and clinically meaningful improvement in agitation related to Alzheimer’s disease and was generally well tolerated in the phase 3 ACCORD trial. 

More than half of participants in the open-label extension period of the randomized clinical trial responded to the medication, which was associated with a 3.6-fold lower risk for relapse compared with placebo. 

“The positive efficacy and favorable safety results with AXS-05 support its potential to fulfill a high unmet need for the treatment of Alzheimer’s disease agitation,” said Anton P. Porsteinsson, MD, director of the Alzheimer’s Disease Care, Research and Education Program, University of Rochester, New York. 

The findings were presented at the 2024 annual meeting of the American Academy of Neurology. 
 

Common and Disruptive

Agitation is reported in up to 70% of patients with Alzheimer’s disease and is characterized by emotional distress, aggressive behaviors, disruptive irritability, and disinhibition. Alzheimer’s disease-related agitation has been associated with increased caregiver burden, decreased functioning, accelerated cognitive decline, earlier nursing home placement, and increased mortality.

A previous phase 2/3 study of AXS-05 showed that the investigative agent led to rapid and significantly improvement in Alzheimer’s disease agitation, as measured by the Cohen-Mansfield Agitation Inventory (CMAI) total score, compared with placebo. 

ACCORD was a phase 3, randomized, double-blind, placebo-controlled withdrawal trial evaluating the efficacy and safety of AXS-05 in patients with Alzheimer’s disease agitation. 

In the open-label period, 178 adults with probable Alzheimer’s disease and clinically significant agitation received AXS-05 (titrated to 45 mg dextromethorphan/105 mg bupropion twice daily) for up to 9 weeks.

A total of 108 (61%) patients had a sustained response, with 30% or more improvement from baseline in the CMAI total score and improvement on the Patient Global Impression of Change that were both maintained for 4 or more consecutive weeks. These patients entered the double-blind phase and were randomly allocated to receive twice-daily AXS-05 or placebo for up to 26 weeks.

In the double-blind period, AXS-05 “substantially and statistically” increased the time to relapse of agitation symptoms compared with placebo (hazard ratio [HR], 0.275; P = .014).

“The risk of relapse was 3.6-fold lower with AXS-05 compared with placebo,” Dr. Porsteinsson reported. 

AXS-05 was also associated with a significantly lower relapse rate compared with placebo (7.5% vs 25.9%; P = .018).

Rates of discontinuation in the double-blind period owing to adverse events (AEs) were low (0% for AXS-05 and 1.9% for placebo). Three serious AEs were reported: one in the AXS-05 group (fecaloma), which was not related to study medication, and two in the placebo group (cardiac arrest, femur fracture).

Falls were reported in four participants in the AXS-05 group, none of which were related to study medication or associated with serious AEs, and in two participants in the placebo group, one of which was associated with femur fracture.

One death was reported in the placebo group. There was no evidence of cognitive decline with AXS-05, and treatment was not associated with sedation. 
 

Promising Agent 

Commenting on this research, Glen R. Finney, MD, director of the Geisinger Memory and Cognition Clinic in Wilkes-Barre, Pennsylvania, said the data “look promising as a safe way to help address acute agitation and reduce agitation reoccurrence.

 

 

“Agitation is a common, distressing, and sometimes safety issue for people fighting Alzheimer’s disease, and there’s very little evidence for efficacy and significant side effect issues for current medical management of agitation in Alzheimer’s disease,” said Dr. Finney, who was not part of the study.

He noted that first-line strategies for addressing agitation involve behavioral and environmental interventions. 

“See if there’s a reason for the agitation and address that. Look for triggers for agitation and avoid those. Find places, things, and interactions that help people with Alzheimer’s disease avoid agitation: familiar locations, music, simple engaging activities. Reassurance, redirection, and distraction can help de-escalate agitation. Provide a safe environment that reduces safety risks,” Dr. Finney explained. 

The next step, when medically appropriate, is trying acetylcholinesterase inhibitors such as donepezil, rivastigmine, and galantamine, and then adding memantine, a weak N-methyl-D-aspartate receptor antagonist. 

“These medications can help reduce the risk of agitation,” Dr. Finney said. 

“Beyond that, the evidence becomes weaker for any specific treatments, and that is where treatments with emerging evidence of efficacy and safety like dextromethorphan-bupropion become important,” Dr. Finney added. 

Last May, the US Food and Drug Administration (FDA) approved the antipsychotic brexpiprazole (Rexulti) for Alzheimer’s disease-related agitation, making it the first FDA-approved drug for this indication. 

The drug includes a boxed warning for medications in this class that older patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk for death.

“There’s certainly a need to have multiple options for treating agitation in individuals with Alzheimer’s disease,” said Rebecca Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association. 

Dr. Edelmayer, who was not part of the study, noted that in the ACCORD study, AXS-05 “significantly delayed the relapse or prevented the relapse with Alzheimer’s disease agitation compared with the placebo group and it was generally well tolerated, but it will be important to make sure that there’s more thorough review of the data overall to be sure that it’s both safe and effective.”

The study was funded by Axsome Therapeutics, the manufacturer of AXS-05. Dr. Porsteinsson has disclosed no relevant conflicts of interest. Dr. Finney and Dr. Edelmayer have no relevant disclosures.

A version of this article appeared on Medscape.com.

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Treatment with AXS-05, a combination of dextromethorphan and bupropion, demonstrated rapid, sustained, and clinically meaningful improvement in agitation related to Alzheimer’s disease and was generally well tolerated in the phase 3 ACCORD trial. 

More than half of participants in the open-label extension period of the randomized clinical trial responded to the medication, which was associated with a 3.6-fold lower risk for relapse compared with placebo. 

“The positive efficacy and favorable safety results with AXS-05 support its potential to fulfill a high unmet need for the treatment of Alzheimer’s disease agitation,” said Anton P. Porsteinsson, MD, director of the Alzheimer’s Disease Care, Research and Education Program, University of Rochester, New York. 

The findings were presented at the 2024 annual meeting of the American Academy of Neurology. 
 

Common and Disruptive

Agitation is reported in up to 70% of patients with Alzheimer’s disease and is characterized by emotional distress, aggressive behaviors, disruptive irritability, and disinhibition. Alzheimer’s disease-related agitation has been associated with increased caregiver burden, decreased functioning, accelerated cognitive decline, earlier nursing home placement, and increased mortality.

A previous phase 2/3 study of AXS-05 showed that the investigative agent led to rapid and significantly improvement in Alzheimer’s disease agitation, as measured by the Cohen-Mansfield Agitation Inventory (CMAI) total score, compared with placebo. 

ACCORD was a phase 3, randomized, double-blind, placebo-controlled withdrawal trial evaluating the efficacy and safety of AXS-05 in patients with Alzheimer’s disease agitation. 

In the open-label period, 178 adults with probable Alzheimer’s disease and clinically significant agitation received AXS-05 (titrated to 45 mg dextromethorphan/105 mg bupropion twice daily) for up to 9 weeks.

A total of 108 (61%) patients had a sustained response, with 30% or more improvement from baseline in the CMAI total score and improvement on the Patient Global Impression of Change that were both maintained for 4 or more consecutive weeks. These patients entered the double-blind phase and were randomly allocated to receive twice-daily AXS-05 or placebo for up to 26 weeks.

In the double-blind period, AXS-05 “substantially and statistically” increased the time to relapse of agitation symptoms compared with placebo (hazard ratio [HR], 0.275; P = .014).

“The risk of relapse was 3.6-fold lower with AXS-05 compared with placebo,” Dr. Porsteinsson reported. 

AXS-05 was also associated with a significantly lower relapse rate compared with placebo (7.5% vs 25.9%; P = .018).

Rates of discontinuation in the double-blind period owing to adverse events (AEs) were low (0% for AXS-05 and 1.9% for placebo). Three serious AEs were reported: one in the AXS-05 group (fecaloma), which was not related to study medication, and two in the placebo group (cardiac arrest, femur fracture).

Falls were reported in four participants in the AXS-05 group, none of which were related to study medication or associated with serious AEs, and in two participants in the placebo group, one of which was associated with femur fracture.

One death was reported in the placebo group. There was no evidence of cognitive decline with AXS-05, and treatment was not associated with sedation. 
 

Promising Agent 

Commenting on this research, Glen R. Finney, MD, director of the Geisinger Memory and Cognition Clinic in Wilkes-Barre, Pennsylvania, said the data “look promising as a safe way to help address acute agitation and reduce agitation reoccurrence.

 

 

“Agitation is a common, distressing, and sometimes safety issue for people fighting Alzheimer’s disease, and there’s very little evidence for efficacy and significant side effect issues for current medical management of agitation in Alzheimer’s disease,” said Dr. Finney, who was not part of the study.

He noted that first-line strategies for addressing agitation involve behavioral and environmental interventions. 

“See if there’s a reason for the agitation and address that. Look for triggers for agitation and avoid those. Find places, things, and interactions that help people with Alzheimer’s disease avoid agitation: familiar locations, music, simple engaging activities. Reassurance, redirection, and distraction can help de-escalate agitation. Provide a safe environment that reduces safety risks,” Dr. Finney explained. 

The next step, when medically appropriate, is trying acetylcholinesterase inhibitors such as donepezil, rivastigmine, and galantamine, and then adding memantine, a weak N-methyl-D-aspartate receptor antagonist. 

“These medications can help reduce the risk of agitation,” Dr. Finney said. 

“Beyond that, the evidence becomes weaker for any specific treatments, and that is where treatments with emerging evidence of efficacy and safety like dextromethorphan-bupropion become important,” Dr. Finney added. 

Last May, the US Food and Drug Administration (FDA) approved the antipsychotic brexpiprazole (Rexulti) for Alzheimer’s disease-related agitation, making it the first FDA-approved drug for this indication. 

The drug includes a boxed warning for medications in this class that older patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk for death.

“There’s certainly a need to have multiple options for treating agitation in individuals with Alzheimer’s disease,” said Rebecca Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association. 

Dr. Edelmayer, who was not part of the study, noted that in the ACCORD study, AXS-05 “significantly delayed the relapse or prevented the relapse with Alzheimer’s disease agitation compared with the placebo group and it was generally well tolerated, but it will be important to make sure that there’s more thorough review of the data overall to be sure that it’s both safe and effective.”

The study was funded by Axsome Therapeutics, the manufacturer of AXS-05. Dr. Porsteinsson has disclosed no relevant conflicts of interest. Dr. Finney and Dr. Edelmayer have no relevant disclosures.

A version of this article appeared on Medscape.com.

 

Treatment with AXS-05, a combination of dextromethorphan and bupropion, demonstrated rapid, sustained, and clinically meaningful improvement in agitation related to Alzheimer’s disease and was generally well tolerated in the phase 3 ACCORD trial. 

More than half of participants in the open-label extension period of the randomized clinical trial responded to the medication, which was associated with a 3.6-fold lower risk for relapse compared with placebo. 

“The positive efficacy and favorable safety results with AXS-05 support its potential to fulfill a high unmet need for the treatment of Alzheimer’s disease agitation,” said Anton P. Porsteinsson, MD, director of the Alzheimer’s Disease Care, Research and Education Program, University of Rochester, New York. 

The findings were presented at the 2024 annual meeting of the American Academy of Neurology. 
 

Common and Disruptive

Agitation is reported in up to 70% of patients with Alzheimer’s disease and is characterized by emotional distress, aggressive behaviors, disruptive irritability, and disinhibition. Alzheimer’s disease-related agitation has been associated with increased caregiver burden, decreased functioning, accelerated cognitive decline, earlier nursing home placement, and increased mortality.

A previous phase 2/3 study of AXS-05 showed that the investigative agent led to rapid and significantly improvement in Alzheimer’s disease agitation, as measured by the Cohen-Mansfield Agitation Inventory (CMAI) total score, compared with placebo. 

ACCORD was a phase 3, randomized, double-blind, placebo-controlled withdrawal trial evaluating the efficacy and safety of AXS-05 in patients with Alzheimer’s disease agitation. 

In the open-label period, 178 adults with probable Alzheimer’s disease and clinically significant agitation received AXS-05 (titrated to 45 mg dextromethorphan/105 mg bupropion twice daily) for up to 9 weeks.

A total of 108 (61%) patients had a sustained response, with 30% or more improvement from baseline in the CMAI total score and improvement on the Patient Global Impression of Change that were both maintained for 4 or more consecutive weeks. These patients entered the double-blind phase and were randomly allocated to receive twice-daily AXS-05 or placebo for up to 26 weeks.

In the double-blind period, AXS-05 “substantially and statistically” increased the time to relapse of agitation symptoms compared with placebo (hazard ratio [HR], 0.275; P = .014).

“The risk of relapse was 3.6-fold lower with AXS-05 compared with placebo,” Dr. Porsteinsson reported. 

AXS-05 was also associated with a significantly lower relapse rate compared with placebo (7.5% vs 25.9%; P = .018).

Rates of discontinuation in the double-blind period owing to adverse events (AEs) were low (0% for AXS-05 and 1.9% for placebo). Three serious AEs were reported: one in the AXS-05 group (fecaloma), which was not related to study medication, and two in the placebo group (cardiac arrest, femur fracture).

Falls were reported in four participants in the AXS-05 group, none of which were related to study medication or associated with serious AEs, and in two participants in the placebo group, one of which was associated with femur fracture.

One death was reported in the placebo group. There was no evidence of cognitive decline with AXS-05, and treatment was not associated with sedation. 
 

Promising Agent 

Commenting on this research, Glen R. Finney, MD, director of the Geisinger Memory and Cognition Clinic in Wilkes-Barre, Pennsylvania, said the data “look promising as a safe way to help address acute agitation and reduce agitation reoccurrence.

 

 

“Agitation is a common, distressing, and sometimes safety issue for people fighting Alzheimer’s disease, and there’s very little evidence for efficacy and significant side effect issues for current medical management of agitation in Alzheimer’s disease,” said Dr. Finney, who was not part of the study.

He noted that first-line strategies for addressing agitation involve behavioral and environmental interventions. 

“See if there’s a reason for the agitation and address that. Look for triggers for agitation and avoid those. Find places, things, and interactions that help people with Alzheimer’s disease avoid agitation: familiar locations, music, simple engaging activities. Reassurance, redirection, and distraction can help de-escalate agitation. Provide a safe environment that reduces safety risks,” Dr. Finney explained. 

The next step, when medically appropriate, is trying acetylcholinesterase inhibitors such as donepezil, rivastigmine, and galantamine, and then adding memantine, a weak N-methyl-D-aspartate receptor antagonist. 

“These medications can help reduce the risk of agitation,” Dr. Finney said. 

“Beyond that, the evidence becomes weaker for any specific treatments, and that is where treatments with emerging evidence of efficacy and safety like dextromethorphan-bupropion become important,” Dr. Finney added. 

Last May, the US Food and Drug Administration (FDA) approved the antipsychotic brexpiprazole (Rexulti) for Alzheimer’s disease-related agitation, making it the first FDA-approved drug for this indication. 

The drug includes a boxed warning for medications in this class that older patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk for death.

“There’s certainly a need to have multiple options for treating agitation in individuals with Alzheimer’s disease,” said Rebecca Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association. 

Dr. Edelmayer, who was not part of the study, noted that in the ACCORD study, AXS-05 “significantly delayed the relapse or prevented the relapse with Alzheimer’s disease agitation compared with the placebo group and it was generally well tolerated, but it will be important to make sure that there’s more thorough review of the data overall to be sure that it’s both safe and effective.”

The study was funded by Axsome Therapeutics, the manufacturer of AXS-05. Dr. Porsteinsson has disclosed no relevant conflicts of interest. Dr. Finney and Dr. Edelmayer have no relevant disclosures.

A version of this article appeared on Medscape.com.

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