Neurology Reviews

SEATTLE – A novel treatment for amyotrophic lateral sclerosis (ALS) that targets brain cell energy production to promote remyelination showed signs of efficacy in a phase 2 trial, though it did not meet its primary endpoint, which was the change in the summated motor unit index (MUNIX) from baseline to week 36.

The drug, CNM-Au8, is being developed by Clene, and would represent a novel mechanism of action. “This is a brand-new approach. We used it complementary with riluzole and it was well tolerated, so I see this as an add-on therapy. I think if we can show some more positivity and longer-term results, it’s going to be a game changer for ALS,” Matthew Kiernan, MBBS, PhD, said in an interview. Dr. Kiernan presented the results at the 2022 annual meeting of the American Academy of Neurology.

Jim Kling/MDedge News

Riluzole (Rilutek), which received Food and Drug Administration approval in 1995, inhibits glutamate release to counter excitotoxicity, which is believed to play a role in ALS, Huntington’s disease, ischemia, and other acute and chronic neurodegenerative diseases. The other FDA-approved agent for ALS is the neuroprotective agent and free-radical scavenger edaravone (Radicava), approved in 2017.

CNM-Au8 is made up of catalytically active gold nanocrystals that cross the blood-brain barrier, but lacks the toxicity associated with other synthetic gold compounds, according to the company. The formulation is also being investigated for the treatment of Parkinson’s disease and multiple sclerosis. Basic research has shown that it stabilizes mitochondria and reduces accumulation of the TDP-43 protein, which is linked to spread of ALS through the brain, Dr. Kiernan said during his presentation.

The treatment is well tolerated. “Normally in an ALS trial, we see about a 25% dropout rate. There were no dropouts on the active compound in the clinical trial. There are less deaths, so improved survival,” said Dr. Kiernan, the Bushell chair of neurology at the University of Sydney and codirector of the Brain and Mind Center in Sydney.
 

Good safety signal

The fact that the trial missed its primary endpoint isn’t too concerning, according to Nicholas Johnson, MD, who comoderated the session where the study was presented. “ALS clinical trials are incredibly difficult to conduct, especially a phase 2 learning-phase clinical trial. At this phase, I’m much more buoyed by the fact that they have a good safety signal, and that they’re willing to move forward to that phase 3 clinical trial,” Dr. Johnson said in an interview. He is vice chair of research at Virginia Commonwealth University, Richmond.

A phase 3 clinical trial is in development in the United States and Europe. The drug also is included as part of the HEALEY ALS Platform Trial, which is testing multiple ALS therapies simultaneously. “The results from that should be available by the second half of this year and it will also inform us as to what the approach should be,” said Dr. Kiernan.

Dr. Johnson also was enthusiastic. “I’m excited to see the results in terms of the primary endpoints for that next phase 3 clinical trial,” he said.
 

Ongoing research

In September 2021, Clene announced a second expanded access program for people with ALS.

The study included a 36-week double-blind treatment period followed by long-term, open-label follow-up. Twenty-three patients received 30 mg CNM-Au8, and 22 received placebo. In the first 36 weeks, the treatment group was more likely to have no disease progression, defined as death, tracheostomy, noninvasive ventilation, or a gastronomy tube (P = .0125). The researchers compared the probability of experiencing a less than 6-point decline in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale. At 12 weeks, it was about 85% in both groups. At 24 weeks, it was about 60% to 50% in favor of the CNM-Au8 group, and at 36 weeks it was about 50% to 20% (P = .0350).

At 36 weeks, quality of life as measured by the ALS Specific Quality of Life–Short Form was better in the treatment group at 36 weeks (mean change, 0.9; P = .0177).

Survival was better in the treatment group at 96 weeks than the mortality derived from a European Network for the Cure of ALS prediction model (hazard ratio [HR], 0.2974; P = .0068). This benefit also was experienced by patients who received drug throughout the study (HR, 0.36; 95% confidence interval [CI], 0.12-1.1) and those who started out on placebo and converted to active drug during the open-label period (HR, 0.24; 95% CI, 0.064-0.88).

The study was funded by Clene and FightMND. Dr. Kiernan and Dr. Johnson have no relevant financial disclosures.

SEATTLE – A novel treatment for amyotrophic lateral sclerosis (ALS) that targets brain cell energy production to promote remyelination showed signs of efficacy in a phase 2 trial, though it did not meet its primary endpoint, which was the change in the summated motor unit index (MUNIX) from baseline to week 36.

The drug, CNM-Au8, is being developed by Clene, and would represent a novel mechanism of action. “This is a brand-new approach. We used it complementary with riluzole and it was well tolerated, so I see this as an add-on therapy. I think if we can show some more positivity and longer-term results, it’s going to be a game changer for ALS,” Matthew Kiernan, MBBS, PhD, said in an interview. Dr. Kiernan presented the results at the 2022 annual meeting of the American Academy of Neurology.

Jim Kling/MDedge News

Riluzole (Rilutek), which received Food and Drug Administration approval in 1995, inhibits glutamate release to counter excitotoxicity, which is believed to play a role in ALS, Huntington’s disease, ischemia, and other acute and chronic neurodegenerative diseases. The other FDA-approved agent for ALS is the neuroprotective agent and free-radical scavenger edaravone (Radicava), approved in 2017.

CNM-Au8 is made up of catalytically active gold nanocrystals that cross the blood-brain barrier, but lacks the toxicity associated with other synthetic gold compounds, according to the company. The formulation is also being investigated for the treatment of Parkinson’s disease and multiple sclerosis. Basic research has shown that it stabilizes mitochondria and reduces accumulation of the TDP-43 protein, which is linked to spread of ALS through the brain, Dr. Kiernan said during his presentation.

The treatment is well tolerated. “Normally in an ALS trial, we see about a 25% dropout rate. There were no dropouts on the active compound in the clinical trial. There are less deaths, so improved survival,” said Dr. Kiernan, the Bushell chair of neurology at the University of Sydney and codirector of the Brain and Mind Center in Sydney.
 

Good safety signal

The fact that the trial missed its primary endpoint isn’t too concerning, according to Nicholas Johnson, MD, who comoderated the session where the study was presented. “ALS clinical trials are incredibly difficult to conduct, especially a phase 2 learning-phase clinical trial. At this phase, I’m much more buoyed by the fact that they have a good safety signal, and that they’re willing to move forward to that phase 3 clinical trial,” Dr. Johnson said in an interview. He is vice chair of research at Virginia Commonwealth University, Richmond.

A phase 3 clinical trial is in development in the United States and Europe. The drug also is included as part of the HEALEY ALS Platform Trial, which is testing multiple ALS therapies simultaneously. “The results from that should be available by the second half of this year and it will also inform us as to what the approach should be,” said Dr. Kiernan.

Dr. Johnson also was enthusiastic. “I’m excited to see the results in terms of the primary endpoints for that next phase 3 clinical trial,” he said.
 

Ongoing research

In September 2021, Clene announced a second expanded access program for people with ALS.

The study included a 36-week double-blind treatment period followed by long-term, open-label follow-up. Twenty-three patients received 30 mg CNM-Au8, and 22 received placebo. In the first 36 weeks, the treatment group was more likely to have no disease progression, defined as death, tracheostomy, noninvasive ventilation, or a gastronomy tube (P = .0125). The researchers compared the probability of experiencing a less than 6-point decline in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale. At 12 weeks, it was about 85% in both groups. At 24 weeks, it was about 60% to 50% in favor of the CNM-Au8 group, and at 36 weeks it was about 50% to 20% (P = .0350).

At 36 weeks, quality of life as measured by the ALS Specific Quality of Life–Short Form was better in the treatment group at 36 weeks (mean change, 0.9; P = .0177).

Survival was better in the treatment group at 96 weeks than the mortality derived from a European Network for the Cure of ALS prediction model (hazard ratio [HR], 0.2974; P = .0068). This benefit also was experienced by patients who received drug throughout the study (HR, 0.36; 95% confidence interval [CI], 0.12-1.1) and those who started out on placebo and converted to active drug during the open-label period (HR, 0.24; 95% CI, 0.064-0.88).

The study was funded by Clene and FightMND. Dr. Kiernan and Dr. Johnson have no relevant financial disclosures.

SEATTLE – A novel treatment for amyotrophic lateral sclerosis (ALS) that targets brain cell energy production to promote remyelination showed signs of efficacy in a phase 2 trial, though it did not meet its primary endpoint, which was the change in the summated motor unit index (MUNIX) from baseline to week 36.

The drug, CNM-Au8, is being developed by Clene, and would represent a novel mechanism of action. “This is a brand-new approach. We used it complementary with riluzole and it was well tolerated, so I see this as an add-on therapy. I think if we can show some more positivity and longer-term results, it’s going to be a game changer for ALS,” Matthew Kiernan, MBBS, PhD, said in an interview. Dr. Kiernan presented the results at the 2022 annual meeting of the American Academy of Neurology.

Jim Kling/MDedge News

Riluzole (Rilutek), which received Food and Drug Administration approval in 1995, inhibits glutamate release to counter excitotoxicity, which is believed to play a role in ALS, Huntington’s disease, ischemia, and other acute and chronic neurodegenerative diseases. The other FDA-approved agent for ALS is the neuroprotective agent and free-radical scavenger edaravone (Radicava), approved in 2017.

CNM-Au8 is made up of catalytically active gold nanocrystals that cross the blood-brain barrier, but lacks the toxicity associated with other synthetic gold compounds, according to the company. The formulation is also being investigated for the treatment of Parkinson’s disease and multiple sclerosis. Basic research has shown that it stabilizes mitochondria and reduces accumulation of the TDP-43 protein, which is linked to spread of ALS through the brain, Dr. Kiernan said during his presentation.

The treatment is well tolerated. “Normally in an ALS trial, we see about a 25% dropout rate. There were no dropouts on the active compound in the clinical trial. There are less deaths, so improved survival,” said Dr. Kiernan, the Bushell chair of neurology at the University of Sydney and codirector of the Brain and Mind Center in Sydney.
 

Good safety signal

The fact that the trial missed its primary endpoint isn’t too concerning, according to Nicholas Johnson, MD, who comoderated the session where the study was presented. “ALS clinical trials are incredibly difficult to conduct, especially a phase 2 learning-phase clinical trial. At this phase, I’m much more buoyed by the fact that they have a good safety signal, and that they’re willing to move forward to that phase 3 clinical trial,” Dr. Johnson said in an interview. He is vice chair of research at Virginia Commonwealth University, Richmond.

A phase 3 clinical trial is in development in the United States and Europe. The drug also is included as part of the HEALEY ALS Platform Trial, which is testing multiple ALS therapies simultaneously. “The results from that should be available by the second half of this year and it will also inform us as to what the approach should be,” said Dr. Kiernan.

Dr. Johnson also was enthusiastic. “I’m excited to see the results in terms of the primary endpoints for that next phase 3 clinical trial,” he said.
 

Ongoing research

In September 2021, Clene announced a second expanded access program for people with ALS.

The study included a 36-week double-blind treatment period followed by long-term, open-label follow-up. Twenty-three patients received 30 mg CNM-Au8, and 22 received placebo. In the first 36 weeks, the treatment group was more likely to have no disease progression, defined as death, tracheostomy, noninvasive ventilation, or a gastronomy tube (P = .0125). The researchers compared the probability of experiencing a less than 6-point decline in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale. At 12 weeks, it was about 85% in both groups. At 24 weeks, it was about 60% to 50% in favor of the CNM-Au8 group, and at 36 weeks it was about 50% to 20% (P = .0350).

At 36 weeks, quality of life as measured by the ALS Specific Quality of Life–Short Form was better in the treatment group at 36 weeks (mean change, 0.9; P = .0177).

Survival was better in the treatment group at 96 weeks than the mortality derived from a European Network for the Cure of ALS prediction model (hazard ratio [HR], 0.2974; P = .0068). This benefit also was experienced by patients who received drug throughout the study (HR, 0.36; 95% confidence interval [CI], 0.12-1.1) and those who started out on placebo and converted to active drug during the open-label period (HR, 0.24; 95% CI, 0.064-0.88).

The study was funded by Clene and FightMND. Dr. Kiernan and Dr. Johnson have no relevant financial disclosures.

Physical fitness has been linked to a lower risk of Alzheimer’s disease, but even moderate levels of cardiorespiratory fitness offer some protection, new findings suggest. “One exciting finding of this study is that as people’s fitness improved, their risk of Alzheimer’s disease decreased – it was not an all-or-nothing proposition,” study investigator Edward Zamrini, MD, of the Washington DC VA Medical Center, said in a news release.

The findings suggest that people can work toward making incremental changes and improvements in their physical fitness, which may help decrease their risk of dementia, Dr. Zamrini added.

The findings were presented at the 2022 annual meeting of the American Academy of Neurology.
 

Effective prevention strategy

Using the Veterans Health Administration database, Dr. Zamrini and colleagues identified 649,605 veterans (mean age, 61 years) free of Alzheimer’s disease and related disorders (ADRD) when they completed standardized exercise treadmill tests between 2000 and 2017.

They divided participants into five age-specific fitness groups, from least fit to most fit, based on peak metabolic equivalents (METs) achieved during the treadmill test: lowest-fit (METs, ±3.8), low-fit (METs, ±5.8), moderate-fit (METs, ±7.5), fit (METs, ±9.2), and highest-fit (METs, ±11.7).

In unadjusted analysis, veterans with the lowest cardiorespiratory fitness developed ADRD at a rate of 9.5 cases per 1,000 person-years, compared with a rate of 6.4 cases per 1,000 person-years for the most fit group (P < .001).

After adjusting for factors that could affect risk of ADRD, compared with the lowest-fit group, the highest-fit and fit groups were 33% and 26% less likely to develop ADRD, respectively, while the moderate-fit and low-fit groups were 20% and 13% less likely to develop the disease, respectively.

The next vital sign?

Commenting on the study, Shaheen E. Lakhan, MD, PhD, a neurologist in Boston, noted that “for decades and with increasing body of support from studies like this, we have known that preventing dementia is based on healthy behaviors for the brain including a proper diet (NASH and/or Mediterranean), exercise regimen (aerobic/cardio more than anaerobic/weight-lifting), sleep hygiene, and social and intellectual engagements.”

“Frankly, what’s good for the body is good for the brain,” said Dr. Lakhan.

“It should be noted that the measure studied here is cardiorespiratory fitness, which has been associated with heart disease and resulting death, death from any cause, and now brain health,” Dr. Lakhan said.

“This powerful predictor may in fact be the next vital sign, after your heart rate and blood pressure, from which your primary care provider can make a personalized treatment plan,” he added.

“Accelerating this process, the ability to measure cardiorespiratory fitness traditionally from huge stationary machines down to wearables like a watch or ring, or even your iPhone or Android, is just on the horizon,” Dr. Lakhan said.

“Instead of tracking just your weight, shape, and BMI, personal fitness may be tailored to optimizing this indicator and further empowering individuals to take charge of their health,” he said.

The study was supported by the National Institute on Aging, the National Institutes of Health, the U.S. Department of Veterans Affairs, the Washington DC VA Medical Center, and George Washington University. Dr. Zamrini and Dr. Lakhan have disclosed no relevant financial relationships.

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

Physical fitness has been linked to a lower risk of Alzheimer’s disease, but even moderate levels of cardiorespiratory fitness offer some protection, new findings suggest. “One exciting finding of this study is that as people’s fitness improved, their risk of Alzheimer’s disease decreased – it was not an all-or-nothing proposition,” study investigator Edward Zamrini, MD, of the Washington DC VA Medical Center, said in a news release.

The findings suggest that people can work toward making incremental changes and improvements in their physical fitness, which may help decrease their risk of dementia, Dr. Zamrini added.

The findings were presented at the 2022 annual meeting of the American Academy of Neurology.
 

Effective prevention strategy

Using the Veterans Health Administration database, Dr. Zamrini and colleagues identified 649,605 veterans (mean age, 61 years) free of Alzheimer’s disease and related disorders (ADRD) when they completed standardized exercise treadmill tests between 2000 and 2017.

They divided participants into five age-specific fitness groups, from least fit to most fit, based on peak metabolic equivalents (METs) achieved during the treadmill test: lowest-fit (METs, ±3.8), low-fit (METs, ±5.8), moderate-fit (METs, ±7.5), fit (METs, ±9.2), and highest-fit (METs, ±11.7).

In unadjusted analysis, veterans with the lowest cardiorespiratory fitness developed ADRD at a rate of 9.5 cases per 1,000 person-years, compared with a rate of 6.4 cases per 1,000 person-years for the most fit group (P < .001).

After adjusting for factors that could affect risk of ADRD, compared with the lowest-fit group, the highest-fit and fit groups were 33% and 26% less likely to develop ADRD, respectively, while the moderate-fit and low-fit groups were 20% and 13% less likely to develop the disease, respectively.

The next vital sign?

Commenting on the study, Shaheen E. Lakhan, MD, PhD, a neurologist in Boston, noted that “for decades and with increasing body of support from studies like this, we have known that preventing dementia is based on healthy behaviors for the brain including a proper diet (NASH and/or Mediterranean), exercise regimen (aerobic/cardio more than anaerobic/weight-lifting), sleep hygiene, and social and intellectual engagements.”

“Frankly, what’s good for the body is good for the brain,” said Dr. Lakhan.

“It should be noted that the measure studied here is cardiorespiratory fitness, which has been associated with heart disease and resulting death, death from any cause, and now brain health,” Dr. Lakhan said.

“This powerful predictor may in fact be the next vital sign, after your heart rate and blood pressure, from which your primary care provider can make a personalized treatment plan,” he added.

“Accelerating this process, the ability to measure cardiorespiratory fitness traditionally from huge stationary machines down to wearables like a watch or ring, or even your iPhone or Android, is just on the horizon,” Dr. Lakhan said.

“Instead of tracking just your weight, shape, and BMI, personal fitness may be tailored to optimizing this indicator and further empowering individuals to take charge of their health,” he said.

The study was supported by the National Institute on Aging, the National Institutes of Health, the U.S. Department of Veterans Affairs, the Washington DC VA Medical Center, and George Washington University. Dr. Zamrini and Dr. Lakhan have disclosed no relevant financial relationships.

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

Physical fitness has been linked to a lower risk of Alzheimer’s disease, but even moderate levels of cardiorespiratory fitness offer some protection, new findings suggest. “One exciting finding of this study is that as people’s fitness improved, their risk of Alzheimer’s disease decreased – it was not an all-or-nothing proposition,” study investigator Edward Zamrini, MD, of the Washington DC VA Medical Center, said in a news release.

The findings suggest that people can work toward making incremental changes and improvements in their physical fitness, which may help decrease their risk of dementia, Dr. Zamrini added.

The findings were presented at the 2022 annual meeting of the American Academy of Neurology.
 

Effective prevention strategy

Using the Veterans Health Administration database, Dr. Zamrini and colleagues identified 649,605 veterans (mean age, 61 years) free of Alzheimer’s disease and related disorders (ADRD) when they completed standardized exercise treadmill tests between 2000 and 2017.

They divided participants into five age-specific fitness groups, from least fit to most fit, based on peak metabolic equivalents (METs) achieved during the treadmill test: lowest-fit (METs, ±3.8), low-fit (METs, ±5.8), moderate-fit (METs, ±7.5), fit (METs, ±9.2), and highest-fit (METs, ±11.7).

In unadjusted analysis, veterans with the lowest cardiorespiratory fitness developed ADRD at a rate of 9.5 cases per 1,000 person-years, compared with a rate of 6.4 cases per 1,000 person-years for the most fit group (P < .001).

After adjusting for factors that could affect risk of ADRD, compared with the lowest-fit group, the highest-fit and fit groups were 33% and 26% less likely to develop ADRD, respectively, while the moderate-fit and low-fit groups were 20% and 13% less likely to develop the disease, respectively.

The next vital sign?

Commenting on the study, Shaheen E. Lakhan, MD, PhD, a neurologist in Boston, noted that “for decades and with increasing body of support from studies like this, we have known that preventing dementia is based on healthy behaviors for the brain including a proper diet (NASH and/or Mediterranean), exercise regimen (aerobic/cardio more than anaerobic/weight-lifting), sleep hygiene, and social and intellectual engagements.”

“Frankly, what’s good for the body is good for the brain,” said Dr. Lakhan.

“It should be noted that the measure studied here is cardiorespiratory fitness, which has been associated with heart disease and resulting death, death from any cause, and now brain health,” Dr. Lakhan said.

“This powerful predictor may in fact be the next vital sign, after your heart rate and blood pressure, from which your primary care provider can make a personalized treatment plan,” he added.

“Accelerating this process, the ability to measure cardiorespiratory fitness traditionally from huge stationary machines down to wearables like a watch or ring, or even your iPhone or Android, is just on the horizon,” Dr. Lakhan said.

“Instead of tracking just your weight, shape, and BMI, personal fitness may be tailored to optimizing this indicator and further empowering individuals to take charge of their health,” he said.

The study was supported by the National Institute on Aging, the National Institutes of Health, the U.S. Department of Veterans Affairs, the Washington DC VA Medical Center, and George Washington University. Dr. Zamrini and Dr. Lakhan have disclosed no relevant financial relationships.

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

A dose-response relationship exists between number of years playing hockey and risk and severity of chronic traumatic encephalopathy (CTE), new research suggests. Early results from a study that examined donor brains showed that each additional year of ice hockey play increased the risk for CTE by 23%.

This information should be on the “radar” of all clinicians, said coinvestigator Jesse Mez, MD, associate professor of neurology at Boston University. “When they’re talking to kids and families and parents about playing contact sports, they should discuss the benefits as well as the risks so all that information can be taken into consideration.”

Dr. Mez noted that clinicians should also consider the amount of hockey played when assessing patients for thinking and memory trouble later in life. “CTE could be in the differential diagnosis,” he said.

The study findings were presented at the 2022 annual meeting of the American Academy of Neurology.
 

Football data

CTE is a neurodegenerative disease associated with repetitive hits to the head. In previous research, the investigators showed that the more that athletes play American football, the more likely they are to develop CTE.

“Hockey, like football, involves repetitive head impacts as part of the game,” said Dr. Mez. “So we hypothesized that we would see a similar type of dose-response relationship in hockey.”

From two brain banks – the Veterans Affairs–Boston University–Concussion Legacy Foundation and the Framingham Heart Study – the researchers accessed 74 consecutive brains from donors who had played ice hockey. They collected information about hockey play during “pretty comprehensive” interviews with next of kin, Dr. Mez reported.

The study participants ranged in age from 13 to 91 years. The cause of death varied; most died with end-stage dementia and neurodegenerative disease, but some died of cardiovascular disease, and others from accidents.

For 9% of the individuals, the highest level of play was a youth league; 34% had reached the high school level, 30% reached the juniors/college level, and 26% played professionally. In addition, 46% played another contact sport – including 43% who played American football.

Primary outcomes included evidence of CTE from stage 0 (no CTE) to stage IV and severity of CTE, which was defined by the amount of neurofibrillary tangle (NFT) burden in 11 brain regions. For this burden, the score ranged from 0 (absent) to 3 (severe) in each region for a total range of 0-33.

Dr. Mez noted that, in CTE, tau protein accumulates abnormally. “It typically begins in the cortex in the frontal lobe and then spreads to other parts of the brain, including to the medial temporal structures, and is widespread by stage IV.”

The researchers estimated the association of duration of ice hockey play in years with each neuropathologic outcome and adjusted for age at death and duration of football play.
 

Consistent findings

Results showed that, of the 74 donors, 40 (54%) had CTE. Each additional year of hockey play corresponded to increased chances for having CTE (odds ratio, 1.23; 95% confidence interval, 11%-36%; P < .01). This increase in risk is similar to that which was found with football players, Dr. Mez noted. This was somewhat surprising, as hockey involves fewer “hits” than football.

“Hits are not as quintessential to the game of hockey as they are in football, where contacts occur with nearly every play,” he said. “In football, you have several hundred impacts over the course of a season.”

Researchers also found a 15% increase in odds for increasing one CTE stage (95% CI, 8%-22%; P < .01), and a .03 standard deviation increase in cumulative NFT burden (95% CI, 0.01-0.05; P < .01).

Dr. Mez noted that the fact that the results were consistent across different outcomes “improves the validity” of the findings.

In a sensitivity analysis that excluded participants who also played football, estimates “were pretty similar” to those in the full analysis, said Dr. Mez.

The investigators have not yet examined the effect of level of hockey play, such as professionally or at the college level, on CTE risk. However, in football players, they found that level of play is another “valuable predictor of CTE pathology,” Dr. Mez said, adding that level of play, position played, and years of play “are all probably contributing” to CTE risk.

Asking about years of play is useful in a clinical setting. “It’s very easy for a clinician to ask patients how many years of hockey they played,” said Dr. Mez.

Overall, the new results are important, as “millions of individuals” play contact sports, whether that is hockey, football, or European soccer, he added. “And for all sports, there seems to be this relationship between more play and risk of this disease.”
 

‘Skewed’ population?

Commenting on the findings, Frank Conidi, MD, director, Florida Center for Health and Sports Neurology, Port St. Lucie, said he was surprised the investigators found a 23% per year increase in risk for CTE among hockey players.

Dr. Conidi has played hockey himself and works with the Florida Panthers of the National Hockey League. In his practice, he treats retired professional football players who have neurodegenerative disorders. From his experience, the number of repetitive direct head impacts in football is significantly higher than in hockey. “Most of the forces seen in hockey are from hits to the body, where the force is transferred to the head,” said Dr. Conidi, who was not involved with the research.

He noted differences in the way hockey is played around the world. In European countries, for example, the ice surface is relatively large and the emphasis tends to be more on skill than hitting.

“It would have been interesting to have the study group analyze the data based on where the athlete grew up,” he said. Dr. Conidi would also like to know when the participants played hockey. “The game is vastly different now than it was in the 1970s, ‘80s, and early ‘90s, when there was more fighting, less protective gear, and more hitting in general.”

As is the case for most studies of CTE in athletes, the study population is “skewed” because the participants likely had neurocognitive and other problems that led to their decision to donate their brain, said Dr. Conidi.

He also doesn’t believe the study should be the sole factor in a decision to continue or stop playing hockey. “We are still in the infancy stages of understanding the effects of high-impact sports on athletes’ brains.”

The study received funding from the National Institute of Neurological Diseases and Stroke and the National Institute on Aging. Dr. Mez and Dr. Conidi have reported no relevant financial relationships.

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

A dose-response relationship exists between number of years playing hockey and risk and severity of chronic traumatic encephalopathy (CTE), new research suggests. Early results from a study that examined donor brains showed that each additional year of ice hockey play increased the risk for CTE by 23%.

This information should be on the “radar” of all clinicians, said coinvestigator Jesse Mez, MD, associate professor of neurology at Boston University. “When they’re talking to kids and families and parents about playing contact sports, they should discuss the benefits as well as the risks so all that information can be taken into consideration.”

Dr. Mez noted that clinicians should also consider the amount of hockey played when assessing patients for thinking and memory trouble later in life. “CTE could be in the differential diagnosis,” he said.

The study findings were presented at the 2022 annual meeting of the American Academy of Neurology.
 

Football data

CTE is a neurodegenerative disease associated with repetitive hits to the head. In previous research, the investigators showed that the more that athletes play American football, the more likely they are to develop CTE.

“Hockey, like football, involves repetitive head impacts as part of the game,” said Dr. Mez. “So we hypothesized that we would see a similar type of dose-response relationship in hockey.”

From two brain banks – the Veterans Affairs–Boston University–Concussion Legacy Foundation and the Framingham Heart Study – the researchers accessed 74 consecutive brains from donors who had played ice hockey. They collected information about hockey play during “pretty comprehensive” interviews with next of kin, Dr. Mez reported.

The study participants ranged in age from 13 to 91 years. The cause of death varied; most died with end-stage dementia and neurodegenerative disease, but some died of cardiovascular disease, and others from accidents.

For 9% of the individuals, the highest level of play was a youth league; 34% had reached the high school level, 30% reached the juniors/college level, and 26% played professionally. In addition, 46% played another contact sport – including 43% who played American football.

Primary outcomes included evidence of CTE from stage 0 (no CTE) to stage IV and severity of CTE, which was defined by the amount of neurofibrillary tangle (NFT) burden in 11 brain regions. For this burden, the score ranged from 0 (absent) to 3 (severe) in each region for a total range of 0-33.

Dr. Mez noted that, in CTE, tau protein accumulates abnormally. “It typically begins in the cortex in the frontal lobe and then spreads to other parts of the brain, including to the medial temporal structures, and is widespread by stage IV.”

The researchers estimated the association of duration of ice hockey play in years with each neuropathologic outcome and adjusted for age at death and duration of football play.
 

Consistent findings

Results showed that, of the 74 donors, 40 (54%) had CTE. Each additional year of hockey play corresponded to increased chances for having CTE (odds ratio, 1.23; 95% confidence interval, 11%-36%; P < .01). This increase in risk is similar to that which was found with football players, Dr. Mez noted. This was somewhat surprising, as hockey involves fewer “hits” than football.

“Hits are not as quintessential to the game of hockey as they are in football, where contacts occur with nearly every play,” he said. “In football, you have several hundred impacts over the course of a season.”

Researchers also found a 15% increase in odds for increasing one CTE stage (95% CI, 8%-22%; P < .01), and a .03 standard deviation increase in cumulative NFT burden (95% CI, 0.01-0.05; P < .01).

Dr. Mez noted that the fact that the results were consistent across different outcomes “improves the validity” of the findings.

In a sensitivity analysis that excluded participants who also played football, estimates “were pretty similar” to those in the full analysis, said Dr. Mez.

The investigators have not yet examined the effect of level of hockey play, such as professionally or at the college level, on CTE risk. However, in football players, they found that level of play is another “valuable predictor of CTE pathology,” Dr. Mez said, adding that level of play, position played, and years of play “are all probably contributing” to CTE risk.

Asking about years of play is useful in a clinical setting. “It’s very easy for a clinician to ask patients how many years of hockey they played,” said Dr. Mez.

Overall, the new results are important, as “millions of individuals” play contact sports, whether that is hockey, football, or European soccer, he added. “And for all sports, there seems to be this relationship between more play and risk of this disease.”
 

‘Skewed’ population?

Commenting on the findings, Frank Conidi, MD, director, Florida Center for Health and Sports Neurology, Port St. Lucie, said he was surprised the investigators found a 23% per year increase in risk for CTE among hockey players.

Dr. Conidi has played hockey himself and works with the Florida Panthers of the National Hockey League. In his practice, he treats retired professional football players who have neurodegenerative disorders. From his experience, the number of repetitive direct head impacts in football is significantly higher than in hockey. “Most of the forces seen in hockey are from hits to the body, where the force is transferred to the head,” said Dr. Conidi, who was not involved with the research.

He noted differences in the way hockey is played around the world. In European countries, for example, the ice surface is relatively large and the emphasis tends to be more on skill than hitting.

“It would have been interesting to have the study group analyze the data based on where the athlete grew up,” he said. Dr. Conidi would also like to know when the participants played hockey. “The game is vastly different now than it was in the 1970s, ‘80s, and early ‘90s, when there was more fighting, less protective gear, and more hitting in general.”

As is the case for most studies of CTE in athletes, the study population is “skewed” because the participants likely had neurocognitive and other problems that led to their decision to donate their brain, said Dr. Conidi.

He also doesn’t believe the study should be the sole factor in a decision to continue or stop playing hockey. “We are still in the infancy stages of understanding the effects of high-impact sports on athletes’ brains.”

The study received funding from the National Institute of Neurological Diseases and Stroke and the National Institute on Aging. Dr. Mez and Dr. Conidi have reported no relevant financial relationships.

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

A dose-response relationship exists between number of years playing hockey and risk and severity of chronic traumatic encephalopathy (CTE), new research suggests. Early results from a study that examined donor brains showed that each additional year of ice hockey play increased the risk for CTE by 23%.

This information should be on the “radar” of all clinicians, said coinvestigator Jesse Mez, MD, associate professor of neurology at Boston University. “When they’re talking to kids and families and parents about playing contact sports, they should discuss the benefits as well as the risks so all that information can be taken into consideration.”

Dr. Mez noted that clinicians should also consider the amount of hockey played when assessing patients for thinking and memory trouble later in life. “CTE could be in the differential diagnosis,” he said.

The study findings were presented at the 2022 annual meeting of the American Academy of Neurology.
 

Football data

CTE is a neurodegenerative disease associated with repetitive hits to the head. In previous research, the investigators showed that the more that athletes play American football, the more likely they are to develop CTE.

“Hockey, like football, involves repetitive head impacts as part of the game,” said Dr. Mez. “So we hypothesized that we would see a similar type of dose-response relationship in hockey.”

From two brain banks – the Veterans Affairs–Boston University–Concussion Legacy Foundation and the Framingham Heart Study – the researchers accessed 74 consecutive brains from donors who had played ice hockey. They collected information about hockey play during “pretty comprehensive” interviews with next of kin, Dr. Mez reported.

The study participants ranged in age from 13 to 91 years. The cause of death varied; most died with end-stage dementia and neurodegenerative disease, but some died of cardiovascular disease, and others from accidents.

For 9% of the individuals, the highest level of play was a youth league; 34% had reached the high school level, 30% reached the juniors/college level, and 26% played professionally. In addition, 46% played another contact sport – including 43% who played American football.

Primary outcomes included evidence of CTE from stage 0 (no CTE) to stage IV and severity of CTE, which was defined by the amount of neurofibrillary tangle (NFT) burden in 11 brain regions. For this burden, the score ranged from 0 (absent) to 3 (severe) in each region for a total range of 0-33.

Dr. Mez noted that, in CTE, tau protein accumulates abnormally. “It typically begins in the cortex in the frontal lobe and then spreads to other parts of the brain, including to the medial temporal structures, and is widespread by stage IV.”

The researchers estimated the association of duration of ice hockey play in years with each neuropathologic outcome and adjusted for age at death and duration of football play.
 

Consistent findings

Results showed that, of the 74 donors, 40 (54%) had CTE. Each additional year of hockey play corresponded to increased chances for having CTE (odds ratio, 1.23; 95% confidence interval, 11%-36%; P < .01). This increase in risk is similar to that which was found with football players, Dr. Mez noted. This was somewhat surprising, as hockey involves fewer “hits” than football.

“Hits are not as quintessential to the game of hockey as they are in football, where contacts occur with nearly every play,” he said. “In football, you have several hundred impacts over the course of a season.”

Researchers also found a 15% increase in odds for increasing one CTE stage (95% CI, 8%-22%; P < .01), and a .03 standard deviation increase in cumulative NFT burden (95% CI, 0.01-0.05; P < .01).

Dr. Mez noted that the fact that the results were consistent across different outcomes “improves the validity” of the findings.

In a sensitivity analysis that excluded participants who also played football, estimates “were pretty similar” to those in the full analysis, said Dr. Mez.

The investigators have not yet examined the effect of level of hockey play, such as professionally or at the college level, on CTE risk. However, in football players, they found that level of play is another “valuable predictor of CTE pathology,” Dr. Mez said, adding that level of play, position played, and years of play “are all probably contributing” to CTE risk.

Asking about years of play is useful in a clinical setting. “It’s very easy for a clinician to ask patients how many years of hockey they played,” said Dr. Mez.

Overall, the new results are important, as “millions of individuals” play contact sports, whether that is hockey, football, or European soccer, he added. “And for all sports, there seems to be this relationship between more play and risk of this disease.”
 

‘Skewed’ population?

Commenting on the findings, Frank Conidi, MD, director, Florida Center for Health and Sports Neurology, Port St. Lucie, said he was surprised the investigators found a 23% per year increase in risk for CTE among hockey players.

Dr. Conidi has played hockey himself and works with the Florida Panthers of the National Hockey League. In his practice, he treats retired professional football players who have neurodegenerative disorders. From his experience, the number of repetitive direct head impacts in football is significantly higher than in hockey. “Most of the forces seen in hockey are from hits to the body, where the force is transferred to the head,” said Dr. Conidi, who was not involved with the research.

He noted differences in the way hockey is played around the world. In European countries, for example, the ice surface is relatively large and the emphasis tends to be more on skill than hitting.

“It would have been interesting to have the study group analyze the data based on where the athlete grew up,” he said. Dr. Conidi would also like to know when the participants played hockey. “The game is vastly different now than it was in the 1970s, ‘80s, and early ‘90s, when there was more fighting, less protective gear, and more hitting in general.”

As is the case for most studies of CTE in athletes, the study population is “skewed” because the participants likely had neurocognitive and other problems that led to their decision to donate their brain, said Dr. Conidi.

He also doesn’t believe the study should be the sole factor in a decision to continue or stop playing hockey. “We are still in the infancy stages of understanding the effects of high-impact sports on athletes’ brains.”

The study received funding from the National Institute of Neurological Diseases and Stroke and the National Institute on Aging. Dr. Mez and Dr. Conidi have reported no relevant financial relationships.

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

The Ohio House of Representatives recently passed a bill that would enable patients to use drug manufacturer coupons and other co-pay assistance as payment toward their annual deductible.

According to the Kaiser Family Foundation, approximately 1 in 4 Americans have difficulty paying for their prescription drugs, while almost half of U.S. adults report difficulty paying out-of-pocket costs not covered by their health insurance.

Supporting the bill that restricts co-pay accumulators are groups such as the Ohio State Medical Association, the Crohn’s and Colitis Foundation, Susan C. Komen, the National Multiple Sclerosis Society, and the American Diabetes Association. The bill faced opposition from health insurers and pharmacy benefit managers, reported The Columbus Dispatch.

“The debate on the management of rising drug costs between manufacturers and insurers unfortunately leaves patients caught in the middle, and practices like co-pay accumulators can have a devastating impact,” Monica Hueckel, senior director of government relations for the Ohio State Medical Association, told this news organization.

“Patients often do not even know about these policies until the coupons are no longer usable. As you can imagine, for patients with expensive medications and/or high deductible health plans, the impact is disastrous,” she said.

Ohio State Representative Susan Manchester, who co-sponsored the bill, told The Columbus Dispatch that the legislation “is needed to assist our constituents who find themselves increasingly subjected to more out-of-pocket costs as part of their insurance coverage.”

Other states blocking health insurers’ co-pay policies

With the passage of the bill, Ohio joins 12 states and Puerto Rico in preventing the use of health insurers’ co-pays to increase patients’ out-of-pocket costs, reported The Columbus Dispatch; 15 states are also considering this type of legislation.

Eighty-three percent of patients are in plans that include a co-pay accumulator, according to consulting firm Avalere, which wrote that, beginning in 2023, the Center for Medicare & Medicaid Services requires patients with Medicaid to receive “the full value of co-pay assistance” on drugs.

According to the National Conference of State Legislatures, co-pay adjustment programs present challenges for patients, with plans that include high cost sharing or co-insurance whereby a patient pays a percentage of the cost instead of a flat amount.

For example, with a co-pay adjustment policy, a patient with a $2,000 deductible plan couldn’t use a $500 coupon toward meeting the deductible, writes the National Conference of State Legislatures. Conversely, a patient in a plan without a co-pay adjustment policy could use the coupon to satisfy their annual deductible.

Patients with complex conditions, such as cancer, rheumatoid arthritis, and diabetes, which often require expensive medications, may have little choice but to fork over the unexpected co-pays, according to the organization that represents state legislatures in the United States.

The bill now moves to the Ohio Senate, reported The Columbus Dispatch.

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

The Ohio House of Representatives recently passed a bill that would enable patients to use drug manufacturer coupons and other co-pay assistance as payment toward their annual deductible.

According to the Kaiser Family Foundation, approximately 1 in 4 Americans have difficulty paying for their prescription drugs, while almost half of U.S. adults report difficulty paying out-of-pocket costs not covered by their health insurance.

Supporting the bill that restricts co-pay accumulators are groups such as the Ohio State Medical Association, the Crohn’s and Colitis Foundation, Susan C. Komen, the National Multiple Sclerosis Society, and the American Diabetes Association. The bill faced opposition from health insurers and pharmacy benefit managers, reported The Columbus Dispatch.

“The debate on the management of rising drug costs between manufacturers and insurers unfortunately leaves patients caught in the middle, and practices like co-pay accumulators can have a devastating impact,” Monica Hueckel, senior director of government relations for the Ohio State Medical Association, told this news organization.

“Patients often do not even know about these policies until the coupons are no longer usable. As you can imagine, for patients with expensive medications and/or high deductible health plans, the impact is disastrous,” she said.

Ohio State Representative Susan Manchester, who co-sponsored the bill, told The Columbus Dispatch that the legislation “is needed to assist our constituents who find themselves increasingly subjected to more out-of-pocket costs as part of their insurance coverage.”

Other states blocking health insurers’ co-pay policies

With the passage of the bill, Ohio joins 12 states and Puerto Rico in preventing the use of health insurers’ co-pays to increase patients’ out-of-pocket costs, reported The Columbus Dispatch; 15 states are also considering this type of legislation.

Eighty-three percent of patients are in plans that include a co-pay accumulator, according to consulting firm Avalere, which wrote that, beginning in 2023, the Center for Medicare & Medicaid Services requires patients with Medicaid to receive “the full value of co-pay assistance” on drugs.

According to the National Conference of State Legislatures, co-pay adjustment programs present challenges for patients, with plans that include high cost sharing or co-insurance whereby a patient pays a percentage of the cost instead of a flat amount.

For example, with a co-pay adjustment policy, a patient with a $2,000 deductible plan couldn’t use a $500 coupon toward meeting the deductible, writes the National Conference of State Legislatures. Conversely, a patient in a plan without a co-pay adjustment policy could use the coupon to satisfy their annual deductible.

Patients with complex conditions, such as cancer, rheumatoid arthritis, and diabetes, which often require expensive medications, may have little choice but to fork over the unexpected co-pays, according to the organization that represents state legislatures in the United States.

The bill now moves to the Ohio Senate, reported The Columbus Dispatch.

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

The Ohio House of Representatives recently passed a bill that would enable patients to use drug manufacturer coupons and other co-pay assistance as payment toward their annual deductible.

According to the Kaiser Family Foundation, approximately 1 in 4 Americans have difficulty paying for their prescription drugs, while almost half of U.S. adults report difficulty paying out-of-pocket costs not covered by their health insurance.

Supporting the bill that restricts co-pay accumulators are groups such as the Ohio State Medical Association, the Crohn’s and Colitis Foundation, Susan C. Komen, the National Multiple Sclerosis Society, and the American Diabetes Association. The bill faced opposition from health insurers and pharmacy benefit managers, reported The Columbus Dispatch.

“The debate on the management of rising drug costs between manufacturers and insurers unfortunately leaves patients caught in the middle, and practices like co-pay accumulators can have a devastating impact,” Monica Hueckel, senior director of government relations for the Ohio State Medical Association, told this news organization.

“Patients often do not even know about these policies until the coupons are no longer usable. As you can imagine, for patients with expensive medications and/or high deductible health plans, the impact is disastrous,” she said.

Ohio State Representative Susan Manchester, who co-sponsored the bill, told The Columbus Dispatch that the legislation “is needed to assist our constituents who find themselves increasingly subjected to more out-of-pocket costs as part of their insurance coverage.”

Other states blocking health insurers’ co-pay policies

With the passage of the bill, Ohio joins 12 states and Puerto Rico in preventing the use of health insurers’ co-pays to increase patients’ out-of-pocket costs, reported The Columbus Dispatch; 15 states are also considering this type of legislation.

Eighty-three percent of patients are in plans that include a co-pay accumulator, according to consulting firm Avalere, which wrote that, beginning in 2023, the Center for Medicare & Medicaid Services requires patients with Medicaid to receive “the full value of co-pay assistance” on drugs.

According to the National Conference of State Legislatures, co-pay adjustment programs present challenges for patients, with plans that include high cost sharing or co-insurance whereby a patient pays a percentage of the cost instead of a flat amount.

For example, with a co-pay adjustment policy, a patient with a $2,000 deductible plan couldn’t use a $500 coupon toward meeting the deductible, writes the National Conference of State Legislatures. Conversely, a patient in a plan without a co-pay adjustment policy could use the coupon to satisfy their annual deductible.

Patients with complex conditions, such as cancer, rheumatoid arthritis, and diabetes, which often require expensive medications, may have little choice but to fork over the unexpected co-pays, according to the organization that represents state legislatures in the United States.

The bill now moves to the Ohio Senate, reported The Columbus Dispatch.

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

Emma Moore felt cornered. At a community health clinic in Portland, Ore., the 29-year-old nurse practitioner said she felt overwhelmed and undertrained. Coronavirus patients flooded the clinic for 2 years, and Ms. Moore struggled to keep up.

Then the stakes became clear. On March 25, about 2,400 miles away in a Tennessee courtroom, former nurse RaDonda Vaught was convicted of two felonies and facing 8 years in prison for a fatal medication mistake.

Like many nurses, Ms. Moore wondered if that could be her. She’d made medication errors before, although none so grievous. But what about the next one? In the pressure cooker of pandemic-era health care, another mistake felt inevitable.

Four days after Ms. Vaught’s verdict, Ms. Moore quit. She said Ms. Vaught’s verdict contributed to her decision.

“It’s not worth the possibility or the likelihood that this will happen,” Ms. Moore said, “if I’m in a situation where I’m set up to fail.”

In the wake of Ms. Vaught’s trial – an extremely rare case of a health care worker being criminally prosecuted for a medical error – nurses and nursing organizations have condemned the verdict through tens of thousands of social media posts, shares, comments, and videos. They warn that the fallout will ripple through their profession, demoralizing and depleting the ranks of nurses already stretched thin by the pandemic. Ultimately, they say, it will worsen health care for all.

Statements from the American Nurses Association, the American Association of Critical-Care Nurses, and the National Medical Association said Ms. Vaught’s conviction set a “dangerous precedent.” Linda H. Aiken, PhD, RN, a nursing and sociology professor at the University of Pennsylvania, Philadelphia, said that although Ms. Vaught’s case is an “outlier,” it will make nurses less forthcoming about mistakes.

“One thing that everybody agrees on is it’s going to have a dampening effect on the reporting of errors or near misses, which then has a detrimental effect on safety,” Dr. Aiken said. “The only way you can really learn about errors in these complicated systems is to have people say, ‘Oh, I almost gave the wrong drug because …’

“Well, nobody is going to say that now.”

Fear and outrage about Ms. Vaught’s case have swirled among nurses on Facebook, Twitter, and Reddit. On TikTok, a video platform increasingly popular among medical professionals, videos with the “#RaDondaVaught” hashtag totaled more than 47 million views.

Ms. Vaught’s supporters catapulted a plea for her clemency to the top of Change.org, a petition website. And thousands also joined a Facebook group planning to gather in protest outside Ms. Vaught’s sentencing hearing in May.

Ashley Bartholomew, BSN, RN, a 36-year-old Tampa nurse who followed the trial through YouTube and Twitter, echoed the fear of many others. Nurses have long felt forced into “impossible situations” by mounting responsibilities and staffing shortages, she said, particularly in hospitals that operate with lean staffing models.

“The big response we are seeing is because all of us are acutely aware of how bad the pandemic has exacerbated the existing problems,” Ms. Bartholomew said. And “setting a precedent for criminally charging [for] an error is only going to make this exponentially worse.”

Ms. Vaught, who worked at Vanderbilt University Medical Center in Nashville, Tenn., was convicted in the death of Charlene Murphey, a 75-year-old patient who died from a drug mix-up in 2017. Ms. Murphey was prescribed a dose of a sedative, Versed, but Ms. Vaught accidentally withdrew a powerful paralyzer, vecuronium, from an automated medication-dispensing cabinet and administered it to the patient.

Prosecutors argued that Ms. Vaught overlooked many obvious signs she’d withdrawn the wrong drug and did not monitor Ms. Murphey after she was given a deadly dose. Ms. Vaught owned up to the error but said it was an honest mistake, not a crime.

Some of Ms. Vaught’s peers support the conviction.

Scott G. Shelp, BSN, RN, a California nurse with a small YouTube channel, posted a 26-minute self-described “unpopular opinion” that Ms. Vaught deserves to serve prison time. “We need to stick up for each other,” he said, “but we cannot defend the indefensible.”

Mr. Shelp said he would never make the same error as Ms. Vaught and “neither would any competent nurse.” Regarding concerns that the conviction would discourage nurses from disclosing errors, Mr. Shelp said “dishonest” nurses “should be weeded out” of the profession anyway.

“In any other circumstance, I can’t believe anyone – including nurses – would accept ‘I didn’t mean to’ as a serious defense,” Mr. Shelp said. “Punishment for a harmful act someone actually did is justice.”

Ms. Vaught was acquitted of reckless homicide but convicted of a lesser charge, criminally negligent homicide, and gross neglect of an impaired adult. As outrage spread across social media, the Nashville district attorney’s office defended the conviction, saying in a statement it was “not an indictment against the nursing profession or the medical community.”

“This case is, and always has been, about the one single individual who made 17 egregious actions, and inactions, that killed an elderly woman,” said the office’s spokesperson, Steve Hayslip. “The jury found that Vaught’s actions were so far below the protocols and standard level of care, that the jury (which included a longtime nurse and another health care professional) returned a guilty verdict in less than four hours.”

The office of Tennessee Gov. Bill Lee confirmed he is not considering clemency for Ms. Vaught despite the Change.org petition, which had amassed about 187,000 signatures as of April 4.

Casey Black, press secretary for Gov. Lee, said that outside of death penalty cases the governor relies on the Board of Parole to recommend defendants for clemency, which happens only after sentencing and a board investigation.

But the controversy around Ms. Vaught’s case is far from over. As of April 4, more than 8,200 people had joined a Facebook group planning a march in protest outside the courthouse during her sentencing May 13.

Among the event’s planners is Tina Visant, the host of “Good Nurse Bad Nurse,” a podcast that followed Ms. Vaught’s case and opposed her prosecution.

“I don’t know how Nashville is going to handle it,” Ms. Visant said of the protest during a recent episode about Ms. Vaught’s trial. “There are a lot of people coming from all over.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Emma Moore felt cornered. At a community health clinic in Portland, Ore., the 29-year-old nurse practitioner said she felt overwhelmed and undertrained. Coronavirus patients flooded the clinic for 2 years, and Ms. Moore struggled to keep up.

Then the stakes became clear. On March 25, about 2,400 miles away in a Tennessee courtroom, former nurse RaDonda Vaught was convicted of two felonies and facing 8 years in prison for a fatal medication mistake.

Like many nurses, Ms. Moore wondered if that could be her. She’d made medication errors before, although none so grievous. But what about the next one? In the pressure cooker of pandemic-era health care, another mistake felt inevitable.

Four days after Ms. Vaught’s verdict, Ms. Moore quit. She said Ms. Vaught’s verdict contributed to her decision.

“It’s not worth the possibility or the likelihood that this will happen,” Ms. Moore said, “if I’m in a situation where I’m set up to fail.”

In the wake of Ms. Vaught’s trial – an extremely rare case of a health care worker being criminally prosecuted for a medical error – nurses and nursing organizations have condemned the verdict through tens of thousands of social media posts, shares, comments, and videos. They warn that the fallout will ripple through their profession, demoralizing and depleting the ranks of nurses already stretched thin by the pandemic. Ultimately, they say, it will worsen health care for all.

Statements from the American Nurses Association, the American Association of Critical-Care Nurses, and the National Medical Association said Ms. Vaught’s conviction set a “dangerous precedent.” Linda H. Aiken, PhD, RN, a nursing and sociology professor at the University of Pennsylvania, Philadelphia, said that although Ms. Vaught’s case is an “outlier,” it will make nurses less forthcoming about mistakes.

“One thing that everybody agrees on is it’s going to have a dampening effect on the reporting of errors or near misses, which then has a detrimental effect on safety,” Dr. Aiken said. “The only way you can really learn about errors in these complicated systems is to have people say, ‘Oh, I almost gave the wrong drug because …’

“Well, nobody is going to say that now.”

Fear and outrage about Ms. Vaught’s case have swirled among nurses on Facebook, Twitter, and Reddit. On TikTok, a video platform increasingly popular among medical professionals, videos with the “#RaDondaVaught” hashtag totaled more than 47 million views.

Ms. Vaught’s supporters catapulted a plea for her clemency to the top of Change.org, a petition website. And thousands also joined a Facebook group planning to gather in protest outside Ms. Vaught’s sentencing hearing in May.

Ashley Bartholomew, BSN, RN, a 36-year-old Tampa nurse who followed the trial through YouTube and Twitter, echoed the fear of many others. Nurses have long felt forced into “impossible situations” by mounting responsibilities and staffing shortages, she said, particularly in hospitals that operate with lean staffing models.

“The big response we are seeing is because all of us are acutely aware of how bad the pandemic has exacerbated the existing problems,” Ms. Bartholomew said. And “setting a precedent for criminally charging [for] an error is only going to make this exponentially worse.”

Ms. Vaught, who worked at Vanderbilt University Medical Center in Nashville, Tenn., was convicted in the death of Charlene Murphey, a 75-year-old patient who died from a drug mix-up in 2017. Ms. Murphey was prescribed a dose of a sedative, Versed, but Ms. Vaught accidentally withdrew a powerful paralyzer, vecuronium, from an automated medication-dispensing cabinet and administered it to the patient.

Prosecutors argued that Ms. Vaught overlooked many obvious signs she’d withdrawn the wrong drug and did not monitor Ms. Murphey after she was given a deadly dose. Ms. Vaught owned up to the error but said it was an honest mistake, not a crime.

Some of Ms. Vaught’s peers support the conviction.

Scott G. Shelp, BSN, RN, a California nurse with a small YouTube channel, posted a 26-minute self-described “unpopular opinion” that Ms. Vaught deserves to serve prison time. “We need to stick up for each other,” he said, “but we cannot defend the indefensible.”

Mr. Shelp said he would never make the same error as Ms. Vaught and “neither would any competent nurse.” Regarding concerns that the conviction would discourage nurses from disclosing errors, Mr. Shelp said “dishonest” nurses “should be weeded out” of the profession anyway.

“In any other circumstance, I can’t believe anyone – including nurses – would accept ‘I didn’t mean to’ as a serious defense,” Mr. Shelp said. “Punishment for a harmful act someone actually did is justice.”

Ms. Vaught was acquitted of reckless homicide but convicted of a lesser charge, criminally negligent homicide, and gross neglect of an impaired adult. As outrage spread across social media, the Nashville district attorney’s office defended the conviction, saying in a statement it was “not an indictment against the nursing profession or the medical community.”

“This case is, and always has been, about the one single individual who made 17 egregious actions, and inactions, that killed an elderly woman,” said the office’s spokesperson, Steve Hayslip. “The jury found that Vaught’s actions were so far below the protocols and standard level of care, that the jury (which included a longtime nurse and another health care professional) returned a guilty verdict in less than four hours.”

The office of Tennessee Gov. Bill Lee confirmed he is not considering clemency for Ms. Vaught despite the Change.org petition, which had amassed about 187,000 signatures as of April 4.

Casey Black, press secretary for Gov. Lee, said that outside of death penalty cases the governor relies on the Board of Parole to recommend defendants for clemency, which happens only after sentencing and a board investigation.

But the controversy around Ms. Vaught’s case is far from over. As of April 4, more than 8,200 people had joined a Facebook group planning a march in protest outside the courthouse during her sentencing May 13.

Among the event’s planners is Tina Visant, the host of “Good Nurse Bad Nurse,” a podcast that followed Ms. Vaught’s case and opposed her prosecution.

“I don’t know how Nashville is going to handle it,” Ms. Visant said of the protest during a recent episode about Ms. Vaught’s trial. “There are a lot of people coming from all over.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Emma Moore felt cornered. At a community health clinic in Portland, Ore., the 29-year-old nurse practitioner said she felt overwhelmed and undertrained. Coronavirus patients flooded the clinic for 2 years, and Ms. Moore struggled to keep up.

Then the stakes became clear. On March 25, about 2,400 miles away in a Tennessee courtroom, former nurse RaDonda Vaught was convicted of two felonies and facing 8 years in prison for a fatal medication mistake.

Like many nurses, Ms. Moore wondered if that could be her. She’d made medication errors before, although none so grievous. But what about the next one? In the pressure cooker of pandemic-era health care, another mistake felt inevitable.

Four days after Ms. Vaught’s verdict, Ms. Moore quit. She said Ms. Vaught’s verdict contributed to her decision.

“It’s not worth the possibility or the likelihood that this will happen,” Ms. Moore said, “if I’m in a situation where I’m set up to fail.”

In the wake of Ms. Vaught’s trial – an extremely rare case of a health care worker being criminally prosecuted for a medical error – nurses and nursing organizations have condemned the verdict through tens of thousands of social media posts, shares, comments, and videos. They warn that the fallout will ripple through their profession, demoralizing and depleting the ranks of nurses already stretched thin by the pandemic. Ultimately, they say, it will worsen health care for all.

Statements from the American Nurses Association, the American Association of Critical-Care Nurses, and the National Medical Association said Ms. Vaught’s conviction set a “dangerous precedent.” Linda H. Aiken, PhD, RN, a nursing and sociology professor at the University of Pennsylvania, Philadelphia, said that although Ms. Vaught’s case is an “outlier,” it will make nurses less forthcoming about mistakes.

“One thing that everybody agrees on is it’s going to have a dampening effect on the reporting of errors or near misses, which then has a detrimental effect on safety,” Dr. Aiken said. “The only way you can really learn about errors in these complicated systems is to have people say, ‘Oh, I almost gave the wrong drug because …’

“Well, nobody is going to say that now.”

Fear and outrage about Ms. Vaught’s case have swirled among nurses on Facebook, Twitter, and Reddit. On TikTok, a video platform increasingly popular among medical professionals, videos with the “#RaDondaVaught” hashtag totaled more than 47 million views.

Ms. Vaught’s supporters catapulted a plea for her clemency to the top of Change.org, a petition website. And thousands also joined a Facebook group planning to gather in protest outside Ms. Vaught’s sentencing hearing in May.

Ashley Bartholomew, BSN, RN, a 36-year-old Tampa nurse who followed the trial through YouTube and Twitter, echoed the fear of many others. Nurses have long felt forced into “impossible situations” by mounting responsibilities and staffing shortages, she said, particularly in hospitals that operate with lean staffing models.

“The big response we are seeing is because all of us are acutely aware of how bad the pandemic has exacerbated the existing problems,” Ms. Bartholomew said. And “setting a precedent for criminally charging [for] an error is only going to make this exponentially worse.”

Ms. Vaught, who worked at Vanderbilt University Medical Center in Nashville, Tenn., was convicted in the death of Charlene Murphey, a 75-year-old patient who died from a drug mix-up in 2017. Ms. Murphey was prescribed a dose of a sedative, Versed, but Ms. Vaught accidentally withdrew a powerful paralyzer, vecuronium, from an automated medication-dispensing cabinet and administered it to the patient.

Prosecutors argued that Ms. Vaught overlooked many obvious signs she’d withdrawn the wrong drug and did not monitor Ms. Murphey after she was given a deadly dose. Ms. Vaught owned up to the error but said it was an honest mistake, not a crime.

Some of Ms. Vaught’s peers support the conviction.

Scott G. Shelp, BSN, RN, a California nurse with a small YouTube channel, posted a 26-minute self-described “unpopular opinion” that Ms. Vaught deserves to serve prison time. “We need to stick up for each other,” he said, “but we cannot defend the indefensible.”

Mr. Shelp said he would never make the same error as Ms. Vaught and “neither would any competent nurse.” Regarding concerns that the conviction would discourage nurses from disclosing errors, Mr. Shelp said “dishonest” nurses “should be weeded out” of the profession anyway.

“In any other circumstance, I can’t believe anyone – including nurses – would accept ‘I didn’t mean to’ as a serious defense,” Mr. Shelp said. “Punishment for a harmful act someone actually did is justice.”

Ms. Vaught was acquitted of reckless homicide but convicted of a lesser charge, criminally negligent homicide, and gross neglect of an impaired adult. As outrage spread across social media, the Nashville district attorney’s office defended the conviction, saying in a statement it was “not an indictment against the nursing profession or the medical community.”

“This case is, and always has been, about the one single individual who made 17 egregious actions, and inactions, that killed an elderly woman,” said the office’s spokesperson, Steve Hayslip. “The jury found that Vaught’s actions were so far below the protocols and standard level of care, that the jury (which included a longtime nurse and another health care professional) returned a guilty verdict in less than four hours.”

The office of Tennessee Gov. Bill Lee confirmed he is not considering clemency for Ms. Vaught despite the Change.org petition, which had amassed about 187,000 signatures as of April 4.

Casey Black, press secretary for Gov. Lee, said that outside of death penalty cases the governor relies on the Board of Parole to recommend defendants for clemency, which happens only after sentencing and a board investigation.

But the controversy around Ms. Vaught’s case is far from over. As of April 4, more than 8,200 people had joined a Facebook group planning a march in protest outside the courthouse during her sentencing May 13.

Among the event’s planners is Tina Visant, the host of “Good Nurse Bad Nurse,” a podcast that followed Ms. Vaught’s case and opposed her prosecution.

“I don’t know how Nashville is going to handle it,” Ms. Visant said of the protest during a recent episode about Ms. Vaught’s trial. “There are a lot of people coming from all over.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

A novel endovascular brain-computer interface is safe and effective, allowing paralyzed patients to use their thoughts to perform daily tasks, results of a small, first-in-human study show.

A potential life changer for patients with amyotrophic lateral sclerosis (ALS), the minimally invasive device enables patients to carry out important activities of daily living.

“Our participants are able to use the device to perform tasks like sending email, texting loved ones and caregivers, browsing the web, and doing personal finances such as online banking,” study investigator Douglas J. Weber, PhD, professor of mechanical engineering and neuroscience, Carnegie Mellon University, Pittsburgh, told a press briefing.

The technology allowed one patient to write a book (due out later this year) and another patient to maintain communication despite losing his ability to speak, said the study’s lead investigator, Bruce Campbell, MBBS, PhD, professor of neurology, Royal Melbourne Hospital, University of Melbourne.

“In addition to providing patients with communicative capabilities not possible as a result of their disease, it is our goal to enable patients to be more independently involved in their care going forward, by enabling effective and faster communication directly with their caregiver and physician,” said Dr. Campbell.

The findings were presented at the 2022 annual meeting of the American Academy of Neurology.
 

Minimally invasive

ALS, also known as Lou Gehrig’s disease, is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. Patients with ALS eventually lose the ability to control muscle movement, often leading to total paralysis.

“Extending the period in which patients are able to communicate with loved ones and caregivers could provide a very meaningful benefit to patients with ALS,” said Dr. Weber.

Brain-computer interfaces measure and translate brain signals, with some functioning as motor neuro-prostheses. These devices provide direct communication between the brain and an external device by recording and decoding signals from the precentral gyrus as the result of movement intention.

“The technology has potential to empower the more than five million people in the U.S. who are severely paralyzed to once again perform important activities of daily living independently,” said Dr. Weber.

Until now, motor neuro-prostheses required surgery to remove a portion of the skull and place electrodes on to the brain. However, the new minimally invasive motor neuro-prostheses reach the brain by vascular access, dispensing with the need for a craniotomy.

“The brain-computer interface device used in our study is unique in that it does not require invasive open surgery to implant,” said Dr. Weber. “Instead this is an endovascular brain-computer interface.”

Using a catheter, surgeons feed the BCI through one of two jugular veins in the neck. They position an array of 16 sensors or electrodes on a stent-like scaffold that deploys against the walls of the superior sagittal sinus.
 

No adverse events

Describing the device, Dr. Weber said the electrodes or sensing elements are tiny and the body of the stent, which serves as a scaffold to support the electrodes, resembles a standard endovascular stent.

“It’s very small at the time of delivery because it’s held within the body of a catheter, but then when deployed it expands to contact the wall of the vein.”

The device transmits brain signals from the motor cortex to an electronics unit, located in a subcutaneous pocket that decodes movement signals. The machine-learning decoder is programmed as follows: When a trainer asked participants to attempt certain movements, like tapping their foot or extending their knee, the decoder analyzes nerve cell signals from those movement attempts. The decoder is able to translate movement signals into computer navigation.

The study included four patients with ALS who were paralyzed because of the disease and were trained to use the device.

A key safety endpoint was device-related serious adverse events resulting in death or increased disability during the post-implant evaluation period. Results showed all four participants successfully completed the 12-month follow-up with no serious adverse events.

Researchers also assessed target vessel patency and incidence of device migration at 3 and 12 months. Postoperative imaging showed that in all participants, the blood vessel that held the implanted device remained open and stayed in place.

Addressing the potential for blood clots, Dr. Weber said that so far there has been no sign of clotting or vascular occlusion.

“The device itself integrates well into the walls of the blood vessel over time,” he said. “Within the acute period after implantation, there’s time where the device is exposed to the blood stream, but once it becomes encapsulated and fully integrated into the blood vessel wall, the risks of thrombosis diminish.”
 

Greater independence

Researchers also recorded signal fidelity and stability over 12 months and use of the brain-computer interface to perform routine tasks. All participants learned to use the motor neuro-prostheses with eye tracking for computer use. Eye tracking technology helps a computer determine what a person is looking at.

Using the system, patients were able to complete tasks without help. These included text messaging and managing finances. “Since the device is fully implanted and easy for patients to use, they can use the technology independently and in their own home,” said Dr. Weber.

Although the study started with patients with ALS, those paralyzed from other causes, such as an upper spinal cord injury or brain-stem stroke could also benefit from this technology, Dr. Weber said. In addition, the technology could be expanded to broaden brain communication capabilities potentially to include robotic limbs, he said.

There’s even the potential to use this minimally invasive brain interface technology to deliver therapies like deep brain stimulation, which Dr. Weber noted is a growing field. “It’s [the] early days, but it’s a very exciting new direction for brain interface technology,” he said.

Researchers are now recruiting patients for the first U.S.-based feasibility trial of the device that will be funded by the NIH, said Dr. Weber. A limitation of the research was the study’s small size.
 

Advancing the field

Reached for a comment, Kevin C. Davis, an MD and PhD student in the department of biomedical engineering, University of Miami Miller School of Medicine, said this new work moves the field forward in an important way.

Dr. Davis and colleagues have shown the effectiveness of another technology used to overcome paralysis – a small portable system that facilitates hand grasp of a patient with a spinal cord injury. He reported on this DBS-based BCI system at the American Association of Neurological Surgeons (AANS) 2021 Annual Meeting.

Developing effective brain-computer interfaces, and motor neural prosthetics that avoid surgery, as the team did in this new study, is “worth exploring,” said Dr. Davis.

However, although the device used in this new study avoids cranial surgery, “sole vascular access may limit the device’s ability to reach other areas of the brain more suitable for upper-limb motor prosthetics,” he said.

“Determining how much function such a device could provide to individuals with locked-in syndrome or paralysis will be important in determining its viability as an eventual clinical tool for patients.”

The study was supported by Synchron, the maker of the device, the U.S. Defense Advanced Research Projects Agency, the Office of Naval Research, the National Health and Medical Research Council of Australia, the Australian Federal Government Foundation, and the Motor Neuron Disease Research Institute of Australia.

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

A novel endovascular brain-computer interface is safe and effective, allowing paralyzed patients to use their thoughts to perform daily tasks, results of a small, first-in-human study show.

A potential life changer for patients with amyotrophic lateral sclerosis (ALS), the minimally invasive device enables patients to carry out important activities of daily living.

“Our participants are able to use the device to perform tasks like sending email, texting loved ones and caregivers, browsing the web, and doing personal finances such as online banking,” study investigator Douglas J. Weber, PhD, professor of mechanical engineering and neuroscience, Carnegie Mellon University, Pittsburgh, told a press briefing.

The technology allowed one patient to write a book (due out later this year) and another patient to maintain communication despite losing his ability to speak, said the study’s lead investigator, Bruce Campbell, MBBS, PhD, professor of neurology, Royal Melbourne Hospital, University of Melbourne.

“In addition to providing patients with communicative capabilities not possible as a result of their disease, it is our goal to enable patients to be more independently involved in their care going forward, by enabling effective and faster communication directly with their caregiver and physician,” said Dr. Campbell.

The findings were presented at the 2022 annual meeting of the American Academy of Neurology.
 

Minimally invasive

ALS, also known as Lou Gehrig’s disease, is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. Patients with ALS eventually lose the ability to control muscle movement, often leading to total paralysis.

“Extending the period in which patients are able to communicate with loved ones and caregivers could provide a very meaningful benefit to patients with ALS,” said Dr. Weber.

Brain-computer interfaces measure and translate brain signals, with some functioning as motor neuro-prostheses. These devices provide direct communication between the brain and an external device by recording and decoding signals from the precentral gyrus as the result of movement intention.

“The technology has potential to empower the more than five million people in the U.S. who are severely paralyzed to once again perform important activities of daily living independently,” said Dr. Weber.

Until now, motor neuro-prostheses required surgery to remove a portion of the skull and place electrodes on to the brain. However, the new minimally invasive motor neuro-prostheses reach the brain by vascular access, dispensing with the need for a craniotomy.

“The brain-computer interface device used in our study is unique in that it does not require invasive open surgery to implant,” said Dr. Weber. “Instead this is an endovascular brain-computer interface.”

Using a catheter, surgeons feed the BCI through one of two jugular veins in the neck. They position an array of 16 sensors or electrodes on a stent-like scaffold that deploys against the walls of the superior sagittal sinus.
 

No adverse events

Describing the device, Dr. Weber said the electrodes or sensing elements are tiny and the body of the stent, which serves as a scaffold to support the electrodes, resembles a standard endovascular stent.

“It’s very small at the time of delivery because it’s held within the body of a catheter, but then when deployed it expands to contact the wall of the vein.”

The device transmits brain signals from the motor cortex to an electronics unit, located in a subcutaneous pocket that decodes movement signals. The machine-learning decoder is programmed as follows: When a trainer asked participants to attempt certain movements, like tapping their foot or extending their knee, the decoder analyzes nerve cell signals from those movement attempts. The decoder is able to translate movement signals into computer navigation.

The study included four patients with ALS who were paralyzed because of the disease and were trained to use the device.

A key safety endpoint was device-related serious adverse events resulting in death or increased disability during the post-implant evaluation period. Results showed all four participants successfully completed the 12-month follow-up with no serious adverse events.

Researchers also assessed target vessel patency and incidence of device migration at 3 and 12 months. Postoperative imaging showed that in all participants, the blood vessel that held the implanted device remained open and stayed in place.

Addressing the potential for blood clots, Dr. Weber said that so far there has been no sign of clotting or vascular occlusion.

“The device itself integrates well into the walls of the blood vessel over time,” he said. “Within the acute period after implantation, there’s time where the device is exposed to the blood stream, but once it becomes encapsulated and fully integrated into the blood vessel wall, the risks of thrombosis diminish.”
 

Greater independence

Researchers also recorded signal fidelity and stability over 12 months and use of the brain-computer interface to perform routine tasks. All participants learned to use the motor neuro-prostheses with eye tracking for computer use. Eye tracking technology helps a computer determine what a person is looking at.

Using the system, patients were able to complete tasks without help. These included text messaging and managing finances. “Since the device is fully implanted and easy for patients to use, they can use the technology independently and in their own home,” said Dr. Weber.

Although the study started with patients with ALS, those paralyzed from other causes, such as an upper spinal cord injury or brain-stem stroke could also benefit from this technology, Dr. Weber said. In addition, the technology could be expanded to broaden brain communication capabilities potentially to include robotic limbs, he said.

There’s even the potential to use this minimally invasive brain interface technology to deliver therapies like deep brain stimulation, which Dr. Weber noted is a growing field. “It’s [the] early days, but it’s a very exciting new direction for brain interface technology,” he said.

Researchers are now recruiting patients for the first U.S.-based feasibility trial of the device that will be funded by the NIH, said Dr. Weber. A limitation of the research was the study’s small size.
 

Advancing the field

Reached for a comment, Kevin C. Davis, an MD and PhD student in the department of biomedical engineering, University of Miami Miller School of Medicine, said this new work moves the field forward in an important way.

Dr. Davis and colleagues have shown the effectiveness of another technology used to overcome paralysis – a small portable system that facilitates hand grasp of a patient with a spinal cord injury. He reported on this DBS-based BCI system at the American Association of Neurological Surgeons (AANS) 2021 Annual Meeting.

Developing effective brain-computer interfaces, and motor neural prosthetics that avoid surgery, as the team did in this new study, is “worth exploring,” said Dr. Davis.

However, although the device used in this new study avoids cranial surgery, “sole vascular access may limit the device’s ability to reach other areas of the brain more suitable for upper-limb motor prosthetics,” he said.

“Determining how much function such a device could provide to individuals with locked-in syndrome or paralysis will be important in determining its viability as an eventual clinical tool for patients.”

The study was supported by Synchron, the maker of the device, the U.S. Defense Advanced Research Projects Agency, the Office of Naval Research, the National Health and Medical Research Council of Australia, the Australian Federal Government Foundation, and the Motor Neuron Disease Research Institute of Australia.

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

A novel endovascular brain-computer interface is safe and effective, allowing paralyzed patients to use their thoughts to perform daily tasks, results of a small, first-in-human study show.

A potential life changer for patients with amyotrophic lateral sclerosis (ALS), the minimally invasive device enables patients to carry out important activities of daily living.

“Our participants are able to use the device to perform tasks like sending email, texting loved ones and caregivers, browsing the web, and doing personal finances such as online banking,” study investigator Douglas J. Weber, PhD, professor of mechanical engineering and neuroscience, Carnegie Mellon University, Pittsburgh, told a press briefing.

The technology allowed one patient to write a book (due out later this year) and another patient to maintain communication despite losing his ability to speak, said the study’s lead investigator, Bruce Campbell, MBBS, PhD, professor of neurology, Royal Melbourne Hospital, University of Melbourne.

“In addition to providing patients with communicative capabilities not possible as a result of their disease, it is our goal to enable patients to be more independently involved in their care going forward, by enabling effective and faster communication directly with their caregiver and physician,” said Dr. Campbell.

The findings were presented at the 2022 annual meeting of the American Academy of Neurology.
 

Minimally invasive

ALS, also known as Lou Gehrig’s disease, is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. Patients with ALS eventually lose the ability to control muscle movement, often leading to total paralysis.

“Extending the period in which patients are able to communicate with loved ones and caregivers could provide a very meaningful benefit to patients with ALS,” said Dr. Weber.

Brain-computer interfaces measure and translate brain signals, with some functioning as motor neuro-prostheses. These devices provide direct communication between the brain and an external device by recording and decoding signals from the precentral gyrus as the result of movement intention.

“The technology has potential to empower the more than five million people in the U.S. who are severely paralyzed to once again perform important activities of daily living independently,” said Dr. Weber.

Until now, motor neuro-prostheses required surgery to remove a portion of the skull and place electrodes on to the brain. However, the new minimally invasive motor neuro-prostheses reach the brain by vascular access, dispensing with the need for a craniotomy.

“The brain-computer interface device used in our study is unique in that it does not require invasive open surgery to implant,” said Dr. Weber. “Instead this is an endovascular brain-computer interface.”

Using a catheter, surgeons feed the BCI through one of two jugular veins in the neck. They position an array of 16 sensors or electrodes on a stent-like scaffold that deploys against the walls of the superior sagittal sinus.
 

No adverse events

Describing the device, Dr. Weber said the electrodes or sensing elements are tiny and the body of the stent, which serves as a scaffold to support the electrodes, resembles a standard endovascular stent.

“It’s very small at the time of delivery because it’s held within the body of a catheter, but then when deployed it expands to contact the wall of the vein.”

The device transmits brain signals from the motor cortex to an electronics unit, located in a subcutaneous pocket that decodes movement signals. The machine-learning decoder is programmed as follows: When a trainer asked participants to attempt certain movements, like tapping their foot or extending their knee, the decoder analyzes nerve cell signals from those movement attempts. The decoder is able to translate movement signals into computer navigation.

The study included four patients with ALS who were paralyzed because of the disease and were trained to use the device.

A key safety endpoint was device-related serious adverse events resulting in death or increased disability during the post-implant evaluation period. Results showed all four participants successfully completed the 12-month follow-up with no serious adverse events.

Researchers also assessed target vessel patency and incidence of device migration at 3 and 12 months. Postoperative imaging showed that in all participants, the blood vessel that held the implanted device remained open and stayed in place.

Addressing the potential for blood clots, Dr. Weber said that so far there has been no sign of clotting or vascular occlusion.

“The device itself integrates well into the walls of the blood vessel over time,” he said. “Within the acute period after implantation, there’s time where the device is exposed to the blood stream, but once it becomes encapsulated and fully integrated into the blood vessel wall, the risks of thrombosis diminish.”
 

Greater independence

Researchers also recorded signal fidelity and stability over 12 months and use of the brain-computer interface to perform routine tasks. All participants learned to use the motor neuro-prostheses with eye tracking for computer use. Eye tracking technology helps a computer determine what a person is looking at.

Using the system, patients were able to complete tasks without help. These included text messaging and managing finances. “Since the device is fully implanted and easy for patients to use, they can use the technology independently and in their own home,” said Dr. Weber.

Although the study started with patients with ALS, those paralyzed from other causes, such as an upper spinal cord injury or brain-stem stroke could also benefit from this technology, Dr. Weber said. In addition, the technology could be expanded to broaden brain communication capabilities potentially to include robotic limbs, he said.

There’s even the potential to use this minimally invasive brain interface technology to deliver therapies like deep brain stimulation, which Dr. Weber noted is a growing field. “It’s [the] early days, but it’s a very exciting new direction for brain interface technology,” he said.

Researchers are now recruiting patients for the first U.S.-based feasibility trial of the device that will be funded by the NIH, said Dr. Weber. A limitation of the research was the study’s small size.
 

Advancing the field

Reached for a comment, Kevin C. Davis, an MD and PhD student in the department of biomedical engineering, University of Miami Miller School of Medicine, said this new work moves the field forward in an important way.

Dr. Davis and colleagues have shown the effectiveness of another technology used to overcome paralysis – a small portable system that facilitates hand grasp of a patient with a spinal cord injury. He reported on this DBS-based BCI system at the American Association of Neurological Surgeons (AANS) 2021 Annual Meeting.

Developing effective brain-computer interfaces, and motor neural prosthetics that avoid surgery, as the team did in this new study, is “worth exploring,” said Dr. Davis.

However, although the device used in this new study avoids cranial surgery, “sole vascular access may limit the device’s ability to reach other areas of the brain more suitable for upper-limb motor prosthetics,” he said.

“Determining how much function such a device could provide to individuals with locked-in syndrome or paralysis will be important in determining its viability as an eventual clinical tool for patients.”

The study was supported by Synchron, the maker of the device, the U.S. Defense Advanced Research Projects Agency, the Office of Naval Research, the National Health and Medical Research Council of Australia, the Australian Federal Government Foundation, and the Motor Neuron Disease Research Institute of Australia.

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

SEATTLE – Use of antiseizure medications while breastfeeding is not associated with differences in child cognitive outcomes at age 3, according to new results from the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study.

The study follows results from the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study, which found no evidence of cognitive harm in children who were exposed in utero to antiepileptic drugs. “[In the NEAD study] we followed our cohort to age 6 and found them to have actually an improvement in cognition by about 4 IQ points by the time they got to age 6,” Kimford J. Meador, MD, said during a presentation of the results of the MONEAD study at the 2022 annual meeting of the American Academy of Neurology.

Breastfeeding has health benefits for both mothers and children, including reduced risk of respiratory tract infections, atopic dermatitis, asthma, and diabetes in children, and reduced risk of diabetes, breast cancer, ovarian cancer, and postpartum depression in mothers. Despite those benefits, concerns about harms from exposure to antiepileptic drugs may prompt some women to avoid breastfeeding.

The results of NEAD and MONEAD should reassure patients, according to Dr. Meador, professor of neurology at Stanford (Calif.) University. “Given the known multiple benefits of breastfeeding … women with epilepsy should be encouraged to breastfeed,” he said.
 

A responsibility to ‘engage and educate’ patients

Jennifer Hopp, MD, who served as a discussant for the presentation, underscored the need for neurologists to address pregnancy with female patients of childbearing agents. “The issues may include fertility, peripartum management, and outcomes that really go through the lifespan to also include issues of menopause,” Dr. Hopp, associate professor of neurology at the University of Maryland, Baltimore, said during her presentation.

Dr. Hopp noted one study showing lower rates of breastfeeding among mothers with epilepsy. “Breastfeeding rates in women with epilepsy are strikingly lower than in women who do not have epilepsy,” said Dr. Hopp. Another study showed that women with epilepsy were less likely to sustain breastfeeding after 6 weeks.

Dr. Hopp implored neurologists to address this. “It’s our responsibility to engage and educate our patients. These data provide us messaging to our patients that the newer drugs do not adversely affect outcome independently of their other exposure, and really support well-informed choices in breastfeeding,” said Dr. Hopp.
 

Outdated attitudes still persist

Dr. Meador referred to the stigma that surrounds epilepsy, including some state laws that called for sterilization of women with epilepsy that lasted until the 1960s. One might think that such attitudes are gone, “but it’s still there,” said Dr. Meador, who recounted a story a colleague told him about a woman on antiseizure medication. In the hospital, the nurse told her not to breastfeed. The neurological consult told her not to breastfeed. She breastfed anyway. “Then they reported her for child neglect, and that was just a few years ago. So I think the message needs to be loud and clear that we encourage [women with epilepsy] to breastfeed because we have the known benefits, and now several studies showing clearly no adverse effects of breastfeeding while taking antiseizure medications,” said Dr. Meador.

MONEAD findings

The MONEAD study included women from 20 different sites, with 145 participating investigators. The researchers compared outcomes in 284 women with epilepsy and 87 healthy women. The maternal mean IQ was 98 among women with epilepsy (95% confidence interval [CI], 96-99), and 105 (95% CI, 102-107) among healthy women. Seventy-six percent of women with epilepsy breastfed, versus 89% of controls.

Among the study cohort, 79% of women with epilepsy were on monotherapy, and 21% were on polytherapy. Thirty-five percent received lamotrigine, 28% levetiracetam, 16% were on another monotherapy, 10% received a combination of lamotrigine and levetiracetam, and 11% received a different combination.

At age 3, there was no association between the verbal index score of the child and whether the mother had epilepsy or not (difference, 0.4; P = .770). The researchers did find associations with the mother’s IQ (0.3; P < .001), male versus female child sex (–4.9; P < .001), Hispanic or Latino ethnicity (vs. Non-Hispanic, –5.5; P < .001), mother without college degree (–7.0; P < .001), average Beck Anxiety Inventory score after birth (–0.4; P < .001), and weeks of gestational age at enrollment.

The researchers found no association between third trimester antiseizure medication blood levels and verbal index score after adjustment (–2.9; P = .149), with the exception of levetiracetam (–9.0; P = .033). “This is interesting (but) not to be overblown, because overall the children on levetiracetam did well. But it must be remembered that teratogens act in an exposure dependent manner, so we’re constantly in this balancing act of trying to make sure you get enough medication on board to stop the seizures and protect the mother and the child, and at the same time, not too much on board where we increase the risk of teratogenicity in the child,” said Dr. Meador.

The study was funded by the National Institutes of Health. Dr. Meador and Dr. Hopp have no relevant financial disclosures.

SEATTLE – Use of antiseizure medications while breastfeeding is not associated with differences in child cognitive outcomes at age 3, according to new results from the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study.

The study follows results from the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study, which found no evidence of cognitive harm in children who were exposed in utero to antiepileptic drugs. “[In the NEAD study] we followed our cohort to age 6 and found them to have actually an improvement in cognition by about 4 IQ points by the time they got to age 6,” Kimford J. Meador, MD, said during a presentation of the results of the MONEAD study at the 2022 annual meeting of the American Academy of Neurology.

Breastfeeding has health benefits for both mothers and children, including reduced risk of respiratory tract infections, atopic dermatitis, asthma, and diabetes in children, and reduced risk of diabetes, breast cancer, ovarian cancer, and postpartum depression in mothers. Despite those benefits, concerns about harms from exposure to antiepileptic drugs may prompt some women to avoid breastfeeding.

The results of NEAD and MONEAD should reassure patients, according to Dr. Meador, professor of neurology at Stanford (Calif.) University. “Given the known multiple benefits of breastfeeding … women with epilepsy should be encouraged to breastfeed,” he said.
 

A responsibility to ‘engage and educate’ patients

Jennifer Hopp, MD, who served as a discussant for the presentation, underscored the need for neurologists to address pregnancy with female patients of childbearing agents. “The issues may include fertility, peripartum management, and outcomes that really go through the lifespan to also include issues of menopause,” Dr. Hopp, associate professor of neurology at the University of Maryland, Baltimore, said during her presentation.

Dr. Hopp noted one study showing lower rates of breastfeeding among mothers with epilepsy. “Breastfeeding rates in women with epilepsy are strikingly lower than in women who do not have epilepsy,” said Dr. Hopp. Another study showed that women with epilepsy were less likely to sustain breastfeeding after 6 weeks.

Dr. Hopp implored neurologists to address this. “It’s our responsibility to engage and educate our patients. These data provide us messaging to our patients that the newer drugs do not adversely affect outcome independently of their other exposure, and really support well-informed choices in breastfeeding,” said Dr. Hopp.
 

Outdated attitudes still persist

Dr. Meador referred to the stigma that surrounds epilepsy, including some state laws that called for sterilization of women with epilepsy that lasted until the 1960s. One might think that such attitudes are gone, “but it’s still there,” said Dr. Meador, who recounted a story a colleague told him about a woman on antiseizure medication. In the hospital, the nurse told her not to breastfeed. The neurological consult told her not to breastfeed. She breastfed anyway. “Then they reported her for child neglect, and that was just a few years ago. So I think the message needs to be loud and clear that we encourage [women with epilepsy] to breastfeed because we have the known benefits, and now several studies showing clearly no adverse effects of breastfeeding while taking antiseizure medications,” said Dr. Meador.

MONEAD findings

The MONEAD study included women from 20 different sites, with 145 participating investigators. The researchers compared outcomes in 284 women with epilepsy and 87 healthy women. The maternal mean IQ was 98 among women with epilepsy (95% confidence interval [CI], 96-99), and 105 (95% CI, 102-107) among healthy women. Seventy-six percent of women with epilepsy breastfed, versus 89% of controls.

Among the study cohort, 79% of women with epilepsy were on monotherapy, and 21% were on polytherapy. Thirty-five percent received lamotrigine, 28% levetiracetam, 16% were on another monotherapy, 10% received a combination of lamotrigine and levetiracetam, and 11% received a different combination.

At age 3, there was no association between the verbal index score of the child and whether the mother had epilepsy or not (difference, 0.4; P = .770). The researchers did find associations with the mother’s IQ (0.3; P < .001), male versus female child sex (–4.9; P < .001), Hispanic or Latino ethnicity (vs. Non-Hispanic, –5.5; P < .001), mother without college degree (–7.0; P < .001), average Beck Anxiety Inventory score after birth (–0.4; P < .001), and weeks of gestational age at enrollment.

The researchers found no association between third trimester antiseizure medication blood levels and verbal index score after adjustment (–2.9; P = .149), with the exception of levetiracetam (–9.0; P = .033). “This is interesting (but) not to be overblown, because overall the children on levetiracetam did well. But it must be remembered that teratogens act in an exposure dependent manner, so we’re constantly in this balancing act of trying to make sure you get enough medication on board to stop the seizures and protect the mother and the child, and at the same time, not too much on board where we increase the risk of teratogenicity in the child,” said Dr. Meador.

The study was funded by the National Institutes of Health. Dr. Meador and Dr. Hopp have no relevant financial disclosures.

SEATTLE – Use of antiseizure medications while breastfeeding is not associated with differences in child cognitive outcomes at age 3, according to new results from the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study.

The study follows results from the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study, which found no evidence of cognitive harm in children who were exposed in utero to antiepileptic drugs. “[In the NEAD study] we followed our cohort to age 6 and found them to have actually an improvement in cognition by about 4 IQ points by the time they got to age 6,” Kimford J. Meador, MD, said during a presentation of the results of the MONEAD study at the 2022 annual meeting of the American Academy of Neurology.

Breastfeeding has health benefits for both mothers and children, including reduced risk of respiratory tract infections, atopic dermatitis, asthma, and diabetes in children, and reduced risk of diabetes, breast cancer, ovarian cancer, and postpartum depression in mothers. Despite those benefits, concerns about harms from exposure to antiepileptic drugs may prompt some women to avoid breastfeeding.

The results of NEAD and MONEAD should reassure patients, according to Dr. Meador, professor of neurology at Stanford (Calif.) University. “Given the known multiple benefits of breastfeeding … women with epilepsy should be encouraged to breastfeed,” he said.
 

A responsibility to ‘engage and educate’ patients

Jennifer Hopp, MD, who served as a discussant for the presentation, underscored the need for neurologists to address pregnancy with female patients of childbearing agents. “The issues may include fertility, peripartum management, and outcomes that really go through the lifespan to also include issues of menopause,” Dr. Hopp, associate professor of neurology at the University of Maryland, Baltimore, said during her presentation.

Dr. Hopp noted one study showing lower rates of breastfeeding among mothers with epilepsy. “Breastfeeding rates in women with epilepsy are strikingly lower than in women who do not have epilepsy,” said Dr. Hopp. Another study showed that women with epilepsy were less likely to sustain breastfeeding after 6 weeks.

Dr. Hopp implored neurologists to address this. “It’s our responsibility to engage and educate our patients. These data provide us messaging to our patients that the newer drugs do not adversely affect outcome independently of their other exposure, and really support well-informed choices in breastfeeding,” said Dr. Hopp.
 

Outdated attitudes still persist

Dr. Meador referred to the stigma that surrounds epilepsy, including some state laws that called for sterilization of women with epilepsy that lasted until the 1960s. One might think that such attitudes are gone, “but it’s still there,” said Dr. Meador, who recounted a story a colleague told him about a woman on antiseizure medication. In the hospital, the nurse told her not to breastfeed. The neurological consult told her not to breastfeed. She breastfed anyway. “Then they reported her for child neglect, and that was just a few years ago. So I think the message needs to be loud and clear that we encourage [women with epilepsy] to breastfeed because we have the known benefits, and now several studies showing clearly no adverse effects of breastfeeding while taking antiseizure medications,” said Dr. Meador.

MONEAD findings

The MONEAD study included women from 20 different sites, with 145 participating investigators. The researchers compared outcomes in 284 women with epilepsy and 87 healthy women. The maternal mean IQ was 98 among women with epilepsy (95% confidence interval [CI], 96-99), and 105 (95% CI, 102-107) among healthy women. Seventy-six percent of women with epilepsy breastfed, versus 89% of controls.

Among the study cohort, 79% of women with epilepsy were on monotherapy, and 21% were on polytherapy. Thirty-five percent received lamotrigine, 28% levetiracetam, 16% were on another monotherapy, 10% received a combination of lamotrigine and levetiracetam, and 11% received a different combination.

At age 3, there was no association between the verbal index score of the child and whether the mother had epilepsy or not (difference, 0.4; P = .770). The researchers did find associations with the mother’s IQ (0.3; P < .001), male versus female child sex (–4.9; P < .001), Hispanic or Latino ethnicity (vs. Non-Hispanic, –5.5; P < .001), mother without college degree (–7.0; P < .001), average Beck Anxiety Inventory score after birth (–0.4; P < .001), and weeks of gestational age at enrollment.

The researchers found no association between third trimester antiseizure medication blood levels and verbal index score after adjustment (–2.9; P = .149), with the exception of levetiracetam (–9.0; P = .033). “This is interesting (but) not to be overblown, because overall the children on levetiracetam did well. But it must be remembered that teratogens act in an exposure dependent manner, so we’re constantly in this balancing act of trying to make sure you get enough medication on board to stop the seizures and protect the mother and the child, and at the same time, not too much on board where we increase the risk of teratogenicity in the child,” said Dr. Meador.

The study was funded by the National Institutes of Health. Dr. Meador and Dr. Hopp have no relevant financial disclosures.

Most surgeons report being affected by performance anxiety in relation to their work, with the anxiety frequently having a negative effect on well-being, a new study of surgeons in the United Kingdom shows.

“Performance anxiety or stage fright is a widely recognized problem in music and sports, and there are many similarities between these arenas and the operating theater,” first author Robert Miller, MRCS, of the Surgical Psychology and Performance Group and the department of plastic and reconstructive surgery at St. George’s Hospital NHS Trust, London, said in an interview. “We were aware of it anecdotally in a surgical context, but for one reason or another, perhaps professional pride and fear of negative perception, this is rarely openly discussed amongst surgeons.”

In the cross-sectional study, published in Annals of Surgery, Dr. Miller and colleagues surveyed surgeons in all specialties working in the United Kingdom who had at least 1 year of postgraduate surgical training.

Of a total of 631 responses received, 523 (83%) were included in the analysis. The median age of those who responded was 41.2 years, and the mean duration of surgical experience was 15.3 years (range, 1-52 years). Among them, 62% were men, and 52% were of consultant/attending grade.

All of the respondents – 100% – said they believed that performance anxiety affected surgeons, 87% reported having experienced it themselves, and 65% said they felt that performance anxiety had an effect on their surgical performance.

Both male and female surgeons who reported experiencing performance anxiety had significantly worse mental well-being, as assessed using the Short Warwick Edinburgh Mental Wellbeing Scale, compared with those who did not have performance anxiety (P < .0001 for men and P < .001 for women).

Overall, however, male surgeons had significantly better mental well-being, compared with female surgeons (P = .003), yet both genders had significantly lower mental well-being scores compared with U.K. population norms (P = .0019 for men and P = .0001 for women).

The gender differences are “clearly an important topic, which is likely multifactorial,” Dr. Miller told this news organization. “The gender well-being gap requires more in-depth research, and qualitative work involving female surgeons is critical.”

Surgical perfectionism was significantly more common among respondents who did have performance anxiety in comparison with those who did not (P < .0001).

“Although perfectionism may be a beneficial trait in surgery, our findings from hierarchical multiple regression analysis also indicate that perfectionism, [as well as] sex and experience, may drive surgical performance anxiety and help predict those experiencing [the anxiety],” the authors noted.
 

Performing in presence of colleagues a key trigger

By far, the leading trigger that was identified as prompting surgeon performance anxiety was the presence – and scrutiny – of colleagues within the parent specialty. This was reported by 151 respondents. Other triggers were having to perform on highly complex or high-risk cases (66 responses) and a lack of experience (30 responses).

Next to planning and preparation, opening up and talking about the anxiety and shedding light on the issue was seen as a leading strategy to help with the problem, but very few respondents reported openly sharing their struggles. Only 9% reported that they had shared it openly; 27% said they had confided in someone, and 47% did not respond to the question.

“I wish we talked about it more and shared our insecurities,” one respondent lamented. “Most of my colleagues pretend they are living gods.”

Only about 45% of respondents reported a specific technique for overcoming their anxiety. In addition to being open about the problem, other techniques included self-care, such as exercise; and distraction outside of work to get perspective; relaxation techniques such as deep or controlled breathing; music; mindfulness; and positive self-statements.

About 9% said they had received psychological counseling for performance anxiety, and only 3% reported using medication for the problem.
 

Anxiety a positive factor?

Surprisingly, 70% of respondents reported feeling that surgical performance anxiety could have a positive impact on surgical performance, which the authors noted is consistent with some theories.

“This may be explained by the traditional bell-curve relationship between arousal and performance, which describes a dose-dependent relationship between performance and arousal until a ‘tipping point,’ after which performance declines,” the authors explained. “A heightened awareness secondary to anxiety may be beneficial, but at high doses, anxiety can negatively affect attentional control and cause somatic symptoms.”

They noted that “the challenge would be to reap the benefits of low-level stimulation without incurring possible adverse effects.”

Dr. Miller said that, in determining whether selection bias had a role in the results, a detailed analysis showed that “our respondents were not skewed to those with only high levels of trait anxiety.

“We also had a good spread of consultants versus trainees [about half and half], and different specialties, so we feel this is likely to be a representative sample,” he told this news organization.

That being said, the results underscore the need for increased awareness – and open discussion – of the issue of surgical performance anxiety.

“Within other professions, particularly the performing arts and sports, performance psychology is becoming an integral part of training and development,” Dr. Miller said. “We feel surgeons should be supported in a similar manner.

“Surgical performance anxiety is normal for surgeons at all levels and not something to be ashamed about,” Dr. Miller added. “Talk about it, acknowledge it, and be supportive to your colleagues.”
 

Many keep it to themselves in ‘prevailing culture of stoicism’

Commenting on the study, Carter C. Lebares, MD, an associate professor of surgery and director of the Center for Mindfulness in Surgery, department of surgery, University of California, San Francisco, said she was not surprised to see the high rates of performance anxiety among surgeons.

“As surgeons, no matter how hard we train or how thoroughly we prepare our intellectual understanding or the patient, the disease process, and the operation, there may be surprises, unforeseen challenges, or off days,” Dr. Lebares said.

“And whatever we encounter, we are managing these things directly under the scrutiny of others – people who can affect our reputation, operating privileges, and mental health. So, I am not surprised this is a prevalent and widely recognized issue.”

Dr. Lebares noted that the reluctance to share the anxiety is part of a “challenging and recognized conundrum in both medicine and surgery and is a matter of the prevailing culture of stoicism.

“We often are called to shoulder tremendous weight intraoperatively (having perseverance, self-confidence, or sustained focus), and in owning the weight of complications (which eventually we all will have),” she said.

“So, we do need to be strong and not complain, [but] we also need to be able to set that aside [when appropriate] and ask for help or allow others to shoulder the weight for a while, and this is not [yet] a common part of surgical culture.”

Dr. Lebares added that randomized, controlled trials have shown benefits of mindfulness interventions on burnout and anxiety.

“We have observed positive effects on mental noise, self-perception, conflict resolution, and resilience in surgical residents trained in mindfulness-based cognitive skills,” she said. “[Residents] report applying these skills in the OR, in their home lives, and in how they approach their training/education.”

The authors disclosed no relevant financial relationships. Dr. Lebares has developed mindfulness-based cognitive skills training for surgeons but receives no financial compensation for the activities.

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

Most surgeons report being affected by performance anxiety in relation to their work, with the anxiety frequently having a negative effect on well-being, a new study of surgeons in the United Kingdom shows.

“Performance anxiety or stage fright is a widely recognized problem in music and sports, and there are many similarities between these arenas and the operating theater,” first author Robert Miller, MRCS, of the Surgical Psychology and Performance Group and the department of plastic and reconstructive surgery at St. George’s Hospital NHS Trust, London, said in an interview. “We were aware of it anecdotally in a surgical context, but for one reason or another, perhaps professional pride and fear of negative perception, this is rarely openly discussed amongst surgeons.”

In the cross-sectional study, published in Annals of Surgery, Dr. Miller and colleagues surveyed surgeons in all specialties working in the United Kingdom who had at least 1 year of postgraduate surgical training.

Of a total of 631 responses received, 523 (83%) were included in the analysis. The median age of those who responded was 41.2 years, and the mean duration of surgical experience was 15.3 years (range, 1-52 years). Among them, 62% were men, and 52% were of consultant/attending grade.

All of the respondents – 100% – said they believed that performance anxiety affected surgeons, 87% reported having experienced it themselves, and 65% said they felt that performance anxiety had an effect on their surgical performance.

Both male and female surgeons who reported experiencing performance anxiety had significantly worse mental well-being, as assessed using the Short Warwick Edinburgh Mental Wellbeing Scale, compared with those who did not have performance anxiety (P < .0001 for men and P < .001 for women).

Overall, however, male surgeons had significantly better mental well-being, compared with female surgeons (P = .003), yet both genders had significantly lower mental well-being scores compared with U.K. population norms (P = .0019 for men and P = .0001 for women).

The gender differences are “clearly an important topic, which is likely multifactorial,” Dr. Miller told this news organization. “The gender well-being gap requires more in-depth research, and qualitative work involving female surgeons is critical.”

Surgical perfectionism was significantly more common among respondents who did have performance anxiety in comparison with those who did not (P < .0001).

“Although perfectionism may be a beneficial trait in surgery, our findings from hierarchical multiple regression analysis also indicate that perfectionism, [as well as] sex and experience, may drive surgical performance anxiety and help predict those experiencing [the anxiety],” the authors noted.
 

Performing in presence of colleagues a key trigger

By far, the leading trigger that was identified as prompting surgeon performance anxiety was the presence – and scrutiny – of colleagues within the parent specialty. This was reported by 151 respondents. Other triggers were having to perform on highly complex or high-risk cases (66 responses) and a lack of experience (30 responses).

Next to planning and preparation, opening up and talking about the anxiety and shedding light on the issue was seen as a leading strategy to help with the problem, but very few respondents reported openly sharing their struggles. Only 9% reported that they had shared it openly; 27% said they had confided in someone, and 47% did not respond to the question.

“I wish we talked about it more and shared our insecurities,” one respondent lamented. “Most of my colleagues pretend they are living gods.”

Only about 45% of respondents reported a specific technique for overcoming their anxiety. In addition to being open about the problem, other techniques included self-care, such as exercise; and distraction outside of work to get perspective; relaxation techniques such as deep or controlled breathing; music; mindfulness; and positive self-statements.

About 9% said they had received psychological counseling for performance anxiety, and only 3% reported using medication for the problem.
 

Anxiety a positive factor?

Surprisingly, 70% of respondents reported feeling that surgical performance anxiety could have a positive impact on surgical performance, which the authors noted is consistent with some theories.

“This may be explained by the traditional bell-curve relationship between arousal and performance, which describes a dose-dependent relationship between performance and arousal until a ‘tipping point,’ after which performance declines,” the authors explained. “A heightened awareness secondary to anxiety may be beneficial, but at high doses, anxiety can negatively affect attentional control and cause somatic symptoms.”

They noted that “the challenge would be to reap the benefits of low-level stimulation without incurring possible adverse effects.”

Dr. Miller said that, in determining whether selection bias had a role in the results, a detailed analysis showed that “our respondents were not skewed to those with only high levels of trait anxiety.

“We also had a good spread of consultants versus trainees [about half and half], and different specialties, so we feel this is likely to be a representative sample,” he told this news organization.

That being said, the results underscore the need for increased awareness – and open discussion – of the issue of surgical performance anxiety.

“Within other professions, particularly the performing arts and sports, performance psychology is becoming an integral part of training and development,” Dr. Miller said. “We feel surgeons should be supported in a similar manner.

“Surgical performance anxiety is normal for surgeons at all levels and not something to be ashamed about,” Dr. Miller added. “Talk about it, acknowledge it, and be supportive to your colleagues.”
 

Many keep it to themselves in ‘prevailing culture of stoicism’

Commenting on the study, Carter C. Lebares, MD, an associate professor of surgery and director of the Center for Mindfulness in Surgery, department of surgery, University of California, San Francisco, said she was not surprised to see the high rates of performance anxiety among surgeons.

“As surgeons, no matter how hard we train or how thoroughly we prepare our intellectual understanding or the patient, the disease process, and the operation, there may be surprises, unforeseen challenges, or off days,” Dr. Lebares said.

“And whatever we encounter, we are managing these things directly under the scrutiny of others – people who can affect our reputation, operating privileges, and mental health. So, I am not surprised this is a prevalent and widely recognized issue.”

Dr. Lebares noted that the reluctance to share the anxiety is part of a “challenging and recognized conundrum in both medicine and surgery and is a matter of the prevailing culture of stoicism.

“We often are called to shoulder tremendous weight intraoperatively (having perseverance, self-confidence, or sustained focus), and in owning the weight of complications (which eventually we all will have),” she said.

“So, we do need to be strong and not complain, [but] we also need to be able to set that aside [when appropriate] and ask for help or allow others to shoulder the weight for a while, and this is not [yet] a common part of surgical culture.”

Dr. Lebares added that randomized, controlled trials have shown benefits of mindfulness interventions on burnout and anxiety.

“We have observed positive effects on mental noise, self-perception, conflict resolution, and resilience in surgical residents trained in mindfulness-based cognitive skills,” she said. “[Residents] report applying these skills in the OR, in their home lives, and in how they approach their training/education.”

The authors disclosed no relevant financial relationships. Dr. Lebares has developed mindfulness-based cognitive skills training for surgeons but receives no financial compensation for the activities.

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

Most surgeons report being affected by performance anxiety in relation to their work, with the anxiety frequently having a negative effect on well-being, a new study of surgeons in the United Kingdom shows.

“Performance anxiety or stage fright is a widely recognized problem in music and sports, and there are many similarities between these arenas and the operating theater,” first author Robert Miller, MRCS, of the Surgical Psychology and Performance Group and the department of plastic and reconstructive surgery at St. George’s Hospital NHS Trust, London, said in an interview. “We were aware of it anecdotally in a surgical context, but for one reason or another, perhaps professional pride and fear of negative perception, this is rarely openly discussed amongst surgeons.”

In the cross-sectional study, published in Annals of Surgery, Dr. Miller and colleagues surveyed surgeons in all specialties working in the United Kingdom who had at least 1 year of postgraduate surgical training.

Of a total of 631 responses received, 523 (83%) were included in the analysis. The median age of those who responded was 41.2 years, and the mean duration of surgical experience was 15.3 years (range, 1-52 years). Among them, 62% were men, and 52% were of consultant/attending grade.

All of the respondents – 100% – said they believed that performance anxiety affected surgeons, 87% reported having experienced it themselves, and 65% said they felt that performance anxiety had an effect on their surgical performance.

Both male and female surgeons who reported experiencing performance anxiety had significantly worse mental well-being, as assessed using the Short Warwick Edinburgh Mental Wellbeing Scale, compared with those who did not have performance anxiety (P < .0001 for men and P < .001 for women).

Overall, however, male surgeons had significantly better mental well-being, compared with female surgeons (P = .003), yet both genders had significantly lower mental well-being scores compared with U.K. population norms (P = .0019 for men and P = .0001 for women).

The gender differences are “clearly an important topic, which is likely multifactorial,” Dr. Miller told this news organization. “The gender well-being gap requires more in-depth research, and qualitative work involving female surgeons is critical.”

Surgical perfectionism was significantly more common among respondents who did have performance anxiety in comparison with those who did not (P < .0001).

“Although perfectionism may be a beneficial trait in surgery, our findings from hierarchical multiple regression analysis also indicate that perfectionism, [as well as] sex and experience, may drive surgical performance anxiety and help predict those experiencing [the anxiety],” the authors noted.
 

Performing in presence of colleagues a key trigger

By far, the leading trigger that was identified as prompting surgeon performance anxiety was the presence – and scrutiny – of colleagues within the parent specialty. This was reported by 151 respondents. Other triggers were having to perform on highly complex or high-risk cases (66 responses) and a lack of experience (30 responses).

Next to planning and preparation, opening up and talking about the anxiety and shedding light on the issue was seen as a leading strategy to help with the problem, but very few respondents reported openly sharing their struggles. Only 9% reported that they had shared it openly; 27% said they had confided in someone, and 47% did not respond to the question.

“I wish we talked about it more and shared our insecurities,” one respondent lamented. “Most of my colleagues pretend they are living gods.”

Only about 45% of respondents reported a specific technique for overcoming their anxiety. In addition to being open about the problem, other techniques included self-care, such as exercise; and distraction outside of work to get perspective; relaxation techniques such as deep or controlled breathing; music; mindfulness; and positive self-statements.

About 9% said they had received psychological counseling for performance anxiety, and only 3% reported using medication for the problem.
 

Anxiety a positive factor?

Surprisingly, 70% of respondents reported feeling that surgical performance anxiety could have a positive impact on surgical performance, which the authors noted is consistent with some theories.

“This may be explained by the traditional bell-curve relationship between arousal and performance, which describes a dose-dependent relationship between performance and arousal until a ‘tipping point,’ after which performance declines,” the authors explained. “A heightened awareness secondary to anxiety may be beneficial, but at high doses, anxiety can negatively affect attentional control and cause somatic symptoms.”

They noted that “the challenge would be to reap the benefits of low-level stimulation without incurring possible adverse effects.”

Dr. Miller said that, in determining whether selection bias had a role in the results, a detailed analysis showed that “our respondents were not skewed to those with only high levels of trait anxiety.

“We also had a good spread of consultants versus trainees [about half and half], and different specialties, so we feel this is likely to be a representative sample,” he told this news organization.

That being said, the results underscore the need for increased awareness – and open discussion – of the issue of surgical performance anxiety.

“Within other professions, particularly the performing arts and sports, performance psychology is becoming an integral part of training and development,” Dr. Miller said. “We feel surgeons should be supported in a similar manner.

“Surgical performance anxiety is normal for surgeons at all levels and not something to be ashamed about,” Dr. Miller added. “Talk about it, acknowledge it, and be supportive to your colleagues.”
 

Many keep it to themselves in ‘prevailing culture of stoicism’

Commenting on the study, Carter C. Lebares, MD, an associate professor of surgery and director of the Center for Mindfulness in Surgery, department of surgery, University of California, San Francisco, said she was not surprised to see the high rates of performance anxiety among surgeons.

“As surgeons, no matter how hard we train or how thoroughly we prepare our intellectual understanding or the patient, the disease process, and the operation, there may be surprises, unforeseen challenges, or off days,” Dr. Lebares said.

“And whatever we encounter, we are managing these things directly under the scrutiny of others – people who can affect our reputation, operating privileges, and mental health. So, I am not surprised this is a prevalent and widely recognized issue.”

Dr. Lebares noted that the reluctance to share the anxiety is part of a “challenging and recognized conundrum in both medicine and surgery and is a matter of the prevailing culture of stoicism.

“We often are called to shoulder tremendous weight intraoperatively (having perseverance, self-confidence, or sustained focus), and in owning the weight of complications (which eventually we all will have),” she said.

“So, we do need to be strong and not complain, [but] we also need to be able to set that aside [when appropriate] and ask for help or allow others to shoulder the weight for a while, and this is not [yet] a common part of surgical culture.”

Dr. Lebares added that randomized, controlled trials have shown benefits of mindfulness interventions on burnout and anxiety.

“We have observed positive effects on mental noise, self-perception, conflict resolution, and resilience in surgical residents trained in mindfulness-based cognitive skills,” she said. “[Residents] report applying these skills in the OR, in their home lives, and in how they approach their training/education.”

The authors disclosed no relevant financial relationships. Dr. Lebares has developed mindfulness-based cognitive skills training for surgeons but receives no financial compensation for the activities.

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

Pregnant women with a history of migraine are at elevated risk for gestational hypertension and preeclampsia, and of delivering their baby preterm, new research suggests. In a large prospective study, researchers also found a link between migraine with aura and increased preeclampsia risk.

Overall, the findings suggest women with a history of migraine may benefit from enhanced monitoring during pregnancy, said coinvestigator Alexandra Purdue-Smithe, PhD, associate epidemiologist at Brigham and Women’s Hospital and instructor of medicine at Harvard Medical School, Boston. “Our results suggest that migraine history may be an important consideration in  obstetric risk assessment,” Dr. Purdue-Smithe added.

The findings will be presented at the 2022 annual meeting of the American Academy of Neurology.
 

Common neurovascular disorder

Migraine is a common neurovascular disorder, affecting about 15% of adults. The condition carries “a pretty remarkable sex bias” as it affects up to three times more women than men, and about a quarter of women in the reproductive age bracket of 18-44 years, Dr. Purdue-Smithe noted.

Despite this, relatively little is known about migraine and pregnancy risks, she said.

What is known is that women with migraine have a higher burden of cardiovascular risk factors such as obesity and chronic hypertension, and these factors can also increase risk for pregnancy complications, she added.

In the study, researchers analyzed data on 30,555 pregnancies in about 19,000 women without a history of cardiovascular disease, type 2 diabetes, or cancer during a 20-year period ending in 2009.

The data came from the Nurses’ Health Study II, a large prospective cohort study established in 1989 when it enrolled women aged 25-42 years. Participants in the ongoing study complete questionnaires every 2 years, reporting information on various health conditions as well as pregnancy and reproductive events.

The investigators estimated associations of physician-diagnosed prepregnancy migraine with preterm delivery, gestational diabetes, gestational hypertension, preeclampsia, and low birth weight (<2,500 grams [5.5 lb]).

About 11% of the women in the study had migraine diagnosed by a physician before pregnancy.

Researchers adjusted for age at pregnancy, race/ethnicity, age at menarche, and prepregnancy chronic hypertension, body mass index, physical activity, smoking status, alcohol intake, history of infertility, parity, oral contraceptive use, and analgesic use.
 

‘A bit surprising’

Results showed that compared with women without a history of migraine, those with such a history had higher risk for preterm delivery (relative risk [RR], 1.17; 95% confidence interval [CI], 1.05-1.30), gestational hypertension (RR, 1.28; 95% CI, 1.11-1.48), and preeclampsia (RR, 1.40; 95% CI, 1.19-1.65).

Prepregnancy migraine was not associated with low birth weight (RR, 0.99; 95% CI, 0.85-1.16) or gestational diabetes (RR, 1.05; 95% CI, .91-1.22).

It was a “bit surprising” that women with migraine had a higher risk for preterm delivery but their babies were not necessarily underweight – although some prior literature had similar findings, said Dr. Purdue-Smithe.

She noted that in her study the association was limited to moderate preterm delivery (gestational age, 32-37 weeks) and not with very preterm births (before 32 weeks).

Researchers also assessed adverse pregnancy outcomes by aura phenotype. “Women with migraine with aura have a higher risk of cardiovascular disease later in life, so we hypothesized that aura might be more strongly associated with adverse pregnancy outcomes with underlying vascular pathology,” Dr. Purdue-Smithe said.

Women with and without aura had elevated risks for preterm delivery and gestational hypertension. Those with aura had a slightly higher risk for preeclampsia (RR, 1.51; 95% CI, 1.22-1.88) than those without aura (RR, 1.29; 95% CI, 1.04-1.61).

As the association between migraine and adverse pregnancy outcomes persisted after adjustment for established cardiovascular and obstetric risk factors, “this suggests there may be subclinical factors that are contributing to elevated risks of these outcomes in women with migraine,” said Dr. Purdue-Smithe.

Such factors could include platelet activation, chronic inflammation, and endothelial dysfunction, she added.

While findings of some previous case-control and retrospective studies suggested a possible link between migraine and adverse pregnancy outcomes, until now few large prospective studies have examined the association.

“Strengths of our study include its prospective design, very large sample size, and more complete adjustment for potential prepregnancy confounders,” Dr. Purdue-Smithe said.
 

Independent risk factor?

In the past, it has been somewhat unclear whether migraine is an independent risk factor for these complications or whether women with migraine just have greater risk factors for adverse pregnancy outcomes.

“Our preliminary findings suggest that migraine is independently associated with these adverse pregnancy outcomes, or at least that’s what it seems,” said Dr. Purdue-Smithe.

The new results could be used by clinicians to “flag” women who may be at risk for complications, she added. “These women may benefit from closer monitoring in pregnancy so that if issues arise, physicians can act quickly.”

She noted that preeclampsia “can come on suddenly and escalate rapidly,” and there are few interventions to treat it besides delivery.

However, low-dose aspirin may be worth investigating. Various health care groups and the U.S. Preventive Services Task Force recommend pregnant women at high risk for preeclampsia take low-dose aspirin (81 mg/d) after 12 weeks’ gestation.

“It would be interesting to see if women with migraine who take aspirin in pregnancy can reduce their risk of preeclampsia, and future research should address this question,” said Dr. Purdue-Smithe.

Additional testing showed that associations with preeclampsia and gestational hypertension did not vary according to age and other obstetrical risks.

The Nurses’ Health Study II did not have information on number and severity of migraine attacks, so the researchers were unable to determine if these factors affect pregnancy outcomes.

“Understanding whether specific migraine features, such as attack frequency, are associated with adverse pregnancy outcomes will be an important area for future research,” said Dr. Purdue-Smithe. She noted prior studies showed the frequency of migraine attacks is related to ischemic stroke and other cardiovascular outcomes.

The authors acknowledged a limitation for the current study: Although migraine history was reported prior to pregnancy, information on migraine aura was collected after most of the pregnancies in the cohort were over. So the findings for migraine aura may have been influenced by participants’ ability to accurately remember their experiences.
 

Collaboration is key

Commenting on the research, Nina Riggins, MD, PhD, director of the Headache and Traumatic Brain Injury Center in the department of neurosciences at the University of California, San Diego, said the study “stands out” because it distinguishes pregnancy complications between those with and without aura among women with migraine. 

Dr. Riggins noted the investigators found the risk of preeclampsia, which on average occurs in about 3%-5% of pregnancies, is higher among women with migraine with aura.  

“The good news is that treatments are available,” she said. “Preconception planning should include this discussion for patients living with migraine.”

However, the study did not compare risks for patients who have frequent migraine attacks versus episodic migraine, Dr. Riggins noted. “We need to learn more about whether any treatments can be safe and effective to decrease risks of complications during pregnancy in this population,” she said.

“I believe, ultimately, what this study reveals is that collaboration among primary care, ob.gyn., maternal-fetal medicine specialists, and neurologists will likely benefit pregnant patients with migraine,” Dr. Riggins said.

The study received funding from the National Institutes of Health. Dr. Purdue-Smithe has disclosed no relevant financial relationships.

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

Pregnant women with a history of migraine are at elevated risk for gestational hypertension and preeclampsia, and of delivering their baby preterm, new research suggests. In a large prospective study, researchers also found a link between migraine with aura and increased preeclampsia risk.

Overall, the findings suggest women with a history of migraine may benefit from enhanced monitoring during pregnancy, said coinvestigator Alexandra Purdue-Smithe, PhD, associate epidemiologist at Brigham and Women’s Hospital and instructor of medicine at Harvard Medical School, Boston. “Our results suggest that migraine history may be an important consideration in  obstetric risk assessment,” Dr. Purdue-Smithe added.

The findings will be presented at the 2022 annual meeting of the American Academy of Neurology.
 

Common neurovascular disorder

Migraine is a common neurovascular disorder, affecting about 15% of adults. The condition carries “a pretty remarkable sex bias” as it affects up to three times more women than men, and about a quarter of women in the reproductive age bracket of 18-44 years, Dr. Purdue-Smithe noted.

Despite this, relatively little is known about migraine and pregnancy risks, she said.

What is known is that women with migraine have a higher burden of cardiovascular risk factors such as obesity and chronic hypertension, and these factors can also increase risk for pregnancy complications, she added.

In the study, researchers analyzed data on 30,555 pregnancies in about 19,000 women without a history of cardiovascular disease, type 2 diabetes, or cancer during a 20-year period ending in 2009.

The data came from the Nurses’ Health Study II, a large prospective cohort study established in 1989 when it enrolled women aged 25-42 years. Participants in the ongoing study complete questionnaires every 2 years, reporting information on various health conditions as well as pregnancy and reproductive events.

The investigators estimated associations of physician-diagnosed prepregnancy migraine with preterm delivery, gestational diabetes, gestational hypertension, preeclampsia, and low birth weight (<2,500 grams [5.5 lb]).

About 11% of the women in the study had migraine diagnosed by a physician before pregnancy.

Researchers adjusted for age at pregnancy, race/ethnicity, age at menarche, and prepregnancy chronic hypertension, body mass index, physical activity, smoking status, alcohol intake, history of infertility, parity, oral contraceptive use, and analgesic use.
 

‘A bit surprising’

Results showed that compared with women without a history of migraine, those with such a history had higher risk for preterm delivery (relative risk [RR], 1.17; 95% confidence interval [CI], 1.05-1.30), gestational hypertension (RR, 1.28; 95% CI, 1.11-1.48), and preeclampsia (RR, 1.40; 95% CI, 1.19-1.65).

Prepregnancy migraine was not associated with low birth weight (RR, 0.99; 95% CI, 0.85-1.16) or gestational diabetes (RR, 1.05; 95% CI, .91-1.22).

It was a “bit surprising” that women with migraine had a higher risk for preterm delivery but their babies were not necessarily underweight – although some prior literature had similar findings, said Dr. Purdue-Smithe.

She noted that in her study the association was limited to moderate preterm delivery (gestational age, 32-37 weeks) and not with very preterm births (before 32 weeks).

Researchers also assessed adverse pregnancy outcomes by aura phenotype. “Women with migraine with aura have a higher risk of cardiovascular disease later in life, so we hypothesized that aura might be more strongly associated with adverse pregnancy outcomes with underlying vascular pathology,” Dr. Purdue-Smithe said.

Women with and without aura had elevated risks for preterm delivery and gestational hypertension. Those with aura had a slightly higher risk for preeclampsia (RR, 1.51; 95% CI, 1.22-1.88) than those without aura (RR, 1.29; 95% CI, 1.04-1.61).

As the association between migraine and adverse pregnancy outcomes persisted after adjustment for established cardiovascular and obstetric risk factors, “this suggests there may be subclinical factors that are contributing to elevated risks of these outcomes in women with migraine,” said Dr. Purdue-Smithe.

Such factors could include platelet activation, chronic inflammation, and endothelial dysfunction, she added.

While findings of some previous case-control and retrospective studies suggested a possible link between migraine and adverse pregnancy outcomes, until now few large prospective studies have examined the association.

“Strengths of our study include its prospective design, very large sample size, and more complete adjustment for potential prepregnancy confounders,” Dr. Purdue-Smithe said.
 

Independent risk factor?

In the past, it has been somewhat unclear whether migraine is an independent risk factor for these complications or whether women with migraine just have greater risk factors for adverse pregnancy outcomes.

“Our preliminary findings suggest that migraine is independently associated with these adverse pregnancy outcomes, or at least that’s what it seems,” said Dr. Purdue-Smithe.

The new results could be used by clinicians to “flag” women who may be at risk for complications, she added. “These women may benefit from closer monitoring in pregnancy so that if issues arise, physicians can act quickly.”

She noted that preeclampsia “can come on suddenly and escalate rapidly,” and there are few interventions to treat it besides delivery.

However, low-dose aspirin may be worth investigating. Various health care groups and the U.S. Preventive Services Task Force recommend pregnant women at high risk for preeclampsia take low-dose aspirin (81 mg/d) after 12 weeks’ gestation.

“It would be interesting to see if women with migraine who take aspirin in pregnancy can reduce their risk of preeclampsia, and future research should address this question,” said Dr. Purdue-Smithe.

Additional testing showed that associations with preeclampsia and gestational hypertension did not vary according to age and other obstetrical risks.

The Nurses’ Health Study II did not have information on number and severity of migraine attacks, so the researchers were unable to determine if these factors affect pregnancy outcomes.

“Understanding whether specific migraine features, such as attack frequency, are associated with adverse pregnancy outcomes will be an important area for future research,” said Dr. Purdue-Smithe. She noted prior studies showed the frequency of migraine attacks is related to ischemic stroke and other cardiovascular outcomes.

The authors acknowledged a limitation for the current study: Although migraine history was reported prior to pregnancy, information on migraine aura was collected after most of the pregnancies in the cohort were over. So the findings for migraine aura may have been influenced by participants’ ability to accurately remember their experiences.
 

Collaboration is key

Commenting on the research, Nina Riggins, MD, PhD, director of the Headache and Traumatic Brain Injury Center in the department of neurosciences at the University of California, San Diego, said the study “stands out” because it distinguishes pregnancy complications between those with and without aura among women with migraine. 

Dr. Riggins noted the investigators found the risk of preeclampsia, which on average occurs in about 3%-5% of pregnancies, is higher among women with migraine with aura.  

“The good news is that treatments are available,” she said. “Preconception planning should include this discussion for patients living with migraine.”

However, the study did not compare risks for patients who have frequent migraine attacks versus episodic migraine, Dr. Riggins noted. “We need to learn more about whether any treatments can be safe and effective to decrease risks of complications during pregnancy in this population,” she said.

“I believe, ultimately, what this study reveals is that collaboration among primary care, ob.gyn., maternal-fetal medicine specialists, and neurologists will likely benefit pregnant patients with migraine,” Dr. Riggins said.

The study received funding from the National Institutes of Health. Dr. Purdue-Smithe has disclosed no relevant financial relationships.

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

Pregnant women with a history of migraine are at elevated risk for gestational hypertension and preeclampsia, and of delivering their baby preterm, new research suggests. In a large prospective study, researchers also found a link between migraine with aura and increased preeclampsia risk.

Overall, the findings suggest women with a history of migraine may benefit from enhanced monitoring during pregnancy, said coinvestigator Alexandra Purdue-Smithe, PhD, associate epidemiologist at Brigham and Women’s Hospital and instructor of medicine at Harvard Medical School, Boston. “Our results suggest that migraine history may be an important consideration in  obstetric risk assessment,” Dr. Purdue-Smithe added.

The findings will be presented at the 2022 annual meeting of the American Academy of Neurology.
 

Common neurovascular disorder

Migraine is a common neurovascular disorder, affecting about 15% of adults. The condition carries “a pretty remarkable sex bias” as it affects up to three times more women than men, and about a quarter of women in the reproductive age bracket of 18-44 years, Dr. Purdue-Smithe noted.

Despite this, relatively little is known about migraine and pregnancy risks, she said.

What is known is that women with migraine have a higher burden of cardiovascular risk factors such as obesity and chronic hypertension, and these factors can also increase risk for pregnancy complications, she added.

In the study, researchers analyzed data on 30,555 pregnancies in about 19,000 women without a history of cardiovascular disease, type 2 diabetes, or cancer during a 20-year period ending in 2009.

The data came from the Nurses’ Health Study II, a large prospective cohort study established in 1989 when it enrolled women aged 25-42 years. Participants in the ongoing study complete questionnaires every 2 years, reporting information on various health conditions as well as pregnancy and reproductive events.

The investigators estimated associations of physician-diagnosed prepregnancy migraine with preterm delivery, gestational diabetes, gestational hypertension, preeclampsia, and low birth weight (<2,500 grams [5.5 lb]).

About 11% of the women in the study had migraine diagnosed by a physician before pregnancy.

Researchers adjusted for age at pregnancy, race/ethnicity, age at menarche, and prepregnancy chronic hypertension, body mass index, physical activity, smoking status, alcohol intake, history of infertility, parity, oral contraceptive use, and analgesic use.
 

‘A bit surprising’

Results showed that compared with women without a history of migraine, those with such a history had higher risk for preterm delivery (relative risk [RR], 1.17; 95% confidence interval [CI], 1.05-1.30), gestational hypertension (RR, 1.28; 95% CI, 1.11-1.48), and preeclampsia (RR, 1.40; 95% CI, 1.19-1.65).

Prepregnancy migraine was not associated with low birth weight (RR, 0.99; 95% CI, 0.85-1.16) or gestational diabetes (RR, 1.05; 95% CI, .91-1.22).

It was a “bit surprising” that women with migraine had a higher risk for preterm delivery but their babies were not necessarily underweight – although some prior literature had similar findings, said Dr. Purdue-Smithe.

She noted that in her study the association was limited to moderate preterm delivery (gestational age, 32-37 weeks) and not with very preterm births (before 32 weeks).

Researchers also assessed adverse pregnancy outcomes by aura phenotype. “Women with migraine with aura have a higher risk of cardiovascular disease later in life, so we hypothesized that aura might be more strongly associated with adverse pregnancy outcomes with underlying vascular pathology,” Dr. Purdue-Smithe said.

Women with and without aura had elevated risks for preterm delivery and gestational hypertension. Those with aura had a slightly higher risk for preeclampsia (RR, 1.51; 95% CI, 1.22-1.88) than those without aura (RR, 1.29; 95% CI, 1.04-1.61).

As the association between migraine and adverse pregnancy outcomes persisted after adjustment for established cardiovascular and obstetric risk factors, “this suggests there may be subclinical factors that are contributing to elevated risks of these outcomes in women with migraine,” said Dr. Purdue-Smithe.

Such factors could include platelet activation, chronic inflammation, and endothelial dysfunction, she added.

While findings of some previous case-control and retrospective studies suggested a possible link between migraine and adverse pregnancy outcomes, until now few large prospective studies have examined the association.

“Strengths of our study include its prospective design, very large sample size, and more complete adjustment for potential prepregnancy confounders,” Dr. Purdue-Smithe said.
 

Independent risk factor?

In the past, it has been somewhat unclear whether migraine is an independent risk factor for these complications or whether women with migraine just have greater risk factors for adverse pregnancy outcomes.

“Our preliminary findings suggest that migraine is independently associated with these adverse pregnancy outcomes, or at least that’s what it seems,” said Dr. Purdue-Smithe.

The new results could be used by clinicians to “flag” women who may be at risk for complications, she added. “These women may benefit from closer monitoring in pregnancy so that if issues arise, physicians can act quickly.”

She noted that preeclampsia “can come on suddenly and escalate rapidly,” and there are few interventions to treat it besides delivery.

However, low-dose aspirin may be worth investigating. Various health care groups and the U.S. Preventive Services Task Force recommend pregnant women at high risk for preeclampsia take low-dose aspirin (81 mg/d) after 12 weeks’ gestation.

“It would be interesting to see if women with migraine who take aspirin in pregnancy can reduce their risk of preeclampsia, and future research should address this question,” said Dr. Purdue-Smithe.

Additional testing showed that associations with preeclampsia and gestational hypertension did not vary according to age and other obstetrical risks.

The Nurses’ Health Study II did not have information on number and severity of migraine attacks, so the researchers were unable to determine if these factors affect pregnancy outcomes.

“Understanding whether specific migraine features, such as attack frequency, are associated with adverse pregnancy outcomes will be an important area for future research,” said Dr. Purdue-Smithe. She noted prior studies showed the frequency of migraine attacks is related to ischemic stroke and other cardiovascular outcomes.

The authors acknowledged a limitation for the current study: Although migraine history was reported prior to pregnancy, information on migraine aura was collected after most of the pregnancies in the cohort were over. So the findings for migraine aura may have been influenced by participants’ ability to accurately remember their experiences.
 

Collaboration is key

Commenting on the research, Nina Riggins, MD, PhD, director of the Headache and Traumatic Brain Injury Center in the department of neurosciences at the University of California, San Diego, said the study “stands out” because it distinguishes pregnancy complications between those with and without aura among women with migraine. 

Dr. Riggins noted the investigators found the risk of preeclampsia, which on average occurs in about 3%-5% of pregnancies, is higher among women with migraine with aura.  

“The good news is that treatments are available,” she said. “Preconception planning should include this discussion for patients living with migraine.”

However, the study did not compare risks for patients who have frequent migraine attacks versus episodic migraine, Dr. Riggins noted. “We need to learn more about whether any treatments can be safe and effective to decrease risks of complications during pregnancy in this population,” she said.

“I believe, ultimately, what this study reveals is that collaboration among primary care, ob.gyn., maternal-fetal medicine specialists, and neurologists will likely benefit pregnant patients with migraine,” Dr. Riggins said.

The study received funding from the National Institutes of Health. Dr. Purdue-Smithe has disclosed no relevant financial relationships.

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

A ketogenic diet may reduce disability and improve quality of life, fatigue, and depression in patients with multiple sclerosis (MS), new research suggests.

High-fat, low-carbohydrate ketogenic diets mimic a fasting state and promote a more efficient use of energy – and have previously been shown to affect immune regulation. The diet helps lower blood sugar in individuals with type 2 diabetes and has been used for years to improve seizure control in patients with epilepsy, researchers note.

However, “there is a paucity of literature on the ketogenic diet in MS currently,” said principal investigator J. Nicholas Brenton, MD, University of Virginia, Charlottesville.

“The current study demonstrates the safety, tolerability, and potential clinical benefits of a ketogenic diet over 6 months in patients with relapsing MS,” Dr. Brenton said.

The were presented at the 2022 annual meeting of the American Academy of Neurology.
 

Palatable, beneficial

The open-label, uncontrolled study included 65 patients with relapsing MS who followed a ketogenic diet for 6 months. Investigators monitored adherence by daily urine ketone testing.

Patient-reported fatigue, depression, and quality-of-life scores were obtained at baseline, in addition to fasting adipokines and pertinent MS-related clinical outcome metrics. Baseline study metrics were repeated at 3 and/or 6 months while on the ketogenic diet.

Of the patient group, 83% adhered to the ketogenic diet for the full 6-month study period.

The ketogenic diet was associated with reductions in fat mass from baseline to 6 months (41.3 vs. 32.0 kg; P < .001) and a significant decline in fatigue and depression scores, the investigators reported.

MS quality-of-life physical and mental composite scores also improved while on the ketogenic diet (P < .001 for both).

A significant decrease from baseline to 6 months in Expanded Disability Status Scale scores, signifying improvement, was observed (2.3 vs. 1.9; P < .001).

Improvements were also shown on the 6-minute walk (1,631 vs. 1,733 feet; P < .001) and the nine-hole peg test (21.5 vs. 20.3 seconds; P < .001).

At 6 months on the diet, fasting serum leptin was significantly lower (25.5 vs. 14 ng/mL; P <.001), and adiponectin was higher (11.4 vs. 13.5 μg/mL, P = .002).
 

Justifies further research

The current study builds on an earlier one that Dr. Brenton and colleagues conducted in 2019 that showed that the ketogenic diet was feasible in patients with MS. “Our data justify the need for future studies of ketogenic diets as a complementary therapeutic approach to the treatment of MS,” Dr. Brenton said.

He noted that there may be multiple mechanisms of benefit when considering the ketogenic diet. “One avenue is via reduction in total body fat. This is an important aspect as we continue to learn more about the role of obesity and fat-derived inflammation in MS,” Dr. Brenton said.

“Ketogenic diets also have immunomodulatory properties,” such as the capacity to reduce oxidative damage from metabolic stress, increase mitochondrial biogenesis, and reduce systemic inflammation, he added. “These intrinsic properties of the ketogenic diet make it appealing to study in immune-mediated diseases, such as MS.”

Dr. Brenton cautioned that the data demonstrate the diet’s safety over 6 months but that the study was not designed to assess its long-term implications in MS. “Thus, while our results support the rationale for a larger-scale study of ketogenic diets as a complementary treatment for MS, our data does not support its widespread adoption outside of a clinical trial,” he said.
 

Remarkable adherence

Commenting on the study, Shaheen E. Lakhan, MD, PhD, a neurologist in Boston, noted that “variations of the ketogenic diet have been popularized in the general population for weight loss and further studied for other medical conditions [that are] largely immune-related, including MS.”

He noted that it was “remarkable” that the vast majority of study participants with MS adhered to the very regimented ketogenic diet for 6 months.

Seeing this translate into the real world “will be the next milestone, in addition to its impact on relapses and brain lesions as seen on MRI,” which are the classic markers of MS, said Dr. Lakhan, who was not involved with the research.

He cautioned that “even if one can follow the ketogenic diet, certain conditions can be made worse. This includes kidney stones, liver disease, reflux, constipation, and other metabolic disorders.”

The study was funded by the National Center for Advancing Translational Sciences of the National Institutes of Health and by the ZiMS Foundation. Dr. Brenton and Dr. Lakhan have reported no relevant financial relationships.

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

A ketogenic diet may reduce disability and improve quality of life, fatigue, and depression in patients with multiple sclerosis (MS), new research suggests.

High-fat, low-carbohydrate ketogenic diets mimic a fasting state and promote a more efficient use of energy – and have previously been shown to affect immune regulation. The diet helps lower blood sugar in individuals with type 2 diabetes and has been used for years to improve seizure control in patients with epilepsy, researchers note.

However, “there is a paucity of literature on the ketogenic diet in MS currently,” said principal investigator J. Nicholas Brenton, MD, University of Virginia, Charlottesville.

“The current study demonstrates the safety, tolerability, and potential clinical benefits of a ketogenic diet over 6 months in patients with relapsing MS,” Dr. Brenton said.

The were presented at the 2022 annual meeting of the American Academy of Neurology.
 

Palatable, beneficial

The open-label, uncontrolled study included 65 patients with relapsing MS who followed a ketogenic diet for 6 months. Investigators monitored adherence by daily urine ketone testing.

Patient-reported fatigue, depression, and quality-of-life scores were obtained at baseline, in addition to fasting adipokines and pertinent MS-related clinical outcome metrics. Baseline study metrics were repeated at 3 and/or 6 months while on the ketogenic diet.

Of the patient group, 83% adhered to the ketogenic diet for the full 6-month study period.

The ketogenic diet was associated with reductions in fat mass from baseline to 6 months (41.3 vs. 32.0 kg; P < .001) and a significant decline in fatigue and depression scores, the investigators reported.

MS quality-of-life physical and mental composite scores also improved while on the ketogenic diet (P < .001 for both).

A significant decrease from baseline to 6 months in Expanded Disability Status Scale scores, signifying improvement, was observed (2.3 vs. 1.9; P < .001).

Improvements were also shown on the 6-minute walk (1,631 vs. 1,733 feet; P < .001) and the nine-hole peg test (21.5 vs. 20.3 seconds; P < .001).

At 6 months on the diet, fasting serum leptin was significantly lower (25.5 vs. 14 ng/mL; P <.001), and adiponectin was higher (11.4 vs. 13.5 μg/mL, P = .002).
 

Justifies further research

The current study builds on an earlier one that Dr. Brenton and colleagues conducted in 2019 that showed that the ketogenic diet was feasible in patients with MS. “Our data justify the need for future studies of ketogenic diets as a complementary therapeutic approach to the treatment of MS,” Dr. Brenton said.

He noted that there may be multiple mechanisms of benefit when considering the ketogenic diet. “One avenue is via reduction in total body fat. This is an important aspect as we continue to learn more about the role of obesity and fat-derived inflammation in MS,” Dr. Brenton said.

“Ketogenic diets also have immunomodulatory properties,” such as the capacity to reduce oxidative damage from metabolic stress, increase mitochondrial biogenesis, and reduce systemic inflammation, he added. “These intrinsic properties of the ketogenic diet make it appealing to study in immune-mediated diseases, such as MS.”

Dr. Brenton cautioned that the data demonstrate the diet’s safety over 6 months but that the study was not designed to assess its long-term implications in MS. “Thus, while our results support the rationale for a larger-scale study of ketogenic diets as a complementary treatment for MS, our data does not support its widespread adoption outside of a clinical trial,” he said.
 

Remarkable adherence

Commenting on the study, Shaheen E. Lakhan, MD, PhD, a neurologist in Boston, noted that “variations of the ketogenic diet have been popularized in the general population for weight loss and further studied for other medical conditions [that are] largely immune-related, including MS.”

He noted that it was “remarkable” that the vast majority of study participants with MS adhered to the very regimented ketogenic diet for 6 months.

Seeing this translate into the real world “will be the next milestone, in addition to its impact on relapses and brain lesions as seen on MRI,” which are the classic markers of MS, said Dr. Lakhan, who was not involved with the research.

He cautioned that “even if one can follow the ketogenic diet, certain conditions can be made worse. This includes kidney stones, liver disease, reflux, constipation, and other metabolic disorders.”

The study was funded by the National Center for Advancing Translational Sciences of the National Institutes of Health and by the ZiMS Foundation. Dr. Brenton and Dr. Lakhan have reported no relevant financial relationships.

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

A ketogenic diet may reduce disability and improve quality of life, fatigue, and depression in patients with multiple sclerosis (MS), new research suggests.

High-fat, low-carbohydrate ketogenic diets mimic a fasting state and promote a more efficient use of energy – and have previously been shown to affect immune regulation. The diet helps lower blood sugar in individuals with type 2 diabetes and has been used for years to improve seizure control in patients with epilepsy, researchers note.

However, “there is a paucity of literature on the ketogenic diet in MS currently,” said principal investigator J. Nicholas Brenton, MD, University of Virginia, Charlottesville.

“The current study demonstrates the safety, tolerability, and potential clinical benefits of a ketogenic diet over 6 months in patients with relapsing MS,” Dr. Brenton said.

The were presented at the 2022 annual meeting of the American Academy of Neurology.
 

Palatable, beneficial

The open-label, uncontrolled study included 65 patients with relapsing MS who followed a ketogenic diet for 6 months. Investigators monitored adherence by daily urine ketone testing.

Patient-reported fatigue, depression, and quality-of-life scores were obtained at baseline, in addition to fasting adipokines and pertinent MS-related clinical outcome metrics. Baseline study metrics were repeated at 3 and/or 6 months while on the ketogenic diet.

Of the patient group, 83% adhered to the ketogenic diet for the full 6-month study period.

The ketogenic diet was associated with reductions in fat mass from baseline to 6 months (41.3 vs. 32.0 kg; P < .001) and a significant decline in fatigue and depression scores, the investigators reported.

MS quality-of-life physical and mental composite scores also improved while on the ketogenic diet (P < .001 for both).

A significant decrease from baseline to 6 months in Expanded Disability Status Scale scores, signifying improvement, was observed (2.3 vs. 1.9; P < .001).

Improvements were also shown on the 6-minute walk (1,631 vs. 1,733 feet; P < .001) and the nine-hole peg test (21.5 vs. 20.3 seconds; P < .001).

At 6 months on the diet, fasting serum leptin was significantly lower (25.5 vs. 14 ng/mL; P <.001), and adiponectin was higher (11.4 vs. 13.5 μg/mL, P = .002).
 

Justifies further research

The current study builds on an earlier one that Dr. Brenton and colleagues conducted in 2019 that showed that the ketogenic diet was feasible in patients with MS. “Our data justify the need for future studies of ketogenic diets as a complementary therapeutic approach to the treatment of MS,” Dr. Brenton said.

He noted that there may be multiple mechanisms of benefit when considering the ketogenic diet. “One avenue is via reduction in total body fat. This is an important aspect as we continue to learn more about the role of obesity and fat-derived inflammation in MS,” Dr. Brenton said.

“Ketogenic diets also have immunomodulatory properties,” such as the capacity to reduce oxidative damage from metabolic stress, increase mitochondrial biogenesis, and reduce systemic inflammation, he added. “These intrinsic properties of the ketogenic diet make it appealing to study in immune-mediated diseases, such as MS.”

Dr. Brenton cautioned that the data demonstrate the diet’s safety over 6 months but that the study was not designed to assess its long-term implications in MS. “Thus, while our results support the rationale for a larger-scale study of ketogenic diets as a complementary treatment for MS, our data does not support its widespread adoption outside of a clinical trial,” he said.
 

Remarkable adherence

Commenting on the study, Shaheen E. Lakhan, MD, PhD, a neurologist in Boston, noted that “variations of the ketogenic diet have been popularized in the general population for weight loss and further studied for other medical conditions [that are] largely immune-related, including MS.”

He noted that it was “remarkable” that the vast majority of study participants with MS adhered to the very regimented ketogenic diet for 6 months.

Seeing this translate into the real world “will be the next milestone, in addition to its impact on relapses and brain lesions as seen on MRI,” which are the classic markers of MS, said Dr. Lakhan, who was not involved with the research.

He cautioned that “even if one can follow the ketogenic diet, certain conditions can be made worse. This includes kidney stones, liver disease, reflux, constipation, and other metabolic disorders.”

The study was funded by the National Center for Advancing Translational Sciences of the National Institutes of Health and by the ZiMS Foundation. Dr. Brenton and Dr. Lakhan have reported no relevant financial relationships.

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