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Neurology Reviews covers innovative and emerging news in neurology and neuroscience every month, with a focus on practical approaches to treating Parkinson's disease, epilepsy, headache, stroke, multiple sclerosis, Alzheimer's disease, and other neurologic disorders.
PML
Progressive multifocal leukoencephalopathy
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The leading independent newspaper covering neurology news and commentary.
Living the introvert’s dream: Alone for 500 days, but never lonely
Beating the allegory of the cave
When Beatriz Flamini spoke with reporters on April 14, she knew nothing of the previous 18 months. The Russian invasion of Ukraine? Nope. The death of Queen Elizabeth? Also no. But before you make fun of her, she has an excuse. She’s been living under a rock.
As part of an experiment to test how social isolation and disorientation affect a person’s mind, sense of time, and sleeping patterns, Ms. Flamini lived in a 70-meter-deep cave in southern Spain for 500 days, starting in November 2021. Alone. No outside communication with the outside world in any way, though she was constantly monitored by a team of researchers. She also had multiple cameras filming her for an upcoming documentary.
This is a massive step up from the previous record for time spent underground for science: A team of 15 spent 50 days underground in 2021 to similar study of isolation and how it affected circadian rhythms. It’s also almost certainly a world record for time spent underground.
All that time alone certainly sounds like some sort of medieval torture, but Ms. Flamini had access to food, water, and a library of books. Which she made liberal use of, reading at least 60 books during her stay. She also had a panic button in case the isolation became too much or an emergency developed, but she never considered using it.
She lost track of time after 2 months, flies invaded the cave on occasion, and maintaining coherence was occasionally a struggle, but she kept things together very well. In fact, she didn’t even want to leave when her team came for her. She wasn’t even finished with her 61st book.
When she spoke with gathered reporters after the ordeal, words were obviously difficult to come by for her, having not spoken in nearly 18 months, but her mind was clearly still sharp and she had a very important question for everyone gathered around her.
Who’s buying the beer?
We approve of this request.
Staphylococcus and the speed of evolution
Bacteria, we know, are tough little buggers that are hard to see and even harder to get rid of. So hard, actually, that human bodies eventually gave up on the task and decided to just incorporate them into our organ systems. But why are bacteria so hard to eliminate?
Two words: rapid evolution. How rapid? For the first time, scientists have directly observed adaptive evolution by Staphylococcus aureus in a single person’s skin microbiome. That’s how rapid.
For their study, the researchers collected samples from the nostrils, backs of knees, insides of elbows, and forearms of 23 children with eczema. They eventually cultured almost 1,500 unique colonies of S. aureus cells from those samples and sequenced the cells’ genomes.
All that sampling and culturing and sequencing showed that it was rare for a new S. aureus strain to come in and replace the existing strain. “Despite the stability at the lineage level, we see a lot of dynamics at the whole genome level, where new mutations are constantly arising in these bacteria and then spreading throughout the entire body,” Tami D. Lieberman, PhD, of the Massachusetts Institute of Technology, Cambridge, said in a written statement from MIT.
One frequent mutation involved a gene called capD, which encodes an enzyme necessary for synthesizing the capsular polysaccharide – a coating that protects S. aureus from recognition by immune cells. In one patient, four different mutations of capD arose independently in different samples before one variant became dominant and spread over the entire microbiome, MIT reported.
The mutation, which actually results in the loss of the polysaccharide capsule, may allow cells to grow faster than those without the mutation because they have more fuel to power their own growth, the researchers suggested. It’s also possible that loss of the capsule allows S. aureus cells to stick to the skin better because proteins that allow them to adhere to the skin are more exposed.
Dr. Lieberman and her associates hope that these variant-containing cells could be a new target for eczema treatments, but we’re never optimistic when it comes to bacteria. That’s because some of us are old enough to remember evolutionary biologist Stephen Jay Gould, who wrote in his book “Full House”: “Our planet has always been in the ‘Age of Bacteria,’ ever since the first fossils – bacteria, of course – were entombed in rocks more than 3 billion years ago. On any possible, reasonable or fair criterion, bacteria are – and always have been – the dominant forms of life on Earth.”
In the distant future, long after humans have left the scene, the bacteria will be laughing at the last rats and cockroaches scurrying across the landscape. Wanna bet?
The height of genetic prediction
Genetics are practically a DNA Scrabble bag. Traits like eye color and hair texture are chosen in the same fashion, based on what gets pulled from our own genetic bag of letters, but what about height? Researchers may now have a way to predict adult height and make it more than just an educated guess.
How? By looking at the genes in our growth plates. The cartilage on the ends of our bones hardens as we age, eventually deciding an individual’s stature. In a recently published study, a research team looked at 600 million cartilage cells linked to maturation and cell growth in mice. Because everything starts with rodents.
After that search identified 145 genes linked to growth plate maturation and formation of the bones, they compared the mouse genes with data from genome-wide association studies (GWAS) of human height to look for hotspots where the height genes exist in human DNA.
The results showed which genes play a role in deciding height, and the GWAS data also suggested that genetic changes affecting cartilage cell maturation may strongly influence adult height, said the investigators, who hope that earlier interventions can improve outcomes in patients with conditions such as skeletal dysplasia.
So, yeah, you may want to be a little taller or shorter, but the outcome of that particular Scrabble game was determined when your parents, you know, dropped the letters in the bag.
Beating the allegory of the cave
When Beatriz Flamini spoke with reporters on April 14, she knew nothing of the previous 18 months. The Russian invasion of Ukraine? Nope. The death of Queen Elizabeth? Also no. But before you make fun of her, she has an excuse. She’s been living under a rock.
As part of an experiment to test how social isolation and disorientation affect a person’s mind, sense of time, and sleeping patterns, Ms. Flamini lived in a 70-meter-deep cave in southern Spain for 500 days, starting in November 2021. Alone. No outside communication with the outside world in any way, though she was constantly monitored by a team of researchers. She also had multiple cameras filming her for an upcoming documentary.
This is a massive step up from the previous record for time spent underground for science: A team of 15 spent 50 days underground in 2021 to similar study of isolation and how it affected circadian rhythms. It’s also almost certainly a world record for time spent underground.
All that time alone certainly sounds like some sort of medieval torture, but Ms. Flamini had access to food, water, and a library of books. Which she made liberal use of, reading at least 60 books during her stay. She also had a panic button in case the isolation became too much or an emergency developed, but she never considered using it.
She lost track of time after 2 months, flies invaded the cave on occasion, and maintaining coherence was occasionally a struggle, but she kept things together very well. In fact, she didn’t even want to leave when her team came for her. She wasn’t even finished with her 61st book.
When she spoke with gathered reporters after the ordeal, words were obviously difficult to come by for her, having not spoken in nearly 18 months, but her mind was clearly still sharp and she had a very important question for everyone gathered around her.
Who’s buying the beer?
We approve of this request.
Staphylococcus and the speed of evolution
Bacteria, we know, are tough little buggers that are hard to see and even harder to get rid of. So hard, actually, that human bodies eventually gave up on the task and decided to just incorporate them into our organ systems. But why are bacteria so hard to eliminate?
Two words: rapid evolution. How rapid? For the first time, scientists have directly observed adaptive evolution by Staphylococcus aureus in a single person’s skin microbiome. That’s how rapid.
For their study, the researchers collected samples from the nostrils, backs of knees, insides of elbows, and forearms of 23 children with eczema. They eventually cultured almost 1,500 unique colonies of S. aureus cells from those samples and sequenced the cells’ genomes.
All that sampling and culturing and sequencing showed that it was rare for a new S. aureus strain to come in and replace the existing strain. “Despite the stability at the lineage level, we see a lot of dynamics at the whole genome level, where new mutations are constantly arising in these bacteria and then spreading throughout the entire body,” Tami D. Lieberman, PhD, of the Massachusetts Institute of Technology, Cambridge, said in a written statement from MIT.
One frequent mutation involved a gene called capD, which encodes an enzyme necessary for synthesizing the capsular polysaccharide – a coating that protects S. aureus from recognition by immune cells. In one patient, four different mutations of capD arose independently in different samples before one variant became dominant and spread over the entire microbiome, MIT reported.
The mutation, which actually results in the loss of the polysaccharide capsule, may allow cells to grow faster than those without the mutation because they have more fuel to power their own growth, the researchers suggested. It’s also possible that loss of the capsule allows S. aureus cells to stick to the skin better because proteins that allow them to adhere to the skin are more exposed.
Dr. Lieberman and her associates hope that these variant-containing cells could be a new target for eczema treatments, but we’re never optimistic when it comes to bacteria. That’s because some of us are old enough to remember evolutionary biologist Stephen Jay Gould, who wrote in his book “Full House”: “Our planet has always been in the ‘Age of Bacteria,’ ever since the first fossils – bacteria, of course – were entombed in rocks more than 3 billion years ago. On any possible, reasonable or fair criterion, bacteria are – and always have been – the dominant forms of life on Earth.”
In the distant future, long after humans have left the scene, the bacteria will be laughing at the last rats and cockroaches scurrying across the landscape. Wanna bet?
The height of genetic prediction
Genetics are practically a DNA Scrabble bag. Traits like eye color and hair texture are chosen in the same fashion, based on what gets pulled from our own genetic bag of letters, but what about height? Researchers may now have a way to predict adult height and make it more than just an educated guess.
How? By looking at the genes in our growth plates. The cartilage on the ends of our bones hardens as we age, eventually deciding an individual’s stature. In a recently published study, a research team looked at 600 million cartilage cells linked to maturation and cell growth in mice. Because everything starts with rodents.
After that search identified 145 genes linked to growth plate maturation and formation of the bones, they compared the mouse genes with data from genome-wide association studies (GWAS) of human height to look for hotspots where the height genes exist in human DNA.
The results showed which genes play a role in deciding height, and the GWAS data also suggested that genetic changes affecting cartilage cell maturation may strongly influence adult height, said the investigators, who hope that earlier interventions can improve outcomes in patients with conditions such as skeletal dysplasia.
So, yeah, you may want to be a little taller or shorter, but the outcome of that particular Scrabble game was determined when your parents, you know, dropped the letters in the bag.
Beating the allegory of the cave
When Beatriz Flamini spoke with reporters on April 14, she knew nothing of the previous 18 months. The Russian invasion of Ukraine? Nope. The death of Queen Elizabeth? Also no. But before you make fun of her, she has an excuse. She’s been living under a rock.
As part of an experiment to test how social isolation and disorientation affect a person’s mind, sense of time, and sleeping patterns, Ms. Flamini lived in a 70-meter-deep cave in southern Spain for 500 days, starting in November 2021. Alone. No outside communication with the outside world in any way, though she was constantly monitored by a team of researchers. She also had multiple cameras filming her for an upcoming documentary.
This is a massive step up from the previous record for time spent underground for science: A team of 15 spent 50 days underground in 2021 to similar study of isolation and how it affected circadian rhythms. It’s also almost certainly a world record for time spent underground.
All that time alone certainly sounds like some sort of medieval torture, but Ms. Flamini had access to food, water, and a library of books. Which she made liberal use of, reading at least 60 books during her stay. She also had a panic button in case the isolation became too much or an emergency developed, but she never considered using it.
She lost track of time after 2 months, flies invaded the cave on occasion, and maintaining coherence was occasionally a struggle, but she kept things together very well. In fact, she didn’t even want to leave when her team came for her. She wasn’t even finished with her 61st book.
When she spoke with gathered reporters after the ordeal, words were obviously difficult to come by for her, having not spoken in nearly 18 months, but her mind was clearly still sharp and she had a very important question for everyone gathered around her.
Who’s buying the beer?
We approve of this request.
Staphylococcus and the speed of evolution
Bacteria, we know, are tough little buggers that are hard to see and even harder to get rid of. So hard, actually, that human bodies eventually gave up on the task and decided to just incorporate them into our organ systems. But why are bacteria so hard to eliminate?
Two words: rapid evolution. How rapid? For the first time, scientists have directly observed adaptive evolution by Staphylococcus aureus in a single person’s skin microbiome. That’s how rapid.
For their study, the researchers collected samples from the nostrils, backs of knees, insides of elbows, and forearms of 23 children with eczema. They eventually cultured almost 1,500 unique colonies of S. aureus cells from those samples and sequenced the cells’ genomes.
All that sampling and culturing and sequencing showed that it was rare for a new S. aureus strain to come in and replace the existing strain. “Despite the stability at the lineage level, we see a lot of dynamics at the whole genome level, where new mutations are constantly arising in these bacteria and then spreading throughout the entire body,” Tami D. Lieberman, PhD, of the Massachusetts Institute of Technology, Cambridge, said in a written statement from MIT.
One frequent mutation involved a gene called capD, which encodes an enzyme necessary for synthesizing the capsular polysaccharide – a coating that protects S. aureus from recognition by immune cells. In one patient, four different mutations of capD arose independently in different samples before one variant became dominant and spread over the entire microbiome, MIT reported.
The mutation, which actually results in the loss of the polysaccharide capsule, may allow cells to grow faster than those without the mutation because they have more fuel to power their own growth, the researchers suggested. It’s also possible that loss of the capsule allows S. aureus cells to stick to the skin better because proteins that allow them to adhere to the skin are more exposed.
Dr. Lieberman and her associates hope that these variant-containing cells could be a new target for eczema treatments, but we’re never optimistic when it comes to bacteria. That’s because some of us are old enough to remember evolutionary biologist Stephen Jay Gould, who wrote in his book “Full House”: “Our planet has always been in the ‘Age of Bacteria,’ ever since the first fossils – bacteria, of course – were entombed in rocks more than 3 billion years ago. On any possible, reasonable or fair criterion, bacteria are – and always have been – the dominant forms of life on Earth.”
In the distant future, long after humans have left the scene, the bacteria will be laughing at the last rats and cockroaches scurrying across the landscape. Wanna bet?
The height of genetic prediction
Genetics are practically a DNA Scrabble bag. Traits like eye color and hair texture are chosen in the same fashion, based on what gets pulled from our own genetic bag of letters, but what about height? Researchers may now have a way to predict adult height and make it more than just an educated guess.
How? By looking at the genes in our growth plates. The cartilage on the ends of our bones hardens as we age, eventually deciding an individual’s stature. In a recently published study, a research team looked at 600 million cartilage cells linked to maturation and cell growth in mice. Because everything starts with rodents.
After that search identified 145 genes linked to growth plate maturation and formation of the bones, they compared the mouse genes with data from genome-wide association studies (GWAS) of human height to look for hotspots where the height genes exist in human DNA.
The results showed which genes play a role in deciding height, and the GWAS data also suggested that genetic changes affecting cartilage cell maturation may strongly influence adult height, said the investigators, who hope that earlier interventions can improve outcomes in patients with conditions such as skeletal dysplasia.
So, yeah, you may want to be a little taller or shorter, but the outcome of that particular Scrabble game was determined when your parents, you know, dropped the letters in the bag.
Mediterranean diet improves cognition in MS
due to a potential neuroprotective mechanism, according to findings of a study that was released early, ahead of presentation at the annual meting of the American Academy of Neurology.
“We were most surprised by the magnitude of the results,” said Ilana Katz Sand, MD, associate professor of neurology at the Corinne Goldsmith Dickinson Center for MS at Mount Sinai in New York. “We hypothesized a significant association between Mediterranean diet and cognition in MS, but we did not anticipate the 20% absolute difference, particularly because we rigorously controlled the demographic and health-related factors, like socioeconomic status, body mass index, and exercise habits.”
The Mediterranean diet consists of predominately vegetables, fruits, legumes, fish, and healthy fats while minimizing the consumption of dairy products, meats, and saturated acids. Previous literature has drawn an association between diet and MS symptomology, notably with regard to the Mediterranean diet. These studies indicated a connection between thalamic volume in patients with early MS as well as objectively captured MS-related disability. In this study, researchers have continued their investigation by exploring how the Mediterranean diet affects cognition.
In this cross-sectional observational study, investigators evaluated 563 people with MS ranging in age from 18 to 65 years (n = 563; 71% women; aged 44.2 ± 11.3 years). To accomplish this task, researchers conducted a retrospective chart review capturing data from patients with MS who had undergone neurobehavioral screenings. Qualifying subjects completed the Mediterranean Diet Adherence Screener (MEDAS) to determine the extent to which they adhered to the Mediterranean diet. A 14-item questionnaire, MEDAS assess a person’s usual intake of healthful foods such as vegetables and olive oil, as well as minimization of unhealthy foods such as butter and red meat. They also completed an analogue of the CICMAS cognitive battery comprised of a composite of Symbol Digit Modalities Test, Hopkins Verbal Learning Test, Revised, and CANTAB Paired Associate Learning.
Researchers evaluated patient-reported outcomes adjusted based on demographics (i.e., age, sex, race, ethnicity, and socioeconomic status) and health-related factors. These elements included body mass index, exercise, sleep disturbance, hypertension, diabetes, hyperlipidemia, and smoking.
The study excluded patients who had another primary neurological condition in addition to MS (n = 24), serious psychiatric illness such as schizophrenia (n = 5) or clinical relapse within 6 weeks (n = 2), or missing data (n = 13).
Based on the diet scores, investigators stratified participants into four groups. Those with the scores ranging from 0 to 4 were classified into the lowest group, while scores of 9 or greater qualified participants for the high group.
Investigators observed a significant association between a higher Mediterranean diet score and condition in the population sampled. They found a mean z-score of –0.67 (0.95). In addition, a higher MEDAS proved an independent indicator of better cognition (B = 0.08 [95% confidence interval (CI), 0.05, 0.11], beta = 0.20, P < .001). In fact, a high MEDAS independently correlated to a 20% lower risk for cognitive impairment (odds ratio [OR] = .80 {95% CI, 0.73, 0.89}, P < .001). Ultimately, the study’s findings demonstrated MEDAS served as the strongest health-related indicator of z-score and cognitive impairment. Moreover, dietary modification based on effect suggested stronger associations between diet and cognition with progressive disease as opposed to relapsing disease, as noted by the relationship between the z-score and cognition.
“Further research is needed,” Dr. Katz Sand said. “But because the progressive phenotype reflects more prominent neurodegeneration, the greater observed effect size in those with progressive MS suggests a potential neuroprotective mechanism.”
This study was funded in part by an Irma T. Hirschl/Monique Weill-Caulier Research Award to Dr. Katz Sand. Dr. Katz Sand and coauthors also received funding from the National Multiple Sclerosis Society.
due to a potential neuroprotective mechanism, according to findings of a study that was released early, ahead of presentation at the annual meting of the American Academy of Neurology.
“We were most surprised by the magnitude of the results,” said Ilana Katz Sand, MD, associate professor of neurology at the Corinne Goldsmith Dickinson Center for MS at Mount Sinai in New York. “We hypothesized a significant association between Mediterranean diet and cognition in MS, but we did not anticipate the 20% absolute difference, particularly because we rigorously controlled the demographic and health-related factors, like socioeconomic status, body mass index, and exercise habits.”
The Mediterranean diet consists of predominately vegetables, fruits, legumes, fish, and healthy fats while minimizing the consumption of dairy products, meats, and saturated acids. Previous literature has drawn an association between diet and MS symptomology, notably with regard to the Mediterranean diet. These studies indicated a connection between thalamic volume in patients with early MS as well as objectively captured MS-related disability. In this study, researchers have continued their investigation by exploring how the Mediterranean diet affects cognition.
In this cross-sectional observational study, investigators evaluated 563 people with MS ranging in age from 18 to 65 years (n = 563; 71% women; aged 44.2 ± 11.3 years). To accomplish this task, researchers conducted a retrospective chart review capturing data from patients with MS who had undergone neurobehavioral screenings. Qualifying subjects completed the Mediterranean Diet Adherence Screener (MEDAS) to determine the extent to which they adhered to the Mediterranean diet. A 14-item questionnaire, MEDAS assess a person’s usual intake of healthful foods such as vegetables and olive oil, as well as minimization of unhealthy foods such as butter and red meat. They also completed an analogue of the CICMAS cognitive battery comprised of a composite of Symbol Digit Modalities Test, Hopkins Verbal Learning Test, Revised, and CANTAB Paired Associate Learning.
Researchers evaluated patient-reported outcomes adjusted based on demographics (i.e., age, sex, race, ethnicity, and socioeconomic status) and health-related factors. These elements included body mass index, exercise, sleep disturbance, hypertension, diabetes, hyperlipidemia, and smoking.
The study excluded patients who had another primary neurological condition in addition to MS (n = 24), serious psychiatric illness such as schizophrenia (n = 5) or clinical relapse within 6 weeks (n = 2), or missing data (n = 13).
Based on the diet scores, investigators stratified participants into four groups. Those with the scores ranging from 0 to 4 were classified into the lowest group, while scores of 9 or greater qualified participants for the high group.
Investigators observed a significant association between a higher Mediterranean diet score and condition in the population sampled. They found a mean z-score of –0.67 (0.95). In addition, a higher MEDAS proved an independent indicator of better cognition (B = 0.08 [95% confidence interval (CI), 0.05, 0.11], beta = 0.20, P < .001). In fact, a high MEDAS independently correlated to a 20% lower risk for cognitive impairment (odds ratio [OR] = .80 {95% CI, 0.73, 0.89}, P < .001). Ultimately, the study’s findings demonstrated MEDAS served as the strongest health-related indicator of z-score and cognitive impairment. Moreover, dietary modification based on effect suggested stronger associations between diet and cognition with progressive disease as opposed to relapsing disease, as noted by the relationship between the z-score and cognition.
“Further research is needed,” Dr. Katz Sand said. “But because the progressive phenotype reflects more prominent neurodegeneration, the greater observed effect size in those with progressive MS suggests a potential neuroprotective mechanism.”
This study was funded in part by an Irma T. Hirschl/Monique Weill-Caulier Research Award to Dr. Katz Sand. Dr. Katz Sand and coauthors also received funding from the National Multiple Sclerosis Society.
due to a potential neuroprotective mechanism, according to findings of a study that was released early, ahead of presentation at the annual meting of the American Academy of Neurology.
“We were most surprised by the magnitude of the results,” said Ilana Katz Sand, MD, associate professor of neurology at the Corinne Goldsmith Dickinson Center for MS at Mount Sinai in New York. “We hypothesized a significant association between Mediterranean diet and cognition in MS, but we did not anticipate the 20% absolute difference, particularly because we rigorously controlled the demographic and health-related factors, like socioeconomic status, body mass index, and exercise habits.”
The Mediterranean diet consists of predominately vegetables, fruits, legumes, fish, and healthy fats while minimizing the consumption of dairy products, meats, and saturated acids. Previous literature has drawn an association between diet and MS symptomology, notably with regard to the Mediterranean diet. These studies indicated a connection between thalamic volume in patients with early MS as well as objectively captured MS-related disability. In this study, researchers have continued their investigation by exploring how the Mediterranean diet affects cognition.
In this cross-sectional observational study, investigators evaluated 563 people with MS ranging in age from 18 to 65 years (n = 563; 71% women; aged 44.2 ± 11.3 years). To accomplish this task, researchers conducted a retrospective chart review capturing data from patients with MS who had undergone neurobehavioral screenings. Qualifying subjects completed the Mediterranean Diet Adherence Screener (MEDAS) to determine the extent to which they adhered to the Mediterranean diet. A 14-item questionnaire, MEDAS assess a person’s usual intake of healthful foods such as vegetables and olive oil, as well as minimization of unhealthy foods such as butter and red meat. They also completed an analogue of the CICMAS cognitive battery comprised of a composite of Symbol Digit Modalities Test, Hopkins Verbal Learning Test, Revised, and CANTAB Paired Associate Learning.
Researchers evaluated patient-reported outcomes adjusted based on demographics (i.e., age, sex, race, ethnicity, and socioeconomic status) and health-related factors. These elements included body mass index, exercise, sleep disturbance, hypertension, diabetes, hyperlipidemia, and smoking.
The study excluded patients who had another primary neurological condition in addition to MS (n = 24), serious psychiatric illness such as schizophrenia (n = 5) or clinical relapse within 6 weeks (n = 2), or missing data (n = 13).
Based on the diet scores, investigators stratified participants into four groups. Those with the scores ranging from 0 to 4 were classified into the lowest group, while scores of 9 or greater qualified participants for the high group.
Investigators observed a significant association between a higher Mediterranean diet score and condition in the population sampled. They found a mean z-score of –0.67 (0.95). In addition, a higher MEDAS proved an independent indicator of better cognition (B = 0.08 [95% confidence interval (CI), 0.05, 0.11], beta = 0.20, P < .001). In fact, a high MEDAS independently correlated to a 20% lower risk for cognitive impairment (odds ratio [OR] = .80 {95% CI, 0.73, 0.89}, P < .001). Ultimately, the study’s findings demonstrated MEDAS served as the strongest health-related indicator of z-score and cognitive impairment. Moreover, dietary modification based on effect suggested stronger associations between diet and cognition with progressive disease as opposed to relapsing disease, as noted by the relationship between the z-score and cognition.
“Further research is needed,” Dr. Katz Sand said. “But because the progressive phenotype reflects more prominent neurodegeneration, the greater observed effect size in those with progressive MS suggests a potential neuroprotective mechanism.”
This study was funded in part by an Irma T. Hirschl/Monique Weill-Caulier Research Award to Dr. Katz Sand. Dr. Katz Sand and coauthors also received funding from the National Multiple Sclerosis Society.
FROM AAN 2023
Obstructive sleep apnea linked to early cognitive decline
In a pilot study out of King’s College London, participants with severe OSA experienced worse executive functioning as well as social and emotional recognition versus healthy controls.
Major risk factors for OSA include obesity, high blood pressure, smoking, high cholesterol, and being middle-aged or older. Because some researchers have hypothesized that cognitive deficits could be driven by such comorbidities, the study investigators recruited middle-aged men with no medical comorbidities.
“Traditionally, we were more concerned with sleep apnea’s metabolic and cardiovascular comorbidities, and indeed, when cognitive deficits were demonstrated, most were attributed to them, and yet, our patients and their partners/families commonly tell us differently,” lead investigator Ivana Rosenzweig, MD, PhD, of King’s College London, who is also a consultant in sleep medicine and neuropsychiatry at Guy’s and St Thomas’ Hospital, London, said in an interview.
“Our findings provide a very important first step towards challenging the long-standing dogma that sleep apnea has little to do with the brain – apart from causing sleepiness – and that it is a predominantly nonneuro/psychiatric illness,” added Dr. Rosenzweig.
The findings were published online in Frontiers in Sleep.
Brain changes
The researchers wanted to understand how OSA may be linked to cognitive decline in the absence of cardiovascular and metabolic conditions.
To accomplish this, the investigators studied 27 men between the ages of 35 and 70 with a new diagnosis of mild to severe OSA without any comorbidities (16 with mild OSA and 11 with severe OSA). They also studied a control group of seven men matched for age, body mass index, and education level.
The team tested participants’ cognitive performance using the Cambridge Neuropsychological Test Automated Battery and found that the most significant deficits for the OSA group, compared with controls, were in areas of visual matching ability (P < .0001), short-term visual recognition memory, nonverbal patterns, executive functioning and attentional set-shifting (P < .001), psychomotor functioning, and social cognition and emotional recognition (P < .05).
On the latter two tests, impaired participants were less likely to accurately identify the emotion on computer-generated faces. Those with mild OSA performed better than those with severe OSA on these tasks, but rarely worse than controls.
Dr. Rosenzweig noted that the findings were one-of-a-kind because of the recruitment of patients with OSA who were otherwise healthy and nonobese, “something one rarely sees in the sleep clinic, where we commonly encounter patients with already developed comorbidities.
“In order to truly revolutionize the treatment for our patients, it is important to understand how much the accompanying comorbidities, such as systemic hypertension, obesity, diabetes, hyperlipidemia, and other various serious cardiovascular and metabolic diseases and how much the illness itself may shape the demonstrated cognitive deficits,” she said.
She also said that “it is widely agreed that medical problems in middle age may predispose to increased prevalence of dementia in later years.
Moreover, the very link between sleep apnea and Alzheimer’s, vascular and mixed dementia is increasingly demonstrated,” said Dr. Rosenzweig.
Although women typically have a lower prevalence of OSA than men, Dr. Rosenzweig said women were not included in the study “because we are too complex. As a lifelong feminist it pains me to say this, but to get any authoritative answer on our physiology, we need decent funding in place so that we can take into account all the intricacies of the changes of our sleep, physiology, and metabolism.
“While there is always lots of noise about how important it is to answer these questions, there are only very limited funds available for the sleep research,” she added.
Dr. Rosenzweig’s future research will focus on the potential link between OSA and neuroinflammation.
In a comment, Liza Ashbrook, MD, associate professor of neurology at the University of California, San Francisco, said the findings “add to the growing list of negative health consequences associated with sleep apnea.”
She said that, if the cognitive changes found in the study are, in fact, caused by OSA, it is unclear whether they are the beginning of long-term cognitive changes or a symptom of fragmented sleep that may be reversible.
Dr. Ashbrook said she would be interested in seeing research on understanding the effect of OSA treatment on the affected cognitive domains.
The study was funded by the Wellcome Trust. No relevant financial relationships were reported.
A version of this article originally appeared on Medscape.com.
In a pilot study out of King’s College London, participants with severe OSA experienced worse executive functioning as well as social and emotional recognition versus healthy controls.
Major risk factors for OSA include obesity, high blood pressure, smoking, high cholesterol, and being middle-aged or older. Because some researchers have hypothesized that cognitive deficits could be driven by such comorbidities, the study investigators recruited middle-aged men with no medical comorbidities.
“Traditionally, we were more concerned with sleep apnea’s metabolic and cardiovascular comorbidities, and indeed, when cognitive deficits were demonstrated, most were attributed to them, and yet, our patients and their partners/families commonly tell us differently,” lead investigator Ivana Rosenzweig, MD, PhD, of King’s College London, who is also a consultant in sleep medicine and neuropsychiatry at Guy’s and St Thomas’ Hospital, London, said in an interview.
“Our findings provide a very important first step towards challenging the long-standing dogma that sleep apnea has little to do with the brain – apart from causing sleepiness – and that it is a predominantly nonneuro/psychiatric illness,” added Dr. Rosenzweig.
The findings were published online in Frontiers in Sleep.
Brain changes
The researchers wanted to understand how OSA may be linked to cognitive decline in the absence of cardiovascular and metabolic conditions.
To accomplish this, the investigators studied 27 men between the ages of 35 and 70 with a new diagnosis of mild to severe OSA without any comorbidities (16 with mild OSA and 11 with severe OSA). They also studied a control group of seven men matched for age, body mass index, and education level.
The team tested participants’ cognitive performance using the Cambridge Neuropsychological Test Automated Battery and found that the most significant deficits for the OSA group, compared with controls, were in areas of visual matching ability (P < .0001), short-term visual recognition memory, nonverbal patterns, executive functioning and attentional set-shifting (P < .001), psychomotor functioning, and social cognition and emotional recognition (P < .05).
On the latter two tests, impaired participants were less likely to accurately identify the emotion on computer-generated faces. Those with mild OSA performed better than those with severe OSA on these tasks, but rarely worse than controls.
Dr. Rosenzweig noted that the findings were one-of-a-kind because of the recruitment of patients with OSA who were otherwise healthy and nonobese, “something one rarely sees in the sleep clinic, where we commonly encounter patients with already developed comorbidities.
“In order to truly revolutionize the treatment for our patients, it is important to understand how much the accompanying comorbidities, such as systemic hypertension, obesity, diabetes, hyperlipidemia, and other various serious cardiovascular and metabolic diseases and how much the illness itself may shape the demonstrated cognitive deficits,” she said.
She also said that “it is widely agreed that medical problems in middle age may predispose to increased prevalence of dementia in later years.
Moreover, the very link between sleep apnea and Alzheimer’s, vascular and mixed dementia is increasingly demonstrated,” said Dr. Rosenzweig.
Although women typically have a lower prevalence of OSA than men, Dr. Rosenzweig said women were not included in the study “because we are too complex. As a lifelong feminist it pains me to say this, but to get any authoritative answer on our physiology, we need decent funding in place so that we can take into account all the intricacies of the changes of our sleep, physiology, and metabolism.
“While there is always lots of noise about how important it is to answer these questions, there are only very limited funds available for the sleep research,” she added.
Dr. Rosenzweig’s future research will focus on the potential link between OSA and neuroinflammation.
In a comment, Liza Ashbrook, MD, associate professor of neurology at the University of California, San Francisco, said the findings “add to the growing list of negative health consequences associated with sleep apnea.”
She said that, if the cognitive changes found in the study are, in fact, caused by OSA, it is unclear whether they are the beginning of long-term cognitive changes or a symptom of fragmented sleep that may be reversible.
Dr. Ashbrook said she would be interested in seeing research on understanding the effect of OSA treatment on the affected cognitive domains.
The study was funded by the Wellcome Trust. No relevant financial relationships were reported.
A version of this article originally appeared on Medscape.com.
In a pilot study out of King’s College London, participants with severe OSA experienced worse executive functioning as well as social and emotional recognition versus healthy controls.
Major risk factors for OSA include obesity, high blood pressure, smoking, high cholesterol, and being middle-aged or older. Because some researchers have hypothesized that cognitive deficits could be driven by such comorbidities, the study investigators recruited middle-aged men with no medical comorbidities.
“Traditionally, we were more concerned with sleep apnea’s metabolic and cardiovascular comorbidities, and indeed, when cognitive deficits were demonstrated, most were attributed to them, and yet, our patients and their partners/families commonly tell us differently,” lead investigator Ivana Rosenzweig, MD, PhD, of King’s College London, who is also a consultant in sleep medicine and neuropsychiatry at Guy’s and St Thomas’ Hospital, London, said in an interview.
“Our findings provide a very important first step towards challenging the long-standing dogma that sleep apnea has little to do with the brain – apart from causing sleepiness – and that it is a predominantly nonneuro/psychiatric illness,” added Dr. Rosenzweig.
The findings were published online in Frontiers in Sleep.
Brain changes
The researchers wanted to understand how OSA may be linked to cognitive decline in the absence of cardiovascular and metabolic conditions.
To accomplish this, the investigators studied 27 men between the ages of 35 and 70 with a new diagnosis of mild to severe OSA without any comorbidities (16 with mild OSA and 11 with severe OSA). They also studied a control group of seven men matched for age, body mass index, and education level.
The team tested participants’ cognitive performance using the Cambridge Neuropsychological Test Automated Battery and found that the most significant deficits for the OSA group, compared with controls, were in areas of visual matching ability (P < .0001), short-term visual recognition memory, nonverbal patterns, executive functioning and attentional set-shifting (P < .001), psychomotor functioning, and social cognition and emotional recognition (P < .05).
On the latter two tests, impaired participants were less likely to accurately identify the emotion on computer-generated faces. Those with mild OSA performed better than those with severe OSA on these tasks, but rarely worse than controls.
Dr. Rosenzweig noted that the findings were one-of-a-kind because of the recruitment of patients with OSA who were otherwise healthy and nonobese, “something one rarely sees in the sleep clinic, where we commonly encounter patients with already developed comorbidities.
“In order to truly revolutionize the treatment for our patients, it is important to understand how much the accompanying comorbidities, such as systemic hypertension, obesity, diabetes, hyperlipidemia, and other various serious cardiovascular and metabolic diseases and how much the illness itself may shape the demonstrated cognitive deficits,” she said.
She also said that “it is widely agreed that medical problems in middle age may predispose to increased prevalence of dementia in later years.
Moreover, the very link between sleep apnea and Alzheimer’s, vascular and mixed dementia is increasingly demonstrated,” said Dr. Rosenzweig.
Although women typically have a lower prevalence of OSA than men, Dr. Rosenzweig said women were not included in the study “because we are too complex. As a lifelong feminist it pains me to say this, but to get any authoritative answer on our physiology, we need decent funding in place so that we can take into account all the intricacies of the changes of our sleep, physiology, and metabolism.
“While there is always lots of noise about how important it is to answer these questions, there are only very limited funds available for the sleep research,” she added.
Dr. Rosenzweig’s future research will focus on the potential link between OSA and neuroinflammation.
In a comment, Liza Ashbrook, MD, associate professor of neurology at the University of California, San Francisco, said the findings “add to the growing list of negative health consequences associated with sleep apnea.”
She said that, if the cognitive changes found in the study are, in fact, caused by OSA, it is unclear whether they are the beginning of long-term cognitive changes or a symptom of fragmented sleep that may be reversible.
Dr. Ashbrook said she would be interested in seeing research on understanding the effect of OSA treatment on the affected cognitive domains.
The study was funded by the Wellcome Trust. No relevant financial relationships were reported.
A version of this article originally appeared on Medscape.com.
FROM FRONTIERS IN SLEEP
Physicians may retire en masse soon. What does that mean for medicine?
The double whammy of pandemic burnout and the aging of baby boomer physicians has, indeed, the makings of some scary headlines. A recent survey by Elsevier Health predicts that up to 75% of health care workers will leave the profession by 2025. And a 2020 study conducted by the Association of American Medical Colleges (AAMC) projected a shortfall of up to 139,000 physicians by 2033.
“We’ve paid a lot of attention to physician retirement,” says Michael Dill, AAMC’s director of workforce studies. “It’s a significant concern in terms of whether we have an adequate supply of physicians in the U.S. to meet our nation’s medical care needs. Anyone who thinks otherwise is incorrect.”
To Mr. Dill,
“The physician workforce as a whole is aging,” he said. “Close to a quarter of the physicians in the U.S. are 65 and over. So, you don’t need any extraordinary events driving retirement in order for retirement to be a real phenomenon of which we should all be concerned.”
And, although Mr. Dill said there aren’t any data to suggest that doctors in rural or urban areas are retiring faster than in the suburbs, that doesn’t mean retirement will have the same impact depending on where patients live.
“If you live in a rural area with one small practice in town and that physician retires, there goes the entirety of the physician supply,” he said. “In a major metro area, that’s not as big a deal.”
Why younger doctors are fast-tracking retirement
Fernando Mendoza, MD, 54, a pediatric emergency department physician in Miami, worries that physicians are getting so bogged down by paperwork that this may lead to even more doctors, at younger ages, leaving the profession.
“I love taking care of kids, but there’s going to be a cost to doing your work when you’re spending as much time as we need to spend on charts, pharmacy requests, and making sure all of the Medicare and Medicaid compliance issues are worked out.”
These stressors may compel some younger doctors to consider carving out a second career or fast-track younger physicians toward retirement.
“A medical degree carries a lot of weight, which helps when pivoting,” said Dr. Mendoza, who launched Scrivas, a Miami-based medical scribe agency, to help reduce the paperwork workload for physicians. “It might be that a doctor wants to get involved in the acquisition of medical equipment, or maybe they can focus on their investments. Either way, by leaving medicine, they’re not dealing with the hassle and churn-and-burn of seeing patients.”
What this means for patients
The time is now to stem the upcoming tide of retirement, said Mr. Dill. But the challenges remain daunting. For starters, the country needs more physicians trained now – but it will take years to replace those baby boomer doctors ready to hang up their white coats.
The medical profession also needs to find ways to support physicians who spend their days juggling an endless array of responsibilities, he said.
The AAMC study found that patients already feel the physician shortfall. Their public opinion research in 2019 said 35% of patients had trouble finding a physician over the past 2 or 3 years, up 10 percentage points since they asked the question in 2015.
Moreover, according to the report, the over-65 population is expected to grow by 45.1%, leaving a specialty care gap because older people generally have more complicated health cases that require specialists. In addition, physician burnout may lead more physicians under 65 to retire much earlier than expected.
Changes in how medicine is practiced, telemedicine care, and medical education – such as disruption of classes or clinical rotations, regulatory changes, and a lack of interest in certain specialties – could also be affected by a mass physician retirement.
What can we do about mass retirement?
The AAMC reports in “The Complexities of Physician Supply and Demand: Projections From 2019 to 2034” that federally funded GME support is in the works to train 15,000 physicians per year, with 3,000 new residency slots added per year over 5 years. The proposed model will add 3,750 new physicians each year beginning in 2026.
Other efforts include increasing use of APRNs and PAs, whose population is estimated to more than double by 2034, improve population health through preventive care, increase equity in health outcomes, and improve access and affordable care.
Removing licensing barriers for immigrant doctors can also help alleviate the shortage.
“We need to find better ways to leverage the entirety of the health care team so that not as much falls on physicians,” Mr. Dill said. “It’s also imperative that we focus on ways to support physician wellness and allow physicians to remain active in the field, but at a reduced rate.”
That’s precisely what Marie Brown, MD, director of practice redesign at the American Medical Association, is seeing nationwide. Cutting back their hours is not only trending, but it’s also helping doctors cope with burnout.
“We’re seeing physicians take a 20% or more cut in salary in order to decrease their burden,” she said. “They’ll spend 4 days on clinical time with patients so that on that fifth ‘day off,’ they’re doing the paperwork and documentation they need to do so they don’t compromise care on the other 4 days of the week.”
And this may only be a Band-Aid solution, she fears.
“If a physician is spending 3 hours a day doing unnecessary work that could be done by another team member, that’s contributing to burnout,” Dr. Brown said. “It’s no surprise that they’ll want to escape and retire if they’re in a financial situation to do so.”
“I advocate negotiating within your organization so you’re doing more of what you like, such as mentoring or running a residency, and less of what you don’t, while cutting back from full-time to something less than full-time while maintaining benefits,” said Joel Greenwald, MD, a certified financial planner in Minneapolis, who specializes in helping physicians manage their financial affairs.
“Falling into the ‘like less’ bucket are usually things like working weekends and taking calls,” he said.
“This benefits everyone on a large scale because those doctors who find things they enjoy are generally working to a later age but working less hard,” he said. “Remaining comfortably and happily gainfully employed for a longer period, even if you’re not working full-time, has a very powerful effect on your financial planning, and you’ll avoid the risk of running out of money.”
A version of this article first appeared on Medscape.com.
The double whammy of pandemic burnout and the aging of baby boomer physicians has, indeed, the makings of some scary headlines. A recent survey by Elsevier Health predicts that up to 75% of health care workers will leave the profession by 2025. And a 2020 study conducted by the Association of American Medical Colleges (AAMC) projected a shortfall of up to 139,000 physicians by 2033.
“We’ve paid a lot of attention to physician retirement,” says Michael Dill, AAMC’s director of workforce studies. “It’s a significant concern in terms of whether we have an adequate supply of physicians in the U.S. to meet our nation’s medical care needs. Anyone who thinks otherwise is incorrect.”
To Mr. Dill,
“The physician workforce as a whole is aging,” he said. “Close to a quarter of the physicians in the U.S. are 65 and over. So, you don’t need any extraordinary events driving retirement in order for retirement to be a real phenomenon of which we should all be concerned.”
And, although Mr. Dill said there aren’t any data to suggest that doctors in rural or urban areas are retiring faster than in the suburbs, that doesn’t mean retirement will have the same impact depending on where patients live.
“If you live in a rural area with one small practice in town and that physician retires, there goes the entirety of the physician supply,” he said. “In a major metro area, that’s not as big a deal.”
Why younger doctors are fast-tracking retirement
Fernando Mendoza, MD, 54, a pediatric emergency department physician in Miami, worries that physicians are getting so bogged down by paperwork that this may lead to even more doctors, at younger ages, leaving the profession.
“I love taking care of kids, but there’s going to be a cost to doing your work when you’re spending as much time as we need to spend on charts, pharmacy requests, and making sure all of the Medicare and Medicaid compliance issues are worked out.”
These stressors may compel some younger doctors to consider carving out a second career or fast-track younger physicians toward retirement.
“A medical degree carries a lot of weight, which helps when pivoting,” said Dr. Mendoza, who launched Scrivas, a Miami-based medical scribe agency, to help reduce the paperwork workload for physicians. “It might be that a doctor wants to get involved in the acquisition of medical equipment, or maybe they can focus on their investments. Either way, by leaving medicine, they’re not dealing with the hassle and churn-and-burn of seeing patients.”
What this means for patients
The time is now to stem the upcoming tide of retirement, said Mr. Dill. But the challenges remain daunting. For starters, the country needs more physicians trained now – but it will take years to replace those baby boomer doctors ready to hang up their white coats.
The medical profession also needs to find ways to support physicians who spend their days juggling an endless array of responsibilities, he said.
The AAMC study found that patients already feel the physician shortfall. Their public opinion research in 2019 said 35% of patients had trouble finding a physician over the past 2 or 3 years, up 10 percentage points since they asked the question in 2015.
Moreover, according to the report, the over-65 population is expected to grow by 45.1%, leaving a specialty care gap because older people generally have more complicated health cases that require specialists. In addition, physician burnout may lead more physicians under 65 to retire much earlier than expected.
Changes in how medicine is practiced, telemedicine care, and medical education – such as disruption of classes or clinical rotations, regulatory changes, and a lack of interest in certain specialties – could also be affected by a mass physician retirement.
What can we do about mass retirement?
The AAMC reports in “The Complexities of Physician Supply and Demand: Projections From 2019 to 2034” that federally funded GME support is in the works to train 15,000 physicians per year, with 3,000 new residency slots added per year over 5 years. The proposed model will add 3,750 new physicians each year beginning in 2026.
Other efforts include increasing use of APRNs and PAs, whose population is estimated to more than double by 2034, improve population health through preventive care, increase equity in health outcomes, and improve access and affordable care.
Removing licensing barriers for immigrant doctors can also help alleviate the shortage.
“We need to find better ways to leverage the entirety of the health care team so that not as much falls on physicians,” Mr. Dill said. “It’s also imperative that we focus on ways to support physician wellness and allow physicians to remain active in the field, but at a reduced rate.”
That’s precisely what Marie Brown, MD, director of practice redesign at the American Medical Association, is seeing nationwide. Cutting back their hours is not only trending, but it’s also helping doctors cope with burnout.
“We’re seeing physicians take a 20% or more cut in salary in order to decrease their burden,” she said. “They’ll spend 4 days on clinical time with patients so that on that fifth ‘day off,’ they’re doing the paperwork and documentation they need to do so they don’t compromise care on the other 4 days of the week.”
And this may only be a Band-Aid solution, she fears.
“If a physician is spending 3 hours a day doing unnecessary work that could be done by another team member, that’s contributing to burnout,” Dr. Brown said. “It’s no surprise that they’ll want to escape and retire if they’re in a financial situation to do so.”
“I advocate negotiating within your organization so you’re doing more of what you like, such as mentoring or running a residency, and less of what you don’t, while cutting back from full-time to something less than full-time while maintaining benefits,” said Joel Greenwald, MD, a certified financial planner in Minneapolis, who specializes in helping physicians manage their financial affairs.
“Falling into the ‘like less’ bucket are usually things like working weekends and taking calls,” he said.
“This benefits everyone on a large scale because those doctors who find things they enjoy are generally working to a later age but working less hard,” he said. “Remaining comfortably and happily gainfully employed for a longer period, even if you’re not working full-time, has a very powerful effect on your financial planning, and you’ll avoid the risk of running out of money.”
A version of this article first appeared on Medscape.com.
The double whammy of pandemic burnout and the aging of baby boomer physicians has, indeed, the makings of some scary headlines. A recent survey by Elsevier Health predicts that up to 75% of health care workers will leave the profession by 2025. And a 2020 study conducted by the Association of American Medical Colleges (AAMC) projected a shortfall of up to 139,000 physicians by 2033.
“We’ve paid a lot of attention to physician retirement,” says Michael Dill, AAMC’s director of workforce studies. “It’s a significant concern in terms of whether we have an adequate supply of physicians in the U.S. to meet our nation’s medical care needs. Anyone who thinks otherwise is incorrect.”
To Mr. Dill,
“The physician workforce as a whole is aging,” he said. “Close to a quarter of the physicians in the U.S. are 65 and over. So, you don’t need any extraordinary events driving retirement in order for retirement to be a real phenomenon of which we should all be concerned.”
And, although Mr. Dill said there aren’t any data to suggest that doctors in rural or urban areas are retiring faster than in the suburbs, that doesn’t mean retirement will have the same impact depending on where patients live.
“If you live in a rural area with one small practice in town and that physician retires, there goes the entirety of the physician supply,” he said. “In a major metro area, that’s not as big a deal.”
Why younger doctors are fast-tracking retirement
Fernando Mendoza, MD, 54, a pediatric emergency department physician in Miami, worries that physicians are getting so bogged down by paperwork that this may lead to even more doctors, at younger ages, leaving the profession.
“I love taking care of kids, but there’s going to be a cost to doing your work when you’re spending as much time as we need to spend on charts, pharmacy requests, and making sure all of the Medicare and Medicaid compliance issues are worked out.”
These stressors may compel some younger doctors to consider carving out a second career or fast-track younger physicians toward retirement.
“A medical degree carries a lot of weight, which helps when pivoting,” said Dr. Mendoza, who launched Scrivas, a Miami-based medical scribe agency, to help reduce the paperwork workload for physicians. “It might be that a doctor wants to get involved in the acquisition of medical equipment, or maybe they can focus on their investments. Either way, by leaving medicine, they’re not dealing with the hassle and churn-and-burn of seeing patients.”
What this means for patients
The time is now to stem the upcoming tide of retirement, said Mr. Dill. But the challenges remain daunting. For starters, the country needs more physicians trained now – but it will take years to replace those baby boomer doctors ready to hang up their white coats.
The medical profession also needs to find ways to support physicians who spend their days juggling an endless array of responsibilities, he said.
The AAMC study found that patients already feel the physician shortfall. Their public opinion research in 2019 said 35% of patients had trouble finding a physician over the past 2 or 3 years, up 10 percentage points since they asked the question in 2015.
Moreover, according to the report, the over-65 population is expected to grow by 45.1%, leaving a specialty care gap because older people generally have more complicated health cases that require specialists. In addition, physician burnout may lead more physicians under 65 to retire much earlier than expected.
Changes in how medicine is practiced, telemedicine care, and medical education – such as disruption of classes or clinical rotations, regulatory changes, and a lack of interest in certain specialties – could also be affected by a mass physician retirement.
What can we do about mass retirement?
The AAMC reports in “The Complexities of Physician Supply and Demand: Projections From 2019 to 2034” that federally funded GME support is in the works to train 15,000 physicians per year, with 3,000 new residency slots added per year over 5 years. The proposed model will add 3,750 new physicians each year beginning in 2026.
Other efforts include increasing use of APRNs and PAs, whose population is estimated to more than double by 2034, improve population health through preventive care, increase equity in health outcomes, and improve access and affordable care.
Removing licensing barriers for immigrant doctors can also help alleviate the shortage.
“We need to find better ways to leverage the entirety of the health care team so that not as much falls on physicians,” Mr. Dill said. “It’s also imperative that we focus on ways to support physician wellness and allow physicians to remain active in the field, but at a reduced rate.”
That’s precisely what Marie Brown, MD, director of practice redesign at the American Medical Association, is seeing nationwide. Cutting back their hours is not only trending, but it’s also helping doctors cope with burnout.
“We’re seeing physicians take a 20% or more cut in salary in order to decrease their burden,” she said. “They’ll spend 4 days on clinical time with patients so that on that fifth ‘day off,’ they’re doing the paperwork and documentation they need to do so they don’t compromise care on the other 4 days of the week.”
And this may only be a Band-Aid solution, she fears.
“If a physician is spending 3 hours a day doing unnecessary work that could be done by another team member, that’s contributing to burnout,” Dr. Brown said. “It’s no surprise that they’ll want to escape and retire if they’re in a financial situation to do so.”
“I advocate negotiating within your organization so you’re doing more of what you like, such as mentoring or running a residency, and less of what you don’t, while cutting back from full-time to something less than full-time while maintaining benefits,” said Joel Greenwald, MD, a certified financial planner in Minneapolis, who specializes in helping physicians manage their financial affairs.
“Falling into the ‘like less’ bucket are usually things like working weekends and taking calls,” he said.
“This benefits everyone on a large scale because those doctors who find things they enjoy are generally working to a later age but working less hard,” he said. “Remaining comfortably and happily gainfully employed for a longer period, even if you’re not working full-time, has a very powerful effect on your financial planning, and you’ll avoid the risk of running out of money.”
A version of this article first appeared on Medscape.com.
Physician compensation continues to climb amid postpandemic change
In addition, gender-based pay disparity among primary care physicians shrank, and the number of physicians who declined to take new Medicare patients rose.
The annual report is based on a survey of more than 10,000 physicians in over 29 specialties who answered questions about their income, workload, challenges, and level of satisfaction.
Average compensation across specialties rose to $352,000 – up nearly 17% from the 2018 average of $299,000. Fallout from the COVID-19 public health emergency continued to affect both physician compensation and job satisfaction, including Medicare reimbursements and staffing shortages due to burnout or retirement.
“Many physicians reevaluated what drove them to be a physician,” says Marc Adam, a recruiter at MASC Medical, a Florida physician recruiting firm.
Adam cites telehealth as an example. “An overwhelming majority of physicians prefer telehealth because of the convenience, but some really did not want to do it long term. They miss the patient interaction.”
The report also revealed that the gender-based pay gap in primary physicians fell, with men earning 19% more – down from 25% more in recent years. Among specialists, the gender gap was 27% on average, down from 31% last year. One reason may be an increase in compensation transparency, which Mr. Adam says should be the norm.
Income increases will likely continue, owing in large part to the growing disparity between physician supply and demand.
The projected physician shortage is expected to grow to 124,000 by 2034, according to the American Association of Medical Colleges. Federal lawmakers are considering passing the Resident Physician Shortage Reduction Act of 2023, which would add 14,000 Medicare-funded residency positions to help alleviate shortages.
Patient needs, Medicare rules continue to shift
Specialties with the biggest increases in compensation include oncology, anesthesiology, gastroenterology, radiology, critical care, and urology. Many procedure-related specialties saw more volume post pandemic.
Some respondents identified Medicare cuts and low reimbursement rates as a factor in tamping down compensation hikes. The number of physicians who expect to continue to take new Medicare patients is 65%, down from 71% 5 years ago.
For example, Medicare reimbursements for telehealth are expected to scale down in May, when the COVID-19 Public Health Emergency, which expanded telehealth services for Medicare patients, winds down.
“Telehealth will still exist,” says Mr. Adam, “but certain requirements will shape it going forward.”
Medicare isn’t viewed negatively across the board, however. Florida is among the top-earning states for physicians – along with Indiana, Connecticut, and Missouri. One reason is Florida’s unique health care environment, explains Mr. Adam, whose Florida-based firm places physicians nationwide.
“Florida is very progressive in terms of health care. For one thing, we have a large aging population and a large Medicare population.” Several growing organizations that focus on quality-based care are based in Florida, including ChenMed and Cano Health. Add to that the fact that owners of Florida’s health care organizations don’t have to be physicians, he explains, and the stage is set for experimentation.
“Being able to segment tasks frees up physicians to be more focused on medicine and provide better care while other people focus on the business and innovation.”
If Florida’s high compensation ranking continues, it may help employers there fulfill a growing need. The state is among those expected to experience the largest physician shortages in 2030, along with California, Texas, Arizona, and Georgia.
Side gigs up, satisfaction (slightly) down
In general, physicians aren’t fazed by these challenges. Many reported taking side gigs, some for additional income. Even so, 73% say they would still choose medicine, and more than 90% of physicians in 10 specialties would choose their specialty again. Still, burnout and stressors have led some to stop practicing altogether.
More and more organizations are hiring “travel physicians,” Mr. Adam says, and more physicians are choosing to take contract work (“locum tenens”) and practice in many different regions. Contract physicians typically help meet patient demand or provide coverage during the hiring process as well as while staff are on vacation or maternity leave.
Says Mr. Adam, “There’s no security, but there’s higher income and more flexibility.”
According to CHG Healthcare, locum tenens staffing is rising – approximately 7% of U.S. physicians (around 50,000) filled assignments in 2022, up 88% from 2015. In 2022, 56% of locum tenens employers reported a reduction in staff burnout, up from 30% in 2020.
The report indicates that more than half of physicians are satisfied with their income, down slightly from 55% 5 years ago (prepandemic). Physicians in some of the lower-paying specialties are among those most satisfied with their income. It’s not very surprising to Mr. Adam: “Higher earners generally suffer the most from burnout.
“They’re overworked, they have the largest number of patients, and they’re performing in high-stress situations doing challenging procedures on a daily basis – and they probably have worse work-life balance.” These physicians know going in that they need to be paid more to deal with such burdens. “That’s the feedback I get when I speak to high earners,” says Mr. Adam.
“The experienced ones are very clear about their [compensation] expectations.”
A version of this article first appeared on Medscape.com.
In addition, gender-based pay disparity among primary care physicians shrank, and the number of physicians who declined to take new Medicare patients rose.
The annual report is based on a survey of more than 10,000 physicians in over 29 specialties who answered questions about their income, workload, challenges, and level of satisfaction.
Average compensation across specialties rose to $352,000 – up nearly 17% from the 2018 average of $299,000. Fallout from the COVID-19 public health emergency continued to affect both physician compensation and job satisfaction, including Medicare reimbursements and staffing shortages due to burnout or retirement.
“Many physicians reevaluated what drove them to be a physician,” says Marc Adam, a recruiter at MASC Medical, a Florida physician recruiting firm.
Adam cites telehealth as an example. “An overwhelming majority of physicians prefer telehealth because of the convenience, but some really did not want to do it long term. They miss the patient interaction.”
The report also revealed that the gender-based pay gap in primary physicians fell, with men earning 19% more – down from 25% more in recent years. Among specialists, the gender gap was 27% on average, down from 31% last year. One reason may be an increase in compensation transparency, which Mr. Adam says should be the norm.
Income increases will likely continue, owing in large part to the growing disparity between physician supply and demand.
The projected physician shortage is expected to grow to 124,000 by 2034, according to the American Association of Medical Colleges. Federal lawmakers are considering passing the Resident Physician Shortage Reduction Act of 2023, which would add 14,000 Medicare-funded residency positions to help alleviate shortages.
Patient needs, Medicare rules continue to shift
Specialties with the biggest increases in compensation include oncology, anesthesiology, gastroenterology, radiology, critical care, and urology. Many procedure-related specialties saw more volume post pandemic.
Some respondents identified Medicare cuts and low reimbursement rates as a factor in tamping down compensation hikes. The number of physicians who expect to continue to take new Medicare patients is 65%, down from 71% 5 years ago.
For example, Medicare reimbursements for telehealth are expected to scale down in May, when the COVID-19 Public Health Emergency, which expanded telehealth services for Medicare patients, winds down.
“Telehealth will still exist,” says Mr. Adam, “but certain requirements will shape it going forward.”
Medicare isn’t viewed negatively across the board, however. Florida is among the top-earning states for physicians – along with Indiana, Connecticut, and Missouri. One reason is Florida’s unique health care environment, explains Mr. Adam, whose Florida-based firm places physicians nationwide.
“Florida is very progressive in terms of health care. For one thing, we have a large aging population and a large Medicare population.” Several growing organizations that focus on quality-based care are based in Florida, including ChenMed and Cano Health. Add to that the fact that owners of Florida’s health care organizations don’t have to be physicians, he explains, and the stage is set for experimentation.
“Being able to segment tasks frees up physicians to be more focused on medicine and provide better care while other people focus on the business and innovation.”
If Florida’s high compensation ranking continues, it may help employers there fulfill a growing need. The state is among those expected to experience the largest physician shortages in 2030, along with California, Texas, Arizona, and Georgia.
Side gigs up, satisfaction (slightly) down
In general, physicians aren’t fazed by these challenges. Many reported taking side gigs, some for additional income. Even so, 73% say they would still choose medicine, and more than 90% of physicians in 10 specialties would choose their specialty again. Still, burnout and stressors have led some to stop practicing altogether.
More and more organizations are hiring “travel physicians,” Mr. Adam says, and more physicians are choosing to take contract work (“locum tenens”) and practice in many different regions. Contract physicians typically help meet patient demand or provide coverage during the hiring process as well as while staff are on vacation or maternity leave.
Says Mr. Adam, “There’s no security, but there’s higher income and more flexibility.”
According to CHG Healthcare, locum tenens staffing is rising – approximately 7% of U.S. physicians (around 50,000) filled assignments in 2022, up 88% from 2015. In 2022, 56% of locum tenens employers reported a reduction in staff burnout, up from 30% in 2020.
The report indicates that more than half of physicians are satisfied with their income, down slightly from 55% 5 years ago (prepandemic). Physicians in some of the lower-paying specialties are among those most satisfied with their income. It’s not very surprising to Mr. Adam: “Higher earners generally suffer the most from burnout.
“They’re overworked, they have the largest number of patients, and they’re performing in high-stress situations doing challenging procedures on a daily basis – and they probably have worse work-life balance.” These physicians know going in that they need to be paid more to deal with such burdens. “That’s the feedback I get when I speak to high earners,” says Mr. Adam.
“The experienced ones are very clear about their [compensation] expectations.”
A version of this article first appeared on Medscape.com.
In addition, gender-based pay disparity among primary care physicians shrank, and the number of physicians who declined to take new Medicare patients rose.
The annual report is based on a survey of more than 10,000 physicians in over 29 specialties who answered questions about their income, workload, challenges, and level of satisfaction.
Average compensation across specialties rose to $352,000 – up nearly 17% from the 2018 average of $299,000. Fallout from the COVID-19 public health emergency continued to affect both physician compensation and job satisfaction, including Medicare reimbursements and staffing shortages due to burnout or retirement.
“Many physicians reevaluated what drove them to be a physician,” says Marc Adam, a recruiter at MASC Medical, a Florida physician recruiting firm.
Adam cites telehealth as an example. “An overwhelming majority of physicians prefer telehealth because of the convenience, but some really did not want to do it long term. They miss the patient interaction.”
The report also revealed that the gender-based pay gap in primary physicians fell, with men earning 19% more – down from 25% more in recent years. Among specialists, the gender gap was 27% on average, down from 31% last year. One reason may be an increase in compensation transparency, which Mr. Adam says should be the norm.
Income increases will likely continue, owing in large part to the growing disparity between physician supply and demand.
The projected physician shortage is expected to grow to 124,000 by 2034, according to the American Association of Medical Colleges. Federal lawmakers are considering passing the Resident Physician Shortage Reduction Act of 2023, which would add 14,000 Medicare-funded residency positions to help alleviate shortages.
Patient needs, Medicare rules continue to shift
Specialties with the biggest increases in compensation include oncology, anesthesiology, gastroenterology, radiology, critical care, and urology. Many procedure-related specialties saw more volume post pandemic.
Some respondents identified Medicare cuts and low reimbursement rates as a factor in tamping down compensation hikes. The number of physicians who expect to continue to take new Medicare patients is 65%, down from 71% 5 years ago.
For example, Medicare reimbursements for telehealth are expected to scale down in May, when the COVID-19 Public Health Emergency, which expanded telehealth services for Medicare patients, winds down.
“Telehealth will still exist,” says Mr. Adam, “but certain requirements will shape it going forward.”
Medicare isn’t viewed negatively across the board, however. Florida is among the top-earning states for physicians – along with Indiana, Connecticut, and Missouri. One reason is Florida’s unique health care environment, explains Mr. Adam, whose Florida-based firm places physicians nationwide.
“Florida is very progressive in terms of health care. For one thing, we have a large aging population and a large Medicare population.” Several growing organizations that focus on quality-based care are based in Florida, including ChenMed and Cano Health. Add to that the fact that owners of Florida’s health care organizations don’t have to be physicians, he explains, and the stage is set for experimentation.
“Being able to segment tasks frees up physicians to be more focused on medicine and provide better care while other people focus on the business and innovation.”
If Florida’s high compensation ranking continues, it may help employers there fulfill a growing need. The state is among those expected to experience the largest physician shortages in 2030, along with California, Texas, Arizona, and Georgia.
Side gigs up, satisfaction (slightly) down
In general, physicians aren’t fazed by these challenges. Many reported taking side gigs, some for additional income. Even so, 73% say they would still choose medicine, and more than 90% of physicians in 10 specialties would choose their specialty again. Still, burnout and stressors have led some to stop practicing altogether.
More and more organizations are hiring “travel physicians,” Mr. Adam says, and more physicians are choosing to take contract work (“locum tenens”) and practice in many different regions. Contract physicians typically help meet patient demand or provide coverage during the hiring process as well as while staff are on vacation or maternity leave.
Says Mr. Adam, “There’s no security, but there’s higher income and more flexibility.”
According to CHG Healthcare, locum tenens staffing is rising – approximately 7% of U.S. physicians (around 50,000) filled assignments in 2022, up 88% from 2015. In 2022, 56% of locum tenens employers reported a reduction in staff burnout, up from 30% in 2020.
The report indicates that more than half of physicians are satisfied with their income, down slightly from 55% 5 years ago (prepandemic). Physicians in some of the lower-paying specialties are among those most satisfied with their income. It’s not very surprising to Mr. Adam: “Higher earners generally suffer the most from burnout.
“They’re overworked, they have the largest number of patients, and they’re performing in high-stress situations doing challenging procedures on a daily basis – and they probably have worse work-life balance.” These physicians know going in that they need to be paid more to deal with such burdens. “That’s the feedback I get when I speak to high earners,” says Mr. Adam.
“The experienced ones are very clear about their [compensation] expectations.”
A version of this article first appeared on Medscape.com.
Thirty years of epilepsy therapy: ‘Plus ça change, plus c’est la même chose’?
Although the past 30 years have stirred up a whirlwind of neurological research that has dramatically expanded therapeutic options for patients with epilepsy, historical pioneers in the field might be disappointed at the fact that treatment response has remained stubbornly stagnant. “Plus ça change, plus c’est la même chose,” they might say: The more things change, the more they stay the same. In fact, since 1993, , with roughly two-thirds of patients achieving seizure freedom and a third still struggling with treatment resistance.
But if you widen the lens and look towards the horizon, things are “on the cusp and going like a rocket,” said Jacqueline A. French, MD, professor of neurology in the Comprehensive Epilepsy Center at NYU Langone Health, New York. While treatment response rates may be stuck, adverse effects of those treatments have plummeted, and even treatment-resistant patients dealing with residual seizures live a much freer life with far fewer and less serious episodes.
Simpler times
In the late 1980s, just as Dr. French was finishing her second epilepsy fellowship at Yale, it was “almost laughable that things were so simple,” she recalls. “There were a few major centers that were doing epilepsy surgery … and in the world of medication, there were just five major drugs: phenobarbital, primidone, carbamazepine, phenytoin, and valproate.” That all changed as she was settling in to her first academic position at the University of Pennsylvania, with the “explosive” introduction of felbamate, a new antiseizure drug whose precipitous rise and fall from favor cast a sobering shadow which set the course for future drug development in the field.
“The felbamate story has a lot to do with what came after, but it was a drug that was much more advantageous in regards to a lot of the things that we didn’t like about antiseizure medicines or antiepileptic drugs as we called them at that time,” she said. The older drugs affected the cerebellum, making people sleepy and unable to concentrate. They also came with the risk of serious adverse effects such as hepatic enzyme induction and teratogenicity. Not only was felbamate nonsedating, “it actually was a little bit alerting,” said Dr. French. “People felt so different and so great on it, and it was effective for some seizure types that we didn’t really have good drugs for.” Very quickly, felbamate became a first-line therapy. Within its first year on the market, 150,000 newly diagnosed patients were started on it, “which is unthinkable now,” she said.
Sure enough, it all came crashing down a year later, on Aug. 1, 1994, when the drug was urgently withdrawn by the U.S. Food and Drug Administration after being linked to the development of aplastic anemia. “There was a day that anybody who was there at the time will remember when we all got the news, that everybody had to be taken off the drug,” Dr. French recalled. “We spent the weekend in the chart room, looking chart by chart by chart, for who was on felbamate.”
Until then, Dr. French had been straddling the line between her interests in pharmacologic versus surgical treatments for epilepsy. In fact, during her second epilepsy fellowship, which was dedicated to surgery, she published “Characteristics of medial temporal lobe epilepsy” in Annals of Neurology, one of the most-cited papers of her career. “Epilepsy from the temporal lobe is the biggest and best shot on goal when you’re talking about sending somebody to epilepsy surgery and rendering them completely seizure free,” she said. “Early in my career at the University of Pennsylvania, it was all about identifying those patients. And you know, there is nothing more gratifying than taking somebody whose life has been devastated by frequent seizures, who is injuring themselves and not able to be independent, and doing a surgery, which is very safe, and then all the seizures are gone – which is probably why I was so excited by surgery at the time.”
For a while, in the early 1990s, temporal lobectomy eclipsed many of the other avenues in epilepsy treatment, but it too has given way to a much wider variety of more complex techniques, which may be less curative but more palliative.
More drug options
Meanwhile, the felbamate story had ignited debate in the field about safer drug development – pushing Dr. French into establishing what was then known as the Antiepileptic Drug Trials conference, later renamed the Epilepsy Therapies & Diagnostics Development Symposium – a forum that encouraged safer, but also swifter movement of drugs through the pipeline and onto the market. “After felbamate, came gabapentin, and then came to topiramate and lamotrigine, and very quickly there were many, many, many choices,” she explained. “But once stung, twice shy. Felbamate really gave us a new perspective on which patients we put on the new drugs. Now we have a process of starting them in people with treatment-resistant epilepsy first. The risk-benefit equation is more reasonable because they have lots of risks. And then we work our way back to people with newly diagnosed epilepsy.”
Disease-modifying therapies
Today, the medications used to treat epilepsy are referred to as antiseizure rather than antiepileptic drugs because they simply suppress seizure symptoms and do not address the cause. But the rocket that Dr. French is watching gain speed and momentum is the disease-modifying gene therapies – true antiepileptics that may significantly move the needle on the number and type of patients who can reach seizure freedom. “We spent the last 25 years not even thinking we would ever have antiepileptic therapies, and now in the last 5 years or so, we were pretty sure we will,” she said. “We have gene therapies that can intervene now – none yet that have actually reached approval, these are all currently in trials – but we certainly have high expectations that they will very soon be available.”
Improving patients’ lives
While gene therapy rockets ahead, new device developments are already improving life for patients, even despite ongoing seizures. A drug-delivering pump is still in trials, but could make a big difference to daily medication adherence, and wearable or implantable devices are being developed to track seizures. More accurate tracking has also revealed that many people’s seizures are actually quite predictable, with regular cycles allowing for the possibility of prophylactic medication when increased seizure activity is expected.
Despite 30 years of no change in the proportion of epilepsy patients experiencing treatment resistance, Dr. French said that drugs, devices, and surgeries have improved the lives of all patients – both treatment resistant and treatment sensitive. “The difference between almost seizure free and completely seizure free is a big one because it means you can’t drive, you may have difficulty with your employment, but being able to take a pill every day and feel otherwise completely normal? We’ve come a long way.”
Although the past 30 years have stirred up a whirlwind of neurological research that has dramatically expanded therapeutic options for patients with epilepsy, historical pioneers in the field might be disappointed at the fact that treatment response has remained stubbornly stagnant. “Plus ça change, plus c’est la même chose,” they might say: The more things change, the more they stay the same. In fact, since 1993, , with roughly two-thirds of patients achieving seizure freedom and a third still struggling with treatment resistance.
But if you widen the lens and look towards the horizon, things are “on the cusp and going like a rocket,” said Jacqueline A. French, MD, professor of neurology in the Comprehensive Epilepsy Center at NYU Langone Health, New York. While treatment response rates may be stuck, adverse effects of those treatments have plummeted, and even treatment-resistant patients dealing with residual seizures live a much freer life with far fewer and less serious episodes.
Simpler times
In the late 1980s, just as Dr. French was finishing her second epilepsy fellowship at Yale, it was “almost laughable that things were so simple,” she recalls. “There were a few major centers that were doing epilepsy surgery … and in the world of medication, there were just five major drugs: phenobarbital, primidone, carbamazepine, phenytoin, and valproate.” That all changed as she was settling in to her first academic position at the University of Pennsylvania, with the “explosive” introduction of felbamate, a new antiseizure drug whose precipitous rise and fall from favor cast a sobering shadow which set the course for future drug development in the field.
“The felbamate story has a lot to do with what came after, but it was a drug that was much more advantageous in regards to a lot of the things that we didn’t like about antiseizure medicines or antiepileptic drugs as we called them at that time,” she said. The older drugs affected the cerebellum, making people sleepy and unable to concentrate. They also came with the risk of serious adverse effects such as hepatic enzyme induction and teratogenicity. Not only was felbamate nonsedating, “it actually was a little bit alerting,” said Dr. French. “People felt so different and so great on it, and it was effective for some seizure types that we didn’t really have good drugs for.” Very quickly, felbamate became a first-line therapy. Within its first year on the market, 150,000 newly diagnosed patients were started on it, “which is unthinkable now,” she said.
Sure enough, it all came crashing down a year later, on Aug. 1, 1994, when the drug was urgently withdrawn by the U.S. Food and Drug Administration after being linked to the development of aplastic anemia. “There was a day that anybody who was there at the time will remember when we all got the news, that everybody had to be taken off the drug,” Dr. French recalled. “We spent the weekend in the chart room, looking chart by chart by chart, for who was on felbamate.”
Until then, Dr. French had been straddling the line between her interests in pharmacologic versus surgical treatments for epilepsy. In fact, during her second epilepsy fellowship, which was dedicated to surgery, she published “Characteristics of medial temporal lobe epilepsy” in Annals of Neurology, one of the most-cited papers of her career. “Epilepsy from the temporal lobe is the biggest and best shot on goal when you’re talking about sending somebody to epilepsy surgery and rendering them completely seizure free,” she said. “Early in my career at the University of Pennsylvania, it was all about identifying those patients. And you know, there is nothing more gratifying than taking somebody whose life has been devastated by frequent seizures, who is injuring themselves and not able to be independent, and doing a surgery, which is very safe, and then all the seizures are gone – which is probably why I was so excited by surgery at the time.”
For a while, in the early 1990s, temporal lobectomy eclipsed many of the other avenues in epilepsy treatment, but it too has given way to a much wider variety of more complex techniques, which may be less curative but more palliative.
More drug options
Meanwhile, the felbamate story had ignited debate in the field about safer drug development – pushing Dr. French into establishing what was then known as the Antiepileptic Drug Trials conference, later renamed the Epilepsy Therapies & Diagnostics Development Symposium – a forum that encouraged safer, but also swifter movement of drugs through the pipeline and onto the market. “After felbamate, came gabapentin, and then came to topiramate and lamotrigine, and very quickly there were many, many, many choices,” she explained. “But once stung, twice shy. Felbamate really gave us a new perspective on which patients we put on the new drugs. Now we have a process of starting them in people with treatment-resistant epilepsy first. The risk-benefit equation is more reasonable because they have lots of risks. And then we work our way back to people with newly diagnosed epilepsy.”
Disease-modifying therapies
Today, the medications used to treat epilepsy are referred to as antiseizure rather than antiepileptic drugs because they simply suppress seizure symptoms and do not address the cause. But the rocket that Dr. French is watching gain speed and momentum is the disease-modifying gene therapies – true antiepileptics that may significantly move the needle on the number and type of patients who can reach seizure freedom. “We spent the last 25 years not even thinking we would ever have antiepileptic therapies, and now in the last 5 years or so, we were pretty sure we will,” she said. “We have gene therapies that can intervene now – none yet that have actually reached approval, these are all currently in trials – but we certainly have high expectations that they will very soon be available.”
Improving patients’ lives
While gene therapy rockets ahead, new device developments are already improving life for patients, even despite ongoing seizures. A drug-delivering pump is still in trials, but could make a big difference to daily medication adherence, and wearable or implantable devices are being developed to track seizures. More accurate tracking has also revealed that many people’s seizures are actually quite predictable, with regular cycles allowing for the possibility of prophylactic medication when increased seizure activity is expected.
Despite 30 years of no change in the proportion of epilepsy patients experiencing treatment resistance, Dr. French said that drugs, devices, and surgeries have improved the lives of all patients – both treatment resistant and treatment sensitive. “The difference between almost seizure free and completely seizure free is a big one because it means you can’t drive, you may have difficulty with your employment, but being able to take a pill every day and feel otherwise completely normal? We’ve come a long way.”
Although the past 30 years have stirred up a whirlwind of neurological research that has dramatically expanded therapeutic options for patients with epilepsy, historical pioneers in the field might be disappointed at the fact that treatment response has remained stubbornly stagnant. “Plus ça change, plus c’est la même chose,” they might say: The more things change, the more they stay the same. In fact, since 1993, , with roughly two-thirds of patients achieving seizure freedom and a third still struggling with treatment resistance.
But if you widen the lens and look towards the horizon, things are “on the cusp and going like a rocket,” said Jacqueline A. French, MD, professor of neurology in the Comprehensive Epilepsy Center at NYU Langone Health, New York. While treatment response rates may be stuck, adverse effects of those treatments have plummeted, and even treatment-resistant patients dealing with residual seizures live a much freer life with far fewer and less serious episodes.
Simpler times
In the late 1980s, just as Dr. French was finishing her second epilepsy fellowship at Yale, it was “almost laughable that things were so simple,” she recalls. “There were a few major centers that were doing epilepsy surgery … and in the world of medication, there were just five major drugs: phenobarbital, primidone, carbamazepine, phenytoin, and valproate.” That all changed as she was settling in to her first academic position at the University of Pennsylvania, with the “explosive” introduction of felbamate, a new antiseizure drug whose precipitous rise and fall from favor cast a sobering shadow which set the course for future drug development in the field.
“The felbamate story has a lot to do with what came after, but it was a drug that was much more advantageous in regards to a lot of the things that we didn’t like about antiseizure medicines or antiepileptic drugs as we called them at that time,” she said. The older drugs affected the cerebellum, making people sleepy and unable to concentrate. They also came with the risk of serious adverse effects such as hepatic enzyme induction and teratogenicity. Not only was felbamate nonsedating, “it actually was a little bit alerting,” said Dr. French. “People felt so different and so great on it, and it was effective for some seizure types that we didn’t really have good drugs for.” Very quickly, felbamate became a first-line therapy. Within its first year on the market, 150,000 newly diagnosed patients were started on it, “which is unthinkable now,” she said.
Sure enough, it all came crashing down a year later, on Aug. 1, 1994, when the drug was urgently withdrawn by the U.S. Food and Drug Administration after being linked to the development of aplastic anemia. “There was a day that anybody who was there at the time will remember when we all got the news, that everybody had to be taken off the drug,” Dr. French recalled. “We spent the weekend in the chart room, looking chart by chart by chart, for who was on felbamate.”
Until then, Dr. French had been straddling the line between her interests in pharmacologic versus surgical treatments for epilepsy. In fact, during her second epilepsy fellowship, which was dedicated to surgery, she published “Characteristics of medial temporal lobe epilepsy” in Annals of Neurology, one of the most-cited papers of her career. “Epilepsy from the temporal lobe is the biggest and best shot on goal when you’re talking about sending somebody to epilepsy surgery and rendering them completely seizure free,” she said. “Early in my career at the University of Pennsylvania, it was all about identifying those patients. And you know, there is nothing more gratifying than taking somebody whose life has been devastated by frequent seizures, who is injuring themselves and not able to be independent, and doing a surgery, which is very safe, and then all the seizures are gone – which is probably why I was so excited by surgery at the time.”
For a while, in the early 1990s, temporal lobectomy eclipsed many of the other avenues in epilepsy treatment, but it too has given way to a much wider variety of more complex techniques, which may be less curative but more palliative.
More drug options
Meanwhile, the felbamate story had ignited debate in the field about safer drug development – pushing Dr. French into establishing what was then known as the Antiepileptic Drug Trials conference, later renamed the Epilepsy Therapies & Diagnostics Development Symposium – a forum that encouraged safer, but also swifter movement of drugs through the pipeline and onto the market. “After felbamate, came gabapentin, and then came to topiramate and lamotrigine, and very quickly there were many, many, many choices,” she explained. “But once stung, twice shy. Felbamate really gave us a new perspective on which patients we put on the new drugs. Now we have a process of starting them in people with treatment-resistant epilepsy first. The risk-benefit equation is more reasonable because they have lots of risks. And then we work our way back to people with newly diagnosed epilepsy.”
Disease-modifying therapies
Today, the medications used to treat epilepsy are referred to as antiseizure rather than antiepileptic drugs because they simply suppress seizure symptoms and do not address the cause. But the rocket that Dr. French is watching gain speed and momentum is the disease-modifying gene therapies – true antiepileptics that may significantly move the needle on the number and type of patients who can reach seizure freedom. “We spent the last 25 years not even thinking we would ever have antiepileptic therapies, and now in the last 5 years or so, we were pretty sure we will,” she said. “We have gene therapies that can intervene now – none yet that have actually reached approval, these are all currently in trials – but we certainly have high expectations that they will very soon be available.”
Improving patients’ lives
While gene therapy rockets ahead, new device developments are already improving life for patients, even despite ongoing seizures. A drug-delivering pump is still in trials, but could make a big difference to daily medication adherence, and wearable or implantable devices are being developed to track seizures. More accurate tracking has also revealed that many people’s seizures are actually quite predictable, with regular cycles allowing for the possibility of prophylactic medication when increased seizure activity is expected.
Despite 30 years of no change in the proportion of epilepsy patients experiencing treatment resistance, Dr. French said that drugs, devices, and surgeries have improved the lives of all patients – both treatment resistant and treatment sensitive. “The difference between almost seizure free and completely seizure free is a big one because it means you can’t drive, you may have difficulty with your employment, but being able to take a pill every day and feel otherwise completely normal? We’ve come a long way.”
Sleep disturbances linked to post-COVID dyspnea
according to data from the U.K.’s CircCOVID study.
The researchers, led by John Blaikley, MRCP, PhD, respiratory physician and clinical scientist from the University of Manchester (England), found that sleep disturbance is a common problem after hospital admission for COVID-19 and may last for at least 1 year.
The study also showed that sleep disturbance after COVID hospitalization was associated with dyspnea and lower lung function. Further in-depth analysis revealed that the effects of sleep disturbance on dyspnea were partially mediated through both anxiety and muscle weakness; however, “this does not fully explain the association, suggesting other pathways are involved,” said Dr. Blaikley.
The study was jointly conducted by researchers from the University of Leicester (England), as well as 20 other U.K. institutes and the University of Helsinki. It was presented at the European Congress of Clinical Microbiology & Infectious Diseases and was simultaneously published in The Lancet Respiratory Medicine.
“Sleep disturbance is a common problem after hospitalization for COVID-19 and is associated with several symptoms in the post-COVID syndrome,” said Dr. Blaikley. “Clinicians should be aware of this association in their post-COVID syndrome clinics.”
He added that further work needs to be done to define the mechanism and to see whether the links are causal. “However, if they are, then treating sleep disturbance could have beneficial effects beyond improving sleep quality,” he said in an interview.
A large study recently showed that 4 in 10 people with post-COVID syndrome had moderate to severe sleep problems. Black people were at least three times more likely than White people to experience sleep problems. A total of 59% of all participants with long COVID reported having normal sleep or mild sleep disturbances, and 41% reported having moderate to severe sleep disturbances.
Unlike prior studies that evaluated sleep quality after COVID-19, which used either objective or subjective measures of sleep disturbance, the current study used both. “Using both measures revealed previously poorly described associations between sleep disturbance, breathlessness, reduced lung function, anxiety, and muscle weakness,” Dr. Blaikley pointed out.
Subjective and objective measures of sleep
The multicenter CircCOVID cohort study aimed to shed light on the prevalence and nature of sleep disturbance after patients are discharged from hospital for COVID-19 and to assess whether this was associated with dyspnea.
The study recruited a total of 2,320 participants who were part of a larger parent PHOSP-COVID study. After attending an early follow-up visit (at a median of 5 months after discharge from 83 U.K. hospitals for COVID-19), 638 participants provided data for analysis as measured by the Pittsburgh Sleep Quality Index (a subjective measure of sleep quality); 729 participants provided data for analysis as measured by actigraphy (an objective, wrist-worn, device-based measure of sleep quality) at a median of 7 months.
Breathlessness, the primary outcome, was assessed using the Dyspnea-12 validated questionnaire.
Actigraphy measurements were compared with an age-matched, sex-matched, body mass index (BMI)–matched, and time from discharge–matched cohort from the UK Biobank (a prepandemic comparator longitudinal cohort of 502,540 individuals, one-fifth of whom wore actigraphy devices). Sleep regularity was found to be 19% less in previously hospitalized patients with post-COVID syndrome, compared with matched controls who had been hospitalized for other reasons.
This “revealed that the actigraphy changes may be, in part, due to COVID-19 rather than hospitalization alone,” said Dr. Blaikley.
Data were collected at two time points after hospital discharge: 2-7 months (early), and 10-14 months (late). At the early time point, participants were clinically assessed with respect to anxiety, muscle function, and dyspnea, and lung function.
After discharge from hospital, the majority (62%) of post–COVID-19 participants reported poor sleep quality on the Pittsburgh Sleep Quality Index questionnaire. A “comparable” proportion (53%) felt that their quality of sleep had deteriorated following hospital discharge according to the numerical rating scale (subjective measure).
Also, sleep disturbance was found likely to persist for at least 12 months, since subjective sleep quality hardly changed between the early and late time points after hospital discharge.
Both subjective metrics (sleep quality and sleep quality deterioration after hospital discharge) and objective, device-based metrics (sleep regularity) were found to be associated with dyspnea and reduced lung function in patients with post-COVID syndrome.
“One of the striking findings in our study is the consistency with breathlessness and reduced lung function across different methods used to evaluate sleep,” highlighted Dr. Blaikley.
“The other striking finding was that participants following COVID-19 hospitalization actually slept longer [65 min; 95% confidence interval, 59-71 min] than participants hospitalized for non-COVID; however, their bedtimes were irregular, and it was this irregularity that was associated with breathlessness,” he added.
In comparison with nonhospitalized controls, also from the UK Biobank, study participants with lower sleep regularity had higher Dyspnea-12 scores (unadjusted effect estimate, 4.38; 95%: CI, 2.10-6.65). Those with poor sleep quality overall also had higher Dyspnea-12 scores (unadjusted effect estimate, 3.94; 95% CI, 2.78-5.10), and those who reported sleep quality deterioration had higher Dyspnea-12 scores (unadjusted effect estimate, 3,00; 95% CI, 1.82-4.28).
In comparison with hospitalized controls, CircCOVID participants had lower sleep regularity index (–19%; 95% CI, –20 to –16) and lower sleep efficiency (3.83 percentage points; 95% CI, 3.40-4.26).
Sleep disturbance after COVID hospitalization was also associated with lower lung function, from a 7% to a 14% reduction in predicted forced vital capacity, depending on which sleep measure used.
In an analysis of mediating factors active in the relationship between sleep disturbance and dyspnea/decreased lung function, the researchers found that reduced muscle function and anxiety, which are both recognized causes of dyspnea, could partially contribute to the association.
Regarding anxiety, and depending on the sleep metric, anxiety mediated 18%-39% of the effect of sleep disturbance on dyspnea, while muscle weakness mediated 27%-41% of this effect, reported Dr. Blaikley. Those with poor sleep quality were more likely to have mild, moderate, or severe anxiety, compared with participants who reported good-quality sleep.
A similar association was observed between anxiety and sleep quality deterioration.
“Two key questions are raised by our study: Do sleep interventions have a beneficial effect in post–COVID-19 syndrome, and are the associations causal?” asked Dr. Blaikley. “We hope to do a sleep intervention trial to answer these questions to explore if this is an effective treatment for post–COVID-19 syndrome.”
‘Underlying mechanisms remain unclear’
Amitava Banerjee, MD, professor of clinical data science and honorary consultant cardiologist, Institute of Health Informatics, UCL, London, welcomed the study but noted that it did not include nonhospitalized post-COVID patients.
“The majority of people with long COVID were not hospitalized for COVID, so the results may not be generalizable to this larger group,” she said in an interview. “Good-quality sleep is important for health and reduces risk of chronic diseases; quality of sleep is therefore likely to be important for those with long COVID in reducing their risk of chronic disease, but the role of sleep in the mechanism of long COVID needs further research.”
In a commentary also published in The Lancet Respiratory Medicine, W. Cameron McGuire, MD, pulmonary and critical care specialist from San Diego, California, and colleagues wrote: “These findings suggest that sleep disturbance, dyspnea, and anxiety are common after COVID-19 and are associated with one another, although the underlying mechanisms remain unclear.”
The commentators “applauded” the work overall but noted that the findings represent correlation rather than causation. “It is unclear whether sleep disturbance is causing anxiety or whether anxiety is contributing to poor sleep. ... For the sleep disturbances, increased BMI in the cohort reporting poor sleep, compared with those reporting good sleep might suggest underlying obstructive sleep apnea,” they wrote.
Dr. McGuire and colleagues added that many questions remain for researchers and clinicians, including “whether anxiety and dyspnoea are contributing to a low arousal threshold [disrupting sleep] ... whether the observed abnormalities (e.g., in dyspnea score) are clinically significant,” and “whether therapies such as glucocorticoids, anticoagulants, or previous vaccinations mitigate the observed abnormalities during COVID-19 recovery.”
Dr. Blaikley has received support to his institute from an MRC Transition Fellowship, Asthma + Lung UK, NIHR Manchester BRC, and UKRI; grants to his institution from the Small Business Research Initiative Home Spirometer and the National Institute of Academic Anaesthesia; and support from TEVA and Therakos for attending meetings. He is a committee member of the Royal Society of Medicine. A coauthor received funding from the National Institutes of Health and income for medical education from Zoll, Livanova, Jazz, and Eli Lilly. Dr. Banerjee is the chief investigator of STIMULATE-ICP (an NIHR-funded study) and has received research funding from AstraZeneca.
A version of this article first appeared on Medscape.com.
according to data from the U.K.’s CircCOVID study.
The researchers, led by John Blaikley, MRCP, PhD, respiratory physician and clinical scientist from the University of Manchester (England), found that sleep disturbance is a common problem after hospital admission for COVID-19 and may last for at least 1 year.
The study also showed that sleep disturbance after COVID hospitalization was associated with dyspnea and lower lung function. Further in-depth analysis revealed that the effects of sleep disturbance on dyspnea were partially mediated through both anxiety and muscle weakness; however, “this does not fully explain the association, suggesting other pathways are involved,” said Dr. Blaikley.
The study was jointly conducted by researchers from the University of Leicester (England), as well as 20 other U.K. institutes and the University of Helsinki. It was presented at the European Congress of Clinical Microbiology & Infectious Diseases and was simultaneously published in The Lancet Respiratory Medicine.
“Sleep disturbance is a common problem after hospitalization for COVID-19 and is associated with several symptoms in the post-COVID syndrome,” said Dr. Blaikley. “Clinicians should be aware of this association in their post-COVID syndrome clinics.”
He added that further work needs to be done to define the mechanism and to see whether the links are causal. “However, if they are, then treating sleep disturbance could have beneficial effects beyond improving sleep quality,” he said in an interview.
A large study recently showed that 4 in 10 people with post-COVID syndrome had moderate to severe sleep problems. Black people were at least three times more likely than White people to experience sleep problems. A total of 59% of all participants with long COVID reported having normal sleep or mild sleep disturbances, and 41% reported having moderate to severe sleep disturbances.
Unlike prior studies that evaluated sleep quality after COVID-19, which used either objective or subjective measures of sleep disturbance, the current study used both. “Using both measures revealed previously poorly described associations between sleep disturbance, breathlessness, reduced lung function, anxiety, and muscle weakness,” Dr. Blaikley pointed out.
Subjective and objective measures of sleep
The multicenter CircCOVID cohort study aimed to shed light on the prevalence and nature of sleep disturbance after patients are discharged from hospital for COVID-19 and to assess whether this was associated with dyspnea.
The study recruited a total of 2,320 participants who were part of a larger parent PHOSP-COVID study. After attending an early follow-up visit (at a median of 5 months after discharge from 83 U.K. hospitals for COVID-19), 638 participants provided data for analysis as measured by the Pittsburgh Sleep Quality Index (a subjective measure of sleep quality); 729 participants provided data for analysis as measured by actigraphy (an objective, wrist-worn, device-based measure of sleep quality) at a median of 7 months.
Breathlessness, the primary outcome, was assessed using the Dyspnea-12 validated questionnaire.
Actigraphy measurements were compared with an age-matched, sex-matched, body mass index (BMI)–matched, and time from discharge–matched cohort from the UK Biobank (a prepandemic comparator longitudinal cohort of 502,540 individuals, one-fifth of whom wore actigraphy devices). Sleep regularity was found to be 19% less in previously hospitalized patients with post-COVID syndrome, compared with matched controls who had been hospitalized for other reasons.
This “revealed that the actigraphy changes may be, in part, due to COVID-19 rather than hospitalization alone,” said Dr. Blaikley.
Data were collected at two time points after hospital discharge: 2-7 months (early), and 10-14 months (late). At the early time point, participants were clinically assessed with respect to anxiety, muscle function, and dyspnea, and lung function.
After discharge from hospital, the majority (62%) of post–COVID-19 participants reported poor sleep quality on the Pittsburgh Sleep Quality Index questionnaire. A “comparable” proportion (53%) felt that their quality of sleep had deteriorated following hospital discharge according to the numerical rating scale (subjective measure).
Also, sleep disturbance was found likely to persist for at least 12 months, since subjective sleep quality hardly changed between the early and late time points after hospital discharge.
Both subjective metrics (sleep quality and sleep quality deterioration after hospital discharge) and objective, device-based metrics (sleep regularity) were found to be associated with dyspnea and reduced lung function in patients with post-COVID syndrome.
“One of the striking findings in our study is the consistency with breathlessness and reduced lung function across different methods used to evaluate sleep,” highlighted Dr. Blaikley.
“The other striking finding was that participants following COVID-19 hospitalization actually slept longer [65 min; 95% confidence interval, 59-71 min] than participants hospitalized for non-COVID; however, their bedtimes were irregular, and it was this irregularity that was associated with breathlessness,” he added.
In comparison with nonhospitalized controls, also from the UK Biobank, study participants with lower sleep regularity had higher Dyspnea-12 scores (unadjusted effect estimate, 4.38; 95%: CI, 2.10-6.65). Those with poor sleep quality overall also had higher Dyspnea-12 scores (unadjusted effect estimate, 3.94; 95% CI, 2.78-5.10), and those who reported sleep quality deterioration had higher Dyspnea-12 scores (unadjusted effect estimate, 3,00; 95% CI, 1.82-4.28).
In comparison with hospitalized controls, CircCOVID participants had lower sleep regularity index (–19%; 95% CI, –20 to –16) and lower sleep efficiency (3.83 percentage points; 95% CI, 3.40-4.26).
Sleep disturbance after COVID hospitalization was also associated with lower lung function, from a 7% to a 14% reduction in predicted forced vital capacity, depending on which sleep measure used.
In an analysis of mediating factors active in the relationship between sleep disturbance and dyspnea/decreased lung function, the researchers found that reduced muscle function and anxiety, which are both recognized causes of dyspnea, could partially contribute to the association.
Regarding anxiety, and depending on the sleep metric, anxiety mediated 18%-39% of the effect of sleep disturbance on dyspnea, while muscle weakness mediated 27%-41% of this effect, reported Dr. Blaikley. Those with poor sleep quality were more likely to have mild, moderate, or severe anxiety, compared with participants who reported good-quality sleep.
A similar association was observed between anxiety and sleep quality deterioration.
“Two key questions are raised by our study: Do sleep interventions have a beneficial effect in post–COVID-19 syndrome, and are the associations causal?” asked Dr. Blaikley. “We hope to do a sleep intervention trial to answer these questions to explore if this is an effective treatment for post–COVID-19 syndrome.”
‘Underlying mechanisms remain unclear’
Amitava Banerjee, MD, professor of clinical data science and honorary consultant cardiologist, Institute of Health Informatics, UCL, London, welcomed the study but noted that it did not include nonhospitalized post-COVID patients.
“The majority of people with long COVID were not hospitalized for COVID, so the results may not be generalizable to this larger group,” she said in an interview. “Good-quality sleep is important for health and reduces risk of chronic diseases; quality of sleep is therefore likely to be important for those with long COVID in reducing their risk of chronic disease, but the role of sleep in the mechanism of long COVID needs further research.”
In a commentary also published in The Lancet Respiratory Medicine, W. Cameron McGuire, MD, pulmonary and critical care specialist from San Diego, California, and colleagues wrote: “These findings suggest that sleep disturbance, dyspnea, and anxiety are common after COVID-19 and are associated with one another, although the underlying mechanisms remain unclear.”
The commentators “applauded” the work overall but noted that the findings represent correlation rather than causation. “It is unclear whether sleep disturbance is causing anxiety or whether anxiety is contributing to poor sleep. ... For the sleep disturbances, increased BMI in the cohort reporting poor sleep, compared with those reporting good sleep might suggest underlying obstructive sleep apnea,” they wrote.
Dr. McGuire and colleagues added that many questions remain for researchers and clinicians, including “whether anxiety and dyspnoea are contributing to a low arousal threshold [disrupting sleep] ... whether the observed abnormalities (e.g., in dyspnea score) are clinically significant,” and “whether therapies such as glucocorticoids, anticoagulants, or previous vaccinations mitigate the observed abnormalities during COVID-19 recovery.”
Dr. Blaikley has received support to his institute from an MRC Transition Fellowship, Asthma + Lung UK, NIHR Manchester BRC, and UKRI; grants to his institution from the Small Business Research Initiative Home Spirometer and the National Institute of Academic Anaesthesia; and support from TEVA and Therakos for attending meetings. He is a committee member of the Royal Society of Medicine. A coauthor received funding from the National Institutes of Health and income for medical education from Zoll, Livanova, Jazz, and Eli Lilly. Dr. Banerjee is the chief investigator of STIMULATE-ICP (an NIHR-funded study) and has received research funding from AstraZeneca.
A version of this article first appeared on Medscape.com.
according to data from the U.K.’s CircCOVID study.
The researchers, led by John Blaikley, MRCP, PhD, respiratory physician and clinical scientist from the University of Manchester (England), found that sleep disturbance is a common problem after hospital admission for COVID-19 and may last for at least 1 year.
The study also showed that sleep disturbance after COVID hospitalization was associated with dyspnea and lower lung function. Further in-depth analysis revealed that the effects of sleep disturbance on dyspnea were partially mediated through both anxiety and muscle weakness; however, “this does not fully explain the association, suggesting other pathways are involved,” said Dr. Blaikley.
The study was jointly conducted by researchers from the University of Leicester (England), as well as 20 other U.K. institutes and the University of Helsinki. It was presented at the European Congress of Clinical Microbiology & Infectious Diseases and was simultaneously published in The Lancet Respiratory Medicine.
“Sleep disturbance is a common problem after hospitalization for COVID-19 and is associated with several symptoms in the post-COVID syndrome,” said Dr. Blaikley. “Clinicians should be aware of this association in their post-COVID syndrome clinics.”
He added that further work needs to be done to define the mechanism and to see whether the links are causal. “However, if they are, then treating sleep disturbance could have beneficial effects beyond improving sleep quality,” he said in an interview.
A large study recently showed that 4 in 10 people with post-COVID syndrome had moderate to severe sleep problems. Black people were at least three times more likely than White people to experience sleep problems. A total of 59% of all participants with long COVID reported having normal sleep or mild sleep disturbances, and 41% reported having moderate to severe sleep disturbances.
Unlike prior studies that evaluated sleep quality after COVID-19, which used either objective or subjective measures of sleep disturbance, the current study used both. “Using both measures revealed previously poorly described associations between sleep disturbance, breathlessness, reduced lung function, anxiety, and muscle weakness,” Dr. Blaikley pointed out.
Subjective and objective measures of sleep
The multicenter CircCOVID cohort study aimed to shed light on the prevalence and nature of sleep disturbance after patients are discharged from hospital for COVID-19 and to assess whether this was associated with dyspnea.
The study recruited a total of 2,320 participants who were part of a larger parent PHOSP-COVID study. After attending an early follow-up visit (at a median of 5 months after discharge from 83 U.K. hospitals for COVID-19), 638 participants provided data for analysis as measured by the Pittsburgh Sleep Quality Index (a subjective measure of sleep quality); 729 participants provided data for analysis as measured by actigraphy (an objective, wrist-worn, device-based measure of sleep quality) at a median of 7 months.
Breathlessness, the primary outcome, was assessed using the Dyspnea-12 validated questionnaire.
Actigraphy measurements were compared with an age-matched, sex-matched, body mass index (BMI)–matched, and time from discharge–matched cohort from the UK Biobank (a prepandemic comparator longitudinal cohort of 502,540 individuals, one-fifth of whom wore actigraphy devices). Sleep regularity was found to be 19% less in previously hospitalized patients with post-COVID syndrome, compared with matched controls who had been hospitalized for other reasons.
This “revealed that the actigraphy changes may be, in part, due to COVID-19 rather than hospitalization alone,” said Dr. Blaikley.
Data were collected at two time points after hospital discharge: 2-7 months (early), and 10-14 months (late). At the early time point, participants were clinically assessed with respect to anxiety, muscle function, and dyspnea, and lung function.
After discharge from hospital, the majority (62%) of post–COVID-19 participants reported poor sleep quality on the Pittsburgh Sleep Quality Index questionnaire. A “comparable” proportion (53%) felt that their quality of sleep had deteriorated following hospital discharge according to the numerical rating scale (subjective measure).
Also, sleep disturbance was found likely to persist for at least 12 months, since subjective sleep quality hardly changed between the early and late time points after hospital discharge.
Both subjective metrics (sleep quality and sleep quality deterioration after hospital discharge) and objective, device-based metrics (sleep regularity) were found to be associated with dyspnea and reduced lung function in patients with post-COVID syndrome.
“One of the striking findings in our study is the consistency with breathlessness and reduced lung function across different methods used to evaluate sleep,” highlighted Dr. Blaikley.
“The other striking finding was that participants following COVID-19 hospitalization actually slept longer [65 min; 95% confidence interval, 59-71 min] than participants hospitalized for non-COVID; however, their bedtimes were irregular, and it was this irregularity that was associated with breathlessness,” he added.
In comparison with nonhospitalized controls, also from the UK Biobank, study participants with lower sleep regularity had higher Dyspnea-12 scores (unadjusted effect estimate, 4.38; 95%: CI, 2.10-6.65). Those with poor sleep quality overall also had higher Dyspnea-12 scores (unadjusted effect estimate, 3.94; 95% CI, 2.78-5.10), and those who reported sleep quality deterioration had higher Dyspnea-12 scores (unadjusted effect estimate, 3,00; 95% CI, 1.82-4.28).
In comparison with hospitalized controls, CircCOVID participants had lower sleep regularity index (–19%; 95% CI, –20 to –16) and lower sleep efficiency (3.83 percentage points; 95% CI, 3.40-4.26).
Sleep disturbance after COVID hospitalization was also associated with lower lung function, from a 7% to a 14% reduction in predicted forced vital capacity, depending on which sleep measure used.
In an analysis of mediating factors active in the relationship between sleep disturbance and dyspnea/decreased lung function, the researchers found that reduced muscle function and anxiety, which are both recognized causes of dyspnea, could partially contribute to the association.
Regarding anxiety, and depending on the sleep metric, anxiety mediated 18%-39% of the effect of sleep disturbance on dyspnea, while muscle weakness mediated 27%-41% of this effect, reported Dr. Blaikley. Those with poor sleep quality were more likely to have mild, moderate, or severe anxiety, compared with participants who reported good-quality sleep.
A similar association was observed between anxiety and sleep quality deterioration.
“Two key questions are raised by our study: Do sleep interventions have a beneficial effect in post–COVID-19 syndrome, and are the associations causal?” asked Dr. Blaikley. “We hope to do a sleep intervention trial to answer these questions to explore if this is an effective treatment for post–COVID-19 syndrome.”
‘Underlying mechanisms remain unclear’
Amitava Banerjee, MD, professor of clinical data science and honorary consultant cardiologist, Institute of Health Informatics, UCL, London, welcomed the study but noted that it did not include nonhospitalized post-COVID patients.
“The majority of people with long COVID were not hospitalized for COVID, so the results may not be generalizable to this larger group,” she said in an interview. “Good-quality sleep is important for health and reduces risk of chronic diseases; quality of sleep is therefore likely to be important for those with long COVID in reducing their risk of chronic disease, but the role of sleep in the mechanism of long COVID needs further research.”
In a commentary also published in The Lancet Respiratory Medicine, W. Cameron McGuire, MD, pulmonary and critical care specialist from San Diego, California, and colleagues wrote: “These findings suggest that sleep disturbance, dyspnea, and anxiety are common after COVID-19 and are associated with one another, although the underlying mechanisms remain unclear.”
The commentators “applauded” the work overall but noted that the findings represent correlation rather than causation. “It is unclear whether sleep disturbance is causing anxiety or whether anxiety is contributing to poor sleep. ... For the sleep disturbances, increased BMI in the cohort reporting poor sleep, compared with those reporting good sleep might suggest underlying obstructive sleep apnea,” they wrote.
Dr. McGuire and colleagues added that many questions remain for researchers and clinicians, including “whether anxiety and dyspnoea are contributing to a low arousal threshold [disrupting sleep] ... whether the observed abnormalities (e.g., in dyspnea score) are clinically significant,” and “whether therapies such as glucocorticoids, anticoagulants, or previous vaccinations mitigate the observed abnormalities during COVID-19 recovery.”
Dr. Blaikley has received support to his institute from an MRC Transition Fellowship, Asthma + Lung UK, NIHR Manchester BRC, and UKRI; grants to his institution from the Small Business Research Initiative Home Spirometer and the National Institute of Academic Anaesthesia; and support from TEVA and Therakos for attending meetings. He is a committee member of the Royal Society of Medicine. A coauthor received funding from the National Institutes of Health and income for medical education from Zoll, Livanova, Jazz, and Eli Lilly. Dr. Banerjee is the chief investigator of STIMULATE-ICP (an NIHR-funded study) and has received research funding from AstraZeneca.
A version of this article first appeared on Medscape.com.
FROM ECCMID 2023
FDA breakthrough designation for spinal cord stimulation device
The U.S. Food and Drug Administration has granted breakthrough device designation to the Avantis spinal cord stimulation system (Reach Neuro), which has been shown in early testing to restore arm and hand movement in patients with post-stroke upper limb paresis.
“We are excited about the FDA’s recognition of our technology’s potential to change the lives of millions of people living with disability,” Marc Powell, PhD, CEO, and co-founder of Reach Neuro, said in a company news release.
“The breakthrough device designation is an incredible opportunity to work closely with FDA experts to expedite the clinical translation of the Avantis system,” Dr. Powell added.
Results of the first-in-human study of the system were published in Nature Medicine.
Investigators percutaneously implanted two linear leads in the dorsolateral epidural space targeting neural circuits that control arm and hand muscles in two chronic post-stroke patients.
In both patients, continuous stimulation of the targeted neural circuits led to significant and immediate improvement in arm and hand strength and dexterity. This enabled the patients to perform movements that they couldn’t perform without spinal cord stimulation.
The process also enabled fine motor skills, such as opening a lock and using utensils to eat independently – tasks that one patient had not been able to do for 9 years.
“Having the stimulation working and being able to move my arm/hand again after 9 years was one of the most surreal experiences of my life – it was as if my brain was in control of my arm again. This technology gave me such immense hope that one day I will regain a sense of independence again,” study participant Heather Rendulic said in the news release.
Surprisingly, some improvements were retained up to 1 month after the study, even without stimulation. No serious adverse events were reported.
Nearly three-quarters of patients with stroke experience lasting deficits in motor control of their arm and hand as a result of permanent damage to the brain’s ability to send signals to muscles.
The early results with the Avantis system provide “promising, albeit preliminary, evidence that spinal cord stimulation could be an assistive as well as a restorative approach for upper-limb recovery after stroke,” the study team said in Nature Medicine.
Reach Neuro was founded in 2021 as a spinout company of the University of Pittsburgh and Carnegie Mellon University, also in Pittsburgh, where the technology is currently being tested in a clinical trial funded by the National Institutes of Health.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration has granted breakthrough device designation to the Avantis spinal cord stimulation system (Reach Neuro), which has been shown in early testing to restore arm and hand movement in patients with post-stroke upper limb paresis.
“We are excited about the FDA’s recognition of our technology’s potential to change the lives of millions of people living with disability,” Marc Powell, PhD, CEO, and co-founder of Reach Neuro, said in a company news release.
“The breakthrough device designation is an incredible opportunity to work closely with FDA experts to expedite the clinical translation of the Avantis system,” Dr. Powell added.
Results of the first-in-human study of the system were published in Nature Medicine.
Investigators percutaneously implanted two linear leads in the dorsolateral epidural space targeting neural circuits that control arm and hand muscles in two chronic post-stroke patients.
In both patients, continuous stimulation of the targeted neural circuits led to significant and immediate improvement in arm and hand strength and dexterity. This enabled the patients to perform movements that they couldn’t perform without spinal cord stimulation.
The process also enabled fine motor skills, such as opening a lock and using utensils to eat independently – tasks that one patient had not been able to do for 9 years.
“Having the stimulation working and being able to move my arm/hand again after 9 years was one of the most surreal experiences of my life – it was as if my brain was in control of my arm again. This technology gave me such immense hope that one day I will regain a sense of independence again,” study participant Heather Rendulic said in the news release.
Surprisingly, some improvements were retained up to 1 month after the study, even without stimulation. No serious adverse events were reported.
Nearly three-quarters of patients with stroke experience lasting deficits in motor control of their arm and hand as a result of permanent damage to the brain’s ability to send signals to muscles.
The early results with the Avantis system provide “promising, albeit preliminary, evidence that spinal cord stimulation could be an assistive as well as a restorative approach for upper-limb recovery after stroke,” the study team said in Nature Medicine.
Reach Neuro was founded in 2021 as a spinout company of the University of Pittsburgh and Carnegie Mellon University, also in Pittsburgh, where the technology is currently being tested in a clinical trial funded by the National Institutes of Health.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration has granted breakthrough device designation to the Avantis spinal cord stimulation system (Reach Neuro), which has been shown in early testing to restore arm and hand movement in patients with post-stroke upper limb paresis.
“We are excited about the FDA’s recognition of our technology’s potential to change the lives of millions of people living with disability,” Marc Powell, PhD, CEO, and co-founder of Reach Neuro, said in a company news release.
“The breakthrough device designation is an incredible opportunity to work closely with FDA experts to expedite the clinical translation of the Avantis system,” Dr. Powell added.
Results of the first-in-human study of the system were published in Nature Medicine.
Investigators percutaneously implanted two linear leads in the dorsolateral epidural space targeting neural circuits that control arm and hand muscles in two chronic post-stroke patients.
In both patients, continuous stimulation of the targeted neural circuits led to significant and immediate improvement in arm and hand strength and dexterity. This enabled the patients to perform movements that they couldn’t perform without spinal cord stimulation.
The process also enabled fine motor skills, such as opening a lock and using utensils to eat independently – tasks that one patient had not been able to do for 9 years.
“Having the stimulation working and being able to move my arm/hand again after 9 years was one of the most surreal experiences of my life – it was as if my brain was in control of my arm again. This technology gave me such immense hope that one day I will regain a sense of independence again,” study participant Heather Rendulic said in the news release.
Surprisingly, some improvements were retained up to 1 month after the study, even without stimulation. No serious adverse events were reported.
Nearly three-quarters of patients with stroke experience lasting deficits in motor control of their arm and hand as a result of permanent damage to the brain’s ability to send signals to muscles.
The early results with the Avantis system provide “promising, albeit preliminary, evidence that spinal cord stimulation could be an assistive as well as a restorative approach for upper-limb recovery after stroke,” the study team said in Nature Medicine.
Reach Neuro was founded in 2021 as a spinout company of the University of Pittsburgh and Carnegie Mellon University, also in Pittsburgh, where the technology is currently being tested in a clinical trial funded by the National Institutes of Health.
A version of this article first appeared on Medscape.com.
Artificial intelligence versus real patients
STAT recently published an article on a new aspect of managed medical care.
They found that
That’s ... kind of scary.
Certainly, computers aren’t bad things. In 2023 America you can’t practice medicine without them. They aren’t malicious. They can analyze a lot of data faster than we can (for the record, the average memory capacity of a human brain is 1 petabyte, so we’re still ahead of the average desktop in that regard).
Computers, though, are pretty uniform. I’m a Mac person, and I can go into any Apple store and buy one. Right off the shelf I know how to work it, how it will run a given program, and can predict how it will handle different commands and such. They’re pretty much the same.
People are not quite as easy. Anatomically and chemically we’re similar, but that’s not the same. There are immune, genetic, and multiple other factors that put a lot of variables into the equation. Part of our training is knowing that and taking it into account when making treatment plans.
Algorithms, and artificial intelligence, can only do so much of that. If they were right all the time sports betting wouldn’t exist. But it does, because sports depends on the participants, who are people (or horses), and they’re not exactly alike ... for that matter how they’ll perform varies from day to day for the same individual.
But medical care isn’t a sport (even though hospital call can seem like a marathon). The data we give computers to use is generally based on averages – a rehab stay of 16.6 days for an 85-year-old woman with a broken shoulder (per the above article). But they don’t realize that averages are actually a collection of data on a bell-shaped curve. An insurance company will be only too happy when one person completes their rehabilitation in 11.6 days, and then feel it’s unreasonable when another takes 21.6.
That said, many of the companies involved say the final decisions are made by humans and that the algorithms are just guidelines.
Maybe so, but the STAT article suggests they’re putting too much credence in what the computer says, and not the specific circumstances of the individual involved.
That ain’t good, at least not for the patients.
Medicine, for better or worse, is a business. In an ideal world it probably wouldn’t be, but we don’t live in one.
But it’s unlike any other business out there, and shouldn’t be run like one. A car repair shop knows what parts to order and generally how long repairs will take. Once they’re done the car should be ready to roll out of the shop.
People aren’t like that.
I understand the need to prevent abuse and overbilling for unnecessary days and services. Medicine, unfortunately, has plenty of opportunities for the dishonest to take advantage of.
It’s a thin line, but, at least today, turning treatment decisions over to algorithms and computers is a bad idea for the people we’re supposed to be caring for.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
STAT recently published an article on a new aspect of managed medical care.
They found that
That’s ... kind of scary.
Certainly, computers aren’t bad things. In 2023 America you can’t practice medicine without them. They aren’t malicious. They can analyze a lot of data faster than we can (for the record, the average memory capacity of a human brain is 1 petabyte, so we’re still ahead of the average desktop in that regard).
Computers, though, are pretty uniform. I’m a Mac person, and I can go into any Apple store and buy one. Right off the shelf I know how to work it, how it will run a given program, and can predict how it will handle different commands and such. They’re pretty much the same.
People are not quite as easy. Anatomically and chemically we’re similar, but that’s not the same. There are immune, genetic, and multiple other factors that put a lot of variables into the equation. Part of our training is knowing that and taking it into account when making treatment plans.
Algorithms, and artificial intelligence, can only do so much of that. If they were right all the time sports betting wouldn’t exist. But it does, because sports depends on the participants, who are people (or horses), and they’re not exactly alike ... for that matter how they’ll perform varies from day to day for the same individual.
But medical care isn’t a sport (even though hospital call can seem like a marathon). The data we give computers to use is generally based on averages – a rehab stay of 16.6 days for an 85-year-old woman with a broken shoulder (per the above article). But they don’t realize that averages are actually a collection of data on a bell-shaped curve. An insurance company will be only too happy when one person completes their rehabilitation in 11.6 days, and then feel it’s unreasonable when another takes 21.6.
That said, many of the companies involved say the final decisions are made by humans and that the algorithms are just guidelines.
Maybe so, but the STAT article suggests they’re putting too much credence in what the computer says, and not the specific circumstances of the individual involved.
That ain’t good, at least not for the patients.
Medicine, for better or worse, is a business. In an ideal world it probably wouldn’t be, but we don’t live in one.
But it’s unlike any other business out there, and shouldn’t be run like one. A car repair shop knows what parts to order and generally how long repairs will take. Once they’re done the car should be ready to roll out of the shop.
People aren’t like that.
I understand the need to prevent abuse and overbilling for unnecessary days and services. Medicine, unfortunately, has plenty of opportunities for the dishonest to take advantage of.
It’s a thin line, but, at least today, turning treatment decisions over to algorithms and computers is a bad idea for the people we’re supposed to be caring for.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
STAT recently published an article on a new aspect of managed medical care.
They found that
That’s ... kind of scary.
Certainly, computers aren’t bad things. In 2023 America you can’t practice medicine without them. They aren’t malicious. They can analyze a lot of data faster than we can (for the record, the average memory capacity of a human brain is 1 petabyte, so we’re still ahead of the average desktop in that regard).
Computers, though, are pretty uniform. I’m a Mac person, and I can go into any Apple store and buy one. Right off the shelf I know how to work it, how it will run a given program, and can predict how it will handle different commands and such. They’re pretty much the same.
People are not quite as easy. Anatomically and chemically we’re similar, but that’s not the same. There are immune, genetic, and multiple other factors that put a lot of variables into the equation. Part of our training is knowing that and taking it into account when making treatment plans.
Algorithms, and artificial intelligence, can only do so much of that. If they were right all the time sports betting wouldn’t exist. But it does, because sports depends on the participants, who are people (or horses), and they’re not exactly alike ... for that matter how they’ll perform varies from day to day for the same individual.
But medical care isn’t a sport (even though hospital call can seem like a marathon). The data we give computers to use is generally based on averages – a rehab stay of 16.6 days for an 85-year-old woman with a broken shoulder (per the above article). But they don’t realize that averages are actually a collection of data on a bell-shaped curve. An insurance company will be only too happy when one person completes their rehabilitation in 11.6 days, and then feel it’s unreasonable when another takes 21.6.
That said, many of the companies involved say the final decisions are made by humans and that the algorithms are just guidelines.
Maybe so, but the STAT article suggests they’re putting too much credence in what the computer says, and not the specific circumstances of the individual involved.
That ain’t good, at least not for the patients.
Medicine, for better or worse, is a business. In an ideal world it probably wouldn’t be, but we don’t live in one.
But it’s unlike any other business out there, and shouldn’t be run like one. A car repair shop knows what parts to order and generally how long repairs will take. Once they’re done the car should be ready to roll out of the shop.
People aren’t like that.
I understand the need to prevent abuse and overbilling for unnecessary days and services. Medicine, unfortunately, has plenty of opportunities for the dishonest to take advantage of.
It’s a thin line, but, at least today, turning treatment decisions over to algorithms and computers is a bad idea for the people we’re supposed to be caring for.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Study compares noninvasive treatments of cutaneous neurofibromas
PHOENIX – after only one treatment, according to preliminary results of an ongoing prospective trial that compared several treatment modalities.
“Neurofibromatosis type 1 is the most common single-gene disease of mankind, but there is so much we have yet to learn about it,” study author Patricia Richey, MD, who practices Mohs surgery and cosmetic dermatology in Washington, D.C., said in an interview in advance of the annual conference of the American Society for Laser Medicine and Surgery, where she presented the results during an abstract session. Dr. Richey also conducts research for the Wellman Center for Photomedicine and the Dermatology Laser and Cosmetic Center at Massachusetts General Hospital, Boston, and is working with R. Rox Anderson, MD, director of the Wellman Center, on this project. In his words, she said, “the lack of better treatments for cNF is a ‘problem worth solving.’ ”
“The accepted and widely available treatments for cNF result in scars and hypopigmentation. Our treatments do not,” she added. Since the epidermis overlying cNF is normal, “there is no reason to use nonselective or surgical methods and destroy a perfectly good epidermis when you don’t need to.”
Four treatments vs. controls
For the study, Dr. Richey and colleagues enrolled 19 adults with a total of 307 cNFs measuring 2-4 mm in size to receive one of four treatments: electrocautery with an insulated radiofrequency needle; 755-nm alexandrite laser with negative pressure (8-mm spot size, 100 J/cm2 fluence, 3-ms pulse duration); 980-nm diode laser (delivered via 8-mm sapphire skin-contact window), and intratumoral injection of 10 mg/mL deoxycholic acid at a volume approximately equal to that of the tumor. The average age of the participants was 49 years and 15 were female.
The investigators applied 5% lidocaine/prilocaine for 40 minutes to treatment sites before randomizing the tumors to treatment or to the control arm (no treatment). They compared safety, tolerability (including pain scores), and efficacy of each modality as measured by the change in cNF volume/height via three-dimensional imaging and clinical improvement via physician assessment at 6 months. All 19 participants have completed the 6-month assessment.
All modalities reduced or eliminated some of the cNFs by 6 months after treatment, with statistically significant reductions in height and volume across all four treatments. A wide variation of responses was observed. Specifically, the mean tumor volume changes for each modality, compared with controls, were –33.4% versus –5.1% among those treated with the 755-nm alexandrite laser; –24.9% versus –9.2% among those treated with the 980-nm diode laser, –23.3% versus –0.8% among those treated with insulated-needle radiofrequency coagulation, and –29.4% versus –3.7% among those treated with deoxycholic acid.
The variation in responses “may be due to histologic diversity of cNF or may indicate a need for more fine-tuned dosimetry, or a combination,” Dr. Richey said. “Our future trials will address this. We will also be treating all skin types in our upcoming trials.”
No adverse events categorized as higher than grade 2 occurred in any of the treatment groups, and no signs of regrowth or growth stimulation have been observed to date.
Tolerability of treatments
As for general tolerability, the 980-nm laser treatment caused moderate to severe pain; the alexandrite laser caused mild pain; insulated-needle radiofrequency coagulation caused mild pain, though more than deoxycholic acid injections or alexandrite laser, and pain associated with the deoxycholic acid injections was minimal.
When residual neurofibroma tumor was present histologically, its appearance was similar to that of untreated tumors in controls. There was no evidence of atypia, mitosis, or tumor inflammation, and mild fibrosis was present at the sites of prior tumor.
“It was surprising that all four modalities did work to some extent,” Dr. Richey said, noting that the lack of ulceration with deoxycholic acid injection “was pleasantly surprising.” Treatment with the 980-nm diode laser “was a bit more painful than we anticipated.”
The positive results of this trial has raised “more questions for us to answer. We have three additional trials in the works to fine tune these treatments and optimize dose/delivery, with the end goal of treating younger people.”
Dr. Richey said that she was “amazed” by how motivated the enrollees were to participate in the trial, noting that many patients with cNF undergo general anesthesia to have dozens of tumors surgically removed at once. “They pay $10,000-$20,000 on average out of pocket, as this surgery is considered cosmetic,” she said.
“This very important study could lead to effective, relatively noninvasive, therapy for small neurofibromas,” said Jeffrey S. Dover, MD, codirector of SkinCare Physicians in Chestnut Hill, Mass., who was not involved with the study and was asked to comment on the results.
“Remarkably, all four treatments worked to varying degrees, but of all the treatments, the selective alexandrite laser appeared to achieve the best results. Further study will be needed to see just how effective these treatments are, and to determine the best and safest treatment parameters. Given how common this autosomal dominant disease is, and how disfiguring neurofibromas become as they enlarge, a well-tolerated noninvasive nonsurgical treatment with limited side effects is highly sought after.”
The study, which was named the best clinical abstract at the meeting, was supported by the Neurofibromatosis Therapeutic Acceleration Program. Dr. Anderson is supported in part as the Lancer Endowed Chair in Dermatology at MGH. Dr. Dover reported having no relevant disclosures.
PHOENIX – after only one treatment, according to preliminary results of an ongoing prospective trial that compared several treatment modalities.
“Neurofibromatosis type 1 is the most common single-gene disease of mankind, but there is so much we have yet to learn about it,” study author Patricia Richey, MD, who practices Mohs surgery and cosmetic dermatology in Washington, D.C., said in an interview in advance of the annual conference of the American Society for Laser Medicine and Surgery, where she presented the results during an abstract session. Dr. Richey also conducts research for the Wellman Center for Photomedicine and the Dermatology Laser and Cosmetic Center at Massachusetts General Hospital, Boston, and is working with R. Rox Anderson, MD, director of the Wellman Center, on this project. In his words, she said, “the lack of better treatments for cNF is a ‘problem worth solving.’ ”
“The accepted and widely available treatments for cNF result in scars and hypopigmentation. Our treatments do not,” she added. Since the epidermis overlying cNF is normal, “there is no reason to use nonselective or surgical methods and destroy a perfectly good epidermis when you don’t need to.”
Four treatments vs. controls
For the study, Dr. Richey and colleagues enrolled 19 adults with a total of 307 cNFs measuring 2-4 mm in size to receive one of four treatments: electrocautery with an insulated radiofrequency needle; 755-nm alexandrite laser with negative pressure (8-mm spot size, 100 J/cm2 fluence, 3-ms pulse duration); 980-nm diode laser (delivered via 8-mm sapphire skin-contact window), and intratumoral injection of 10 mg/mL deoxycholic acid at a volume approximately equal to that of the tumor. The average age of the participants was 49 years and 15 were female.
The investigators applied 5% lidocaine/prilocaine for 40 minutes to treatment sites before randomizing the tumors to treatment or to the control arm (no treatment). They compared safety, tolerability (including pain scores), and efficacy of each modality as measured by the change in cNF volume/height via three-dimensional imaging and clinical improvement via physician assessment at 6 months. All 19 participants have completed the 6-month assessment.
All modalities reduced or eliminated some of the cNFs by 6 months after treatment, with statistically significant reductions in height and volume across all four treatments. A wide variation of responses was observed. Specifically, the mean tumor volume changes for each modality, compared with controls, were –33.4% versus –5.1% among those treated with the 755-nm alexandrite laser; –24.9% versus –9.2% among those treated with the 980-nm diode laser, –23.3% versus –0.8% among those treated with insulated-needle radiofrequency coagulation, and –29.4% versus –3.7% among those treated with deoxycholic acid.
The variation in responses “may be due to histologic diversity of cNF or may indicate a need for more fine-tuned dosimetry, or a combination,” Dr. Richey said. “Our future trials will address this. We will also be treating all skin types in our upcoming trials.”
No adverse events categorized as higher than grade 2 occurred in any of the treatment groups, and no signs of regrowth or growth stimulation have been observed to date.
Tolerability of treatments
As for general tolerability, the 980-nm laser treatment caused moderate to severe pain; the alexandrite laser caused mild pain; insulated-needle radiofrequency coagulation caused mild pain, though more than deoxycholic acid injections or alexandrite laser, and pain associated with the deoxycholic acid injections was minimal.
When residual neurofibroma tumor was present histologically, its appearance was similar to that of untreated tumors in controls. There was no evidence of atypia, mitosis, or tumor inflammation, and mild fibrosis was present at the sites of prior tumor.
“It was surprising that all four modalities did work to some extent,” Dr. Richey said, noting that the lack of ulceration with deoxycholic acid injection “was pleasantly surprising.” Treatment with the 980-nm diode laser “was a bit more painful than we anticipated.”
The positive results of this trial has raised “more questions for us to answer. We have three additional trials in the works to fine tune these treatments and optimize dose/delivery, with the end goal of treating younger people.”
Dr. Richey said that she was “amazed” by how motivated the enrollees were to participate in the trial, noting that many patients with cNF undergo general anesthesia to have dozens of tumors surgically removed at once. “They pay $10,000-$20,000 on average out of pocket, as this surgery is considered cosmetic,” she said.
“This very important study could lead to effective, relatively noninvasive, therapy for small neurofibromas,” said Jeffrey S. Dover, MD, codirector of SkinCare Physicians in Chestnut Hill, Mass., who was not involved with the study and was asked to comment on the results.
“Remarkably, all four treatments worked to varying degrees, but of all the treatments, the selective alexandrite laser appeared to achieve the best results. Further study will be needed to see just how effective these treatments are, and to determine the best and safest treatment parameters. Given how common this autosomal dominant disease is, and how disfiguring neurofibromas become as they enlarge, a well-tolerated noninvasive nonsurgical treatment with limited side effects is highly sought after.”
The study, which was named the best clinical abstract at the meeting, was supported by the Neurofibromatosis Therapeutic Acceleration Program. Dr. Anderson is supported in part as the Lancer Endowed Chair in Dermatology at MGH. Dr. Dover reported having no relevant disclosures.
PHOENIX – after only one treatment, according to preliminary results of an ongoing prospective trial that compared several treatment modalities.
“Neurofibromatosis type 1 is the most common single-gene disease of mankind, but there is so much we have yet to learn about it,” study author Patricia Richey, MD, who practices Mohs surgery and cosmetic dermatology in Washington, D.C., said in an interview in advance of the annual conference of the American Society for Laser Medicine and Surgery, where she presented the results during an abstract session. Dr. Richey also conducts research for the Wellman Center for Photomedicine and the Dermatology Laser and Cosmetic Center at Massachusetts General Hospital, Boston, and is working with R. Rox Anderson, MD, director of the Wellman Center, on this project. In his words, she said, “the lack of better treatments for cNF is a ‘problem worth solving.’ ”
“The accepted and widely available treatments for cNF result in scars and hypopigmentation. Our treatments do not,” she added. Since the epidermis overlying cNF is normal, “there is no reason to use nonselective or surgical methods and destroy a perfectly good epidermis when you don’t need to.”
Four treatments vs. controls
For the study, Dr. Richey and colleagues enrolled 19 adults with a total of 307 cNFs measuring 2-4 mm in size to receive one of four treatments: electrocautery with an insulated radiofrequency needle; 755-nm alexandrite laser with negative pressure (8-mm spot size, 100 J/cm2 fluence, 3-ms pulse duration); 980-nm diode laser (delivered via 8-mm sapphire skin-contact window), and intratumoral injection of 10 mg/mL deoxycholic acid at a volume approximately equal to that of the tumor. The average age of the participants was 49 years and 15 were female.
The investigators applied 5% lidocaine/prilocaine for 40 minutes to treatment sites before randomizing the tumors to treatment or to the control arm (no treatment). They compared safety, tolerability (including pain scores), and efficacy of each modality as measured by the change in cNF volume/height via three-dimensional imaging and clinical improvement via physician assessment at 6 months. All 19 participants have completed the 6-month assessment.
All modalities reduced or eliminated some of the cNFs by 6 months after treatment, with statistically significant reductions in height and volume across all four treatments. A wide variation of responses was observed. Specifically, the mean tumor volume changes for each modality, compared with controls, were –33.4% versus –5.1% among those treated with the 755-nm alexandrite laser; –24.9% versus –9.2% among those treated with the 980-nm diode laser, –23.3% versus –0.8% among those treated with insulated-needle radiofrequency coagulation, and –29.4% versus –3.7% among those treated with deoxycholic acid.
The variation in responses “may be due to histologic diversity of cNF or may indicate a need for more fine-tuned dosimetry, or a combination,” Dr. Richey said. “Our future trials will address this. We will also be treating all skin types in our upcoming trials.”
No adverse events categorized as higher than grade 2 occurred in any of the treatment groups, and no signs of regrowth or growth stimulation have been observed to date.
Tolerability of treatments
As for general tolerability, the 980-nm laser treatment caused moderate to severe pain; the alexandrite laser caused mild pain; insulated-needle radiofrequency coagulation caused mild pain, though more than deoxycholic acid injections or alexandrite laser, and pain associated with the deoxycholic acid injections was minimal.
When residual neurofibroma tumor was present histologically, its appearance was similar to that of untreated tumors in controls. There was no evidence of atypia, mitosis, or tumor inflammation, and mild fibrosis was present at the sites of prior tumor.
“It was surprising that all four modalities did work to some extent,” Dr. Richey said, noting that the lack of ulceration with deoxycholic acid injection “was pleasantly surprising.” Treatment with the 980-nm diode laser “was a bit more painful than we anticipated.”
The positive results of this trial has raised “more questions for us to answer. We have three additional trials in the works to fine tune these treatments and optimize dose/delivery, with the end goal of treating younger people.”
Dr. Richey said that she was “amazed” by how motivated the enrollees were to participate in the trial, noting that many patients with cNF undergo general anesthesia to have dozens of tumors surgically removed at once. “They pay $10,000-$20,000 on average out of pocket, as this surgery is considered cosmetic,” she said.
“This very important study could lead to effective, relatively noninvasive, therapy for small neurofibromas,” said Jeffrey S. Dover, MD, codirector of SkinCare Physicians in Chestnut Hill, Mass., who was not involved with the study and was asked to comment on the results.
“Remarkably, all four treatments worked to varying degrees, but of all the treatments, the selective alexandrite laser appeared to achieve the best results. Further study will be needed to see just how effective these treatments are, and to determine the best and safest treatment parameters. Given how common this autosomal dominant disease is, and how disfiguring neurofibromas become as they enlarge, a well-tolerated noninvasive nonsurgical treatment with limited side effects is highly sought after.”
The study, which was named the best clinical abstract at the meeting, was supported by the Neurofibromatosis Therapeutic Acceleration Program. Dr. Anderson is supported in part as the Lancer Endowed Chair in Dermatology at MGH. Dr. Dover reported having no relevant disclosures.
AT ASLMS 2023